Carbon Dioxide, Blood Pressure, and Perioperative Stroke: A Retrospective Case–Control Study

Abstract

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. Non-cardiac, non-intracranial, and non-major vascular surgical cases (age ≥18 years) 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 (<55 mmHg, <60 mmHg, <65 mmHg) and outside of specific end-tidal carbon dioxide thresholds (≤30 mmHg, ≤35 mmHg, ≥45 mmHg) 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 MAP <55 mmHg (adjusted odds ratio per 10 mmHg-min, 1.17 [95% confidence interval, 1.10 – 1.23], p<0.0001) and end-tidal carbon dioxide ≥45 mmHg (adjusted odds ratio per 10 mmHg-min, 1.11 [95% confidence interval, 1.10 – 1.11], p<0.0001). There was no interaction effect observed between blood pressure and carbon dioxide. Conclusion Intraoperative hypotension and carbon dioxide dysregulation may each independently increase postoperative stroke risk.

Carbon Dioxide, Blood Pressure, and Stroke: Comment

“…In their article, Vlisides et al . 1 present retrospective associations between hypotension, hypocarbia, and hypercarbia and clinically apparent postoperative strokes, with 122 used in the analysis. (Covert strokes are nearly 10 times as common, 2 but were not considered.)…”

“…Sessler W e thank Dr. Sessler 1 for his interest in our article. 2 Stroke is a devastating complication for surgical patients and a challenging outcome to study. Dr. Sessler raises important points, and we welcome the opportunity to engage in constructive dialogue to raise clinical and scientific awareness of this important topic.…”

“…Last, it is important that we provide readers with the complete last sentence of our published article: "These physiologic perturbations may serve as risk factors that can be modified to reduce the incidence of postoperative stroke." 2 This sentence was modified and misquoted in Dr. Sessler's letter to the editor in a way that misrepresents the causal significance we ascribed to the findings. Indeed, hypotension and dyscarbia may serve as stroke risk factors, but confirmatory, prospective trials are ultimately required, as we originally stated in our article.…”

Year in Review: Synopsis of Selected Articles in Neuroanesthesia and Neurocritical Care from 2022

“…30 In the pursuit of finding intraoperative risk factors, Vlisides et al conducted a multicenter, retrospective, observational case-control study to find the relationship between changes in intraoperative EtCO 2 , hypotension and perioperative ischemic stroke (within 30 days after surgery) in adult patients scheduled for noncardiac, nonintracranial, and nonmajor vascular surgeries. 31 One of the physiologic basis of their study was that reduced cerebral blood flow (due to hypotension) and carbon dioxide dysregulation can lead to watershed infarction by hypoperfusion or impaired clearance of microemboli. 32 In this study, they included 122 patients with stroke and 496 matched (1:4) controls.…”

Carbon Dioxide, Blood Pressure, and Stroke: Reply

“…11 These adjustments were made in addition to the Mahalanobis distance case-control matching process described in our prespecified analysis plan. 12 Thus, while residual confounding is certainly a possibility, we used mitigation strategies targeted to both comorbid and physiologic confounding where possible.…”