Combined effects of nitrous oxide and propofol on the dynamic cerebrovascular response to step changes in end-tidal Pco2 in humans

Abstract

Background: Nitrous oxide (N2O) and propofol exhibit directionally opposite effects on the cerebral circulation, vasodilation and vasoconstriction, respectively. The authors investigated an interaction between the two anesthetic agents on the dynamic cerebrovascular response to step changes in end-tidal pressure of carbon dioxide (PETCO2) in humans. Methods: Participants with no systemic diseases were allocated into two groups, each of which was anesthetized sequentially with two protocols. Patients in group 1 were anesthetized with 30% O2 + 70% N2O. A continuous intravenous infusion of propofol (7-10 mg · kg-1 · h-1) was then added to the N2O. Patients in group 2 were anesthetized first with continuous infusion of propofol (10 mg · kg-1 · h-1), and then 30% O2 + 70% N2O was added to the propofol anesthesia. Using transcranial Doppler ultrasonography, blood flow velocity at the middle cerebral artery (FVMCA) was measured during a step increase (on-response) followed by a step decrease (off-response) in PETCO2, with PETCO2 ranging between approximately 28 and 50 mmHg. The dynamic FVMCA-PETCO2 relationship was analyzed using a mathematical model that was characterized with a pure time delay, and a time constant and a gain each for the on- or off-response. Results: The addition of propofol to the N2O anesthesia increased the on-response time constant (P < 0.01), whereas the addition of N2O to the propofol anesthesia increased the time constants for on- (P < 0.01) and off-responses (P < 0.05). However, the addition of either anesthetic did not affect the gains. Conclusions: Propofol and N2O, when one is added to the other, produce similar dynamic FVMCA responses to sudden changes in PETCO2. Addition of each anesthetic slows the dynamic response and produces the response whose magnitude is proportional to the baseline FVMCA.