High Prevalence of Severe Circulatory Complications with Diazoxide in Premature Infants

Abstract

Background: Since diazoxide was approved for clinical use in Japan in 2008, its prescription for the treatment of infants with hyperinsulinemic hypoglycemia (HIH) has rapidly expanded. Concomitantly, reports of complications associated with diazoxide are increasing. Objectives: To clarify the trends and problems associated with the treatment of infants with HIH, we planned a nationwide surveillance in Japan. Methods: Questionnaires were sent to 255 institutions belonging to the Japanese Neonatologist Association inquiring about neonatal cases of HIH from 2009 to 2011. Results: One hundred nineteen cases of neonates with transient HIH (THIH) related to perinatal problems and 15 cases with permanent HIH (PHIH; hypoglycemia persisting beyond a year) or genetic HIH were reported. Sixty-four infants (53.8%) with THIH were administered diazoxide, and the administration was completed within 3 months in 46 infants (71.9%). Fourteen of the PHIH or genetic cases were treated with diazoxide and 7 of them (50%) had hypoglycemia persisting beyond a year. Circulatory complications were reported in 15 infants, i.e. 10 with THIH and 5 with PHIH. Multiple regression analysis revealed that a younger gestational age at birth and higher maximum doses of diazoxide were significant risk factors for circulatory complications. Conclusions: Diazoxide is widely prescribed for infants with HIH as a first-line medicine in Japan, but prophylactic diuretics are uncommon. Under these circumstances, a high prevalence of severe circulatory complications in very-low-birth-weight infants was reported.

Diazoxide‐induced pulmonary hypertension in hyperinsulinaemic hypoglycaemia: Recommendations from a multicentre study in the United Kingdom

“…Previous case reports and case series were small in numbers, 13,[16][17][18] Due to the availability of data on diazoxide-treated HH patients who did not develop PH, we were able to study the risk factors associated with diazoxide-induced PH relative to those who did not develop diazoxide-induced PH. Although previous studies and case reports have described prematurity and lower birth weight as predisposing factors for PH development following diazoxide treatment, 11,13,16,18,19 we did not find these factors to be associated with PH. These suggest the development of PH to be more likely directly correlated with the diazoxide treatment.…”

“…13,19,21 However, we did not find a significant difference between the diazoxide doses in our PH and non-PH groups. 13,19,21 However, we did not find a significant difference between the diazoxide doses in our PH and non-PH groups.…”

Experience of Octreotide Therapy for Hyperinsulinemic Hypoglycemia in Neonates Born Small for Gestational Age: A Case Series

“…The most common adverse effect of diazoxide is hypertrichosis. Another side effect is water retention, which could cause serious problems such as congestive heart failure or the reopening of the ductus arteriosus [15,16]. These heart and vascular complications are mostly observed in preterm children, raising the question of its contraindication in premature patients.…”

Congenital hyperinsulinism: current status and future perspectives

“…Hypertrichosis occurs in most patients and could be a serious concern. Other side effects include water retention, which could cause serious problems such as congestive heart failure or reopening of the ductus arteriosus65,66). This side effect may be of particular concern in patients with a low birth weight, as in transient CHI.…”