Prone Positioning in Moderate to Severe Acute Respiratory Distress Syndrome Due to COVID-19: A Cohort Study and Analysis of Physiology.

BACKGROUND: Coronavirus disease 2019 (COVID-19) can lead to acute respiratory distress syndrome (ARDS) but it is unknown whether prone positioning improves outcomes in mechanically ventilated patients with moderate to severe ARDS due to COVID-19. METHODS: A cohort study at a New York City hospital at the peak of the early pandemic in the United States, under crisis conditions. The aim was to determine the benefit of prone positioning in mechanically ventilated patients with ARDS due to COVID-19. The primary outcome was in-hospital death. Secondary outcomes included changes in physiologic parameters. Fine-Gray competing risks models with stabilized inverse probability treatment weighting (sIPTW) were used to determine the effect of prone positioning on outcomes. In addition, linear mixed effects models (LMM) were used to assess changes in physiology with prone positioning. RESULTS: Out of 335 participants who were intubated and mechanically ventilated, 62 underwent prone positioning, 199 met prone positioning criteria and served as controls and 74 were excluded. The intervention and control groups were similar at baseline. In multivariate-adjusted competing risks models with sIPTW, prone positioning was significantly associated with reduced mortality (SHR 0.61, 95% CI 0.46-0.80, P < 0.005). Using LMM to evaluate the impact of positioning maneuvers on physiological parameters, the oxygenation-saturation index was significantly improved during days 1-3 (P < 0.01) whereas oxygenation-saturation index (OSI), oxygenation-index (OI) and arterial oxygen partial pressure to fractional inspired oxygen (PaO2: FiO2) were significantly improved during days 4-7 (P < 0.05 for all). CONCLUSIONS: Prone positioning in patients with moderate to severe ARDS due to COVID-19 is associated with reduced mortality and improved physiologic parameters. One in-hospital death could be averted for every 8 patients treated. Replicating results and scaling the intervention are important, but prone positioning may represent an additional therapeutic option in patients with ARDS due to COVID-19.

Elevations in inflammatory cytokines are associated with poor outcomes in mechanically ventilated burn patients.

BACKGROUND: The treatment of burn patients who undergo mechanical ventilation is complicated by many factors; patient outcomes and mortality could potentially be improved with predictive biomarkers. Severe burn provokes a systemic inflammatory response characterized by the release of a host of cytokines. Recent studies evaluated the prognostic value of temporal changes in cytokine levels in several patient populations, but few have compared differences in the cytokine profiles of survivors and nonsurvivors following severe burn. We previously compared high-frequency percussive ventilation and low-tidal-volume ventilation and found no difference in mortality or cytokine levels between the two treatments. Since it is unknown whether cytokine levels are predictive of mortality in these patients, we performed a post hoc analysis comparing cytokine levels in survivors and nonsurvivors. METHODS: We evaluated plasma levels of several cytokines (interleukin 1ß [IL-1ß], IL-6, IL-8, granulocyte-macrophage colony-stimulating factor, and tumor necrosis factor α) for their prognostic biomarker potential related to mortality at 0, 3, and 7 days in survivors and nonsurvivors of burns. RESULTS: While the majority of values for IL-1ß, granulocyte-macrophage colony-stimulating factor, and tumor necrosis factor α fell below the limit of quantification, univariate analysis demonstrated higher plasma levels of IL-6 and IL-8 in nonsurvivors on Day 7. Logistic regression revealed that elevated plasma IL-8 was independently associated with an increased likelihood of the composite end point of death or ventilator-associated pneumonia with odds ratios of 7.9, 26, and 7.3 on Days 0, 3, and 7, respectively. CONCLUSION: Early increases in plasma IL-8 are associated with a multifold increase in death or ventilator-associated pneumonia in mechanically ventilated burn patients. LEVEL OF EVIDENCE: Prognostic/epidemiologic study, level IV; therapeutic study, level IV.

High-frequency percussive ventilation and low tidal volume ventilation in burns: a randomized controlled trial.

OBJECTIVES: In select burn intensive care units, high-frequency percussive ventilation is preferentially used to provide mechanical ventilation in support of patients with acute lung injury, acute respiratory distress syndrome, and inhalation injury. However, we found an absence of prospective studies comparing high-frequency percussive ventilation with contemporary low-tidal volume ventilation strategies. The purpose of this study was to prospectively compare the two ventilator modalities in a burn intensive care unit setting. DESIGN: Single-center, prospective, randomized, controlled clinical trial, comparing high-frequency percussive ventilation with low-tidal volume ventilation in patients admitted to our burn intensive care unit with respiratory failure. SETTING: A 16-bed burn intensive care unit at a tertiary military teaching hospital. PATIENTS: Adult patients ≥ 18 yrs of age requiring prolonged (> 24 hrs) mechanical ventilation were admitted to the burn intensive care unit. The study was conducted over a 3-yr period between April 2006 and May 2009. This trial was registered with ClinicalTrials.gov as NCT00351741. INTERVENTIONS: Subjects were randomly assigned to receive mechanical ventilation through a high-frequency percussive ventilation-based strategy (n = 31) or a low-tidal volume ventilation-based strategy (n = 31). MEASUREMENTS AND MAIN RESULTS: At baseline, both the high-frequency percussive ventilation group and the low-tidal volume ventilation group had similar demographics to include median age (interquartile range) (28 yrs [23-45] vs. 33 yrs [24-46], p = nonsignificant), percentage of total body surface area burn (34 [20-52] vs. 34 [23-50], p = nonsignificant), and clinical diagnosis of inhalation injury (39% vs. 35%, p = nonsignificant). The primary outcome was ventilator-free days in the first 28 days after randomization. Intent-to-treat analysis revealed no significant difference between the high-frequency percussive ventilation and the low-tidal volume ventilation groups in mean (± sd) ventilator-free days (12 ± 9 vs. 11 ± 9, p = nonsignificant). No significant difference was detected between groups for any of the secondary outcome measures to include mortality except the need for "rescue" mode application (p = .02). Nine (29%) in the low-tidal volume ventilation arm did not meet predetermined oxygenation or ventilation goals and required transition to a rescue mode. By contrast, two in the high-frequency percussive ventilation arm (6%) required rescue. CONCLUSIONS: A high-frequency percussive ventilation-based strategy resulted in similar clinical outcomes when compared with a low-tidal volume ventilation-based strategy in burn patients with respiratory failure. However, the low-tidal volume ventilation strategy failed to achieve ventilation and oxygenation goals in a higher percentage necessitating rescue ventilation.