Effect of Lower vs Higher Oxygen Saturation Targets on Survival to Hospital Discharge Among Patients Resuscitated After Out-of-Hospital Cardiac Arrest

Abstract

ImportanceThe administration of a high fraction of oxygen following return of spontaneous circulation in out-of-hospital cardiac arrest may increase reperfusion brain injury.ObjectiveTo determine whether targeting a lower oxygen saturation in the early phase of postresuscitation care for out-of-hospital cardiac arrest improves survival at hospital discharge.Design, Setting, and ParticipantsThis multicenter, parallel-group, randomized clinical trial included unconscious adults with return of spontaneous circulation and a peripheral oxygen saturation (Spo2) of at least 95% while receiving 100% oxygen. The trial was conducted in 2 emergency medical services and 15 hospitals in Victoria and South Australia, Australia, between December 11, 2017, and August 11, 2020, with data collection from ambulance and hospital medical records (final follow-up date, August 25, 2021). The trial enrolled 428 of a planned 1416 patients.InterventionsPatients were randomized by paramedics to receive oxygen titration to achieve an oxygen saturation of either 90% to 94% (intervention; n = 216) or 98% to 100% (standard care; n = 212) until arrival in the intensive care unit.Main Outcomes and MeasuresThe primary outcome was survival to hospital discharge. There were 9 secondary outcomes collected, including hypoxic episodes (Spo2 <90%) and prespecified serious adverse events, which included hypoxia with rearrest.ResultsThe trial was stopped early due to the COVID-19 pandemic. Of the 428 patients who were randomized, 425 were included in the primary analysis (median age, 65.5 years; 100 [23.5%] women) and all completed the trial. Overall, 82 of 214 patients (38.3%) in the intervention group survived to hospital discharge compared with 101 of 211 (47.9%) in the standard care group (difference, −9.6% [95% CI, −18.9% to −0.2%]; unadjusted odds ratio, 0.68 [95% CI, 0.46-1.00]; P = .05). Of the 9 prespecified secondary outcomes collected during hospital stay, 8 showed no significant difference. A hypoxic episode prior to intensive care was observed in 31.3% (n = 67) of participants in the intervention group and 16.1% (n = 34) in the standard care group (difference, 15.2% [95% CI, 7.2%-23.1%]; OR, 2.37 [95% CI, 1.49-3.79]; P < .001).Conclusions and RelevanceAmong patients achieving return of spontaneous circulation after out-of-hospital cardiac arrest, targeting an oxygen saturation of 90% to 94%, compared with 98% to 100%, until admission to the intensive care unit did not significantly improve survival to hospital discharge. Although the trial is limited by early termination due to the COVID-19 pandemic, the findings do not support use of an oxygen saturation target of 90% to 94% in the out-of-hospital setting after resuscitation from cardiac arrest.Trial RegistrationClinicalTrials.gov Identifier: NCT03138005

Hyperoxemia after reperfusion in cardiac arrest patients: a potential dose–response association with 30-day survival

“…It is reasonable to believe that the level of hyperoxemia in these studies was too modest and/or too late to cause harm. In the recently published EXACT-trial, that randomized lower (SpO 2 90–94%) vs higher (SpO 2 99–100%) O 2 saturation targets in resuscitated cardiac arrest patients in the prehospital setting, the lower SpO 2 -target group had more hypoxic events and a trend towards lower survival [ 17 ] which is in agreement with our findings. The median first PaO 2 in ICU in the higher SpO 2 -target group was 15.2 kPa (114 mmHg), i.e.…”

“…Oxygen therapy after cardiac arrest has become a major research question in post resuscitation management [ 44 ]. In practice, it may be difficult to titrate oxygen saturation in a controlled and safe manner in the prehospital setting, which was recently highlighted in the EXACT trial [ 17 ]. Most often, there is no possibility to analyze arterial blood gases and measurement of oxygen saturation by pulse oximetry (SpO 2 ) may be unreliable due to for example vasoconstriction.…”

“…Clinical studies investigating hyperoxemia after cardiac arrest with ROSC are heterogenous and have shown varying results [ 15 – 17 ]. For example, there is a wide variation in timing of PaO 2 measurements wherein some cases only one single PaO 2 -value up to 24 h after ICU arrival has been analysed [ 18 , 19 ].…”

Lower vs Higher Oxygen Saturation Targets and Survival to Hospital Discharge Among Patients Resuscitated After Out-of-Hospital Cardiac Arrest—Reply

“…The arterial blood gas measurement was performed after emergency department physicians had provided patients with mechanical ventilation. Of note, although it was not included in our article, the mean end-tidal carbon dioxide measurement at emergency department arrival was 40 mm Hg in the titrated group and 41 mm Hg in the control group, which may have reassured treating clinicians that the minute ventilation on the ventilator was adequate prior to obtaining the arterial blood gas measure. The unexpected finding of a significant difference between end-tidal carbon dioxide and P co 2 on hospital arrival was an important observation, and we would therefore recommend that a lower end-tidal carbon dioxide measure (25-35 mm Hg) is targeted during prehospital transport and initial evaluation in the emergency department of unconscious patients with out-of-hospital cardiac arrest.…”

“…In Reply Regarding our recent study, Drs Wetsch and Böttiger are concerned that a target oxygen saturation of 90% to 94% in the EXACT trial should be considered hypoxia. This target oxygen saturation was justified by a meta-analysis of previous phase 2 trials testing a lower oxygen target in patients with out-of-hospital cardiac arrest .…”