Abstract and Introduction
Abstract
Introduction: Refractory septic shock has dismal prognosis despite aggressive therapy. The purpose of the present study is to report the effects of terlipressin (TP) as a rescue treatment in children with catecholamine refractory hypotensive septic shock.
Methods: We prospectively registered the children with severe septic shock and hypotension resistant to standard intensive care, including a high dose of catecholamines, who received compassionate therapy with TP in nine pediatric intensive care units in Spain, over a 12-month period. The TP dose was 0.02 mg/kg every four hours.
Results: Sixteen children (age range, 1 month-13 years) were included. The cause of sepsis was meningococcal in eight cases, Staphylococcus aureus in two cases, and unknown in six cases. At inclusion the median (range) Pediatric Logistic Organ Dysfunction score was 23.5 (12-52) and the median (range) Pediatric Risk of Mortality score was 24.5 (16-43). All children had been treated with a combination of at least two catecholamines at high dose rates. TP treatment induced a rapid and sustained improvement in the mean arterial blood pressure that allowed reduction of the catecholamine infusion rate after one hour in 14 out of 16 patients. The mean (range) arterial blood pressure 30 minutes after TP administration increased from 50.5 (37-93) to 77 (42-100) mmHg (P < 0.05). The noradrenaline infusion rate 24 hours after TP treatment decreased from 2 (1-4) to 1 (0-2.5) µg/kg/min (P < 0.05). Seven patients survived to the sepsis episode. The causes of death were refractory shock in three cases, withdrawal of therapy in two cases, refractory arrhythmia in three cases, and multiorgan failure in one case. Four of the survivors had sequelae: major amputations (lower limbs and hands) in one case, minor amputations (finger) in two cases, and minor neurological deficit in one case.
Conclusion: TP is an effective vasopressor agent that could be an alternative or complementary therapy in children with refractory vasodilatory septic shock. The addition of TP to high doses of catecholamines, however, can induce excessive vasoconstriction. Additional studies are needed to define the safety profile and the clinical effectiveness of TP in children with septic shock.
Introduction
Septic shock is a severe clinical condition with a complex pathophysiology and poor prognosis despite intensive therapy. In sepsis, a cascade of macrocirculatory and microcirculatory alterations may induce an inability to maintain vasoconstriction, and can lead to severe hypotension. When hypotension becomes refractory to current intensive treatments, the prognosis of septic shock is very poor.
Prompted by the desperate situation of patients who fail to respond to aggressive therapy with fluid expansion, vasopressors, inotropes, and other therapies, alternative or complementary vasoconstrictors have been used. Vasopressin (AVP) has potent vasoconstrictive effects mediated via V1 receptors and has been shown effective in catecholamine-resistant hypotension due to septic shock.
Terlipressin (TP) is a synthetic analog of AVP with a similar pharmacodynamic profile, but with a significantly longer halflife, that has showed promising effects in some case reports of adult patients and of children with refractory vasodilatory septic shock. On the other hand, concerns have been raised about possible adverse effects of these alternative pressor agents. New clinical evidence is therefore needed to define the role of both AVP and TP in vasodilatory septic shock.
In the present article, we report the results of the use of TP as a last-resource compassionate therapy in critically ill children with catecholamine-resistant hypotension due to septic shock.