Objectives The effects of hypercapnia on regional cerebral oxygen saturation (rSOdos) during surgery are unclear. We conducted a randomised controlled trial to investigate the relationship between mild hypercapnia and rSO2. We hypothesised that, compared with targeted normocapnia (TN), targeted mild hypercapnia (TMH) during major surgery would increase rSO2.
Interventions TMH (partial pressure of carbon dioxide in arterial blood, PaCO2, 45–55 mm Hg) or TN (PaCO2 35–40 mm Hg) was delivered via controlled ventilation throughout surgery.
Primary and secondary outcome measures The primary endpoint was the absolute difference between the two groups in percentage change in rSO2 from baseline to completion of surgery. Secondary endpoints included intraoperative pH, bicarbonate concentration, base excess, serum potassium concentration, incidence of postoperative delirium and length of stay (LOS) in hospital.
Importance and you will limitations with the data
Results The absolute difference between the two groups in percentage change in rSO2 from the baseline to the completion of surgery was 19.0% higher in both hemispheres with TMH (p<0.001). On both sides, the percentage change in rSO2 was greater in the TMH group than the TN group throughout the duration of surgery. The difference between the groups became more noticeable over time. Furthermore, postoperative delirium was higher in the TN group (risk difference 0.3, 95% CI 0.1 to 0.5, p=0.02). LOS was similar between groups (5 days vs 5 days; p=0.99).
Conclusion TMH was associated with a stable increase in rSO2 from the baseline, while TN was associated with a decrease in rSO2 in both hemispheres in patients undergoing major surgery. This resulted in a clear separation of percentage change in rSO2 from the baseline between TMH and TN over time. Our findings provide the rationale for larger studies on TMH during surgery.
- delirium
- hypercapnia
- oximetry
- breathing, phony
- spectroscopy, close infrared
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Inclusion
In patients undergoing major surgery, the effects of mild hypercapnia on regional cerebral oxygen saturation (rSO2) have not been fully examined, and any beneficial or harmful effects of hypercapnia as a therapeutic ventilation strategy to improve cerebral oxygenation are unknown. In animal models, CO2 is a well-known vasodilator, improving cerebral blood flow.1–3 The neuroprotective mechanisms of mild hypercapnia, while 
not completely understood, have been postulated to be a result of an increase in cerebral blood flow, enhancement of oxygen delivery, improvements in cerebral glucose use and oxidative metabolism4 5 and activation of adenosine triphosphate-sensitive potassium channels to maintain normal neuronal activity in the setting of ischaemia.6
The recent emergence of near-infrared spectroscopy (NIRS) cerebral oximetry has provided a practical method to measure rSO2 continuously and non-invasively. This technology has gained substantial supportive evidence in resuscitation, critical care and surgical applications.7–9 Numerous studies have shown that NIRS can be applied clinically in the resuscitation and cardiac surgery settings, where cerebral desaturation events can be both effectively monitored and managed.10–13 However, while absolute and relative saturation thresholds theoretically requiring prompt interventions have been proposed,14 these thresholds have not been validated, and there is a lack of consensus on the indication and timing of interventions. In patients undergoing surgery, rSO2 was reported to be higher with mild hypercapnia; however, the intraoperative temporal relationship between rSO2 and mild hypercapnia remains unclear.15
Accordingly, we conducted a randomised controlled trial to test the hypothesis that targeted mild hypercapnia (TMH), defined as the partial pressure of carbon dioxide in arterial blood (PaCO2) between 45 and 55 mm Hg, during elective major surgery would increase cerebral oxygen saturation compared with targeted normocapnia (TN), defined as PaCO2 between 35 and 40 mm Hg. As a secondary aim, we evaluated whether TMH would affect the development of postoperative delirium, a commonly reported complication that is linked to functional decline, institutionalisation and higher mortality.16–18