Current Medical Issues

: 2022  |  Volume : 20  |  Issue : 3  |  Page : 191--193

Resolve or refer? A difficult choice in the management of neonatal refractory hypoglycemia

Vinod Kumar Palaparthy1, Karen Edith Kiruba1, Monica Thapwal2,  
1 Department of Pediatrics, Herbertpur Christian Hospital, Dehradun, Uttarakhand, India
2 Department of Nursing, Herbertpur Christian Hospital, Dehradun, Uttarakhand, India

Correspondence Address:
Dr. Vinod Kumar Palaparthy
Herbertpur Christian Hospital, Dehradun, Uttarakhand


Hypoglycemia is the most common metabolic abnormality in the neonatal period. Refractory hypoglycemia is challenging to manage in resource-limited settings. We aim to report the challenges faced and the lessons learnt while managing a neonate with refractory hypoglycemia.

How to cite this article:
Palaparthy VK, Kiruba KE, Thapwal M. Resolve or refer? A difficult choice in the management of neonatal refractory hypoglycemia.Curr Med Issues 2022;20:191-193

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Palaparthy VK, Kiruba KE, Thapwal M. Resolve or refer? A difficult choice in the management of neonatal refractory hypoglycemia. Curr Med Issues [serial online] 2022 [cited 2022 Oct 3 ];20:191-193
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Full Text


Hypoglycemia is common in the neonatal period. While transient hypoglycemia resolves spontaneously or with supportive care, refractory hypoglycemia is difficult to manage even at tertiary centers because of morbidity and mortality. Referral to a tertiary care center is difficult and increases morbidity because of poor transfer facilities. Even though definitive etiological evaluation may not always be possible at resource-limited settings, it may be possible to manage some of these sick neonates.

 Case Report

A newborn was delivered by cesarean section in view of fetal distress and meconium-stained amniotic fluid at 39+6 weeks of gestation with a birth weight of 2500 g. The baby was mildly tachypneic at birth which got worsened by 7 h of life associated with lethargy. The baby was shifted to the intensive care unit and started on oxygen and intravenous (IV) fluids with 10% dextrose. Empiric antibiotics were started. Supplemental oxygen was stopped by 57 h of life. Nasogastric tube feed was started at 24 h of life. By 48 h of life, feed volume increased to 90 ml/kg. At 64 h of life, blood sugar was recorded to be low. The baby remained hypoglycemic despite a gradual increase of glucose infusion rate (GIR) to 13mg/kg/min by increasing concentration (12.5%) and volume (150 ml/kg) of dextrose through peripheral line in addition to IV hydrocortisone at 2.5mg/kg/dose every 6 hourly. Hence, an umbilical venous (UV) line was placed, and 25% dextrose infusion was started. Euglycemia was achieved at a GIR of 18.5 mg/kg/min. GIR was gradually reduced to 13.5 mg/min over the next 4 days at which hypoglycemia recurred (random blood sugar – 34 mg/dl); hence, GIR was increased to 15 mg/kg/min at which euglycemia achieved. [Table 1] depicts key glucose measurements and various interventions undertaken.{Table 1}

Blood gas showed pH – 7.32, bicarbonate – 19 meq/L, base excess – 2, serum sodium – 132 meq/L, potassium – 4.6 meq/L, and creatinine – 1.05mg/L. The blood culture was sterile. There were no midfacial anomalies, ambiguous genitalia, and dysmorphism. Urine ketone could not be done. Cord TSH was 22.143 mIU/L. Referral was considered but not feasible. It was planned to start diazoxide on day 7 of life, but the drug was not available. Diazoxide was procured from another city 140 km away, and it was started on day 9 of life at 10 mg/kg/day. GIR was 15 mg/kg/min at the start of diazoxide. There was no hypoglycemia from the start of diazoxide. Hydrocortisone was tapered and stopped as there was no improvement documented. Diazoxide dose was tailored as per sugar monitoring. Tapering of 25% dextrose infusion started 6 h after the first dose of diazoxide and discontinued by 24 h. Within 48 h of initiation of diazoxide, GIR was reduced from 15 to 7.5mg/kg/min. NG feeds were gradually increased, and IV fluids stopped by day 12 of life. Breastfeeding was initiated by day 14 of life. The baby was discharged on day 15 of life. Diazoxide dose was gradually tapered and stopped over the next 3 weeks post discharge. There was no documented hypoglycemia post discharge.


Pediatric Endocrine Society states that in the initial hours of life, healthy neonates have lower plasma glucose concentrations. By 48–72 h of life, plasma glucose levels should be equal to that of older children.[1] Neonates at risk for severe hypoglycemia within 48 h of life include small for gestational age, large for gestational age, premature or postmature delivery, and infant of diabetic mother.[2] This subset of neonates can be screened to identify severe hypoglycemia. Hypoglycemia persisting beyond 3 days of life despite treatment is termed refractory or persistent hypoglycemia.[3] The most common cause of refractory hypoglycemia is hyperinsulinism. Hyperinsulinism should be suspected in a neonate requiring high infusion rates of dextrose (10 mg/kg/min) to maintain normoglycemia.[4] Well-appearing neonates with hyperinsulinism may miss sugar monitoring if they do not have any risk factors.[5] Other causes of refractory hypoglycemia include endocrine disorders, inborn errors of metabolism, and genetic syndromes. In resource-limited setting, the challenge is not only the treatment of refractory hypoglycemia but also etiological confirmation. The diagnosis of hyperinsulinemia requires critical sampling (insulin, cortisol, and beta-hydroxybutyrate) which is done when blood glucose drops below 40 mg/dl. Other advanced investigations to diagnose inborn errors of metabolism are not readily available at resource-limited settings. Referral to a tertiary care center is not always feasible and carries an increased risk of irreversible brain injury as it is difficult to maintain euglycemia during transfer. As the most common cause of refractory hypoglycemia is hyperinsulinism, the clinician can have a pragmatic approach to rule out inborn errors of metabolism, endocrine disorders, and syndromes. Infusion of a high concentration of dextrose (>12.5%) which is often required, can be given through UV line.[6] Of the various therapeutic modalities available for the treatment of refractory hypoglycemia, diazoxide and nifedipine are the only enteral options.[7] Compared to nifedipine, diazoxide has long been the first-line agent for hyperinsulinemia. If effective, the response can be seen within 48 h.[8] In our case, hypoglycemia responded well to diazoxide. From the start of diazoxide, no further hypoglycemia was noted, and 25% dextrose infusion was stopped within 2 days. Although it is laborious and not always possible to manage refractory hypoglycemia in resource-limited settings, a suitable case can be managed with life-saving procedures like UV line and not so expensive drugs like diazoxide.


Whether to refer an unstable patient or to offer help is a common tussle encountered in resource-limited settings. Neither decision is easy. An unstable patient may not be able to reach the referral center in time and to manage such a patient with limited resources is a great challenge. Refractory hypoglycemia can be very challenging to manage at resource-limited settings. Simple but life-saving procedures like UV line placement and a good clinical approach to narrow down the etiology of refractory hypoglycemia and access to not so commonly used drugs like diazoxide can be lifesaving to those who respond to therapy.


We have obtained appropriate consent from the patient to report the clinical information.

Declaration of patient consent

The authors certify that they have obtained all appropriate patient consent forms. In the form, the legal guardian has given his consent for images and other clinical information to be reported in the journal. The guardian understands that names and initials will not be published, and due efforts will be made to conceal patient identity, but anonymity cannot be guaranteed.

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Conflicts of interest

There are no conflicts of interest.


1Thornton PS, Stanley CA, De Leon DD, Harris D, Haymond MW, Hussain K, et al. Recommendations from the Pediatric Endocrine Society for evaluation and management of persistent hypoglycemia in neonates, infants, and children. J Pediatr 2015;167:238-45.
2Thompson-Branch A, Havranek T. Neonatal hypoglycemia. Pediatr Rev 2017;38:147-57.
3Eichenwald EC, Hansen AR, Martin CR, Stark AR. Cloherty and Stark's Manual of Neonatal Care. 8th ed. Wolters Kluver India Pvt Ltd; 2017.
4De León DD, Stanley CA. Mechanisms of disease: Advances in diagnosis and treatment of hyperinsulinism in neonates. Nat Clin Pract Endocrinol Metab 2007;3:57-68.
5Stanley CA, Rozance PJ, Thornton PS, De Leon DD, Harris D, Haymond MW, et al. Re-evaluating “transitional neonatal hypoglycemia”: Mechanism and implications for management. J Pediatr 2015;166:1520-5.e1.
6Pereira-da-Silva L, Virella D, Henriques G, Rebelo M, Serelha M, Videira-Amaral JM. A simple equation to estimate the osmolarity of neonatal parenteral nutrition solutions. JPEN J Parenter Enteral Nutr 2004;28:34-7.
7Sweet CB, Grayson S, Polak M. Management strategies for neonatal hypoglycemia. J Pediatr Pharmacol Ther 2013;18:199-208.
8Touati G, Poggi-Travert F, Ogier de Baulny H, Rahier J, Brunelle F, Nihoul-Fekete C, et al. Long-term treatment of persistent hyperinsulinaemic hypoglycaemia of infancy with diazoxide: A retrospective review of 77 cases and analysis of efficacy-predicting criteria. Eur J Pediatr 1998;157:628-33.