Marina Rubinshtein

Terlipressin as rescue therapy for intractable hypotension due to septic shock in children.

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.

Beneficial effects of terlipressin in prolonged pediatric cardiopulmonary resuscitation: a case series.

Objective:Arginine vasopressin was found in experimental and clinical studies to have a beneficial effect in cardiopulmonary resuscitation. The American Heart Association 2000 guidelines recommended its use for adult ventricular fibrillation arrest, and the American Heart Association 2005 guidelines noted that it may replace the first or second epinephrine dose. There is little reported experience with arginine vasopressin in cardiopulmonary resuscitation of children. Terlipressin, a long-acting analog of arginine vasopressin, has recently emerged as a treatment for vasodilatory shock in both adults and in children, but evidence of its effectiveness in the pediatric setting is sparse. The objective of this retrospective study is to describe our experience in adding terlipressin to the conventional protocol in children with cardiac arrest. Design:Retrospective case series study. Setting:An 18-bed pediatric critical care department at a university-affiliated tertiary care childrens hospital. Patients:Seven pediatric patients with asystole, aged 2 months to 5 yrs, who experienced eight episodes of refractory cardiac arrest and did not respond to conventional therapy. Interventions:Addition of terlipressin to epinephrine during cardiopulmonary resuscitation of children. Measurements and Main Results:Return of spontaneous circulation was monitored and achieved in six out of eight episodes of cardiac arrest. One patient died 12 hrs after return of spontaneous circulation, and four patients survived to discharge with no neurologic sequelae. Conclusions:The combination of terlipressin to epinephrine during cardiopulmonary resuscitation may have a beneficial effect in children with cardiac arrest. More studies on this drugs safety and efficacy in this setting are mandated.

Transillumination of the palm for venipuncture in infants

Aim To assess the efficacy of transillumination of the palm of the hand in establishing venous access in small infants. Methods One hundred infants aged 2 to 36 months were considered for venipuncture under transillumination following failure to find an accessible vein or a failed venipuncture attempt. Results In 40 of the 100 infants, a vein was visible with transillumination. In 22 of these children, previous attempts to achieve a venous line failed (mean number of failed venipunctures 2.11 ± 0.6) and in 18 infants, no vein could be identified. Using transillumination, venous access was established with just one venipuncture in 39 of the 40 patients. Conclusions Transillumination of the palm can aid in establishing venous access in infants. This can be easily carried out using a common otoscope.

Terlipressin as rescue therapy for intractable hypotension during neonatal septic shock.

Objective To report the successful use of terlipressin in an 8-day-old infant for treatment of intractable hypotension caused by septic shock. Design Descriptive case report. Setting An 18-bed pediatric intensive care unit at a tertiary care children’s hospital. Patient An 8-day-old child with intractable hypotension due to septic shock after heart surgery. Interventions General supportive intensive care including mechanical ventilatory support, volume replacement, and inotropic support with dopamine 20 &mgr;g·kg−1·min−1, milrinone 0.75 &mgr;g·kg−1·min−1, and epinephrine 0.8 &mgr;g·kg−1·min−1. Measurements and Main Results Terlipressin (7 &mgr;g/kg per dose twice daily) was added as rescue therapy because of profound intractable hypotension. Shortly after the beginning of treatment, blood pressure and perfusion dramatically improved. Conclusions 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.

Terlipressin for Children with Extremely Low Cardiac Output After Open Heart Surgery

Background: Terlipressin, a long-acting analog of vasopressin, has been used successfully in patients with extremely low cardiac output, but its application in children following open heart surgery is limited. Objective: To describe our experience using terlipressin in children with extremely low cardiac output after open heart surgery. Methods: Records were reviewed of all pediatric patients between January 2003 and December 2005 who had undergone open heart surgery, experienced extremely low cardiac output, and were treated with terlipressin as rescue therapy. Mean arterial blood pressure, heart rate, urine output, and lactate and oxygenation index values were retrieved and analyzed when available. Results: Twenty-nine children who were considered gravely ill despite conventional vasoactive agents received terlipressin as rescue therapy, which rapidly yielded significant improvements in all measured hemodynamic and respiratory indices. Mean ± SD arterial blood pressure increased significantly, from 49 ± 17 to 57 ± 16 mm Hg after 10 minutes (p = 0.004) and to 64 ± 15 mm Hg 24 hours after treatment onset (p = 0.001). Twenty-four hours following terlipressin administration, urine output increased from 1.5 ± 2.1 to 3.0 ± 2.3 mL/kg/h (p = 0.001), the oxygenation index decreased from 16.5 ± 27.9 to 9.5 ± 16.7 in the survivors (p = 0.023), and the inotropic score decreased from 41.9 ± 19.9 to 32.6 ± 18.8 (p = 0.009). Conclusions: Terlipressin caused significant improvement in hemodynamic, respiratory, and renal indices in children with extremely low cardiac output after open heart surgery. Further controlled studies are needed to confirm the drugs safety and efficacy in this population.

Glutaric Aciduria type I and acute renal failure - Coincidence or causality?

Glutaric Aciduria type I (GA-I) is a rare organic acidemia, caused by mutations in the GCDH gene, and characterized by encephalopathic crises with neurological sequelae. We report herein a patient with GA-I who presented with severe acute renal failure requiring dialysis, following an acute diarrheal illness. Histopathological evaluation demonstrated acute tubular necrosis, and molecular diagnosis revealed the patient to be homozygous for a previously unreported mutation, p.E64D. As renal impairment is not part of the clinical spectrum typical to GA-I, possible associations of renal failure and the underlying inborn error of metabolism are discussed, including recent advancements made in the understanding of the renal transport of glutaric acid and its derivatives during metabolic disturbance in GA-I.

Cardiac failure in very long chain acyl-CoA dehydrogenase deficiency requiring extracorporeal membrane oxygenation (ECMO) treatment: A case report and review of the literature

Fatty acid oxidation (FAO) defects often present with multi-system involvement, including several life-threatening cardiac manifestations, such as cardiomyopathy, pericardial effusion and arrhythmias. We report herein a fatal case of cardiac dysfunction and rapid-onset tamponade following an acute illness in a neonate with molecularly proven very long chain acyl-CoA dehydrogenase (VLCAD) deficiency (harboring the known del799_802 mutation), requiring 15 days of extracorporeal membrane oxygenation (ECMO) treatment. As data regarding the use of ECMO in FAO defects in general, and VLCAD in particular, are scarce, we review the literature and discuss insights from in vitro models and several successful reported cases.

Mutations in PPCS, Encoding Phosphopantothenoylcysteine Synthetase, Cause Autosomal-Recessive Dilated Cardiomyopathy

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.