Intractable hypotension due to septic shock is associated with high mortality rates in critically ill children worldwide. The use of terlipressin (triglycyl-lysine-vasopressin), an analog of vasopressin with a longer duration of action, recently emerged as a treatment of hypotension not responsive to vasopressors and inotropes. This was a retrospective study set in an 18-bed pediatric critical care department in a tertiary care children's hospital. We reviewed the files of all children with septic shock who were treated with terlipressin between January 2003 and February 2004. Fourteen children (mean age, 5.6 years; range, 4 days to 17.7 years) were treated with terlipressin in 16 septic shock episodes. Significant improvements in respiratory and hemodynamic indices were noted shortly after treatment. Mean arterial blood pressure increased significantly from 54 +/- 3 to 72 +/- 5 mmHg 10 min after terlipressin administration (P = 0.001). Heart rate decreased from 153.0 +/- 6.5 beats/min to 138.0 +/- 7.5 beats/min 12 h after treatment onset (P = 0.003). Epinephrine infusion was decreased or stopped in eight patients after terlipressin administration. Urine output increased from 1.6 +/- 0.5 mL/kg/h to 4.3 +/- 1.2 mL/kg/h 1 h after treatment onset (P = 0.011). PaO2 increased from 95.1 +/- 12.3 mmHg to 110.1 +/- 20.5 mmHg, and the oxygenation index decreased from 10.2 +/- 2.2 to 9.2 +/- 1.7. Terlipressin treatment of hypotension due to septic shock was successful in eight out of 16 episodes. Six of the 14 patients with poor prognosis for survival recovered. We conclude that terlipressin improves hemodynamic indices and renal function in critically ill children. Terlipressin should be considered as a rescue therapy in intractable shock not responsive to catecholamines in children.

Coenzyme A (CoA) is an essential metabolic cofactor used by around 4% of cellular enzymes. Its role is to carry and transfer acetyl and acyl groups to other molecules. Cells can synthesize CoA de novo from vitamin B5 (pantothenate) through five consecutive enzymatic steps. Phosphopantothenoylcysteine synthetase (PPCS) catalyzes the second step of the pathway during which phosphopantothenate reacts with ATP and cysteine to form phosphopantothenoylcysteine. Inborn errors of CoA biosynthesis have been implicated in neurodegeneration with brain iron accumulation (NBIA), a group of rare neurological disorders characterized by accumulation of iron in the basal ganglia and progressive neurodegeneration. Exome sequencing in five individuals from two unrelated families presenting with dilated cardiomyopathy revealed biallelic mutations in PPCS, linking CoA synthesis with a cardiac phenotype. Studies in yeast and fruit flies confirmed the pathogenicity of identified mutations. Biochemical analysis revealed a decrease in CoA levels in fibroblasts of all affected individuals. CoA biosynthesis can occur with pantethine as a source independent from PPCS, suggesting pantethine as targeted treatment for the affected individuals still alive.

There is circumstantial evidence that the administration of terlipressin caused the increase in blood pressure. We suggest that terlipressin should be considered as rescue therapy when high-dose catecholamine therapy does not result in sufficient perfusion pressure. Further investigation is needed to prove terlipressin's effectiveness and safety in infants and children.