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Complications of diazoxide treatment in persistent neonatal hyperinsulinism
Y K Abu-Osba1, K B Manasra, P M Mathew
1Neonatology/Perinatology Section, King Faisal Specialist Hospital and Research Centre, Riyadh, Saudi Arabia.
Insights
Diazoxide toxicity in infants with persistent neonatal hyperinsulinism is linked to the diazoxide toxicity index. This index can predict toxicity risk and guide safe diazoxide dosing for this condition.
Area of Science:
- Pediatric Endocrinology
- Neonatal Medicine
- Clinical Pharmacology
Background:
- Persistent neonatal hyperinsulinism is a severe condition requiring careful management.
- Diazoxide is a common treatment for hyperinsulinism, but carries risks of toxicity.
- Cardiorespiratory failure is a significant adverse effect of diazoxide treatment in infants.
Purpose of the Study:
- To investigate the relationship between diazoxide dosage, disease severity, and toxicity in infants with persistent neonatal hyperinsulinism.
- To develop a predictive index for diazoxide toxicity in this patient population.
- To establish guidelines for safe diazoxide dosing.
Main Methods:
- Retrospective analysis of seven infants treated for persistent neonatal hyperinsulinism.
- Calculation of the insulin:glucose ratio and a novel diazoxide toxicity index (diazoxide dose × insulin:glucose ratio).
- Correlation of the toxicity index with the occurrence of diazoxide-induced cardiorespiratory failure.
Main Results:
- Cardiorespiratory failure (toxicity) occurred in 73% of treatment occasions.
- A diazoxide toxicity index > 1533 was consistently associated with toxicity.
- A toxicity index < 675 was associated with no symptoms of toxicity.
- Toxicity was significantly related to both disease severity and diazoxide dose.
Conclusions:
- The diazoxide toxicity index is a valuable tool for predicting the risk of cardiorespiratory toxicity in infants with persistent neonatal hyperinsulinism.
- This index can aid in calculating safe and effective diazoxide doses, balancing treatment efficacy with patient safety.
- Further research may refine the use of this index for personalized diazoxide therapy.
Abstract:
Seven infants with persistent neonatal hyperinsulinism were treated in Dhahran Health Centre from 1983 to 1986. The insulin:glucose ratio (serum insulin concentration pmol/l) divided by the blood glucose concentration (mmol/l) 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), had no symptoms of toxicity. Symptoms were significantly related to the severity of the disease and the diazoxide dose. It is possible to use the toxicity index to predict the risk of toxicity and to calculate a safe dose of diazoxide in infants with persistent neonatal hyperinsulinism.