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Cerebrovascular Reactivity to Carbon Dioxide Under Anesthesia: A Qualitative Systematic Review

Mariappan, Ramamani MD*; Mehta, Jigesh MD*; Chui, Jason MBChB, FANZCA, FHKCA; Manninen, Pirjo MD, FRCPC*; Venkatraghavan, Lashmi MD, FRCA, FRCPC*

Journal of Neurosurgical Anesthesiology: April 2015 - Volume 27 - Issue 2 - p 123–135
doi: 10.1097/ANA.0000000000000092
Review Articles

Introduction: Controlling the arterial carbon dioxide tension (PaCO2) to reduce the cerebral blood flow (CBF) and the intracranial pressure is a common practice in neuroanesthesia. A change in CBF in response to change in PaCO2 is termed as cerebrovascular reactivity to carbon dioxide (CVR-CO2). Studies have shown that, both inhalational and intravenous anesthetic agents have variable effects on CVR-CO2 and the effect of anesthetic agents on CVR also varies with many physiological and pathologic conditions. The objectives of this review were to evaluate the effect of anesthetic agents on the CVR-CO2 in adults and to determine how this response is modified by other physiological and pathologic factors.

Methods: We conducted a systematic search of the databases of Medline, Embase, Cochrane Central Register of Controlled Trials, and Cochrane Database of Systematic Reviews using related term components for both CVR-CO2 and anesthesia. Our primary outcome of this review was to determine whether the CVR-CO2 is maintained under anesthesia. The other endpoints of this review are to determine the effect of other factors (age, sex, medical comorbidities, and cerebrovascular pathology) on the CVR-CO2 under anesthesia. Because of the methodological heterogeneity in the primary studies, quantitative analysis of the data was not possible, and therefore, we have summarized the data qualitatively.

Results: Our search strategy yielded 1356 citations. After excluding nonpertinent papers, 38 studies were included for the systematic review. Nineteen randomized controlled trials and 19 observational studies met inclusion criteria and a total of 793 patients were studied. Transcranial Doppler was the most commonly used method for measuring CBF and changing the respiratory rate and/or minute ventilation were the most commonly used method to change the CO2 tension. CVR-CO2 is maintained with both inhalational and intravenous anesthetic agents within the range of concentrations used in clinical anesthesia. At doses leading to a broadly equivalent depth of anesthesia, the reactivity value was highest with isoflurane and the least with propofol. Individual agents differ in their degree of reactivity to hypercapnic and hypocapnic stimuli. CVR-CO2 is impaired in elderly patients when compared with young patients with both sevoflurane and propofol anesthesia. In patients with medical comorbidities, the CVR-CO2 impairment under anesthesia was associated with the severity of the underlying diseases and not the anesthetic agents.

Conclusions: Our systematic review showed that within the clinical anesthesia concentrations, CVR-CO2 is maintained under both propofol and inhalational agents. However, most of the information available is from non-neurosurgical patients and these studies also suffer from significant methodological heterogeneity. Therefore, we were limited by the amount and the quality of data available for this review.

Supplemental Digital Content is available in the text.

*Department of Anesthesia, Toronto Western Hospital, University Health Network, University of Toronto, Toronto

Department of Anesthesia and Perioperative Medicine, London Health Science Centre, University of Western Ontario, London, ON, Canada

Supplemental Digital Content is available for this article. Direct URL citations appear in the printed text and are provided in the HTML and PDF versions of this article on the journal's Website,

R.M. helped with study design, literature review, data entry, data analysis, and writing the manuscript. J.M. helped with literature search, data collection, and writing the manuscript. J.C. helped with literature review, data entry, and writing the manuscript. P.M. helped to write the manuscript. L.V. helped with study design, data analysis, and writing the manuscript. All the authors approved the final manuscript.

The authors have no funding or conflicts of interest to disclose.

Reprints: Lashmi Venkatraghavan, MD, FRCA, FRCPC, Department of Anesthesia, Toronto Western Hospital, University Health Network, University of Toronto, 399 Bathurst Street, Toronto, ON, Canada M5T 2S8 (e-mail:

Received March 2, 2014

Accepted June 25, 2014

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