Acute lung injury: surprisingly common in the neurologic intensive care unit.

Acute lung injury and the acute respiratory distress syndrome (ALI/ARDS) are syndromes of acute respiratory failure that most commonly occur in the setting of severe sepsis, pneumonia, or severe traumatic injuries (1). Patients with critical neurologic disorders have therefore not been well represented in investigations of risk factors for ALI/ARDS, which have focused largely on patients admitted to medical, surgical, or trauma intensive care units (ICUs) (2). Clinical trials of interventions for ALI/ARDS have also typically excluded patients with acute neurologic illness (4). As dedicated neurologic critical care units staffed by neurointensivists become more common, there is a real and growing need to better understand the incidence and risk factors for ALI/ ARDS among patients with neurologic critical illness. In this issue of Critical Care Medicine, Hoesch and colleagues (5) report the incidence of and risk factors for ALI/ARDS in a cohort of systemically evaluated patients who were mechanically ventilated for 48 hrs in the neurologic ICU at a large, academic medical center. Remarkably, over one third (68 of the 192 patients in the study) met stringent diagnostic criteria for ALI/ ARDS, suggesting that ALI/ARDS is one of the more common non-neurologic diagnoses encountered in the neurologic ICU setting. Over a 3-yr period, Hoesch et al prospectively evaluated 192 consecutive patients who met eligibility requirements using a thorough diagnostic algorithm to identify patients with ALI/ARDS. Specifically, those with bilateral infiltrates on chest radiograph and PaO2/FIO2 ratios 200 or 300 were classified as having ARDS or ALI, respectively, unless a pulmonary arterial occlusion pressure 18 mm Hg, left ventricular ejection fraction 40%, serum N-terminal pro-brain natriuretic peptide 100 pg/mL, or vascular pedicle width 65 mm were identified. The inclusion of consecutive eligible patients clearly enhances the potential generalizability of the findings. After excluding only moribund or brain-dead patients as well as those with chronic lung disease, 192 patients were included, with a diverse array of primary neurologic diagnoses that represent the common problems that are encountered by a neurointensivist. The most common diagnoses were intracerebral hemorrhage, subarachnoid hemorrhage, traumatic brain injury, and subdural hemorrhage, with other patients having ischemic stroke, status epilepticus, hydrocephalus, and other diagnoses. Using data obtained for clinical (rather than research) purposes, the authors went to great lengths to stringently evaluate each patient for ALI/ARDS rather than relying on diagnoses made by the ICU team. Although this algorithmic approach strengthens the study, one caveat should be considered. The approach used to exclude cardiogenic or hydrostatic pulmonary edema as the cause of bilateral pulmonary infiltrates was derived from physiologic reasoning and published guidelines, but this algorithm has not been validated. For the primary analysis, patients with any evidence of cardiogenic pulmonary edema were classified as not having ALI/ARDS, an approach that is likely overly conservative since ALI/ARDS and elevated pulmonary microvascular pressures can coexist. For example, in the National Institutes of Health Fluid and Catheter Treatment Trial (FACTT), nearly one third of patients with ALI/ARDS had an elevated pulmonary arterial occlusion pressure when it was measured within 48 hrs of meeting diagnostic criteria for ALI/ARDS (4, 6). This elevated pulmonary arterial occlusion pressure likely reflects the combined effects of aggressive fluid resuscitation and myocardial dysfunction in the setting of underlying lung injury. The lack of validated algorithms for definitively making a clinical diagnosis of ALI/ARDS is a major problem for clinical investigators in this field and underscores the need for more specific diagnostic tools, such as circulating biomarkers. After identifying patients with ALI/ ARDS, Hoesch et al examined numerous potential risk factors for ALI/ARDS, including pneumonia, aspiration, sepsis, and loss of cough or gag reflex. Although their methods (univariate selection and stepwise regression) can markedly increase the risk of obtaining false-positive results, i.e., overfitting (7), their results have face validity and may bear out in future studies. Importantly, the underlying cause of neurologic critical illness did not appear to have much effect on risk for ALI/ARDS in this patient population. Rather, loss of lower cranial nerve function, specifically loss of cough and/or gag reflex, was the strongest risk factor, a risk factor that has not been previously identified in this population or any other. Whether loss of cough and gag reflex results from the primary neurologic insult or from sedation and/or paralysis (variables that were not captured in this study), this association suggests that monitoring of cough and gag may be helpful when considering the need for ICU admission and/or endotracheal intubation for patients with severe, acute neurologic disorders. In addition, this finding may lend some insight into the pathogenesis of what has been termed “neurogenic pulmonary edema. ” Researchers have postulated that acute pulmonary edema occurring in the setting of severe neurologic injury is caused by catecholamine surges and resultant increases in pulmonary microvascular pressure and permeability. In a study of 12 patients with neurogenic pulmonary edema, however, Smith and Matthay (8) reported that only seven of the 12 patients had a pulmonary edema fluid-to-plasma protein ratio 0.65, which would be consistent with pulmonary edema from hydrostatic mechanisms (9). Unfortunately, the current study by Hoesch et al did not collect hemodynamic or other *See also p. 587.