Prophylactic use of the phospodiesterase III inhibitor enoximone in elderly cardiac surgery patients: effect on hemodynamics, inflammation, and markers of organ function.
OBJECTIVE
Elderly patients appear prone to develop overwhelming post-bypass inflammation and organ dysfunction. We assessed the effect of prophylactic administration of the phosphodiesterase III inhibitor enoximone on inflammation and organ function.


METHODS
Prospective, blinded, randomized, placebo-controlled study.


METHODS
Clinical investigations on a surgical intensive care unit.


METHODS
40 consecutive patients aged over 80 years undergoing first-time coronary artery bypass grafting.


METHODS
Enoximone was given to 20 patients after induction of anesthesia (initial bolus 0.5 mg/kg) followed by a continuous infusion of 2.5 micro g/kg per minute until the 2nd postoperative day. Control patients ( n=20) received saline solution.


RESULTS
Interleukins 6, 8, and 10 and soluble adhesion molecules were measured. Liver function was assessed by the monoethylglycine-xylidide test and by measuring alpha-glutathione S-transferase plasma levels; splanchnic perfusion by continuous gastric tonometry; renal function by measuring creatinine and alpha(1)-microglobulin. Interleukins increased significantly more in controls than in the enoximone-pretreated patients. Soluble adhesion molecules were significantly more increased in controls. Liver function was more altered in controls than in the enoximone-pretreated patients. alpha(1)-Microglobulin increased significantly more in controls than in the enoximone group, indicating less tubular damage in the verum group.


CONCLUSIONS
. Prophylactic use of enoximone in cardiac surgery patients aged over 80 years resulted in less post-bypass inflammation and improvement in markers of organ function than in the placebo group. The exact mechanisms by which enoximone exerts its beneficial effects in these patients remains to be elucidated.
Boldt
Joachim
J
Department of Anesthesiology and Intensive Care Medicine, Klinikum der Stadt Ludwigshafen, Bremserstrasse 79, 67063 Ludwigshafen, Germany. BoldtJ@gmx.net
Brosch
Christian
C
Suttner
Stefan
S
Piper
Sven N
SN
Lehmann
Andreas
A
Werling
Christiane
C
D015105:3',5'-Cyclic-AMP Phosphodiesterases / Q000037:antagonists & inhibitors*; D000368:Aged; D000369:Aged, 80 and over; D015415:Biomarkers / Q000032:analysis*; D002315:Cardiopulmonary Bypass / Q000009:adverse effects*; D054684:Cyclic Nucleotide Phosphodiesterases, Type 3; D017335:Enoximone / Q000494:pharmacology / Q000627:therapeutic use*; D005260:Female; D005858:Germany; D006439:Hemodynamics / Q000187:drug effects*; D006801:Humans; D007249:Inflammation / Q000188:drug therapy* / Q000209:etiology; D008297:Male; D010726:Phosphodiesterase Inhibitors / Q000494:pharmacology / Q000627:therapeutic use*; D010919:Placebos; D011446:Prospective Studies
D015415:Biomarkers; D010726:Phosphodiesterase Inhibitors; D010919:Placebos; D017335:Enoximone; D015105:3',5'-Cyclic-AMP Phosphodiesterases; D054684:Cyclic Nucleotide Phosphodiesterases, Type 3