Effect of diazepam on adenosine 3',5'-cyclic monophosphate (cAMP) plasma levels in anesthetized patients.
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.


CONCLUSIONS
In this preliminary study, diazepam increased cAMP plasma levels in anesthetized patients, presumably through inhibition of PDE4 activity.
Carceles
Maria D
MD
Department of Anesthesia, Hospital CSV Arrixaca, Spain.
Ribó
Antonio R
AR
Dávalos
Ramón
R
Martinez
Teresa
T
Hernández
Jesús
J
D015105:3',5'-Cyclic-AMP Phosphodiesterases / Q000037:antagonists & inhibitors; D000758:Anesthesia; D018686:Anesthetics, Intravenous / Q000009:adverse effects*; D000242:Cyclic AMP / Q000097:blood*; D054703:Cyclic Nucleotide Phosphodiesterases, Type 4; D003975:Diazepam / Q000009:adverse effects*; D004837:Epinephrine / Q000097:blood; D005260:Female; D006801:Humans; D007297:Inpatients; D008297:Male; D008875:Middle Aged; D009204:Myocardial Revascularization; D009638:Norepinephrine / Q000097:blood; D011446:Prospective Studies
D018686:Anesthetics, Intravenous; D000242:Cyclic AMP; D015105:3',5'-Cyclic-AMP Phosphodiesterases; D054703:Cyclic Nucleotide Phosphodiesterases, Type 4; D003975:Diazepam; D009638:Norepinephrine; D004837:Epinephrine