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

Abstract

The purpose of this study was to compare and understand differences in the use of low tidal volume ventilation (LTVV) between females and males with acute respiratory distress syndrome (ARDS) related to coronavirus disease 2019 (COVID-19). This is a post-hoc analysis of an observational study in invasively ventilated patients with ARDS related to COVID-19 in 22 ICUs in the Netherlands. The primary endpoint was the use of LTVV, defined as having received a median tidal volume (VT) ≤6 ml/kg predicted body weight (PBW) during controlled ventilation. A mediation analysis was used to investigate the impact of anthropometric factors, next to the impact of sex per se. The analysis included 934 patients, 251 females and 683 males. All the patients had ARDS, and there were no differences in ARDS severity between the sexes. On the first day of ventilation, females received ventilation with a higher median VT compared with males [6.8 (interquartile range (IQR) 6.0–7.6 vs. 6.3 (IQR 5.8–6.9) ml/kg PBW; p < 0.001]. Consequently, females received LTVV less often than males (23 vs. 34%; p = 0.003). The difference in the use of LTVV became smaller but persisted over the next days (27 vs. 36%; p = 0.046 at day 2 and 28 vs. 38%; p = 0.030 at day 3). The difference in the use LTVV was significantly mediated by sex per se [average direct effect of the female sex, 7.5% (95% CI, 1.7–13.3%); p = 0.011] and by differences in the body height [average causal mediation effect, −17.5% (−21.5 to −13.5%); p < 0.001], but not by the differences in actual body weight [average causal mediation effect, 0.2% (−0.8 to 1.2%); p = 0.715]. In conclusion, in this cohort of patients with ARDS related to COVID-19, females received LTVV less often than males in the first days of invasive ventilation. The difference in the use of LTVV was mainly driven by an anthropometric factor, namely, body height. Use of LTVV may improve by paying attention to correct titration of VT, which should be based on PBW, which is a function of body height.

COVID‐19 is associated with bystander polyclonal autoreactive B cell activation as reflected by a broad autoantibody production, but none is linked to disease severity

“…It is well known that women are better at producing autoantibodies than men and are at higher risk for most autoimmune diseases. However, there is a sex difference in COVID‐19 severity that men tend to be more severe compared to women, 27,28 which may not be explained by autoantibody‐mediated COVID‐19 severity.…”

Decreased Utilization of Low Tidal Volume Ventilation Outside of the Intensive Care Unit as Compared to Inside

“…4–7 We believe these findings are also evidence that improving the utilization of LTVV within a hospital system is an achievable area of process improvement both inside and outside of ICUs. In prior literature, female sex and elevated BMI have frequently been reported as factors associated with inappropriately high tidal volumes, 12,18,49–53 our stratified analysis found that these subgroups were still more likely to receive LTVV inside the ICU than outside (Supplemental Figure 2).…”