Drug-overdose associated acute hypoxemic respiratory failure: A secondary analysis

INTRODUCTION The majority of fatal drug overdose cases are due to acute hypoxemic respiratory failure (AHRF). We examined whether AHRF associated with drug overdose has distinct features from AHRF associated with other risk factors. METHODS We performed a secondary analysis of patient -level data from the LOTUS FRUIT study, a multicenter, prospective, observational study conducted by the PETAL Network. We classified patients with AHRF into the 'drugoverdose associated AHRF' (when PETAL investigators listed drug overdose as a risk factor of AHRF) versus the 'non -drug -overdose associated AHRF' group. To assess the association between drug overdose and 28 -day mortality, we used a Cox proportional hazards regression analysis, both unadjusted and adjusted, and a mediation analysis. RESULTS Of the 1280 patients with AHRF, 48 (3.8%) had drug -overdose associated AHRF. They were younger (42.0 vs 60.0 years), more likely to develop rapidly improving AHRF (50.0% vs 24.5%) and had lower unadjusted mortality than patients with non -drug -overdose associated AHRF (16.7% vs 34.4.%) (hazard ratio, HR=0.450; 95% CI: 0.223-0.905). However, after adjustment, drug overdose was no longer associated with lower mortality (adjusted hazard ratio, AHR=0.584; 95% CI: 0.288-1.185). Also, in mediation analysis, lower unadjusted mortality among patients with drug -overdose AHRF was significantly mediated by the development of rapidly improving AHRF (p<0.001 for the average causal mediation effect). CONCLUSIONS Patients with drug -overdose associated AHRF were younger and had lower unadjusted mortality than patients with non -drug -overdose associated AHRF. However, this difference in mortality seemed to be due to confounders, such as age, and to be mediated by the development of rapidly improving AHRF.