Complications of diazoxide treatment in persistent neonatal hyperinsulinism.

Abstract

SUMMARY Seven infants with persistent neonatal hyperinsulinism were treated in Dhahran Health Centre from 1983 to 1986. The insulin:glucose ratio (serum insulin concentration pmolIl) divided by the blood glucose concentration (mmolI1) ranged from 12 to 636, mean (SD) 177 (201). To control hypoglycaemia, diazoxide (12-24 mg/kg/day) was given in a continuous intravenous glucose infusion (12-22 mg/kg/min) on 11 separate occasions, four infants twice each and three infants once each. An increase of more than one standard deviation in the heart and respiratory rates, together with other symptoms of heart failure, was considered to be evidence of diazoxide toxicity. Cardiorespiratory failure (toxicity) occurred on eight of the 11 occasions (73%) in seven infants. The average daily fluid intake, weight change, respiratory rate and heart rate before treatment were similar whether or not the infant developed toxicity. A diazoxide toxicity index was obtained by multiplying the dose of diazoxide by the insulin:glucose ratio to relate the diazoxide dose to the severity of the disease. In all instances when the toxicity index was more than 1533 (mean (SD) 3732 (2741)) cardiac toxicity developed. In contrast, infants with a toxicity index of less than 675 (mean (SD) 364 (270)

Long-term treatment of persistent hyperinsulinaemic hypoglycaemia of infancy with diazoxide: a retrospective review of 77 cases and analysis of efficacy-predicting criteria

“…Haematological side-eects like immuno-allergic neutropenia occurred in two of our patients and may disrupt the treatment. DZX has been reported to cause troublesome¯uid retention [1], essentially in neonates after iv infusion of the drug at a high dose (>15 mg/kg per day). This eect usually regresses when the dose is reduced and, if necessary, thiazide diuretics are added.…”

High Prevalence of Severe Circulatory Complications with Diazoxide in Premature Infants

“…Such Japanese trends would have affected the relatively high prevalence of circulatory complications. Given the risk of severe circulatory complications in preterm infants identified in this study, prophylactic use of diuretics should be recommended to Japanese neonatologists, especially for high-risk infants with circulatory problems, such as VLBW infants or infants with congenital heart disease [25,26,27]. …”

Pulmonary hypertension, heart failure and neutropenia due to diazoxide therapy

“…3-6 A clinical picture mimicking sepsis has also been reported. 4 Haematological side effects like immuno-allergic neutropenia have also been reported in three paediatric patients. 3,7 After diazoxide was withdrawn, neutropenia resolved.…”

“…Although diazoxide is usually well tolerated, rare adverse effects have been described. 3,4 We present a 4-month-old girl who developed pulmonary hypertension, heart failure and neutropenia during diazoxide therapy.…”