The Effect of Varying Continuous Propofol Infusions on Plasma Cyclic Guanosine 3′,5′-Monophosphate Concentrations in Anesthetized Children

Abstract

The glutamate-nitric oxide-cyclic guanosine 3',5'-monophosphate (cGMP) pathway is potentially an effective target for general anesthetics. Plasma cGMP concentrations are reduced after an increase in predicted plasma propofol concentrations during sedation in healthy adult volunteers. We hypothesized that an increase in measured plasma propofol concentration leads to a reduction in plasma cGMP in anesthetized children. Eighteen healthy children aged 46.8 (+/-19.6) mo, requiring general anesthesia for lower body surgical procedures were enrolled. After inhaled induction, tracheal intubation and initiation of intermittent positive pressure ventilation, caudal epidural analgesia was performed. Anesthesia was maintained using a continuous propofol infusion adapted from a previously published regimen to achieve predicted propofol plasma concentration of 6, 3, and 1.5 microg/mL after 30, 50, and 70 min, respectively. Samples for propofol and cGMP plasma concentrations were collected and analyzed using high-performance liquid chromatography and an enzyme immunoassay system. The plasma cGMP concentrations varied significantly (median [range]) 19.2 [11.8-23.5], 21.3 [14.6-30.8], and 24.9 [15.7-37.8] nmol/L among each predicted plasma propofol concentration, P < 0.0001. The correlation coefficient (r) was -0.62. This study demonstrates that an increase in plasma propofol concentration leads to a decrease in plasma cGMP in healthy children, and could serve as a biochemical marker for depth of propofol anesthesia in children.