Arginine-vasopressin in severe forms of septic shock

LETTERS TO THE EDITOR

We read with interest the article by Irazuzta et al. on the pharmacological support of infants and children in septic shock.¹ Apart from conventional inotropes, the authors suggest the use of vasopressin in severe forms of septic shock.¹ We agree with the authors that arginine-vasopressin and its long-acting analogue, terlipressin, are potent vasopressors that may be useful rescue agents in the treatment of catecholamine-resistant septic shock.² However, there is still no clear concept when to start arginine-vasopressin and terlipressin therapy in catecholamine-resistant shock. Recently, a large clinical study in adults with septic shock demonstrated the beneficial effects of initiating arginine-vasopressin therapy before norepinephrine requirements exceed 0.6 µg/kg/minute.³ This is in accordance with our own limited experience in preterm neonates.⁴ In a small series of extremely low birth weight infants, the surviving infants received norepinephrine and epinephrine in a dosage < 0.6 µg/kg/minute prior to arginine-vasopressin medication.⁴ Moreover, there is still no clear concept about the precise (starting) dose of arginine-vasopressin/terlipressin therapy in the pediatric population. Due to the lack of reference values in children, the doses are often extrapolated from adult patient reports.² In order to shed more light on these important issues, there is a need for large prospective studies in children on the use of arginine-vasopressin and terlipressin in severe forms of septic shock in children.

References

1. Irazuzta J, Sullivan KJ, Garcia PC, Piva JP. Pharmacologic support of infants and children in septic shock. J Pediatr (Rio J). 2007;83(2 Suppl):S36-S45.

2. Rodriguez-Nunez A, Lopez-Herce J, Gil-Anton J, Hernandez A, Rey C; RETSPED Working Group of the Spanish Society of Pediatric Intensive Care. Rescue treatment with terlipressin in children with refractory septic shock: a clinical study. Crit Care. 2006;10:R20.

3. Meyer S, Gottschling S, Baghai A, Wurm D, Gortner L. Arginine-vasopressin in catecholamine-refractory septic versus non-septic shock in extremely low birth weight infants with acute renal injury. Crit Care. 2006;10:R71.

4. Luckner G, Dunser MW, Jochberger S, Mayr VD, Wenzel V, Ulmer H, et al. Arginine-vasopressin in 316 patients with advanced vasodilatory shock. Crit Care Med. 2005;33:2659-66.

S. Meyer

The Centre for Newborn Care, Medical School, The Canberra Hospital, Australian National University, Canberra, Australia

G. Shamdeen

Department of Neuropediatrics, University Hospital of the Saarland, Saarbrücken, Germany

S. Gottschling

Department of Pediatrics and Neonatology, University Hospital of the Saarland, Saarbrücken, Germany

L. Gortner

Department of Pediatrics and Neonatology, University Hospital of the Saarland, Saarbrücken, Germany

Authors' reply

We agree with the final comments that large protective studies in children are lacking on the use of arginine-vasopressin and terlipressin in septic shock. However, there is a significant amount of pediatric experience utilizing vasopressin as a rescue treatment in septic shock with low systemic vascular resistance. We would be inclined to start vasopressin after the patient has been adequately fluid resuscitated, without hypocalcemia or hypoglycemia, with adequate catecholamine and corticosteroid support. In general, we believe that if there is no significant improvement in systemic vascular resistance with a norepinephrine dose above 1 µg/kg/minute, vasopressin should be considered. A common starting dose is an adjustment of the adult dose at 0.0003 units per kg/min up to 0.002 units/kg/min.

Two authors of our article (Garcia PC & Piva JP) have conducted two studies involving vasopressin infusion in children (data still not published). One study assessed children with septic shock after fluid resuscitation and corticosteroid administration who were refractory to norepinephrine (above 1 µg/kg/min) infusion. We agreed to use a vasopressin dose of 0.0005 U/kg/min (dilution of 200 U/mL), gradually titrating the dose to 0.002 U/kg/min (ideal dose).¹ The maximum dose was defined as 0.008 U/kg/min. The first 12 patients included in this study showed a significant increment in arterial blood pressure and in cardiac output, allowing a reduction in norepinephrine infusion.

We have just ended our second study, a double-blind, randomized controlled trial that assessed the use of low-dose vasopressin in children with severe respiratory disease.² Children under mechanical ventilation were randomized (1:1 ratio) to receive either vasopressin (0.0005 U/kg/min) or NaCl 0.9% (0.01 mL/kg/min) infusions for a period of 48 hours. The initial mean arterial pressure (MAP) was similar in both groups, but after the infusions were started, the MAP of children in the vasopressin group was significantly higher (p < 0.05). Hyponatremia was more frequent in children in the vasopressin group (58% vs. 8%, p < 0.01). Urine output was smaller in children that received vasopressin (2.4 vs. 4.2 mL/kg/hour, p = 0.033), and after the end of the infusions, children who received vasopressin had higher urine output than children that received placebo (7.4 vs. 3.8 mL/kg/hour, p = 0.037). Low-dose vasopressin infusion increased MAP in children requiring mechanical ventilation. However, vasopressin decreased urine output and sodium concentration, increasing the incidence of hyponatremia.

We want to extend our appreciation to the writer for sharing his own experience with the use of arginine-vasopressin in preterm neonates.

References

1. Dyke PC, Tobias JD. Vasopressin: applications in clinical practice. J Intensive Care Med. 2004;19:220-8.

2. Garcia PC, Baldasso E, Piva J, Branco RG, Lisboa B, Almeida CL, et al. Use of low dose vasopressin in children requiring mechanical ventilation. Pediatr Crit Care Med. 2007;In press.

José Irazuzta

MD. Division of Pediatric Critical Care Medicine, Health Science Center, University of Florida, Jacksonville, FL, USA

Kevin J. Sullivan

MD. Division of Pediatric Critical Care Medicine, Health Science Center, University of Florida, Jacksonville, FL, USA

Pedro Celiny R. Garcia

MD, PhD. Department of Pediatrics, Hospital São Lucas and Medical School, Pontifícia Universidade Católica do Rio Grande do Sul (PUCRS), Porto Alegre, RS, Brasil.

Jefferson Pedro Piva

MD, PhD. Department of Pediatrics, Hospital São Lucas and Medical School, Pontifícia Universidade Católica do Rio Grande do Sul (PUCRS), Porto Alegre, RS, Brasil.

Elisa Baldasso

MD. Department of Pediatrics, Hospital São Lucas and Medical School, Pontifícia Universidade Católica do Rio Grande do Sul (PUCRS), Porto Alegre, RS, Brasil.

Department of Pediatrics and Neonatology, University Hospital of the Saarland, Saarbrücken, Germany

Arginine-vasopressin in severe forms of septic shock

Dear Editor,

Publication Dates

• Publication in this collection
  27 Aug 2007
• Date of issue
  Aug 2007