Faculty Bibliography

OBJECTIVES:In mechanically ventilated patients, deep sedation is often assumed to induce "respirolysis," that is, lyse spontaneous respiratory effort, whereas light sedation is often assumed to preserve spontaneous effort. This study was conducted to determine validity of these common assumptions, evaluating the association of respiratory drive with sedation depth and ventilator-free days in acute respiratory failure. DESIGN:Prospective cohort study. SETTING:Patients were enrolled during 2 month-long periods in 2016-2017 from five ICUs representing medical, surgical, and cardiac specialties at a U.S. academic hospital. PATIENTS:Eligible patients were critically ill adults receiving invasive ventilation initiated no more than 36 hours before enrollment. Patients with neuromuscular disease compromising respiratory function or expiratory flow limitation were excluded. INTERVENTIONS:Respiratory drive was measured via P0.1, the change in airway pressure during a 0.1-second airway occlusion at initiation of patient inspiratory effort, every 12 ± 3 hours for 3 days. Sedation depth was evaluated via the Richmond Agitation-Sedation Scale. Analyses evaluated the association of P0.1 with Richmond Agitation-Sedation Scale (primary outcome) and ventilator-free days. MEASUREMENTS AND MAIN RESULTS:Fifty-six patients undergoing 197 bedside evaluations across five ICUs were included. P0.1 ranged between 0 and 13.3 cm H2O (median [interquartile range], 0.1 cm H2O [0.0-1.3 cm H2O]). P0.1 was not significantly correlated with the Richmond Agitation-Sedation Scale (RSpearman, 0.02; 95% CI, -0.12 to 0.16; p = 0.80). Considering P0.1 terciles (range less than 0.2, 0.2-1.0, and greater than 1.0 cm H2O), patients in the middle tercile had significantly more ventilator-free days than the lowest tercile (incidence rate ratio, 0.78; 95% CI, 0.65-0.93; p < 0.01) or highest tercile (incidence rate ratio, 0.58; 95% CI, 0.48-0.70; p < 0.01). CONCLUSIONS:Sedation depth is not a reliable marker of respiratory drive during critical illness. Respiratory drive can be low, moderate, or high across the range of routinely targeted sedation depth.

PURPOSE/OBJECTIVE:International clinical practice guidelines call for initial volume resuscitation of at least 30 mL/kg body weight for patients with sepsis-induced hypotension or shock. Although not considered in the guidelines, preexisting cardiac dysfunction may be an important factor clinicians weigh in deciding the quantity of volume resuscitation for patients with septic shock. METHODS:We conducted a multicenter survey of clinicians who routinely treat patients with sepsis to evaluate their beliefs, behaviors, knowledge, and perceived structural barriers regarding initial volume resuscitation for patients with sepsis and concomitant heart failure with reduced ejection fraction (HFrEF) <40%. Initial volume resuscitation preferences were captured as ordinal values, and additional testing for volume resuscitation preferences was performed using McNemar and Wilcoxon signed rank tests as indicated. Univariable logistic regression models were used to identify significant predictors of ≥30 mL/kg fluid administration. RESULTS:< .01). Emergency medicine physicians were most likely to feel that <30 mL/kg was most appropriate in patients with septic shock and HFrEF. CONCLUSIONS:Clinical equipoise exists regarding initial volume resuscitation for patients with sepsis-induced hypotension or shock and concomitant HFrEF. Future studies and clinical practice guidelines should explicitly address resuscitation in this subpopulation.

Ventilator-induced lung injury remains a key contributor to the morbidity and mortality of acute respiratory distress syndrome (ARDS). Efforts to minimize this injury are typically limited by the need to preserve adequate gas exchange. In the most severe forms of the syndrome, extracorporeal life support is increasingly being deployed for severe hypoxemia or hypercapnic acidosis refractory to conventional ventilator management strategies. Data from a recent randomized controlled trial, a post hoc analysis of that trial, a meta-analysis, and a large international multicenter observational study suggest that extracorporeal life support, when combined with lower Vt and airway pressures than the current standard of care, may improve outcomes compared with conventional management in patients with the most severe forms of ARDS. These findings raise important questions not only about the optimal ventilation strategies for patients receiving extracorporeal support but also regarding how various mechanisms of lung injury in ARDS may potentially be mitigated by ultra-lung-protective ventilation strategies when gas exchange is sufficiently managed with the extracorporeal circuit. Additional studies are needed to more precisely delineate the best strategies for optimizing invasive mechanical ventilation in this patient population.

PURPOSE OF REVIEW:Most clinical trials of lung-protective ventilation have tested one-size-fits-all strategies with mixed results. Data are lacking on how best to tailor mechanical ventilation to patient-specific risk of lung injury. RECENT FINDINGS:Risk of ventilation-induced lung injury is determined by biological predisposition to biophysical lung injury and physical mechanical perturbations that concentrate stress and strain regionally within the lung. Recent investigations have identified molecular subphenotypes classified as hyperinflammatory and hypoinflammatory acute respiratory distress syndrome (ARDS), which may have dissimilar risk for ventilation-induced lung injury. Mechanically, gravity-dependent atelectasis has long been recognized to decrease total aerated lung volume available for tidal ventilation, a concept termed the 'ARDS baby lung'. Recent studies have demonstrated that the aerated baby lung also has nonuniform stress/strain distribution, with potentially injurious forces concentrated in zones of heterogeneity where aerated alveoli are adjacent to flooded or atelectatic alveoli. The preponderance of evidence also indicates that current standard-of-care tidal volume management is not universally protective in ARDS. When considering escalation of lung-protective interventions, potential benefits of the intervention should be weighed against tradeoffs of accompanying cointerventions required, for example, deeper sedation or neuromuscular blockade. A precision medicine approach to lung-protection would weigh. SUMMARY:A precision medicine approach to lung-protective ventilation requires weighing four key factors in each patient: biological predisposition to biophysical lung injury, mechanical predisposition to biophysical injury accounting for spatial mechanical heterogeneity within the lung, anticipated benefits of escalating lung-protective interventions, and potential unintended adverse effects of mandatory cointerventions.

OBJECTIVES:Survival from acute respiratory distress syndrome is improving, and outcomes beyond mortality may be important for testing new treatments. The "ventilator-free days" score, is an established composite that equates ventilation on day 28 to death. A hierarchical outcome treating death as a worse than prolonged ventilation would enhance face validity, but performance characteristics and reporting of such an outcome are unknown. We therefore evaluated the performance of a novel hierarchical composite endpoint, the Alive and Ventilator Free score. DESIGN:Using data from four Acute Respiratory Distress Syndrome Network clinical trials, we compared Alive and Ventilator Free to the ventilator-free days score. Alive and Ventilator Free compares each patient with every other patient in a win-lose-tie for each comparison. Duration of mechanical ventilation is only compared if both patients survived. We evaluated power of Alive and Ventilator Free versus ventilator-free days score under various circumstances. SETTING:ICUs within the Acute Respiratory Distress Syndrome Network. PATIENTS:Individuals enrolled in four Acute Respiratory Distress Syndrome Network trials. INTERVENTIONS:None for this analysis. MEASUREMENTS AND MAIN RESULTS:Within the four trials (n = 2,410 patients), Alive and Ventilator Free and ventilator-free days score had similar power, with Alive and Ventilator Free slightly more powerful when a mortality difference was present, and ventilator-free days score slightly more powerful with a difference in duration of mechanical ventilation. Alive and Ventilator Free less often found in favor of treatments that increased mortality and increased days free of ventilation among survivors. CONCLUSIONS:A hierarchical composite endpoint, Alive and Ventilator Free, preserves statistical power while improving face validity. Alive and Ventilator Free is less prone to favor a treatment with discordant effects on survival and days free of ventilation. This general approach can support complex outcome hierarchies with multiple constituent outcomes. Approaches to interpretation of differences in Alive and Ventilator Free are also presented.

Neural respiratory drive, i.e., the activity of respiratory centres controlling breathing, is an overlooked physiologic variable which affects the pathophysiology and the clinical outcome of acute respiratory distress syndrome (ARDS). Spontaneous breathing may offer multiple physiologic benefits in these patients, including decreased need for sedation, preserved diaphragm activity and improved cardiovascular function. However, excessive effort to breathe due to high respiratory drive may lead to patient self-inflicted lung injury (P-SILI), even in the absence of mechanical ventilation. In the present review, we focus on the physiological and clinical implications of control of respiratory drive in ARDS patients. We summarize the main determinants of neural respiratory drive and the mechanisms involved in its potentiation, in health and ARDS. We also describe potential and pitfalls of the available bedside methods for drive assessment and explore classical and more "futuristic" interventions to control drive in ARDS patients.

BACKGROUND:Concerns exist regarding the prevalence and impact of unnecessary oxygen use in patients with acute respiratory distress syndrome (ARDS). We examined this issue in patients with ARDS enrolled in the Large observational study to UNderstand the Global impact of Severe Acute respiratory FailurE (LUNG SAFE) study. METHODS:≥ 0.60 during hyperoxemia). RESULTS:55-100 mmHg) patients (P = 0.47). CONCLUSIONS:Hyperoxemia and excess oxygen use are both prevalent in early ARDS but are most often non-sustained. No relationship was found between hyperoxemia or excessive oxygen use and patient outcome in this cohort. TRIAL REGISTRATION:LUNG-SAFE is registered with ClinicalTrials.gov, NCT02010073.

Ventilation-induced lung injury results from mechanical stress and strain that occur during tidal ventilation in the susceptible lung. Classical descriptions of ventilation-induced lung injury have focused on harm from positive pressure ventilation. However, injurious forces also can be generated by patient effort and patient-ventilator interactions. While the role of global mechanics has long been recognized, regional mechanical heterogeneity within the lungs also appears to be an important factor propagating clinically significant lung injury. The resulting clinical phenotype includes worsening lung injury and a systemic inflammatory response that drives extrapulmonary organ failures. Bedside recognition of ventilation-induced lung injury requires a high degree of clinical acuity given its indistinct presentation and lack of definitive diagnostics. Yet the clinical importance of ventilation-induced lung injury is clear. Preventing such biophysical injury remains the most effective management strategy to decrease morbidity and mortality in patients with acute respiratory distress syndrome and likely benefits others at risk.

The estimation of pleural pressure with esophageal manometry has been used for decades, and it has been a fertile area of physiology research in healthy subject as well as during mechanical ventilation in patients with lung injury. However, its scarce adoption in clinical practice takes its roots from the (false) ideas that it requires expertise with years of training, that the values obtained are not reliable due to technical challenges or discrepant methods of calculation, and that measurement of esophageal pressure has not proved to benefit patient outcomes. Despites these criticisms, esophageal manometry could contribute to better monitoring, optimization, and personalization of mechanical ventilation from the acute initial phase to the weaning period. This review aims to provide a comprehensive but comprehensible guide addressing the technical aspects of esophageal catheter use, its application in different clinical situations and conditions, and an update on the state of the art with recent studies on this topic and on remaining questions and ways for improvement.