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It was the aim of this study was to investigate the optimum duration of hypercapnia. This point is assumed to be the time at which buffer systems become active, cause an adaptation to changes of the arterial partial pressure of carbon dioxide (PaCO<jats:sub>2<\/jats:sub>) and annihilate a possible therapeutic effect. In this prospective interventional study in a neurosurgical ICU the arterial partial pressure of carbon dioxide (PaCO<jats:sub>2<\/jats:sub>) was increased to a target range of 55\u00a0mmHg for 120\u00a0min by modification of the respiratory minute volume (RMV) one time a day between day 4 and 14 in 12 mechanically ventilated poor-grade SAH-patients. Arterial blood gases were measured every 15\u00a0min. CBF and brain tissue oxygen saturation (StiO<jats:sub>2<\/jats:sub>) were the primary and secondary end points. Intracranial pressure (ICP) was controlled by an external ventricular drainage. Under continuous hypercapnia (PaCO<jats:sub>2<\/jats:sub> of 53.17\u2009\u00b1\u20095.07), CBF was significantly elevated between 15 and 120\u00a0min after the start of hypercapnia. During the course of the trial intervention, cardiac output also increased significantly. To assess the direct effect of hypercapnia on brain perfusion, the increase of CBF was corrected by the parallel increase of cardiac output. The maximum direct CBF enhancing effect of hypercapnia of 32% was noted at 45\u00a0min after the start of hypercapnia. Thereafter, the CBF enhancing slowly declined. No relevant adverse effects were observed. CBF and StiO<jats:sub>2<\/jats:sub> reproducibly increased by controlled hypercapnia in all patients. After 45\u00a0min, the curve of CBF enhancement showed an inflection point when corrected by cardiac output. It is concluded that 45\u00a0min might be the optimum duration for a therapeutic use and may provide an optimal balance between the benefits of hypercapnia and risks of a negative rebound effect after return to normal ventilation parameters.<\/jats:p><jats:p><jats:bold>Trial registration:<\/jats:bold> The study was approved by the institutional ethics committee (AZ 230\/14) and registered at ClinicalTrials.gov (Trial-ID: NCT01799525). Registered 01\/01\/2015.<\/jats:p>","DOI":"10.1038\/s41598-021-91007-7","type":"journal-article","created":{"date-parts":[[2021,6,3]],"date-time":"2021-06-03T10:15:03Z","timestamp":1622715303000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":13,"title":["Therapeutic hypercapnia for prevention of secondary ischemia after severe subarachnoid hemorrhage: physiological responses to continuous hypercapnia"],"prefix":"10.1038","volume":"11","author":[{"given":"Christian","family":"Stetter","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Franziska","family":"Weidner","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nadine","family":"Lilla","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Judith","family":"Weiland","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ekkehard","family":"Kunze","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ralf-Ingo","family":"Ernestus","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ralf Michael","family":"Muellenbach","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Thomas","family":"Westermaier","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2021,6,3]]},"reference":[{"key":"91007_CR1","doi-asserted-by":"publisher","first-page":"915","DOI":"10.3171\/jns.1993.78.6.0915","volume":"78","author":"MN Diringer","year":"1993","unstructured":"Diringer, M. 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