Journal: J Cardiothorac Vasc Anesth 22(5):699-705, 2008.
Reprint: Dept of Anesthesiology, Division of Cardiothoracic and Vascular Anesthesiology, Academic Medical Center, University of Amsterdam, Meibergdreef 9, 1100 AZ Amsterdam, The Netherlands (SG De Hert, MD)
Faculty Disclosure: Abstracted by T. Tilton, who has nothing to disclose.
Levosimendan enhances myofilament responsiveness to calcium by binding to cardiac troponin C (increases myocardial contraction without increasing myocardial oxygen consumption) and produces coronary and peripheral vasodilation by activation of mitochondrial KATP channels in the vascular smooth muscle cells. The authors hypothesized that in cardiac surgery patients with severely compromised myocardial function, hemodynamic support with levosimendan initiated before cardiopulmonary bypass (CPB) would result in better postoperative function with less myocardial damage than with the usual practice of administering levosimendan after CPB.
Patients were randomly divided into 3 groups. All patients received dobutamine, 5 mcg/kg/min, initiated after release of the aortic cross-clamp; and either milrinone, 0.5 mcg/kg/min after release of cross-clamp (group A) or levosimendan 0.1 mcg/kg/min after induction of anesthesia (group B), or after cross-clamp release (group C). All cardiac medications were continued until the morning of surgery except for angiotensin-converting enzyme inhibitors, clopidogrel, and aspirin. Preoperative medication consisted of 2.5 mg sublingual lorazepam with intramuscular fentanyl, 1 mcg/kg/min, and glycopyrrolate, 50 mcg/kg. Induction and maintenance consisted of remifentanil and sevoflurane. Other intraoperative medications were methylprednisolone and aprotinin. Following release of the cross-clamp, a cardiac index <2.5 L/min/m2 was treated by increasing the dobutamine up to a maximum of 10 mcg/kg/min. Persistent hypotension was treated with norepinephrine 0.1 mcg/kg/min.
Demographics were similar between groups (n=20 each group). Six patients in each group required preoperative intra-aortic balloon pump for hemodynamic support. Heart rate, central venous pressure, and mean arterial pressures were not different between groups; stroke volume (SV) was significantly higher in group B versus the other two post-CPB and higher than group A upon arrival to the ICU. Twelve hours after ICU arrival, SV was higher in group B and C. Administration of the study drug continued for 72 ± 41 hr with milrinone versus 22 ± 4 hr and 23 ± 3 hr in the levosimendan groups (p<0.001). Total dosing and duration of administration was also higher in group A.
Troponin I levels were not significantly different between groups. All cardiac isoenzymes were significantly increased compared to baseline except creatinine; group A had significantly higher levels than groups B and C. Duration of tracheal intubation and total hospitalization were longer in group A. The incidence of postoperative atrial fibrillation was significantly lower in group B (10 in group A, 1 in group B, and 7 in group C). Death occurred in 4 patients in group A and in 1 patient in group C within 30 days of surgery.
Initiating levosimendan before CPB was associated with a higher initial SV and a lower incidence of atrial fibrillation. No effect on troponin I release was noted. Further research is needed to identify whether this effect is also associated with better postoperative outcome. |
