Supplementary file 1_Temporal overlap of intraoperative hypotension and hypocapnia and postoperative outcomes after major open intracranial surgery: a time-weighted dual-hit cohort study.docx

Patient-clustered multivariable logistic regression simultaneously modeled hypotension-only, hypocapnia-only, and concurrent exposure burdens.</p>Results<p>The final cohort included 2,286 operations in 2,092 patients. Concurrent hypotension and hypocapnia occurred in 708 operations (31.0%), and the composite outcome occurred after 676 operations (29.6%). Each 5-percentage-point increase in DHCB was associated with higher odds of the composite outcome (adjusted odds ratio, 1.19; 95% CI, 1.10–1.28; P < 0.001), whereas hypotension-only and hypocapnia-only burdens were not independently associated with the outcome.

Adding DHCB improved model fit but only minimally increased apparent discrimination (C-statistic, 0.764 to 0.767). Results remained consistent across progressively adjusted and sensitivity analyses. Restricted cubic spline analysis showed an overall association (P < 0.001) but no significant evidence of nonlinearity (P for nonlinearity = 0.143).

The standardized risk increased from 27.3% at DHCB = 0% to 45.6% at DHCB = 30%, although estimates at higher burdens were less precise.</p>Conclusions<p>Greater temporal overlap between intraoperative hypotension and hypocapnia was associated with adverse short-term postoperative outcomes beyond the corresponding non-overlapping exposure burdens. DHCB should be interpreted as a hypothesis-generating marker of concurrent physiological exposure rather than evidence of two independent causal insults, and requires external validation with neurologically specific outcomes before clinical application.</p>