Introduction 1 2  2 3 Despite a wide range of available inotropic agents, no consensus exists regarding the treatment of LCOS post-CPB. This review examines the pharmacological options for providing inotropic support in the period after CPB and evaluates the literature systematically in order to establish, present and classify the available evidence regarding the use of inotropic drugs after cardiac surgery in adults. We do not discuss exclusive or mostly vasopressor drugs such as vasopressin and norepinephrine (noradrenaline). Methods We conducted a systematic Medline and PubMed search, over the period 1982–2003, using the following keywords: cardiac surgery, cardiopulmonary bypass, coronary artery bypass grafting, inotropic support, epinephrine, dopamine, dopexamine, dobutamine, amrinone, enoximone, milrinone and levosimendan. Agents considered to be primarily vasopressors (e.g. norepinephrine, arginine vasopressin and phenylephrine) and mechanical support (e.g. intra-aortic balloon counter-pulsation and assist devices) are not considered. For reasons of space and the likelihood that they would behave like other agents in their class, the more obscure phosphodiesterase inhibitors (PDIs; e.g. olprinone) not in common usage in the UK and Australia are not considered. in vitro  4 1 Data covering the application of each therapy were examined. Where possible, 'evidence-based' recommendations were developed. Results 1 Catecholamines Natural and synthetic catecholamines have different haemodynamic effects because of their differential abilities to stimulate adrenergic receptors. Accordingly, each must be considered separately. Epinephrine 1 5 5 6 7 5 8 5 9 10 11 12 13 14 15 No studies were found regarding the effect of epinephrine on major clinical outcomes or survival. Dopamine Dopamine is a naturally occurring catecholamine that binds to both α- and β-receptor subgroups, with β effects predominating at low dose and α effects predominating at high dose. Doses of 2–10 μg/kg per min are commonly used for inotropy, with doses of 1.5–3.0 μg/kg per min still used by some for renal protection ('renal dose') because of the binding of the drug to specific dopaminergic receptors in the kidney. Our literature search identified a total of 21 papers relating to the use of dopamine in cardiac surgical patients, all of which were retrieved. None of these papers specifically compared the haemodynamic effects of dopamine with those of placebo. When the effects of dopamine on CI were compared with baseline data, dopamine at a dose of between 2.5 and 5.0 μg/kg per min produced significant increases in CI (range 16.3–57.9%). In all studies except one there was a significant rise in HR (range 4.5–45.7%). 16 17 2 2  18 19 20 23 24 25 26 27 28 29 n  No data were found regarding the effect of dopamine on major clinical outcomes or survival. Dobutamine 2 31 2 18 32 2 2  P  18 33 41 44 44 34 39 39 P  37 10 37 31 36 38 26 31 34 36 We were unable to find any data relating to the effect of dobutamine on major clinical outcomes or survival. Dopexamine 2 1 46 47 48 47 48 17 37 n  49 50 37 48 51 52 50 28 53 54 55 No studies were found relating to the effect of dopexamine on major clinical outcomes or survival. Phosphodiesterase inhibitors 1 Amrinone 56 57 57 P  58 59 60 61 62 60 62 63 5 8 34 39 64 n  57 61 65 66 Enoximone Enoximone is an imidazolone derivative phosphodiesterase-III inhibitor. It is typically used in doses of 0.5–1.5 mg/kg followed by an infusion of 5–10 μg/kg per min. It has a half-life of 2 hours in normal patients but this may be prolonged in patients with cardiac failure. 67 68 67 68 69 62 18 70 44 n  71 1 67 n  n  72 73 74 74 67 Milrinone Milrinone is a bipyridine methyl carbo-nitryl phosphodiesterase-III inhibitor. Loading doses of 20–50 μg/kg are typically given, followed by an infusion of 0.2–0.75 μg/kg per min. It has a half-life of 30–60 min. 3 60 75 83 85 85 n  80 83 60 2 60 62 79 27 64 78 81 78 81 13 76 We were unable to find any data relating to the effect of milrinone on major clinical outcomes or survival in cardiac surgery patients. Levosimendan There is little published work on the use of the novel calcium sensitizer levosimendan in cardiac surgical patients with LCOS. Levosimendan is a new inodilator that exerts its inotropic effect by interacting with troponin C (the binding protein for calcium) to enhance the calcium sensitivity of cardiac myocytes. 95 96 Conclusion 4 Studies investigating the use of PDIs in cardiac surgery have shown them to be potent inotropes, but vasodilation is a prominent feature of their use, and so concomitant administration of a vasoconstrictor such as norepinephrine or phenylephrine is often required. Such vasoconstrictor agents may or may not have adverse effects of their own. The effects of PDIs on HR appear to be minimal, and there is evidence to suggest that diastolic relaxation and flow through arterial grafts is improved. However, because of their pharmacokinetic profile, the time of onset and offset are longer (a loading dose is required) and they have the potential to accumulate in renal failure. These features can render the PDIs clinically less practical. 2 2 n  97 Following our systematic analysis of the literature, we believe that – despite the limitations of the data – some recommendations can be made, each with a particular level of evidence. • Recommendation 1 (level C). β-Agonists or PDIs are more efficacious at increasing cardiac output than placebo for the treatment of LCOS after cardiac surgery. Beta-agonists are associated with a greater incidence of tachycardia and tachyarrhythmia. Administration of a vasoconstrictor is often required with PDIs. • Recommendation 2 (level C). Catecholamines such as dopamine, epinephrine and dopexamine have no clear advantages over dobutamine and may be associated with a greater incidence of adverse effects. Epinephrine has been successfully used as salvage therapy. • Recommendation 3 (level C). Administration of PDIs before separation from CPB increases the likelihood of successful weaning compared with placebo, and decreases the use of catecholamines during the postoperative period. Concerns regarding amrinone and thrombocytopenia have limited its use. • Recommendation 4 (level C). There is no evidence that inotropes should be selected for their effects on regional perfusion. • Recommendation 5 (level C). Administration of milrinone increases flow through arterial grafts. • Recommendation 6 (level C). Milrinone and probably other PDIs reduce mean pulmonary artery pressure and improve right heart performance in pulmonary hypertension. We believe that the field of clinical research into inotropic support for adult cardiac surgery has reasonably established the superiority of catecholamines and PDIs over placebo. However, insufficient evidence exists to guide the choice of one group of drugs versus the other. The role of the new calcium sensitizers remains unknown. It is biologically plausible that the use of catecholamines or PDIs may lead to different clinical outcomes and the clinical scenario of LCOS is relatively common, and so suitably powered, multicentre, randomized controlled trials should be a clinical research priority in adult cardiac surgery patients. Abbreviations CABG = coronary artery bypass grafting; CI = cardiac index; CPB = cardiopulmonary bypass; HR = heart rate; ICG = indocyanine green; ICU = intensive care unit; IMA = internal mammary artery; LCOS = low cardiac output syndrome; LVEF = left ventricular ejection fraction; MAP = mean arterial pressure; NO = nitric oxide; PDI = phosphodiesterase inhibitor; pHi = intramucosal pH; PVR = pulmonary vascular resistance; SVR = systemic vascular resistance; SVI = stroke volume index. Competing interests The author(s) declare that they have no competing interests.