Chapter 19Monitoring Tissue Perfusion and OxygenationKenneth WaxmanShock occurs when tissue oxygen delivery is inadequate to meet metabolic demands, and cellular dysfunction results. Since a primary goal of treating shock is elimination of cellular hypoxia, it logically follows that detecting and treating shock would best be monitored by measuring the state of tissue perfusion and cellular oxygenation. To this end, many devices that have the capability of monitoring tissue perfusion and oxygenation have been developed. However, to date, none of these devices has gained widespread acceptance in clinical practice. Why is this? This chapter will outline underlying principles of tissue perfusion and oxygenation and review the complexities of making clinically useful measurements with existing monitoring approaches.There are multiple components of the circulation that contribute to cellular oxygenation, each of which is related to monitoring of tissue perfusion and oxygenation. As shown in Figure 19.1, tissue perfusion is determined by cardiac output, the distribution of cardiac output to regional tissue beds, and the state of the microcirculation. Tissue oxygenation is determined by perfusion as well as by arterial oxygenation, nutritional blood flow, and cellular extraction of oxygen. This is a complex system, which is highly dynamic: Alteration of any component has physiologic impact upon other components. Moreover, there is enormous heterogeneity within the circulation, both between organs and within organs. Hence tissue perfusion and oxygenation is never uniform between organs, nor even in particular tissue beds. Nonetheless, despite these complexities, there are several principles that allow useful monitoring to occur:Peripheral perfusion and oxygenation monitors are not replacements for other commonly used monitors, but instead provide unique physiologic information.

A measured decrease in peripheral tissue perfusion may provide a significant and early warning of circulatory insufficiency.

In low-flow shock states (such as hemorrhagic or cardiogenic shock), there is a characteristic redistribution of regional blood flow, such that blood flow to the heart and brain is preserved, while peripheral blood flow is decreased. Blood flow to the skin decreases very early in this process; hence, monitoring skin perfusion is a very sensitive indicator of circulatory shock. Blood flow to other tissues such as the intestinal tract also decreases relatively early in shock, making the gut an alternative sensitive monitoring site. Unfortunately, in high-flow shock states (such as septic shock), the distribution of regional blood flow is less predictable, and interpretation of peripheral perfusion data becomes more complex.

A measured decrease in peripheral tissue oxygenation may be a significant warning of decreased tissue perfusion, decreased hemoglobin concentration, arterial oxygenation, or increased cellular utilization of oxygen. Sorting out these alternative explanations for abnormal tissue oxygenation can lead to prompt diagnosis and treatment of the underlying problem.

Monitors of tissue perfusion and oxygenation can be used in several ways. They can serve as early sensitive but nonspecific warning devices to alarm when decreases of blood flow or oxygenation occur. In addition, these monitoring approaches can be used as components of a system of monitoring, such that their specificity is enhanced. For example, combining tissue oxygen monitoring with pulse oximetry can indicate that a decreased tissue oxygen value is not due to arterial hypoxemia.

Monitoring changes of tissue oxygenation in response to changes in cardiac output or arterial oxygen may provide meaningful clinical information. The use of these devices in response to physiologic challenges adds another dimension to their potential value

Monitoring TechniquesPulse OximetryPulse oximeters are designed to monitor arterial oxygen saturation, not tissue perfusion or oxygenation. In fact, the technology of pulse oximetry is precisely designed to detect oxyhemoglobin saturation, even when blood flow is greatly reduced. Estimation of arterial oxygen saturation is thus of great benefit in monitoring arterial oxygenation, but of little value in assessing the circulation. A patient in shock may have 100% arterial oxygen saturation, and pulse oximetry will reflect this regardless of the state of the circulation, as long as the probe can detect pulsation. When pulsations can no longer be detected, the monitor ceases to function. Hence, it is only the absence of a signal that indicates very low flow, and this absence is both insensitive and nonspecific. Pulse oximetry is, however, useful in combination with tissue oxygen monitors to indicate whether low tissue oxygenation is due to arterial hypoxemia or to inadequate circulation.Transcutaneous OxygenIn 1956 Clark developed a practical polarographic electrode to measure oxygen tension, using a semipermeable polyethylene membrane-covered platinum cathode (1). The Clark electrode has become the standard for blood gas analysis. Subsequently, P.194the Clark electrode was placed into a heated probe, and utilized for transcutaneous oxygen monitoring. Heating of the skin by the transcutaneous electrode is necessary to allow diffusion of oxygen across the stratum corneum. This occurs because heating the skin to 44C or higher rapidly (over minutes) melts the lipoprotein barrier to oxygen diffusion. Heating the skin, however, also affects this tissue, dilating the underlying vessels and increasing local blood flow. In addition, heating decreases oxygen solubility, shifting the oxyhemoglobin dissociation curve to the right (2). Initial measurements must be delayed for up to 5 minutes for the skin to heat. Moreover, transcutaneous oxygen tension (PtcO2) values may be site specific, sometimes with lower values in the extremities of patients with peripheral vascular disease. For critical care monitoring, most studies utilize the torso. Despite these confounding issues, transcutaneous oxygen monitoring provides useful physiologic data that are meaningfully related to tissue oxygenation.

Figure 19.1. Tissue perfusion and oxygenation is determined by a complex interaction of systemic and regional blood flow and oxygenation, as well as by the state of the microcirculation and by cellular metabolism.

Experimental studies have shown that transcutaneous oxygen monitoring is sensitive to arterial oxygen tension during normal cardiac output, but is more sensitive to perfusion in low-flow shock (3). In adult patients, PtcO2 is approximately 80% of the arterial oxygen tension (PaO2) during normal hemodynamic conditions. However, when blood flow is diminished, PtcO2 also decreases. PtcO2 is therefore related to both perfusion and oxygenation. When perfusion is normal, PtcO2 varies with arterial oxygenation. When perfusion is inadequate, PtcO2 varies with cardiac output. Hence, a normal PtcO2 value indicates that both oxygenation and perfusion are relatively normal. A low PtcO2 indicates that either oxygenation and/or cardiac output are inadequate. If arterial oxygenation is normal (as indicated by blood gases or pulse oximetry), low PtcO2 indicates low-flow shock (4).The relationship between PtcO2 and PaO2 can be quantitated, utilizing the PtcO2 index, which is simply defined as PaO2/PtcO2. In a study that simultaneously measured cardiac index, PtcO2, and PaO2 in a large number of critically ill surgical patients, it was found that when cardiac output was relatively normal (cardiac index >2.2 L/minute/m2), the PtcO2 index averaged 0.79 0.12. In individual patients with these normal cardiac outputs, PtcO2 varied linearly with PaO2. When cardiac output decreased, however, the PtcO2 index decreased as well. For patients with a cardiac index between 1.5 and 2.2 L/minute/m2, the PtcO2 index averaged 0.48 0.07. For patients with a cardiac index below 1.5 L/minute/m2, the PtcO2 index was 0.12 0.12 (4). These data confirm that when blood flow is relatively normal, PtcO2 varies with arterial oxygenation. However, with low-flow shock, PtcO2 becomes very sensitive to changes in cardiac output.Clinical studies have demonstrated the usefulness of trans cutaneous oxygen monitoring in detecting shock. When PtcO2 monitors are placed during acute emergency resuscitation, low PtcO2 values detect both hypoxemia and hemorrhagic shock. Moreover, the response of PtcO2 during fluid infusion is a sensitive indicator of the efficacy of shock resuscitation (5,6).Transcutaneous oxygen monitoring thus has benefit both as an early detector of shock and as a monitor to titrate resuscitation to a physiologic end point. It is noninvasive and inexpensive, and is therefore widely applicable for patients at risk, such as during emergency resuscitation of trauma and acute surgical emergencies, in the perioperative and postanesthesia period, and in the intensive care unit (ICU). However, while end points of successful resuscitation utilizing transcutaneous oxygen monitoring have been suggested, such values have not been validated in large prospective studies. The only risk of transcutaneous oxygen monitoring is minor skin burn beneath the probe if probe temperatures exceed 44C or if the device is left in place for excessive periods of time.Tissue Oxygen MonitorsIn addition to transcutaneous oxygen probes, alternative direct tissue oxygen monitoring techniques have been developed. An advantage of such tissue probes is that heating of the skin is not necessary. In addition, specific tissues can be monitored to provide organ-specific information. Probes may be placed into the subcutaneous tissue, which is very sensitive to low flow. They may also be placed into muscle, which is perhaps less sensitive to low flow, but more rapidly responsive to resuscitation. Probes may also be placed directly into organs. For example, specific probes are now available for placement in the brain to provide a measure of cerebral oxygenation.Two techniques for direct tissue oxygen monitoring are available. Polarographic electrodes incorporated into needles have been most widely utilized. In addition, a technique utilizing the phenomenon of fluorescence quenching is available. Tissue oxygen probes contain a fluorescent compound that is O2 sensitive, such that its fluorescent emission is diminished in direct proportion to the amount of O2 present. Energy from the monitor is transmitted through fiberoptic elements to the florescent compound in the probe, resulting in the emission of light, which is then measured by sensors in the tissue probe. The intensity of the emitted light is inversely proportional to the tissue pO2 (7).Another method of tissue oxygen monitoring is transconjunctival. The conjunctiva of the eye does not have a stratum corneum, so oxygen is freely diffusable. Transconjunctival probes are placed against the eye, and allow continuous tissue oxygen monitoring without heating; the technology has been utilized both during anesthesia and shock (8).P.195Direct tissue oxygen monitoring devices offer alternatives to transcutaneous monitoring, with the potential advantages of more rapid initial readings, a variety of monitoring sites, and no heating necessary. However, there are little clinical data to determine the relative sensitivities and specificities of these various techniques.Near-infrared SpectroscopyNear-infrared spectroscopy (NIS) has been developed as a noninvasive measure of tissue oxygenation (9,10,11,12). NIS measures the ratio of oxygenated hemoglobin to total hemoglobin (StO2) in the microcirculation of the underlying muscle by measuring the absorption and reflectance of light. Using cutaneous probes placed upon the thenar eminence, values of 87% 6% have been measured in normal volunteers. Early clinical experience suggests that StO2 values decrease during shock and increase with successful resuscitation. A recent multicenter trial in trauma patients suggested that a StO2 value of 75% may be a therapeutic goal. This monitoring approach has potential value, as it provides convenient, continuous, noninvasive measurements. However, clinical data are limited. Tissue edema may be a confounding factor, as the distance between the probe and the underlying muscle affects measurements. Again, the sensitivity and specificity of this device compared to other tissue oxygen monitoring devices has not been studied. NIS has been demonstrated to have a close relationship to base deficit in critically injured patients (13) as well as predicting development of organ failure in traumatic shock patients (14).NIS has also been utilized as a cerebral oximeter. By passing light through the scalp and skull, this technology provides a noninvasive measure of cerebral oxygenation.Gastric TonometryThe mesenteric circulatory bed, particularly the gut mucosa, is prone to hypoperfusion and ischemia during shock. Tonometry has been developed as a technique to detect adequacy of gastrointestinal mucosal perfusion (14). The technique is based upon calculation of the gastrointestinal intramucosal pH (pHi). The basis of this measurement is that the gastrointestinal mucosal pCO2 equilibrates with the gastric luminal pCO2. Measurement of luminal pCO2 was originally accomplished by placing a tube with an attached balloon into the stomach, allowing time for the CO2 to diffuse; measuring pCO2 in the balloon, assuming that luminal pCO2 equals mucosal pCO2; and then calculating pHi by the Henderson-Hasselbalch equation as follows:pHi = 6.1 + log(HCO3-)/(pCO2) 0.031Gastric pHi monitoring has recently been improved by utilizing gas tonometry without the need for balloons, utilizing capnography. This improvement decreases the lag time necessary for equilibration of carbon dioxide, and allows for more continuous measurements.The potential usefulness of gastric tonometry has been suggested in clinical studies, in which pHi has been reported to reflect the severity of shock and to increase during successful resuscitation (14). However, the technique has not gained widespread acceptance, in part because the accuracy of the pHi measurement has been questioned. Utilization of arterial bicarbonate as an estimate of mucosal bicarbonate concentrations may be inaccurate. Measurements can be also be altered by gastric acid secretion, because buffering of gastric acid by bicarbonate can produce CO2 in the gastric lumen, which will confound the estimate of mucosal pCO2. Enteral feeding may also affect pHi, although this effect is variable. To minimize these errors, it has been suggested that gastric feeding be withheld and antacid medication given prior to pHi monitoring. However, the variation and inaccuracies of gastric tonometry have limited its widespread application. Moreover, clear treatment end points have not been validated.Several alternatives to gastric tonometry have been studied. Sublingual capnography is a less invasive technique, which shows promise as a sensitive indicator of tissue acidosis in shock models and in early clinical reports (15). This device was recalled in 2004 for infectious complications and may be reinstated in the future. Alternative luminal monitoring sites, such as the small intestine, rectum, and bladder, have also been proposed as monitoring sites for pHi monitoring (16).Transcutaneous and End-tidal Carbon DioxideTranscutaneous carbon dioxide may be measured using the Severinghaus carbon dioxide electrode. Because CO2 is more diffusible than is O2, heating of the probe is not necessary. In analogy with PtcO2 monitoring, transcutaneous CO2 parallels arterial values when cardiac output is relatively normal, although transcutaneous values are normally 10 to 30 mm Hg higher than arterial. During low-flow shock, transcutaneous pCO2 is increased, due to accumulation of carbon dioxide in the tissues due to inadequate perfusion (2). Increased transcutaneous pCO2 may thus be utilized as an indicator of inadequate circulation, particularly if arterial pCO2 is normal. In combination with low PtcO2, increased transcutaneous pCO2 gives additional evidence of circulatory shock. End-tidal CO2 may also be utilized as a measure of perfusion; end-tidal CO2 is decreased during low-flow states due to decreased pulmonary flow (17). Decreased end-tidal CO2 values in combination with increased transcutaneous pCO2 and normal arterial pCO2 values are strong evidence of circulatory shock. This is an example of how combining noninvasive monitoring data can provide additional information.Tissue Blood FlowMeasuring tissue blood flow can provide an indication of the adequacy of both cardiac output and regional blood flow. In critical illness, blood flow measurement has the particular potential to be combined with tissue oxygen monitoring to help determine if inadequate tissue oxygenation is due to perfusion deficits. Hence, a reliable tissue perfusion monitor has great appeal.Many technologies have been developed to measure tissue perfusion. The best studied of these is laser Doppler. Laser Doppler utilizes analysis of scattering of light to determine quantitative blood flow in a small area around the probe (18). A variety of probes have been developed, which can be placed noninvasively onto the skin, or into tissues with needle probes. Laser Doppler measurements have been shown to be useful in detecting changes in blood flow under many experimental P.196conditions. However, clinical utility has been limited due to the large variation in blood flow within tissues (19). Because of these variations, no normal values, no optimal values, and no therapeutic goal values for blood flow have been determined.Numerous alternative approaches to monitoring tissue perfusion have also been developed. Measurement of local blood flow by thermal diffusion has been developed as an alternative to light scattering, and implantable probes using this technology are available. In addition, magnetic resonance imaging, positron emission tomography, and contrast-enhanced ultrasonography have been used to measure tissue perfusion, although these are not available as continuous monitoring devices. Fluorescence microangiography has also been developed to provide both visual imaging of the microcirculation and measurements of local blood flow (20,21). As with laser Doppler monitoring, validated clinical applications for these technologies have yet to be defined.The Oxygen Challenge TestAn approach to utilize tissue oxygen monitoring in a more dynamic manner was proposed by Dr. Hunt's group in San Francisco (22). Endeavoring to assess adequacy of tissue perfusion in postoperative patients, they measured subcutaneous pO2 before and after patients breathed high inspired O2 concentrations. The expected response in well-perfused patients was a rapid increase in tissue pO2. Many postoperative patients failed to demonstrate this response, which was, however, restored with intravenous fluid infusion. A physiologic explanation for the responses of tissue pO2 to inspired O2 is interesting. If there is no cellular O2 deficit, then additional dissolved O2 supplied after breathing O2 is not required nor utilized by cells, and therefore results in increased tissue pO2. However, if there is a cellular O2 deficit (shock), then any additional dissolved O2 would be rapidly utilized, and would thus not result in increased tissue pO2. The tissue pO2 response to inspired O2 may then be a relatively rapid and minimally invasive method to detect cellular hypoxia. This approach, named the oxygen challenge test, was evaluated in trauma patients (22,23) (Table 19.1). The O2 challenge test had 100% sensitivity and specificity in detecting flow-dependent O2 consumption in invasively monitored patients in the intensive care unit. It also appeared to be a very sensitive indicator of shock during acute resuscitation. This method, utilizing either transcutaneous or direct tissue O2 monitors, has potential to detect which patients require fluid resuscitation, to provide a physiologic end point for resuscitation, and to detect the patients in whom initial resuscitation is inadequate and who therefore require additional monitoring and therapy. Using a noninvasive transcutaneous (PtcO2) monitor, Yu et al. have studied the O2 challenge test in patients in the intensive care unit and have validated the sensitivity and specificity of the test in identifying patients in occult shock. In addition, their data has defined an increase in PtcO2 of greater than 20 to 25 mm Hg in response to a FiO2 of 1.0 as a therapeutic endpoint (24,25). In a prospective randomized trial using the oxygen challenge test as an end point of resuscitation compared to the oxygen delivery variables from the pulmonary artery catheter, an improved survival was reported (25). The skin is the first to vasoconstrict (even before the gastrointestinal tract) and the last to perfuse in shock states, and the use of the PtcO2 monitor may give an early warning signal of occult shock. The same authors used the oxygen challenge test to identify patients who may benefit from activated protein C (26). Monitoring and treating the peripheral tissue oxygenation state does not exclude utilization of central hemodynamic parameters such as cardiac output and oxygen delivery (DO2), but does allow manipulation of DO2 to reach a specific goal of tissue perfusion rather than aiming for a general DO2 value.Table 19.1 Oxygen challenge testSelect patients who have baseline arterial O2 saturation over 90% on FiO2 2025 torr, patient can be assumed to have no flow-dependent oxygen consumption.

If transcutaneous (or tissue) pO2 increases 72 h)Nostril stricture

Laryngeal ulcer, granuloma, or polyp

Laryngotracheal webs

Laryngeal or tracheal stenosis

Vocal cord synechiae

Vocal cord paralysis and arytenoid dislocation and dysfunction may be appreciated following extubation (198,199,200,201,202,203,204). Paralysis may be unilateral or bilateral, with the left cord twice as frequently affected as the right, and males predominating with this complication. Damage to the external laryngeal nerve may cause lasting voice change, with unilateral nerve injury usually causing hoarseness. Paralysis can result and, if the injury is bilateral, may lead to airway obstruction.Late ComplicationsLate postextubation complications include laryngeal ulcer, granuloma, polyp, synechiae (fusion) of the vocal cords, laryngotracheal membrane webs, laryngeal or tracheal fibrosis, and nostril stricture from damage to the alae (202,203,205). Laryngeal ulcerations or granulomata are more commonly located at the posterior region of the vocal cords where the endotracheal tube tends to have more continual contact. The patient may complain of foreign body sensation, fullness or discomfort at the back of the throat, and persistent hoarseness. Any patient complaining of airway-related pain, discomfort, fever, or systemic signs of infection following difficult airway management should be evaluated for tissue injury in the upper and lower airway and pharyngoesophageal region (27,92).Extubation of the Difficult Airway in the Intensive Care UnitAirway management also constitutes maintaining control of the airway into the postextubation period. The known or suspected difficult airway patient should be evaluated in regard to factors that may contribute to his or her inability to tolerate extubation. A comprehensive review of medical and surgical conditions and previous airway interventions, an evaluation of the airway, and formulation of a primary plan for extubation as well as a rescue plan for intolerance are essential for optimizing safety (206,207,208). Reintubation, immediately or within 24 hours, may be required in up to 25% of ICU patients (209,210,211). Measures to avert reintubation such as noninvasive ventilation for those at highest risk for extubation failure are effective in preventing reintubation and may reduce mortality rate if done so upon extubation (212). However, a delay in the P.549application of noninvasive ventilation when the patient displays signs of early or late postextubation respiratory distress or failure results in a less effective application in most patients, except those with COPD (213,214,215,216). Factors beyond routine extubation criteria that may be helpful in predicting failure include neurologic impairment, previous extubation failure, secretion control, and alterations in metabolic, renal, systemic, or cardiopulmonary issues (209,210,211).Table 38.12 Risk factors for difficult extubationKnown difficult airway
Suspected difficult airway based on the following factors:
Restricted access to airway
Cervical collar, Halo-vest
Head and neck trauma, procedures, or surgery
ET size, duration of intubation
Head and neck positioning (i.e., prone vs. supine)
Traumatic intubation, self-extubation
Patient bucking or coughing
Drug or systemic reactions
Angioedema
Anaphylaxis
Sepsis-related syndromes
Excessive volume resuscitation

ET, endotracheal tube.

Difficult extubation is defined as the clinical situation when a patient presents with known or presumed risk factors that may contribute to difficulty re-establishing access to the airway (Table 38.12). The extubation of the patient with a known or presumed difficult airway and the potential for subsequent intolerance of the extubated state poses an increased risk to patient safety. An extubation strategy should be developed that allows the airway manager to (a) replace the ET in a timely manner and (b) ventilate and oxygenate the patient while he or she is being prepared for reintubation, as well as during the reintubation itself (30).The practitioner should assess the patient's risk on two levels: The patient's predicted ability to tolerate the extubated state and the ability (or inability) to re-establish the airway if reintubation becomes necessary (206,207,208). Weaning criteria and extubation parameters will not be discussed as they vary by locale, practitioner, and the patient's clinical situation. Table 38.13 outlines two categories for pre-extubation evaluation (208).NPO StatusThe NPO status of the patient to be extubated and the subsequent need for reintubation has not been thoroughly studied, but it makes clinical sense to consider 2 to 4 hours off of distal enteral feeds prior to extubation while maintaining the NPO status post extubation until the patient appears at low risk for failing the extubation trial. Unfortunately, the ICU patient may succumb to reintubation based on a multitude of factors; hence, predictability of failure and when it will occur is difficult to discern.Table 38.13 The difficult extubation: Two categories for evaluationEvaluate the patient's inability to tolerate extubationAirway obstruction (partial or complete)

Hypoventilation syndromes

Hypoxemic respiratory failure

Failure of pulmonary toilet

Inability to protect airway

Evaluate for potential difficulty re-establishing the airwayDifficult airway

Limited access to the airway

Inexperienced personnel pertaining to airway skills

Airway injury, edema formation

Modified from Cooper RM. Extubation and changing endotracheal tube. In Benumof J, ed. Airway Management. St. Louis: Mosby; 1995.

The Cuff LeakHypopharyngeal narrowing from edema or redundant tissues, supraglottic edema, vocal cord swelling, and narrowing in the subglottic region of any etiology may contribute to the lack of a cuff leak (217,218,219,220,221,222). Too large of a tracheal tube in a small airway should, of course, be considered. A higher risk of post extubation stridor or the need for reintubation is prevalent in those without a cuff leak, in women, and in patients with a low Glasgow coma score (217,218,219,220,221,222). Attempting to determine the etiology for the lack of a cuff leak may impact patient care, as individuals may remain intubated longer than is required or receive an unneeded tracheostomy. If airway edema is the culprit, steps to decrease airway edema include elevation of the head, diuresis, steroid administration, minimizing further airway manipulation, and time (223,224,225). The cuff leak test as an indicator for predicting postextubation stridor is helpful, but the performance of a cuff leak test varies by institution and protocol, as does its interpretation by the individual physician. Testing to predict successful extubation is inconclusive (223,224,225). A relatively crude yet effective method of cuff leak test involves auscultation for cuff leak with or without a stethoscope. A more precise method is to take an indirect measurement of the volume of gas escaping around the ET following cuff deflation, determined by calculating the average difference between inspiratory and expiratory volume while on assisted ventilation (218,225). Cuff leak volume (CLV) may be measured as the difference of tidal volume delivered with and without cuff deflation and stated as a percentage of leak, or as an absolute volume. The percentage CLV will vary with the tidal volume administered during the test (8 mL/kg vs. 1012 mL/kg), but several authors have found an absolute CLV less than 110 to 130 mL (218,219) or 10% to 24% of delivered tidal volume as helpful in predicting postextubation stridor (219,220,221,225). Stridor increases the risk of reintubation. Single- or multiple-dose steroids may reduce postextubation airway obstruction in pediatric patients, depending on dosing protocols, patient age, and duration of intubation (223). Steroid use in adults administered 6 hours prior to extubationrather than 1 hour priormay reduce postextubation stridor and decrease the need for reintubation in critically ill patients (210,223,224,225).P.550Risk Assessment: Direct Inspection of the AirwayGarnering useful information about the airway status may need to go well beyond the cuff leak test since it is relatively crude, provides little direct data regarding one's ability to access the airway in the event of a need for reintubation, and is relatively uninformative as to the actual status of the glottis. While it is mandatory that the records of the known difficult airway patient be reviewed, it is also the case that a record of previous airway interventions in a patient who may have undergone a marked alteration in their airway status could be less than informative. Practitioners should weigh the pros and cons of evaluating such an airway to determine ease or difficulty in the ability to gain access via conventional or advanced techniques. Additionally, some patients may need evaluation of their hypopharyngeal structures and supraglottic airway to assess airway patency and resolution of edema, swelling, and tissue injury. Conventional laryngoscopy is a standard choice for evaluation, but often fails due to a poor line of sight. Additionally, the relationship of grading and comparing the laryngeal view of a nonintubated to an intubated glottis is inconsistent (226). Flexible fiberoptic evaluation is useful but may be limited by secretions and edema (124). Video-laryngoscopy and other indirect visualization techniques that allow one to see around the corner are especially helpful. The Airtraq, as may other optical or video-laryngoscopy devices, has been found to be particularly useful by offering outstanding wide-angle visualization of the periglottic structures in the critically ill patient with a known difficult airway (144).American Society of Anesthesiologists Practice Guidelines Statement Regarding Extubation of the Difficult AirwayThe ASA guidelines (30) have suggested that a preformulated extubation strategy should include:A consideration of the relative merits of awake extubation versus extubation before the return of consciousness; this is clearly more applicable to the operating room setting than to the ICU

An evaluation for general clinical factors that may produce an adverse impact on ventilation after the patient has been extubated

The formulation of an airway management plan that can be implemented if the patient is not able to maintain adequate ventilation after tracheal decannulation

Consideration of the short-term use of a device that can serve as a guide to facilitate intubation and/or provide a conduit for ventilation/oxygenation

Clinical Decision Plan for the Difficult ExtubationA variety of methods are available to assist the practitioner's ability to maintain continuous access to the airway following extubation, each with limitations and restrictions. Though no method guarantees control and the ability to re-secure the airway at all times, the LMA offers the ability for fiberoptic-assisted visualization of the supraglottic structures while serving as a ventilating and reintubating conduit; it is hampered by a limited time frame in which it may be left in place. The bronchoscope is useful for periglottic assessment following extubation, but requires advanced skills and minimal secretions. Moreover, it offers only a brief moment for airway assessment and access to the airway following extubation (124). Conversely, the airway exchange catheter (AEC, Fig. 38.14) allows continuous control of the airway after extubation, is well tolerated in most patients, and serves as an adjunct for reintubation and oxygen administration (206,227,228,229). Patient intolerance, accidental dislodgment, and mucosal and tracheobronchial wall injury have been reported, but are rare (230,231,232,233,234). Carinal irritation may be treated with proximal repositioning, the instillation of topical agents to anesthetize the airway, and explanation and reassurance. Dislodgment may occur, resultant from an uncooperative patient or a poorly secured catheter. Observation in a monitored environment with experienced personnel should be given top priority, as should the immediate availability of difficult airway equipment in the event of intolerance to tracheal decannulation (206,207,208). Tips for success with the use of this device are shown in Table 38.14.Table 38.14 Airway exchange catheter (AEC)-assisted extubation: Tips for successAccess to advanced airway equipment

PersonnelRespiratory therapist

Individual competent with surgical airway?

Prepare circumferential tape to secure the airway catheter after extubation

Sit patient upright; discuss with patient

Suction ET, nasopharynx, and oropharynx

Pass lubricated AEC to 2326 cm depth

Remove the ET while maintaining the AEC in its original position

Secure the AEC with the tape (circumferential); mark AEC airway only

Administer oxygen:Nasal cannula

Face mask

Humidified O2 via AEC (12 L/min)

Maintain NPO

Aggressive pulmonary toilet

ET, endotracheal tube.

Clinical judgment and the patient's cardiopulmonary and other systemic conditions, combined with the airway status, should guide the clinician in establishing a reasonable time period for maintaining a state of reversible extubation with the indwelling AEC (Table 38.15) (206).Exchanging an Endotracheal TubeExchanging an ET due to cuff rupture, occlusion, damage, kinking, a change in surgical or postoperative plans, or self-extubation masquerading as a cuff leak, or when the P.551requesting team prefers a different size or alteration in location, is a common procedure. Preparation for the possible failure of the exchange technique and appreciation of the potential complications is imperative (30).Table 38.15 Suggested guidelines for maintaining presence of airway exchange catheterDifficult airway only, no respiratory issues, no anticipated airway swelling12 h

Difficult airway, no direct respiratory issues, potential for airway swelling>2 h

Difficult airway, respiratory issues, multiple extubation failures>4 h

Four methods typify the airway manager's armamentarium of exchanging an ET: Direct laryngoscopy, a flexible or rigid fiberscope, the airway exchange catheter, or a combination of these techniques (2). Proper preparation is imperative and patients should undergo a comprehensive airway exam. Access to a variety of airway rescue devices is of paramount importance in the event of difficulty with ET exchange (208).Direct LaryngoscopyDL is the most common and easiest technique for exchanging an ET, but has several pitfalls and limitations. Airway collapse following removal of the ET may impede visualization and, thus, reintubation. This method leaves the patient without continuous access to the airway and should be restricted to the uncomplicated easy airway (94).Fiberscopic Bronchoscopeassisted ExchangeFiberscopic bronchoscopeassisted exchange (FBAE) is useful for nasal to oral or vice versa exchanges and oral-to-oral exchanges, as well as for immediate confirmation of ET placement within the trachea and positioning precision (3,4,5). Though difficult in the edematous or secretion-filled airway, FBAE allows continuous airway access in skilled hands. Passing the flexible fiberscope through the glottis along the side of the existing ET, although not without significant difficulty, the old ET can be backed out, followed by advancing the ETpreloaded onto the fiberoptic bronchoscopeinto the trachea. Conversely, the preloaded flexible fiberscope may be placed immediately adjacent to the glottis. The old ET is then backed out over an AEC and the glottis is intubated with the FOB-ET complex. A larger flexible model is better maneuvered than a pediatric-sized scope. Passing a lubricated, warmed ET that is rotated 90 degrees will reduce arytenoid-glottic impingement. Rigid fiberscopes such as the Bullard, the Wu scope, the Upsher, and the Airtraq are very useful for visualizing the otherwise difficult airway during the exchange by offering the ability to see around the corner (124,235,236,237,238). The fiberscope may be rendered useless by unrecognizable airway landmarks, edema, and secretions as well as operator inexperience.Airway Exchange CatheterThe AEC incorporates the Seldinger technique for maintaining continuous access to the airway. Strategy and preparation are the keys to successful and safe exchange (Table 38.16). Proper sizing of the AEC to best approximate the inner diameter of the ET will allow a smoother replacement. A chin liftjaw thrust maneuver and/or laryngoscopy will assist the passing of a well-lubricated warmed ET that may need to be rotated counterclockwise by 90 degrees to reduce glottic impingement. A larger-diameter (19 French is the size we most often use) AEC is best in passing an adult-sized ET. Exchanging a tracheostomy tube over an AEC is especially valuable when the peristomal tissues are immature. The use of a tracheal hook to elevate the tracheal cartilage and proper head/neck positioning (shoulder roll) will optimize the exchange. The exchange is often performed blindly since laryngoscopy in the ICU patient often reveals little to no view of the supraglottic airway. Thus, incorporation of any of the advanced laryngoscopes that assist in seeing around the corner (Bullard, Wu, Glidescope, McGrath, Airtraq, etc.) offer certain advantages to the operator and the patient: (a) assessment of the airway is improved; (b) there is better estimation of what size ET the glottis will accept; (c) visualization during the exchange offers the ability to direct the new ET into the trachea and reduce arytenoid hang-up or impingement; (d) it confirms that the AEC remains in the trachea during the exchange; and (e) it allows visual confirmation that the ET is placed in the trachea and the ET cuff is lowered below the glottis. Finally, the advanced airway device would be in position to assist in reintubation if any unforeseen difficulties arise during the exchange.Table 38.16 Strategy and preparation for endotracheal tube (ET) exchangePlace on 100% oxygen

Review patient history, problem list, medications, and level of ventilatory support

Assemble conventional and rescue airway equipment including capnography

Assemble personnel (nursing, respiratory therapy, surgeon, airway colleagues)

Prepare sedation/analgesia neuromuscular blocking agents

Optimal positioning; consider DL of airway

Discuss primary/rescue strategies and role of team members; choose new ET (soften in warm water)

Suction airway; advance lubricated large AEC via ET to 2226 cm depth

Elevate airway tissues with laryngoscope/hand, remove old ET, and pass new ET

Remove AEC and check ET with capnography/bronchoscope or use a closed system and place small bronchoscope through swivel adapter while at the same time ventilating, checking for CO2, with the AEC still in place

DL, direct laryngoscopy; AEC, airway exchange catheter.

P.552Minimizing the gap between the ET and the AEC is important for ease of exchange. If, due to luminal size restrictions, the smaller-sized AEC (4 mm, 11 French) is used when going from, for example, a double-lumen to a single-lumen ET in a high-risk ICU patient, then temporary reintubation with a smaller warmed (6.5 mm) ET as opposed to a larger (89 mm) ET may ease passage into the trachea. Once secured, a larger AEC may be passed via the indwelling ET with subsequent exchange to a larger ET. Various AEC exchange techniques are practiced, and customized variations of the standard methods assist the practitioner to tackle individual patient characteristics (94,235,236,237,238).ET exchange, while simple conceptually, is not a simple procedure as hypoxemia, esophageal intubation, and loss of the airway may occur. The decision on the method of exchange is based on known or suspected airway difficulty, edema and secretions, and most significantly, the experience and judgment of the clinician. It is recommended that continuous airway access be maintained in all but the simplest and most straightforward airway situations (94).Follow-up CareFollowing a life-threatening airway encounter with a patient, dissemination of such information is often overlooked and there is currently no standard method of relaying information from one caregiver to another (30,89). Notes written in the chart are a start, as is a discernible or highly visible label on the outside of the medical chart, but these may be inadequate. Informative and accurate medical records of airway interventions should be promoted as a potentially life-saving exercise; hence, detailed accounting of an intubation with more information written in the chartnot lessis best for patient care. However, a caveat to note is as follows:If the chart states difficulty was encountered, assume it will again be difficult; if the notes states it was easy or no details are provided, assume and plan on the potential for difficulty.Discussing difficulties with the patient in this setting is certainly different from the elective surgical case in the operating room. For the future care of the patient, opening a Medic Alert file has many advantages for improved dissemination of patient care information, especially in our mobile society. Obtaining medical records in a timely fashion is a constant deterrent. However, the Medic Alert file will not assist the care for the current hospitalization, only in future ones (27,30,89). Hence, steps for the current hospitalization can be taken to improve communication for efficient transfer of needed information to the airway team. Initially identifying the patient by a colorful wrist bracelet, analogous to a medication or latex allergy bracelet, is a simple but effective trigger for the airway team to investigate the patient's airway status. A computerized medical record may allow a Difficult Airway Alert to be readily and prominently displayed, thus allowing identification of the patient on the current and possibly future hospitalizationsalthough only at the current hospital. Future airway interventions in the unrecognizable or unanticipated difficult airway are particularly benefited by flagging the patient. The Medic Alert system is dependent on patient compliance and payment.

Chapter 39Hyperbaric Oxygen TherapyRichard E. MoonJohn Paul M. LongphreThe first recorded attempt to use hyperbaric therapy was in 1662, when Henshaw in Britain used an organ bellows to manipulate the pressure within an enclosed chamber designed to seat a patient. He recommended high pressure for acute diseases and low pressure for chronic diseases (1). The pressure fluctuations in either direction were probably quite small. Widespread use of hyperbaric therapy began in the 19th century. At that time, powerful pneumatic pumps were designed, which could be used to compress chambers with air. Physicians in France and Britain used compressed air treatment for miscellaneous conditions. Junod used pressures of 1.5 atmospheres absolute (ATA) to treat patients, but did experiments up to 4 ATA (2). Simpson, using pressures in the range of 1.3 to 1.5 ATA, reported treating a variety of complaints, including dysphonia, asthma, tuberculosis, menorrhagia, and deafness (1), although without any physiologic basis.Compressed air construction work was also developed in the 1800s, in which men were exposed to elevated ambient pressure within compartments for the purpose of excavating tunnels or bridge piers in muddy soil that was otherwise subject to flooding. Upon decompression at the end of a work shift, workers often developed joint pains or neurologic manifestations (caisson disease, the bends, or decompression sickness). Although the pathophysiology (nitrogen bubble formation in tissues; see below) was not understood, it was observed that recompression of these individuals could relieve the symptoms. Administration of recompression therapy became routine during construction of the Hudson River tunnel in the 1890s (3). All of these treatments used compressed air. Although oxygen breathing under pressure had been suggested for the treatment of decompression sickness as early as 1897 (4) and was used intermittently over the next 30 years, systematic study and use of hyperbaric oxygen would not occur until much later.Oxygen administration during recompression therapy for decompression sickness increased the efficacy of the treatment (5,6) and is now routinely used for both decompression sickness and gas embolism. The administration of oxygen at increased ambient pressure became known as hyperbaric oxygen (HBO) therapy. In the 1950s, pilot investigations were performed of HBO as a therapy for diseases other than those related to gas bubbles, including carbon monoxide poisoning, clostridial myonecrosis (gas gangrene), and later, selected chronic wounds.For many years, the Undersea and Hyperbaric Medical Society has regularly reviewed and published information regarding the use of HBO in selected diseases (7), and its recommendations have been widely accepted. The list of accepted indications (7) contains a heterogeneous group of conditions (Table 39.1), suggesting that more than one mechanism mediates the clinical effects of HBO, including the increase in ambient pressure (partly responsible for its efficacy in conditions caused by gas bubble disease) and pharmacologic effects of supraphysiologic increases in blood and tissue PO2 as discussed below.Effects of HyperoxiaBlood Gas ValuesUnder normal clinical HBO therapy conditions (23 ATA), breathing 100% oxygen can lead to arterial PO2 (PaO2) values that are 10 to 17 times higher than normal (8,9). PaO2 levels can rise from the normal of 90 to 100 mm Hg (breathing air at sea level, i.e., 1 ATA or normobaria) to 1,000 to 1,700 mm Hg in healthy subjects breathing 100% oxygen at 2 to 3 ATA (see Table 39.2).Table 39.2 Blood gas and hemodynamic values in 14 healthy adults breathing spontaneously (mean standard deviation)ConditionPaO2 (mm Hg)SaO2 (%)P[v with bar above]O2 (mm Hg)S[v with bar above]O2 (%)PaCO2 (mm Hg)P[v with bar above]CO2 (mm Hg)Hb (g/dL)Arterial O2 content (mL/dL)Dissolved O2 (%)

1 ATA, air93 996 242 276 338 342 312.7 0.816.6 1.11.7 0.2

3 ATA, 100% O21,493 22498 3378 16498 235 243 312.7 0.821.1 1.321.2 3.0

ConditionHR (bpm)Cardiac output (L min-1)Mean arterial pressure (mm Hg)Mean pulmonary artery pressure (mm Hg)PA wedge pressure (mm Hg)SVR (dynes sec cm-5)PVR (dynes sec cm-5)

1 ATA, air66.6 8.26.5 1.192.5 10.513.6 3.48.2 3.91,118 23567 24

3 ATA, 100% O262.7 12.55.9 1.094.9 9.412.4 2.19.3 2.51,286 30941 11

ATA, atmospheres absolute; HR, heart rate; SVR, systemic vascular resistance; PVR, pulmonary vascular resistance. These data obtained in part from McMahon TJ, Moon RE, Luschinger BP, et al. Nitric oxide in the human respiratory cycle. Nat Med. 2002;8:711717.

One effect is an increase in blood oxygen content:

where Hb is hemoglobin concentration (g/dL), SaO2 is arterial Hb-O2 saturation, and PaO2 is arterial oxygen tension.The second term of Eq. 1 represents the dissolved oxygen proportion, which under normal circumstances represents a small fraction of total arterial oxygen content, and is therefore often disregarded. However, during HBO, this dissolved fraction is substantially increased (see Table 39.2). In fact, mixed venous Hb-O2 saturation is 100% under resting conditions while breathing 100% oxygen at 3 ATA. Thus, oxygen delivery can be maintained under these circumstances without hemoglobin. This was shown by Boerema et al. in a swine model (10).PaCO2 is not significantly affected by the increased pressure (8,9,11), although the venoarterial PCO2 difference is slightly increased, mostly because of a reduction in cardiac output.Table 39.1 Conditions amenable to treatment with hyperbaric oxygen therapyGas bubble disease
Air or gas embolisma (236,237,238)
Decompression sicknessa (237,238)
Poisonings
Carbon monoxide poisoninga (151,152,153,239)
Cyanide (154,165)
Carbon tetrachloride (176,240)
Hydrogen sulfide (154,168,169)
Necrotizing soft tissue infections
Clostridial myositis and myonecrosisa (181,241,242,243)
Mixed aerobic/anaerobic necrotizing soft tissue infectionsa (182,184,243,244)
Mucormycosis (187,245)
Aerobic infections
Refractory osteomyelitisa (7)
Intracranial abscessa (7)
Streptococcal myositis (48)
Acute ischemia
Crush injury, compartment syndrome, and other acute traumatic ischemic conditionsa (246)
Compromised skin grafts and flapsa (31,33,247,248)
Acute hypoxia
Acute exceptional anemiaa (191)
Support of oxygenation during therapeutic lung lavage (219,249)
Thermal burnsa (197,198,200,250)
Delayed radiation injury (soft tissue and osteoradionecrosis)a (7,251,252,253,254)
Enhancement of healing in selected problem woundsa (7,255)
Envenomation
Brown recluse spider bite (256,257)

aApproved by the Undersea and Hyperbaric Medical Society (Gesell LB, ed. Hyperbaric Oxygen Therapy: A Committee Report. Durham, NC. Undersea and Hyperbaric Medical Society; 2008; see also: http://www.uhms.org).

P.557VasoconstrictionHyperoxia causes peripheral vasoconstriction (8,9,12), regardless of atmospheric pressure (13). At a mere 2 ATA, systemic vascular resistance can increase by 30% in dogs (14). The mechanisms for this include scavenging of nitric oxide (NO) by superoxide anion (O2-) (15) and increased binding of NO at high PO2 to hemoglobin, forming S-nitrosohemoglobin (9). Vasoconstriction has the positive effect of reducing edema in injured tissues and surgical flaps (discussed later). During HBO, the arterial blood O2 content is sufficiently high that despite vasoconstriction and reduced blood flow, oxygen delivery is increased (16) (see also Table 39.2). Although peripheral vasoconstriction occurs in normal skin during hyperbaric oxygen exposure, repetitive intermittent HBO appears to increase the microvascular blood flow of healing wounds (17).HemodynamicsHeart rate and cardiac output both decrease by 13% to 35% under hyperbaric conditions (Table 39.2) (8,9,14,18,19). Small changes may occur in systemic and pulmonary artery pressure, with an increase in systemic vascular resistance (SVR) and a decrease in pulmonary vascular resistance (PVR) (9). Despite the reduced cardiac output, oxygen delivery is increased (Fig. 39.1).Organ Blood FlowStudies in large animals indicate that the decrease in peripheral blood flow is limited primarily to the cerebral and peripheral vascular beds, with other organs unaffected (14). In rats, HBO has been shown to decrease organ blood flow, including the myocardium, kidney, brain, ocular globe, and gut (15,20,21,22). In autonomically blocked conscious dogs at 3 ATA, coronary blood flow is decreased (23). Another dog study at 2 ATA revealed no change in coronary, hepatic, renal, or mesenteric blood flow (14).Cellular and Tissue EffectsIn a myocutaneous flap model during reperfusion following 4 hours of ischemia, Zamboni et al. described a delayed decrease in blood flow (24). This flow reduction appears to be associated with adherence of leukocytes to the endothelium of the small vessels, an effect that is significantly inhibited by HBO. A delayed reduction in cerebral blood flow has also been observed after arterial gas embolism in the brain (25), which has similarly been attributed to leukocyte accumulation in the capillaries (26). HBO reduces cerebral infarct volume and myeloperoxidase activity, a marker of neutrophil recruitment (27). In other studies using animal models, it has been observed that HBO pretreatment reduces ischemia/reperfusion injury to the liver (28). HBO reduces ischemia/reperfusion injury to the intestine (29,30) and muscle (31), as well as reducing ischemia-induced necrosis in muscle (32,33,34,35,36,37), brain (38,39), and kidney (40). One mechanism for this effect of HBO appears to be the inhibition of leukocyte 2-integrin function (41,42,43). Part of the beneficial effect of HBO in these settings is speculated to be due to the prevention of endothelial leukocyte adherence. After focal ischemia, HBO also reduces postischemic bloodbrain barrier damage and edema (44) and has an antiapoptotic effect (45).Antibacterial EffectsThe increase in PO2 during HBO can be toxic to anaerobic bacteria, which lack antioxidant defense mechanisms. In addition, HBO has effects on aerobic organisms via neutrophil mechanisms. Killing of aerobic bacteria by leukocytes is related to the O2-dependent generation of reactive oxygen species within the lysosomes. In vitro studies have demonstrated that phagocytic killing of Staphylococcus aureus by polymorphonuclear leukocytes becomes less effective as ambient PO2 is decreased. This mechanism appears to be important in vivo when tissue P.558P.559PO2 is low (e.g., in osteomyelitis) (46). In an animal model of osteomyelitis, the cidal effect of tobramycin against Pseudomonas was increased when tissue PO2 was raised by the administration of 100% O2 at increased ambient pressure (47). Published evidence also supports an augmentation of penicillin by HBO in the treatment of soft tissue streptococcal infections (48).

Figure 39.1. Arterial O2 content and delivery while breathing air at 1 atmosphere absolute (ATA) or 100% oxygen at 3 ATA. Measurements are shown in a group of normal volunteers. (Data from McMahon TJ, Moon RE, Luschinger BP, et al. Nitric oxide in the human respiratory cycle. Nat Med. 2002;8:711717.)

Oxygen ToxicityPharmacologyExposure of an animal to increased partial pressure of oxygen results in higher rates of endogenous production of reactive oxygen species, including superoxide anion (O2-), hydroxyl radical (OH), hydrogen peroxide (H2O2), and singlet oxygen, which are responsible for tissue oxygen toxicity (49,50,51). Tissue O2 toxicity includes the following: Lipid peroxidation, sulfhydryl group inactivation, oxidation of pyridine nucleotides, inactivation of Na+K+ATPase and inhibition of DNA, and protein synthesis. Toxic effects of these species depend upon both dose and duration of O2 exposure. In the central nervous system, HBO initially reduces NO availability and causes vasoconstriction. HBO stimulates neuronal nitric oxide production and causes the accumulation of peroxynitrite. Prior to onset of a seizure, NO levels and blood flow both increase above control levels (52,53). This, in turn, decreases brain -aminobutyric acid (GABA) levels, creating an imbalance between glutamatergic and GABAergic synaptic function, which is believed to be partly responsible for central nervous system (CNS) O2 toxicity (54).Clinical EffectsAt sufficiently high PO2, any organ can be susceptible to oxygen toxicity. However, within the clinical range of inspired PO2 (13 ATA), the most susceptible tissues are the lung, brain, retina, lens, and peripheral nerve.BrainOxygen toxicity of the central nervous system produces a wide variety of manifestations (55). The most common mild symptom is nausea; the most dramatic is generalized nonfocal convulsions. These are usually self-limited, even without pharmacologic treatment, and have no long-term effects. The occurrence of a hyperoxic seizure does not imply the development of a convulsive disorder. Factors that increase the risk of CNS oxygen toxicity include hypercapnia and probably fever.CNS O2 toxicity is uncommon when inspired PO2 is less than 3 ATA. While in-water convulsions in divers have been recorded at an inspired PO2 of 1.3 ATA, convulsions during clinical hyperbaric oxygen therapy occur in only a small fraction of treatments. Approximately 0.02% of treatments at an inspired PO2 of 2 ATA and 4% at 3 ATA. At an inspired PO2 less than 3 ATA, the risk of convulsions increases markedly, particularly in patients with sepsis. While anecdotal reports suggest that HBO may precipitate seizures in patients who have an underlying predisposition (56), there are no epidemiologic data to confirm this. When indicated, HBO should not be withheld on the basis of an underlying seizure disorder.Both CNS and pulmonary toxicity can be delayed by the use of air breaks (a period of a few minutes where air is administered in lieu of 100% oxygen) (57,58,59,60). Oftentimes, the aura of a hyperoxic convulsion occurs in the form of nausea or facial paresthesias. The patient can be given an air break to avert such a convulsion. Once the symptoms have resolved (usually within a few minutes), the oxygen can be restarted without recurrence. During the tonic-clonic phase of a seizure, the airway may be obstructed. Therefore, it is imperative that chamber pressure not be reduced during this time in order to avoid pulmonary barotrauma and the possibility of arterial gas embolism. After a convulsion, some practitioners recommend administering prophylactic medication for the duration of HBO.Prophylactic anticonvulsants such as phenytoin, phenobarbital, or benzodiazepines can reduce the chance of convulsions when utilizing clinical treatment schedules with a significant risk of CNS O2 toxicity (e.g., treatment pressure >3 ATA). The authors' practice is to load septic patients intravenously with phenobarbital as tolerated, up to 12 mg/kg, prior to hyperbaric oxygen treatment at 3 ATA, with doses every 8 hours to maintain a serum concentration in the therapeutic anticonvulsant range. When using inspired PO2 2.8 ATA, the risk of CNS toxicity is sufficiently low that prophylactic anticonvulsant therapy is not required.Hyperoxic seizures and other CNS manifestations in diabetics can be caused by HBO-induced reduction in blood glucose. Therefore, the occurrence of CNS O2 toxicity in a patient with diabetes during HBO treatment should prompt the immediate measurement of plasma glucose. When blood PO2 is extremely high, bedside glucose measurement devices, particularly those dependent upon a glucose oxidase reaction, can be inaccurate, producing measurements that significantly underestimate the true value (61). Laboratory-based glucose measurement is usually accurate.P.560LungsPulmonary oxygen toxicity during hyperbaric oxygen therapy is also PO2 and time dependent. Clinical HBO protocols have been empirically developed to minimize the risk of pulmonary O2 toxicity, which almost never occurs during routine daily or twice-daily clinical treatments. However, it can occur during extended treatments that are used for treating gas embolism or decompression sickness, in which inspired PO2 is as high as 2.8 ATA. The initial manifestation is usually a burning substernal chest pain and cough (62), which is most likely due to tracheobronchitis. Continued exposure to oxygen can produce more severe manifestations such as dyspnea and acute respiratory distress syndrome (ARDS). Measurable abnormalities include reduced forced vital capacity and carbon monoxide transfer factor (DLCO). Pulmonary oxygen toxicity symptoms may not be evident in patients who are sedated and mechanically ventilated. Moreover, such patients often have pulmonary infiltrates for a variety of reasons and it may be impossible to distinguish the possible additive effects of pulmonary O2 toxicity.While the maximum safe inspired PO2 during clinical hyperbaric oxygen therapy is based mainly upon CNS O2 toxicity limits, the safe exposure duration is determined by pulmonary limits. Prediction formulas have been developed that approximate the average reduction in vital capacity after continuous oxygen exposure (63,64,65). However, the usefulness of these algorithms for individual patients is severely limited due to individual variability and comorbid factors that may affect O2 susceptibility, such as prior exposure, intermittent exposure, and endotoxemia. HBO treatment schedules that include periods of air breathing (air breaks) interspersed between O2 periods reduce the rate of onset of both pulmonary and CNS toxic manifestations and can increase the overall dose of oxygen that is tolerated. In the awake patient, the occurrence of burning, retrosternal chest pain is a more useful indicator of incipient pulmonary toxicity.If standard HBO treatment schedules are used (e.g., 2 ATA/2 hours, 2.5 ATA/90 minutes one to two times daily, or U.S. Navy treatment tables), pulmonary O2 toxicity is almost never clinically evident. It is seen only with the most extreme levels of hyperbaric exposure such as may be required for severe neurologic decompression illness. Furthermore, most minor pulmonary oxygen toxicity resolves within 12 to 24 hours of air breathing. Complete reversal of vital capacity (VC) decrements, as large as 40% of control, has been observed after extended O2 exposure at 2 ATA (66). Therefore, in clinical situations requiring aggressive HBO therapy such as spinal cord decompression sickness or arterial gas embolism, some degree of pulmonary O2 toxicity is acceptable.Supplemental O2 administration at 1 ATA between HBO treatments can accelerate the onset of symptoms of pulmonary O2 toxicity during subsequent HBO. Thus, if O2 is absolutely required between HBO treatments, it is prudent to use the lowest concentration.Some antineoplastic agents, such as bleomycin (67,68) and mitomycin C (69), can predispose to fatal pulmonary O2 toxicity, probably due to drug-induced reduction in antioxidant defenses. The risk of pulmonary O2 toxicity due to HBO therapy in patients with previous exposure to either of these agents is unknown, although 6 months after the agent has been discontinued, HBO seems to be safe. Even after this point, in some patients, HBO induces mild pulmonary O2 toxicity symptoms such as retrosternal burning chest pain, which can be managed with air breaks.EyeRepetitive hyperbaric oxygen therapy causes myopia, which is due to a reversible refractive change in the lens (70). A measurable change in visual acuity usually does not occur until after 20 or so treatments. The myopia usually resolves over several weeks, in about the same time period as the onset; however, some residual myopia may remain. On the basis of one study, it has been suggested that HBO treatment may predispose to nuclear cataract formation (71). However, many of the patients in this study received hundreds of hours of HBO, considerably more than is customary. Furthermore, nuclear cataracts are more common in diabetes, which is frequently a comorbidity in patients requiring HBO. Extended exposure to PO2 of 3 ATA can also cause retinal toxicity, manifested by tunnel vision (72,73). However, such exposures are beyond the range used clinically.Peripheral NerveAfter hyperbaric oxygen exposure, some patients experience paresthesias, usually in their fingers and toes, generally after several HBO exposures but occasionally after a single prolonged treatment. The physical exam is normal, and the symptoms resolve within a few hours. This manifestation has no known clinical significance and is not a reason to discontinue hyperbaric therapy.Physical Effects of Compression/DecompressionBoyle's LawClinically, the complications of HBO therapy that most frequently occur are those related to the body's gas-containing spaces (74). Dealing with volume changes in these gas-containing spaces is unique to HBO therapy. For a gas, absolute pressure and volume are inversely related. The increase in pressure during HBO treatment will therefore decrease the volume of closed gas-containing spaces within the body, such as the gastrointestinal tract or middle ear and, in the event of gas embolism or decompression sickness, bubbles.Effects of Gases Other than OxygenNitrogenThe narcotic properties of compressed air were first reported by Junod in 1835 as described by Bennett and Rostain (75). Hyperbaric nitrogen causes narcosis or pleasant intoxication at pressures greater than about 4 ATA in most individuals and near unconsciousness at greater than 10 ATA (76). Since patients breathe oxygen, nitrogen narcosis is only a problem for tenders in multiplace hyperbaric chambers. However, most hyperbaric treatments occur between 2 and 3 ATA, where symptoms of nitrogen narcosis are exceedingly mild.Nitrogen (and other inert breathing gases such as helium) is the major causative agent of decompression sickness. During decompression, excess tissue nitrogen can become P.561supersaturated, come out of solution, and form bubbles. This can lead to decompression sickness, with manifestations depending on their location and secondary effects.Trace GasesThe pharmacologic effects of gases are proportional to their partial pressures. Although a trace gas may only be present in minute quantities, as the chamber pressure rises, so does the partial pressure of a gas. Therefore, gases such as carbon monoxide or carbon dioxide in concentrations that have no pharmacologic or toxic effects at 1 ATA may exert measurable effects in a hyperbaric environment.Use of Hyperbaric Oxygen for Specific DiseasesGas Embolism and Decompression SicknessGas bubbles in the body can be due to direct gas entry via veins or arteries (arterial or venous gas embolism) or via in situ formation due to gas supersaturation in divers, compressed air workers, or aviators (decompression sickness). Since the two conditions often both occur in the same patient (particularly in divers), the principles of treatment of the two are the same. The syndrome of either or both condition is commonly referred to as decompression illness (DCI).Arterial and Venous Gas EmbolismEntry of gas into the circulation can occur via several mechanisms. Gas embolism has recently been reviewed (77,78). In divers breathing compressed gas, arterial gas embolism (AGE) can ensue if decompression (ascent) occurs while the diver holds his or her breath or due to gas trapping caused by focal or generalized airways obstruction. AGE due to this mechanism can result after an ascent to the surface of as little as 1 meter. AGE can also occur during diagnostic or therapeutic procedures such as angiography.Venous gas embolism (VGE) can result due to direct injection or entry via an open vein in which ambient pressure exceeds venous pressure. This can exist during laparoscopic surgical procedures due to the elevated intra-abdominal pressure, or open procedures in which venous pressure in the surgical wound is subatmospheric. The classic scenario for this is an intracranial procedure in the sitting position. However, it has also been described in procedures such as liver resection, cesarean section, and spine surgery. VGE can also occur due to oral hydrogen peroxide (H2O2) ingestion. H2O2 absorbed into the circulation is broken down by catalase into water and oxygen bubbles. VGE can result if a central venous catheter is opened to air, particularly if the patient is breathing spontaneously. It has also been reported in patients with ARDS being ventilated with positive end-expiratory pressure (79). VGE has been described during orogenital sex after blowing air intravaginally (80). Intravenous injection is better tolerated than intra-arterial injection because of the pulmonary filter. However, if the rate of entry of gas into the veins is sufficiently high, bubbles can traverse the pulmonary capillary network and become arterial emboli. Large volumes can obstruct the right heart or pulmonary artery and cause cardiac arrest.Large volumes of arterial gas can cause acute obstruction of large vessels. Small quantities tend to remain in the circulation only transiently; however, they can precipitate a sustained reduction in local blood flow (25). The mechanism appears to be endothelial damage (81) and adherence of leukocytes (26,82,83,84). Endothelial barrier function is also impaired in both the brain and lung, resulting in edema (85,86) and impaired endothelial-dependent vasoactivity (87). Animal models of AGE have revealed a significant elevation of intracranial pressure (ICP) and depression of cerebral PO2 (88,89). In a pig model, hyperventilation failed to correct these parameters (90); however, HBO at 2.8 ATA (U.S. Navy Table 6, Fig. 39.4) restored both ICP and brain PO2 toward normal (Fig. 39.3).Clinical manifestations of AGE include acute loss of consciousness, confusion, focal neurologic abnormalities, and cerebral edema. VGE causes acute dyspnea, tachypnea, hypotension, cardiac ischemia or arrest, and pulmonary edema (86). In monitored patients, VGE is often heralded by a decrease in end-tidal PCO2 (91), although sometimes, with small volumes of CO2 embolism such as during laparoscopy, it may be increased. A mill-wheel murmur can be heard in some patients, although this sign is neither sensitive nor specific. Venous gas bubbles in sufficient quantities can cross into the arterial circulation (producing AGE) either through the pulmonary capillary network or via an intracardiac shunt, such as a patent foramen ovale.Imaging is not useful for diagnosing either VGE or AGE. Gas bubbles are rarely visible on radiographic images (92). Except in cases where associated conditions such as pneumothorax are suspected or neurologic conditions such as hemorrhage require exclusion, imaging studies are not necessary and tend to delay definitive treatment.Decompression SicknessDuring diving or exposure to a compressed gas environment such as a hyperbaric chamber, inert gas (usually nitrogen) is taken up by tissues. During decompression, inert gas can become supersaturated and form bubbles in situ in tissues. Certain tissues are more susceptible to in situ bubble formation.Manifestations of decompression sickness (DCS) can range from mild to severe (Fig. 39.2). The most common P.562manifestations are joint pain and paresthesias. Although mild cases can progress to severe, severe manifestations almost always occur within 12 hours after surfacing.

Figure 39.2. Effect of hyperbaric oxygen (HBO) on intracranial pressure (ICP) and brain PO2 in pigs after air embolism. Top panel: HBO initially at 2.8 atmospheres absolute (ATA) (U.S. Navy Table 6) reduces ICP compared with no treatment, whether it is started 3 minutes or 60 minutes after embolization. Bottom panel: Brain tissue PO2 in the two groups of animals. For the 60-minute group, the closed circles represent PbrO2 in the first 10 minutes after embolization; the open circles represent PbrO2 in the first 10 minutes after the start of HBO. Values in lower panel are mean standard deviation. (Redrawn from van Hulst RA, Drenthen J, Haitsma JJ, et al. Effects of hyperbaric treatment in cerebral air embolism on intracranial pressure, brain oxygenation, and brain glucose metabolism in the pig. Crit Care Med. 2005;33:841846.)

Figure 39.3. Top: U.S. Navy (USN) Treatment Table 5. According to USN guidelines, this table may be used for symptoms involving skin (except for cutis marmorata), the lymphatic system, muscles and joints, with a normal neurologic exam, and when all symptoms have completely resolved within 10 minutes of reaching 2.8 atmospheres absolute (ATA). Bottom: USN Treatment Table 6. This table may be used for all types of decompression illness. Extensions (additional oxygen breathing cycles) can be administered at either treatment pressure (2.8 and 1.9 ATA). (Data from Navy Department. US Navy Diving Manual. Revision 4. Vol. 5: Diving Medicine and Recompression Chamber Operations. NAVSEA 0910-LP-1038009. Washington, DC: Naval Sea Systems Command; 2005.)

Treatment of Decompression Sickness and Arterial Gas EmbolismPrehospital TreatmentIn addition to standard first aid principles, prehospital treatment of DCI consists of the administration of a high concentration of oxygen and fluid resuscitation. Oxygen administration reduces bubble size and can sometimes abolish symptoms and signs of decompression illness. A published study has provided epidemiologic evidence for its efficacy (93). Use of high concentrations of oxygen (preferably 100%) is recommended until definitive treatment is available. Periodic air breaks to reduce toxicity may be appropriate (e.g., 5 minutes every 30 minutes). The administration of oxygen for longer than 12 hours should be based upon the severity of the injury or the presence of hypoxemia breathing room air.Both head-down and lateral decubitus positions have been recommended based on animal studies (94,95). However, the hemodynamic response to venous gas embolism is unaffected by body position (96,97), and prolonged head-down position may exacerbate cerebral edema (98). Supine position is therefore recommended, also because patient access and supportive therapies can be more easily administered in this position.Hospital TreatmentStandard treatment of gas embolism includes airway and ventilatory management, maintaining a high PaO2 and normal PaCO2 (99) (Fig. 39.3), and support of arterial pressure. Like other forms of neurologic injury, it is recommended that when managing neurologic DCI, both hyperthermia and hyperglycemia (>140185 mg/dL, 7.810.3 mM/L) should be avoided or treated (100).Physical Removal of GasPhysical removal of gas after massive arterial gas embolism has been described in cardiopulmonary bypass (101,102). Venous gas embolism has been successfully treated with chest compression (103) and aspiration through catheters in the right atrium (104,105) or pulmonary artery (106).RecompressionAlthough symptomatic improvement can be obtained with oxygen at 1 ATA, the definitive treatment of both forms of decompression illness is hyperbaric oxygen. The safety and efficacy of HBO for the treatment of divers was initially shown 70 years ago (6). Since then, treatment protocols have been P.563empirically developed that have been shown to have a high degree of success with a low probability of oxygen toxicity (107). The most widely used treatment protocols (tables) were developed by the U.S. Navy and promulgated via the Diving Manual (108) (Fig. 39.4). Both U.S. Navy Treatment Tables 5 and 6 use 100% oxygen breathing periods (O2 cycles) interspersed with air breathing periods (air breaks) at 2.8 and 1.9 ATA in a two-step pattern (see Fig. 39.4). Guidelines are available to administer additional O2 cycles (extensions) at both pressures (108). The vast majority, if not all cases, of DCI can be adequately treated using U.S. Navy treatment tables.

Figure 39.4. Symptoms of decompression illness in a series of recreational divers. (Redrawn from Divers Alert Network. Annual Diving Report. Durham, NC: Divers Alert Network; 2006.)

The U.S. Navy tables were designed for use in multiplace chambers, where air breaks can easily be administered by discontinuing O2. Since monoplace chambers were designed to be compressed with 100% O2, shorter alternate treatment tables were designed for their use (109,110) (Fig. 39.5). Although direct comparisons with U.S. Navy tables have never been performed, case series suggest that these tables are efficacious for DCI (110). Monoplace chambers fitted with an air supply and delivery system can be used to administer treatment according to traditional Navy tables (111).

Figure 39.5. Hart-Kindwall monoplace treatment table. This table was designed for use in monoplace chambers without the capability of administering air breaks. Except for the lack of air breaks and limited ability for extension, it is similar to U.S. Navy Table 5, with a shorter time at 2.8 atmospheres absolute (ATA) and longer time at 1.9 ATA. (Data from Boerema I, Meyne NG, Brummelkamp WH, et al. Life without blood. J Cardiovasc Surg [Torino]. 1960;1:133146.)

P.564Adjunctive MeasuresIn the 19th and early 20th century, recompression was the only treatment administered to patients with decompression illness. While hyperbaric oxygen remains the definitive treatment of bubble disease, there is increasing recognition that adjunctive therapies such as correction of hypovolemia may also be important (112).FluidsSevere decompression sickness is often associated with capillary leak, intravascular volume depletion, and hemoconcentration. The Undersea and Hyperbaric Medical Society (UHMS) recommends (level 1C) fluid administration to replenish intravascular volume, reverse hemoconcentration, and support blood pressure (113). Measures that augment cardiac preload such as supine position, head-down tilt, and water immersion (114) significantly increase the rate of inert gas washout. Thus, even in divers who are not dehydrated, there may be some benefit to extra fluid loading. Intravenous isotonic fluids without glucose (e.g., lactated Ringer solution, normal saline, or colloids) are recommended for severe DCI. Patients with mild symptoms may be treated with oral hydration fluids. For chokes (cardiorespiratory decompression sickness, in which high bubble loads cause pulmonary edema), animal studies suggest that aggressive fluid resuscitation can exacerbate pulmonary edema. Thus, for the patient with chokes, aggressive fluid resuscitation may not be warranted, particularly if advanced life support modalities such as endotracheal intubation and mechanical ventilation are not immediately available. For isolated AGE, in which the pathology is limited to cerebral infarction, aggressive fluid administration is also unwarranted.AnticoagulantsIntravascular bubbles can induce platelet accumulation, adherence, and thrombus formation. Indeed, in a canine model of arterial gas embolism, therapeutic anticoagulation promoted a return in a short-term outcome: evoked potential amplitude, but only when heparin was combined with prostaglandin I2 (PGI2) and indomethacin (115). In this model, heparin alone was ineffective. In other experiments, heparin given either prophylactically or therapeutically to dogs with DCI was not beneficial (116). Furthermore, tissue hemorrhage can occur in decompression illness involving the spinal cord (117,118,119), brain (120,121), and inner ear (122,123). Thus, full therapeutic anticoagulation is not recommended.Although anticoagulants are not indicated for the primary injury in DCI, patients with leg immobility due to DCI-induced spinal cord injury are at increased risk of deep vein thrombosis (DVT) and pulmonary thromboembolism (PE). Standard prophylactic anticoagulant measures, typically low-molecular-weight heparin (LMWH), are therefore recommended as soon as feasible after the onset of injury. Full anticoagulation is appropriate for established DVT/PE. If LMWH is contraindicated, elastic stockings or intermittent pneumatic calf compression is recommended, although their efficacy in preventing DVT or thromboembolism in DCI is unknown. Recommendations have been extrapolated from guidelines for traumatic spinal cord injury; neither their efficacy nor safety in neurologic DCI has been specifically confirmed. Thus, when facilities exist, a screening test for DVT a few days after injury is appropriate (113).LidocaineThe administration of lidocaine for arterial gas embolism is supported by several animal studies (124). No controlled human studies in accidental AGE have been performed. However, gas emboli are frequently observed in cardiopulmonary bypass. In this setting, two studies have demonstrated a beneficial effect of lidocaine administered in traditional antiarrhythmic doses on postoperative neurocognitive function (125,126). Another study has shown benefit for nondiabetics but not for diabetics (127). Human data directly pertinent to DCI are confined to three cases of decompression sickness or arterial gas embolism, published as case reports, which appeared to benefit from intravenous lidocaine (128,129). The UHMS does not recommend the routine use of lidocaine for DCI; however, recommendations have been made for its dosing (113). An appropriate end point is a serum concentration suitable for an antiarrhythmic effect (26 mg/L).Nonsteroidal Anti-inflammatory DrugsThese drugs are commonly used empirically for treatment of bends pain that does not completely resolve with recompression. A randomized, controlled trial has been published in which tenoxicam, a nonselective cyclo-oxygenase inhibitor, was compared with placebo. Tenoxicam or placebo was administered during the first air break of the first hyperbaric treatment and continued daily for 7 days. Using as an end point the number of hyperbaric treatments required to achieve complete relief of symptoms or a clinical plateau of effect, the tenoxicam group required a median of two treatments versus three for the placebo group. The outcome at 6 weeks was not different (130). The UHMS guidelines have assigned nonsteroidal anti-inflammatory drugs a level 2B recommendation (113).CorticosteroidsUnless given prophylactically, corticosteroids have not been shown to be of benefit in animal models of DCI (131,132,133). In a pig study, methylprednisolone treatment did not protect against severe DCS, and the treated animals had a greater mortality (134). In the absence of human trials of corticosteroids in DCI and the lack of benefit in animal studies, corticosteroids are not recommended.PerfluorocarbonsPerfluorocarbons (PFCs) are a family of chemically inert, water-insoluble, synthetic compounds with a high solubility for both inert gases and oxygen, which may eventually become available for human use as blood substitutes. Intravenous injection of PFC emulsions could augment oxygen delivery to ischemic tissues with impaired circulation and facilitate inert gas washout from tissues (135). Indeed, beneficial effects have been observed in animal studies of both decompression sickness and gas embolism (136,137,138,139,140). There may also be a benefit from the surfactant properties in the treatment of intravascular gas bubbles (141).Arterial Gas Embolism and Decompression Sickness Treatment SummaryImmediate treatment of AGE or DCS includes standard principles of first aid, including the administration of oxygen and fluids during transport to a hyperbaric chamber. If the patient is in an extremely remote location from which transport is not feasible and the manifestations are minor, if the patient's condition does not progress for 24 hours, and if the neurologic P.565exam is normal, the risk of emergent transport may exceed the risk of conservative treatment (142).Carbon MonoxideCarbon monoxide (CO) is an important cause of unintentional poisoning fatalities in the United States each year (143). CO binds to hemoproteins, including hemoglobin and myoglobin, interfering with oxygen transport. It also binds to the mitochondrial cytochrome C oxidase in the electron transport chain (similar to cyanide), impairing oxidative phosphorylation, stopping the cell's energy production, and resulting in cellular hypoxia (144,145,146) and oxidative stress (147). In addition, CO exposure induces intravascular plateletneutrophil activation (148). CO-related oxidative stress can cause chemical alterations in myelin basic protein (149), triggering immune-mediated neurologic deficits.The symptoms and signs of CO poisoning include headache (or tightness across forehead), weakness, nausea and vomiting, syncope, tachycardia, tachypnea, and encephalopathy. Myocardial ischemia is also a common finding.For survivors of this poisoning, the most debilitating results can be the late neurologic sequelae. These are often cognitive problems such as a decrement in short-term memory (150,151,152). Some patients improve clinically and then deteriorate several days after the event.HBO therapy is known to accelerate the elimination of CO (153,154). Pace et al. found that the half-life of CO was longest when breathing air (214 minutes). Half-life decreased to 42 minutes breathing 100% O2 at 1 ATA and further to 18 minutes with 100% O2 at 2.5 ATA (153). The reduction in half-life may be important in preventing cell death by allowing mitochondrial adenosine triphosphate (ATP) production to resume before the cell would have otherwise died (144,155). In animal studies, HBO administration after acute CO exposure appears to minimize the lipid peroxidation in the brain, which occurs during or after removal of CO (147), and results in more rapid repletion of brain energy stores (155).A double-blind randomized control trial carried out by Weaver et al. indicates that HBO therapy can prevent the occurrence of the late neurologic sequelae of CO poisoning if the patients are treated within 24 hours of the exposure (152).All patients should be initially treated with 100% normobaric oxygen. HBO therapy is usually reserved for patients who have more severe poisoning, as determined by high HbCO level (e.g. 25%), loss of consciousness, or other neurologic manifestations, or myocardial ischemia, arrhythmias, or other cardiac abnormalities (152,154,156,157,158). A systematic analysis of 163 patients with CO poisoning who did not receive HBO revealed the following two risk factors for sequelae: older age and longer CO exposure (159). However, some patients without these risk factors also developed sequelae. The authors concluded that, in addition to other indications, regardless of HbCO level or loss of consciousness, anyone older than 36 years with symptoms should receive HBO.Pregnant women should be treated according to maternal indications. Pregnant women may therefore have an HbCO level that is 10% to 15% less than that of the fetus. There is evidence that short periods of HBO therapy are not dangerous to the fetus or mother (160).CyanideCyanide leads to hypoxia on a cellular level by rapidly binding to mitochondrial cytochrome oxidase. Inhalation of high concentrations of cyanide (270 ppm) is rapidly fatal in humans (with blood levels reaching 3 g/mL), whereas ingestion of cyanide is less rapidly fatal (161). When very low doses of cyanide are absorbed (whole blood levels of 0.52.53 g/mL), tachycardia and decreased level of consciousness are possible (161,162).There are very few studies and case reports of the use of HBO therapy in the treatment of cyanide poisoning (163,164,165,166,167). This is likely due partly to the effectiveness of chemical treatments (with sodium nitrite and thiosulfate) but also possibly related to the fact that the bonding of cyanide to the mitochondria's cytochrome C oxidase is not an oxygen-dependent mechanism. Chemical treatment of cyanide poisoning leads to the formation of methemoglobin. Utilizing HBO therapy to increase the amount of circulating dissolved oxygen has been shown to have both prophylactic and antagonistic effects on cyanide poisoning in rabbits (166). Human case reports also hint that HBO therapy may be useful when the response to chemical antidotes has been incomplete (165).Hydrogen SulfideLike CO and cyanide, hydrogen sulfide (H2S) reacts with mitochondrial cytochrome C oxidase, impairing electron transport. This is not an oxygen-dependent mechanism. The rationale for using HBO therapy is the same as for cyanide poisoning, in that HBO therapy can increase the dissolved fraction of oxygen. Use of HBO therapy for H2S poisoning is based on two case reports suggesting a positive benefit (168,169).Carbon TetrachlorideCarbon tetrachloride (CCl4) is a CNS depressant, hepatotoxin, and nephrotoxin, with renal failure being the most common cause of death from very high-level exposures (170). In the setting of CCl4 poisoning of the rat, HBO has been shown to improve survival (171), decrease liver necrosis (172), decrease conversion of CCl4 to toxic free-radical metabolites (173,174), and decrease CCl4 metabolite-induced lipid peroxidation (175). One case report describes an obtunded patient treated with HBO for presumed CO poisoning. There was no historical evidence for CO exposure; the patient improved, regained consciousness, and admitted to ingestion of a normally lethal dose of 250 mL of CCl4 (176).Necrotizing InfectionsClostridial InfectionsThis soil-based a