Faculty Bibliography

RATIONALE: OBJECTIVES:To determine the relation of ventilatory ratio with Vd/Vt in ARDS. METHODS:First, in a single-center, prospective observational study of ARDS, we tested the association of Vd/Vt with ventilatory ratio. With in-hospital mortality as the primary outcome and ventilator-free days as the secondary outcome, we tested the role of ventilatory ratio as an outcome predictor. The findings from this study were further verified in secondary analyses of two NHLBI ARDS Network randomized controlled trials. MEASUREMENTS AND MAIN RESULTS: CONCLUSIONS:Ventilatory ratio correlates well with Vd/Vt in ARDS, and higher values at baseline are associated with increased risk of adverse outcomes. These results are promising for the use of ventilatory ratio as a simple bedside index of impaired ventilation in ARDS.

OBJECTIVES:A recently published simulation study suggested that women are inferior leaders of cardiopulmonary resuscitation efforts. The aim of this study was to compare female and male code leaders in regard to cardiopulmonary resuscitation outcomes in a real-world clinical setting. DESIGN:Retrospective cohort review. SETTING:Two academic, urban hospitals in San Diego, California. SUBJECTS:One-thousand eighty-two adult inpatients who suffered cardiac arrest and underwent cardiopulmonary resuscitation. INTERVENTIONS:None. MEASUREMENTS AND MAIN RESULTS:We analyzed whether physician code leader gender was independently associated with sustained return of spontaneous circulation and survival to discharge and with markers of quality cardiopulmonary resuscitation. Of all arrests, 327 (30.1%) were run by female physician code leaders with 251 (76.8%) obtaining return of spontaneous circulation, and 122 (37.3%) surviving to discharge. Male physicians ran 757 codes obtaining return of spontaneous circulation in 543 (71.7%) with 226 (29.9%) surviving to discharge. When adjusting for variables, female physician code leader gender was independently associated with a higher likelihood of return of spontaneous circulation (odds ratio, 1.36; 95% CI, 1.01-1.85; p = 0.049) and survival to discharge (odds ratio, 1.53; 95% CI, 1.15-2.02; p < 0.01). Additionally, the odds ratio for survival to discharge was 1.62 (95% CI, 1.13-2.34; p < 0.01) for female physicians with a female code nurse when compared with male physician code leaders paired with a female code nurse. Gender of code leader was not associated with cardiopulmonary resuscitation quality. CONCLUSIONS:In contrast to data derived from a simulated setting with medical students, real life female physician leadership of cardiopulmonary resuscitation is not associated with inferior outcomes. Appropriately, trained physicians can lead high-quality cardiopulmonary resuscitation irrespective of gender.

PURPOSE OF REVIEW:The most effective strategies for treating the patient with acute respiratory distress syndrome center on minimizing ventilation-induced lung injury (VILI). Yet, current standard-of-care does little to modify mechanical ventilation to patient-specific risk. This review focuses on evaluation of bedside respiratory mechanics, which when interpreted in patient-specific context, affords opportunity to individualize lung-protective ventilation in patients with acute respiratory distress syndrome. RECENT FINDINGS:Four biophysical mechanisms of VILI are widely accepted: volutrauma, barotrauma, atelectrauma, and stress concentration. Resulting biotrauma, that is, local and systemic inflammation and endothelial activation, may be thought of as the final common pathway that propagates VILI-mediated multiorgan failure. Conventional, widely utilized techniques to assess VILI risk rely on airway pressure, flow, and volume changes, and remain essential tools for determining overdistension of aerated lung regions, particularly when interpreted cognizant of their limitations. Emerging bedside tools identify regional differences in mechanics, but further study is required to identify how they might best be incorporated into clinical practice. SUMMARY:Quantifying patient-specific risk of VILI requires understanding each patient's pulmonary mechanics in context of biological predisposition. Tailoring support at bedside according to these factors affords the greatest opportunity to date for mitigating VILI and alleviating associated morbidity.

IMPORTANCE:Adjusting positive end-expiratory pressure (PEEP) to offset pleural pressure might attenuate lung injury and improve patient outcomes in acute respiratory distress syndrome (ARDS). OBJECTIVE:To determine whether PEEP titration guided by esophageal pressure (PES), an estimate of pleural pressure, was more effective than empirical high PEEP-fraction of inspired oxygen (Fio2) in moderate to severe ARDS. DESIGN, SETTING, AND PARTICIPANTS:Phase 2 randomized clinical trial conducted at 14 hospitals in North America. Two hundred mechanically ventilated patients aged 16 years and older with moderate to severe ARDS (Pao2:Fio2 ≤200 mm Hg) were enrolled between October 31, 2012, and September 14, 2017; long-term follow-up was completed July 30, 2018. INTERVENTIONS:Participants were randomized to PES-guided PEEP (n = 102) or empirical high PEEP-Fio2 (n = 98). All participants received low tidal volumes. MAIN OUTCOMES AND MEASURES:The primary outcome was a ranked composite score incorporating death and days free from mechanical ventilation among survivors through day 28. Prespecified secondary outcomes included 28-day mortality, days free from mechanical ventilation among survivors, and need for rescue therapy. RESULTS:Two hundred patients were enrolled (mean [SD] age, 56 [16] years; 46% female) and completed 28-day follow-up. The primary composite end point was not significantly different between treatment groups (probability of more favorable outcome with PES-guided PEEP: 49.6% [95% CI, 41.7% to 57.5%]; P = .92). At 28 days, 33 of 102 patients (32.4%) assigned to PES-guided PEEP and 30 of 98 patients (30.6%) assigned to empirical PEEP-Fio2 died (risk difference, 1.7% [95% CI, -11.1% to 14.6%]; P = .88). Days free from mechanical ventilation among survivors was not significantly different (median [interquartile range]: 22 [15-24] vs 21 [16.5-24] days; median difference, 0 [95% CI, -1 to 2] days; P = .85). Patients assigned to PES-guided PEEP were significantly less likely to receive rescue therapy (4/102 [3.9%] vs 12/98 [12.2%]; risk difference, -8.3% [95% CI, -15.8% to -0.8%]; P = .04). None of the 7 other prespecified secondary clinical end points were significantly different. Adverse events included gross barotrauma, which occurred in 6 patients with PES-guided PEEP and 5 patients with empirical PEEP-Fio2. CONCLUSIONS AND RELEVANCE:Among patients with moderate to severe ARDS, PES-guided PEEP, compared with empirical high PEEP-Fio2, resulted in no significant difference in death and days free from mechanical ventilation. These findings do not support PES-guided PEEP titration in ARDS. TRIAL REGISTRATION:ClinicalTrials.gov Identifier NCT01681225.

The acute respiratory distress syndrome (ARDS) is a common cause of respiratory failure in critically ill patients and is defined by the acute onset of noncardiogenic pulmonary oedema, hypoxaemia and the need for mechanical ventilation. ARDS occurs most often in the setting of pneumonia, sepsis, aspiration of gastric contents or severe trauma and is present in ~10% of all patients in intensive care units worldwide. Despite some improvements, mortality remains high at 30-40% in most studies. Pathological specimens from patients with ARDS frequently reveal diffuse alveolar damage, and laboratory studies have demonstrated both alveolar epithelial and lung endothelial injury, resulting in accumulation of protein-rich inflammatory oedematous fluid in the alveolar space. Diagnosis is based on consensus syndromic criteria, with modifications for under-resourced settings and in paediatric patients. Treatment focuses on lung-protective ventilation; no specific pharmacotherapies have been identified. Long-term outcomes of patients with ARDS are increasingly recognized as important research targets, as many patients survive ARDS only to have ongoing functional and/or psychological sequelae. Future directions include efforts to facilitate earlier recognition of ARDS, identifying responsive subsets of patients and ongoing efforts to understand fundamental mechanisms of lung injury to design specific treatments.

Mechanical ventilation practices in patients with acute respiratory distress syndrome (ARDS) have progressed with a growing understanding of the disease pathophysiology. Paramount to the care of affected patients is the delivery of lung-protective mechanical ventilation which prioritizes tidal volume and plateau pressure limitation. Lung protection can probably be further enhanced by scaling target tidal volumes to the specific respiratory mechanics of individual patients. The best procedure for selecting optimal positive end-expiratory pressure (PEEP) in ARDS remains uncertain; several relevant issues must be considered when selecting PEEP, particularly lung recruitability. Noninvasive ventilation must be used with caution in ARDS as excessively high respiratory drive can further exacerbate lung injury; newer modes of delivery offer promising approaches in hypoxemic respiratory failure. Airway pressure release ventilation offers an alternative approach to maximize lung recruitment and oxygenation, but clinical trials have not demonstrated a survival benefit of this mode over conventional ventilation strategies. Rescue therapy with high-frequency oscillatory ventilation is an important option in refractory hypoxemia. Despite a disappointing lack of benefit (and possible harm) in patients with moderate or severe ARDS, possibly due to lung hyperdistention and right ventricular dysfunction, high-frequency oscillation may improve outcome in patients with very severe hypoxemia.

BACKGROUND:Neurological status at hospital discharge is routinely used to assess patient outcome after cardiac arrest. However, attribution of impairment to the arrest is valid only if baseline neurological status is known. This study evaluated whether incorporating baseline neurological status improves performance of a widely employed neurological outcome scale for quantifying arrest-attributable morbidity. METHODS:Retrospective cohort study of two U.S. hospitals. Neurological function was assessed via Cerebral performance category (CPC), an ordinal five-point scale with 1 indicating sufficient cognition to lead an independent life and 5 representing brain death. Hospitalized adult patients who suffered in-hospital cardiac arrest for which cardiopulmonary resuscitation was attempted between 2011-2015 were included. Patients were identified through a quality improvement registry that captures all inpatient arrests in the two hospitals. RESULTS:Of 486 patients who suffered in-hospital cardiac arrest, 124 (25.5%) had baseline abnormal neurological function (pre-hospitalization CPC>1). Although 54 patients had a normal discharge CPC of 1, 80 patients had no change in CPC from their prior baseline (11.1% vs. 16.5% met criterion for "normal" outcome defined as CPC of 1 vs. change-in-CPC of 0; McNemar p < .01; kappa for agreement: .78, 95% CI .69-.86). Across several formulations of criteria for "good" neurological outcome, similar discordance existed between conventional definitions considering only discharge CPC and modified definitions that included change-in-CPC from baseline. CONCLUSIONS:Incorporating change-in-CPC into criteria for "good" neurological outcome post-arrest yields discordant results from traditional approaches that consider discharge CPC only and increases face validity of reporting arrest-related morbidity.

BACKGROUND:Post-resuscitation hemodynamic instability following out-of-hospital cardiac arrest (OHCA) may occur from myocardial dysfunction underlying cardiogenic shock and/or inflammation-mediated distributive shock. Distinguishing the predominant shock subtype with widely available clinical metrics may have prognostic and therapeutic value. METHODS:A two-hospital cohort was assembled of patients in shock following OHCA. Left ventricular ejection fraction (LVEF) was assessed via echocardiography or cardiac ventriculography within 1 day post arrest and used to delineate shock physiology. The study evaluated whether higher LVEF, indicating distributive-predominant shock physiology, was associated with neurocognitive outcome (primary endpoint), survival, and duration of multiple organ failures. The study also investigated whether volume resuscitation exhibited a subtype-specific association with outcome. RESULTS:Of 162 patients with post-resuscitation shock, 48% had normal LVEF (> 40%), consistent with distributive shock physiology. Higher LVEF was associated with less favorable neurocognitive outcome (OR 0.74, 95% CI 0.58-0.94 per 10% increase in LVEF; p = 0.01). Higher LVEF also was associated with worse survival (OR 0.81, 95% CI 0.67-0.97; p = 0.02) and fewer organ failure-free days (β = - 0.67, 95% CI - 1.28 to - 0.06; p = 0.03). Only 51% of patients received a volume challenge of at least 30 ml/kg body weight in the first 6 h post arrest, and the volume received did not differ by LVEF. Greater volume resuscitation in the first 6 h post arrest was associated with favorable neurocognitive outcome (OR 1.59, 95% CI 0.99-2.55 per liter; p = 0.03) and survival (OR 1.44, 95% CI 1.02-2.04; p = 0.02) among patients with normal LVEF but not low LVEF. CONCLUSIONS:In post-resuscitation shock, higher LVEF-indicating distributive shock physiology-was associated with less favorable neurocognitive outcome, fewer days without organ failure, and higher mortality. Greater early volume resuscitation was associated with more favorable neurocognitive outcome and survival in patients with this shock subtype. Additional studies with repeated measures of complementary hemodynamic parameters are warranted to validate the clinical utility for subtyping post-resuscitation shock.

Prone positioning was first proposed in the 1970s as a method to improve gas exchange in ARDS. Subsequent observations of dramatic improvement in oxygenation with simple patient rotation motivated the next several decades of research. This work elucidated the physiological mechanisms underlying changes in gas exchange and respiratory mechanics with prone ventilation. However, translating physiological improvements into a clinical benefit has proved challenging; several contemporary trials showed no major clinical benefits with prone positioning. By optimizing patient selection and treatment protocols, the recent Proning Severe ARDS Patients (PROSEVA) trial demonstrated a significant mortality benefit with prone ventilation. This trial, and subsequent meta-analyses, support the role of prone positioning as an effective therapy to reduce mortality in severe ARDS, particularly when applied early with other lung-protective strategies. This review discusses the physiological principles, clinical evidence, and practical application of prone ventilation in ARDS.