Impact of sex on use of low tidal volume ventilation in invasively ventilated ICU patients—A mediation analysis using two observational cohorts

Abstract

Background Studies in patients receiving invasive ventilation show important differences in use of low tidal volume (VT) ventilation (LTVV) between females and males. The aims of this study were to describe temporal changes in VT and to determine what factors drive the sex difference in use of LTVV. Methods and findings This is a posthoc analysis of 2 large longitudinal projects in 59 ICUs in the United States, the ‘Medical information Mart for Intensive Care III’ (MIMIC III) and the ‘eICU Collaborative Research DataBase’. The proportion of patients under LTVV (median VT < 8 ml/kg PBW), was the primary outcome. Mediation analysis, a method to dissect total effect into direct and indirect effects, was used to understand which factors drive the sex difference. We included 3614 (44%) females and 4593 (56%) males. Median VT declined over the years, but with a persistent difference between females (from median 10.2 (9.1 to 11.4) to 8.2 (7.5 to 9.1) ml/kg PBW) vs. males (from median 9.2 [IQR 8.2 to 10.1] to 7.3 [IQR 6.6 to 8.0] ml/kg PBW) (P < .001). In females versus males, use of LTVV increased from 5 to 50% versus from 12 to 78% (difference, –27% [–29% to –25%]; P < .001). The sex difference was mainly driven by patients’ body height and actual body weight (adjusted average causal mediation effect, –30% [–33% to –27%]; P < .001, and 4 [3% to 4%]; P < .001). Conclusions While LTVV is increasingly used in females and males, females continue to receive LTVV less often than males. The sex difference is mainly driven by patients’ body height and actual body weight, and not necessarily by sex. Use of LTVV in females could improve by paying more attention to a correct calculation of VT, i.e., using the correct body height.

Sex Differences in Use of Low Tidal Volume Ventilation in COVID-19—Insights From the PRoVENT–COVID Study

“…An earlier analysis showed that a one SD increases in V T , PBW meant an increase of 28% in 28-day mortality ( 5 ). The finding that females received ventilation with a higher median V T than males in this cohort is in line with results from several investigations originating from before the COVID-19 pandemic ( 13 – 16 , 44 ). It interesting to note that V T , in both females and males, was lower than in those previous cohorts, suggesting a temporal trend toward the use of lower V T in critically ill patients ( 16 ).…”

“…The finding that females received ventilation with a higher median V T than males in this cohort is in line with results from several investigations originating from before the COVID-19 pandemic ( 13 – 16 , 44 ). It interesting to note that V T , in both females and males, was lower than in those previous cohorts, suggesting a temporal trend toward the use of lower V T in critically ill patients ( 16 ). Despite the improved use of LTVV, however, differences between females and males persist.…”

“…The findings of the mediation analysis are in line with findings of the previous studies in patients in the ICU ( 16 ) and in the operating room ( 12 ). In contrary to previous findings, we see that differences are only partly explained by sex per se .…”

“…We did not perform a formal power calculation; the sample size was based on the number of patients available in the database. With 1,000 patients, the study has >80% power to detect an absolute difference ranging from 9 and 15% in the use of LTVV considering a use rate of 50% in the female patients as shown previously ( 16 ).…”

“…Differences between females and males with regard to the use of LTVV have been described in surgery patients during general anesthesia (7)(8)(9)(10)(11)(12) as well as critically ill patients in the ICU-and irrespective of the presence of ARDS (13)(14)(15)(16)44). It is uncertain if the sex difference in the use of LTVV also exists in patients with COVID-19.…”