Low-Output Syndrome after Heart Surgery: Is a Monotherapy with Phosphodiesterase-III Inhibitors Feasible? A Comparitive Study of Amrinone and Enoximone

Abstract

In order to determine whether the primary use of a phosphodiesterase-III (PDE) inhibitor as monotherapy for severe cardiac low-output states (LOS) is in fact practicable, we investigated the haemodynamic effects of amrinone and enoximone in a prospective randomized study. After elective CABG, AVR, or MVR, patients with cardiac LOS were given amrinone (n = 10) or enoximone (n = 9). Following bolus saturation (1.0-2.0 mg/kg [XA = 1.4] or 0.5-1 mg/kg [XE = 0.9] in total), a dose of 5-10 microgram/kg/min was given by infusion. The standard monitoring program included discontinuous haemodynamic measurements (Swan-Ganz) over a maximum time period of 48 hours, arterial and venous blood-gas analyses, and clinical chemistry. The preoperative clinical and haemodynamic status of the enoximone (E) group (55% CABG patients; MPAP 27 +/- 2.5 mmHg, PCWP 20 +/- 2.9 mmHg, PVR 201 +/- 35 dyn.s.cm-5) was considerably worse than that of the amrinone (A) group (70% CABG patients; MPAP 23 +/- 2.3 mmHg, PCWP 16 +/- 3.5 mmHg, PVR 153 +/- 28 dyn.s.cm-5). Both PDE inhibitor preparations led to a significant increase in cardiac index (from 1.9 +/- 0.1 to 2.5 +/- 0.12 L/min/m2 (A) and from 1.98 +/- 0.1 to 2.6 +/- 0.18 L/min/m2 (E) within 30 minutes, accompanied by a simultaneous decrease in filling pressures and vascular resistances. For up to 2 hours, 3/10 (A) and 2/9 (E) patients required additional positive inotropic support with adrenaline. There were no significant differences between the two groups at any time.(ABSTRACT TRUNCATED AT 250 WORDS)

Massive diltiazem overdose treated with extracorporeal membrane oxygenation

“…M1 concentrations are usually 10% to 20% of the parent drug DTZ and are usually less than MA concentrations. Removal of the drug from plasma is usually ineffective because DTZ is highly protein bound (70% to 80%) and extensively distributed into tissues (1,6). The pharmacodynamic profile of DTZ was markedly abnormal in this patient, with the elimination half-life of DTZ ranging between 28 and 40 hrs (normal 4 -6 hrs).…”

“…Saturable metabolism has been described in massive DTZ overdose (1). DTZ levels on the fifth day were still ten times greater than the recommended therapeutic level of 100 g/mL (6). The concentrations of M1 relative to DTZ remained unusually high (Ͼ40%), only decreasing toward expected values by 115 hrs, indicating that metabolism from DTZ to M1 is not a rate-limiting step.…”

“…Excessive systemic vasodilation and direct myocardial depression (particularly the atria) also occur frequently, leading to hypotension. The metabolites of DTZ also have some vasodilatory effect but are less potent than the parent drug (6).…”

Effects of a new calcium sensitizer, levosimendan, on haemodynamics, coronary blood flow and myocardial substrate utilization early after coronary artery bypass grafting

“…This is similar to another inotropic compound, pimobendan, which does not increase heart rate during long-term treatment [24,25] , although it increases heart rate in acute intravenous use more than does devosimendan [24][25][26][27] . In the present study, the increase in heart rate after the higher dose of levosimendan was of the same magnitude as after efficacious doses of milrinone, amrinone, enoximone and dubutamine [15,[28][29][30] . Like other drugs with potent vasodilating activity, levosimendan increased intrapulmonary shunting.…”

Cardiac rescue with enoximone in volume and catecholamine refractory septic shock

“…Despite high volume fluid replacement and early use of catecholamines, refractory septic shock has been observed to be one of the main risk factors for mortality in Waterhouse-Friderichsen syndrome (1,2). There is evidence from animal experiments in vitro, and clinical studies undertaken with patients after cardiopulmonary bypass or endstage heart failure, that phosphodiesterase (PDE)-III inhibitors may increase cardiac contractility via elevation of adenosine 3',5'-cyclic monophosphate (cAMP) in the face of ␤-receptor blockade, and decrease vascular resistance via increased cyclic guanosine 3',5'-monophosphate (cGMP) levels (3)(4)(5)(6). In December 2000 and February 2001, two children with suspected meningococcal septicaemia were admitted to our pediatric intensive care unit with a GMSPS of 12 points and catecholamine refractory shock.…”