Research from JAMA — Vasopressin, Steroids, and Epinephrine and Neurologically Favorable Survival After In-Hospital Cardiac Arrest — A Randomized Clinical Trial

Research from JAMA Internal Medicine — Vasopressin, Epinephrine, and Corticosteroids for In-Hospital Cardiac Arrest

The present authors hypothesised that in severe acute respiratory distress syndrome (ARDS), pronation may reduce ventilator-induced overall stress (i.e.transpulmonary pressure (P_L)) and strain of lung parenchyma (i.e.tidal volume (V_T)/end-expiratory lung volume (EELV) ratio), which constitute major ventilator-induced lung injury determinants. The authors sought to determine whether potential pronation benefits are maintained in post-prone semirecumbent (SR_PP) posture under pressure-volume curve-dependent optimisation of positive end-expiratory pressure (PEEP).A total of 10 anesthetised/paralysed, mechanically ventilated (V_T = 9.0±0.9 mL·kg⁻¹predicted body weight; flow = 0.91±0.04 L·s⁻¹; PEEP = 9.4±1.3 cmH₂O) patients with early/severe ARDS were studied in pre-prone semirecumbent (SR_BAS), prone, and SR_PPpositions. Partitioned respiratory mechanics were determined during iso-flow (0.91 L·s⁻¹) experiments (V_Tvaried within 0.2–1.0 L), along with haemodynamics, gas exchange, and EELV.Compared with SR_BAS, pronation/SR_PPresulted in reduced peak/plateauP_LatV_Ts≥0.6 L; static lung elastance and additional lung resistance decreased and chest wall elastance (in prone position) increased; EELV increased (23–33%);V_T/EELV decreased (27–33%); arterial oxygen tension/inspiratory oxygen fraction and arterial carbon dioxide tension improved (21–43/10–14%, respectively), and shunt fraction/physiological dead space decreased (21–50/20–47%, respectively).In early/severe acute respiratory distress syndrome, pronation under positive end-expiratory pressure optimisation may reduce ventilator-induced lung injury risk. Pronation benefits may be maintained in post-prone semirecumbent position.

Rationale: High-frequency oscillatory ventilation (HFOV) is theoretically beneficial for lung protection, but the results of clinical trials are inconsistent, with study-level meta-analyses suggesting no significant effect on mortality. Objectives: The aim of this individual patient data meta-analysis was to identify acute respiratory distress syndrome (ARDS) patient subgroups with differential outcomes from HFOV. Methods: After a comprehensive search for trials, two reviewers independently identified randomized trials comparing HFOV with conventional ventilation for adults with ARDS. Prespecified effect modifiers were tested using multivariable hierarchical logistic regression models, adjusting for important prognostic factors and clustering effects. Measurements and Main Results: Data from 1,552 patients in four trials were analyzed, applying uniform definitions for study variables and outcomes. Patients had a mean baseline PaO2/FiO2 of 114 ± 39 mm Hg; 40% had severe ARDS (PaO2/FiO2 <100 mm Hg). Mortality at 30 days was 321 of 785 (40.9%) for HFOV patients versus 288 of 767 (37.6%) for control subjects (adjusted odds ratio, 1.17; 95% confidence interval, 0.94–1.46; P = 0.16). This treatment effect varied, however, depending on baseline severity of hypoxemia (P = 0.0003), with harm increasing with PaO2/FiO2 among patients with mild-moderate ARDS, and the possibility of decreased mortality in patients with very severe ARDS. Compliance and body mass index did not modify the treatment effect. HFOV increased barotrauma risk compared with conventional ventilation (adjusted odds ratio, 1.75; 95% confidence interval, 1.04–2.96; P = 0.04). Conclusions: HFOV increases mortality for most patients with ARDS but may improve survival among patients with severe hypoxemia on conventional mechanical ventilation.