The effect of varying continuous propofol infusions on plasma cyclic guanosine 3',5'-monophosphate concentrations in anesthetized children.
BACKGROUND
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.


METHODS
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.


RESULTS
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.


CONCLUSIONS
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.
Engelhardt
Thomas
T
Department of Anaesthesia and Laboratory Medicine, The Hospital for Sick Children, University of Toronto, Toronto, Ontario, Canada. t.engelhardt@nhs.net
Chan
Man K
MK
McCheyne
Alan J
AJ
Karsli
Cengiz
C
Luginbuehl
Igor
I
Bissonnette
Bruno
B
D018686:Anesthetics, Intravenous / Q000008:administration & dosage* / Q000097:blood; D015415:Biomarkers / Q000097:blood; D002675:Child, Preschool; D002851:Chromatography, High Pressure Liquid; D003243:Consciousness / Q000187:drug effects*; D006152:Cyclic GMP / Q000097:blood*; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D015536:Down-Regulation; D004569:Electroencephalography; D006801:Humans; D007124:Immunoenzyme Techniques; D015742:Propofol / Q000008:administration & dosage* / Q000097:blood; D011446:Prospective Studies; D015398:Signal Transduction / Q000187:drug effects*; D013514:Surgical Procedures, Operative
D018686:Anesthetics, Intravenous; D015415:Biomarkers; D006152:Cyclic GMP; D015742:Propofol