Does phosphodiesterase III inhibition reverse the cardiodepressive effects of propofol?
Propofol decreases arterial blood pressure as a result of reduced cardiac output and peripheral vasodilation, raising concerns about its safety in patients with impaired cardiovascular function. Phosphodiesterase III inhibitors (PDE-III-Inh) have gained attention as inotropic drugs. We therefore studied whether the cardiac effects of propofol could be abrogated by enoximone. Twenty-one patients with moderately reduced cardiac function scheduled for major surgery were allocated to this randomized, double-blind, placebo-controlled study. Measurement of cardiovascular data was performed before induction, 15 min after initiation of total intravenous anesthesia, 15 min after a first bolus of 0.25 mg/kg enoximone or placebo, and 15 min after a second bolus of 0.25 mg/kg enoximone or placebo. Propofol led to the expected reduction of cardiac output and bradycardia. Both doses of enoximone increased the cardiac index, reaching nearly preinduction values at a cumulative dose of 0.5 mg/kg enoximone. This change was primarily the result of significantly increased heart rate rather than increased ejection fraction or stroke volume index. Mean arterial pressure remained constant, which indicates uncompromised coronary perfusion pressure. Based on our results, we cannot recommend enoximone for the treatment of propofol-induced cardiac impairment.


CONCLUSIONS
Total intravenous anesthesia with propofol is used increasingly in patients with impaired cardiac function. Enoximone, a drug suggested for congestive heart failure, had no effect on stroke volume or mean arterial pressure, but it increased heart rate. Enoximone is not recommended to treat impairment of cardiac function in patients anesthetized with propofol.
Pernerstorfer
T
T
Department of Clinical Pharmacology, Vienna General Hospital, University of Vienna, Austria.
Mayer
N
N
Jilma
B
B
Krenn
C G
CG
Bayer
G S
GS
Eichler
H G
HG
D000328:Adult; D000368:Aged; D001794:Blood Pressure / Q000187:drug effects; D003864:Depression, Chemical; D004311:Double-Blind Method; D017335:Enoximone / Q000494:pharmacology*; D005260:Female; D006321:Heart / Q000187:drug effects* / Q000502:physiology; D006801:Humans; D008297:Male; D008875:Middle Aged; D010726:Phosphodiesterase Inhibitors / Q000494:pharmacology*; D015742:Propofol / Q000009:adverse effects*
D010726:Phosphodiesterase Inhibitors; D017335:Enoximone; D015742:Propofol