Background: Since 2000, the prevalence of recreational nitrous oxide (N 2O) use has increased in the Western world. Although N 2O is a relatively safe drug, the overall increase in the use of N 2O has concomitantly also initiated a modest but important increase in the number of young excessive users. The recent introduction of large 2 kg N 2O tanks, allowing high and prolonged dosing, has facilitated this excessive use. This is of concern, because repeated exposure to high doses of N 2O for a prolonged time is known to induce neurological damage, such as (irreversible) neuropathy and paralysis due to N 2O-induced vitamin B 12 deficiency. The increasing trend of recreational users with N 2O-induced neurological damage at emergency departments confirms the urgency of this development. Objective/Methods: This narrative review describes recent trends in N 2O use and misuse, the adverse health effects associated with excessive use and the risk factors of excessive use. Results: Considering the rising trend in N 2O use, particularly among young and other vulnerable people, we propose to take legislative action to limit the availability of N 2O, and also advocate for better and timely education of non-users, users and medical professionals about the serious side-effects associated with excessive N 2O use. Conclusion: It is concluded that the increase in excessive N 2O use is of serious concern.
Background: Ventilation management may differ between COVID–19 ARDS (COVID–ARDS) patients and patients with pre–COVID ARDS (CLASSIC–ARDS); it is uncertain whether associations of ventilation management with outcomes for CLASSIC–ARDS also exist in COVID–ARDS. Methods: Individual patient data analysis of COVID–ARDS and CLASSIC–ARDS patients in six observational studies of ventilation, four in the COVID–19 pandemic and two pre–pandemic. Descriptive statistics were used to compare epidemiology and ventilation characteristics. The primary endpoint were key ventilation parameters; other outcomes included mortality and ventilator–free days and alive (VFD–60) at day 60. Results: This analysis included 6702 COVID–ARDS patients and 1415 CLASSIC–ARDS patients. COVID–ARDS patients received lower median VT (6.6 [6.0 to 7.4] vs 7.3 [6.4 to 8.5] ml/kg PBW; p < 0.001) and higher median PEEP (12.0 [10.0 to 14.0] vs 8.0 [6.0 to 10.0] cm H2O; p < 0.001), at lower median ΔP (13.0 [10.0 to 15.0] vs 16.0 [IQR 12.0 to 20.0] cm H2O; p < 0.001) and higher median Crs (33.5 [26.6 to 42.1] vs 28.1 [21.6 to 38.4] mL/cm H2O; p < 0.001). Following multivariable adjustment, higher ΔP had an independent association with higher 60–day mortality and less VFD–60 in both groups. Higher PEEP had an association with less VFD–60, but only in COVID–ARDS patients. Conclusions: Our findings show important differences in key ventilation parameters and associations thereof with outcomes between COVID–ARDS and CLASSIC–ARDS. Trial registration: Clinicaltrials.gov (identifier NCT05650957), December 14, 2022.