A case of severe diazoxide toxicity

Abstract

Hyperinsulism is a rare cause of persistent hypoglycemia in the neonatal period. Therapy can be accomplished either surgically or pharmacologically. Diazoxide treatment remains the mainstay of medical therapy. Tolerance of diazoxide is usually excellent, but several adverse effects of this drug have been described. A case of severe diazoxide intoxication with fluid retention, congestive heart failure, and respiratory failure is reported. The patient was a 43-day-old infant, affected by persistent and severe hypoglycemia. After the diagnosis, hyperinsulinism was established he was treated with diazoxide (17 mg x kg(-1) daily) and octreotide (12 microg x kg(-1) daily). A few days later he presented with hepatomegaly, severe fluid retention, diffuse edema, congestive heart failure, and respiratory failure requiring mechanical ventilation. After introduction of ACE inhibitors he developed acute renal failure. The clinical condition worsened and he developed pulmonary hypertension requiring high-frequency oscillatory ventilation. Diazoxide was stopped on the 12th day in spite of poor control of blood sugar. During the next 5 days his hemodynamic status dramatically improved and he was weaned from catecholamines: he lost weight, had a negative fluid balance, and the edema disappeared, a normal diuresis resumed and renal function improved. Improvement of respiratory patterns and gas exchange made it possible to switch back to conventional ventilation and then to extubate the patient. Echocardiography demonstrated reduction of the PA pressure to normal and resolution of atrial enlargement. The patient was scheduled for elective subtotal pancreatectomy. Diagnosis and management of diazoxide intoxication are discussed.

High Prevalence of Severe Circulatory Complications with Diazoxide in Premature Infants

“…The analysis revealed that the maximum dosage is the only factor for the overall incidence of complications associated with diazoxide. These findings are consistent with previous reports [14,19]. Infants who were administered diazoxide at more than 15 mg/kg/day showed a higher incidence of complications (76.4%) than those on less than 15 mg/kg/day (26.2%) (p < 0.05).…”

“…In 2008, it was approved for the treatment of patients with HIH, and its use is considered to be expanding rapidly. Although the usefulness of diazoxide for HIH is well established [11], several life-threatening complications have been reported [12,13,14]. …”

Minimally invasive surgical interventions in the treatment of primary persistent hyperinsulinemic hypoglycemia of infancy

“…Prevalent complications, such as hypertrichosis, have also been proposed for diazoxide. Serious complications including pulmonary hypertension, heart failure and neutropenia (16), hepatomegaly, severe fluid retention, diffuse edema, congestive heart failure, and respiratory failure requiring mechanical ventilation (17) have also been reported. Another problem that exists in our country is the fact that diazoxide is not always available, due to sanctions.…”

Management Approach to Hypoglycemia

“…Appart from acting as a diuretic, chlorothiazide has also direct β-cell pottasium channel opening activity. In a purpose to supply sufficient glucose, large volumes of intravenous fluids are infused to hyperinsulinemic infants and enhance the danger of severe water retention (Silvani et al, 2004). Somatostatin analogues are able to inhibit insulin secretion in various manners by inducing hyperpolarisation of β-cells, direct inhibition of the voltage-gated calcium channel and more distal insulin secretory pathways.…”