Cardiac rescue with enoximone in volume and catecholamine refractory septic shock

Abstract

In December 2000 and February 2001, two children with suspected meningococcal disease were admitted to our pediatric intensive unit. Their Glasgow Meningococcal Septicaemia Prognostic score was 12 points. General treatment including antibiotics, steroids in case of meningitis, and fluid replacement, was performed. Despite appropriate volume replacement, intubation and ventilation, noradrenaline and adrenaline continuous infusions < or =1.0 microg/kg/min, and additional bolus infusions, cardiac output deteriorated within minutes in both children. Calcium and bicarbonate were given without sustained effect. Echocardiography demonstrated no pericardial effusion and shortening fraction was <10%. External cardiac massage had to be performed immediately in one case for electromechanical uncoupling. Both patients received a bolus of enoximone 2 mg/kg and 5 mg/kg body weight, respectively, followed by a continuous infusion of 20-23 microg/kg/min. Thereafter, both children had an adequate blood pressure and their shortening fraction increased to >30%. Within minutes, the catecholamine infusion could be reduced in both patients. The children completely recovered from their life-threatening situations. In patients with severe prolonged catecholamine and volume refractory endotoxin shock in Waterhouse-Friderichsen syndrome, even with electromechanical uncoupling and complete myocardial arrest, enoximone can immediately restore myocardial contractility.

Clinical practice parameters for hemodynamic support of pediatric and neonatal septic shock: 2007 update from the American College of Critical Care Medicine*

“…Because one of the pathogenic mechanisms of endotoxin-induced heart dysfunction is desensitization of Ca ++ /actin/tropomyosin complex binding (197–202), this drug allows treatment at this fundamental level of signal transduction overcoming the loss of contractility that characterizes septic shock. Enoximone is a type III PDEI with 10 times more β 1 cAMP hydrolysis inhibition than β 2 cAMP hydrolysis inhibition (203–205). Hence, it can be used to increase cardiac performance with less risk of undesired hypotension.…”

Myocardial dysfunction in meningococcal septic shock

“…In these children, amrinone produced an increase in cardiac output by up to 40% at a dose of 15 mg/kg/min, again because of a reduction in SVR [42]. In support of this approach, two children with severe MCD being treated with adrenaline and noradrenaline both demonstrated remarkable recovery from cardiovascular collapse after enoximone was commenced [43]. One of the children required cardiac massage but stabilised once enoximone was given.…”

Surviving Sepsis Campaign

“…In two RCTs, pentoxifylline reduced mortality from severe sepsis in newborns (510,(560)(561)(562)(563)(564)(565)(566)(567)(568)(569) Rationale. The choice of vasoactive agent is initially determined by the clinical examination; however, for the child with invasive monitoring in place and demonstration of a persistent low cardiac output state with high systemic vascular resistance and normal blood pressure despite fluid resuscitation and inotropic support, vasodilator therapy can reverse shock.…”