CARDIAC AND RESPIRATORY CAREPERTINENT CONCEPTS AND PRACTICES FOR THE GENERAL SURGEON

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IntroductionCardiac and respiratory complications are the two most frequent and most lethal

groups of complications that occur after general surgery operations. Using modern un-derstandings of cardiac and pulmonary pathophysiology, surgeons can now prevent or manage these events with frequent patient salvage and full recovery. This issue of Se-lected Readings in General Surgery (SRGS) reviews current information pertinent to the successful management of cardiac and respiratory diseases and complications in gen-eral surgery patients.

Perioperative cardiac complicationsEvidence of atherosclerotic cardiovascular disease is found at autopsy on nearly all

patients dying after the age of 40 years. Symptoms of atherosclerotic cardiovascular disease have become increasingly common as the population of the United States ages and cardiovascular disease is the leading cause of death among older adults in North America. Increasingly, older patients with moderate-to-severe comorbid cardiovascular diseases are presenting for surgical care. Current data estimate that 60%-80% of post-operative deaths after elective operation are traceable to cardiovascular complications of surgical procedures. In the first section of the overview for this issue of SRGS, we re-view pertinent data on the topic of perioperative cardiac complications. Important is-sues relevant to risk recognition, risk modification, and prevention are discussed. Data pertinent to the diagnosis and management of myocardial infarction, cardiac failure, ar-rhythmias, and cardiac arrest will be reviewed. Fundamental aspects of the diagnosis and management of cardiac conduction system disorders and management of pacemak-ers and implantable defibrillators are included.

Risk factors for postoperative cardiac complicationsEffective prevention of perioperative cardiac complications is possible only if pa-

tients at risk can be identified. Identification of high-risk patients can lead to develop-ment and use of preventive strategies. These approaches obviously will be most useful for patients who are scheduled to undergo elective operations. In this patient group, there is time for a detailed history and physical examination, laboratory studies, elec-trocardiogram, and imaging. The articles reviewed in this section of the overview detail the fundamental features of perioperative cardiac risk assessment and risk modifica-tion.

The first article reviewed is by Davenport and coauthors1 entitled, “Multivariable predictors of postoperative cardiac adverse events after general and vascular surgery: results from the patient safety in surgery study.” This article is supplied as a full-text re-print with this issue of SRGS. The authors begin noting that cardiac complications occur

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after 1%-5% of surgical procedures. Given an annual number of operations currently exceeding 30 million, this estimate would result in as many as 1.5 million adverse car-diac events annually. The estimated mortality for adverse cardiac events exceeds 50%. Thus, as many as 750,000 deaths could be expected annually.

The authors cite data that have identified age > 75years, diabetes mellitus, hyper-tension, and baseline electrocardiographic findings indicative of ischemia as risk factors for perioperative adverse cardiac events. The current means of estimating the risk of perioperative cardiac events are summarized in three available scoring systems focus-ing on factors pertinent to the operation (elective versus emergency; simple versus complex), and on cardiac-specific risk factors such as a history of hypertension, sympto-matic ischemic heart disease, diabetes, and cardiac failure. The authors stress that pop-ular risk scoring systems, introduced in the late 1980s, award one point for each of sev-eral risk factors; clinical reviews of these systems have noted increased risk of adverse cardiac events with increasing risk scores. Nonetheless, there remains controversy over the ability of the available scoring systems to identify accurately patients for whom the procedure should be delayed in order to conduct further evaluation. Furthermore, as-signing a specific risk to an individual patient is difficult using existing scoring systems.

In an attempt to clarify and improve cardiac risk scoring for surgical patients, Dav-enport and coauthors used the Patient Safety in Surgery database that contains a stan-dard dataset for patients from 128 Veterans Administration hospitals and from 14 aca-demic medical centers. This database contains multiple demographic, preoperative, pe-rioperative, and outcomes variables obtained from medical record reviews conducted in a standard fashion by experienced nurse reviewers using standardized definitions. Data on more than 180,000 patients were subjected to multivariate logistic regression analysis. Adverse cardiac events were defined as cardiac arrest or acute myocardial in-farction within 30 days of operation. Adverse cardiac events were recorded in 2362 pa-tients and the mortality rate for these events was 60%. The authors tested a predictive model on a sample of patients drawn from the database after logistic regression model-ling of risk factors from the entire database.

Prediction of adverse events was accurate using a model that included ASA score, operation complexity (as reflected in procedure relative value work units), age, and type of operation. Interestingly, none of the conventional cardiac specific risk factors such as hypertension, prior history of myocardial infarction, or prior history of a car-diac surgical procedure was valuable as a predictor of perioperative adverse cardiac events. When the subgroup of patients from non-VA medical facilities was considered, the authors found that these patients, as a group, were younger and contained more women than the VA cohort. The frequency of adverse cardiac events was less in this subgroup but cardiac-specific risk factors failed to predict outcomes in this subgroup

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also. The authors provide a table of risk point assignments for the factors they identi-fied as most influential in determining outcomes. A graph in their report indicates that significant cardiac risk (>1% risk of adverse event) is recognized beginning with a total risk score of 12-15 points.

Davenport and colleagues emphasize the diminished predictive power of conven-tional cardiac specific risk factors and report that these factors become less predictive when considered together with more global risk indicators such as ASA score. They also note that, in the current era, patients with known conventional risk factors are often treated preoperatively with medications and, occasionally, interventions that serve to reduce risk. This would also work to reduce the influence of cardiac-specific risk fac-tors.

They further emphasize the lethality of adverse cardiac events. The mortality risk for patients who sustain these events is large, and recognition of this serves as a stimu-lus to improve perioperative management. Use of measures such as avoiding emer-gency operation, preoperative stabilization of cardiac failure and rhythm disturbances, optimization of intraoperative monitoring, use of regional anesthesia, and use of drugs to control heart rate and stabilize atherosclerotic plaque, are potentially useful mea-sures. These are discussed in more detail in the following sections of the overview. If emergency operation can be avoided, preoperative approaches to optimize coagulation, renal function, and nutrition might assist in minimizing the risk of cardiac adverse events. The authors conclude that their approach to outcomes prediction is well suited for inclusion in efforts to identify high and low performing hospitals as is done in the National Surgical Quality Improvement Program (NSQIP) sponsored by the American College of Surgeons. Furthermore, their risk scoring system is designed for easy incor-poration into electronic medical records. The risk prediction model could be made available at the bedside on a hand-held computer.

Risk assessmentAdditional detailed data relevant to cardiac risk assessment is in an article by Pold-

ermans and coauthors2 in the Journal of the American College of Cardiology, 2008. These authors report European experience with adverse cardiac events in the perioperative period. An annual rate of 400,000 perioperative cardiac events has been recorded in the European Union. One hundred thirty-three thousand deaths occurred because of these complications. They agree with Davenport and colleagues that the type of operation is a major driver of risk. They cite data showing that patients older than 40 years of age have a 2.5% risk of adverse cardiac events after operation. The risk rises to more than 6% in patients undergoing vascular surgical procedures. They stress that the incidence of perioperative cardiac events varies because of the means used to make the diagnosis. When the diagnosis was made with Troponin T or I assays, the frequency of events rose

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to 25% in high-risk patients. They further agree that advancing age is a driver of cardiac risk.

Postoperative myocardial infarction is the most important adverse cardiac event. The pathophysiology of this complication is complex. Patients whose preoperative im-ages show discrete areas of impaired myocardial perfusion are thought to be at in-creased risk for perioperative myocardial infarction. It is now clear, however, that "cul-prit" coronary lesions are not the predominant cause of perioperative myocardial in-farction. Plaque rupture and thrombosis in coronary arteries at sites of noncritical coro-nary artery stenosis are frequent causes of perioperative myocardial infarction. This understanding helps to explain the lack of benefit of preoperative myocardial revascu-larization of culprit lesions. Emphasis has shifted away from identification of culprit coronary lesions and toward global pharmacologic measures for reducing cardiac risk. The topic of preoperative interventions is discussed in a later section of the overview.

Poldermans and associates note that features of the metabolic response to opera-tion contribute to imbalances in myocardial oxygen demand and availability. The in-creased secretion of catecholamines results in tachycardia, which can create unfavor-able myocardial oxygen demand/supply situations. This topic is addressed in more de-tail in a report by Sander and coauthors3 in Critical Care Medicine, 2005. These authors identified 69 patients deemed at high risk for adverse cardiac events. In a subgroup of 39 patients with sustained (>12 hours) tachycardia (heart rate > 95 bpm), the risk of a major adverse cardiac event was 49%. In the 30 high-risk patients who did not have tachycardia, the risk of an adverse cardiac event was 13%. The majority of the tachy-cardic rhythms were sinus tachycardia, although there were 16 patients with new-on-set atrial fibrillation.

The authors cite data that document an association of tachycardia with prolonged ST-segment depression, a finding known to predict perioperative myocardial infarction. Poldermans and coauthors2 agree, noting that prolonged ST-segment depression is a known precursor of perioperative myocardial infarction in patients undergoing vascu-lar surgical procedures. In Sander’s report, tachycardia occurred during the 24-hour pe-riod in which the myocardial infarction occurred in 90% of patients. Sander and asso-ciates conclude with the observation that the subgroup of their patients where no tachycardia occurred were more likely to be receiving -blocking drugs and epidural βanalgesia. They suggest that these factors might be protective against tachycardia and the adverse cardiac events that accompany this change in cardiac rhythm.

Poldermans and colleagues point out that the inflammatory response that some-times follows major surgery procedures creates an environment that contributes to hy-percoagulability because of activation of the coagulation mechanism and reduced fibri-

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nolytic activity. As noted in the discussion of atherosclerotic vascular disease in a previ-ous three-issue series of SRGS (Volume 35, Numbers 1-3), inflammatory cytokines are potent forces that produce plaque instability and rupture. Inflammation might also con-tribute to the onset of postoperative tachyarrhythmias. This topic is discussed in an ar-ticle by Anselmi and coauthors4 in Annals of Thoracic Surgery, 2009, focusing on causes of new-onset atrial fibrillation after cardiac operations.

These authors note that cardiopulmonary bypass is a potent stimulus of the inflam-matory response. Inflammation, as evidenced by elevated levels of C-reactive protein, is associated with increased risk of atrial fibrillation in surgery and nonsurgery patients. Lower C-reactive protein levels have also been associated with improved responses to cardioversion for new-onset atrial fibrillation. They cite one study where reduction of risk for recurrent atrial fibrillation occurred with specific anti-inflammatory therapy with the antioxidant Vitamin C. Anselmi and associates point out that reductions of pe-rioperative inflammation observed with off-pump coronary artery bypass, use of peri-operative corticosteroids, and use of preoperative statin drugs are all associated with lowered risk of atrial fibrillation. These observations support an association between perioperative inflammation and perioperative atrial fibrillation.

Because new-onset atrial fibrillation is associated with perioperative cardiac events, as noted by Sander and associates3, efforts to control the inflammatory response seem warranted. Available pharmacologic therapies that reduce inflammation such as -βblockers and statins are discussed in a subsequent section of the overview.

Poldermans and coauthors2 go on to note that existing cardiac risk scoring systems are imprecise. Improved risk assessment would result with the inclusion of global risk factors such as age and operation characteristics. This assertion is in agreement with the findings of Davenport and coauthors1, noted above. The difficulty encountered by clinicians attempting to quantify cardiac risk preoperatively using the available scoring systems has stimulated researchers to investigate alternative means of assessing risk for perioperative cardiac events. Two of these approaches are discussed here.

Normal cardiac function depends, in large measure, on an appropriate balance be-tween the influences of the sympathetic and parasympathetic nervous systems. This balance is assessable clinically by use of special ambulatory electrocardiographic moni-toring with assessment of heart rate variability. Heart rate variability is a sign of healthy cardiac function, while loss of variability signals an imbalance in the relative in-fluences of the sympathetic and parasympathetic nervous systems on the heart. Loss of heart rate variability has been associated with an increased risk of sudden cardiac death, an increased risk of death in multiple trauma patients, and adrenal insufficiency in the critically ill surgical patient.

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The fundamental physiology of heart rate variability and the potential application of this assessment to the preoperative evaluation are discussed in an article by Laitio and coauthors5 in Anesthesia and Analgesia in 2007. These authors begin by noting that heart rate variability is an indicator of the integrated function of the parasympathetic nervous system (especially vagus nerve activity), the sympathetic nervous system, and the baroreceptor system. They describe the various measures used in analyses of heart rate variability, including time domain analyses that express variability in terms of in-stantaneous heart rate and intervals between normal QRS complexes. Frequency do-main analyses commonly express variability in terms of “power-law” spectral analyses of RR-interval variability.

These methods of assessing heart rate variability are time-tested and accepted but they do not adequately describe the complex, fractal system that is heart rate variabil-ity. Because of this, dynamic assessments of heart rate variability have been developed to analyze correlations of multiple time series of RR intervals. These analyses can be graphed and patterns typical of normal patients, patients with heart failure, and pa-tients prone to ischemic events can be displayed. Similar graphic displays are obtained using Poincare plots. These show typical compact “comet shaped” patterns in normal patients and patients analyzed after myocardial revascularization. These graphs show diurnal variation. Heart rate variability changes during ischemic episodes are charac-terized by irregular widely spread graphic patterns with loss of diurnal variation.

The actions of anesthetic drugs to down-regulate vagal activity result in changes in heart rate variability. Changes in heart rate variability accurately predict hypotensive episodes after induction of spinal anesthesia especially when the block reaches the tho-racic spinal levels. Loss of heart rate variability in elderly patients and in diabetic pa-tients with dysfunction of the autonomic nervous system accurately predicts episodes of hemodynamic instability. The authors cite several studies that have related loss of heart rate variability to short- and long-term operative mortality from myocardial is-chemia and prolonged ICU stays.

The presence of heart rate variability abnormalities improves the predictive capa-bility of the available cardiac risk scales, especially for predicting long-term cardiac mortality. In the cited studies, the combination of abnormal heart rate variability and high-risk scores accurately predicted perioperative cardiac morbidity for patients un-dergoing cardiac and noncardiac procedures. Laitio and colleagues speculate that loss of heart rate variability indicates unopposed sympathetic influence on the heart that might increase myocardial oxygen demand by augmenting ventricular contractility. This situation favors the development of ischemia in susceptible patients. The need for 24-hour electrocardiographic monitoring and manual assessment of the tracings are significant disincentives that have reduced the utility of heart rate variability measure-

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ments for preoperative patients. With improved, computer-assisted methodologies, these disadvantages might be overcome.

Additional data on the use of heart rate variability assessments as a means of pre-dicting perioperative cardiac morbidity risk are found in an article by Hanss and coau-thors6 in Anaesthesia, 2008. These authors report an initial analysis of 50 patients who underwent heart rate variability analysis preoperatively and, during the postoperative period, had 24-hour electrocardiographic monitoring and sequential measurements of creatine kinase MB band in blood samples. Cardiac events were detected by a combina-tion of electrocardiographic changes and elevations of the CPK-MB level. Seventeen of the initial patients had cardiac events and the authors established that a heart rate vari-ability power value <400 ms2 Hz-1 was a useful cut-off value for prediction of cardiac events. This cut-off value was then assessed prospectively in 50 additional patients. Cardiac events and hospital length of stay were both increased in the 26 patients with low power scores in the prospective group. The authors conclude that heart rate vari-ability power analysis is a useful predictor of postoperative cardiac events and the addi-tional information might improve the predictive power of cardiac risk scoring systems.

Additional predictive power can be obtained using serum markers that reflect vul-nerability of the myocardium to ischemia. Two of these, B-type natriuretic peptide (BNP) and N-terminal pro-brain natriuretic peptide (NT-proBNP), are discussed. The first of these is by Cuthbertson and coauthors7 in the British Journal of Anaesthesia, 2007, who analyzed outcomes data on 204 patients undergoing major noncardiac surgery procedures. Preoperative BNP levels were obtained in each patient. Periopera-tive cardiac events were defined as an elevation of the troponin level or death within three days of operation. The authors found that a preoperative elevation of BNP >40 pg/mL was predictive of perioperative cardiac events. They performed rigorous multi-variate statistical analysis and found that the preoperative BNP level was more accurate for risk prediction than findings on history, physical examination, or electrocardiogram. BNP was more predictive than the revised cardiac risk score. Nonetheless, five patients with significant postoperative cardiac events were not identified by the preoperative BNP elevation. This observation suggests that BNP cannot be used alone to establish risk for perioperative adverse cardiac events.

An article analyzing the potential usefulness of NT-proBNP levels assessed preoper-atively and with a single postoperative sample by Mahla and coauthors8 appeared in Anesthesiology, 2007. These authors analyzed results in 218 patients who underwent major vascular reconstructive procedures. Patients were followed for 30 months post-operatively. Twenty percent sustained a significant cardiac event during the followup interval. The authors found that a preoperative value for NT-proBNP equal to 280 pg/mL coupled with a postoperative increase to 557 pg/mL accurately predicted short-

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and long-term cardiac morbidity. The authors state that NT-proBNP is released from cardiac myocytes in response to ischemia and stretch and, therefore, this hormone might be a good candidate for prediction of perioperative myocardial ischemia. The ac-curacy of the preoperative and postoperative levels combined was good, with an area under the receiver-operating-characteristic curve of 0.8 that is as good as or better than all available risk-scoring systems. The authors conclude that this test might offer im-proved prediction of cardiac events in high-risk patients undergoing major vascular op-erations.

Preoperative evaluation for coronary artery disease and preoperative interventionsOnce a high-risk patient is identified, the next decision concerns the need for addi-

tional preoperative cardiac testing. Exercise testing, dobutamine stress echocardiogra-phy, and myocardial scintigraphy with vasodilator stress are tests commonly contem-plated. Recommendations by the American Heart Association state that testing is indi-cated in patients who have symptoms suggesting unstable cardiac syndromes (decom-pensated cardiac failure or unstable angina), patients who have poor functional capac-ity where a high-risk operation is contemplated (major vascular reconstruction), and patients with known valvular heart disease. Poldermans and colleagues stress the lack of a positive contribution of preoperative cardiac testing in cardiac stable patients, es-pecially those who are already using -blocking drugs and statins with good control of βheart rate. They further emphasize that coronary artery bypass in cardiac stable pa-tients has not resulted in improved surgical outcomes and the intervention delays the planned noncardiac procedure. Percutaneous coronary interventions similarly delay the planned procedure because the risk of stent thrombosis is substantial in the first weeks following stent placement when multiple drug antiplatelet therapy is used. With drug-eluting stents, this interval might be as long as one year.

Additional data on the use of extensive preoperative cardiac testing and preopera-tive cardiac interventions to prevent perioperative adverse cardiac events are reported by Jaroszewski and coauthors9 in the Journal of Thoracic and Cardiovascular Surgery, 2008, who performed a retrospective review of 294 patients who underwent thoraco-tomy for a noncardiac operation in a single institution. One hundred eighty-four pa-tients underwent extensive preoperative assessment including, in addition to history and physical examination with 12-lead electrocardiogram, stress testing, stress echocardiography, and/or myocardial scintigraphy. Based on preoperative test find-ings, 40 patients were selected to undergo coronary angiography and four of these had preoperative coronary revascularization by either operation or stenting. There was no difference in the frequency of perioperative myocardial infarction in patients who had testing and intervention compared with those who did not have testing. In fact, of the four patients who underwent revascularization, two had perioperative myocardial in-farction. One of these was from perioperative coronary stent thrombosis. These authors

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concluded that there was no benefit to testing and intervention in cardiac stable pa-tients.

Medications for reducing cardiac riskPoldermans and coauthors2 stress the importance of general medical approaches to

cardiac risk modification in patients undergoing major elective operations. These ap-proaches have generally consisted of careful risk stratification, and use of pharmaco-logic approaches designed to alter, favorably, myocardial oxygen consumption/oxygen demand relationships as well as stabilize plaque through control of perioperative in-flammatory responses. The authors note that the high catecholamine release states cre-ated by the stress of operation alter both myocardial energetics and inflammation. Ini-tial approaches to balancing myocardial energetics included the use of -blocking βdrugs. Initially, drugs used were combined -1 and -2 agents, such as propranolol. β β

As additional human trial data have become available, important lessons have been learned. Poldermans and associates describe these progressive steps. For example, they stress the observation that trials of beta blockade have generally shown reductions in the frequency of perioperative cardiac events but some trials have disclosed risks of hy-potension and stroke, especially in older patients not judged at high risk for cardiac events. Two prospective, randomized trials cited by these authors (references 40 and 45 in their bibliography) showed effective reduction in cardiac events but at the cost of a significantly increased risk of stroke and overall mortality. These trials disclosed the potential danger of pharmacologically lowering blood pressure to 100 mmHg or lower in elderly patients. The type of beta-blocking drug used, timing of drug therapy, and dosing are also important features of approaches that achieve maximum success. Drugs that are -1 selective agents (such as bisoprolol) are more effective than drugs that tarβ -get both the -1 and -2 receptors. Blockade of both receptor types results in a state of β βpredominant receptor stimulation that results in hypertension and increased myocarα -dial stress.

Prospective, randomized trials have shown no impact of beta blockade on the risk of perioperative cardiac events if the drug is started on the day before or the day of the op-eration. This finding implies that maximum stabilization of cardiac energetics and plaque requires time. In fact, the DECREASE trial (reference 37 in Poldermans’ bibliog-raphy) started treatment, on average, 37 days before operation and with incremental adjustment of the dose upward based on blood pressure and heart rate. This study dis-closed a 10-fold reduction in the risk of perioperative cardiac events and death.

All of the data cited by Poldermans and associates support the use of -1 selective βdrugs with a long half-life. The drug should be started at least one month before opera-tion and adjusted to obtain optimum heart rate (current American Heart Association

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recommendations are resting heart rates in the 60-66 bpm range) without episodes of hypotension. Patients at low risk for cardiac events should not take beta-blocking drugs unless they are using these drugs chronically. Moderate risk patients undergoing major vascular operations are acceptable candidates for beta-blocking therapy and high-risk patients undergoing any type of major operation are excellent candidates for this ap-proach. Drugs should not be withdrawn in the perioperative period because benefit has been shown for protection against both short-term and long-term cardiac morbidity. Downsides of beta-blocking drug usage include a range of contraindications (asthma, for example) and consistent observations that up to 25% of patients have episodes of tachycardia in the perioperative period despite seemingly adequate beta blockade.

Further analysis of the use of beta blockade for prevention of perioperative cardiac events comes from a review by Chopra and coauthors10 entitled “Perioperative beta-blockers for major noncardiac surgery: Primum non nocere.” This article appeared in The American Journal of Medicine in 2009 and a full-text reprint of the article is pro-vided with this issue of SRGS. These authors review the actions of beta-blocking drugs. They note that there are three subtypes of beta-receptors and these receptors are pre-sented on the cell surface of many types of human tissue. Beta one receptors are found in the myocardium, the kidney, and the eye. Beta two receptors are found in adipose tis-sue, liver, pancreas, smooth muscle, and skeletal muscle. Beta three receptors are pri-marily involved with metabolic regulation and lipolytic pathways. The receptors are G-coupled proteins that activate intracellular adenyl cyclase and produce intracellular ef-fects via adenosine monophosphate production and opening of excitatory channels. Chopra and associates confirm the observations of Poldermans and coauthors2 and sug-gest that beta blockade use be targeted toward patients at high risk for perioperative cardiac events. Beta-blocking drug therapy should be started at least one month before operation, and tight heart rate control should be sought with maximum protection against hypotensive events. Drug therapy should be continued during the postoperative period, and that use of statins and/or aspirin should be considered.

Supporting data on the value of tight heart rate control is in a meta-analysis au-thored by Beattie and coauthors11 in Anesthesia and Analgesia, 2008. These authors pro-vide an analysis that specifically focuses on reasons for inadequate heart rate control in trials of beta-blocking drugs. They emphasize that early implementation of beta block-ade with progressive upward adjustment of dose to obtain consistent resting heart rates in the 60-65 bpm range is associated with maximum reductions of risk of periop-erative cardiac events. Several recent trials have shown that fixed dose approaches do not produce maximum protection against perioperative cardiac events. They stress that the available trial data strongly indicate that variation in achieving optimum heart rate control accounts for 60% of the variability in trial results. They also document that the

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type of drug used and the concomitant use of calcium channel blockers might alter the heart rate response.

Based on their analysis they recommend that beta-blocking drugs other than meto-prolol be chosen, especially in patients concomitantly using calcium channel blockers. Most of the available trials disclose failure to achieve heart rate goals in 20%-35% of patients. Suboptimum heart rate control might be the result, according to Beattie and colleagues, of the presence of the AA variant of the beta-receptor resistant to the beta-blocking drugs. In the setting where optimum heart rate is not achieved, combination therapy with calcium channel blockers might be necessary.

Beattie and colleagues point out that available data does not adequately address the risk of exacerbation of congestive heart failure from tight heart rate control with beta-blockers. Nor does the data adequately evaluate the use of other approaches to stabi-lization of myocardial energetics such as the use of regional anesthesia/analgesia and

-2 receptor agonists, which have both been shown to reduce the frequency of periopα -erative cardiac events. The authors recommend therapy to obtain optimum heart rate control but caution that the best approach to achieve this goal might not be available yet.

An alternative approach to achieving optimum balance between control of heart rate and maintenance of cardiac output is described in an article by Suttner and coau-thors12 in the British Journal of Anesthesia, 2009. These authors note that concerns about the effect of beta-blocking drugs on blood pressure and cardiac output have led to reluctance on the part of some clinicians to use beta blockade for high-risk patients, es-pecially those who might need urgent or emergent intervention. In the current study, an analysis is presented of results in 75 high-risk (as defined by three or more risk factors) vascular surgery patients randomized to receive continuous perioperative beta block-ade with intravenous esmolol alone, esmolol plus enoximone (a phosphodiesterase type III inhibitor), and standard therapy.

Perioperative cardiac events were documented by elevations of troponin or BNP. The authors explain that phosphodiesterase inhibitors such as enoximone and milri-none have the potential to maintain cardiac contractile function when catecholamine pathways are pharmacologically blocked. In this study, they noted no abnormalities of troponin in either group receiving esmolol. BNP was lowest in the esmolol + enoximone group and this group had the best maintenance of cardiac index. They suggest that enoximone support of cardiac index occurred because of its action that promotes influx of calcium into myocytes, thereby favoring increased contractility. In vascular smooth muscle, enoximone promotes calcium efflux, favoring vasodilation.

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These authors rightly caution that dosing of esmolol and enoximone should be man-aged carefully because higher doses might predispose to new-onset arrhythmias. While these salutary effects were obtained in high-risk vascular surgery patients, the numbers of patients are small. Furthermore, even though these patients were said to be at high risk for perioperative cardiac events, fewer than 20% of each group received preopera-tive beta-blocker and/or statin therapy. The results of this study suggest, but do not prove, that an approach such as described might have protective effects in high-risk pa-tients who are not using beta-blocking drugs and who require urgent or emergent oper-ation.

Additional plaque stability effects accrue to patients from the use of drugs such as statins and aspirin. Several trials have shown protection against perioperative cardiac events, and both short- and long-term mortality with the use of statins. Sustained re-lease preparations are preferred because intravenous statin preparations are not avail-able. As with beta-blocking drugs, therapy should not be withdrawn postoperatively, and patients who are chronically using statins should have these continued in the post-operative period. Low-dose aspirin has also been shown to be protective against both short- and long-term cardiac events and death.

Because of data suggesting benefit in terms of reduction of perioperative cardiac events for high-risk patients from statins and from beta-blocking drugs, it is useful to determine whether using the drugs in combination would be helpful. This issue is ad-dressed in a study by Dunkelgrun and coauthors13 in Annals of Surgery, 2009. This arti-cle concerns a randomized prospective trial of beta blockade using bisoprolol compared with the use of a statin drug (fluvastatin) alone, a combination of the two drugs, or nei-ther drug. The patients were deemed intermediate risk (cardiac event risk of up to 6%). The authors noted that cardiac event rates were significantly reduced in patients re-ceiving beta blockade with or without the statin drug. A lesser reduction (nonsignifi-cant) was seen with the statin drug alone. Although this study does not support the ad-dition of statin drugs to beta blockade as a means of gaining additional control of car-diac event risk, the study is limited because of the small number of enrolled patients.

From the perspective of the editor, there is convincing evidence to support careful preoperative cardiac risk assessment. Furthermore, it is expected that an increasing number of patients will present for operation already taking beta-blocking drugs, statins, or both. In this case, drug therapy with both drugs should be continued during and after the perioperative period with dose and type of drug adjusted to make certain that full effects of both drugs are maintained. For intermediate-risk patients undergoing high-risk operations (abdominal or thoracic vascular procedures) and for high-risk pa-tients, beta-blocking drug therapy, at least, should be implemented and dosage adjusted progressively during the preoperative interval to obtain a resting heart rate in the 55-

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65 bpm range. Therapy should continue into the postoperative recovery period. Other adjuncts, such as regional anesthesia/analgesia, aspirin therapy, and statin therapy might be useful.

Perioperative myocardial infarctionIn the foregoing discussion, emphasis was placed on the vulnerability of coronary

artery plaque and the hazard of plaque rupture with thrombosis of the coronary artery as the proximate cause of perioperative myocardial infarction. The significant, and in-creasing, prevalence of coronary artery disease in surgery patients is a reminder to sur-geons that this problem is a continuing challenge. Increased resource consumption from postoperative myocardial infarction is significant. In a 2006 report by Mackey and coauthors,14 results from a prospective analysis of 236 patients deemed at high risk showed significant incremental increases in both hospital and ICU lengths of stay when vascular surgery patients developed a perioperative myocardial infarction. Periopera-tive myocardial infarction was a marker for long-term use of healthcare resources as well.

Nearly one-quarter of the study patients discharged alive returned to the emergency department for care during the year after discharge. Frequently, postoperative myocar-dial infarction occurs without chest pain. Nonspecific signs such as hypotension, dysp-nea, arrhythmia, onset of new cardiac murmur, and alterations in the level of conscious-ness might be the only clinical symptoms. Electrocardiographic diagnosis and labora-tory diagnosis using serum markers such as troponin might yield nonspecific results. The typical electrocardiographic findings of spontaneous myocardial infarction include the appearance of Q waves, ST-segment elevation, and T-wave inversion. In contrast, postoperative myocardial infarction is associated with intervals, occasionally pro-longed, of ST-segment depression indicating subendocardial ischemia. Increasingly, echocardiographic cardiac imaging is used to obtain diagnostic information. Features of the pathophysiology, diagnosis, and management of perioperative myocardial infarc-tion will be discussed.

Pathophysiology of myocardial infarctionThe first article discussed is by Burke and Virmani15 entitled “Pathophysiology of

myocardial infarction.” The review appeared in Medical Clinics of North America in 2007. The authors begin by noting that 80% of spontaneous myocardial infarctions are caused by thrombosis of coronary arteries critically narrowed by atherosclerotic plaque. Unusual causes of myocardial infarction are coronary embolization, coronary spasm, and thromboses of nondiseased coronary arteries. Concentric subendocardial necrosis that might result from prolonged global ischemia from cardiac arrest can also lead to coronary artery thrombosis. Myocardial ischemia results in acute pallor of the myocardium, visible grossly within 12 hours of the onset of ischemia. Tetrazolium salt

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staining of the myocardium can detect myocardial necrosis within 2-3 hours of the on-set of ischemia. After 5-7 days, the infarcted area is soft with a hyperemic border. If reperfusion occurs, the infarcted area might be reddened from trapped red blood cells. Healing of a myocardial infarction takes from 4 weeks to 3 months and the lesion evolves into a white scar, which might be the source of rhythm disturbances. Histologic findings begin with the development of tissue eosinophilia followed by typical inflam-matory changes, followed by fibrosis and scarring. Infarctions that involve more than 50% of the myocardial wall thickness are termed transmural and these produce Q-wave changes in the electrocardiogram.

In humans, reperfusion of ischemic myocardium within 4-6 hours of the onset of is-chemia results in myocardial salvage. In this circumstance, the ischemic area remains subendocardial and transmural extension does not occur.

Myocardial energy metabolism depends upon the oxidation of free fatty acids to produce ATP. Ischemia causes an immediate shift to anaerobic glycolysis. Exhaustion of ATP supply leads to inhibition of Na/K ATPase with breakdown of cell membrane de-fenses and influx of sodium and chloride into the myocardial cell. Increases in cytosolic calcium and cellular acidosis lead to myocyte contractile dysfunction. Cell death can re-sult from necrosis, oncosis, apoptosis, or autophagy. Because apoptosis is an energy consuming function, this occurs in perfused myocardium surrounding the necrotic area. Autophagic cell death also requires energy and occurs in a manner that is independent of the caspase-mediated pathway leading to apoptosis.

Infarct size is determined by the extent and efficiency of coronary collateral circula-tion. Well-developed coronary collaterals are present in approximately 40% of adult men and these individuals are resistant to the development of transmural infarctions. Rather, coronary atherosclerosis in these patients produces anginal pain. In patients with well-developed collateral circulation, another means of myocardial protection is ischemic preconditioning. Ischemic preconditioning is the term applied to the phenom-enon of preservation of myocyte energy-producing capability after an ischemic event preceded by a short interval (10 minutes) of ischemia followed by reperfusion. Potas-sium-ATP channels play a central role in ischemic preconditioning. Blockage of these channels prevents the protective effect of ischemic preconditioning. Interestingly, car-diac myocyte protection can be induced by ischemic events in distant tissue sites. This phenomenon is known as remote ischemic preconditioning.

A review of the potential for remote ischemic preconditioning to produce cardiac myocyte protection comes from an article by Walsh and coauthors16 in the Journal of Vascular Surgery, 2009. These authors report that myocyte protection has been pro-duced after the production of ischemia to kidney, intestine, and skeletal muscle. Preop-

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erative tourniquet ischemia of an upper extremity was associated with reduced risk for postoperative cardiac events in patients undergoing coronary artery bypass grafting. These authors report results of ischemic preconditioning in randomized analysis in-volving 82 patients undergoing open abdominal aortic aneurysm repair. Ten minutes of ischemia to each leg was produced by clamping the iliac arteries individually. Thirteen of the 42 control patients developed clinically significant perioperative myocardial is-chemia. Only two of the 40 patients who had ischemic preconditioning developed my-ocardial ischemic events. Because this study was conducted in patients who had under-gone maximum preoperative preparation with beta-blocking drugs, the results suggest there might be incremental protection because of ischemic preconditioning; this tech-nique should be further evaluated.

Burke and Virmani15 assert that plaque instability universally preceded coronary thrombosis. Seventy-five percent of coronary thromboses are the result of plaque rup-ture and the remaining 25% result from plaque erosion. The left anterior descending coronary artery is the most frequent site of thrombosis, followed by the right coronary artery and the left circumflex coronary artery. Arrhythmias and contractile dysfunction in myocardium distal to a thrombosis might be aggravated by post-thrombosis mi-croembolization. Complications of myocardial infarction include cardiac rupture, ven-tricular aneurysm, mural thrombus with embolization, mitral valve insufficiency from papillary muscle rupture, and pericardial effusion.

Additional information on complications of myocardial infarction is in a review by Wilansky and coauthors17 in Critical Care Medicine in 2007. These authors provide short descriptions of clinical characteristics of the most important complications of myocar-dial infarction. Left ventricular free wall rupture, a frequently lethal complication of my-ocardial infarction, traditionally has afflicted up to 6% of patients sustaining myocardial infarction. With the onset of rapid reperfusion protocols and angioplasty, the frequency of this complication has dropped to 1%. Nonetheless, up to 17% of the deaths from my-ocardial infarction result from ventricular free wall rupture. This complication occurs within the first week after infarction with nearly half occurring during the first 24 hours. Older age, male gender, first infarction, single vessel disease, lack of ventricular hypertrophy, transmural infarction and anterior location of the infarction are all risk factors for left ventricular free wall rupture. This condition can result in acute hemopericardium and pericardial tamponade.

Approximately one-third of patients with free wall rupture present with a more sub-acute clinical picture characterized by persistent chest pain, right heart failure, and hemodynamic deterioration. Electrocardiogram findings are nonspecific. Echocardiog-raphy might show pericardial effusion. As noted in the article by Burke and Vimani,15 approximately 25% of myocardial infarction patients will have nonspecific pericardial

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effusion, and this will make diagnosis of cardiac rupture difficult. Doppler imaging or contrast echocardiography might be needed to show pericardial blood clot or the rup-ture site. Surgical repair of the rupture will be required. Some patients might be amenable to stabilization with fluids, pressors, and/or intraaortic balloon pump.

A variant of cardiac rupture is ventricular septal rupture. Older age, female gender, hypertension, absence of a smoking history, and anterior infarction location are risk factors for septal rupture. Clinically, this complication presents with hemodynamic col-lapse in the presence of a new systolic murmur. Diagnosis is established with echocar-diography. Surgical revascularization and septal repair are therapies of choice.

Left ventricular outflow tract obstruction from severe systolic anterior motion of the mitral valve is an unusual complication of myocardial infarction. The clinical pre-sentation is one of a new systolic murmur and refractory hypotension in the setting of an apical infarction. Echocardiography can confirm the diagnosis. Therapy includes vol-ume expansion, beta-blocking drugs to reduce hyperdynamic contraction of the heart, and alpha agonists to support blood pressure.

Mitral regurgitation might complicate myocardial infarction because of ischemia of the valve or from papillary muscle rupture. Ischemic mitral regurgitation might be clini-cally silent and evidenced only by the presence of a cardiac murmur. Transesophageal echocardiography is the mainstay of diagnosis. Management varies according to the clinical status of the patient and the hemodynamic effects of the valvular dysfunction. Papillary muscle rupture is a critical care emergency with acute pulmonary edema and cardiogenic shock commonly present. A loud systolic murmur is present. Immediate management includes support of cardiac function with afterload reduction and the use of an intraaortic balloon pump. Transesophageal echocardiography provides accurate delineation of the valvular anatomy and the extent of dysfunction. Surgical management of the mitral regurgitation and critical coronary stenoses is associated with significant operative mortality (25%-40%), but survivors have good quality of life in long-term fol-lowup.

Diagnosis and management of postoperative myocardial infarctionTraditionally, the diagnosis of myocardial infarction is made based on the presence

of typical chest pain, electrocardiographic evidence of ischemia (ST-segment elevation, presence of Q waves), and elevation of biomarkers such as troponin. As noted previ-ously, perioperative myocardial infarction might be clinically silent. Chest pain might be absent because patients are receiving analgesics, are sedated for mechanical ventila-tion, or are emerging from general anesthesia. Troponin levels might be elevated in surgery patients in the absence of myocardial infarction, but persistent elevations of troponin > 3, especially combined with ST segment depression intervals of > 60 min on

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electrocardiographic monitoring, predict an increased risk of myocardial infarction and mortality.

An article evaluating diagnostic accuracy of the electrocardiogram in critically ill pa-tients by Lim and coauthors appeared 18 in Critical Care Medicine, 2006. These authors determined intra- and inter-rater reliability for electrocardiogram interpretation in pa-tients at high risk for myocardial infarction in a single ICU. The authors reaffirm the dif-ficulties in detecting clinical symptoms of myocardial ischemia. Interpreting troponin levels in patients recovering from noncardiac operations and in patients who are criti-cally ill is also challenging. Lim and colleagues state that the lack of reliability of tro-ponin measurements has led to increased emphasis on electrocardiographic changes as a means of confirming the diagnosis of myocardial infarction. This study was an analy-sis by two observers of all electrocardiograms obtained on patients at risk for myocar-dial infarction in a single ICU during two months.

The changes sought as evidence of myocardial infarction were those recommended by the European Society of Cardiology/American College of Cardiology diagnostic crite-ria. The findings included pathologic Q waves, ST-segment elevation in at least two con-tiguous leads, ST-segment depression in at least two contiguous leads, symmetric inver-sion of T-waves (> 1mm) in at least two contiguous leads, T-wave flattening, and new onset left bundle branch block. The last criterion was chosen because left bundle branch block could obscure ST-segment elevation. The analysis of rater performance indicated that intra-rater and inter-rater reliability was poor when the raters had no knowledge of the serum troponin level. The raters were more likely to diagnose accurately electro-cardiographic signs of myocardial infarction if they knew that there was a significant el-evation of the serum troponin level. Electrocardiographic abnormalities most often identified accurately were T-wave inversion, Q-waves, and left bundle branch block. These authors conclude that accurate diagnosis of myocardial infarction in critically ill patients (who have physiologic similarities to postoperative patients) are facilitated us-ing a synthesis of clinical information that includes the electrocardiogram, troponin lev-els, and, possibly, echocardiographic imaging.

In an editorial by Engel19 that accompanies Lim’s article, the difficulty in arriving at an accurate diagnosis of myocardial infarction is reemphasized. Engel agrees that use of the electrocardiogram as the principle means of diagnosis of myocardial infarction in postoperative or critically ill patients is hazardous. Furthermore, choosing interven-tional therapy in this patient subgroup is challenging because thrombolysis, coronary angiography, and percutaneous coronary interventions requiring antiplatelet therapy might not be safe.

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Management of the patient who has had a perioperative myocardial infarction is based on providing support for the patient’s heart function while planning for appropri-ate means of revascularization. Support from cardiologists and cardiothoracic surgeons will be needed to facilitate these decisions. Cardiogenic shock is the most common lethal complication of perioperative myocardial infarction. Management of this condi-tion is discussed in detail in the next issue of SRGS.

Perioperative cardiac arrhythmiaIn an earlier portion of this overview, we noted the association of postoperative in-

flammation, postoperative tachycardia, and postoperative atrial fibrillation with cardiac morbidity. In patients at high risk for perioperative cardiac events, control of heart rate and rapid diagnosis and therapy for treatable tachycardias are important for preven-tion of cardiac complications. The most common treatable tachycardias encountered in postoperative patients are supraventricular tachycardias and atrial flutter/fibrillation. In this section of the overview, we review pertinent features of the diagnosis and man-agement of these cardiac rhythm disorders.

Management of supraventricular tachycardia and atrial fibrillationSupraventricular tachycardia is the subject of a review by Fox and coauthors20 in

Mayo Clinic Proceedings, 2008. A full-text reprint of this article is included with this is-sue of SRGS. The authors provide a working definition of supraventricular tachycardia that includes all tachycardias arising cephalad to the bifurcation of the His bundle and all tachycardias dependent on the His bundle for impulse transmission. These tachycar-dias usually have rates exceeding 100 bpm (unless atrioventricular conduction block is present), and QRS morphology is usually normal. In the presence of bundle branch block, however, QRS complexes might be widened or otherwise abnormal in shape. Data from long-term ambulatory electrocardiographic monitoring have permitted esti-mates of the incidence of supraventricular tachycardia. The authors cite data that dis-close an incidence of 76% in a group of elderly patients with a 20% incidence of symp-tomatic coronary artery disease. In studies of asymptomatic healthy patients aged 18-65 years, the incidence ranged from 12-18%.

Supraventricular tachycardia is usually of sudden onset and might spontaneously terminate. The patient might complain of chest pain, and syncope occasionally occurs (usually in very rapid tachycardias associated with reductions in cardiac output). Al-though no clear association between chest pain during a tachycardia episode and coro-nary artery disease has been established, the diagnosis might be suspected in elderly patients with tachycardia and chest pain. Patients usually complain of palpitations; pa-tients with chronic heart failure might not sense the palpitations but, instead, present with cardiac decompensation. The catecholamine response stimulated by tachycardia and hypotension serves to perpetuate the rhythm disturbance.

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These authors note that atrioventricular nodal re-entry, atypical atrioventricular nodal re-entry, or atrial tachycardias are the usual mechanisms of these rhythm distur-bances. Atrioventricular node dependent tachycardias are usually terminated by induc-ing atrioventricular nodal block with a vagal stimulating maneuver (Valsalva, carotid si-nus massage, or immersion of the face in cold water), or pharmacologically. Atrioven-tricular node independent rhythms include atrial flutter and atrial fibrillation.

Diagnosis of tachycardia is usually possible using a 12 lead electrocardiogram, which is preferred over a rhythm strip. QRS morphology is usually normal with QRS du-ration of 90 milliseconds or less. QRS complexes might be abnormal if there is intermit-tent or permanent bundle branch block. Other factors to be considered in interpreting the electrocardiogram are the heart rate, mode of onset and termination of the tachy-cardia, relative position of the P-wave within the RR interval, and morphology of the P wave. The tachycardia rate is usually higher than 100 bpm and can be variable. A steady rate of 150 bpm suggests atrial flutter with a 2:1 atrioventricular block, according to Fox and associates.

Another means of determining the type of tachycardia is by examining the relation-ship of the P wave to the preceding and subsequent R wave. When the distance between the R wave and the next P wave is longer than the subsequent PR interval, the tachycar-dia is a “long RP” rhythm. If the distance between the R wave and the subsequent P wave is shorter than the subsequent PR interval, the rhythm is termed “short RP.” Long RP tachycardias are atrial and might progress to flutter or fibrillation. Supraventricular tachycardias, according to these authors, are mainly short RP rhythms. At very rapid heart rates, RP and PR intervals become very short and might be difficult to interpret.

Management of supraventricular tachycardia is usually straightforward because the patients are usually hemodynamically stable. If there is instability, the patient is man-aged according to the typical ABC approach emphasizing airway, breathing, and circula-tion. Vagal maneuvers such as carotid sinus massage might terminate the rhythm promptly and these maneuvers are ineffective in atrial flutter/fibrillation. Carotid sinus massage should not be done if there is a carotid bruit present. Pharmacologic manage-ment of supraventricular tachycardia is accomplished using adenosine, calcium channel blockers, or -blocking drugs. Adenosine is the first-line drug and is given in 6 mg or 12 βmg boluses. Smaller doses are used in patients taking dipyridamole.

Broadening of the QRS complex might occur in supraventricular tachycardia if there is bundle branch block. Fox and colleagues caution that if the patient is older than 70 years or there is a history of symptomatic coronary artery disease, a broad QRS tachy-cardia should be considered a ventricular tachycardia until proved otherwise. An article discussing the use of response to adenosine bolus therapy as a means of differentiating

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supraventricular from ventricular tachycardia when wide QRS tachycardia comes from Critical Care Medicine, 2009, by Marill and coauthors.21 The authors note that differenti-ation of atrial from ventricular tachycardia when the heart rate is steady and the QRS complex is widened is important, but current algorithms are neither sensitive nor spe-cific in identifying the type of rhythm present. Drug therapy using procainamide or amiodarone might effectively treat the rhythm but side effects such as hypotension limit the usefulness of these agents. Electrical cardioversion is effective but is painful, does not protect against recurrence of the rhythm, and offers little diagnostic informa-tion.

These authors hypothesize that adenosine will safely terminate most supraventricu-lar tachycardias, will slow heart rate enough to allow detection of atrial flutter or fibril-lation, and will be not predictably alter ventricular tachycardia. In a 15-year interval, these authors treated 197 patients with steady-rate wide QRS complex tachycardia with a 12 mg bolus of adenosine. Patients determined to have ventricular tachycardia were older, more often had a history of myocardial infarction and prior episodes of ventricu-lar tachycardia. Two of 81 patients with ventricular tachycardia responded to adeno-sine while 104 of 116 patients with nonventricular tachycardia responded to adeno-sine. There were no serious adverse events (defined as emergent drug therapy or elec-trical shock) observed in either subgroup. These authors concluded that nonresponse to adenosine was the only factor that diagnosed ventricular tachycardia with a high sen-sitivity and specificity.

The nondihydropyridine group of calcium channel blockers (verapamil and dilti-azem) are alternative drugs used to terminate supraventricular tachycardia. A sum-mary of the data supporting these drugs in comparison to adenosine, by Anugwom and coauthors22 appeared in American Family Physician, 2007. These authors reviewed data from eight studies involving nearly 600 patients. The data disclose that adenosine and calcium channel blockers are equivalently effective in terminating paroxysmal supraventricular tachycardias. Transient, minor side effects such as flushing, nausea, and headache are common with adenosine. Severe side effects (cardiac arrest and hy-potension) were observed only in patients treated with calcium channel blockers. These authors note that the American Heart Association guidelines recommend adenosine as first-line therapy for paroxysmal supraventricular tachycardia because of the low risk of severe side effects, the rapid onset of action, and the short half-life of the drug. The advanced cardiac life support course also recommends adenosine for the management of supraventricular tachycardia.

Of the atrial arrhythmias, atrial fibrillation is the most commonly encountered. A discussion of the management of acute atrial fibrillation is in an article by Siu and coau-thors23 in Critical Care Medicine, 2009. These authors report a randomized, nonblinded

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trial comparing the effectiveness of diltiazem, digoxin, and amiodarone for rate control and symptom improvement in patients presenting acutely with symptomatic, new-on-set atrial fibrillation. The authors note that atrial fibrillation is a common arrhythmia and the frequency of this condition is increasing. Traditionally, two approaches have been used to manage atrial fibrillation, rhythm control and rate control. Rhythm control approaches use direct current cardioversion; this modality might not be available on a 24/7 basis.

Guidelines published from the American Heart Association recommend emergency direct current cardioversion only for patients with acute atrial fibrillation who are hemodynamically unstable. Direct current cardioversion might require that the patient be anticoagulated, especially if there is atrial enlargement. This fact limits application of this modality to postoperative patients. The authors analyzed results in 166 patients. Patients were excluded from the study if they were unstable, had evidence of sympto-matic coronary artery disease, were hypotensive, had an implanted defibrillator, had a history of recent myocardial infarction, had a history of heart failure, or had angina pec-toris. Drug therapies used were diltiazem, digoxin, and amiodarone. The endpoints ex-amined were control of heart rate (heart rate < 90 bpm, sustained, at 24 hours after ini-tiation of therapy) and improvement of symptoms. In this study, rate control and symp-tom improvement was best achieved with diltiazem. There was only one adverse event recorded, an episode of phlebitis at the injection site, in one of the patients receiving amiodarone.

In an editorial by Karth24 that accompanies Siu’s article, the editorialist stresses that these data, though valuable and convincing, were obtained in relatively healthy patients and, because of this, the data might not be directly applicable to typical postoperative patients since surgical patients are increasingly presenting with significant comorbid conditions. Nonetheless, there is sufficient reason, based on the data reported by Siu, to consider diltiazem as initial therapy in patients with acute, new-onset atrial fibrillation when rhythm control strategies are not appropriate.

In surgery patients, prevention of postoperative atrial fibrillation would be desir-able if risk for the development of this arrhythmia could be quantified, and if safe, phar-macologic prevention strategies were available. A prevention strategy is discussed in a report by Zebis and coauthors25 in Annals of Thoracic Surgery, 2007. These authors re-port a randomized, placebo controlled, double blind trial comparing amiodarone with placebo in a group of patients undergoing coronary artery bypass (a known high-risk group for the development of postoperative atrial fibrillation). These authors noted a 14% absolute risk reduction for patients treated prophylactically with amiodarone. Of the patients in the placebo group who developed atrial fibrillation, more than 80% were symptomatic; just over 40% of the patients in the amiodarone group who developed

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atrial fibrillation were symptomatic. While these data have limited application to typical general surgery patients, a preventive strategy might be considered in patients who have previously undergone cardioversion for atrial fibrillation if antiarrhythmia drugs are not already being used.

Management of surgical patients with disorders of the cardiac conduction systemA single review article is discussed in this section of the overview by Allen26 from

Anaesthesia in 2006. The article is entitled “Pacemakers and implantable cardioverter defibrillators” and a full-text reprint of this article is provided with this issue of SRGS. The author opens the discussion noting that pacemaker implantation is increasing with increasing age of the surgery patient population. Likewise, the number of implanted cardioverter defibrillators is increasing. Patients who have these devices are elderly with histories of significant symptomatic heart disease.

The author notes that modern pacemakers work by delivering, via an intracardiac electrode, a low-voltage impulse to cardiac muscle. Devices in current use are capable of detecting the intrinsic electrical signals within the heart so that the devices deliver pac-ing impulses only when they are needed. Improvement in pacing lead design has led to “active fixation” leads that ensure optimum contact with the endocardial surface of the heart. These leads also are designed to elute steroid medications to minimize inflamma-tion at the contact site.

Battery life has improved so that battery replacement is only necessary once in each 10-year interval. Furthermore, the titanium casing of modern pacemakers is light and protects the device from outside electromagnetic interference so that patients can safely use microwave ovens, electric shavers, and mobile telephones. In addition, mod-ern devices carry electromagnetic interference detection software that offers additional protection. For patients who undergo surgical procedures, the most common form of electromagnetic interference comes from use of electrical coagulation devices. Bipolar diathermy is preferred when the patient has an implanted cardiac device. If monopolar diathermy use is unavoidable, the contact plate should be placed as far away from the pacemaker as possible. Advice from the clinician who implanted the pacemaker can be sought to reprogram the device if necessary. Reprogramming ideally occurs just before beginning the procedure. Ideally, the physician who inserted the pacemaker would re-main in the area until the procedure is completed.

While earlier devices paced the ventricle alone, current devices offer dual-channel pacing which improves cardiac output by taking advantage of atrial systolic contraction. Allen emphasizes data that have documented reductions in risk for mitral and tricuspid regurgitation and reductions in frequency of heart failure and chronic atrial fibrillation with dual-chamber pacing.

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Allen goes on to provide information on the various pacing modes of current pace-maker devices. More than three-quarters of currently used pacemakers are rate-sensing so that pacing current is supplied only when heart rates fall below a preselected level. More than half of currently implanted devices are dual-chamber pacing devices. Cur-rently, rate-sensing pacemakers adjust current output based on surrogates for in-creased physical activity such as body movement and respiratory excursion. Ideally, rate-sensing devices would assess catecholamine levels or autonomic activity. Such sen-sors are under development but, as of 2006, were not available. Pacemaker rate sensors can sometimes interpret signals from intraoperative monitoring devices (such as respi-ratory rate monitors that determine thoracic impedance) as body movement. This re-sults in rapid pacing.

In patients with chronic heart failure, multiple sites within the cardiac chambers are paced; this is termed cardiac resynchronization therapy. In these devices, impulse de-livery to both ventricles in multiple sites can be timed to maximize cardiac output. Im-planted cardioverter defibrillators are equipped with complex algorithm software that tailors a response to a detected dangerous ventricular rhythm. Rate, beat-to-beat varia-tion, atrial activity, and QRS morphology can be detected by the software and electrical shocks are delivered based on the rhythm detected. All implantable cardiac convertor defibrillators have pacemaker capability. These devices are not generally sensitive to external electromagnetic interference, but it will be wise to obtain advice from the clini-cian who implanted the device about any precautions anticipated during anesthesia and surgery.

Cardiac failure in the surgical patientCardiac failure is an extremely common medical problem. More than 1 million hos-

pitalizations annually in the United States are for cardiac failure; there is a 50% likeli-hood of death or recurrence of cardiac failure during the six months subsequent to a hospital admission. Cardiac failure will develop in up to one-third of patients with symptomatic ischemic cardiac disease; this condition will develop in 15% of diabetics and 10% of patients with hypertension. While it is unlikely that surgeons will be in-volved in the first-line management of patients with acutely decompensated cardiac failure, surgeons will be called to assist in the care of patients with heart failure who de-velop conditions requiring elective or urgent surgical conditions. It is important that surgeons understand the fundamentals of disordered cardiac function characteristic of the various forms of heart failure, and the pharmacology and side effects of the various therapies employed in these patients. This set of topics is reviewed in this section of the overview.

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Systolic cardiac failureThe first article reviewed by Chatterjee and Rame27 appears in Critical Care

Medicine, 2008, entitled “Systolic heart failure: chronic and acute syndromes.” The au-thors define systolic cardiac failure as inadequate function of the heart as a pump mani-fest by reduced ejection fraction. The condition most often emerges in patients with di-abetes, hypertension, or ischemic heart disease. Systolic heart failure might also be en-countered in patients with dilated cardiomyopathy from other conditions such as my-ocarditis. Systolic cardiac failure results from a process termed “ventricular remod-elling.” The ventricles take on a more globular shape and chamber size increases. Al-though ventricular muscle mass increases, chamber size increases results in an in-creased chamber/ventricular wall ratio. The alteration in the chamber/ventricular wall ratio results in increased ventricular wall stress; the result of these changes is an in-crease in end diastolic and end systolic chamber volumes, resulting in diminished ejec-tion fraction.

Chatterjee and Rame emphasize the importance or neurohumoral activation as the process required for progression of systolic cardiac failure. Adrenergic, renin-an-giotensin, and aldosterone systems are all activated and the degree of activation is lin-early related to severity of symptoms and outcome. In the cardiac myocyte, results of neurohumoral activation are hypertrophy, apoptosis, necrosis, and fibrosis. There is ev-idence of increased oxidative stress that produces additional cytotoxicity. Increases in peripheral vascular resistance, ventricular filling pressures, and arterial stiffness are also results of neurohumoral activation, and these features contribute to cardiac failure progression.

Additional insight into the complex metabolic processes that influence the severity and progression of heart failure is from an article by Ashrafian and coauthors28 in Circu-lation, 2007. These authors open their discussion with a description of myocardial en-ergy metabolism and the balances necessary for efficient energy use. They point out that daily myocardial ATP turnover is much greater than the myocardial ATP pool, and normal myocardial energy metabolism extracts only 25% of available substrate. Be-cause of these facts, subtle changes in the efficiency of myocardial energy metabolism have far-reaching implications for cellular energy levels. One of the most important ar-eas of study has been altered myocardial carbohydrate metabolism and the related state of myocardial insulin resistance. At the cellular level, as insulin concentrations vary, an attenuated glucose response results. These authors cite research data that demonstrate a steadily increasing risk of heart failure with age in diabetic patients. There is also an increasing risk of heart failure as hemoglobin A1c levels increase. Per-sistent hyperglycemia predicts increased risk for the development of heart failure and for heart-failure-related hospitalizations. They refer to additional evidence supporting a linkage between myocardial insulin resistance and the subsequent development of car-

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diac failure. Neurohumoral disorders characteristic of cardiac failure also facilitate the development of hyperglycemia. Persistent inflammation, demonstrable in patients with cardiac failure, contributes to hyperglycemia and myocardial insulin resistance.

The aggregate result of the metabolic dysfunctions noted in cardiac failure is a heart that is energy deficient. Because the heart must produce ATP in amounts many times the weight of the heart, energy deficiency becomes a major factor in the onset and pro-gression of heart failure. In addition, heart failure is associated with major reductions (approximating 70%) in phosphocreatine, the “energy reserve” of the heart.

Implications for management of cardiac failure emphasize control of the neurohu-moral dysfunction concurrently with optimization of glucose levels as a means of com-bating insulin resistance. Ashrafian and associates discuss several new pharmacologic agents that have the potential to improve myocardial energetics in cardiac failure pa-tients.

Patients with Type 2 diabetes and the metabolic syndrome are at increased risk for the development of cardiac failure. Management of this patient group is challenging be-cause the two mainstays of diabetic therapy for Type 2 diabetes, the biguanides (met-formin) and the thiazolidinediones (rosiglitazone) are currently contraindicated in pa-tients with clinical evidence of cardiac failure. Several classes of diabetic drugs are available as adjuncts to conventional neurohumoral modulating agents in this patient group. This topic is reviewed in detail in an article by Masoudi and Inzucchi.29 Inter-ested readers are encouraged to review this article.

Anemia is an additional condition frequently observed in patients with cardiac fail-ure. A discussion of this topic comes from an article by Mitchell30 in the American Jour-nal of Cardiology, 2007. The author notes that anemia is present, overall, in 33% of heart failure patients and the proportion of patients who are judged to be anemic (he-moglobin level < 12 gm/dL) increases with increasing severity of heart failure. New York Heart Association Class IV patients have a 76% prevalence of anemia. The causes of anemia are complex, with contributions from impaired erythropoietin synthesis and utilization, hemodilution, impaired iron and vitamin B12 absorption, and persistent gas-trointestinal bleeding in patients who take aspirin.

Anemia, like other disease features, is associated with increased levels of proinflam-matory mediators and oxidative stress factors. Anemia is known to be an independent driver for increased rates of heart failure hospitalization and death. Mitchell cites sev-eral confirming data sources. Mortality risk is particularly high when anemia and renal insufficiency coexist. Because ischemic cardiac disease is an important precursor of car-diac failure, assessment of this patient group for anemia has been carried out by several investigators cited by Mitchell. Data disclose an association of anemia with the onset

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and progression of ischemic cardiac disease. Anemia might lead to increased cardiac output that contributes to imbalances of myocardial energy availability/utilization that contribute to progression of cardiac failure.

Mitchell notes that elevation of hemoglobin levels is associated with improved left ventricular ejection fraction and improved quality of life indices. Elevation of hemoglo-bin levels with erythropoietin analogues and iron is desirable. Red blood cell transfu-sion has lowered short-term mortality in a small group of elderly patients but it is not clear, according to this author, whether the benefit of transfusion outweighs the risks. Additional information on this topic is in an article by Gerber31 in Critical Care Medicine, 2008. The focus of this article is the use of transfusion in patients with ischemic cardiac disease. It is likely, however, that many of the basic findings pertinent to the ischemic cardiac disease patient will also be appropriately applied to patients with cardiac fail-ure.

The author begins by reviewing the complications of transfusion with acute compli-cations such as transfusion reaction and transfusion-related lung injury (this topic is discussed in more detail later in the overview), and the medium term complication of blood-borne disease transmission. Because there are significant risks to transfusion, the decision to use transfusion must depend on an assessment of the extent to which oxy-gen availability to cells will be increased by raising the number of red blood cells with transfused cells and documentation of improved outcomes in anemic heart disease pa-tients who receive transfusions. Gerber notes that the average storage age of transfused red blood cells is 17 days. Currently, stored red cells have lost 2,3 diphosphoglycerate and the p50 of the cells has changed so that cellular affinity for oxygen is increased and the ability to offload oxygen from transfused red cells to tissue is reduced. Structural changes in red cells have also occurred and the cells have become stiff so that passage into and through the microcirculation is impaired. Although measured oxygen content of blood might increase following transfusion of stored red cells, increased cellular oxy-gen availability is by no means assured.

Data from studies of septic patients and patients in septic shock, cited by Gerber, suggest that cellular oxygen delivery is not increased by red blood cell transfusion. Ger-ber then reviews several studies where outcomes have been analyzed in anemic heart disease patients who have been transfused. Only one study has shown improved out-comes, and the improvement was observed only in elderly patients with admission hematocrits < 33%. In all the other studies there was no improvement, with several studies suggesting worse outcomes in transfused patients. He concludes by stressing that there is no convincing evidence to support the routine use of transfusion to im-prove outcomes in anemic patients with cardiac disease.

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Diastolic cardiac failureApproximately 50% of patients with acute symptoms of cardiac failure, manifest as

dyspnea with radiologic signs of pulmonary edema, have preserved left ventricular ejection fraction, according to data presented in an article by Kumar and coauthors32 in Critical Care Medicine, 2008. Patients with this form of cardiac failure are often elderly, female, and less likely to be African American than are patients with other forms of car-diac failure. The clinical presentation in many patients consists of signs of acute pul-monary edema associated with elevated systolic blood pressure. Because echocardio-graphic imaging that documents maintenance of left ventricular ejection fraction is per-formed, in many patients, after treatment for heart failure has begun, the suggestion has been made that ejection fractions were depressed at the time of symptom onset and im-proved with treatment. Kumar and associates cite a report of echocardiographic analy-ses performed in patients acutely and after 24 hours of treatment. There was mainte-nance of left ventricular ejection fraction at both time points, suggesting that heart fail-ure occurred in the presence of normal left ventricular ejection fraction.

These authors note that diastolic cardiac failure and pulmonary edema are likely caused when venous return to the right ventricle acutely increases and an increased volume of blood is delivered to the pulmonary circulation. Left ventricular dysfunction creates a situation in which the left ventricle cannot accept the increased blood flow without elevating left atrial pressure. In the setting of elevated left ventricular pressure (especially with a peak late in systole), left ventricular relaxation is impaired. Pul-monary blood volume increases and this overcomes the ability of the pulmonary lym-phatics to remove fluid from the pulmonary interstitium. Pulmonary edema is the re-sult.

Additional data on diastolic cardiac function are found in an article entitled “Left ventricular diastolic function” by Hoit33 in Critical Care Medicine, 2007. Hoit notes that cardiac diastole is the result of processes whereby the heart loses ability to generate contractile force produced by myocyte shortening. The heart returns to a precontractile state in preparation for filling and the subsequent systole. Responsible for this series of events are myocardial relaxation and the pressure/volume properties of the ventricle. Relaxation is an energy-consuming process. Calcium is released from troponin C and actin-myosin cross bridges detach. Calcium is sequestered in the sarcoplasmic reticu-lum and, simultaneously, calcium is extruded from myocyte cytoplasm by active sodium-calcium exchange. Multiple factors influence the left ventricular end diastolic pressure-volume relationship including left ventricular physical properties (stiffness), the efficiency of relaxation, and extrinsic factors such as pericardial restraint and in-trapleural pressure. Echocardiography is a valuable means for quantifying left ventricu-lar diastolic function. Ventricular compliance and left atrial volume can be assessed with echocardiographic imaging. Using Doppler imaging, flow velocities across the mi-

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tral valve and in the pulmonary veins can be measured and the relaxation dynamics of the left ventricle can be determined.

Acute echocardiographic imaging is emerging as an important tool permitting quan-tification of cardiac function and intravascular volume status in patients with suspected myocardial infarction, hypovolemia, or cardiac failure. Features of acute echocardio-graphic evaluation are reviewed in detail in an article by Glassberg and coauthors34 in Critical Care Medicine, 2008. These authors describe the use of Doppler echocardio-graphic imaging to assess preload and afterload. They note that recent data disclose an increased rate of cardiac adverse events in patients with acute cardiac decompensation monitored using pulmonary artery catheters. They further note that Doppler echocar-diography has the capability of providing accurate estimates of cardiac output, right atrial pressure, pulmonary artery mean, systolic, and diastolic pressures as well as left ventricular filling pressure. Echocardiographic imaging might produce clinical informa-tion that is equivalent to the information gained from the pulmonary artery catheter without the risk of central venous catheterization. They conclude that acute echocardio-graphic imaging is an important component of the evaluation of patients with acute hemodynamic instability where cardiac failure is an important part of the differential diagnosis.

Management of heart failure in the surgical patientWhere systolic or diastolic cardiac failure is suspected, the history, physical exami-

nation, and acute echocardiographic imaging are used to establish a diagnosis. Labora-tory studies, including serum assays of brain natriuretic peptide (BNP) or N-terminal pro-brain natriuretic peptide (NT-proBNP) might be helpful in providing additional di-agnostic information. The use of these serum markers is discussed in an article by Om-land35 in Critical Care Medicine, 2008. Omland stresses the value of diagnostic informa-tion that can be gained from serum levels of BNP or NT-proBNP obtained in the emer-gency department or in the ICU when patients present with acute dyspnea. Abnormal BNP or NT-proBNP was 84%-90% accurate diagnosing diastolic cardiac failure as the cause of acute dyspnea in several studies cited by this author. Omland stresses that BNP levels are frequently normal in patients with chronic heart failure. Furthermore, BNP and NT-proBNP levels were not consistently useful as means of assessing progression or improvement of cardiac failure. Data discussed earlier describe the limitations of serum tests in postoperative patients.

Therapy for systolic cardiac failure depends on the clinical presentation. The pres-ence of echocardiographic evidence of increased filling pressures suggests the use of loop diuretics (furosemide) to improve pulmonary congestion, dyspnea, and hypoxia. Significant low cardiac output states in patients with systolic cardiac failure can be treated with afterload reduction using vasodilators. Sublingual nitroglycerin is the first-

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line approach in this regard. With very low cardiac output, short duration inotropic therapy can be considered.

The use of inotropic drugs for systolic cardiac failure is the topic of an article by Pe-tersen and Felker36 in Critical Care Medicine, 2008. These authors emphasize data, which they review in this article, indicating a lack of clinical value of inotropic drugs in patients without clearly documented end-organ hypoperfusion. They further report the clinical challenges in documenting end-organ hypoperfusion. Traditionally, this diagno-sis has been made by documenting worsening renal function. Petersen and Felker note that increases in serum creatinine after the institution of loop diuretic therapy might in-dicate presence of cardiorenal syndrome and not end-organ hypoperfusion. These au-thors note that some patients with very low cardiac output states will maintain normal levels of serum creatinine.

These patients will frequently have nonspecific symptoms such as abdominal pain, nausea, fatigue, and diminished cognitive function. Documentation of low cardiac out-put with echocardiography or pulmonary artery catheter monitoring will likely provide confirmatory evidence. The authors note that documented low cardiac output in pa-tients with systolic heart failure is a marker for increased short-term mortality. If in-otropic therapy is contemplated, dobutamine and milrinone are the first-line drugs. Both drugs produce improvements in cardiac output via augmentation of cellular cyclic AMP. Milrinone has greater vasodilating function than dobutamine and might have lower risk of inciting arrhythmias. Devices useful for supporting cardiac function in-clude the intraaortic balloon pump, left ventricular assist devices, and ultrafiltration de-vices. These devices reliably support cardiac function until definitive therapies using revascularization or transplantation can be organized and implemented. These devices are discussed in a review by Kale and Fang37 in Critical Care Medicine, 2008.

According to Kumar and coauthors,32 treatment of acute pulmonary edema, the main clinical manifestation of diastolic cardiac failure, focuses on improving oxygenation and relieving patient symptoms. Noninvasive ventilation with continuous positive airway pressure is valuable for reversing hypoxia. Early administration of a loop diuretic along with intravenous -blocking drugs will improve pulmonary congestion, lower blood βpressure and heart rate, and relieve patient symptoms. These authors stress that di-uretic-naïve patients might have a very brisk diuresis and, therefore, lower diuretic doses initially might provide a greater margin of safety. Morphine is helpful for reliev-ing symptoms also. Afterload reduction with sublingual nitrate drugs is frequently help-ful.

Perioperative management of diastolic cardiac failure is discussed in a review by Pirrachio and coauthors38 in the British Journal of Anesthesia, 2007, who stress that the

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focus of perioperative management is to choose an anesthetic strategy that will not de-crease left ventricular function. Intravenous agents such as propofol and most muscle relaxants do not affect left ventricular function. Volatile anesthetics such as sevoflurane and desflurane also do not change left ventricular function. These authors stress the im-portance of aggressively controlling the catecholamine response that accompanies op-eration and they recommend preoperative beta blockade supplemented by intravenous short-acting agents such as esmolol for management of hypertension and tachycardia.

Cardiopulmonary resuscitationData on the frequency of out-of-hospital and in-hospital cardiac arrest appear in ar-

ticles by Ramsay and Maxwell,39 Ali and Zafari,40 and Ehlenbach and coauthors.41 The ar-ticles by Ramsay and Maxwell and Ali and Zarari are supplied as full-text reprints with this issue of SRGS. These articles confirm that there are more than 400,000 sudden deaths annually ascribed to cardiac disease resulting in cardiac arrest. Ramsay and Maxwell cite data indicating that there are 165,000 witnessed episodes of out-of-hospi-tal cardiac arrest in the United States each year. In-hospital cardiac arrest occurs at a rate of nearly three events/1000 admissions, according to data cited by Ehlenbach and coauthors. Cardiac arrest is the cause of 5.6% of all deaths annually in the United States, according to data cited in the article by Ali and Zafari. Despite the availability of effec-tive methods of cardiopulmonary resuscitation, mortality for witnessed out-of-hospital and in-hospital cardiac arrest exceeds 80%. All the authors cited note the disappointing statistics indicating that nearly three-quarters of the patients who sustain witnessed cardiac arrest have no attempt at resuscitation made. In this section of the overview, we review several topics pertinent to effective management of witnessed out-of-hospital cardiac arrest and in-hospital cardiac arrest.

History of cardiopulmonary resuscitationRamsay and Maxwell describe a short history of cardiopulmonary resuscitation in

their article from The American Surgeon in 2009. The authors note that descriptions of mouth-to-mouth rescue breathing appear in the Old Testament. In the 14th century, rescue breaths were administered using bellows devices placed intranasally or through a reed inserted into the trachea via an anterior neck incision. During the 18th and 19th centuries, “humane societies” were formed in several European countries to foster the use of artificial respiration techniques for drowning victims. In studies on animals, John Hunter noted that cessation of breathing led to cardiac standstill and immediate re-sumption of breathing led to restoration of cardiac action.

The use of electricity for defibrillation was championed by Wiggers who also sup-ported the use of open cardiac massage. Open massage was used for resuscitation of in-traoperative cardiac arrest by Beck of Johns Hopkins Medical School, and this method of resuscitation was the focus of his research from 1920–1937. Closed chest massage was

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developed at Johns Hopkins and described in a 1960 publication in the Journal of the American Medical Association by Kouwenhoven, Knickerbocker, and surgeon James Jude. Training in techniques of cardiopulmonary resuscitation for emergency medical services personnel and citizen responders was made simpler and more effective by the development of life-like mannequins for intubation and resuscitation by Safar and Laerdal. Currently, national standards for citizen, emergency medical services, and in-hospital cardiopulmonary resuscitation are promulgated by courses sponsored by the American Heart Association (Basic Cardiac Life Support and Advanced Cardiac Life Sup-port).

Current practice and outcomes for cardiopulmonary resuscitationAli and Zafari40 note that sudden cardiac arrest is, in the main, caused by coronary

artery disease. They cite data from autopsy studies indicating that more than 80% of nonsurvivors of cardiac arrest have severe coronary artery disease confirmed by post-mortem examination. Other causes of cardiac arrest are aortic stenosis, Wolf-Parkin-son-White syndrome, cardiomyopathy, and congenital cardiac disease. The presence of a “shockable” (ventricular tachycardia or ventricular fibrillation) rhythm is associated with better outcomes of cardiopulmonary resuscitation. These authors note that these rhythms are being documented less often during cardiopulmonary resuscitation events. Fewer than one-third of patients have a shockable rhythm on initial electrocardio-graphic tracing. Asystole and pulseless electrical activity rhythms are being recorded with increasing frequency.

These authors describe a “four phase” classification of a cardiac arrest event. The “electrical phase” extends from time 0–4 minutes after arrest. The “circulatory phase” extends from 4-10 minutes post arrest. The “metabolic phase” begins at 10 minutes post arrest. During the electrical phase, defibrillation is the most effective therapy if a shockable rhythm is noted. During the circulatory phase, qood-quality cardiac compres-sion is critical. In the metabolic phase, resuscitative efforts focus on reversing the ef-fects of global ischemia. The importance of defibrillation during the electrical phase supports the distribution of automatic defibrillators and the use of these devices by trained citizen rescuers since it is unlikely that trained emergency medical services per-sonnel will arrive on the scene before the late circulatory or metabolic phase of resusci-tation.

Data cited in Table 2 of the article by Ali and Zafari confirm the value of early defib-rillation if a shockable rhythm is discovered within the first five minutes following the arrest event.

Adequate cardiac compressions (optimum rate with optimum excursion) given be-fore defibrillation shock are associated with improved outcomes, according to data

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cited by Ali and Zafari. They also note that optimum cardiac compressions provide coronary perfusion that serves to minimize the depleting affect of ventricular fibrilla-tion on cardiomyocyte energy stores. Rescue breaths (two breaths administered by mouth-to-mouth or mouth-to-airway respiration before instituting cardiac compres-sion) are currently recommended by the American Heart Association, but this is contro-versial and subject to change.

Ramsay and Maxwell39 note that current recommendations urge rescuers to per-form chest compressions with two hands in adults at a rate of 100 compressions/minute with a compression excursion of 4 cm. For patients who have an airway placed, the ratio of compressions/breaths is recommended at 30:2. Mouth-to-mouth and mouth-to-airway “rescue breaths” previously recommended to precede chest compres-sions are now eliminated in many regional protocols recognizing that encouragement to administer mouth-to-mouth breaths is a strong disincentive to provision of any sort of rescue resuscitation. As noted above, in current studies, no resuscitation attempt is made in the majority of witnessed out-of-hospital cardiac arrests. Recent data cited by Ramsay and Maxwell (reference 9 in their bibliography) indicate that chest compres-sions without rescue breaths result in improved outcomes for cardiopulmonary resus-citation in witnessed out-of-hospital cardiac arrest events.

A more favorable neurologic outcome, more frequent occurrence of shockable car-diac rhythm on initial electrocardiogram, and improved overall survival when resusci-tation was begun within four minutes of cardiac arrest were all confirmed in the study cited. These observations have lent support to the primacy of supplying effective chest compressions. Rescue personnel are no longer encouraged to supply a “stack” of three electrical defibrillation shocks when a shockable rhythm (ventricular tachycardia or ventricular fibrillation) is discovered on the initial electrocardiogram. Instead, a single shock is applied and compressions are resumed. In addition, drug administration (in-travenous or endotracheal instillation) is recommended while compressions continue rather than a “drug-breath-shock-compression” cycle. Despite dissemination of this in-formation nationally, data cited by Ramsay and Maxwell indicate an unsatisfactory level of compliance with these guidelines. In a study of in-hospital cardiac arrest, compres-sion rates of less than 100/min were noted in more than 90% of resuscitations (refer-ence 10 in their bibliography). An additional finding of this study was a disturbing fre-quency of “no-flow” intervals (intervals during which there are no compressions). These exceeded 10 seconds/minute of resuscitation events.

Research confirming the critical importance of high-quality chest compressions is from a report by Ristagno and coauthors42 in Chest, 2007. These authors performed a study in pigs; cardiac arrest was produced by ligation of the left anterior descending coronary artery. Chest compressions were begun 5 minutes after onset of cardiac ar-

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rest. “Adequate” chest compression was defined as compression excursion equal to 25% of the anterior-posterior chest diameter (6 cm excursion) and “conventional” chest compression as 4 cm excursion. A single defibrillation shock of 150 joules was delivered before or after compressions began, according to the experimental protocol for each an-imal group; each group consisted of six animals. The data presented indicate that end-tidal PCO2 and coronary perfusion pressures (both variables are related to adequate myocardial and peripheral perfusion) were lower in animals receiving conventional compressions. With optimal chest compressions, fewer shocks were required to restore cardiac rhythm and all animals were resuscitated.

No animals were resuscitated when defibrillation shock preceded conventional compressions. Two of six animals were resuscitated successfully when shocks were ad-ministered after a period of conventional chest compression. This animal study sup-ports current clinical recommendations that stress the importance of adequate chest compressions. Adequacy of chest compression is important whether a “shock first” or “shock after compression” protocol is followed. These data lend support to the urgent need to improve the quality of compressions offered to patients who sustain cardiac ar-rest. These authors cite data that indicate adequacy of chest compressions in less than one-third of cardiopulmonary resuscitation events, and they stress the importance of aggressive educational efforts to improve the quality of chest compressions in car-diopulmonary resuscitation events.

Ramsay and Maxwell go on to discuss methods for ventilating the intubated patient during a cardiac arrest event. The foregoing discussion has noted the recommendation of a breath-to-compression ratio of 30:2. Hyperventilation raises intrathoracic pres-sures with resultant reduction in venous return and depression of compression medi-ated cardiac output. With increased intrathoracic pressure, coronary perfusion is re-duced. If hypocarbia is induced, cerebral vasoconstriction might reduce cerebral oxy-genation. Placement of an impedance threshold device in the ventilation circuit serves to reduce intrathoracic pressure and improve venous return. This device works by re-ducing air entry into the lung during the chest recoil phase that follows a cardiac com-pression. Lowered intrathoracic pressures, improved end-tidal PCO2, and improved coronary perfusion pressures have been documented with the use of this device during experimental and clinical cardiopulmonary resuscitation.

A meta-analysis of research results relevant to the use of the impedance threshold device is reported by Cabrini and coauthors43 in Critical Care Medicine, 2008. These au-thors reviewed data from five high-quality studies involving more than 800 patients. They found that use of the impedance threshold device was associated with significant improvements in return of effective cardiac rhythm, early survival, and early favorable neurologic outcomes with no significant effect noted on long-term survival. The authors

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note that this study focused on data generated from studies of out-of-hospital cardiac arrest. They further note that optimum results in terms of improved venous return to the heart depend on rescuers permitting full recoil of the chest wall by lifting the palms off the chest after each compression. They stress that data they reviewed showed im-proved outcomes even in patients with event-to-compression times of 10 minutes or more. Improvements are also noted in outcomes of patients with unfavorable rhythms such as asystole.

The use of adjunctive drug therapy during cardiopulmonary resuscitation is re-viewed by Ali and Zafari.40 The objective of initial drug therapy is to provide strong -αreceptor agonist capability. Alpha stimulation works to redistribute blood flow to the brain. Epinephrine 1mg intravenously or instilled into the endotracheal tube has been the initial drug for a number of years. Recently, additional pressor activity has been achieved with vasopressin in a dose of 40 international units given intravenously. These authors cite data from studies comparing epinephrine and vasopressin; no difference in survival-to-hospital discharge was noted in either group. A subsequent study showed improved survival in patients receiving both epinephrine and vasopressin. Current rec-ommendations support use of both drugs in combination.

Although epinephrine has been used for many years to improve brain blood flow, research data questions whether this drug results in true increases in brain cellular oxygen delivery. This issue is the topic of a research study by Ristagno and coauthors44 in Critical Care Medicine, 2009. These authors conducted experiments on pigs and note that the sine qua non of successful cardiopulmonary resuscitation is successful recovery of brain function. The alpha-receptor stimulating properties of epinephrine have been thought to facilitate redistribution of blood flow to the brain during cardiopulmonary resuscitation. These authors cite evidence for beta-receptor stimulating activity of nor-epinephrine during experimental shock. This property resulted in failure of the drug to restore appropriate nutrient tissue blood flow.

In these experiments, the authors assessed brain nutrient delivery by measuring mi-crocirculatory blood flow using orthogonal polarization spectral imaging. Tissue carbon dioxide and oxygen tensions were also measured. Ventricular fibrillation was induced and drug therapy administered after three minutes. Animals were divided into groups that received placebo, epinephrine, and epinephrine in the presence of two different forms of alpha and beta receptor blockade. The data disclosed reductions in both brain oxygen tension and microcirculatory blood flow in animals receiving epinephrine. This was accompanied by increased brain tissue carbon dioxide levels. The effect was traced to the alpha stimulatory effects of epinephrine.

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Drug therapy has also been suggested to facilitate the return of effective cardiac rhythm. This topic is also reviewed by Ali and Zafari. Drugs used for this purpose in-clude lidocaine, atropine, and amiodarone. Studies of atropine use have not demon-strated statistically improved survival although there might be improved conversion of slow pulseless electrical activity with atropine use. Lidocaine is currently not recom-mended as a means of improving conversion from ventricular tachycardia and fibrilla-tion to an effective rhythm. Amiodarone is the current drug of choice to assist with rhythm conversion. Concern that the diluent in which amiodarone is delivered (polysorbate 80 and benzoyl alcohol) might be a cause of hypotension has been voiced but data, to date, do not support this as a frequent complication. There is now an aque-ous preparation of amiodarone that can be infused rapidly and this preparation has not shown increased frequencies of hypotension. The current recommended dose of amio-darone is 300 mg. Another drug occasionally used in cardiopulmonary resuscitation is magnesium sulfate. This drug is used in 1-2 gram doses for one specific rhythm, torsade de pointes. This rhythm is a polymorphic ventricular tachycardia associated with a pro-longed QT interval.

Recovery of effective cardiac activity after cardiopulmonary arrest is associated with a pro-inflammatory state characterized by elaboration of inflammatory cytokines, changes in coagulation, and increased oxidative stress. Because of this observation and because adrenal insufficiency has also been observed after cardiopulmonary arrest, anti-inflammatory therapy has been suggested as a means of improving outcomes. This topic is addressed by Mentzelopoulos and coauthors45 in an article entitled “Vaso-pressin, epinephrine, and corticosteroids for in-hospital cardiac arrest.” These authors begin by citing animal experiment data supporting the use of vasopressin, epinephrine, and corticosteroids as a means of improving neurologic outcomes of cardiac arrest. These authors conducted a single-center, randomized, prospective, double-blind study to assess effects of this drug combination with the use of stress dose corticosteroid re-placement in patients found to have adrenal insufficiency on the outcomes of cardiopul-monary resuscitation. The authors noted improved recovery of effective cardiac rhythm and improved survival-to-hospital discharge in patients who received the corticos-teroid drug combination. Two patients in the corticosteroid group survived to hospital discharge versus none in the control group. Unfortunately, both survivors had severe neurologic deficits. Although this study is suggestive of a benefit in a very high-risk group of patients, the small numbers and the questionable clinical significance of two neurologically disabled survivors versus none indicates that these results should be in-terpreted very cautiously.

Optimization of recovery of effective cardiac rhythm, myocardial perfusion, and cerebral perfusion are efforts directed toward the electrical and circulatory phases of cardiac arrest. The main attempt to ameliorate the effects of the metabolic phase of car-

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diopulmonary resuscitation has emphasized the use of therapeutic hypothermia. Ram-say and Maxwell39 note experimental data indicating a reduction in brain oxidative stress and oxygen demand when post-cardiac arrest hypothermia is used. These au-thors review data from the Hypothermia After Cardiac Arrest Group. This group con-ducted a randomized trial of hypothermia (bladder temperature 32-34°C for 24 hours) following successful resuscitation in patients with ventricular fibrillation. There were significantly improved neurologic outcomes (55% good outcomes versus 39% in con-trols) when hypothermia was used. Six-month mortality was 41% in the hypothermia patients versus 55% in controls. These data support use of post-resuscitation hypother-mia in patients with witnessed out-of-hospital cardiac arrest where successful defibril-lation occurs.

The topic of hypothermia application is discussed in more detail in two additional reviews and an editorial which accompanied one the reviews.46-48 One of these articles, by Schneider and coauthors,48 is a detailed, yet readable comprehensive review of meta-bolic approaches to cardiac arrest and this article is included as a full-text reprint with this issue of SRGS. These articles stress the importance of maximizing nutrient blood flow by optimizing compressions, improving venous return, and protecting against hy-perventilation and lung hyperinflation. They also note the utility of mild post-arrest hy-pothermia in patients who have witnessed arrests, prompt resuscitation, and a shock-able rhythm. Hypothermia is designed to protect cerebral tissue metabolism.

The articles and the editorial stress the cellular causes of cerebral dysfunction, which result from massive accumulations of calcium in brain cells after cardiac arrest. Currently, hypothermia is indicated for children remaining comatose following cardiac arrest and adults with recovery of spontaneous circulation after out-of-hospital ventric-ular fibrillation. Hypothermia can potentially assist recovery of patients with other rhythms, but data confirming this benefit are not available. Data are badly needed be-cause ventricular fibrillation is declining as the main rhythm for out-of-hospital cardiac arrest. For in-hospital cardiac arrest, ventricular fibrillation is not often discovered on the initial electrocardiogram. The authors of these three articles note that the multiple comorbid conditions found in victims of in-hospital cardiac arrest makes recovery in these patients less likely. These reports note the potential for agents such as growth fac-tors and apoptosis inhibitors; data about these approaches should be forthcoming in the future.

Another approach to applying hypothermia and circulatory support for victims of cardiac arrest is with the use of extracorporeal membrane oxygenation. This topic is the subject of a report by Thiagarajan and coauthors 49 in Annals of Thoracic Surgery, 2009, of an analysis of a large extracorporeal membrane oxygenation database. Eleven per-cent of patients in the database had the device applied as an adjunct to management of

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cardiac arrest. The most frequent diagnosis recorded was “cardiac disease.” The au-thors documented a 27% survival in these patients. The proportion of in-hospital ver-sus out-of hospital cardiac arrests is not provided, and the presence of a shockable rhythm is likewise unknown. These data suggest potential utility of the extracorporeal membrane oxygenator in patients sustaining cardiac arrest. Improved outcomes oc-curred when the device was applied within two hours of arrest. A diagnosis other than myocarditis was also associated with improved survival. Renal insufficiency requiring dialysis was associated with increased mortality risk.

Cardiopulmonary resuscitation for in-hospital cardiac arrest: epidemiology and outcomesAs has been noted previously, outcomes for in-hospital cardiac arrest are, in general,

worse than those for out-of-hospital cardiac arrest, primarily due to the multiplicity of unfavorable risk factors in patients who sustain in-hospital cardiac arrest. In addition, the presenting rhythms for patients with in-hospital cardiac arrest are more often pulseless electrical activity or asystole. The first article examining the epidemiology of in-hospital cardiac arrest in elderly patients is by Ehlenbach and coauthors 41 in the New England Journal of Medicine, 2009. These authors analyzed data from the Medicare database over the interval 1992-2005. They examined data from records of 434,000 pa-tients who underwent in-hospital cardiopulmonary resuscitation. The overall survival of these patients was 18%, which is, interestingly, very close to the overall survival for out-of-hospital cardiac arrest.

Survival of nonwhite patients was worse than survival in white patients. The au-thors note that the data for nonwhite patients were drawn, disproportionately, from hospitals with lower overall cardiac arrest survival and this might explain the racial dis-crepancy, at least in part. The analysis indicated that results of in-hospital resuscitation did not improve during the study interval. In the discussion section of this report, the authors make several interesting observations and speculations. They note, for exam-ple, that between-hospital comparisons suggest that hospitals that make use of more extensive monitoring seem to have faster responses to cardiac arrest and improved out-comes.

One approach to shortening response time for cardiac arrest has been to institute rapid response teams. This topic is the subject of a report by Chan and coauthors50 in the Journal of the American Medical Association, 2008. These authors compared the rates of cardiorespiratory arrest codes and mortality for cardiopulmonary resuscitation before and after implementation of a rapid response team. Nearly 25,000 patients were available for analysis in each group. The analysis was performed prospectively in a sin-gle institution. The results of the analysis indicated that there were 376 rapid response team activations in the 20 months of experience analyzed after team implementation. The frequency of out-of-ICU codes declined (this is a hoped-for result of rapid response

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team implementation). Unfortunately, there was no reduction in the overall mortality when the two periods were compared.

The authors note that there is no standard approach to rapid response team activa-tion and no standard organization of the team. These problems make comparisons diffi-cult. It is interesting to note recent developments in several hospitals where rapid re-sponse team activation can be accomplished by patients or patients’ families without the need to summon nursing staff. Additional data will be interesting to document the potential effectiveness of rapid response teams.

Ehlenbach and coauthors note that their data indicate that the proportion of in-hos-pital deaths preceded by formal efforts at cardiopulmonary resuscitation increased dur-ing each year of the study they conducted. They speculate that this increase might be because nonwhite patients tend to have lower rates of do-not-resuscitate orders than do white patients. They further speculate that do-not-resuscitate orders might be ig-nored in a significant proportion of in-hospital cardiac arrest incidents.

Prearrest predictors of survival after cardiopulmonary resuscitation have been sought. This subject is the topic of an analysis authored by Gonzalez and coauthors51 in Circulation, 2008, who examined outcomes of cardiopulmonary resuscitation in a group of patients who had undergone echocardiographic assessment of left ventricular func-tion on average 11 days before the arrest event. The authors found that a left ventricu-lar ejection fraction of less than 45% predicted a worse outcome. Mortality in the group with diminished left ventricular function was 92% compared with 81% in patients with normal left ventricular function.

The analysis also produced data showing that post-cardiopulmonary resuscitation of left ventricular function was depressed in all patients by an average of 25%. The au-thors concluded that the depression of ventricular function attendant to cardiopul-monary resuscitation could not be tolerated in patients with depressed ventricular function before the cardiac arrest event. This analysis is interesting. The high propor-tion of echocardiographic analyses before arrest (77%) suggests that these patients were largely patients hospitalized with cardiac disease and generalization of these data to other patient groups might not be possible. The authors speculate that the hypera-drenergic state that follows restoration of cardiac rhythm might be especially stressful for patients with diminished left ventricular function.

Ehlenbach and associates also noted differences in outcomes of resuscitation de-pending on the day and time of cardiac arrest occurrence. This topic is the focus of a re-port by Peberdy and coauthors52 in the Journal of the American Medical Association, 2008. These authors analyzed data from cardiac arrest events occurring from 0700-2259 versus 2300-0700. They also compared mortalities from cardiac arrests occurring

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from 2300 on Friday to 0659 on Monday. The database analyzed was the National Reg-istry of Cardiopulmonary Resuscitation that contains data from more than 500 partici-pating hospitals. They noted significant reductions in survival-to-discharge and good neurologic outcomes in patients who sustained cardiac arrest at night or on weekends. This difference was stable when the data were adjusted for differences in patient co-morbidity and risk. The data suggested a somewhat increased odds of death for cardiac arrest occurring in the operating room or ICU and a slight (nonsignificant) reduction of risk for cardiac arrest occurring in the emergency department. Patients admitted after injuries were, as a group, slightly more likely to survive cardiac arrest.

Data such as those discussed above suggest the need to improve effective cardiopul-monary resuscitation in hospitals. Educational activities such as performance debrief-ings and feedback might function to improve cardiopulmonary resuscitation perfor-mance and, perhaps, results. The first article that deals with this topic is by Edelson and coauthors53 and is entitled “Improving in-hospital cardiac arrest process and outcomes with performance debriefing.” This article appeared in Archives of Internal Medicine, 2008. A debriefing conference was held for residents who participated in cardiopul-monary resuscitation events. Data from sensing defibrillators and observations made by trained observers were used to identify areas for improvement and training. One hundred twenty-three patient events after implementation of the debriefing session were compared with 101 historic controls. These authors found that adherence to na-tional recommendations about compression rate, excursion, and ventilation improved in the post-debriefing period. There was an increased rate of return of spontaneous cir-culation in the post-debriefing patients but there was no improvement in survival-to-discharge. Another method of performance assessment and improvement includes the use of real-time audiovisual feedback combined with debriefing. This approach is ana-lyzed in a study by Dine and coauthors54 in Critical Care Medicine, 2008. These authors compared debriefing alone with debriefing with real-time audiovisual feedback in two groups of nurses undergoing training using a cardiopulmonary resuscitation simulator. The authors found that performance, evidenced by compliance with recommendations for compression rate and excursion, improved with debriefing alone. The addition of audiovisual feedback provided significant additional improvement. Overall, twice as many participants provided optimum compressions after debriefing with audiovisual feedback as with debriefing alone.

Editorial commentFrom the perspective of the editor, it seems clear that we have the capability to pre-

dict perioperative cardiac complications using global risk factors that overcome, at least partially, the imprecision associated with the use of risk scoring systems that focus on risk factors specific to the cardiovascular system. Once high-risk patients or patients at moderate risk who are scheduled to undergo high-risk operations (open vascular re-

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construction or thoracotomy) are identified, careful preoperative preparation using beta-blocking drugs (selective beta-1 receptor blocking drugs) will provide control of heart rate and blood pressure in approximately 80% of this patient group. Preparation will need to begin at least one month preoperatively. If patients have indications for statin drugs based on lipid profiles or risk scores for cardiac disease (such as the Fram-ingham score), statin drugs and low-dose aspirin are potentially useful additions. Ide-ally, these measures will have been implemented by the patient’s primary care physi-cian. Surgeons need to insure that there is no interruption of drug therapy during the perioperative interval.

Perioperative myocardial infarction is a potentially lethal complication occurring as a result of coronary artery plaque instability or rupture with coronary artery thrombo-sis. Prediction of which plaque will rupture is not possible currently. Because of this, planning preoperative revascularization interventions based on identification of a “cul-prit” coronary stenosis does not reliably reduce risk of perioperative myocardial infarc-tion. Indications for preoperative coronary imaging and revascularization are made based on conventional indications, and these are undertaken in patients with “unstable” ischemic diseases such as unstable angina, recent myocardial infarction, and cardiac failure. The usual diagnostic clues for diagnosis of myocardial infarction (chest pain, Q-waves or ST segment elevation on electrocardiogram, and elevated troponin levels) lack specificity in the patient who has recently undergone a surgical procedure. Clinical signs of perioperative myocardial infarction might be vague and include intermittent hypotension, changing mental status, new onset arrhythmia, and ST-segment depres-sion on electrocardiographic tracings. Because of these facts, a low threshold for use of serial troponin levels, continuous electrocardiographic monitoring, and echocardio-graphic imaging are necessary to make a prompt diagnosis.

Perioperative tachycardia will occasionally require pharmacologic intervention or even electrical cardioversion. Knowledge of the elements of diagnosis and emergency treatment of these arrhythmias will be valuable. Even though surgeons will not nor-mally be the lead caregiver for patients with cardiac failure, it is useful to understand the pathophysiology of this condition so that factors that increase cardiac stress can be minimized during the perioperative interval. Echocardiography is the most useful modality for quantification of the severity of cardiac failure.

Finally, the features of successful resuscitation of patients who sustain out-of-hospi-tal or in-hospital cardiac arrest are important components of the knowledge base of surgeons. Resuscitation maneuvers such as chest compressions and ventilation maneu-vers are frequently not performed in compliance with recommendations from national groups like the American Heart Association. It is important to recall that maneuvers to

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provide effective chest compression and optimum venous return to the heart are criti-cal features leading to successful resuscitation.

Surgeons will be consulted to assist in the management of injuries sustained during cardiopulmonary resuscitation. Injuries from cardiopulmonary resuscitation are rela-tively common; clinically significant injuries are discovered in 10%-15% of autopsied patients. Injuries might be discovered in a larger proportion of survivors. Rib fracture and/or costochondral separation are the most commonly diagnosed injuries. Pneu-mothorax, hemothorax, diaphragm injury, and lacerations of the liver and spleen are oc-casionally encountered.

Perioperative respiratory complicationsRespiratory complications after major surgical procedures might range from minor

complications like microatelectasis that can be cleared with coughing, deep breathing, and early ambulation, to major, life threatening events such as postoperative respira-tory failure. Risk of major respiratory failure requiring ventilatory intervention is in-creasing as the surgical patient population ages and the frequency of preexisting respi-ratory diseases, such as obstructive sleep apnea, is increasingly recognized. The pro-in-flammatory state stimulated by anesthesia, operation, and transfusion leads to acute lung injury that often progresses to acute respiratory distress syndrome. In order to minimize the negative impact of postoperative respiratory complications, surgeons re-quire knowledge of the pathophysiology, effective preventive measures, features of di-agnosis, and therapies available. These topics will be addressed in this section of the overview.

Risk factors for respiratory complicationsDiscussion of risk factors for development of postoperative respiratory complica-

tions and postoperative respiratory failure opens with a review of an article by Johnson and coauthors55 entitled “Multivariable predictors of postoperative respiratory failure after general and vascular surgery: results from the patient safety in surgery study.” This article was published in the Journal of the American College of Surgeons in 2007 and a full-text reprint accompanies this issue of SRGS. This article is one part of a series of reports detailing the results of the patient safety in surgery study that was the pre-cursor of NSQIP. Another component of this series was cited previously in the overview in the discussion of risk factors for postoperative cardiac events.

These authors analyzed demographic and outcomes data from 128 Veterans Admin-istration hospitals and 14 academic medical centers. Postoperative respiratory failure was defined as the need for unplanned postoperative intubation and/or more than 48 hours of mechanical ventilation assistance postoperatively. In contrast to the previously discussed analysis of postoperative cardiac complications where global risk factors

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markedly reduced the impact of cardiac-specific risk factors, this analysis found that postoperative respiratory failure was best predicted using a combination of global and lung-specific risk factors. More than 180,000 patients were analyzed. Respiratory fail-ure occurred in 3% of this group. Global risk factors such as higher ASA score, the need for emergency operation, more complex procedures, preoperative sepsis, and signs of renal insufficiency all predicted postoperative respiratory failure. Patients who devel-oped postoperative respiratory failure tended to be male and older.

Smoking, a diagnosis of chronic obstructive pulmonary disease (COPD), and a his-tory of congestive heart failure were risk factors specific to the cardiopulmonary sys-tem that also predicted postoperative respiratory failure. The authors developed a “res-piratory risk index” by assigning points based on rounding of the calculated odds ratio for respiratory failure determined from the risk analysis. For example, a calculated odds ratio of 1.25 would add one point to the respiratory risk index. Patients were then di-vided into risk groups of low, medium, and high risk based on the calculated probability of respiratory failure. The risk scoring system was validated in a separate sample drawn from the database. The data disclose that respiratory risk index of eight or lower is associated with a 0.1% risk of respiratory failure. Risk index score of 8-12 is associ-ated with a 1% incidence of respiratory failure. For scores >12, overall risk is 7% but the risk steadily increases with increasing risk score; a score of 25 predicts a frequency of respiratory failure of 40%.

The authors use the discussion section of the article to confirm that respiratory fail-ure is associated with more healthcare resource utilization than any other group of postoperative complications. They further note that other analyses have identified simi-lar arrays of risk factors, both global and lung specific, that predict postoperative respi-ratory failure. Not surprisingly, the risk of respiratory failure increases with a thoracic incision. After sternotomy or thoracotomy for cardiac procedures, the overall frequency of respiratory failure was 7% compared with 3% associated with general and vascular procedures in the analysis presented by Johnson and colleagues.

Obstructive sleep apnea is being diagnosed with increasing frequency. The presence of this disorder in obese patients and patients with the “metabolic syndrome” of obe-sity, hypertension, and hyperglycemia is firmly established. The diagnosis of obstruc-tive sleep apnea is predictive of postoperative respiratory complications. The next arti-cle reviewed investigates the possibility that preoperative testing for obstructive sleep apnea might identify patients at increased risk for episodes of postoperative hypox-emia. The article is by Gali and coauthors56 and appeared in Anesthesiology, 2009. The authors cite data indicating a substantial rate of underdiagnosis of obstructive sleep ap-nea. They refer to 1993 reports (references 6 and 7 in their bibliography) that esti-mated that 4% of men and 2% of women in the 30-60 year age group had obstructive

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sleep apnea and that this condition was an independent risk factor for postoperative mortality.

By the end of the 1990s, there had been a 12-fold increase in the diagnosis of ob-structive sleep apnea. Later estimates have concluded that 82% of men and 93% of women with obstructive sleep apnea remain undiagnosed. It is likely that many of these individuals will require surgical care and that this group will be at increased risk for pe-rioperative respiratory complications. The authors describe the pathophysiology of res-piratory complications in patients with obstructive sleep apnea. The anatomic and physiologic abnormalities of obstructive sleep apnea can be brought on by the dimin-ished responses to hypoxia and hypercapnia as well as the diminished pharyngeal tone produced by anesthetic and analgesic medications.

In this report, the authors hypothesize that a preoperative risk assessment for ob-structive sleep apnea applied in patients not known to have obstructive sleep apnea, coupled with post-anesthesia monitoring for hypoxemic events, will identify patients at risk and prevent complications. The preoperative assessment used consisted of obtain-ing a sleep apnea clinical score. This score assigns points based on responses to ques-tions about the presence of hypertension and a history that patients had been told by persons sharing their sleeping area that they snore. For this question, 1 point is as-signed for snoring 3-5 times/week or for snoring every night. The patients are also asked whether they have been told that they gasp, choke, or snort while sleeping. The point assignments are based on frequency of symptoms.

The final assessment is a measurement of neck circumference. Points are assigned for various neck circumferences with hypertension, historic features, or both. A score of >15 indicates a high likelihood of obstructive sleep apnea. Postoperative monitoring of patients enrolled in this study included continuous oxygen saturation monitoring, and monitoring for apnea, bradypnea, and pain level/sedation mismatch. The last assess-ment is accomplished when a patient indicates severe pain on a visual-analog scale but appears too sedated to receive additional analgesia.

In all, 673 patients were enrolled. Sleep apnea scores of > 15 predicted episodes of desaturation and recurrent potential hypoxemic events in the post-anesthesia care area. The combination of a high sleep apnea score and post-anesthesia area hypoxemic events predicted postoperative respiratory complications. A high sleep apnea clinical score was recorded in nearly 32% of this patient group. This patient group had higher ASA scores also. Patients with high clinical scores and recurrent hypoxemic events in the post-anesthesia care area had a frequency of diagnosed postoperative respiratory complications of 33%. Patients with low scores and recurrent post-anesthesia events had a frequency of postoperative respiratory complications of 11%. Patients with low

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scores and no events developed postoperative respiratory complications in less than 1% of patients. The authors note that the gold standard for diagnosis of obstructive sleep apnea is polysomnography.

Validation of the sleep apnea clinical score with comparisons to other scores and polysomnography are found in two articles57-58 conducted in 1994 and 2003 confirming that the sleep apnea clinical score has a positive predictive value for an accurate diag-nosis of obstructive sleep apnea of more than 80% compared with polysomnography. A limitation of the study authored by Gali and associates is that polysomnography was not used to validate the findings reported. Nonetheless, the data suggest that obstruc-tive sleep apnea might be underdiagnosed. Furthermore, sleep apnea clinical scores of > 15 are, when combined with assessments performed in the post-anesthesia care area, predictive of postoperative respiratory complications. Finally, this straightforward as-sessment can be used to identify patients at risk.

Because obstructive sleep apnea is a common condition accompanying morbid obe-sity, identification of patients with this condition who are scheduled to undergo bariatric procedures could lead to preventive interventions, reduction of risk for post-operative pulmonary failure, and lower consumption of healthcare resources. An article dealing with this topic by Hallowell and coauthors 59 appeared in Surgery, 2007. This analysis compares the need for ICU admission for respiratory complications in a group of 318 morbidly obese patients undergoing bariatric procedures. Polysomnography for diagnosis of obstructive sleep apnea was performed in all the patients. The frequency of ICU admission in this group was compared with a historic control group. In the control group, obstructive sleep apnea assessment using polysomnography was used based on clinical suspicion and/or surgeon preference.

After implementation of routine polysomnography, ICU admission for respiratory complications decreased from 5% to less than 1%. The authors note other changes in their practice that occurred simultaneously. They note an increasing use of laparoscopic gastric bypass in the second group. They also note that the rate of ICU admission for any reason was already declining in their practice. In spite of these limitations, the analysis does disclose a significant risk for undiagnosed obstructive sleep apnea in morbidly obese patients. Improving the rate of diagnosis of obstructive sleep apnea in this patient group could create an opportunity for implementing preventive measures to reduce pe-rioperative respiratory complications.

In the discussion section of the article, Hallowell and colleagues review the changes occurring because of increasing body weight that contribute to respiratory complica-tions. These include upward displacement of the diaphragm, increased chest wall mass leading to decreased chest wall compliance, and increased pulmonary vascular resis-

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tance resulting from chronically expanded blood volume. These authors also stress that obstructive sleep apnea might be occult in this patient group. The use of preoperative and postoperative noninvasive ventilation with continuous positive airway pressure is one effective preventive measure. The authors note that concerns over application of continuous positive airway pressure in a patient with a newly constructed gastroje-junostomy seem unfounded. They cite data from clinical reviews documenting no in-crease in anastomotic leak rates in patients who used continuous positive airway pres-sure devices. They conclude by reviewing the costs of the measures they used to pre-vent respiratory complications leading to ICU admission. They note that ICU admission for two days would add more than $12,000 of hospital costs in their institution. Polysomnography and perioperative continuous positive airway pressure add less than $3000 of additional cost.

Editorial commentFrom the perspective of the editor, it seems that easily obtained information from

the history and physical examination could identify patients for use of polysomnogra-phy and/or preventive continuous positive airway pressure. Information on a history of hypertension, snoring, obesity, and neck circumference > 17 inches would provide a ba-sis for further evaluation.

Prevention of respiratory complicationsPatients having the constellation of risk factors discussed above are candidates for

preventive strategies to reduce risk of respiratory complications. Multivariable risk studies have identified systemic risk factors such as elevated ASA score, smoking, obe-sity, older age, and need for complex operation as significant predictors of postopera-tive respiratory complications. Congestive heart failure and COPD are patient-specific factors potentially modifiable. It is well recognized that smoking cessation and mea-sures to stabilize cardiovascular disease require two months or more of preoperative effort for a meaningful impact on complication risk to occur. Lung specific interventions such as treatment of lung infection, sputum reduction measures, use of bronchodilators, and preoperative respiratory muscle training have potential value. These topics will be discussed in the following section of the overview.

Preoperative maneuversThe first article reviewed here is by Gore60 in Gerontology, 2007. The article is enti-

tled “Preoperative maneuvers to avert postoperative respiratory failure in elderly pa-tients.” The author opens the review by emphasizing the clinical importance of abnor-mal postoperative ventilation, hypoxemia, and hypercarbia. These lead to the need for intubation and mechanical ventilator support. Dysfunctional ventilation leading to intu-bation greatly increases the risk of ventilator-associated pneumonia associated with a mortality risk exceeding 50% (see discussion in SRGS, Vol. 35, No. 7). Mortality rates for

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ventilator-associated pneumonia have not changed in many years. This consistent ob-servation supports the importance of preventive strategies to reduce the need for intu-bation in this patient group.

Particular problems that might predispose elderly patients to perioperative respira-tory complications include 1) a gradual decline in one-second forced expiratory volume (FEV1) with advancing age; 2) increased ventilation/perfusion mismatching caused by increased early airway closure in dependent lung units; and 3) depressed responses to hypoxemia and hypercarbia. Gore cites data that document decreased FEV1 as an accu-rate predictor of postoperative respiratory complications, especially in patients with COPD. Ventilation/perfusion mismatching causes an age-related decline in resting arte-rial oxygen tension. Furthermore, older patients develop blunted responses to hypox-emia and hypercarbia and are vulnerable to analgesic and sedative-induced respiratory depression. Age-related decreases in mucociliary function reduce clearance of bacteria from the airway and contribute to increases in risk for perioperative pneumonia. This abnormality is particularly pronounced in smokers.

Preoperative evaluation can include easily obtained data from the history and physi-cal examination that can guide subsequent preventive efforts. In addition to obstructive sleep apnea screening (discussed above) a history of smoking, reactive airway disease, allergy, cough, and excessive sputum production can be obtained. The degree of chronic cough can be ascertained using a “cough test.” The patient is asked to cough. If the cough results in production of sputum or repeated coughing, additional testing (such as quantification of FEV1) might be helpful. If excessive sputum production is documented, a sputum culture is obtained. Recovery of a pathogen such as H. influenza, S. Pneumo-niae, or MRSA can prompt a short course of preemptive antibiotics. Additional interven-tions that can strengthen cough and reduce sputum production include postural drainage, assisted cough, and deep breathing exercises.

Inhaled bronchodilators are indicated preoperatively in patients with reactive air-way disease and in patients with chronic bronchitis. Data cited by Gore suggest that ipratropium bromide (Atrovent®) is a useful first-line inhalant. Aminophylline has also been used for this purpose but data cited by Gore suggest that the association of this drug with tachycardia limits its use in elderly surgical patients. In patients with docu-mented COPD, preoperative corticosteroid therapy might be useful. Effectiveness of steroid therapy is monitored with sequential assessments of FEV1. If this variable im-proves with steroid therapy, preoperative and postoperative therapy is valuable. Gore stresses that, overall, fewer than one-third of COPD patients will have significant re-sponses to corticosteroids although degrees of improvement in some patients are sub-stantial. Gore emphasizes the importance of continuing preoperative therapy into the postoperative recovery period.

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Postoperative maneuversTime-honored patient care processes for minimizing postoperative pulmonary com-

plications include early ambulation, encouraging cough, elevation of the head of the bed, and judicious use of analgesics and sedatives. These interventions are valuable for preventing atelectasis and maintaining lung inflation. One device used for maintenance of lung inflation is the incentive spirometer. Use of this device is the topic of an article by Westwood and coauthors61 in Surgeon, 2007. These authors analyzed data from 263 patients; the study was not randomized. One group of patients had intensive chest physiotherapy supported by a physiotherapist visit at least once daily during the post-operative hospitalization. The other group had similar physiotherapy with the addition of the incentive spirometer. Respiratory complications were defined as new fever > 38°C, signs of atelectasis or infiltrate on chest radiograph, and/or institution of antimi-crobial therapy for suspected pulmonary infection. Both patient groups consisted of el-derly patients (mean age 68 years); more than half of each group had a history of smok-ing and both groups underwent high-risk abdominal or noncardiac thoracic operations. Respiratory complications, according to the authors’ definition, occurred in 17% of con-trols and 6% of patients using the incentive spirometer.

The Westwood article and the article authored by Gore60 review data from other studies relevant to the use of the incentive spirometer. Of the available studies, half show benefit from use of the device and half show no favorable effect on postoperative respiratory complications. The available studies vary in the application of other ap-proaches such as intensive chest physiotherapy. The main complication of incentive spirometer use is gastric dilatation, which has been reported several times.

Westwood’s study reports no instances of this complication. It is difficult to ascribe a consistent clinical benefit to incentive spirometer use as an isolated intervention. Sig-nificant benefit for the device when it is added to dedicated chest physical therapy might be associated with the fact that a well-trained patient can use the device during the intervals between physical therapist visits.

A randomized trial evaluating intensive inspiratory muscle training under the su-pervision of a physical therapist as a means of reducing perioperative respiratory com-plications by Dronkers and coauthors62 appeared in Clinical Rehabilitation, 2008. In this study, 20 patients undergoing open abdominal aortic aneurysm repair were random-ized to receive intensive inspiratory muscle training (one physical therapist supervised session and five unsupervised sessions/week for two weeks prior to operation). This group was compared with a control group receiving instruction in deep breathing and incentive spirometer use. The primary endpoint of this study was detection of atelecta-sis on chest radiograph. The analysis disclosed a nonsignificant trend toward less at-electasis in the group that received intensive inspiratory muscle training. Maximum in-

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spiratory force increased by 10% in the intervention group. Patient satisfaction with the intervention was high. The authors acknowledge the need for additional studies in-volving larger patient groups.

A meta-analysis of available data from studies evaluating prophylactic respiratory physical therapy by Pasquina and coauthors63 from Chest, 2006, evaluated 35 trials that provided data on the possible value of respiratory physical therapy as a means of pre-venting perioperative respiratory complications. Significant differences in postopera-tive respiratory events were reported in only four studies that included a “no interven-tion” control group. In some studies differences occurred in the frequency of atelectasis (usually defined as a change on chest radiograph). Most studies did not focus on impor-tant complications such as pneumonia, need for intubation, or ventilator support.

In the single study analyzing effects of respiratory physical therapy on the fre-quency of pneumonia, a significant reduction was recorded but the frequency of pneu-monia in the control group was higher than baseline rates for this complication recorded in other clinical series. This fact limits the external validity of this study. Un-specified respiratory complications were reduced in one analysis. These authors con-cluded that routine use of physiotherapy is not indicated in low and moderate risk pa-tients undergoing abdominal operations. There were no reports of adverse events asso-ciated with the use of physical therapy. Readers will recall that we noted earlier reports of gastric distention associated with the use of the incentive spirometer but few of the studies supporting use of this device report occurrences of gastric distention. Failure to consider potential harm from an intervention weakens data supporting use of the inter-vention.

Gore60 concludes his article with a discussion of nutritional support and cessation of alcohol use as a means of preventing perioperative respiratory complications. He notes that use of supplemental parenteral nutrition as a means of improving nutrition has been limited by the known complications of this intervention (hyperglycemia, liver dys-function), its cost, and the need for central venous access. Use of this intervention is un-usual except in patients who have lost more than 5% of ideal body weight or patients who were profoundly hypoalbuminemic from nutritional impairment. Use of preopera-tive enteral nutrition is also unusual because of the need for enteral access and limited patient tolerance. Enteral access should be acquired in patients undergoing high-risk abdominal procedures where preoperative weight loss and/or hypoalbuminemia sug-gest nutritional deficit. Although there are data indicating value of human growth hor-mone therapy in managing burn patients (especially burned children), Gore stresses that there are no high-quality data supporting use of this agent to reduce perioperative respiratory complications.

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Gore concludes his article by emphasizing the importance of cessation of alcohol use by heavy drinkers before a major operation. This will require careful counseling of each individual patient. Abstinence from alcohol use, even for short intervals before opera-tion might be valuable. Acute cessation of alcohol use might precipitate clinical alcohol withdrawal syndrome, which carries its own risk of mortality. This eventuality should be avoided to the extent possible.

Editorial commentIn the section of the overview, we have discussed preoperative and postoperative

maneuvers that might be helpful for prevention of respiratory complications. Interpre-tation of the available data is challenging because of the variable definitions of respira-tory complications and the small patient groups that make up most of the available studies. Most patients undergoing abdominal or thoracic operations should have early ambulation, elevation of the head of the bed, brief training in coughing and deep breath-ing, and careful pain control. Interventions such as preoperative antibiotics, inhaled bronchodilators, continuous positive airway pressure breathing, and corticosteroids should be applied in carefully selected patients.

The most consistent marker for postoperative respiratory complications is the need for intubation in the postoperative period. Analyses of this event in two recent studies64-

65 indicated that intubation in the post-anesthesia care unit is closely related to the presence of residual neuromuscular blockade. Careful tracking and recording of the level of neuromuscular blockade effectively prevented early, unplanned intubations. In populations of postoperative general surgery patients, unplanned intubation is an event associated mainly with nonmodifiable events such as chronic disorders of conscious-ness, severe cardiovascular and/or pulmonary disease, and the development of postop-erative sepsis.

Data indicate that the overall incidence of unplanned postoperative intubation is low (less than 3%) but the event carries a mortality risk in excess of 40%. Current pre-ventive interventions such as emergency response teams have had limited impact on the frequency and mortality risk of this complication. Most unplanned postoperative in-tubations occur in patients who are already in the ICU. Prevention of unplanned intuba-tion seems to be most useful for patients in the post-anesthesia care unit. Recognition of risk factors such as severe cardiopulmonary disease and chronic depressed level of con-sciousness might help identify patients at increased risk for postoperative unplanned intubation.

Noninvasive ventilation for postoperative respiratory complicationsIncreasing recognition that the morbidity of postoperative respiratory failure is

driven, at least in part, by complications of intubation and mechanical ventilation (espe-

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cially ventilator-associated pneumonia) has stimulated efforts to use nonintubation in-terventions for early treatment of this complication. The first article reviewed that deals with this topic is by Michelet and coauthors66 from the British Journal of Surgery, 2009. This article is supplied as a full-text reprint with this issue of SRGS. The authors note that respiratory failure and anastomotic leak are linked complications in patients un-dergoing esophagectomy. Anastomotic leak occurs when ischemia or diminished oxy-gen delivery to the anastomotic area occurs. Thus, hypoxia, which might accompany the onset of postoperative respiratory failure, can contribute to the risk of anastomotic leak.

The reported study is a case-control design study in which a group of patients treated with postoperative noninvasive ventilation was compared with a group of pa-tients who did not receive this intervention. In all other aspects, the patient groups were comparable. Thirty-six patients comprised each study group. Acute respiratory failure was characterized by dyspnea and use of accessory muscles of ventilation, new infiltrates visible on chest radiograph, purulent sputum, fever, and hypoxemia (Pa02/FI02 ratio of < 200). Noninvasive ventilation was delivered with a face mask and a venti-lator. Continuous positive airway pressure and positive end-expiratory pressure were used and pressures incrementally increased until tidal volume reached a level of 6 mL/kg estimated ideal body weight and arterial oxygen saturation exceeded 90%. Max-imum inspiratory pressure was maintained below 25 cm H20. Episodes of noninvasive ventilation were interspersed with 45-60 minute intervals without assisted ventilation.

Nine of 36 patients in the noninvasive ventilation group eventually required endo-tracheal intubation, but only one of these because of intolerance of the mask. In com-parison, 19/36 patients in the control group required intubation. This very low inci-dence of mask intolerance contrasts with data from a report by Conti and coauthors67 that describes a comparison between a mask and a helmet interface for delivery of non-invasive ventilation. In this study, the patients treated with the helmet device were compared with historic control patients treated with mask ventilation. Diagnostic crite-ria for postoperative acute respiratory failure used by Conti and colleagues were simi-lar to the criteria used by Michelet and associates. Twenty percent of the helmet pa-tients and 48% of the mask patients required intubation and the main reason was intol-erance of the noninvasive intervention.

Both studies indicate that noninvasive ventilation can effectively improve oxygena-tion and prevent the need for intubation in many patients. Overall, 20%-50% of pa-tients in whom noninvasive ventilation is attempted will fail and failure is often times because the patient cannot tolerate the device. Careful patient selection and availability of close bedside supervision of the ventilation might reduce this risk, but at significant added cost in terms of respiratory therapist and nursing time. In general, patients se-

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lected for noninvasive ventilation should have normal sensorium and not have severe dyspnea or difficulty managing secretions. If these criteria can be met, this intervention is often effective as a means of supporting oxygenation and avoiding intubation.

The use of noninvasive ventilation in patients with more severe forms of respiratory failure is controversial. The main benefit of this approach would be to avoid intubation with the attendant reduction in risk of ventilator-induced lung injury and ventilator-as-sociated pneumonia. This subject is the focus of two articles reviewed at this time. The first is by Antonelli and coauthors68 in Critical Care Medicine, 2007. The authors cite data from other studies indicating the possibility that intubation rates for patients with early acute respiratory distress syndrome might be reduced by as much as 50% with use of noninvasive ventilation. This report deals with 147 patients admitted to two ICUs. The authors note that both units have extensive experience in the use of noninva-sive ventilation. The patients were diagnosed with acute respiratory distress syndrome using standard criteria. Noninvasive ventilation was supplied using a mask or a helmet device. Continuous positive airway pressure and positive end-expiratory pressure were gradually increased in increments until exhaled volumes reached 6 mL/kg, respiratory rate was < 25 breaths/min, and oxygen saturation was consistently >90%. Failure to achieve these goals and/or failure of the patient to tolerate noninvasive ventilation de-fined failure of noninvasive ventilation.

The authors achieved success avoiding intubation in 54% of the patients enrolled in this study. They noted predictors of failure of noninvasive ventilation as higher severity of illness scores, older age, requirement for PEEP > 12 cm H20, and failure to improve oxygenation after one hour of noninvasive ventilation. Patients who required intuba-tion were more likely to have severe sepsis or septic shock and a mortality rate of 54% was recorded in the group requiring intubation. Only 12% of patients could not tolerate noninvasive ventilation. It is likely that the extensive experience of these clinicians with noninvasive ventilation contributed to this level of success.

Contrasting data are presented in an article by Rana and coauthors69 in Critical Care, 2006, entitled “Failure of noninvasive ventilation in patients with acute lung injury: ob-servational cohort study.” This report presents data on 54 patients who had noninva-sive ventilation attempted as the first intervention for respiratory distress requiring ad-mission to the ICU. The patients were severely ill with sepsis diagnosed in 88% of pa-tients. Septic shock was present in 19 of the 54 patients. Data on Pa02/Fi02 ratios dis-close that this patient group met criteria for acute respiratory distress syndrome rather than acute lung injury in essentially all patients. This was, thus, a high-risk cohort of pa-tients. The authors observed failure of noninvasive ventilation in 70% of patients.

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The presence of shock, acidosis, and severe hypoxemia were predictive of failure of noninvasive ventilation. The higher failure rate in this series serves to emphasize the importance of patient selection. Severely ill patients, especially those with severe hy-poxemia and hemodynamic instability, are at increased risk for failure of noninvasive ventilation. These findings are similar to those of Antonelli and coauthors68 discussed above. Because concerns have been raised about possible harmful effects of delaying in-tubation in patients who are at high risk of progressing to severe acute respiratory dis-tress syndrome, candidates for noninvasive ventilation should be carefully selected.

Acute lung injury and acute respiratory distress syndromeAcute lung injury is a term applied to a complex response of the lung to systemic

and localized inflammatory stimuli. A multitude of injuring agents, acting singly or in combination, can produce the histologic, radiologic, and clinical manifestations of acute lung injury. These agents might act by direct injury to the lung tissue (pulmonary contu-sion, pulmonary blast injury) or to the airway (aspiration, inhalation injury). In other instances, the inflammatory process begins with a remote stimulus (peritonitis, pancre-atitis, sepsis, combined traumatic injury, shock, and resuscitation) and the lung is in-jured because of circulating factors that act directly on the lung microcirculation and/or lung tissue or through activation of inflammatory mediators within the lung microcircu-lation. Pneumonia can trigger the development of acute lung injury in adjacent nonin-fected lung through propagation of the inflammatory process.

Patients can recover from acute lung injury or might progress to acute respiratory distress syndrome, a clinical entity that is manifest by hypoxemia from ventilation/per-fusion mismatching, loss of lung compliance because of alveolar flooding and consolida-tion of lung tissue, and increased dead space ventilation resulting from pulmonary mi-crovascular occlusion. There is no specific therapy for acute lung injury. Support of ven-tilation and oxygenation using adjuvant ventilation therapies can assist the lungs in the effort to maintain oxygen transfer from alveolus to blood but these therapies have no positive effect on the severity or clinical course of acute respiratory distress syndrome. In fact, as clinicians have learned over the past decade, adjuvant ventilator therapy can produce additional injury in the lung through effects of pressure, volume, cycling of ventilation, and promotion of the inflammatory process.

In this section of the overview, we discuss important clinical features of the patho-physiology, diagnosis, and management of acute lung injury and acute respiratory dis-tress syndrome. Entire volumes have been written on these topics and, because of the vastness of the information available, this review will not be comprehensive; the review will focus on clinically valid understandings and effective interventions.

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PathophysiologyBiomarkers of inflammation, altered coagulation, fibrinolysis, and increased oxida-

tive stress are activated, elevated, or suppressed to varying degrees and with different trajectories in all inflammation-mediated diseases including acute lung injury. Pro-in-flammatory cytokines can be recovered from blood and from alveolar fluid in animals and patients with acute lung injury and adult respiratory distress syndrome. Elevations of some biomarkers such as interleukin-6 (IL-6), interleukin-8 (IL-8), and intercellular adhesion molecule-1 (ICAM-1) are associated with poorer clinical outcomes for acute lung injury. This is also true for coagulation factors. Lower levels of Protein C and eleva-tions of thrombomodulin indicate a pro-coagulant state; this pattern is associated with poor outcomes. Finally, impaired fibrinolysis is indicated by elevations of plasminogen activator inhibitor-1 (PAI-1) and elevated levels of this substance have been associated with poor outcomes of acute lung injury and acute respiratory distress syndrome.

Recent changes in clinical approaches to acute respiratory distress syndrome in-clude the use of low tidal volume (6 mL/kg), low mean airway pressures (25 cm H20), positive end expiratory pressure (12 cm H20), and permissive hypercapnia as clinicians attempt to minimize inflammatory stimuli and reduce the impact of ventilator-associ-ated lung injury. This approach is termed “open-lung” ventilation or “lung-protective” ventilation. There are data suggesting that “open-lung” ventilation reduces inflamma-tory mediators and the reduction is associated with improved clinical outcomes. The first article discussed in this section analyzes the effect of open lung ventilation on in-flammatory mediators and seeks to explore the question whether patterns of inflamma-tory mediator levels remain predictive of outcomes in the era of “open-lung” ventila-tion. The article by McClintock and coauthors70 appeared in Critical Care, 2008.

The authors collected ventilator data and serum levels of biomarkers in 50 patients with acute respiratory distress syndrome. The causes of acute respiratory distress syn-drome varied and included most of the common causes; no single cause predominated. The ventilator data confirmed that patients were treated with the “open-lung” ap-proach. Serum biomarker patterns were significantly different in survivors and nonsur-vivors. After adjustment for various risk factors, elevated levels of ICAM-1 and IL-8, and depressed levels of Protein C were predictive of mortality. The authors concluded that patterns of biomarker activation are predictive of outcomes and this predictive value has not been eliminated by “open-lung” ventilation strategies. In the discussion section of this report, lower levels of Protein C were predictive of mortality even when the data were adjusted for the frequency of sepsis as the cause of acute respiratory distress syn-drome. This observation suggests that Protein C administration might favorably affect recovery in some patients with acute respiratory distress syndrome. It is disappointing that recent data have not shown a benefit for administration of Protein C in patients with acute respiratory distress syndrome.

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Burn induced lung injury combined with inhalation injury is a prototypical example of combined lung parenchyma and airway injury. The features of combined burn/in-halation injury are discussed in an article by Enkhbaatar and Traber71 in Clinical Sci-ence, 2004. The article is supplied as a full-text reprint accompanying this issue of SRGS. The authors begin by noting that inflammation induced increases in microcirculatory permeability characterizes burn injuries that exceed 30% of the body surface area. This hyperpermeability affects the microcirculation at the burn site and in tissues remote from the site of the burn injury. The result is a large flux of fluid and protein from the intravascular to the interstitial space with edema formation in the area of the burn and in all tissues. Inhalation injury alone and combined burn and inhalation injury cause in-creased pulmonary microcirculatory permeability. Pulmonary edema occurs not only because of flux of protein and fluid from the pulmonary circulation but also because of enormous increases in blood flow to the tracheal-bronchial tree. Anatomic connections between the bronchial arteries and the pulmonary circulation deliver a portion of this increased blood flow to the pulmonary circulation and this contributes to pulmonary edema formation. In animal experiments these investigators noted that occlusion of the bronchial-pulmonary connecting channels in a smoke inhalation model greatly reduces pulmonary edema and improves lung function after inhalation injury.

In burn-induced acute lung injury, there is also a strong pro-inflammatory state. Ni-tric oxide and metabolites of this substance play major roles in the inflammation-in-duced lung injury caused by burn. The authors have shown in experimental prepara-tions that there is upregulation of nitric oxide production. Stable plasma metabolites of nitric oxide increase 2-2.5 fold after burn injury.

Nitric oxide exists in three forms, neuronal nitric oxide (nNOS), endothelial nitric oxide (eNOS), and inducible nitric oxide (iNOS); nNOS and eNOS are constitutive iso-forms and iNOS is induced by multiple components of the pro-inflammatory state. These authors note that the pro-inflammatory factors IL-1 and endotoxin activate nu-clear factor -B. This factor is a potent stimulus for production of iNOS. This same actiκ -vation pathway leads to increased production of superoxide that contributes to the ox-idative stress characteristic of the pro-inflammatory state. Elevated levels of iNOS also contribute to the oxidative stress by combining with superoxide to produce peroxyni-trite, which can damage the alveolar capillary membrane. When stores of arginine are depleted, iNOS produces superoxide, which can cause tissue damage.

The authors note that experimental studies have demonstrated arginine depletion in combined inhalation/burn injury with pulmonary dysfunction. The vasodilating properties of iNOS contribute to one of the most important features of acute lung injury, ventilation/perfusion mismatching. Hypoxic vasoconstriction, the protective reaction that redistributes blood from underventilated alveoli to ventilated alveoli, cannot func-

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tion in a high iNOS environment. In acute lung injury, underventilated alveoli have sus-tained perfusion leading to delivery of unoxygenated blood to the pulmonary veins. The finding of hypoxemia and an abnormal alveolar-arterial gradient in patients with acute lung injury can be explained by the failure of the hypoxic vasoconstriction. Data from the authors’ laboratory have shown improved lung function when animals are pre-treated with an iNOS inhibitor.

Enkhbaatar and Traber caution that iNOS is a component of the complex defense against inflammation and a contributor to the pathophysiology of acute lung injury. Be-cause of this, inhibition of iNOS has not produced improved outcomes in clinical studies of pro-inflammatory states such as septic shock. Specific inhibitors of one or another of the NOS isoforms might produce better outcomes. The authors note data from animal experiments showing improved lung function in acute lung injury treated with a spe-cific nNOS inhibitor or with the anti-inflammatory agent, ketorolac.

Another factor activated by inflammation with resultant cell damage and death is poly-(ADP-ribose)-polymerase or PARP. This substance is activated in cells in response to DNA damage and this factor is active in DNA repair processes. Over activation results in depletion of cellular energy stores that can lead to necrotic cell death. PARP is an im-portant contributor to endotoxin-induced lung inflammation and inhibition of PARP can preserve ATP levels in the lung after acute lung injury according to data cited in the re-port by Enkhbaatar and Traber.

Combined inhalation and burn injury results in small airway obstruction because of leakage of exudate rich in neutrophils and products of coagulation, such as fibrin, into the airway lumen. Airway obstruction results in increasing dead space ventilation and contributing to the pathophysiology of acute lung injury. Experimental data from stud-ies completed by these authors demonstrate that this process can be reversed, partially by using nebulized tissue plasminogen activator.

The complex pathophysiology of acute lung injury is produced by inflammatory in-jury to the lung microcirculation, the alveolar capillary interface, and the airways. Each component is present, to varying degrees, depending on the agent producing the in-flammatory state and the resulting lung injury. Transfusion of banked blood is one cause of acute lung injury. This topic is reviewed by Swanson and coauthors72 in Lung, 2006. Trauma and critical care surgeons have consistently observed an association be-tween massive transfusion and post-trauma acute respiratory distress syndrome. That single transfusions of blood products (except albumin) can cause lung injury and respi-ratory distress acutely was first recognized in 1951. Characterization of transfusion re-lated lung injury as a transfusion reaction resulted from studies demonstrating anti-leu-cocyte antibodies in patients with acute lung injury closely following transfusion. The

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term transfusion related lung injury (TRALI) was first coined in a 1983 report cited by Swanson and coauthors.

The TRALI clinical syndrome affects approximately 0.2% of patients who receive transfusions. Eight percent of transfusion reactions result in lung injury and this entity is the cause of 13% of transfusion-related fatalities. Overall mortality for a TRALI episode is 5%-10%. Respiratory distress usually develops within six hours of transfu-sion. The clinical picture is typical of acute lung injury and consists of hypoxemia, tachypnea, and pulmonary infiltrates on chest radiograph. Supplemental oxygen is re-quired in all patients and nearly three-quarters of the symptomatic patients will require intubation and ventilator support. The typical TRALI episode will resolve with support-ive care in 48-96 hours.

A definitive clinical diagnosis requires exclusion of other causes of acute lung injury. Most patients who require blood product transfusions are significantly injured or ill and exclusion of other causes for acute lung injury might not be possible. Recovery of anti-HLA and/or anti-leucocyte antibodies from donor blood supports a diagnosis of TRALI, especially if the recipient is shown to have a leucocyte antigen phenotype matching the antibody recovered from donor blood. Culprit antibodies are found in up to 90% of donor blood samples when a TRALI episode occurs. Despite this observation, TRALI episodes occur without demonstrable immune reaction. The observation that older banked blood is more likely to cause TRALI has led to the development of nonimmune models of TRALI. These involve factors that prime neutrophils and are present in in-creased concentrations in older banked blood. The specific factor or factors responsible are not known but plasma from recipients who develop TRALI contains increased con-centrations of neutrophil-priming substances. Histopathology of the lung shows pro-nounced leucocyte sequestration in the lung. It is likely that lung damage is caused by oxygen free radicals induced by the sequestered leucocytes.

Therapy for TRALI is mainly focused on support of oxygenation until the process re-solves. Prevention of TRALI is challenging. Rejection of blood donation by donors impli-cated in a TRALI episode is one avenue. Probably the most effective approach will be to adopt conservative transfusion protocols so that banked blood transfusion is reduced, overall.

Epidemiology and outcomes of acute lung injury and acute respiratory distress syndromeTwo older articles are discussed in this section to provide perspective about mor-

bidity and mortality associated with acute lung injury and acute respiratory distress syndrome. Prognostic factors will also be discussed. The first article discussed is by Luhr and coauthors73 from the American Journal of Respiratory and Critical Care Medicine, 1999. These authors begin by citing several reports that document mortality

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rates for acute respiratory failure and acute respiratory distress syndrome ranging from 40%-50%. They note, also, that several reports have suggested that mortality for acute respiratory distress syndrome might be decreasing. Interpretation of data is chal-lenging because of the variability of clinical definitions used in the reported studies. The aim is this analysis was to perform a prospective cohort study involving patients aged 15 years and older admitted to ICUs in Sweden, Denmark, and Iceland during an eight-week interval.

Acute respiratory failure was defined as endotracheal intubation followed by 24 hours or more of ventilator support. Acute lung injury and acute respiratory distress syndrome were defined according to criteria promulgated by the American-European Consensus Conference on ARDS. The consensus conference definition includes the fol-lowing criteria 1) acute symptom onset; 2) Pa02/FI02 ratio of < 300 for acute lung injury and < 200 for acute respiratory distress syndrome; 3) bilateral infiltrates on chest ra-diograph; and 4) pulmonary artery occlusion pressure < 18 mmHg or no clinical evi-dence of left atrial hypertension. Each patient was enrolled at the time of the first ad-mission to the ICU and this admission was the only incident of respiratory distress counted in the study. The study included 1231 patients who fulfilled criteria of acute respiratory failure. Of this group 287 patients fulfilled criteria for acute lung injury and 221 fulfilled criteria for acute respiratory distress syndrome. Mortality for the total group was 41%. Mortality rates for acute lung injury (42.2%) and acute respiratory dis-tress syndrome (41.2%) were nearly identical to the total group mortality. The question of whether these patients died from the respiratory disease or died with the respiratory disease remains unanswered by these data.

The authors note that the close agreement of death rates for all three clinical diag-noses suggests that death from refractory hypoxemia might be less common than death from a condition associated with or, perhaps, precipitating hypoxemia. Luhr and asso-ciates were able to demonstrate significant mortality prediction from the presence of liver disease, advanced age, and a nonpulmonary cause of respiratory dysfunction. These factors also suggest that death might not have occurred solely because of respira-tory insufficiency. Additional perspective on this issue appears in an article by Rocco and coauthors74 in Annals of Surgery, 2001. These authors conducted a retrospective, single institution review analyzing mortality and prognostic factors in 980 consecutive patients who were intubated and who received ventilator support in the ICU. Among these were 111 patients who fulfilled the American-European Consensus Conference on ARDS criteria for acute respiratory distress syndrome (see discussion above).

Lung injury scores were calculated for each patient. The lung injury score assigns points for assessments of the chest radiograph, degree of hypoxemia, level of PEEP, and lung compliance. A score of 2.5 or more is indicative of acute respiratory distress syn-

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drome. Lung injury scores were > 2.5 in all 111 patients. Patients were divided into sub-groups depending on whether the patient was a “surgical” patient or a “trauma” patient. Patients were also divided into a group of patients admitted between January 1, 1990, and December 31, 1994, and those admitted between January 1, 1995, and December 31, 1998. The data indicate that surgical patients were older and more likely to have respiratory failure related to intraabdominal infection. Trauma patients were more likely to have respiratory failure related to multiple injuries and/or direct thoracic in-jury. Mortality rates declined in both periods but the magnitude of decline was statisti-cally significant for trauma patients only.

In the second interval, overall mortality for acute respiratory distress syndrome de-clined from 72% to 38% and this decline was statistically significant. The authors em-phasize that the decline in mortality occurred even though the patients in the second in-terval were older. One characteristic of the more recent group was that emergency op-eration frequency declined. A decrease in emergency operations was probably associ-ated with a lower risk for intraabdominal infection, which was the most common cause of fatal acute respiratory distress syndrome. The authors also point out that they used lower tidal volumes and lower mean airway pressures as ventilator strategies in the later group. The authors note that advanced age and comorbid illness (particularly liver disease) were strongly predictive of mortality.

Editorial commentThe data discussed above document the correlation between age, increasing illness

severity, infection, and acute respiratory distress syndrome. The role of inflammation in the genesis of acute lung injury and as a driver of progression to acute respiratory dis-tress syndrome is confirmed in the clinical series. Younger patients with direct lung in-jury (trauma patients) are more likely, as a group, to survive. Ventilator strategies might also play a role in producing the improved outcomes observed in the article by Rocco and colleagues.74 The current approaches to ventilator support for patients with acute lung injury and acute respiratory distress syndrome is discussed in more detail in the next section.

Ventilator strategiesThe approach to ventilator therapy for patients with acute lung injury and acute res-

piratory distress syndrome has changed in one major and several minor ways over the past three to five years. Traditionally the approach to ventilation has been designed to maintain oxygenation and carbon dioxide removal. An understanding of the basic mech-anisms of acute respiratory failure (many of these discussed above) has improved un-derstanding. Most importantly, surgeons are now aware of the potential patient harm that might accompany ventilator therapy. The effects of ventilator pressures and vol-umes on hemodynamics have been well recognized for many years.

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More recently, a group of phenomena has been recognized known as ventilator-in-duced lung injury. Included in this category are barotrauma (mediastinal emphysema, pneumothorax), which refers to lung damage from disruption of alveoli resulting from excess alveolar pressures. Barotrauma can also result from the combination of rapid ventilator rates with PEEP that produces “auto-PEEP,” a phenomenon that produces successively increasing airway pressure because the rapid respiratory rate does not al-low return of airway pressure to the set PEEP level before the next breath is delivered. Volutrauma refers to alveolar damage caused by ventilation of high-compliance areas of the lung with large inspired volumes. The large volumes are delivered to high-compli-ance areas because consolidated areas of the lung lose compliance and the inspired gas is “shunted” to the high-compliance alveoli. Atelectrauma is the term for alveolar injury that occurs from successive deflation and inflation of alveoli during the ventilator cycle. Unstable alveoli might collapse at end expiration and have to be reopened with the next inspiration, which produces injury to the alveolus. The “collapse-reopen” cycle also in-creases the intensity of the lung inflammatory response. Production of pro-inflamma-tory cytokines is stimulated and this phenomenon contributes to ventilator-associated lung injury.

The approach to minimizing ventilator-associated lung injury is based on an under-standing that lung injury results from interactions of the ventilator cycle, mean airway pressure, and tidal volume. High mean airway pressure required to deliver high tidal volumes is the main cause of ventilator-associated lung injury. Approaches to lung-pro-tective ventilation strategies emphasize the need to lower tidal volume and lower mean airway pressure. In patients with acute respiratory distress syndrome, microcirculatory obstruction and small airway obstruction might increase dead space ventilation to the extent that PaC02 rises. This rise can be made tolerable for the patient so that additional respiratory distress does not occur. The process of allowing PaC02 to increase is termed “permissive hypercapnia” and this is a component of lung-protective ventilation strate-gies.

Data from randomized trials have demonstrated a significant reduction in mortality for acute respiratory distress syndrome with the use of lung-protective ventilation. In this section of the overview, we will review some recent contributions to the medical literature pertinent to ventilator therapy for patients with acute respiratory distress syndrome. The scientific basis and clinical effectiveness of “recruitment maneuvers” de-signed to reopen and maintain alveoli and alternative strategies for “weaning” the pa-tient from ventilator therapy are reviewed.

The first article was published in 2003 in Critical Care Medicine75 and is a random-ized controlled trial of alveolar recruitment maneuvers sponsored by the ARDSNet group of investigators. A full-text reprint of this article accompanies this issue of SRGS.

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Brower and coauthors note that lung-protective ventilation has been shown to decrease mortality. From the available data, it is not clear that lung protective ventilation con-tributed to alveolar recruitment, lowered risk of ventilator-associated lung injury, or improved outcomes in terms of lung function. This study was performed to assess the effectiveness of maneuvers designed to reopen and maintain alveolar inflation. In the experimental group, recruitment maneuvers were administered on the first and third or second and fourth mornings after enrollment. The recruitment maneuver consisted of changing the ventilator mode to continuous positive airway pressure mode and in-creasing airway pressure in increments up to 35-40 cmH20 depending on body weight. The recruitment maneuver was held for 30 seconds unless hemodynamic instability, cardiac arrhythmia, decreased oxygen saturation, or tachycardia (>130 bpm) occurred. The control patient group received sham recruitment maneuvers. PEEP was adjusted according to the level of inspired oxygen required by the patient. An upper limit of 24 cmH20 was permitted.

The authors noted immediate improved oxygenation after the use of recruitment maneuvers but the effect diminished over time. The authors note that this observation might have occurred because near maximal alveolar inflation had already been achieved using PEEP. They note that the single recruitment maneuver might not be as effective as repeated maneuvers. The topic of multiple recruitment maneuvers is the fo-cus of the next article reviewed.

The second article is by Meade and coauthors76 in the Journal of the American Medi-cal Association, 2008. These authors report a randomized trial of patients whose acute respiratory distress syndrome was diagnosed by standard criteria. One group of pa-tients was treated with standard lung-protective ventilation (respiratory rate < 25, tidal volume of 6 mL/kg, and PEEP of 8-12 cmH20). Another group had lung protective venti-lation combined with recruitment maneuvers (inspiration with breath hold at a steady pressure of 40 cm H20 for 10-15 seconds during each ventilator disconnection for suc-tioning or other reasons up to 4 times/day). In the experimental group, PEEP was set dependent on the Fi02 required by the patient. PEEP pressures ranged from 5-10 cmH20 for Fi02 of 0.6 or less and ranged up to 24 cmH20 for patients requiring Fi02 of 1.0. Vol-ume-controlled assisted breaths were used in control patients and pressure-controlled ventilation was used in the experimental group. “Rescue therapies” (prone position, high frequency oscillation ventilation, extracorporeal membrane support) were permit-ted for patients with refractory hypoxemia and/or acidosis.

The frequency of barotrauma (mediastinal emphysema, pneumothorax) was recorded. The data demonstrate that the experimental group had improved oxygena-tion with no increase in the risk of barotrauma or rescue interventions. The mortality for the entire group was 38% and there was no significant difference in mortality risks

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for the two groups. Of interest is that attributable mortality for refractory adult respira-tory syndrome was only 6% overall. The experimental group had a significant reduction in mortality from refractory hypoxemia. The authors concluded that addition of recruit-ment maneuvers and incremental increases in PEEP (based on the required inspired oxygen concentration) resulted in improved oxygenation that was durable over time. This strategy represents an acceptable alternative to conventional therapy.

An abiding question regarding the effectiveness of recruitment maneuvers relates to whether recruitment maneuvers, combined with optimum PEEP, distend already in-flated alveoli or recruit previously contracted or collapsed alveoli. This issue is the topic of an article by Schreiter and coauthors77 in Critical Care Medicine, 2004. This study ana-lyzed helical CT images obtained before and after recruitment maneuvers and PEEP ad-justment in 17 patients with direct lung trauma resulting in acute respiratory distress syndrome. The authors observed increased lung inflation on CT images that was ob-tained by reducing consolidated lung area rather than expanding inflated lung. They concluded that recruitment maneuvers combined with optimum PEEP reopens con-tracted or collapsed alveoli and provides sustained inflation of these lung areas.

The next article reviewed by Mercat and coauthors78 appeared in the Journal of the American Medical Association, 2008. This report describes a randomized controlled trial in patients who had acute respiratory distress syndrome diagnosed by standard crite-ria. One group of patients was treated with lung-protective ventilation with PEEP levels set from 5-9 cmH20 based on the level of oxygenation. The second group of patients had PEEP adjusted upward to establish a plateau airway pressure of 28-30 cmH20. In this study the experimental group had higher fluid requirements (probably because of the hemodynamic effects of higher airway pressures), but experienced better oxygenation, a lower risk of requiring “rescue” interventions, and decreased ventilator and organ failure days. The authors caution that the patients in this study who met criteria for acute lung injury versus acute respiratory distress syndrome had less benefit from the higher PEEP strategy, and this patient group might actually experience lung injury from high PEEP.

The data about the durability of alveolar recruitment are variable, as is obvious from the articles previously reviewed. A systematic review of available data on recruit-ment maneuvers by Fan and coauthors79 in the American Journal of Respiratory and Crit-ical Care Medicine, 2008, analyzed data from studies involving nearly 1200 patients. Available studies all showed improved oxygenation after application of recruitment ma-neuvers but most studies also disclosed that improvement was transient. Adverse events are unusual but arterial hypotension accompanies most recruitment maneuvers. Hypotension is noted more often in patients with less severe lung injury. They note that PEEP elevations after a recruitment maneuver improve the durability of the improve-

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ment in oxygenation. The authors conclude with the caution that the value of transient improved oxygenation noted after recruitment maneuvers is currently unknown. Signif-icant impact of recruitment maneuvers on global outcomes measures such as mortality has not been demonstrated. These authors urge that the decision to employ recruitment maneuvers be based on the severity of respiratory distress (less severely hypoxemic patients probably do not benefit) and the response of the individual patient to PEEP and recruitment maneuvers. The least improvement in oxygenation was observed in patients with low lung compliance. This might indicate that such patients have limited capacity for alveolar recruitment.

The fundamental concept supporting the use of PEEP and recruitment maneuvers is that alveolar collapse is a major driver of ventilation/perfusion mismatching, hypox-emia, and loss of compliance in acute lung injury. An experimental study examining this question is by Mertens and coauthors80 appeared in Critical Care Medicine, 2009. These authors used darkfield intravital microscopy to view the lung parenchyma visualized through a transthoracic window. Lung injury was induced with intratracheal hy-drochloric acid.

These authors found that alveolar distention increases with ventilation pressure in normal lungs with a sigmoid shaped curve demonstrated when the percent increase in alveolar volume was plotted against inflation pressure. Damage to the lung resulted in alveolar thickening and reduced alveolar volume but alveolar collapse was not ob-served. In an editorial by Hubmightr accompanying Mertens’ article, the editorialist notes that the elegant observations reported in the work of Mertens and colleagues shows that in the normal lung alveoli are not recruited but distend and contract. The lung damage produced in this study did not result in lung edema, and Hubmightr notes that alveolar damage leading to alveolar collapse can result from fracture of liquid bridges in the edematous lung with inflation and deflation. Thus, the injury in this study might not have reproduced the pathophysiology of acute lung injury. He concludes that additional work is required before a full understanding is achieved of alveolar inflation in the face of lung injury.

Another ventilation strategy for patients with severe acute respiratory distress syn-drome is high-frequency oscillatory ventilation. This modality is used frequently in pre-mature infants with respiratory distress. Ventilation of the lung occurs from rapid ad-ministration of very small tidal volumes (1-3 mL/kg) delivered at high ventilatory rates that allow mixing of gas within the lung so that oxygenation is preserved and carbon dioxide is removed. High-frequency oscillating ventilation allows maintenance of high end-expiratory lung volume without overdistention of alveoli. The topic of high-fre-quency oscillatory ventilation and ventilator-induced lung injury is addressed in an ar-ticle by Imai and Slutsky81 in Critical Care Medicine, 2005. Consistent data from studies

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in neonates indicate the effectiveness of high-frequency oscillatory ventilation com-bined with maneuvers designed to maintain lung inflation volumes using recruitment maneuvers and PEEP adjustments. Minimal frequencies of ventilator-associated lung in-jury were observed in these studies.

The authors note that studies in adult patients with acute respiratory distress syn-drome have not shown consistent benefit from the use of high-frequency oscillatory ventilation. Ideal strategies for maximizing pressure in the proximal and distal airways and optimizing lung volumes with this ventilatory strategy have not yet been developed and this limits application of this modality. Although there are data to suggest transient improvement in oxygenation, there is no demonstration of improved mortality out-comes and routine use of this modality is not recommended.

The main objectives of lung-protective ventilation are to preserve adequate oxy-genation, maintain lung inflation, facilitate re-inflation of contracted or collapsed alve-oli, and minimize the risk of ventilator-associated lung injury. Continuous positive air-way pressure strategies are well suited to these objectives. The limitations of continu-ous positive airway approaches include that use of these approaches requires an alert; cooperative, spontaneously breathing patient and these approaches are sometimes dif-ficult to apply in intubated patients. In addition, a relatively small proportion of ICU ventilators can deliver continuous positive airway pressure efficiently. Thus, continu-ous positive airway pressure is most useful during the “liberation” or “weaning” process as the patient is assisted through the transition from ventilator support to nor-mal breathing. One variant of continuous positive airway pressure, airway pressure re-lease ventilation, can be used in intubated patients. The patient must be breathing spontaneously in order for this mode of ventilation to work properly. In suitable pa-tients, airway pressure release ventilation can maintain lung inflation and recruit addi-tional alveoli in the dependent areas of the lung during spontaneous breathing inter-vals.

An article describing airway pressure release ventilation is by Habashi82 in Critical Care Medicine, 2005. This article is supplied as a full-text reprint with this issue of SRGS. Habashi notes that airway pressure release ventilation was initially described in two ar-ticles authored by Stock and Downs in 1987. This approach to ventilation uses continu-ous positive airway pressure (Phigh) to maintain lung inflation for a preselected interval (Thigh). Elimination of carbon dioxide is facilitated by scheduling periodic releases of air-way pressure that permit airway pressure to fall to a preselected level (Plow). Low pres-sure is maintained for a preselected interval (Tlow) and carbon dioxide is eliminated by this exhalation. Spontaneous, patient-generated breaths assist in recruiting alveoli by supplying diaphragmatic contractions. The recruited alveoli are in the dependent lung areas adjacent to the diaphragm. The author notes that the process of alveolar recruit-

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ment proceeds along variable time courses because inflation of one group of alveoli af-fects the inflation rate of neighboring alveoli. Recruitment, therefore, proceeds in a wave or “avalanche” fashion. Maintenance of continuous positive airway pressure as-sists in maintaining inflation as additional alveolar units open. Recruitment occurs be-cause of decreases in pleural pressure rather than increases in airway pressure and Habashi emphasizes that the intermittent airway pressure releases also work to pre-vent lung overdistention. To minimize de-recruitment, low pressure intervals are kept as short as possible (0.2–0.8 seconds in adults).

Airway pressure release ventilation contrasts with pure continuous positive airway pressure breathing in that the work of breathing increases with continuous positive air-way pressure alone because of the need for the patient to expend energy to remove car-bon dioxide. In patients with decreased lung compliance and respiratory muscle decon-ditioning, this increased work of breathing might not be tolerated by the patient. Air-way pressure release ventilation effectively addresses this problem. Habashi notes that alveolar ventilation is intermittent while carbon dioxide delivery to the alveolus is con-tinuous. The intermittent pressure releases refreshed alveolar gas and re-establishes the gradient for diffusion of carbon dioxide from blood to alveolar gas.

Improvement of oxygenation during airway pressure release ventilation occurs be-cause of maintenance of high mean airway pressure that serves to increase the number of ventilated, perfused alveoli. Spontaneous breaths during the high-pressure interval serve to recruit additional alveoli in the dependent, perfused lung areas and this mecha-nism assists in supporting oxygenation as well. The author notes that resistance of the artificial airway during the early phase of the pressure release interval provides airway resistance that effectively produces PEEP which also assists in supporting oxygenation. Because of the PEEP that results from airway resistance, the low pressure setting is preferably zero.

Initial set-up of airway pressure release ventilation is accomplished depending on whether the patient is newly intubated or whether this modality is being used to assist in transition to weaning. Suggested set-up strategies are presented in Table 2 of Habashi’s article. For example, an adult patient newly intubated would have a desired plateau airway pressure selected (20-35 cmH20), and this would be the high-pressure setting. Higher pressures might be required where combined lung and chest wall com-pliance are reduced (obese patients). Low pressure would be set at zero. The high time interval would be set at 4-6 seconds and the low time interval would be 0.2-0.8 seconds. Longer low-time intervals might be required in patients with chronic obstructive lung disease. These settings would produce 10-12 exhalations/minute. In patients who are transitioning from conventional ventilator support, the high pressure is set at the prior ventilation mode plateau pressure.

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Habashi notes that airway pressure release ventilation is a useful ventilation mode for spontaneously breathing patients who are ventilated in the prone position or in ki-netic beds (see discussion in SRGS, Vol. 35, No. 6). He also notes that addition of pres-sure support ventilation to airway pressure release ventilation produces unfavorable increases in transpulmonary pressure. The author notes that spontaneous breathing is required for effective use of airway pressure release ventilation and, therefore, this ap-proach is not indicated in patients who require aggressive sedation/analgesia or neuro-muscular blockade. The modality is associated with less patient discomfort from the use of adjuvant ventilation compared with conventional ventilation. This consistent obser-vation suggests that intervals of heavy sedation use or neuromuscular blockade might be shortened by applying airway pressure release ventilation. Habashi concludes by noting that weaning from airway pressure release ventilation is a simple process in-volving reductions of the high pressure setting and extension of the high pressure time interval. Decreasing the number of releases as the pressure changes are made facilitates transition to normal patient breathing. Finally, Habashi notes that this modality can be applied using noninvasive ventilation interfaces.

Comparative clinical data documenting the benefit of airway pressure release venti-lation are found in a review by Siau and Stewart83 in Clinics in Chest Medicine, 2008. These authors note that clinical series evaluating airway pressure release ventilation have been retrospective observational studies or comparative studies employing his-toric controls. These studies suggest a reduction of mortality with the use of this modal-ity in traumatic lung injury patients. There has been little control of confounding vari-ables in these analyses and, because of this, a definite reduction in mortality cannot be assumed. Reductions in ICU lengths of stay and ventilator intervals have been reported. Direct comparisons of airway pressure release ventilation to lung-protective ventilation have not been reported. Siau and Stewart conclude that airway pressure release venti-lation is appropriate for carefully selected patients but a recommendation for wide-spread use of this approach cannot be made based on current evidence.

One area where airway pressure release ventilation might be valuable is in patients who need a transition between conventional ventilation and implementation of a for-mal “weaning” protocol. Weaning from ventilator support is clinically challenging. Dur-ing full ventilator support respiratory muscle deconditioning occurs and, because of this, muscle weakness might limit ventilatory effort. Lung and chest wall compliance are decreased by the primary lung disease, body habitus (obesity), pain from incisions, chest drainage tubes, and rib fractures. Successful weaning requires that the primary disease causing acute respiratory distress syndrome be under control. In addition, the patient should be capable of initiating spontaneous breathing efforts. Ideally, use of se-dation and analgesia are reduced to the point that the patient can cough, make deep breathing efforts, and participate in patient care by changing position in the bed or

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moving from bed to chair with assistance. Correction of nutritional deficits should be underway. Once these conditions are met, transition to an assisted-ventilation strategy is a first step. Spontaneous breathing trials can be scheduled three or four times daily under nursing and/or respiratory therapist supervision, and intervals of spontaneous breathing can be incrementally increased (“wind sprints”). When extubation is possible, noninvasive interfaces can be used to assist patients with “graduation” to normal breathing. These approaches are particularly useful in patients with COPD.

A systematic review of available data on the use of noninvasive ventilation as a weaning adjunct appears in an article by Burns and coauthors84 in British Medical Jour-nal, 2009. These authors reviewed 12 trials involving 530 patients. They note that most patients enrolled in weaning trials using noninvasive ventilation had COPD. COPD was not necessarily the main contributor to the need for ventilator support in the reported trials. The authors note that pooled data suggest a reduction in mortality and ICU length of stay for patients with COPD weaned with noninvasive ventilation protocols. There was no increased risk of weaning failure, pneumonia, or reintubation in the reported trials. These authors conclude that the evidence in support of noninvasive ventilation as a means of facilitating weaning is sufficiently strong to recommend this modality in pa-tients with COPD.

Editorial commentFrom the perspective of the editor, weaning critically ill surgical patients from me-

chanical ventilation is highly dependent on the success of efforts to control the process that led to the need for ventilation in the first place. Deconditioning is an especially challenging problem that limits success of weaning in the elderly and in patients with severe comorbid conditions. Failure of weaning with deterioration of oxygenation and lung compliance leading to reinstitution of ventilation is a high price the patient pays for suboptimal timing of weaning. Weaning failure and extubation failure resulting in the need to reinstitute mechanical ventilation are, in my view, largely avoidable compli-cations. Underestimation of the need for analgesia/sedation, underuse of assistive exer-cise physical therapy programs, inadequate patient counseling, delay or nonuse of nu-tritional support, and suboptimal level of consciousness are common modifiable factors contributing to weaning failure. Education of nurses, physical therapists, and respira-tory therapists in the use of weaning protocols permits weaning and extubation when criteria for acceptable patient-controlled breathing are fulfilled. Use of these multidisci-plinary protocols can improve the success rates for weaning in critically ill surgical pa-tients.

Nonventilator adjunctive measuresSeveral adjuncts to traditional ventilator therapy might improve outcomes of acute

lung injury and acute respiratory distress syndrome in carefully selected patient

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groups. These adjuncts can be categorized as 1) measures for reducing the risk of addi-tional lung injury (fluid therapy); 2) measures that modulate the inflammatory process (corticosteroid therapy); 3) interventions that modify pulmonary hypertension (nitric oxide); 4) measures designed to improve distribution of ventilation and perfusion (prone positioning, discussed in SRGS, Vol. 35, No. 6); 5) adjuncts that replace lung function (extracorporeal membrane oxygenation); and 6) interventions that alter the airway (tracheostomy). In this section of the overview, we review these topics.

The first article reviewed appeared in the New England Journal of Medicine in 200685

entitled “Comparison of two fluid-management strategies in acute lung injury.” This ar-ticle is supplied as a full-text reprint with this issue of SRGS. The article by Wiedemann and coauthors is a report of a randomized, prospective trial comparing two approaches to fluid management in patients with acute respiratory distress syndrome. The study was conducted by the ARDSNet group of investigators. One thousand patients were en-rolled and randomly assigned to a conservative or liberal fluid management group. The characteristics of fluid management for each enrolled patient were determined in real time depending on the central venous pressure or pulmonary artery pressure, the pres-ence of shock (arterial pressure < 60 mmHg), and external signs of inadequate perfu-sion, such as skin mottling or oliguria. Thus, a patient with effective circulation and no oliguria who had a central venous pressure of >13 and was assigned to the conservative fluid group would receive furosemide and intravenous fluids at a minimum rate until central venous pressure was in the 9-13 cm H20 range.

Patients in shock were treated with fluids and vasoactive agents as needed until ap-propriate hemodynamic response and venous or pulmonary artery target pressures were achieved. All patients enrolled met standard criteria for acute respiratory distress syndrome and all were ventilated with standard ventilator strategies. The investigators found that there was no statistically significant difference in mortality in the two groups of patients. There were significant improvements in oxygenation in the conservative strategy group. Ventilator days and ICU stay were reduced in the conservative group and there was no increase in the frequency of renal insufficiency or the diagnosis of shock in the conservative therapy group.

In the discussion section, data indicate that small increases in pulmonary artery oc-clusion pressure above the normal range can be associated with large increases in ex-travascular lung water. The authors also cite studies indicating that removal of excess interstitial space fluid with furosemide is associated with improved oxygenation. Sup-plemental albumin infusion given to hypoalbuminemic patients to improve oncotic pressure did not result in improved oxygenation unless furosemide was given along with the colloid infusion. These results suggest that there is a “mobilizable” fluid space within the lung amenable to movement of fluid along pressure gradients but that pro-

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tein leakage might limit the effectiveness of efforts to improve oncotic pressure. The lack of mortality difference in this study most likely relates to the fact that patients who died were actually dying of an associated illness, and not from acute respiratory insuffi-ciency.

Recognition of the role of inflammation in the pathophysiology of acute lung injury has stimulated evaluation of anti-inflammatory strategies for treatment of acute respi-ratory distress syndrome. This topic is the subject of a report by Tang and coauthors86 in Critical Care Medicine, 2009, who report a meta-analysis of randomized controlled trials and observational studies of low-dose corticosteroids (0.5-2.5 mg/kg/day) in pa-tients with acute respiratory distress syndrome. For cohort studies, analyses of data drawn from 307 patients were included. Randomized trials included 341 patients. Both types of studies demonstrated improved mortality risk and both types of studies demonstrated improved oxygenation and decreased ICU length of stay. Overall, there was a 38% reduction in risk of death for patients treated with low dose methylpred-nisolone. There was no increased risk of infection, neuromyopathy, or major complica-tions in the steroid treated groups.

The authors note that their study effectively deals with the challenges faced by other investigators who attempted to determine whether there was a benefit to corticos-teroid treatment with no increase in complications. Earlier analyses dealt with widely varying dosage ranges, differing types of steroid drugs, and heterogeneous patient groups. This study dealt with studies using low-dose medication with standard defini-tions of acute respiratory distress syndrome and standard reporting of outcomes. The authors conducted subgroup analysis that indicated efficacy of low-dose corticosteroids even when treatment was started several days after the onset of acute respiratory dis-tress syndrome. In addition, treatment effect was independent of the use of “open lung” ventilation strategies. The analysis also confirmed that the treatment effect was inde-pendent of any affect on the outcomes of sepsis. The authors conclude that low-dose steroid treatment is effective and safe in patients with acute respiratory distress syn-drome. The data indicate that steroid therapy should be tapered and not stopped abruptly. Abrupt cessation of steroids can be associated with rebound inflammation and worsening of lung function. Tang and associates acknowledge that this study is lim-ited by the fact that they had no knowledge of the presence or absence of dysfunction of the pituitary-adrenal axis in these studies.

An approach to the diagnosis of adrenal insufficiency in critically ill patients is the topic of a consensus report by Marik and coauthors87 in Critical Care Medicine, 2008. This article is supplied as a full-text reprint with this issue of SRGS These authors rec-ommend that the diagnosis of adrenal insufficiency in critically ill patients can be estab-lished by documenting an increase of less than 9 g/dL of total serum cortisol after a μ

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dose of adrenocorticotrophic hormone of 250 g or a random total serum cortisol level μof < 10 g/dL. Once the diagnosis is established, treatment with corticosteroid replaceμ -ment is valuable especially in patients with septic shock and inadequate responses to fluids and vasoactive drugs. Steroid therapy is useful in the treatment of early acute res-piratory distress syndrome confirming the observations of Tang and coauthors, dis-cussed earlier. Readers should note that the treatment benefit observed by Tang and colleagues was not limited to early acute respiratory distress syndrome.

Inhaled nitric oxide has potent pulmonary vasodilating properties and, according to some data, anti-inflammatory features also. Thus, this agent has been suggested as a means of improving ventilation/perfusion matching in patients with acute respiratory distress syndrome. A meta-analysis of data pertinent to this topic appears in an article by Adhikari and coauthors88 in the British Medical Journal, 2007; analyzed data from 12 trials of acceptable quality that had enrolled more than 1200 patients. The data dis-closed modest, transient, improvements in oxygenation but no affect on mortality from acute respiratory distress syndrome. In addition, patients receiving nitric oxide in-curred a significant increased risk of renal dysfunction. The authors concluded that available data do not support a role for inhaled nitric oxide in the treatment of acute respiratory distress syndrome.

Another adjunctive therapy applied to patients with acute respiratory distress syn-drome is extracorporeal membrane oxygenator support. Using this support device in-volves connecting a membrane oxygenation device and a heat exchanger to the patient using a venovenous circuit or, in patients with hemodynamic instability, a venoarterial circuit. Limited anticoagulation is required for the circuit to function. Blood is drawn from a central venous or arterial source and returned via a second venous access after oxygenation and warming. This device has been primarily used as “rescue” therapy for patients who cannot be adequately ventilated. Intuitively, the best results should be ob-tained in patients with isolated lung damage caused by noninfectious etiologies. For these reasons, patients with direct pulmonary injury would be a patient group where the device would probably achieve the best results.

A clinical series reporting results of extracorporeal membrane oxygenator usage in patients with multiple injuries is reported in an article by Cordell-Smith and coauthors89

in Injury, 2005. These authors report a series of 28 patients who received extracorpo-real membrane oxygenator support for severe acute respiratory distress syndrome de-veloping after direct pulmonary traumatic injury or after multiple trauma (mostly pelvic and long bone fractures). Because of the need for anticoagulation, use of this res-cue approach would be limited in patients with central nervous system injuries or in-traabdominal injuries. The authors note that the duration of support in this patient group was, on average, 141 hours. This support interval is shorter than intervals of sup-

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port used in other patient groups. Twenty of the 28 patients survived. Nonsurvival was noted more often in patients with systemic sepsis or pulmonary infection.

The report does not detail the characteristics of the ventilator therapy used in these patients and it is, therefore, not completely clear whether the use of extracorporeal membrane oxygenation was to “rescue” patients or not. This mortality rate is somewhat lower than the mortality reported for patient groups containing both surgery and trauma patients treated with aggressive “open-lung” ventilation strategies, but the pa-tient numbers in this report are small and the process of selecting the patients for ther-apy with the external device is not described in detail. Nonetheless, trauma patients might represent a favorable group for use of extracorporeal membrane oxygenator sup-port.

Long-term results of extracorporeal membrane oxygenator support are important because these data provide insight into the process of lung healing and offer the oppor-tunity to assess potential chronic adverse effects of extracorporeal support. An article providing data relevant to this topic, by Linden and coauthors,90 appeared in Acta Anaesthesiologica Scandinavica, 2009. These authors report results of high-resolution lung CT scans, extensive pulmonary function tests, lung scintigraphy, and lung-specific quality of life questionnaire responses in a group of 21 patients who survived severe acute respiratory distress syndrome treated with extracorporeal membrane oxygenator support. During extracorporeal membrane oxygenator support episodes, patients were maintained on low-level continuous positive airway pressure ventilation. Clinical as-sessments were performed at least one year after therapy in all patients. High-resolu-tion CT images disclosed changes consistent with lung fibrosis in all patients, but the ex-tent of the changes was limited and the distribution of CT changes was not the typical anterior distribution of ventilator induced lung injury. Pulmonary function tests showed abnormal carbon dioxide diffusing capacity in nearly two-thirds of the patients tested. The abnormality was small, however, and functional impairment was mild. Over-all, pulmonary function tests were within the normal range. Pulmonary scintigraphy showed residual airway obstructive patterns in all patients characterized by prolonged washout intervals for the inhaled radioisotope. Exercise testing was performed; re-duced exercise tolerance was seen in one-third of patients, but the limitation was leg fa-tigue rather than pulmonary symptoms in all of these patients.

All the patients responded to the quality of life questionnaire and all stated that quality of life was reduced after treatment with extracorporeal membrane oxygenator support. Importantly, none of the patients required supplemental oxygen and all were employed full-time in the same occupations held before their illness. The authors con-cluded that long-term impairment after extracorporeal membrane oxygenator support is usually mild.

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Tracheostomy is an adjunctive treatment used in patients with acute respiratory distress syndrome. The objective of tracheostomy use is mainly to improve patient comfort, permit speech, reduce the risk for laryngeal injury, and optimize airway access. Available data suggest that tracheostomy facilitates discharge of patients from the ICU, shortens ventilator intervals, and, possibly, reduces the frequency and severity of venti-lator-associated pneumonia. These potential benefits are accompanied by costs and complications.

Tracheostomy, at a minimum, results in disfiguring scarring of the anterior neck. Airway bleeding, tracheal ring fracture, tracheal stenosis, and esophageal injury might occur. Tracheal-innominate artery fistula is a complication that has nearly disappeared with reductions in post-tracheostomy local wound infection and appropriate choice of the level of tracheostomy tube insertion (third tracheal ring). Bedside percutaneous tra-cheostomy techniques have reduced the need to transfer patients to the operating room for formal surgical procedures. Overall reductions in healthcare resource use have been reported with the use of bedside percutaneous tracheostomy; bedside tracheostomy re-quires partial removal of the endotracheal tube and use of the flexible fiberoptic bron-choscope to guide tracheostomy tube insertion. Thus, additional costs are incurred along with the risk for sudden airway loss during the procedure. In this section of the overview, several articles dealing with the use of tracheostomy as an adjunct to other treatments for acute respiratory distress syndrome are discussed.

The first article discussed is by De Leyn and coauthors.91 It appeared in the Euro-pean Journal of Cardio-Thoracic Surgery, 2007, and is supplied as a full-text reprint ac-companying this issue of SRGS. It reports practice guidelines for the use of tra-cheostomy developed by a joint committee of the Belgian Society of Pneumonology and the Belgian Association for Cardiothoracic Surgery. The process of guideline develop-ment is described in the article. This process included collection and evaluation of peer-reviewed articles, discussion in committee meetings, posting of proposed guidelines on-line for comment, and final promulgation of the guidelines.

The authors begin by listing the indications for tracheostomy, which include long-term ventilation, failure to wean, upper airway obstruction, and copious secretions. They also list contraindications such as active soft tissue infection in the anterior neck, and extensive scarring from earlier surgical procedures and/or radiation therapy. Cur-rent approaches to the care of patients with cervical spine injury might include early open reduction and internal fixation of spinal fractures. The presence of a fresh surgical incision with implanted devices is a relative contraindication to tracheostomy. The au-thors next discuss technique for open tracheostomy. If possible, the patient is posi-tioned with the neck extended. The conventional approach is to make a transverse or vertical skin incision 1 cm below the lower border of the cricoid cartilage. Soft tissues

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are separated and, if necessary, the thyroid isthmus is divided and retracted. The ante-rior tracheal wall is identified and the second and third tracheal rings are located. The endotracheal tube is withdrawn until the distal orifice is above the tracheostomy site. The trachea is entered and the opening is dilated. Incision of the tracheal ring above or below the opening is sometimes necessary to facilitate insertion of the tracheostomy appliance.

The authors recommend using a tracheostomy appliance with a low-pressure cuff. Lubrication of the tracheostomy appliance facilitates insertion because the low-pres-sure cuff is redundant and might “hang-up” on the tracheal rings. Advance preparation should be made to connect the airway circuit to the tracheostomy appliance immedi-ately on completion of successful insertion. Some surgeons, including the editor, prefer to perform immediate fiberoptic bronchoscopy to make certain that blood clots and mucous plugs are cleared from the airway and that there is no residual airway bleeding.

De Leyn and colleagues discuss percutaneous dilational tracheostomy. The two most commonly used devices are the “Blue Rhino®” device and the “Percu-twist®” de-vice. Each device uses a percutaneous needle for tracheal access, and optimal patient safety concerns have dictated the use of flexible fiberoptic bronchoscopic control of the procedure so that the point of needle entry and tracheostomy device placement is docu-mented. The main difference between the two devices lies in the means of dilation of the skin, subcutaneous tissue, and tracheal wall channel into the tracheal lumen. The Blue Rhino device uses a curved, hydrophilic-coated dilator, which needs to be passed through the channel a minimum of three passages using the previously placed guidewire. The Percu-twist device uses a hydrophilic-coated screw that is rotated in a clockwise direction to create the entry channel for the tracheostomy device.

The authors list and discuss early and late complications of both surgical and percu-taneous dilational tracheostomy. They note that conventional wound care approaches are necessary to reduce the risk of peri-tracheostomy infection. In addition, they note that the swallowing dysfunction that accompanies tracheostomy usually means that pa-tients will not be able to eat normally. Aspiration episodes are frequent and collection of secretions above the tracheostomy balloon must be anticipated. If ventilator support can be interrupted, patients might be able to speak if the tracheostomy tube orifice is covered with a gloved finger. Tracheostomy appliance balloons tend to increase in vol-ume over time with concomitant increases in balloon pressure. Pressures in excess of 25 mmHg might interrupt tracheal mucosal blood flow. Tracheostomy cuff pressure should be monitored to keep pressures in the appropriate range.

A comparison of surgical tracheostomy to percutaneous tracheostomy is the topic of a report by Beltrame and coauthors92 in Minerva Anesthesiologica, 2008. These authors

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report an analysis comparing surgical tracheostomy to percutaneous tracheostomy. Three hundred sixty-seven patients undergoing percutaneous tracheostomy were com-pared with 161 historic control patients who had surgical tracheostomy. Procedure du-ration was shorter for percutaneous tracheostomy. Complications were low and equiva-lent for both techniques. ICU length of stay was shorter for percutaneous tracheostomy patients; there is no report of concomitant changes in ICU patient care processes that might have worked to shorten ICU stay in the later group. The authors cite data show-ing that patients with tracheostomy might require less analgesia and sedation com-pared to patients with endotracheal tubes. The authors note that analgesia/sedation protocols are not standardized in most reports so it is not possible to determine whether intubated patients are simply oversedated.

De Leyn and colleagues note there is controversy over the timing of tracheostomy and the impact of tracheostomy on outcomes of ventilation for acute respiratory dis-tress syndrome. Observational studies and one randomized clinical trial demonstrating reduced mortality, intensive care length of stay, and reduced frequency of pneumonia are cited by these authors. The numbers of patients in these studies are small and, be-cause of this, categorical statements of benefit from early tracheostomy cannot be made. They cite, in addition, a systematic review of early tracheostomy in trauma pa-tients that did not demonstrate clear evidence of benefit from early tracheostomy. Much of the debate centers on the definition of “early tracheostomy.” Studies that do not show benefit usually report tracheostomy performed within the first 10 days of ventilation; studies showing benefit report tracheostomy performed within the first 48 hours of ventilation. Obviously, both approaches are subject to selection bias since pre-diction of outcomes within the first 48 hours is challenging and, in the reported studies, some patients subjected to early tracheostomy are weaned from the ventilator within 3-4 days of the tracheostomy. This subgroup of patients could possibly have been weaned to extubation without the tracheostomy. Patients who have tracheostomy at the end of the first week of ventilation are probably patients who are going to require prolonged support regardless of the approach to airway management.

A comparison of “early” versus “late” tracheostomy in injured patients is the focus of a report by Arabi and coauthors93 in Critical Care, 2004. These authors queried a prospectively managed trauma ICU database and compared a group of 29 patients who had tracheostomy performed earlier to day 7 of ventilation with 107 patients who had tracheostomy performed after 7 days. Lower ICU lengths of stay were noted in the pa-tients who had “early” tracheostomy. The authors noted that the patients having early tracheostomy were more likely to have severe brain injury and this raises the question whether early tracheostomy was associated with benefit in terms of improved out-comes for respiratory failure or, rather, the tracheostomy facilitated transfer of brain-

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injured patients to other care areas. Overall hospital outcomes was not influenced by early tracheostomy in this study.

A report of an analysis of the affects of early tracheostomy versus late tracheostomy on patient outcomes from a statewide trauma database is the topic of a report by Schauer and coauthors94 in the Journal of Trauma, 2009. These authors reviewed pa-tient data on 685 patients who underwent tracheostomy. Early tracheostomy was de-fined as tracheostomy performed within the first four days after injury. The authors cal-culated survival probability using standard injury severity indices. Low survival proba-bility was defined as a probability of survival of less than 25%. The authors noted there was high early mortality in the patients in the low survival probability group and this group of patients did not benefit from early tracheostomy. In patients with survival probability of more than 25%, early tracheostomy resulted in shorter ICU lengths of stay and shorter hospital lengths of stay.

With the increased use of percutaneous dilational tracheostomy, patients referred to surgeons for formal surgical tracheostomy are often patients with very obese necks, prior neck scarring, patients who cannot be optimally positioned, and patients with dif-ficult upper airway anatomy and/or history of difficult intubation. These changes in pa-tient characteristics mean that surgical tracheostomy usually means a formal procedure performed under general anesthesia in the operating room. Patients will frequently not have optimum ventilator support during transport and in the operating room (see dis-cussion of ventilatory associated pneumonia in SRGS, Vol. 35 No. 6). Careful coordina-tion of the surgical and anesthesia teams is necessary because of the hazard of airway loss. Surgical exposure is often challenging and technical measures to minimize the risk of bleeding include positioning the patient in a slightly head-up position (to lower ve-nous pressure in neck veins), ventilation of the patient using low airway pressures, and the use of larger incisions.

Editorial commentFrom the perspective of the editor, it seems clear that early tracheostomy facilitates

the care of certain types of injured patients. This patient group consists mainly of pa-tients with moderate-to-severe brain injury who can be expected to survive and, per-haps, recover brain function over time. Tracheostomy can facilitate transfer of such pa-tients to rehabilitation facilities or to assisted care facilities. The reductions in ICU lengths of stay and hospital lengths of stay reported in the articles discussed above sup-ports this conclusion. This patient group is also at increased risk for pneumonia and tra-cheostomy might improve the diagnostic process for pneumonia. By reducing aspira-tion of secretions, pneumonia risk might be reduced. The reasons for decreased length of ventilator support reported by some authors in patients undergoing tracheostomy

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(especially early tracheostomy) are not clear. Reductions in airway-related complica-tions and pneumonia risk could contribute to such reductions.

The available data, and clinical experience, have shown that provision of consistent open-lung ventilation (discussed in the previous section) with minimal interruption of ventilation will maximize the likelihood of weaning and recovery of lung function as long as the process producing acute respiratory distress syndrome can be adequately controlled and ventilator-associated pneumonia can be avoided.

In the editor’s experience, clinical judgment can usually determine, with acceptable accuracy, those patients who will likely require prolonged ventilator support. In this pa-tient group, early tracheostomy is likely to have its greatest benefit. In my view, tra-cheostomy facilitates the diagnosis of ventilator-associated pneumonia using bron-choalveolar lavage. I have consistently observed less use of supine positioning and more frequent suctioning of patients with tracheostomies. Patients with tracheostomies are repositioned in bed more frequently and are easier to move from bed to chair com-pared with patients who have endotracheal tubes. These features might contribute to lowering of pneumonia risk.

Percutaneous tracheostomy is the most efficient procedure and this approach is, in the experience of the editor, associated with the shortest interval of interruption of ven-tilator therapy. As higher risk patients have increasingly been selected for open tra-cheostomy under general anesthesia in the operating room, maneuvers to safely place the tracheostomy when exposure is limited have been sought.

One valuable maneuver, in the experience of the editor, is to use the percutaneous dilational tracheostomy insertion equipment to assist in placing the tracheostomy ap-pliance once the anterior tracheal wall is identified. The needle and guidewire are in-serted using bronchoscopic control and the dilator is used to establish entry into the tracheal lumen. Stay sutures are placed on each side of the trachea entry site so that the trachea can be elevated. The tracheostomy appliance (sometimes a long appliance is necessary and advanced planning to make certain such devices are available is helpful) can then be placed safely.

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