Analgesia and Sedation Use During Noninvasive Ventilation for Acute Respiratory Failure.

OBJECTIVES: To describe U.S. practice regarding administration of sedation and analgesia to patients on noninvasive ventilation (NIV) for acute respiratory failure (ARF) and to determine the association of this practice with odds of intubation or death. DESIGN: A retrospective multicenter cohort study. SETTING: A total of 1017 hospitals contributed data between January 2010 and September 2020 to the Premier Healthcare Database, a nationally representative healthcare database in the United States. PATIENTS: Adult (≥ 18 yr) patients admitted to U.S. hospitals requiring NIV for ARF. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: We identified 433,357 patients on NIV of whom (26.7% [95% CI] 26.3%-27.0%) received sedation or analgesia. A total of 50,589 patients (11.7%) received opioids only, 40,646 (9.4%) received benzodiazepines only, 20,146 (4.6%) received opioids and benzodiazepines, 1.573 (0.4%) received dexmedetomidine only, and 2,639 (0.6%) received dexmedetomidine in addition to opioid and/or benzodiazepine. Of 433,357 patients receiving NIV, 50,413 (11.6%; 95% CI, 11.5-11.7%) patients underwent invasive mechanical ventilation on hospital days 2-5 or died on hospital days 2-30. Intubation was used in 32,301 patients (7.4%; 95% CI, 7.3-7.6%). Further, death occurred in 24,140 (5.6%; 95% CI, 5.5-5.7%). In multivariable analysis adjusting for relevant covariates, receipt of any medication studied was associated with increased odds of intubation or death. In inverse probability weighting, receipt of any study medication was also associated with increased odds of intubation or death (average treatment effect odds ratio 1.38; 95% CI, 1.35-1.40). CONCLUSIONS: The use of sedation and analgesia during NIV is common. Medication exposure was associated with increased odds of intubation or death. Further investigation is needed to confirm this finding and determine whether any subpopulations are especially harmed by this practice.

Flow-Limited and Reverse-Triggered Ventilator Dyssynchrony Are Associated With Increased Tidal and Dynamic Transpulmonary Pressure.

OBJECTIVES: Ventilator dyssynchrony may be associated with increased delivered tidal volumes (V t s) and dynamic transpulmonary pressure (ΔP L,dyn ), surrogate markers of lung stress and strain, despite low V t ventilation. However, it is unknown which types of ventilator dyssynchrony are most likely to increase these metrics or if specific ventilation or sedation strategies can mitigate this potential. DESIGN: A prospective cohort analysis to delineate the association between ten types of breaths and delivered V t , ΔP L,dyn , and transpulmonary mechanical energy. SETTING: Patients admitted to the medical ICU. PATIENTS: Over 580,000 breaths from 35 patients with acute respiratory distress syndrome (ARDS) or ARDS risk factors. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Patients received continuous esophageal manometry. Ventilator dyssynchrony was identified using a machine learning algorithm. Mixed-effect models predicted V t , ΔP L,dyn , and transpulmonary mechanical energy for each type of ventilator dyssynchrony while controlling for repeated measures. Finally, we described how V t , positive end-expiratory pressure (PEEP), and sedation (Richmond Agitation-Sedation Scale) strategies modify ventilator dyssynchrony's association with these surrogate markers of lung stress and strain. Double-triggered breaths were associated with the most significant increase in V t , ΔP L,dyn , and transpulmonary mechanical energy. However, flow-limited, early reverse-triggered, and early ventilator-terminated breaths were also associated with significant increases in V t , ΔP L,dyn , and energy. The potential of a ventilator dyssynchrony type to increase V t , ΔP L,dyn , or energy clustered similarly. Increasing set V t may be associated with a disproportionate increase in high-volume and high-energy ventilation from double-triggered breaths, but PEEP and sedation do not clinically modify the interaction between ventilator dyssynchrony and surrogate markers of lung stress and strain. CONCLUSIONS: Double-triggered, flow-limited, early reverse-triggered, and early ventilator-terminated breaths are associated with increases in V t , ΔP L,dyn , and energy. As flow-limited breaths are more than twice as common as double-triggered breaths, further work is needed to determine the interaction of ventilator dyssynchrony frequency to cause clinically meaningful changes in patient outcomes.

Extracorporeal Membrane Oxygenation for Refractory Asthma Exacerbations With Respiratory Failure.

BACKGROUND: Asthma exacerbations with respiratory failure (AERF) are associated with hospital mortality of 7% to 15%. Extracorporeal membrane oxygenation (ECMO) has been used as a salvage therapy for refractory AERF, but controlled studies showing its association with mortality have not been performed. RESEARCH QUESTION: Is treatment with ECMO associated with lower mortality in refractory AERF compared with standard care? STUDY DESIGN AND METHODS: This is a retrospective, epidemiologic, observational cohort study using a national, administrative data set from 2010 to 2020 that includes 25% of US hospitalizations. People were included if they were admitted to an ECMO-capable hospital with an asthma exacerbation, and were treated with short-acting bronchodilators, systemic corticosteroids, and invasive ventilation. People were excluded for age < 18 years, no ICU stay, nonasthma chronic lung disease, COVID-19, or multiple admissions. The main exposure was ECMO vs No ECMO. The primary outcome was hospital mortality. Key secondary outcomes were ICU length of stay (LOS), hospital LOS, time receiving invasive ventilation, and total hospital costs. RESULTS: The study analyzed 13,714 patients with AERF, including 127 with ECMO and 13,587 with No ECMO. ECMO was associated with reduced mortality in the covariate-adjusted (OR, 0.33; 95% CI, 0.17-0.64; P = .001), propensity score-adjusted (OR, 0.36; 95% CI, 0.16-0.81; P = .01), and propensity score-matched models (OR, 0.48; 95% CI, 0.24-0.98; P = .04) vs No ECMO. Sensitivity analyses showed that mortality reduction related to ECMO ranged from OR 0.34 to 0.61. ECMO was also associated with increased hospital costs in all three models (P < .0001 for all) vs No ECMO, but not with decreased ICU LOS, hospital LOS, or time receiving invasive ventilation. INTERPRETATION: ECMO was associated with lower mortality and higher hospital costs, suggesting that it may be an important salvage therapy for refractory AERF following confirmatory clinical trials.

The Association Between Ventilator Dyssynchrony, Delivered Tidal Volume, and Sedation Using a Novel Automated Ventilator Dyssynchrony Detection Algorithm.

OBJECTIVE: Ventilator dyssynchrony is potentially harmful to patients with or at risk for the acute respiratory distress syndrome. Automated detection of ventilator dyssynchrony from ventilator waveforms has been difficult. It is unclear if certain types of ventilator dyssynchrony deliver large tidal volumes and whether levels of sedation alter the frequency of ventilator dyssynchrony. DESIGN: A prospective observational study. SETTING: A university medical ICU. PATIENTS: Patients with or at risk for acute respiratory distress syndrome. INTERVENTIONS: Continuous pressure-time, flow-time, and volume-time data were directly obtained from the ventilator. The level of sedation and the use of neuromuscular blockade was extracted from the medical record. Machine learning algorithms that incorporate clinical insight were developed and trained to detect four previously described and clinically relevant forms of ventilator dyssynchrony. The association between normalized tidal volume and ventilator dyssynchrony and the association between sedation and the frequency of ventilator dyssynchrony were determined. MEASUREMENTS AND MAIN RESULTS: A total of 4.26 million breaths were recorded from 62 ventilated patients. Our algorithm detected three types of ventilator dyssynchrony with an area under the receiver operator curve of greater than 0.89. Ventilator dyssynchrony occurred in 34.4% (95% CI, 34.41-34.49%) of breaths. When compared with synchronous breaths, double-triggered and flow-limited breaths were more likely to deliver tidal volumes greater than 10 mL/kg (40% and 11% compared with 0.2%; p < 0.001 for both comparisons). Deep sedation reduced but did not eliminate the frequency of all ventilator dyssynchrony breaths (p < 0.05). Ventilator dyssynchrony was eliminated with neuromuscular blockade (p < 0.001). CONCLUSION: We developed a computerized algorithm that accurately detects three types of ventilator dyssynchrony. Double-triggered and flow-limited breaths are associated with the frequent delivery of tidal volumes of greater than 10 mL/kg. Although ventilator dyssynchrony is reduced by deep sedation, potentially deleterious tidal volumes may still be delivered. However, neuromuscular blockade effectively eliminates ventilator dyssynchrony.

Association Between Resilience and Family Member Psychologic Symptoms in Critical Illness.

OBJECTIVES: There are increased rates of depression, anxiety, and stress disorders in families of critically ill patients. Interventions directed at family members may help their ability to cope with this stress. Specifically, resilience is a teachable psychologic construct describing a person's ability to adapt to traumatic situations. Resilience can inherently assist individuals to diminish adverse psychologic outcomes. Consequently, we determined the relationship between resilience and symptoms of depression, anxiety, and acute stress in family members of critically ill patients. DESIGN: This is a cross-sectional study. SETTING: Three medical ICUs were screened by study staff. PATIENTS: Family members of ICU patients admitted for greater than 48 hours were approached for enrollment. INTERVENTIONS: The Connor-Davidson Resilience Scale was used to stratify family members as resilient or nonresilient. MEASUREMENTS AND MAIN RESULTS: The Hospital Anxiety and Depression Scale, Impact of Event Scale-Revised, and Family Satisfaction in the ICU were collected prior to ICU discharge to measure symptoms of depression, anxiety, and acute stress, as well as satisfaction with care. One-hundred and seventy family members were enrolled. Seventy-eight family members were resilient. Resilient family members had fewer symptoms of anxiety (14.2% vs 43.6%; p < 0.001), depression (14.1% vs 44.9%; p < 0.001), and acute stress (12.7% vs 36.3%; p = 0.001). Resilient family members were more satisfied with care in the ICU (76.7 vs 70.8; p = 0.008). Resilience remained independently associated with these outcomes after adjusting for family member age and gender, as well as the patient's need for mechanical ventilation. CONCLUSIONS: When caring for the critically ill, resilient family members have fewer symptoms of depression, anxiety, and acute stress. Resilient families were generally better satisfied with the care delivered. These data suggest that interventions aimed at increasing resilience may improve a family member's experience in the ICU.