title: The prophylactic use of the beta-blocker esmolol in combination with phosphodiesterase III inhibitor enoximone in elderly cardiac surgery patients.
abstract: We assessed the influence of the prophylactic use of a combination of the IV beta-adrenergic blocker, esmolol, and the phosphodiesterase III inhibitor, enoximone, on postbypass hemodynamic status, inflammation, and endothelial and organ function in a prospective, randomized, placebo-controlled study in 42 patients aged >65 yr undergoing aortocoronary bypass grafting. In 21 patients, esmolol (aim: heart rate <70 bpm) plus enoximone (initial bolus of 0.5 mg/kg followed by a continuous infusion of 2.5 microg x kg(-1) x min(-1)) was started after induction of anesthesia and continued until the morning of the first postoperative day; another 21 patients received saline solution as placebo. Hemodynamics, splanchnic perfusion (gastric-arterial CO(2) gap), liver function (glutathione transferase-alpha plasma levels), renal function (creatinine clearance, urine concentrations of N-acetyl-beta-D-glucosaminidase), myocardial ischemia (creatine-kinase MB and troponin T plasma levels), inflammation (elastase, interleukin-6 and -8 plasma levels), and endothelial integrity (adhesion molecules plasma levels) were assessed at baseline, before and after cardiopulmonary bypass (CPB), and in the intensive care unit until the first postoperative day. Catecholamine requirements were significantly less in the treated than in the nontreated patients. Heart rate was significantly slower, cardiac index was higher, and gastric-arterial CO(2) gap was significantly lower in the treatment group. Troponin T, beta-N-acetyl-beta-D-glucosaminidase, glutathione transferase-alpha, and soluble adhesion molecules increased significantly in the untreated control, but remained almost normal in the esmolol+enoximone patients. Inflammatory responses (elastase/interleukins) were attenuated by esmolol+enoximone. We conclude that, in comparison to an untreated control, the prophylactic use of a combination of esmolol and enoximone in elderly patients undergoing cardiac surgery with cardiopulmonary bypass resulted in overall beneficial effects on postbypass hemodynamic status, organ function, inflammatory response, and endothelial integrity.
authors.affiliation: Departments of *Anesthesiology and Intensive Care Medicine and †Cardiac Surgery, Klinikum der Stadt Ludwigshafen, Ludwigshafen, Germany.
authors.forename: Joachim
authors.initials: J
authors.lastname: Boldt
authors.forename: Christian
authors.initials: C
authors.lastname: Brosch
authors.forename: Andreas
authors.initials: A
authors.lastname: Lehmann
authors.forename: Stephan
authors.initials: S
authors.lastname: Suttner
authors.forename: Frank
authors.initials: F
authors.lastname: Isgro
mesh_terms: D015105:3',5'-Cyclic-AMP Phosphodiesterases / Q000378:metabolism*; D000319:Adrenergic beta-Antagonists / Q000627:therapeutic use*; D000368:Aged; D015415:Biomarkers; D001784:Blood Gas Analysis; D006348:Cardiac Surgical Procedures / Q000009:adverse effects*; D002315:Cardiopulmonary Bypass / Q000009:adverse effects; D054684:Cyclic Nucleotide Phosphodiesterases, Type 3; D004730:Endothelium, Vascular / Q000502:physiology; D017335:Enoximone / Q000627:therapeutic use*; D005260:Female; D005982:Glutathione Transferase / Q000378:metabolism; D006339:Heart Rate / Q000187:drug effects / Q000502:physiology; D006439:Hemodynamics / Q000187:drug effects; D006801:Humans; D007249:Inflammation / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control; D007677:Kidney Function Tests; D008297:Male; D016343:Monitoring, Intraoperative; D017202:Myocardial Ischemia / Q000378:metabolism / Q000503:physiopathology / Q000517:prevention & control; D010726:Phosphodiesterase Inhibitors / Q000627:therapeutic use*; D011183:Postoperative Complications / Q000473:pathology / Q000517:prevention & control*; D011412:Propanolamines / Q000627:therapeutic use*; D013152:Splanchnic Circulation / Q000502:physiology
chemical_list: D000319:Adrenergic beta-Antagonists; D015415:Biomarkers; D010726:Phosphodiesterase Inhibitors; D011412:Propanolamines; D017335:Enoximone; D005982:Glutathione Transferase; D015105:3',5'-Cyclic-AMP Phosphodiesterases; D054684:Cyclic Nucleotide Phosphodiesterases, Type 3; C036604:esmolol