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The effect of fenoldopam and dopexamine on hepatic blood flow and hepatic function following coronary artery bypass grafting with hypothermic cardiopulmonary bypass

Department of Cardiac Surgery, Cardiac Anaesthesia and Clinical Perfusion, Nottingham City Hospital, Hucknall Road, Nottingham NG5 1PB, United Kingdom

Received 17 June 2008; received in revised form 10 December 2008; accepted 12 January 2009.

^_* Corresponding author. Address: Department of Cardiac Surgery, Trent Cardiac Centre, Nottingham City Hospital, Hucknall Road, Nottingham NG5 1PB, United Kingdom. Tel.: +44 1159691169x56125; fax: +44 1158402605. (Email: arkrishnap{at}yahoo.com).

Background: Hypothermic cardiopulmonary bypass is associated with low perfusion state causing a mismatch between demand and supply to various organs such as gut, kidneys and brain. The consequences are thought to be responsible for postoperative complications like systemic inflammatory response, renal failure, neurological injury, etc. Pharmacological agents like dopamine, dopexamine and dobutamine have been used in an attempt to reduce hypoperfusion and hence complications. Fenoldopam, a dopamine analog (DA-1 receptor agonist), has recently been shown to be specific reno-splanchnic vasodilator in animal studies. We studied the haemodynamic effects of fenoldopam and its effect on hepatic blood flow (HBF) during and after cardiopulmonary bypass and compared these with dopexamine. Methods: Ethics committee approval was obtained. Forty-two consecutive patients with good/moderate left ventricular function undergoing either elective/urgent coronary artery bypass grafting were included in the study. Patients were randomised to receive either fenoldopam (0.2 µg/kg min) (F; n = 14) or dopexamine (2.0 µg/kg min) (Dx; n = 14) normal saline (NS; n = 14) continuously after induction of anaesthesia for 24 h following completion of surgery. HBF was measured using the Indocyanine green dye disappearance rate method, before, during and after cardiopulmonary bypass. Data were collected pre-, intra- and postoperatively. Serum liver enzymes were measured during the perioperative period. Repeated measures ANOVA test was used to compare timed samples in both groups. Results: The study groups were comparable in pre- and intraoperative variables. In the fenoldopam and dopexamine groups there was a significant increase in heart rate 15 min following the commencement of the infusion (NS:F:DX::–2.0 ± 7.8 beats/min:13.6 ± 8.1 beats/min (p = 0.007):18.36 ± 20.2 beats/min (p = 0.004)). However the change in mean arterial blood pressure was similar (NS:F:DX::–12.7 ± 14.9:–4.0 ± 23.1 (p = 0.699):–2.6 ± 22.3) (p = 0.235). Cardiac index increased and systemic vascular resistance decreased (requiring noradrenaline infusion) in the fenoldopam group, however this did not reach statistical significance. Hepatic blood flow reduced during CPB and returned to near preoperative levels in all three groups with no statistical difference between groups. Conclusions: Fenoldopam infusion induced transient tachycardia, with no augmentation of hepatic blood flow whereas dopexamine induced tachycardia and did not augment hepatic blood flow. Fenoldopam and dopexamine may have hepato-protective effect.

Key Words: Splanchnic perfusion • Cardiopulmonary bypass • Gut ischaemia • Liver function