Oxygen targets and 6-month outcome after out of hospital cardiac arrest: a pre-planned sub-analysis of the targeted hypothermia versus targeted normothermia after Out-of-Hospital Cardiac Arrest (TTM2) trial

Abstract

Background Optimal oxygen targets in patients resuscitated after cardiac arrest are uncertain. The primary aim of this study was to describe the values of partial pressure of oxygen values (PaO2) and the episodes of hypoxemia and hyperoxemia occurring within the first 72 h of mechanical ventilation in out of hospital cardiac arrest (OHCA) patients. The secondary aim was to evaluate the association of PaO2 with patients’ outcome. Methods Preplanned secondary analysis of the targeted hypothermia versus targeted normothermia after OHCA (TTM2) trial. Arterial blood gases values were collected from randomization every 4 h for the first 32 h, and then, every 8 h until day 3. Hypoxemia was defined as PaO2 < 60 mmHg and severe hyperoxemia as PaO2 > 300 mmHg. Mortality and poor neurological outcome (defined according to modified Rankin scale) were collected at 6 months. Results 1418 patients were included in the analysis. The mean age was 64 ± 14 years, and 292 patients (20.6%) were female. 24.9% of patients had at least one episode of hypoxemia, and 7.6% of patients had at least one episode of severe hyperoxemia. Both hypoxemia and hyperoxemia were independently associated with 6-month mortality, but not with poor neurological outcome. The best cutoff point associated with 6-month mortality for hypoxemia was 69 mmHg (Risk Ratio, RR = 1.009, 95% CI 0.93–1.09), and for hyperoxemia was 195 mmHg (RR = 1.006, 95% CI 0.95–1.06). The time exposure, i.e., the area under the curve (PaO2-AUC), for hyperoxemia was significantly associated with mortality (p = 0.003). Conclusions In OHCA patients, both hypoxemia and hyperoxemia are associated with 6-months mortality, with an effect mediated by the timing exposure to high values of oxygen. Precise titration of oxygen levels should be considered in this group of patients. Trial registration: clinicaltrials.gov NCT02908308, Registered September 20, 2016.

Developments in Post-Resuscitation Care for Out-of-Hospital Cardiac Arrests in Adults—A Narrative Review

“…Robba et al performed a secondary analysis of the TTM 2 trial, investigating the effects of hypo-and hyperoxemia within the first 72 h of admission on mortality and neurological status at 6 months. This multivariate Cox regression also showed a U-shaped distribution for PaO 2 with an increased risk for mortality below 69 mm Hg (hypoxemia) and above 195 mm Hg (hyperoxemia); however, it found no correlation for poor neurological outcomes [21]. PaO 2 was significantly lower in non-survivors for up to 32 h after ICU admission.…”

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

“…The PaO 2 -cut point for worse outcome started at ≥ 40 kPa. In a recently published sub-analysis of the Target Temperature Management 2 (TTM2) trial, both hypoxemia and severe hyperoxemia were significantly associated with 6 month-mortality [ 43 ]. The best cut-off point associated with 6 month-mortality was 195 mmHg (26 kPa), which resembles the results in our study.…”

Ventilatory targets following brain injury

“…Evidence consistently points to the association of hypoxemia with worse clinical outcomes in patients with ABI. In cardiac arrest patients, a sub-analysis of the TTM2 trial found that the best hypoxemia threshold for predicting 6-month mortality was PaO 2 <69 mmHg [59 ▪ ]. Hyperoxemia has also been associated with worse outcomes [60,61], putatively via free radical production and nitric oxygen scavenging [62].…”