Highlight
- In a cohort of over 82,000 critically ill patients in India, adjusted ICU and hospital mortality did not significantly differ between sexes.
- Females received less invasive organ support such as mechanical ventilation, kidney replacement therapy, and vasopressors compared to males.
- Females were more commonly treated with noninvasive ventilation, suggesting possible differences in clinical management approaches.
- These findings prompt consideration of potential sex-based differences in critical care delivery and outcomes in low- and middle-income country settings.
Study Background
Sex-based disparities in critical care have been explored predominantly in high-income countries, yet there remains limited evidence from diverse healthcare settings like India. Understanding whether biologic sex influences clinical outcomes in critical illness is important for ensuring equitable care and optimizing resource allocation. This study investigates associations between sex assigned at birth and clinical outcomes among critically ill adults admitted to intensive care units (ICUs) in India, a country characterized by varied health infrastructure and significant population heterogeneity. The potential impact of sex differences in receipt of organ support therapies and mortality is largely unexplored in this context.
Study Design
This retrospective registry-embedded cohort study utilized data from 45 ICUs participating in the Indian Registry of IntenSive care (IRIS). The cohort included 82,151 adults aged 16 years and older, admitted between unspecified dates. No interventions were administered as part of the study; patients were managed per usual clinical care. Sex assigned at birth was the primary exposure variable. The primary outcome was ICU mortality, with secondary outcomes including hospital mortality, use of mechanical ventilation (invasive and noninvasive), kidney replacement therapy, and vasopressor administration. Logistic regression models adjusted for prespecified baseline covariates assessed associations between sex and outcomes. Sensitivity analyses were performed to test robustness.
Key Findings
The cohort had a median age of 60 years (interquartile range 45–70), with females constituting 38.2% (31,409) of patients. Baseline characteristics including illness severity were similar between males and females.
Regarding mortality outcomes, ICU mortality was slightly lower in females (9.5%) compared to males (10.3%), but this difference was not statistically significant after adjustment (adjusted odds ratio [adjOR] 0.95; 95% CI, 0.90–1.00; p=0.07). Hospital mortality was comparable between females (19.4%) and males (20.8%) with an adjOR of 1.00 (95% CI, 0.97–1.03; p=0.66).
Use of organ support therapies differed by sex:
– Females were less likely to receive invasive mechanical ventilation (22.2% vs. 26.3%; adjOR 0.78; 95% CI, 0.75–0.82; p<0.001).
– Kidney replacement therapy was used less frequently among females (4.9% vs. 6.3%; adjOR 0.73; 95% CI, 0.68–0.78; p<0.001).
– Vasopressor use was marginally lower in females (19.1% vs. 20.2%; adjOR 0.95; 95% CI, 0.92–0.99; p=0.03).
– Conversely, females more commonly received noninvasive ventilation (11.7% vs. 9.7%; odds ratio 1.23; 95% CI, 1.18–1.30; p<0.001).
Sensitivity analyses confirmed these primary results, supporting their robustness across different model specifications.
Expert Commentary
This study is one of the largest evaluations of sex-based differences in critical care using a robust registry dataset from a lower-middle-income country. The lack of a significant mortality difference aligns with findings from some high-resource settings, where sex is not an independent predictor of ICU death after adjusting for confounders. However, the observation that females received less invasive organ support despite similar illness severity raises important questions about potential underlying clinical decision-making biases, patient preferences, access issues, or differences in presentation.
Biological factors such as sex hormones and immune responses are thought to influence susceptibility and outcomes in critical illness, but these do not fully explain observed practice patterns. Moreover, social and cultural factors relevant to the Indian healthcare context may contribute to differential treatment approaches by sex. The increased use of noninvasive ventilation in females may reflect clinician preference to limit invasive procedures or patient tolerance differences.
Limitations include the retrospective observational design, potential residual confounding, and lack of granular data on reasons for organ support decisions or long-term functional outcomes. Also, sex assigned at birth rather than gender identity was recorded, which may overlook additional psychosocial determinants of care equity.
Future research should focus on elucidating causes for these treatment disparities, including qualitative studies, and explore if modifying clinical practices could improve equity while maintaining outcomes.
Conclusion
In this large registry-embedded cohort of critically ill patients in India, females received fewer invasive organ support interventions but had similar adjusted ICU and hospital mortality compared with males. These findings highlight an important paradox warranting further investigation, as equitable access to life-saving intensive care should be a priority. Understanding and addressing sex-based differences in critical care delivery can inform policy and bedside practices in India and similar settings globally.
Funding and Clinical Trials
The study was conducted by the Indian Registry of IntenSive care (IRIS) collaboration. Specific funding details were not reported in the abstract. This was a retrospective registry analysis, and no interventional trial was registered.
References
1. Tirupakuzhi Vijayaraghavan BK, Patodia S, Gamage Dona D, et al; Indian Registry of IntenSive care (IRIS) collaboration. Association Between Sex and Clinical Outcomes for Critically Ill Patients in India: A Registry-Embedded Cohort Study. Crit Care Med. 2026 May 14;54(7):1647-1655. doi:10.1097/CCM.0000000000006001. PMID: 42132466.
2. Fowler RA, Sabur N, Li YY, et al. Sex- and gender-based differences in critical illness and intensive care. Crit Care Res Pract. 2017;2017:3912906.
3. Anesi GL, Moss M. Sex and gender differences in critical illness: challenges for evidence synthesis and implementation. Hosp Pract (1995). 2019;47(1):28-37.
4. Wunsch H, Linde-Zwirble WT, Angus DC, et al. The epidemiology of mechanical ventilation use in the United States. Crit Care Med. 2010;38(10):1947-53.
5. Knaus WA, Draper EA, Wagner DP, et al. APACHE II: a severity of disease classification system. Crit Care Med. 1985;13(10):818-29.
6. Kane HC. Gender bias in clinical decision making in critical care. J Intensive Care Soc. 2011;12(2):102-4.
