El Rol de La Ventilacion Mecanica en Neurologia

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The Role of Mechanical Ventilation

in Acute Brain Injury

Robert D. Stevens, MDa,*, Christos Lazaridis, MDa,Julio A. Chalela, MDb

aDivision of Neurosciences Critical Care, Department of Anesthesiology Critical Care

Medicine, Johns Hopkins University School of Medicine, Johns Hopkins Hospital,

Meyer 8-140, 600 North Wolfe Street, Baltimore, MD 21287, USAbNeurosciences Intensive Care Unit, Department of Neurology,

Medical University of South Carolina, Charleston, SC, USA

Endotracheal intubation (ETI) and mechanical ventilation (MV) are

essential to the resuscitation of patients who have acute brain injury, fulfilling

multiple goals, including ensuring protection of the airway, participating in

tissue oxygen delivery, and indirectly modulating cerebral vascular reactivity.

MV also carries significant risks most notably ventilator-associated pneumo-

nia (VAP), ventilator-induced lung injury (VILI), delirium, and the frequent

need for sedation, which decreases the sensitivity of neurologic assessment

and can occult critical clinical information. Positive pressure ventilation

may adversely affect cerebral perfusion pressure (CPP), although the impor-

tance of this effect may be overestimated in most clinical settings. Patients

who have severe brain injury are at increased risk for acute lung injury/acute

respiratory distress syndrome (ALI/ARDS) and may develop VILI. When

there is concurrent intracranial hypertension and ALI/ARDS, therapies

aimed at optimizing brain physiology may conflict with MV strategies aimed

at lung protection. Recent research has begun to clarify some key questions

regarding the pathophysiology and management of MV in patients who are

brain injured [1,2].

Epidemiology of mechanical ventilation in acute brain injury

Among patients admitted to ICUs, it is estimated that the principal indi-cation for instituting MV is an acute neurologic disorder in 20% of cases,

* Corresponding author.

E-mail address: [email protected] (R.D. Stevens).

0733-8619/08/$ - see front matter 2008 Elsevier Inc. All rights reserved.

doi:10.1016/j.ncl.2008.03.014 neurologic.theclinics.com

Neurol Clin 26 (2008) 543563
mailto:[email protected]://www.neurologic.theclinics.com/http://www.neurologic.theclinics.com/mailto:[email protected]


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with half of these patients receiving MV for neuromuscular disease and the

other half for coma or central nervous system dysfunction [3]. Patients me-

chanically ventilated for a primary neurologic disease have longer periods ofMV and increased mortality when compared to non-neurologic patients

[3,4]. Among patients receiving MV, neurologic factors contribute to pro-

longation of MV in 32% to 41% of cases [5]. In a multicenter evaluation,

neurologic patients required MV for longer periods of time than those

with other medical disorders (median time 16 days versus 10 days) [3].

Indications for MV in patients who have central neurologic disorders

may be classified according to whether MV was instituted as part of the

management of a primary brain disorder or because of a primary respiratory

disorder; however, in many cases, neurologic and respiratory indicationscoexist. The most common indication is the inability to protect the airway,

but other reasons include recurrent seizures or status epilepticus, elevated

intracranial pressure (ICP), high aspiration risk, pre-existing or coexisting

pulmonary disorders, and the need to perform diagnostic or therapeutic

procedures under sedation.

Neurologic indications

ComaPatients in coma almost invariably need MV, although patients who are

transiently unresponsive, such as those who are postictal or postsyncopal,

may be supported momentarily with bag-mask ventilation until the level

of consciousness improves. Reductions in the level of consciousness are as-

sociated with decreases in respiratory drive, and hypoventilation is a com-

mon finding in most encephalopathies regardless of cause [6]. Respiratory

function may be depressed because of a hemispheric insult, brainstem dam-

age or dysfunction, spinal cord injury, or systemic factors. Airway patency

may be compromised by foreign objects, secretions, orofacial fractures, orsoft tissue edema associated with cervical injuries. In addition, oropharyn-

geal muscle tone is significantly decreased in comatose patients, leading to

posterior displacement of the tongue and airway obstruction. Patients

who have traumatic coma may have associated systemic disorders that

can compromise ventilation and oxygenation, such as drug or alcohol over-

dose, aspiration pneumonia, pulmonary contusions, fat emboli, pneumotho-

rax, flail chest, and pulmonary edema [68].

In addition to the problems discussed previously, traumatic brain injury

(TBI) results in dramatic biochemical derangements that have significanteffects on pulmonary physiology. Brain injury results in a systemic inflam-

matory response characterized by the release of proinflammatory cytokines

and neuropeptides with unique effects on the lungs [9,10]. The biologic effect

of such inflammatory mediators is associated with pulmonary vascular ex-

pression of adhesion molecules and leukocyte infiltration of lung tissue.

TBI patients may exhibit abnormal respiratory mechanics even in the

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absence of an intrinsic pulmonary pathology; in a recent study, patients with

severe head injury (Glasgow Coma Scale [GCS]!8) had abnormal lung

elasticity and resistance as early as day 1 post injury [11].Ischemic stroke and primary intracerebral hemorrhages may present with

coma, although hemorrhages are more likely to lead to reduced level of

consciousness. Up to 10% of patients who have acute stroke need MV

[12], nearly always because of a decreased level of consciousness [13].

Coma is a predictor of mortality among stroke patients receiving MV [13].

Patients with posterior circulation strokes may require intubation due to im-

paired bulbar function that results in decreased ventilatory drive, inability to

protect the airway, and difficulty handling secretions. Patients who have

large (malignant) hemispheric strokes often need ETI and MV becauseof impaired level of consciousness and intracranial hypertension.

Comatose patients commonly develop abnormal respiratory patterns

that may have clinical implications [6,7,14]. Recognition of these patterns

may be challenging since spontaneous breathing activity is masked by

MV and sedation. The anatomically localizing significance of certain

respiratory patterns has often been cited, and some patterns may be asso-

ciated with a poor prognosis [15]. Cheyne-Stokes respiration (escalating

hyperventilation with decremental hypoventilation followed by apnea) is

seen in patients who have large unilateral strokes or severe cardiopulmo-nary disease. Patients with brainstem injury (basilar artery occlusion) may

develop apneustic breathing. Elderly patients with underlying cerebrovas-

cular disease or dementia may show apraxia of breathing after suffering

a frontal stroke (usually in association with other apraxias). Lastly, a com-

pletely erratic pattern, termed ataxic breathing, may be seen in patients

with extensive medullary lesions.

Brainstem dysfunction

Brainstem dysfunction can affect respiration in several ways. The brain-stem contains critical breathing centers, including the pneumotaxic center in

the pons and the dorsal and ventral respiratory centers in the medulla [6,7].

The pontine pneumotaxic center receives afferent input from the cerebral

cortex (from the lungs via the vagus nerve), modulates respiratory fre-

quency, and influences fine control of respiratory function. Medullary respi-

ratory centers are located in the dorsomedial and rostral venterolateral

medulla and are responsible for generating the automatic inspiratory

rhythms. Lesions involving the medulla result in ineffective respirations

with resulting alveolar hypoventilation in the setting of a preserved alveo-loarterial gradient (unless pulmonary disease coexists). Conscious patients

may compensate by voluntarily increasing their respiratory drive; however,

when these patients fall asleep or receive sedatives, such drive is lost and

severe hypoventilation can occur. Unilateral lesions involving the pontome-

dullary reticular formation and the nucleus tractus solitarius may result in

severe respiratory failure affecting automatic and voluntary respiration [16].

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The most extreme forms of ventilatory dysfunction in patients with brain-

stem injury is Ondines curse, in which automatic respirations are abolished.

The lesion in Ondines curse usually is located in the lateral medulla affectingthe ventral respiratory group and its connections with the dorsal respiratory

group. The majority of patients who have Ondines curse require long-term

MV. There seems to be a left-sided dominance for breathing in the medulla,

thus patients who have left medullary infarctions are more likely to experi-

ence Ondines curse. Ondines curse may be an under-recognized cause of

death in patients who have medullary stroke [17].

In addition to causing hypoventilation, brainstem lesions can affect the

ability to cough, phonate, swallow, and perform sighs, with deleterious clin-

ical consequences. Unfortunately, such impairments may not be obvious toclinicians until a failed extubation reveals a patients inability to protect the

airway and clear secretions. Upper airway obstruction (floppy airway)

and inability to handle secretions secondary to brainstem dysfunction are

common reasons for reintubating neurosurgical patients [18,19]. Conversely,

early tracheostomy in neurosurgical patients may be associated with shorter

ICU stays and respiratory complications, perhaps by allowing more effective

pulmonary toilet in patients who have compromised bulbar function [20].

Patients who have brainstem damage may have marked abnormalities in

voluntary and reflex cough. Aerodynamic studies of patients with brainstemstroke show abnormal inspiration phase volume, peak inspiratory flow, du-

ration of glottic closure, and delayed onset to peak of the expulsive phased

all of which can contribute to ineffective cough and an increased risk for

aspiration pneumonia [21].

The most common etiology of respiratory dysfunction associated with

brainstem injury is cerebrovascular disease, but trauma, demyelinating

disease, infections, neoplasms, and degenerative disorders also can have sig-

nificant respiratory effects. Respiratory involvement is an often overlooked

aspect of multiple sclerosis. Lesions in the cervical cord, medulla, or ponscan result in diaphragmatic paralysis, apneustic breathing, paralysis of

automatic respiration, and even neurogenic pulmonary edema. Tumors

involving the posterior fossa may be associated with impaired respiratory

function; surgery for such lesions can lead to desaturations and aspiration

events leading to a need for a tracheostomy. Degenerative diseases (Parkin-

son disease and Parkinson diseaselike disorders) can cause prominent

bulbar dysfunction with an increased risk for aspiration and a restrictive

pattern of respiration [22].

Intracranial hypertension

MV is necessary in nearly all patients who have increased ICP. Such pa-

tients almost invariably have an impaired level of consciousness mandating

ETI, and MV is needed to allow specific therapies aimed at lowering ICP

(eg, pharmacologic coma) and for therapeutic hyperventilation. Current

guidelines recommend against prophylactic hyperventilation, and therapeutic

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hyperventilation should be used only for short periods of time, targeting

a modest reduction in PCO2 to approximately 30 to 35 mm Hg [2326].

Anticipation of neurologic deterioration

In certain clinical circumstances, it is prudent to institute, or to continue,

MV based on the expected natural history of the underlying condition. For

instance, in patients with aneurysmal subarachnoid hemorrhage and severe

symptomatic vasospasm, the best strategy may be to intubate and maintain

MV, thereby protecting the airway in case of neurologic deterioration and

ensuring adequate pulmonary gas exchange in the face of hemodynamic

augmentation therapy, which may cause pulmonary edema and hypoxemia.

In patients who have incipient hydrocephalus in whom the condition islikely to progress, early ETI may facilitate further therapeutic measures

(ventriculostomy drainage, for instance) when they become necessary. Pa-

tients with hemispheric strokes and malignant edema may need early ETI

in anticipation of the need for therapeutic measures, including transient

hyperventilation, pharmacologic coma, or decompressive hemicraniectomy.

Finally, early ETI may be indicated in patients who have severe pre-existing

pulmonary disease (eg, chronic obstructive pulmonary disease) in whom

acute neurologic injury is likely to cause cardiopulmonary decompensation

[27].

Respiratory indications

Patients who have acute neurologic disorders are at increased risk for

major pulmonary complications [2830]. The acute neurologic injury

may predispose patients to secondary pulmonary problems (eg, aspiration

pneumonia or pulmonary embolism), or patients may present with chronic

cardiopulmonary disease that is decompensated by acute cardiopulmonary

stress or by treatment efforts (eg, hemodynamic augmentation therapy for

vasospasm may decompensate underlying heart failure).

Hypoxemic respiratory failure

Hypoxemic respiratory failure is a frequent complication in patients who

have acute brain injury, and the most common causes are aspiration, pneu-

monia, ALI/ARDS, pulmonary embolism, and atelectasis [29]. MV is typi-

cally indicated in all patients not improving rapidly with supplemental

oxygen or noninvasive ventilation.

Acute lung injury/acute respiratory distress syndrome

Patients who have central nervous injury can present with hypoxemic

respiratory failure as a result of pulmonary edema. Pulmonary edema

may develop secondary to increased hydrostatic pressure (eg, congestive

heart failure) or from increased capillary permeability (eg, ALI/ARDS).

ALI/ARDS is found in 10% to 30% of patients who have severe TBI



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[3034] and aneurysmal subarachnoid hemorrhage [35,36] and is a predictor

of poor outcomes in these settings. Risk for ALI/ARDS in this population

may be increased because of exposure to aspiration, transfusion, and sepsis.As discussed below, the management of ALI/ARDS in the setting of brain

injury presents unique challenges, because brain- and lung-directed thera-

peutic strategies may be discordant.

Neurogenic pulmonary edema

Some patients who are brain injured develop a syndrome that is clinically

indistinguishable from ALI/ARDS but in the absence of traditional ALI/

ARDS risk factors; in these cases, the only precipitating event is the

underlying brain insult, hence the term, neurogenic pulmonary edema[37]. The pathophysiology of neurogenic pulmonary edema is debated, al-

though both hydrostatic and capillary leak mechanisms are suggested

[38,39]. According to the hydrostatic hypothesis, the sudden adrenergic dis-

charge associated with brain injury induces intense pulmonary vasoconstric-

tion with resulting pulmonary capillary hypertension. The capillary leak

hypothesis postulates an inflammatory mechanism in which circulating in-

flammatory mediators lead to altered vascular permeability.

Pulmonary embolismPulmonary embolism is a less commonly recognized cause of hypoxemic

respiratory failure in patients who have acute brain injury [28]. Risk for

thromboembolic disease in this population may be increased by immobility,

hypercoagulability, endothelial dysfunction, and associated spinal cord in-

jury. The management of pulmonary embolism in the setting of acute cere-

bral hemorrhage is challenging, as anticoagulants or fibrinolytic agents

often are contraindicated. A useful approach is to perform a risk stratifica-

tion based on clinical, laboratory, and imaging findings. Patients who have

hemodynamic instability, elevated troponin, elevated B-type natriuretic pep-tide, and CT or echocardiographic evidence of right ventricular dysfunction

are considered at high risk for death and warrant consideration of aggres-

sive interventions, such as mechanical thrombectomy [40]. Patients who

have milder forms of pulmonary embolism in whom anticoagulation is con-

traindicated may benefit from the insertion of an inferior vena cava filter to

prevent recurrent embolism.

Mechanical ventilation and intracranial physiology

The physiologic events that occur in the thoracic cavity and their reper-

cussions on arterial blood gases are closely linked to intracranial phy-

siology, and this relationship may be significantly altered in the presence

of pulmonary or cerebral dysfunction. Therapeutic maneuvers used to

improve oxygenation or ventilation in patients with lung injury may have

unwanted effects on ICP and CBF. Positive pressure ventilation, in

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particular positive end-expiratory pressure (PEEP), increases functional re-

sidual capacity, prevents alveolar de-recruitment, and improves oxygena-

tion; however, PEEP may have detrimental neurologic effects in selectedclinical circumstances.

The role of intrathoracic pressure

Theoretically, increases in intrathoracic pressure caused by positive pres-

sure ventilation can result in raised ICP through several mechanisms [41].

Because of the anatomic proximity of the thoracic cavity and the cranial

vault, it has been suggested that changes in intrathoracic pressure are

transmitted directly through the neck to the intracranial cavity. Raisedintrathoracic pressure also causes decreased venous return to the right

atrium and a rise in jugular venous pressure, leading to an increase in

CBV and in ICP. Decreased venous return also leads to a drop in cardiac

output and blood pressure, thereby reducing CPP. If cerebral autoregula-

tion is intact, decreases in CPP are compensated for by cerebral vasodila-

tion, increasing CBV and potentially exacerbating ICP; if autoregulation

is impaired, decreased CPP may lead to cerebral ischemia.

An additional mechanism to explain the relationship between PEEP and

ICP was suggested in a recent study of patients who had concomitant braininjury and ALI/ARDS [42]. ICP increased significantly when PEEP was

associated with increased PaCO2 due to alveolar overdistension, whereas

ICP was unchanged when PEEP led to a decrease in elastance and in

PaCO2, presumably through alveolar recruitment. Thus, it may be inferred

that patients who are brain injured and who have intracranial hypertension

and condolidative lung processes, such as ARDS or pneumonia, may have

opposite ICP responses depending on how the lung responds to PEEP.

Another recent report found that respiratory system compliance may help

predict how PEEP influences CPP [43]. In patients who have normal respi-ratory system compliance, PEEP reduced mean arterial pressure and CPP,

but this effect was not observed in patients who had poor compliance. Thus,

patients with ALI/ARDS, in whom respiratory system compliance is char-

acteristically reduced, may be comparatively protected against the poten-

tially deleterious hemodynamic and intracranial effects of elevated

intrathoracic pressure. This report and others [44] indicate that PEEP

does not impair ICP or CBF but indirectly affects cerebral perfusion via

its effect on systemic hemodynamic variables. Loss of autoregulation ren-

ders the injured brain particularly vulnerable with fluctuations in CPP;hence, it is recommended that hemodynamic changes induced by MV

should be reversed with intravascular volume loading and with titration

of vasopressors [44]. Corroborating these observations, transcranial Dopp-

ler studies suggest that when cerebral autoregulation is preserved or par-

tially preserved, PEEP-induced changes in CPP may be clinically

insignificant [42,45].



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Although there are many theoretical reasons to be concerned about the

relationship between PEEP and ICP, the preponderance of available studies

suggest that this effect is quantitatively modest [4450]. Some investigatorshave hypothesized that the increased cerebral venous pressure induced by

positive pressure ventilation may have beneficial consequences on regional

CBF by reducing cerebral venous steal and correcting abnormalities in

perilesional perfusion [51]. In conclusion, PEEP seems well tolerated in the

vast majority of patients who are brain injured, and a proposed rule of thumb,

based on available data, is that PEEP is unlikely to have deleterious intracra-

nial effects if it is maintained below ICP [52].

The role of carbon dioxide

Arterial CO2 tension is a powerful physiologic modulator of CBF, and

hence of ICP. The relationship between PaCO2 and CBF is nearly linear

within a physiologic range of PaCO2 values, whereas the impact of PaO2on CBF is seen only in the setting of severe hypoxemia. Hypercapnia is as-

sociated with vasodilatationdincreased CBF and CBV, whereas hypopcap-

nia results in vasoconstrictionddecreased CBF and CBV. According to the

Monro-Kellie doctrine, in patients whose intracranial compliance is re-

duced, changes in CBV are accompanied by changes ICP. These relation-ships have long been exploited in the treatment of patients who are brain

injured [23,53,54]. It also is clear that the vasoconstrictive effects of hypo-

capnia are transient, because brain extracellular pH tends to normalize

over a period of hours, and rebound vasodilatation may be observed with

discontinuation of hyperventilation [55].

The mechanisms governing the relationship between PaCO2 and CBF are

incompletely understood. Increases in CO2 tension relax pial arterioles and

it is believed that this response is mediated by interactions involving not

only endothelium and smooth muscle but also pericytes, adjacent neurons,and glia. Experimental data indicate that cerebral blood vessels are sensitive

to changes in extracellular pH rather than to any direct effects of CO2 or

bicarbonate [56]. Extracellular pH may exert effects on smooth muscle

tone through second messenger systems, including nitric oxide, prostanoids,

cyclic nucleotides, potassium, and calcium [23]. The range in which PaCO2has the greatest impact on cerebral vessel caliber is 20 to 60 mm Hg. Within

this range, CBF changes 3% for every 1 mm Hg change in Pa CO2 [57].

The known vasoconstrictive effect of hypocapnia has elicited concern that

cerebral ischemia might be induced or worsened during therapeutic hyper-ventilation. CBF may be markedly reduced regionally and globally in the

early period after TBI and this reduction in CBF is associated with worse

clinical outcomes [58,59]. Whether or not the institution of hyperventilation

in this setting is likely to precipitate ischemia is the subject of debate. Mea-

surements using intracerebral oxygen probes show that hyperventilation re-

duces brain tissue PO2 in a virtually linear relationship and that these

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changes closely mirror concomitant reductions in CBF [6062]. These find-

ings have been contested in other studies indicating that brain tissue PO2 is

not affected by hyperventilation [63] or even increased by it [64]. It is arguedthat in patients who have TBI, pericontusional tissues may have abnormally

elevated CO2 reactivity, increasing their vulnerability to hyperventilation-

induced ischemia [65]. Alternatively, it has been noted in severe TBI that

although moderate hyperventilation leads to a global decrease in CBF, ce-

rebral oxygen extraction fraction is unchanged, refuting an ischemic process

[66]. Based on observations regional brain hyperperfusion in a subset of

patients who had TBI, a strategy of hyperventilation has been proposed

in which PaCO2 is adjusted according to measurements of cerebral oxygen

extraction obtained through jugular venous oximetry [67,68]. More recently,in a series of reports using jugular venous oximetry, cerebral microdialysis,

and positron emission tomography, the Cambridge neurocritical care group

has demonstrated that hyperventilation increases the risk of cerebral ische-

mia in TBI and that ischemic changes may be overlooked when global

monitors of brain oxygenation are used [6971]. In another study using

microdialysis, Marion and colleagues [25] observed that that hyperventila-

tion instituted 24 to 36 hours after TBI was associated with a significant in-

crease in brain lactate/pyruvate ratio, whereas this change was not observed

3 to 4 days after injury. The degree to which delay after injury influences theeffect of hyperventilation also is debated. Although the latter report found

the greatest risk for hyperventilation-induced ischemia occurs early after

brain injury, other groups show that large decrements in brain tissue oxy-

genation may be observed in response to hyperventilation at 5 days [61]

or that this response actually may increase with time [62].

In the only published randomized controlled trial evaluating the effect of

hyperventilation on clinical outcomes after TBI [24], 113 patients who had

severe head injury were randomized to three groupsda hyperventilation

group with a PaCO2 goal of 25 mm Hg, a normoventilation group witha PaCO2 goal of 35 mm Hg, and a group that received hyperventilation

and the bicarbonate buffer, tromethamine. At 3 and 6 months after injury,

patients in the hyperventilation group who had an initial GCS motor score

of 4 or 5 had significantly higher risk for death or severe disability than

patients in the other groups. These data were analyzed further in a Cochrane

review, which found that the difference in death or disability between the

three groups was not significant [72]. Current brain injury guidelines recom-

mend against prophylactic or prolonged use of hyperventilation, but recog-

nize that brief periods of hyperventilation may be indicated in the presenceof acute neurologic deterioration (herniation or sudden ICP elevation) [26].

Collectively, available data are mixed regarding the role of hyperventila-

tion in patients who are brain injured. It is likely that the risk/benefit

relationship of hyperventilation varies depending on several factors, includ-

ing baseline cerebral perfusion status, the presence or absence of intracranial

hypertension, and the time since injury. A rational approach may be to use



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normocapnic ventilation in the majority of patients who are brain injured

while reserving hyperventilation for selected patients who have intracranial

hypertension that is poorly responsive to other measures but only inconjunction with one or preferably several measures of cerebral oxygenation

status, such as jugular venous oximetry, brain tissue oxygenation, and

microdialysis.

Strategies of mechanical ventilation in acute brain injury

Lung-protective mechanical ventilation

Traditional resuscitative paradigms in acute brain injury and intracranialhypertension have included a cardiopulmonary strategy centered on protect-

ing the airway, optimization of oxygen delivery to the brain, strict control of

PaCO2, and minimizing the postulated adverse effects of positive pressure

ventilation on ICP. Such a brain-directed strategy was typically achieved us-

ing larger tidal volumes, high inspired O2, low or zero PEEP, intravascular

fluid loading, and administration of vasopressors to maintain adequate

CPP.

A large body of evidence indicates that MV can itself exacerbate under-

lying lung injury or even initiate it in susceptible individuals. This ventilator-induced lung injury (VILI) results in a histologic pattern indistinguishable

from the diffuse alveolar damage seen in ALI/ARDS, and may contribute

significantly to morbidity and mortality in patients with ALI/ARDS [73].

Although understanding of VILI pathogenesis is incomplete, a prevailing

hypothesis is that cellular detection of mechanical changes caused by alveo-

lar overdistension (volotrauma) and atelectasis (atelectrauma) leads to the

expression of inflammatory mediators, leukocyte recruitment and activa-

tion, and propagation of the inflammatory process to the bloodstream

and remote organs (biotrauma) [74]. Although original accounts describedVILI in the setting of pre-existing ALI/ARDS, it has become apparent

that VILI may contribute to the development of ALI/ARDS in a subset

of high-risk patients [75,76].

Lung-protective MV is based on the concept that VILI can be prevented

or attenuated through the use of low tidal volumes and plateau pressures to

minimize overdistension, and PEEP to limit atelectasis [77]. This postulate

was strengthened with the publication of a multicenter randomized trial

demonstrating that a lung-protective MV strategy in patients with ALI/

ARDS reduced in-hospital mortality by 21% [78]. In another multicentertrial of ALI/ARDS patients, a restrictive fluid management strategy

improved lung function and shortened the duration of MV and ICU stay

without increasing nonpulmonary organ failures compared with a strategy

of liberal fluid administration [79]. Lung-protective ventilation has gained

a prominent place in treatment of ALI/ARDS and its implementation

may account for the decrease in ALI/ARDS mortality observed in recent

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years [80]. The importance of VILI in patients who have acute neurologic

disease is uncertain, however, and there are theoretical obstacles to imple-

menting lung-protective MV in this population.Emerging data show that VILI may be a considerable problem in acute

brain injury. The lungs of rabbits exposed to a head trauma and then to an

injurious MV strategy (high tidal volumes and low PEEP) had significantly

greater pulmonary edema and hemorrhage than the lungs of animals without

head injury [81]. In a multicenter cohort of patients who were brain injured,

Mascia and colleagues [82] found that the use of high tidal volumes was an

independent predictor of ALI/ARDS (odds ratio 5.4; 95% CI, 1.519.2).

These results support a multiple-hit model of ALI/ARDS pathogenesis,

in which brain injury might prime extracranial organs for dysfunctionand failure [37,83], and provide a rationale for lung-protective MV in

this population. There are, nevertheless, concerns about such an approach.

Low tidal volume ventilation may be associated with significant reductions

in minute ventilation leading to deliberate, permissive hypercapnia,

which is often well tolerated from a systemic physiologic standpoint and

may even present benefits [84], but which can be highly detrimental in

patients with intracranial hypertension; high levels of PEEP may have

adverse consequences on cerebral venous return and on CPP; and fluid re-

striction may be associated with hypotension compromising CPP. Becauseof these concerns, patients who have acute brain injury were deliberately

excluded from the large ALI/ARDS randomized trials [78,79].

Notwithstanding, the available studies do not support these concerns.

A lung-protective strategy may be accomplished without hypercapnia, as

evidenced by normal PaCO2 levels in the cited randomized trial [78], and

moderate to high levels of PEEP are well tolerated in the majority of

patients who are brain injured (discussed previously). Preliminary data indi-

cate that a low tidal volume approach may be applied safely and effectively

in patients who have acute intracranial disorders [36,85].

High-frequency oscillatory ventilation

High-frequency oscillatory ventilation (HFOV) uses a combination of

elevated mean airway pressures and very small tidal volumes delivered at

a rapid rate. HFOV has been widely used for MV of neonatal and pediatric

patients and more recently was introduced in adults with ALI/ARDS [86].

Postulated advantages of HFOV over conventional modes of MV are a su-

perior ability to prevent alveolar derecruitment and to limit overdistension,suggesting HFOV might be ideally suited to protect against VILI. Clinical

trials show that HFOV is a safe and effective means to improve oxygenation

in severe ARDS compared with conventional modes of MV [87,88].

The potential applications of HFOV in patients who have concomitant

ARDS and acute brain injury have been evaluated in few studies [8992].

Salim and colleagues [92] studied 10 patients, finding that HFOV was



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associated with improved oxygenation and ventilation and decreased ICP.

In a study of five patients that included 390 periods of observation, David

and colleagues [91] reported that HFOV increased PaO2 and was generallywell tolerated; however, they noted increases in ICP and decreased CPP in

a minority of patients and recommend that patients who are brain injured

and receiving HFOV have ICP monitoring. In an earlier study of 38 patients

who had TBI and who had hypoxemic respiratory failure, Hurst and co-

workers reported that use of high-frequency percussive ventilation resulted

in a modest but significant reduction in ICP [89].

Prone positioning

Placing patients who have ALI/ARDS in the prone position is associated

with physiologic benefits, including recruitment of atelectatic lung units,

decreased ventilation-perfusion mismatch, improved respiratory mechanics,

increased secretion drainage, reduced and improved distribution of injurious

mechanical forces, and decreased propensity for developing VILI [93].

Available randomized trials indicate that prone positioning in patients who

have ALI/ARDS improves oxygenation but does not influence mortality

[94,95].

A few studies have evaluated prone positioning in patients with concur-

rent brain injured and ALI/ARDS or respiratory failure [9698], with mixed

results. In a randomized trial of mechanically ventilated comatose patients,

prone positioning was associated with lower lung injury scores and ventila-

tor-associated pneumonia rates but increased ICP compared with the supine

position [96]. In a retrospective analysis of patients who had aneurysmal

subarachnoid hemorrhage and ARDS, prone positioning was associated

with significant increases in arterial and brain tissue oxygenation, but ICP

was increased and CPP was decreased [97]. These data contrasted with

another study of ARDS patients who had TBI or intracerebral hemorrhage,

in which prone positioning had no effect on ICP or CPP but significantlyameliorated oxygenation and respiratory system compliance [98].

Nitric oxide

Inhaled nitric oxide induces selective vasodilation in ventilated lung units,

thereby decreasing ventilation-perfusion mismatch, improving oxygenation,

and attenuating pulmonary hypertension [99]. A meta-analysis of random-

ized trials concluded that inhaled nitric oxide given to patients who have

ALI/ARDS improves oxygenation but is not associated with any survivaladvantage and may even cause harm [100]. Published data on the use of

inhaled nitric oxide in the setting of brain injury are limited. In a case report

of a 10-year-old patient who had concurrent TBI, ARDS, and pulmonary

hypertension, use of inhaled nitric oxide improved oxygenation and pulmo-

nary vascular resistance but had no significant effects on middle cerebral

artery blood flow velocities, jugular venous oxygen saturation, or ICP

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[101]. In another report, inhaled nitric oxide was used successfully to correct

hypoxemia in a patient who had aneurysmal subarachnoid hemorrhage and

ARDS undergoing surgical aneurysm clipping [102].

Liberation from mechanical ventilation in acute brain injury

Although the provision of MV is an essential step in the acute resuscita-

tion of patients who are brain injured, it is important to recognize at what

point MV can be reduced and discontinued. Timely liberation from MV and

extubation reduces the risk for VILI, VAP, airway injury, unnecessary seda-

tion, delirium, and prolonged ICU stay. These benefits need to be weighed

against the risks of premature ventilator and artificial airway discontinua-tion, including ventilatory muscle fatigue, gas exchange failure, and loss

of airway protection.

The morbidity of MV in acute brain injury may be appreciated by

considering VAP, which is exceedingly common in patients who have brain

injury. Data from a National Nosocomial Infections Surveillance system

report indicate that neurosurgical ICUs have the third highest rate of

VAP compared with 10 different ICU subspecialty types [103]. Available

studies indicate that 20% to 45% of patients who have TBI [104106] or

subarachnoid hemorrhage [28] develop VAP and that VAP is associatedwith increased length of stay [105,106] and even increased mortality [104].

Patients who are brain injured commonly achieve independence from

positive pressure ventilation without difficulty, but MV is continued because

of concerns regarding poor mental status and brainstem dysfunction with

deficient airway protective mechanisms. Essential data are lacking to guide

clinicians in making decisions about how and when to liberate neurologic

patients from MV, leading to wide variations in clinical practice [107].

Role of protocolized weaning strategies

In 2001, the American College of Chest Physicians, the Society of Critical

Care Medicine, and the American Association for Respiratory Care

proposed that liberation from MV be guided by the following principles

[108]: (1) frequent assessment is required to determine whether or not ven-

tilatory support and the artificial airway still are needed; (2) factors that

contribute to ventilator dependence must be re-evaluated continually; and

(3) ventilator discontinuation and weaning protocols can be performed

effectively by nonphysician providers.In recent years, several randomized trials have demonstrated that the

length of MV can be decreased significantly when the process of liberation

is protocolized. The beneficial effects of protocolized weaning strategies

have been demonstrated in medical [109], surgical [110], and multidis-

ciplinary critical care populations. These studies support the notion that

integrated assessments together with a carefully monitored spontaneous



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breathing trial (SBT), in which ventilator support is provocatively reduced

to a minimum, provide the most useful information to guide extubation.

The SBT is a safe procedure and the additional information obtainedthrough the measurement of sophisticated weaning parameters may not

add significant predictive value over the SBT [111,112]. Most of the ventila-

tor weaning trials did not include patients who were brain injured and there

are few data addressing the specific and unique needs of patients who have

primary neurologic impairment.

Studies of ventilator liberation in neurologic patients

In a prospective observational study of mechanically ventilated patientswho had acute brain injury, Coplin and colleagues [107] assessed readiness

for extubation using respiratory and hemodynamic criteria together with neu-

rologic parameters, namely a stable neurologic examination, ICP less than

20 mm Hg, and CPP greater than or equal to 60 mm Hg. The investigators

defined extubation delay as the period between the day patients met criteria

for extubation and the actual day of extubation. Extubation was delayed in 37

of 136 (27%) patients and occurred a median of 3 days after criteria had been

met. Patients who had extubation delay had been receiving MV for longer

periods of time before meeting readiness criteria and had lower GCS. Extu-bation was delayed in nearly half (48%) of patients who had a GCS less

than or equal to 8 versus only 12% of patients who had a GCS greater

than 8; however, at least half of patients who had extubation delay showed

no neurologic improvement from the day they met readiness criteria to the

day of extubation. One quarter of patients developed pneumonia and delayed

extubation was associated with nearly fourfold-increased odds of this compli-

cation. Reintubation occurred in 18% of patients and earlier extubation

when criteria was not associated with a higher reintubation rate. Level of con-

sciousness and bulbar dysfunction did not seem to predict extubation out-come. Successful extubation occurred in 80% of patients who had a GCS

less than or equal to 8 and in 90% of those who had a GCS less than or equal

to 4. Eighty-eight percent of subjects who had an absent or weak gag reflex

were successfully extubated as were 82% of those who had an absent or

weak cough. The findings of Coplin and colleagues make a strong case against

extubation delay in patients who are brain injured and who otherwise meet

criteria; they challenge widely held assumptions about the ability to protect

the airway based on the level of consciousness and the presence of bulbar

reflexes.In a randomized trial conducted in a neurosurgical ICU, Namen and

colleagues [18] evaluated the impact of a ventilator weaning protocol incor-

porating a daily screen (evaluating physiologic and respiratory criteria) and

SBTs. Median duration of ventilation (6 days) and time to successful extu-

bation (10 days) were similar in both groups. Only one quarter of patients

who passed the daily screen/SBT were extubated promptly. The principal

556 STEVENS et al


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reason for not proceeding with extubation despite meeting readiness criteria

was decreased mental status. In marked contrast to the Coplin study, in this

trial the GCS was the best predictor of successful extubation. The odds ofsuccessful extubation rose by 39% for every 1-point increase in the GCS

and a receiver operating characteristic analysis suggested that GCS greater

than 8 was associated with best prediction for successful extubation. The

lack of any difference between randomization groups in outcomes was inter-

preted as a failure of the protocol to alter caregiver behavior toward venti-

lator liberation, the main reason being that the protocol did not incorporate

neurologic criteria into the daily screening of these patients.

These studies underscore the need for ventilator liberation protocols de-

signed to identify neurologically impaired patients who can be liberatedfrom MV promptly and safely. A randomized trial evaluating such a proto-

col is currently underway in the Johns Hopkins Neurosciences Critical Care

Unit, testing the hypothesis that the implementation of an integrated screen

associated with SBTs leads to expeditious and safe liberation from MV in

this population.

Tracheostomy in patients who are brain injured

Tracheostomy is a common procedure in critically ill patients and is in-creasingly performed at the bedside using a percutaneous dilational tech-

nique [113]. The potential advantages of tracheostomy over continued

translaryngeal ETI include decreased risk for self-extubation and of sinusitis,

reduced airway resistance and dead space resulting in decreased work of

breathing, better subjective tolerance, lesser need for sedation, and decreased

duration of MV, although this last point has been the subject of debate [114].

Risks of tracheostomy include surgical site infection, hemorrhage, pneumo-

thorax, and esophageal perforation.

The indications and timing of tracheostomy in critically ill patients aredebated. In a consensus conference convened in 1989, the recommendations

were to perform tracheostomy if the anticipated need for an artificial airway

exceeds 21 days [115], a view maintained in a recent multisociety task force

report [116]. The latter document formulated a set of indications for trache-

ostomy in ICUs: patients requiring high levels of sedation to tolerate trans-

laryngeal tubes; patients who have marginal respiratory mechanics in whom

a tracheostomy tube having lower resistance might reduce the risk for

muscle fatigue; patients likely to derive considerable psychological, benefit

from the ability to eat and to communicate by articulated speech; and thosein whom enhanced mobility is critically needed to enhance physical therapy

[116].

Data on the value of tracheostomy in patients who have acute brain

injury are limited. A recent meta-analysis of trauma studies indicated that

tracheostomy has no effect on mortality, rates of pneumonia, and laryngo-

tracheal injury but may hasten liberation from MV in patients who have



16/21

severe TBI [117]. The latter conclusion was based largely on one small

randomized trial of patients with TBI, in which the mean duration of MV

was 3 days shorter in the tracheostomy group (14.5 7.3 days versus17.5 10.6; P .02) [118]. Larger randomized trials are needed to define

the role of tracheostomy in this population.

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El Rol de La Ventilacion Mecanica en Neurologia