Neurol Clin 26 (2008) 543563

The Role of Mechanical Ventilation in Acute Brain Injury

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

Division 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, USA b Neurosciences 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, fullling multiple goals, including ensuring protection of the airway, participating in tissue oxygen delivery, and indirectly modulating cerebral vascular reactivity. MV also carries signicant risks most notably ventilator-associated pneumonia (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 aect cerebral perfusion pressure (CPP), although the importance of this eect 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 conict 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 indication for instituting MV is an acute neurologic disorder in 20% of cases,
* Corresponding author. E-mail address: rstevens@jhmi.edu (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

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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 mechanically ventilated for a primary neurologic disease have longer periods of MV and increased mortality when compared to non-neurologic patients [3,4]. Among patients receiving MV, neurologic factors contribute to prolongation 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 classied 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 indications coexist. 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 Coma Patients 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 associated with decreases in respiratory drive, and hypoventilation is a common nding in most encephalopathies regardless of cause [6]. Respiratory function may be depressed because of a hemispheric insult, brainstem damage or dysfunction, spinal cord injury, or systemic factors. Airway patency may be compromised by foreign objects, secretions, orofacial fractures, or soft tissue edema associated with cervical injuries. In addition, oropharyngeal muscle tone is signicantly 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 overdose, aspiration pneumonia, pulmonary contusions, fat emboli, pneumothorax, ail chest, and pulmonary edema [68]. In addition to the problems discussed previously, traumatic brain injury (TBI) results in dramatic biochemical derangements that have signicant eects on pulmonary physiology. Brain injury results in a systemic inammatory response characterized by the release of proinammatory cytokines and neuropeptides with unique eects on the lungs [9,10]. The biologic eect of such inammatory mediators is associated with pulmonary vascular expression of adhesion molecules and leukocyte inltration 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 impaired bulbar function that results in decreased ventilatory drive, inability to protect the airway, and diculty handling secretions. Patients who have large (malignant) hemispheric strokes often need ETI and MV because of 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 signicance of certain respiratory patterns has often been cited, and some patterns may be associated 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 cardiopulmonary disease. Patients with brainstem injury (basilar artery occlusion) may develop apneustic breathing. Elderly patients with underlying cerebrovascular disease or dementia may show apraxia of breathing after suering a frontal stroke (usually in association with other apraxias). Lastly, a completely erratic pattern, termed ataxic breathing, may be seen in patients with extensive medullary lesions. Brainstem dysfunction Brainstem dysfunction can aect respiration in several ways. The brainstem 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 aerent input from the cerebral cortex (from the lungs via the vagus nerve), modulates respiratory frequency, and inuences ne control of respiratory function. Medullary respiratory 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 ineective respirations with resulting alveolar hypoventilation in the setting of a preserved alveoloarterial 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 pontomedullary reticular formation and the nucleus tractus solitarius may result in severe respiratory failure aecting automatic and voluntary respiration [16].

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The most extreme forms of ventilatory dysfunction in patients with brainstem injury is Ondines curse, in which automatic respirations are abolished. The lesion in Ondines curse usually is located in the lateral medulla aecting the 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 experience 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 aect the ability to cough, phonate, swallow, and perform sighs, with deleterious clinical consequences. Unfortunately, such impairments may not be obvious to clinicians until a failed extubation reveals a patients inability to protect the airway and clear secretions. Upper airway obstruction (oppy 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 eective pulmonary toilet in patients who have compromised bulbar function [20]. Patients who have brainstem damage may have marked abnormalities in voluntary and reex cough. Aerodynamic studies of patients with brainstem stroke show abnormal inspiration phase volume, peak inspiratory ow, duration of glottic closure, and delayed onset to peak of the expulsive phased all of which can contribute to ineective 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 signicant respiratory eects. Respiratory involvement is an often overlooked aspect of multiple sclerosis. Lesions in the cervical cord, medulla, or pons can 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 (Parkinson 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 patients almost invariably have an impaired level of consciousness mandating ETI, and MV is needed to allow specic 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 is likely to progress, early ETI may facilitate further therapeutic measures (ventriculostomy drainage, for instance) when they become necessary. Patients 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 eorts (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, pneumonia, ALI/ARDS, pulmonary embolism, and atelectasis [29]. MV is typically 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 therapeutic 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, although both hydrostatic and capillary leak mechanisms are suggested [38,39]. According to the hydrostatic hypothesis, the sudden adrenergic discharge associated with brain injury induces intense pulmonary vasoconstriction with resulting pulmonary capillary hypertension. The capillary leak hypothesis postulates an inammatory mechanism in which circulating inammatory mediators lead to altered vascular permeability. Pulmonary embolism Pulmonary 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 injury. The management of pulmonary embolism in the setting of acute cerebral hemorrhage is challenging, as anticoagulants or brinolytic agents often are contraindicated. A useful approach is to perform a risk stratication based on clinical, laboratory, and imaging ndings. Patients who have hemodynamic instability, elevated troponin, elevated B-type natriuretic peptide, and CT or echocardiographic evidence of right ventricular dysfunction are considered at high risk for death and warrant consideration of aggressive interventions, such as mechanical thrombectomy [40]. Patients who have milder forms of pulmonary embolism in whom anticoagulation is contraindicated may benet from the insertion of an inferior vena cava lter to prevent recurrent embolism. Mechanical ventilation and intracranial physiology The physiologic events that occur in the thoracic cavity and their repercussions on arterial blood gases are closely linked to intracranial physiology, and this relationship may be signicantly 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 eects on ICP and CBF. Positive pressure ventilation, in

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particular positive end-expiratory pressure (PEEP), increases functional residual capacity, prevents alveolar de-recruitment, and improves oxygenation; however, PEEP may have detrimental neurologic eects in selected clinical circumstances. The role of intrathoracic pressure Theoretically, increases in intrathoracic pressure caused by positive pressure 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. Raised intrathoracic 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 autoregulation is intact, decreases in CPP are compensated for by cerebral vasodilation, 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 brain injury and ALI/ARDS [42]. ICP increased signicantly 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 inuences CPP [43]. In patients who have normal respiratory system compliance, PEEP reduced mean arterial pressure and CPP, but this eect was not observed in patients who had poor compliance. Thus, patients with ALI/ARDS, in whom respiratory system compliance is characteristically reduced, may be comparatively protected against the potentially deleterious hemodynamic and intracranial eects of elevated intrathoracic pressure. This report and others [44] indicate that PEEP does not impair ICP or CBF but indirectly aects cerebral perfusion via its eect on systemic hemodynamic variables. Loss of autoregulation renders the injured brain particularly vulnerable with uctuations 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 Doppler studies suggest that when cerebral autoregulation is preserved or partially preserved, PEEP-induced changes in CPP may be clinically insignicant [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 eect is quantitatively modest [4450]. Some investigators have hypothesized that the increased cerebral venous pressure induced by positive pressure ventilation may have benecial 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 intracranial eects 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 PaO2 on CBF is seen only in the setting of severe hypoxemia. Hypercapnia is associated with vasodilatationdincreased CBF and CBV, whereas hypopcapnia results in vasoconstrictionddecreased CBF and CBV. According to the Monro-Kellie doctrine, in patients whose intracranial compliance is reduced, changes in CBV are accompanied by changes ICP. These relationships have long been exploited in the treatment of patients who are brain injured [23,53,54]. It also is clear that the vasoconstrictive eects of hypocapnia 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 eects of CO2 or bicarbonate [56]. Extracellular pH may exert eects on smooth muscle tone through second messenger systems, including nitric oxide, prostanoids, cyclic nucleotides, potassium, and calcium [23]. The range in which PaCO2 has 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 PaCO2 [57]. The known vasoconstrictive eect of hypocapnia has elicited concern that cerebral ischemia might be induced or worsened during therapeutic hyperventilation. 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. Measurements using intracerebral oxygen probes show that hyperventilation reduces brain tissue PO2 in a virtually linear relationship and that these

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changes closely mirror concomitant reductions in CBF [6062]. These ndings have been contested in other studies indicating that brain tissue PO2 is not aected by hyperventilation [63] or even increased by it [64]. It is argued that in patients who have TBI, pericontusional tissues may have abnormally elevated CO2 reactivity, increasing their vulnerability to hyperventilationinduced ischemia [65]. Alternatively, it has been noted in severe TBI that although moderate hyperventilation leads to a global decrease in CBF, cerebral 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 ischemia 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 hyperventilation instituted 24 to 36 hours after TBI was associated with a signicant increase in brain lactate/pyruvate ratio, whereas this change was not observed 3 to 4 days after injury. The degree to which delay after injury inuences the eect 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 oxygenation 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 eect 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 with a PaCO2 goal of 35 mm Hg, and a group that received hyperventilation and the bicarbonate buer, 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 signicantly 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 dierence in death or disability between the three groups was not signicant [72]. Current brain injury guidelines recommend against prophylactic or prolonged use of hyperventilation, but recognize that brief periods of hyperventilation may be indicated in the presence of acute neurologic deterioration (herniation or sudden ICP elevation) [26]. Collectively, available data are mixed regarding the role of hyperventilation in patients who are brain injured. It is likely that the risk/benet relationship of hyperventilation varies depending on several factors, including 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 in conjunction 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 intracranial hypertension have included a cardiopulmonary strategy centered on protecting the airway, optimization of oxygen delivery to the brain, strict control of PaCO2, and minimizing the postulated adverse eects of positive pressure ventilation on ICP. Such a brain-directed strategy was typically achieved using larger tidal volumes, high inspired O2, low or zero PEEP, intravascular uid loading, and administration of vasopressors to maintain adequate CPP. A large body of evidence indicates that MV can itself exacerbate underlying lung injury or even initiate it in susceptible individuals. This ventilatorinduced lung injury (VILI) results in a histologic pattern indistinguishable from the diuse alveolar damage seen in ALI/ARDS, and may contribute signicantly 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 alveolar overdistension (volotrauma) and atelectasis (atelectrauma) leads to the expression of inammatory mediators, leukocyte recruitment and activation, and propagation of the inammatory process to the bloodstream and remote organs (biotrauma) [74]. Although original accounts described VILI 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 multicenter trial of ALI/ARDS patients, a restrictive uid 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 uid 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 implementing 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 signicantly 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 dysfunction and 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 signicant reductions in minute ventilation leading to deliberate, permissive hypercapnia, which is often well tolerated from a systemic physiologic standpoint and may even present benets [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 uid restriction may be associated with hypotension compromising CPP. Because of 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 indicate that a low tidal volume approach may be applied safely and eectively 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 superior 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 eective 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, nding that HFOV was

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associated with improved oxygenation and ventilation and decreased ICP. In a study of ve patients that included 390 periods of observation, David and colleagues [91] reported that HFOV increased PaO2 and was generally well 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 coworkers reported that use of high-frequency percussive ventilation resulted in a modest but signicant reduction in ICP [89]. Prone positioning Placing patients who have ALI/ARDS in the prone position is associated with physiologic benets, 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 inuence mortality [94,95]. A few studies have evaluated prone positioning in patients with concurrent 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 ventilator-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 signicant 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 eect on ICP or CPP but signicantly ameliorated 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 randomized trials concluded that inhaled nitric oxide given to patients who have ALI/ARDS improves oxygenation but is not associated with any survival advantage 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 pulmonary vascular resistance but had no signicant eects on middle cerebral artery blood ow 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 resuscitation 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 sedation, delirium, and prolonged ICU stay. These benets need to be weighed against the risks of premature ventilator and articial airway discontinuation, 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 dierent 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 associated with increased length of stay [105,106] and even increased mortality [104]. Patients who are brain injured commonly achieve independence from positive pressure ventilation without diculty, but MV is continued because of concerns regarding poor mental status and brainstem dysfunction with decient 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 ventilatory support and the articial 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 eectively by nonphysician providers. In recent years, several randomized trials have demonstrated that the length of MV can be decreased signicantly when the process of liberation is protocolized. The benecial eects of protocolized weaning strategies have been demonstrated in medical [109], surgical [110], and multidisciplinary 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 obtained through the measurement of sophisticated weaning parameters may not add signicant predictive value over the SBT [111,112]. Most of the ventilator weaning trials did not include patients who were brain injured and there are few data addressing the specic 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 patients who had acute brain injury, Coplin and colleagues [107] assessed readiness for extubation using respiratory and hemodynamic criteria together with neurologic parameters, namely a stable neurologic examination, ICP less than 20 mm Hg, and CPP greater than or equal to 60 mm Hg. The investigators dened 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. Extubation 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 complication. Reintubation occurred in 18% of patients and earlier extubation when criteria was not associated with a higher reintubation rate. Level of consciousness and bulbar dysfunction did not seem to predict extubation outcome. 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 reex were successfully extubated as were 82% of those who had an absent or weak cough. The ndings 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 reexes. In a randomized trial conducted in a neurosurgical ICU, Namen and colleagues [18] evaluated the impact of a ventilator weaning protocol incorporating a daily screen (evaluating physiologic and respiratory criteria) and SBTs. Median duration of ventilation (6 days) and time to successful extubation (10 days) were similar in both groups. Only one quarter of patients who passed the daily screen/SBT were extubated promptly. The principal

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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 of successful 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 dierence between randomization groups in outcomes was interpreted as a failure of the protocol to alter caregiver behavior toward ventilator 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 designed to identify neurologically impaired patients who can be liberated from MV promptly and safely. A randomized trial evaluating such a protocol 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 increasingly performed at the bedside using a percutaneous dilational technique [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, pneumothorax, and esophageal perforation. The indications and timing of tracheostomy in critically ill patients are debated. In a consensus conference convened in 1989, the recommendations were to perform tracheostomy if the anticipated need for an articial 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 tracheostomy in ICUs: patients requiring high levels of sedation to tolerate translaryngeal 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, benet from the ability to eat and to communicate by articulated speech; and those in 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 eect on mortality, rates of pneumonia, and laryngotracheal injury but may hasten liberation from MV in patients who have

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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 versus 17.5 10.6; P .02) [118]. Larger randomized trials are needed to dene the role of tracheostomy in this population. References
[1] Stevens RD, Dowdy DW, Michaels RK, et al. Neuromuscular dysfunction acquired in critical illness: a systematic review. Intensive Care Med 2007;33(11):187691. [2] Mehta S. Neuromuscular disease causing acute respiratory failure. Respir Care 2006;51(9): 101621. [3] Esteban A, Anzueto A, Alia I, et al. How is mechanical ventilation employed in the intensive care unit? An international utilization review. Am J Respir Crit Care Med 2000;161(5): 14508. [4] Esteban A, Anzueto A, Frutos F, et al. Characteristics and outcomes in adult patients receiving mechanical ventilation: a 28-day international study. JAMA 2002;287(3):34555. [5] Kelly BJ, Matthay MA. Prevalence and severity of neurologic dysfunction in critically ill patients. Inuence on need for continued mechanical ventilation. Chest 1993;104(6): 181824. [6] Bolton CF. Anatomy and physiology of the nervous system control of respiration. In: Bolton CF, Chen R, Wijdicks EFM, et al, editors. Neurology of breathing. Philadelphia: Butterworth Heineman; 2004. p. 1935. [7] Bolton C. Respiration in central nervous system disorders. In: Bolton C, Chen R, Wijdicks E, et al, editors. Neurology of breathing. Philadelphia: Butterworth Heinemann; 2004. p. 15164. [8] Johnson VE, Huang JH, Pilcher WH. Special cases: mechanical ventilation of neurosurgical patients. Crit Care Clin 2007;23(2):27590, x. [9] Woiciechowsky C, Schoning B, Cobanov J, et al. Early IL-6 plasma concentrations correlate with severity of brain injury and pneumonia in brain-injured patients. J Trauma 2002; 52(2):33945. [10] Kalsotra A, Zhao J, Anakk S, et al. Brain trauma leads to enhanced lung inammation and injury: evidence for role of P4504Fs in resolution. J Cereb Blood Flow Metab 2007;27(5): 96374. [11] Koutsoukou A, Perraki H, Raftopoulou A, et al. Respiratory mechanics in brain-damaged patients. Intensive Care Med 2006;32(12):194754. [12] Mayer SA, Copeland D, Bernardini GL, et al. Cost and outcome of mechanical ventilation for life-threatening stroke. Stroke 2000;31(10):234653. [13] Bushnell CD, Phillips-Bute BG, Laskowitz DT, et al. Survival and outcome after endotracheal intubation for acute stroke. Neurology 1999;52(7):137481. [14] Rowat AM, Wardlaw JM, Dennis MS. Abnormal breathing patterns in stroke: relationship with location of acute stroke lesion and prior cerebrovascular disease. J Neurol Neurosurg Psychiatry 2007;78(3):2779. [15] Posner JB, Plum F. Plum and Posners diagnosis of stupor and coma. 4th edition. New York: Oxford University Press; 2007. [16] Bogousslavsky J, Khurana R, Deruaz JP, et al. Respiratory failure and unilateral caudal brainstem infarction. Ann Neurol 1990;28(5):66873. [17] Terao S, Miura N, Osano Y, et al. Rapidly progressive fatal respiratory failure (Ondines curse) in the lateral medullary syndrome. J Stroke Cerebrovasc Dis 2004;13(1):414. [18] Namen AM, Ely EW, Tatter SB, et al. Predictors of successful extubation in neurosurgical patients. Am J Respir Crit Care Med 2001;163(3 Pt 1):65864.

MECHANICAL VENTILATION IN ACUTE BRAIN INJURY

559

[19] Koh WY, Lew TW, Chin NM, et al. Tracheostomy in a neuro-intensive care setting: indications and timing. Anaesth Intensive Care 1997;25(4):3658. [20] Teoh WH, Goh KY, Chan C. The role of early tracheostomy in critically ill neurosurgical patients. Ann Acad Med Singapore 2001;30(3):2348. [21] Smith Hammond CA, Goldstein LB, Zajac DJ, et al. Assessment of aspiration risk in stroke patients with quantication of voluntary cough. Neurology 2001;56(4):5026. [22] Polkey MI, Lyall RA, Moxham J, et al. Respiratory aspects of neurological disease. J Neurol Neurosurg Psychiatry 1999;66(1):515. [23] Stocchetti N, Maas AI, Chieregato A, et al. Hyperventilation in head injury: a review. Chest 2005;127(5):181227. [24] Muizelaar JP, Marmarou A, Ward JD, et al. Adverse eects of prolonged hyperventilation in patients with severe head injury: a randomized clinical trial. J Neurosurg 1991;75(5):7319. [25] Marion DW, Puccio A, Wisniewski SR, et al. Eect of hyperventilation on extracellular concentrations of glutamate, lactate, pyruvate, and local cerebral blood ow in patients with severe traumatic brain injury. Crit Care Med 2002;30(12):261925. [26] Guidelines for the management of severe traumatic brain injury. XIV. Hyperventilation. J Neurotrauma 2007;24(Suppl 1):S8790. [27] Deem S. Management of acute brain injury and associated respiratory issues. Respir Care 2006;51(4):35767. [28] Friedman JA, Pichelmann MA, Piepgras DG, et al. Pulmonary complications of aneurysmal subarachnoid hemorrhage. Neurosurgery 2003;52(5):102531. [29] Berthiaume L, Zygun D. Non-neurologic organ dysfunction in acute brain injury. Crit Care Clin 2006;22(4):75366, abstract, x. [30] Mascia L, Sakr Y, Pasero D, et al. Extracranial complications in patients with acute brain injury: a post-hoc analysis of the SOAP study. Intensive Care Med 2008;34:7207. [31] Schirmer-Mikalsen K, Vik A, Gisvold SE, et al. Severe head injury: control of physiological variables, organ failure and complications in the intensive care unit. Acta Anaesthesiol Scand 2007;51(9):1194201. [32] Holland MC, Mackersie RC, Morabito D, et al. The development of acute lung injury is associated with worse neurologic outcome in patients with severe traumatic brain injury. J Trauma 2003;55(1):10611. [33] Bratton SL, Davis RL. Acute lung injury in isolated traumatic brain injury. Neurosurgery 1997;40(4):70712 [discussion: 712]. [34] Robertson CS, Valadka AB, Hannay HJ, et al. Prevention of secondary ischemic insults after severe head injury. Crit Care Med 1999;27(10):208695. [35] Gruber A, Reinprecht A, Gorzer H, et al. Pulmonary function and radiographic abnormalities related to neurological outcome after aneurysmal subarachnoid hemorrhage. J Neurosurg 1998;88(1):2837. [36] Kahn JM, Caldwell EC, Deem S, et al. Acute lung injury in patients with subarachnoid hemorrhage: incidence, risk factors, and outcome. Crit Care Med 2006;34(1):196202. [37] Stevens RD, Nyquist PA. The systemic implications of aneurysmal subarachnoid hemorrhage. J Neurol Sci 2007;261(12):14356. [38] Smith WS, Matthay MA. Evidence for a hydrostatic mechanism in human neurogenic pulmonary edema. Chest 1997;111(5):132633. [39] West JB, Mathieu-Costello O. Structure, strength, failure, and remodeling of the pulmonary blood-gas barrier. Annu Rev Physiol 1999;61:54372. [40] Koning R, Cribier A, Gerber L, et al. A new treatment for severe pulmonary embolism: percutaneous rheolytic thrombectomy. Circulation 1997;96(8):2498500. [41] Lowe GJ, Ferguson ND. Lung-protective ventilation in neurosurgical patients. Curr Opin Crit Care 2006;12(1):37. [42] Mascia L, Grasso S, Fiore T, et al. Cerebro-pulmonary interactions during the application of low levels of positive end-expiratory pressure. Intensive Care Med 2005;31(3): 3739.

560

STEVENS

et al

[43] Caricato A, Conti G, Della Corte F, et al. Eects of PEEP on the intracranial system of patients with head injury and subarachnoid hemorrhage: the role of respiratory system compliance. J Trauma 2005;58(3):5716. [44] Muench E, Bauhuf C, Roth H, et al. Eects of positive end-expiratory pressure on regional cerebral blood ow, intracranial pressure, and brain tissue oxygenation. Crit Care Med 2005;33(10):236772. [45] Georgiadis D, Schwarz S, Baumgartner RW, et al. Inuence of positive end-expiratory pressure on intracranial pressure and cerebral perfusion pressure in patients with acute stroke. Stroke 2001;32(9):208892. [46] Cooper KR, Boswell PA, Choi SC. Safe use of PEEP in patients with severe head injury. J Neurosurg 1985;63(4):5525. [47] Burchiel KJ, Steege TD, Wyler AR. Intracranial pressure changes in brain-injured patients requiring positive end-expiratory pressure ventilation. Neurosurgery 1981;8(4): 4439. [48] McGuire G, Crossley D, Richards J, et al. Eects of varying levels of positive end-expiratory pressure on intracranial pressure and cerebral perfusion pressure. Crit Care Med 1997;25(6): 105962. [49] Frost EA. Eects of positive end-expiratory pressure on intracranial pressure and compliance in brain-injured patients. J Neurosurg 1977;47(2):195200. [50] Huynh T, Messer M, Sing RF, et al. Positive end-expiratory pressure alters intracranial and cerebral perfusion pressure in severe traumatic brain injury. J Trauma 2002;53(3): 48892. [51] Pranevicius M, Pranevicius O. Cerebral venous steal: blood ow diversion with increased tissue pressure. Neurosurgery 2002;51(5):126773. [52] Andrews PJ. Pressure, ow and Occams Razor: a matter of steal? Intensive Care Med 2005;31(3):3234. [53] Obrist WD, Langtt TW, Jaggi JL, et al. Cerebral blood ow and metabolism in comatose patients with acute head injury. Relationship to intracranial hypertension. J Neurosurg 1984;61(2):24153. [54] Lundberg N, Kjallquist A, Bien C. Reduction of increased intracranial pressure by hyperventilation. A therapeutic aid in neurological surgery. Acta Psychiatr Scand Suppl 1959; 34(139):164. [55] Muizelaar JP, van der Poel HG, Li ZC, et al. Pial arteriolar vessel diameter and CO2 reactivity during prolonged hyperventilation in the rabbit. J Neurosurg 1988;69(6):9237. [56] Kontos HA, Raper AJ, Patterson JL. Analysis of vasoactivity of local pH, PCO2 and bicarbonate on pial vessels. Stroke 1977;8(3):35860. [57] Fortune JB, Feustel PJ, Graca L, et al. Eect of hyperventilation, mannitol, and ventriculostomy drainage on cerebral blood ow after head injury. J Trauma 1995;39(6):10917 [discussion: 10979]. [58] Bouma GJ, Muizelaar JP, Stringer WA, et al. Ultra-early evaluation of regional cerebral blood ow in severely head-injured patients using xenon-enhanced computerized tomography. J Neurosurg 1992;77(3):3608. [59] Jaggi JL, Obrist WD, Gennarelli TA, et al. Relationship of early cerebral blood ow and metabolism to outcome in acute head injury. J Neurosurg 1990;72(2):17682. [60] Hemphill JC 3rd, Knudson MM, Derugin N, et al. Carbon dioxide reactivity and pressure autoregulation of brain tissue oxygen. Neurosurgery 2001;48(2):37783. [61] van Santbrink H, Maas AI, Avezaat CJ. Continuous monitoring of partial pressure of brain tissue oxygen in patients with severe head injury. Neurosurgery 1996;38(1):2131. [62] Carmona Suazo JA, Maas AI, van den Brink WA, et al. CO2 reactivity and brain oxygen pressure monitoring in severe head injury. Crit Care Med 2000;28(9):326874. [63] Schneider GH, Sarrafzadeh AS, Kiening KL, et al. Inuence of hyperventilation on brain tissue-PO2, PCO2, and pH in patients with intracranial hypertension. Acta Neurochir Suppl 1998;71:625.

MECHANICAL VENTILATION IN ACUTE BRAIN INJURY

561

[64] Imberti R, Bellinzona G, Langer M. Cerebral tissue PO2 and SjvO2 changes during moderate hyperventilation in patients with severe traumatic brain injury. J Neurosurg 2002;96(1):97102. [65] McLaughlin MR, Marion DW. Cerebral blood ow and vasoresponsivity within and around cerebral contusions. J Neurosurg 1996;85(5):8716. [66] Diringer MN, Yundt K, Videen TO, et al. No reduction in cerebral metabolism as a result of early moderate hyperventilation following severe traumatic brain injury. J Neurosurg 2000; 92(1):713. [67] Cruz J, Jaggi JL, Hostad OJ. Cerebral blood ow, vascular resistance, and oxygen metabolism in acute brain trauma: redening the role of cerebral perfusion pressure? Crit Care Med 1995;23(8):14127. [68] Cruz J, Jaggi JL, Hostad OJ. Cerebral blood ow and oxygen consumption in acute brain injury with acute anemia: an alternative for the cerebral metabolic rate of oxygen consumption? Crit Care Med 1993;21(8):121824. [69] Coles JP, Minhas PS, Fryer TD, et al. Eect of hyperventilation on cerebral blood ow in traumatic head injury: clinical relevance and monitoring correlates. Crit Care Med 2002; 30(9):19509. [70] Hutchinson PJ, Gupta AK, Fryer TF, et al. Correlation between cerebral blood ow, substrate delivery, and metabolism in head injury: a combined microdialysis and triple oxygen positron emission tomography study. J Cereb Blood Flow Metab 2002;22(6): 73545. [71] Coles JP, Fryer TD, Coleman MR, et al. Hyperventilation following head injury: eect on ischemic burden and cerebral oxidative metabolism. Crit Care Med 2007;35(2):56878. [72] Roberts I, Schierhout G. Hyperventilation therapy for acute traumatic brain injury. Cochrane Database Syst Rev 1997 Issue 4. Art. No.:CD000566. [73] Tremblay LN, Slutsky AS. Ventilator-induced lung injury: from the bench to the bedside. Intensive Care Med 2006;32(1):2433. [74] Dos Santos CC, Slutsky AS. Invited review: mechanisms of ventilator-induced lung injury: a perspective. J Appl Phys 2000;89(4):164555. [75] Gajic O, Dara SI, Mendez JL, et al. Ventilator-associated lung injury in patients without acute lung injury at the onset of mechanical ventilation. Crit Care Med 2004;32(9):181724. [76] Gajic O, Frutos-Vivar F, Esteban A, et al. Ventilator settings as a risk factor for acute respiratory distress syndrome in mechanically ventilated patients. Intensive Care Med 2005;31(7):9226. [77] Tobin MJ. Advances in mechanical ventilation. N Engl J Med 2001;344(26):198696. [78] Ventilation with lower tidal volumes as compared with traditional tidal volumes for acute lung injury and the acute respiratory distress syndrome. The acute respiratory distress syndrome network. N Engl J Med 2000;342(18):13018. [79] Wiedemann HP, Wheeler AP, Bernard GR, et al. Comparison of two uid-management strategies in acute lung injury. N Engl J Med 2006;354(24):256475. [80] Zambon M, Vincent JL. Mortality rates for patients with ALI/ARDS have decreased over time. Chest 2008 (in press). [81] Lopez-Aguilar J, Villagra A, Bernabe F, et al. Massive brain injury enhances lung dam in an isolated lung model of ventilator-induced lung injury. Crit Care Med 2005;33(5):107783. [82] Mascia L, Zavala E, Bosma K, et al. High tidal volume is associated with the development of acute lung injury after severe brain injury: an international observational study. Crit Care Med 2007;35(8):181520. [83] Gajic O, Manno EM. Neurogenic pulmonary edema: another multiple-hit model of acute lung injury. Crit Care Med 2007;35(8):197980. [84] Laey JG, OCroinin D, McLoughlin P, et al. Permissive hypercapniadrole in protective lung ventilatory strategies. Intensive Care Med 2004;30(3):34756. [85] Wolf S, Schurer L, Trost HA, et al. The safety of the open lung approach in neurosurgical patients. Acta Neurochir Suppl 2002;81:99101.

562

STEVENS

et al

[86] Chan KP, Stewart TE, Mehta S. High-frequency oscillatory ventilation for adult patients with ARDS. Chest 2007;131(6):190716. [87] Derdak S, Mehta S, Stewart TE, et al. High-frequency oscillatory ventilation for acute respiratory distress syndrome in adults: a randomized, controlled trial. Am J Respir Crit Care Med 2002;166(6):8018. [88] Bollen CW, van Well GT, Sherry T, et al. High frequency oscillatory ventilation compared with conventional mechanical ventilation in adult respiratory distress syndrome: a randomized controlled trial [ISRCTN24242669]. Crit Care 2005;9(4):R4309. [89] Hurst JM, Branson RD, Davis K Jr. High-frequency percussive ventilation in the management of elevated intracranial pressure. J Trauma 1988;28(9):13637. [90] Bennett SS, Graagnino C, Borel CO, et al. Use of high frequency oscillatory ventilation (HFOV) in neurocritical care patients. Neurocrit Care 2007;7(3):2216. [91] David M, Karmrodt J, Weiler N, et al. High-frequency oscillatory ventilation in adults with traumatic brain injury and acute respiratory distress syndrome. Acta Anaesthesiol Scand 2005;49(2):20914. [92] Salim A, Miller K, Dangleben D, et al. High-frequency percussive ventilation: an alternative mode of ventilation for head-injured patients with adult respiratory distress syndrome. J Trauma 2004;57(3):5426. [93] Pelosi P, Brazzi L, Gattinoni L. Prone position in acute respiratory distress syndrome. Eur Respir J 2002;20(4):101728. [94] Gattinoni L, Tognoni G, Pesenti A, et al. Eect of prone positioning on the survival of patients with acute respiratory failure. N Engl J Med 2001;345(8):56873. [95] Guerin C, Gaillard S, Lemasson S, et al. Eects of systematic prone positioning in hypoxemic acute respiratory failure: a randomized controlled trial. JAMA 2004;292(19): 237987. [96] Beuret P, Carton MJ, Nourdine K, et al. Prone position as prevention of lung injury in comatose patients: a prospective, randomized, controlled study. Intensive Care Med 2002;28(5):5649. [97] Reinprecht A, Greher M, Wolfsberger S, et al. Prone position in subarachnoid hemorrhage patients with acute respiratory distress syndrome: eects on cerebral tissue oxygenation and intracranial pressure. Crit Care Med 2003;31(6):18318. [98] Thelandersson A, Cider A, Nellgard B. Prone position in mechanically ventilated patients with reduced intracranial compliance. Acta Anaesthesiol Scand 2006;50(8): 93741. [99] Klinger JR. Inhaled nitric oxide in ARDS. Crit Care Clin 2002;18(1):4568, vi. [100] Adhikari NK, Burns KE, Friedrich JO, et al. Eect of nitric oxide on oxygenation and mortality in acute lung injury: systematic review and meta-analysis. BMJ 2007;334(7597): 77987. [101] Vavilala MS, Roberts JS, Moore AE, et al. The inuence of inhaled nitric oxide on cerebral blood ow and metabolism in a child with traumatic brain injury. Anesth Analg 2001;93(2): 3513, 353rd contents page. [102] Grady RE, Strickland RA, Fabi AY, et al. Intraoperative use of nitric oxide during intracranial aneurysm clipping in a patient with acute respiratory distress syndrome. J Neurosurg Anesthesiol 1999;11(2):1246. [103] National nosocomial infections surveillance (NNIS) system report, data summary from January 1992 through June 2003, issued August 2003. Am J Infect Control 2003;31(8): 48198. [104] Kallel H, Chelly H, Bahloul M, et al. The eect of ventilator-associated pneumonia on the prognosis of head trauma patients. J Trauma 2005;59(3):70510. [105] Rincon-Ferrari MD, Flores-Cordero JM, Leal-Noval SR, et al. Impact of ventilatorassociated pneumonia in patients with severe head injury. J Trauma 2004;57(6):123440. [106] Zygun DA, Zuege DJ, Boiteau PJ, et al. Ventilator-associated pneumonia in severe traumatic brain injury. Neurocrit Care 2006;5(2):10814.

MECHANICAL VENTILATION IN ACUTE BRAIN INJURY

563

[107] Coplin WM, Pierson DJ, Cooley KD, et al. Implications of extubation delay in braininjured patients meeting standard weaning criteria. Am J Respir Crit Care Med 2000; 161(5):15306. [108] Ely EW, Meade MO, Haponik EF, et al. Mechanical ventilator weaning protocols driven by nonphysician health-care professionals: evidence-based clinical practice guidelines. Chest 2001;120(6 Suppl):454S63S. [109] Ely EW, Baker AM, Dunagan DP, et al. Eect on the duration of mechanical ventilation of identifying patients capable of breathing spontaneously. N Engl J Med 1996;335(25): 18649. [110] DeHaven CB Jr, Hurst JM, Branson RD. Evaluation of two dierent extubation criteria: attributes contributing to success. Crit Care Med 1986;14(2):924. [111] Tanios MA, Nevins ML, Hendra KP, et al. A randomized, controlled trial of the role of weaning predictors in clinical decision making. Crit Care Med 2006;34(10):25305. [112] Fessler HE. Does weaning postpone liberation? Crit Care Med 2006;34(10):26767. [113] Ciaglia P, Firsching R, Syniec C. Elective percutaneous dilatational tracheostomy. A new simple bedside procedure; preliminary report. Chest 1985;87(6):7159. [114] Griths J, Barber VS, Morgan L, et al. Systematic review and meta-analysis of studies of the timing of tracheostomy in adult patients undergoing articial ventilation. BMJ 2005; 330(7502):12438. [115] Plummer AL, Gracey DR. Consensus conference on articial airways in patients receiving mechanical ventilation. Chest 1989;96(1):17880. [116] MacIntyre NR, Cook DJ, Ely EW Jr, et al. Evidence-based guidelines for weaning and discontinuing ventilatory support: a collective task force facilitated by the American college of chest physicians; the American association for respiratory care; and the American college of critical care medicine. Chest 2001;120(6 Suppl):375S95S. [117] Dunham CM, Ransom KJ. Assessment of early tracheostomy in trauma patients: a systematic review and meta-analysis. Am Surg 2006;72(3):27681. [118] Bouderka MA, Fakhir B, Bouaggad A, et al. Early tracheostomy versus prolonged endotracheal intubation in severe head injury. J Trauma 2004;57(2):2514.