Carbon Dioxide, Blood Pressure, and Perioperative Stroke

A Retrospective Case-Control Study

Phillip E. Vlisides, M.D., Graciela Mentz, Ph.D.; Aleda M. Leis, M.S.; Douglas Colquhoun, M.B.Ch.B., M.Sc., M.P.H.; Jonathon McBride, M.S., Bhiken I. Naik, M.B.B.Ch., M.S.C.R.; Lauren K. Dunn, M.D., Ph.D., Michael F. Aziz, M.D.; Kamila Vagnerova, M.D.; Clint Christensen, M.D.; Nathan L. Pace, M.D., M.Stat.; Jeffrey Horn, M.D.; Kenneth Cummings III, M.D.; Jacek Cywinski, M.D.; Annemarie Akkermans, M.D.; Sachin Kheterpal, M.D.; Laurel E. Moore, M.D.; George A. Mashour, M.D., Ph.D.


Anesthesiology. 2022;137(4):434-445. 

In This Article

Abstract and Introduction


Background: The relationship between intraoperative physiology and postoperative stroke is incompletely understood. Preliminary data suggest that either hypo- or hypercapnia coupled with reduced cerebrovascular inflow (e.g., due to hypotension) can lead to ischemia. This study tested the hypothesis that the combination of intraoperative hypotension and either hypo- or hypercarbia is associated with postoperative ischemic stroke.

Methods: We conducted a retrospective, case–control study via the Multicenter Perioperative Outcomes Group. Noncardiac, nonintracranial, and nonmajor vascular surgical cases (18 yr or older) were extracted from five major academic centers between January 2004 and December 2015. Ischemic stroke cases were identified via manual chart review and matched to controls (1:4). Time and reduction below key mean arterial blood pressure thresholds (less than 55 mmHg, less than 60 mmHg, less than 65 mmHg) and outside of specific end-tidal carbon dioxide thresholds (30 mmHg or less, 35 mmHg or less, 45 mmHg or greater) were calculated based on total area under the curve. The association between stroke and total area under the curve values was then tested while adjusting for relevant confounders.

Results: In total, 1,244,881 cases were analyzed. Among the cases that screened positive for stroke (n = 1,702), 126 were confirmed and successfully matched with 500 corresponding controls. Total area under the curve was significantly associated with stroke for all thresholds tested, with the strongest combination observed with mean arterial pressure less than 55 mmHg (adjusted odds ratio per 10 mmHg-min, 1.17 [95% CI, 1.10 to 1.23], P < 0.0001) and end-tidal carbon dioxide 45 mmHg or greater (adjusted odds ratio per 10 mmHg-min, 1.11 [95% CI, 1.10 to 1.11], P < 0.0001). There was no interaction effect observed between blood pressure and carbon dioxide.

Conclusions: Intraoperative hypotension and carbon dioxide dysregulation may each independently increase postoperative stroke risk.


Stroke is a potentially devastating surgical complication, with an incidence of up to 3% in high-risk noncardiac surgery populations.[1,2] Recent observational data also indicate that the risk of perioperative stroke, as detected by magnetic resonance imaging rather than clinical criteria, may be as high as 7% for older patients after noncardiac surgery.[3] Furthermore, postoperative stroke recognition is often delayed, and thrombolytic interventions are less commonly performed for surgical patients compared with stroke patients in the community setting.[4,5] Given the increased mortality, major disability, delayed diagnosis and treatment, and prolonged hospitalization,[1,4,5] identification of modifiable risk factors for perioperative stroke is of paramount importance.

Although several comorbidity-based preoperative risk factors have been identified,[1,6] there is a paucity of known intraoperative risk factors that may be modifiable. One such candidate risk factor is cerebral malperfusion. Emerging data suggest that intraoperative mean arterial pressure (MAP) may commonly fall below autoregulatory thresholds that maintain cerebral blood flow.[7,8] The combination of reduced cerebral perfusion (e.g., due to hypotension and compromised autoregulation) and impaired vasodilatory reserve (e.g., mediated by hypo- and hypercapnia) creates conditions for cerebral ischemia.[9] Indeed, functional magnetic resonance imaging data demonstrate that such vascular malperfusion can occur in watershed regions during periods of carbon dioxide dysregulation.[10] However, these data have been derived primarily from human volunteers, and it remains unclear whether the combination of hypotension and either hypo- or hypercarbia contributes to stroke risk in a surgical setting.

The primary objective of this study was therefore to determine the relationship between major perturbations in end-tidal carbon dioxide (ETco2), intraoperative hypotension, and postoperative ischemic stroke. Specifically, this study tested the hypothesis that the combination of intraoperative hypo- or hypercarbia and intraoperative hypotension—defined by specified total area under the curve thresholds—is associated with postoperative stroke. A multicenter electronic health record registry—with detailed intraoperative physiologic data—was used for retrospective data extraction.[11] A secondary objective was to identify stroke characteristics such as etiology, vascular territory affected, severity, management strategy, and outcomes.