Heybati, K

Abstract Rationale Lung-protective ventilation protocols use predicted body weight (PBW) to set tidal volumes. However, biases exist in these formulas, with overestimation of lung capacity in older, shorter, female, and non-White patients—groups that experience higher mortality rates during invasive mechanical ventilation (IMV). This study investigated associations between pre-admission forced vital capacity (FVC), driving pressure, and patient outcomes. Methods This multicenter retrospective study included adults (18-95 years old) with pre-admission spirometry who required IMV between 01/01/2016 and 05/31/2025 across the Mayo Clinic, spanning 11 ICUs within 5 hospitals in 4 states. Patients were stratified by FVC/PBW ratio quartiles. The primary outcome was 28-day mortality. Trends were assessed using linear or logistic regression, with FVC/PBW as a continuous variable. Mediation analysis examined pathways between FVC/PBW and mortality, with driving pressure (cm H2O, standardized) as the mediator, and adjusted for covariates including age, sex, SOFA score, and BMI. Absolute risk differences and number needed to harm (NNH) were estimated for key thresholds (e.g. FVC/PBW ≥45 mL/kg, PFTs within 2 years). Results Among 4,839 patients (38.7% female, mean (±SD) age 64.5±13.5 years), FVC/PBW ratio demonstrated substantial individual variation, with a mean of 48.3 ± 13.4 mL/kg. There was systematic variation by demographics (Figure): females had significantly lower ratios than males (45.4 versus 50.2 mL/kg, P < 0.001), and ratios were lower with older age from 52.5 mL/kg in patients <65 to 43.2 mL/kg in those ≥85 years (P < 0.001 for trend). Patients in the lowest FVC/PBW quartile had higher 28-day mortality compared to the highest quartile (26.0% versus 17.0%, P < 0.001) and higher driving pressures (14.0 versus 10.0 cm H2O, P < 0.001; Figure). In mediation analysis (n = 4,147), driving pressure mediated the relationship between FVC and mortality. Each 1-SD increase in FVC/PBW was associated with 0.364-SD lower driving pressure (P < 0.001) and 2.4% lower mortality. The adjusted indirect effect through driving pressure was significant (ACME -0.024, 95% CI: -0.029 to -0.019), accounting for the mortality effect. Sensitivity analyses across binary thresholds, age quartiles, outlier exclusion, and obstructive pathology confirmed robust mediation. Patients with FVC/PBW <45 mL/kg (N = 1,644; 39.6%) had 28-day mortality of 17.8% versus 13.5% for ≥45 mL/kg (risk difference 4.3%, 95% CI 1.8-6.8%; NNH: 23 patients). Conclusions Pre-admission lung function was strongly associated with mortality in adults receiving IMV through driving pressure-mediated pathways. Driving pressure is a modifiable target, especially in patients with smaller lung capacities at highest risk for ventilator-induced lung injury. Further prospective investigation is needed to confirm these findings. This abstract is funded by: National Heart, Lung, and Blood Institute (NHLBI) of the National Institute of Health (NIH) Grant Number K23HL151671

Abstract Rationale Major advances in precision medicine and immunotherapy have led to improved outcomes for patients with metastatic cancer, but have also introduced new, severe toxicities that can necessitate ICU admission. The overall mortality remains substantial; however, prior studies have often been single centered with small sample sizes. Therefore, we sought to provide an overview of the current literature with pooled estimates of short- and long-term mortality. Methods This study was registered a priori on Open Science Framework (10.17605/OSF.IO/438RY) and conducted per the Cochrane Handbook. A medical librarian searched MEDLINE, Embase, PubMed, Cochrane Central Register for Controlled Trials, supplemented by hand searching. Eligible studies included randomized and observational designs with >10 patients; studies were included if ≥ 70% of participants had metastatic disease when subgroup data were unavailable. The primary outcome was ICU mortality. Other outcomes included hospital, 30-day, 3-month, 6-month, and 12-month mortality. Pooled prevalence and 95% CIs were estimated using a random-effects model with Freeman-Tukey transformation. Risk of bias was assessed using the validated 10-item tool for prevalence studies. Results Of 4752 unique citations, 49 were included (N = 168,209). All studies were rated as having low risk of bias with the main threat to external validity being single-center design. Fourteen studies were multi-centered and 3 were multi-national, with the rest being single center. Across 23 studies (N = 2,918), the ICU mortality was 32% (95% CI: 25-39%; I2 = 89%; Figure 1). Across 5 studies (N = 400) with a focus on lung cancer, there was significantly higher ICU mortality (53% [43-64%]; I2 = 75% versus 26% [20-34%]; I2 = 86%; PQ = <0.01). Among 5 studies (N = 474) focusing on acute respiratory failure (ARF), ICU mortality was numerically higher but not statistically significant (49% [33-66%]; I2 = 91% versus 26% [20-34%]; I2 = 85%; PQ=0.07). Hospital mortality was 50% (44-56%; I2 = 99%; N = 157,682), 30-day mortality was 48% (39-57%; I2 = 84%; N = 1,067), 3-month mortality was 69% (62-74%; I2 = 80%; N = 1,296), 6-month mortality was 70% (59-79%; I2 = 91%; N = 1,310), and 12-month mortality was 84% (71-91%; I2 = 95%; N = 1,446; Figure 1). Conclusions Among critically ill adults with metastatic cancer, about one-third died in the ICU, half survived to hospital discharge, and 12-month mortality was 84%. There was considerable heterogeneity in mortality estimates, with worse outcomes in lung cancer. Given that ICU admission criteria and illness severity may differ, large multi-center studies are needed to clarify temporal trends and identify management strategies to improve outcomes. This abstract is funded by: None