Hyperoxia for accidental hypothermia and increased mortality: a post-hoc analysis of a multicenter prospective observational study

Abstract

Background Supraphysiologic oxygen administration causes unfavorable clinical outcomes in various diseases, including traumatic brain injury, post–cardiac arrest syndrome, and acute lung injury. Accidental hypothermia is a critical illness that reduces oxygen demands, and excessive oxygen is likely to emerge. This study aimed to determine whether hyperoxia would be associated with increased mortality in patients with accidental hypothermia. Methods A post-hoc analysis of a nationwide multicenter prospective observational study (ICE-CRASH study) on patients with accidental hypothermia admitted in 2019–2022 was conducted. Adult patients without cardiac arrest whose core body temperature was < 32 °C and whose arterial partial pressure of oxygen (PaO2) was measured at the emergency department were included. Hyperoxia was defined as a PaO2 level of 300 mmHg or higher, and 28-day mortality was compared between patients with and without hyperoxia before rewarming. Inverse probability weighting (IPW) analyses with propensity scores were performed to adjust patient demographics, comorbidities, etiology and severity of hypothermia, hemodynamic status and laboratories on arrival, and institution characteristics. Subgroup analyses were conducted according to age, chronic cardiopulmonary diseases, hemodynamic instability, and severity of hypothermia. Results Of the 338 patients who were eligible for the study, 65 had hyperoxia before rewarming. Patients with hyperoxia had a higher 28-day mortality rate than those without (25 (39.1%) vs. 51 (19.5%); odds ratio (OR) 2.65 (95% confidence interval 1.47–4.78); p < 0.001). IPW analyses with propensity scores revealed similar results (adjusted OR 1.65 (1.14–2.38); p = 0.008). Subgroup analyses showed that hyperoxia was harmful in the elderly and those with cardiopulmonary diseases and severe hypothermia below 28 °C, whereas hyperoxia exposure had no effect on mortality in patients with hemodynamic instability on hospital arrival. Conclusions Hyperoxia with PaO2 levels of 300 mmHg or higher before initiating rewarming was associated with increased 28-day mortality in patients with accidental hypothermia. The amount of oxygen to administer to patients with accidental hypothermia should be carefully determined. Trial Registration: The ICE-CRASH study was registered at the University Hospital Medical Information Network Clinical Trial Registry on April 1, 2019 (UMIN-CTR ID, UMIN000036132).

Risk Factors and Prediction of 28-Day-All Cause Mortality Among Critically Ill Patients with Acute Pancreatitis Using Machine Learning Techniques: A Retrospective Analysis of Multi-Institutions

“…Body temperature was another important variable in our model, which potentially leads to excessive oxygen molecules that cannot be fully utilized by the tissue. 40 According to its SHAP analysis, lower body temperature was an important predictive factor for 28-d mortality. Regarding laboratory tests, five variables were selected to develop models.…”

Oxygen is Toxic in the Cold inC. elegans

“…Research has also shown that humans, similar to C. elegans, decrease their whole-body oxygen consumption by half for every 10 °C reduction in temperature, a phenomenon known as the Q10 effect 25 . While the use of anoxia to treat hypothermia has not been attempted to our knowledge, recent analysis has shown that hypothermia patients with hyperoxic arterial oxygen concentrations had a 28-day mortality rate twice that of normoxic patients 26 . Further research to understand if the observations made here extend to other animals and humans may improve our ability to use oxygen concentration and temperature to improve clinical outcomes.…”

Hyperoxia for sepsis and development of acute lung injury with increased mortality

“… 9 Several studies on traumatic brain injury reported that supranormal oxygen suppressed cell metabolism, resulting in neuronal death. 33 Additionally, hyperoxia in the early resuscitation phase was related to increased 28-day mortality risk and/or length of ICU stay among patients with severe injury or accidental hypothermia, 6 34 suggesting that redundant oxygen by hyperoxia may affect tissue or cell metabolism particularly in patients with systemic inflammation, which becomes problematic as organ dysfunction can occur days later rather than during resuscitation. Of note, the incidence of sepsis-related mortality (failure to resuscitation from sepsis) was comparable regardless of hyperoxia exposure in this study.…”

“…1 2 However, a supraphysiological amount of oxygen in the blood and/or tissue has been related to unfavourable clinical outcomes in various diseases, including postcardiac arrest syndrome, accidental hypothermia, traumatic brain injury and postcardiac surgery. [3][4][5][6] A recent randomised controlled trial (RCT) on patients receiving mechanical ventilation showed that oxygen titration targeting at 70-100 mm Hg of arterial partial pressure of oxygen (PaO 2 ) reduced the mortality rate in the intensive care unit (ICU). 7 The pathophysiology behind the harmful effects of hyperoxia has been investigated, and oxygen toxicity in the brain and pulmonary tissues affects critically ill patients.…”