{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T06:01:46Z","timestamp":1790834506524,"version":"4.1.0"},"reference-count":23,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T00:00:00Z","timestamp":1790812800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Med."],"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Intraoperative hypotension reduces cerebral perfusion pressure, whereas hypocapnia may reflect either ventilation-related cerebral vasoconstriction or reduced pulmonary perfusion during a low-flow state. We evaluated whether the time-weighted overlap of hypotension and hypocapnia was associated with adverse postoperative outcomes after major open intracranial surgery.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      We conducted a retrospective cohort study using INSPIRE version 1.4.2. Adults undergoing major open intracranial surgery were included if mean arterial pressure (MAP) and end-tidal carbon dioxide (EtCO\n                      <jats:sub>2<\/jats:sub>\n                      ) had at least 80% synchronous coverage. Dual-hit cerebral hypoperfusion burden (DHCB) was defined as the proportion of synchronously valid monitoring time with simultaneous MAP &amp;lt;65\u2005mmHg and EtCO\n                      <jats:sub>2<\/jats:sub>\n                      \u2009&amp;lt;\u200930\u2005mmHg. The primary outcome was a composite of in-hospital death, postoperative intensive care unit stay of at least 2 days, or prolonged postoperative hospitalization. Patient-clustered multivariable logistic regression simultaneously modeled hypotension-only, hypocapnia-only, and concurrent exposure burdens.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      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\u20131.28;\n                      <jats:italic>P<\/jats:italic>\n                      \u2009&amp;lt;\u20090.001), 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 (\n                      <jats:italic>P<\/jats:italic>\n                      \u2009&amp;lt;\u20090.001) but no significant evidence of nonlinearity (\n                      <jats:italic>P<\/jats:italic>\n                      for nonlinearity\u2009=\u20090.143). The standardized risk increased from 27.3% at DHCB\u2009=\u20090% to 45.6% at DHCB\u2009=\u200930%, although estimates at higher burdens were less precise.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats: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.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fmed.2026.1946283","type":"journal-article","created":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T05:42:06Z","timestamp":1790833326000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Temporal overlap of intraoperative hypotension and hypocapnia and postoperative outcomes after major open intracranial surgery: a time-weighted dual-hit cohort study"],"prefix":"10.3389","volume":"13","author":[{"given":"Xing","family":"Yan","sequence":"first","affiliation":[{"name":"Hunan Key Laboratory of the Research and Development of Novel Pharmaceutical Preparations, School of Public Health, Changsha Medical University","place":["Changsha, China"]},{"name":"Hunan Provincial University Key Laboratory of the Fundamental and Clinical Research on Neurodegenerative Diseases, Changsha Medical University","place":["Changsha, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xuemin","family":"Zou","sequence":"additional","affiliation":[{"name":"Hunan Key Laboratory of the Research and Development of Novel Pharmaceutical Preparations, School of Public Health, Changsha Medical University","place":["Changsha, China"]},{"name":"Hunan Provincial University Key Laboratory of the Fundamental and Clinical Research on Neurodegenerative Diseases, Changsha Medical University","place":["Changsha, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ruowen","family":"Yang","sequence":"additional","affiliation":[{"name":"Hunan Key Laboratory of the Research and Development of Novel Pharmaceutical Preparations, School of Public Health, Changsha Medical University","place":["Changsha, China"]},{"name":"Hunan Provincial University Key Laboratory of the Fundamental and Clinical Research on Neurodegenerative Diseases, Changsha Medical University","place":["Changsha, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jinyun","family":"Wang","sequence":"additional","affiliation":[{"name":"Hunan Key Laboratory of the Research and Development of Novel Pharmaceutical Preparations, School of Public Health, Changsha Medical University","place":["Changsha, China"]},{"name":"Hunan Provincial University Key Laboratory of the Fundamental and Clinical Research on Neurodegenerative Diseases, Changsha Medical University","place":["Changsha, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lemei","family":"Zhu","sequence":"additional","affiliation":[{"name":"Hunan Key Laboratory of the Research and Development of Novel Pharmaceutical Preparations, School of Public Health, Changsha Medical University","place":["Changsha, China"]},{"name":"Hunan Provincial University Key Laboratory of the Fundamental and Clinical Research on Neurodegenerative Diseases, Changsha Medical University","place":["Changsha, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,10,1]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"3463","DOI":"10.1113\/JP272012","article-title":"Carbon dioxide-mediated vasomotion of extra-cranial cerebral arteries in humans: a role for prostaglandins?","volume":"594","author":"Hoiland","year":"2016","journal-title":"J Physiol (Lond)"},{"key":"B2","doi-asserted-by":"publisher","first-page":"456","DOI":"10.1177\/106002809002400501","article-title":"Hyperventilation-induced reduction in cerebral blood flow: assessment by positron emission tomography","volume":"24","author":"Bednarczyk","year":"1990","journal-title":"DICP"},{"key":"B3","doi-asserted-by":"publisher","first-page":"132","DOI":"10.1097\/ANA.0b013e3181c9fbf1","article-title":"Cerebral autoregulation and CO2 reactivity before and after elective supratentorial tumor resection","volume":"22","author":"Sharma","year":"2010","journal-title":"J Neurosurg Anesthesiol"},{"key":"B4","doi-asserted-by":"publisher","first-page":"585","DOI":"10.1213\/01.ane.0000295804.41688.8a","article-title":"Does hyperventilation improve operating condition during supratentorial craniotomy? 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