Plasma cyclic guanosine 3',5'-monophosphate levels: a marker of glutamate-nitric
oxide-guanyl cyclase activity?
Author(s): Engelhardt T, Zaarour C, Crawford MW.
Affiliation(s): Department of Anesthesia and Pain Medicine, The Hospital for Sick Children,
University of Toronto, Ontario, Canada.
Publication date & source: 2011, J Opioid Manag. , 7(6):462-6
OBJECTIVES: Remifentanil-based anesthesia can lead to acute opioid tolerance
and/or hyperalgesia. A low-dose intraoperative infusion of the
N-methyl-D-aspartate (NMDA) receptor antagonist ketamine did not result in
reduced postoperative morphine consumption after remifentanil-based anesthesia in
adolescents. This study investigates the potential role of the glutamate-nitric
oxide-cyclic guanosine 3'5'-monophosphate (cyclic GMP) pathway in the failure of
low-dose ketamine to prevent remifentanil-induced acute opioid tolerance and/or
hyperalgesia.
DESIGN AND SETTING: Prospective, double-blind, placebo-controlled randomized
clinical trial at a university teaching hospital. PATIENTS, PARTICIPANTS, AND
INTERVENTIONS: Thirty-four adolescents receiving remifentanil-based anesthesia
for surgical correction of idiopathic scoliosis were randomly assigned to receive
either intraoperative ketamine administered as a bolus dose of 0.5 mg/kg in 10 mL
of normal saline and a continuous intravenous infusion of 4.0 microg/kg/min or an
equal volume of saline. Main outcome measures: Blood samples were collected
before and after the administration of ketamine for analyzing the concentrations
of cyclic GMP, ketamine, and norketamine. Blood samples were analyzed using
high-performance liquid chromatography and an enzyme immunoassay.
RESULTS: The median (interquartile range) value of the concentration of plasma
cyclic GMP decreased from 23.7 (17.4-26.7) to 14.8 (14.0-17.3) nmol/L after
ketamine infusion (p < 0.005) and from 23.9 (16.3-29.2) to 163 (14.5-18.6) nmol/L
after saline infusion (p < 0.005). The median value of the concentration of
plasma cyclic GMP at the end of ketamine infusion did not differ significantly
when compared with that after saline infusion (p = 0.07). The concentration of
plasma cyclic GMP was inversely correlated with the concentration of plasma
ketamine (r = -0.61).
CONCLUSIONS: This study suggests that the low dose of intraoperative ketamine
infused was insufficient to suppress the NMDA receptor pathway. The
concentrations of plasma cyclic GMP may serve as an indirect biological marker of
ketamine-induced NMDA receptor antagonism.
|
