Effects of PaCO₂ derangements on clinical outcomes after cerebral injury: A systematic review

Objective: Partial pressure of arterial carbon dioxide (PaCO₂) is a major regulator of cerebral blood flow (CBF). Derangements in PaCO₂ have been thought to worsen clinical outcomes after many forms of cerebral injury by altering CBF. Our aim was to systematically analyze the biomedical literature to determine the effects of PaCO₂ derangements on clinical outcomes after cerebral injury. Methods: We performed a search of Cochrane Library, PUBMED, CINHAL, conference proceedings, and other sources using a comprehensive strategy. Study inclusion criteria were (1) human subjects; (2) cerebral injury; (3) mechanical ventilation post-injury; (4) measurement of PaCO₂; and (5) comparison of a clinical outcome measure (e.g. mortality) between different PaCO₂ exposures. We performed a qualitative analysis to collate and summarize effects of PaCO₂ derangements according to the recommended methodology from the Cochrane Handbook. Results: Seventeen studies involving different etiologies of cerebral injury (six traumatic brain injury, six post-cardiac arrest syndrome, two cerebral vascular accident, three neonatal ischemic encephalopathy) met all inclusion and no exclusion criteria. Three randomized control trials were identified and only one was considered a high quality study as per the Cochrane criteria for assessing risk of bias. In 13/17 (76%) studies examining hypocapnia, and 7/10 (70%) studies examining hypercapnia, the exposed group (hypercapnia or hypocapnia) was associated with poor clinical outcome. Conclusion: The majority of studies in this report found exposure to hypocapnia and hypercapnia after cerebral injury to be associated with poor clinical outcome. However, the optimal PaCO₂ range associated with good clinical outcome remains unclear.