Background: It has been previously demonstrated that diazepam inhibits the cyclic nucleotide phosphodiesterase type 4 isozyme (PDE4). PDE enzymes mediate the hydrolysis of the nucleotide adenosine 3',5'-cyclic monophosphate (cAMP).
Objective: The aim of this study was to determine whether IV administration of diazepam affects cAMP plasma levels in anesthetized patients.
Methods: In this prospective study, patients scheduled to undergo elective myocardial revascularization surgery with anesthetization with etomidate (0.3 mg/kg), fentanyl (total dose 20-25 microg/kg), and cisatracurium (150 microg/kg), supplemented with sevoflurane (2% in an oxygen/air mixture), were randomly assigned to 1 of 3 groups to receive diazepam (0.28 mg/kg IV), diazepam vehicle (alcohol and propylene glycol IV), or saline. Before the start of the surgical procedure, at 5 and 10 minutes after administration of diazepam, vehicle, or saline, blood samples were obtained for determination of the diazepam, cAMP, and catecholamine levels.
Results: Ten patients received diazepam, 10 received vehicle, and 5 received saline. The mean (SEM) arterial serum concentrations of diazepam were 2.1 (0.2) microg/mL and 1.1 (0.4) microg/mL, respectively, at 5 and 10 minutes after administration. cAMP plasma levels increased from mean (SEM) baseline values of 30.0 (1.7) nmol/L to 35.5 (1.5) nmol/L (P < 0.05) and 43.1 (1.7) nmol/L (P < 0.05) at 5 and 10 minutes, respectively, after diazepam administration. No significant changes in cAMP plasma levels were observed compared with the mean (SEM) baseline value of 32.0 (1.7) nmol/L at 5 minutes (31.8 [1.3] nmol/L) and 10 minutes (30.9 [1.4] nmol/L) after vehicle administration. Epinephrine plasma concentration increased from a mean (SEM) baseline value of 0.13 (0.02) ng/mL to 0.22 (0.02) ng/mL (P < 0.05) at 10 minutes after administration of vehicle and 0.21 (0.02) ng/mL (P < 0.05) at 10 minutes after administration of diazepam.
Conclusion: In this preliminary study, diazepam increased cAMP plasma levels in anesthetized patients, presumably through inhibition of PDE4 activity.
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