Aiman Suleiman

Low tidal volume (Vt) ventilation is the standard of care among critically ill patients. Guidelines recommend scaling Vt to the predicted body weight (PBW) to avoid ventilator-induced lung injury (VILI). Concerns exist that the PBW overestimates lung volumes of critically ill females. We investigated whether this applies to clinically relevant measures of lung volume, whether PBW-guided mechanical ventilation yields comparable risk of lung stress among male and female patients, and whether this affects mortality. Mechanically ventilated, critically ill patients from ten randomized trials and two real-world retrospective clinical datasets were analyzed. Risk of high driving pressures (≥ 15 cmH₂O) at comparable Vt/kg PBW as well as measures of anatomical and functional lung sizes, including computed tomography-measured lung volumes at the same PBW were compared between female and male patients. Among 30,516 patients (39.4% female), ventilation with comparable tidal volumes standardized to PBW (ml/kg PBW) was associated with 4.2% (95% CI 3.2-5.3; aOR 1.26, 95% CI 1.19-1.33; p < 0.001) higher absolute risk of high driving pressures among females, mediating 8.4% of excess 28-day mortality (p < 0.001). At the same PBW, female patients had lower anatomical and aerated lung volumes (- 343 ml, 95% CI - 449 to - 237, p < 0.001; and - 188, 95% CI - 282 to - 94, p < 0.001, respectively) than males. The widely used PBW equation overestimates lung volumes in female critically ill patients, resulting in excess risk of injurious driving pressures among females, mediating higher mortality. Personalized mechanical ventilation by using driving pressure-guided strategies might mitigate these disparities.

Background: Acetaminophen and 5-hydroxytryptamine type 3 (5-HT₃) receptor antagonists are administered as standard prophylaxes for postoperative pain, nausea, and vomiting. Preclinical studies, however, suggest that 5-HT₃ antagonists may compromise acetaminophen’s analgesic effect. This hospital registry study investigates whether 5-HT₃ antagonists mitigate the analgesic effect of prophylactic acetaminophen in a perioperative setting. Methods: This study included 55,016 adult patients undergoing general anesthesia for ambulatory procedures at a tertiary healthcare center in Massachusetts from 2015 to 2022. Using binary exposure variables and a comprehensive selection of preplanned patient- and procedure-related covariates for confounder control, the authors investigated whether intraoperative 5-HT₃ antagonists affected the association between pre- or intraoperative acetaminophen and postoperative opioid consumption, gauged by opioid dose in milligram oral morphine equivalents (OME) administered in the postanesthesia care unit. A multivariable, zero-inflated negative binomial regression model was applied. Results: A total of 3,166 patients (5.8%) received only acetaminophen, 15,438 (28.1%) only 5-HT₃ antagonists, 31,850 (57.9%) both drugs, and 4,562 (8.3%) neither drug. The median postanesthesia care unit opioid dose was 7.5 mg OME (interquartile range, 7.5 to 14.3 mg OME) among 16,640 of 55,016 (30.2%) patients who received opioids, and the mean opioid dose was 3.2 mg OME across all patients (maximum cumulative dose, 20.4 mg OME). Acetaminophen administration was associated with a –5.5% (95% CI, –9.6 to –1.4%; P = 0.009; adjusted absolute difference, –0.19 mg OME; 95% CI, –0.33 to –0.05; P = 0.009) reduction in opioid consumption among patients who did not receive a 5-HT₃ antagonist, while there was no effect in patients who received a 5-HT₃ antagonist (adjusted absolute difference, 0.00 mg OME; 95% CI, –0.06 to 0.05; P = 0.93; P for interaction = 0.013). Conclusions: A dose-dependent association of pre- or intraoperative acetaminophen with decreased postoperative opioid consumption was not observed when 5-HT₃ antagonists were coadministered, suggesting that physicians might consider reserving 5-HT₃ antagonists as rescue medication for postoperative nausea or vomiting when acetaminophen is administered for pain prophylaxis. Editor’s Perspective: What We Already Know about This Topic: What This Article Tells Us That Is New: