The association between ventilator parameters in the initial 48h and outcomes after out-of-hospital cardiac arrest. A sub-study of the TAME trial

Background Out-of-hospital cardiac arrest (OHCA) is frequently complicated by lung injury and the acute respiratory distress syndrome (ARDS), which has been associated with worse outcomes. Lung protective ventilation, tidal volume (TV) =6-8mL/kg, is recommended post-resuscitation care but these recommendations are extrapolated from ARDS-populations. In the Targeted Therapeutic Mild Hypercapnia After Resuscitated Cardiac Arrest (TAME) trial hypercapnia was achieved by lowering TV and respiratory frequencies (RF), which may impact both lung injury and outcomes. Purpose We investigated the association between ventilator settings in the initial 48h and six-month mortality. Secondarily, we assessed the incidence of ARDS, and its effect on mortality. Methods Single-centre, prospective, sub-study of the TAME trial. Comatose adults with OHCA of a cardiac cause were randomised 1:1 to mild hypercapnia (PaCO2=50-55 mmHg) or normocapnia (PaCO2=35-45 mmHg) for 24 hours. Patients had to survive ≥48 hours and receive mechanical ventilation ≥24 hours. ARDS was defined as 2 consecutive arterial blood gases with a ratio of the partial pressure of oxygen to the fraction of inspired oxygen (PaO2:FiO2) ≤300 mmHg and bilateral lung opacities. Serial right heart catheterisation (RHC) and echocardiography was used to rule out congestion as the primary cause of respiratory failure. Depending on the distribution the mean or median across 0-24h and 28-48h of each ventilator variable were used for survival analysis. Cox proportional hazard models, adjusted for baseline variables and treatment-group allocation, were used for time-to-event analysis. Results 123 patients were assessed with 58 and 65 randomised to hypercapnia and normocapnia, respectively. Baseline characteristics and survival rates were similar between treatment-groups (p >0.05). Overall, the median age was 64 years, median time to ROSC was 23 min and 93 % had a shockable rhythm. Targeting hypercapnia was associated with lower RF, TV, driving pressures and plateau pressures (p <0.05). Positive end-expiratory pressure (PEEP) and PaO2:FiO2-ratio was similar (p >0.05). RF, PEEP, plateau pressures and driving pressures during the intervention and the following 24 hours were independently associated with six-mortality, and with higher levels were associated with worse outcomes (p <0.05). Driving pressure was the strongest predictor with a hazard ratio of 1.15 (95 % CI 1.06-1.24), p <0.001. At 48h, 86 (70%) patients met the criteria for ARDS with no treatment group difference overall and with regards to ARDS severity. ARDS grade 3 (PaO2:FiO2<100 mmHg), compared to no ARDS, was associated with an increased 6-month mortality (p =0.030). Conclusions Among patients with OHCA, high ventilator pressures and RF in the initial 48h after resuscitation were associated with increased mortality. Mild hypercapnia did not impact the severity of respiratory failure, and ARDS grade 3 was associated with worse outcomes.