Neonate with hypoglycemia for pancreatectomy: Anesthetic challenge.

Persistent hyperinsulinemic hypoglycemia of infancy (PHHI) is rare and an important cause of hypoglycemia in neonates. It can lead to brain damage or death secondary to severe hypoglycemia. We present the anesthetic management in a diagnosed case of PHHI in an 8-day-old male neonate for total pancreatectomy.

INTRODUCTION

Neonates with hypoglycemia present with irritability, listlessness, nausea, vomiting, tachypnoea, hypothermia and with long-term sequelae such as seizures, developmental delay, focal neurologic deficits, or death.[1] Initial management is mainly medical with a high concentration of glucose infusion, frequent high calorie feeds, hydrocortisone, diazoxide, and diuretic. However, when hypoglycemia is resistant and unresponsive to traditional therapies, surgical resection of the pancreas is carried out. We describe the peri-operative course of this condition in a neonate who presented with recurrent hypoglycemic episodes. Initial management is mainly medical with a high concentration of glucose infusion, frequent high calorie feeds, hydrocortisone, diazoxide, and diurectic.[12]

However, when hypoglycemia is resistant and unresponsive to traditional therapies, surgical resection of the pancreas is carried out. We describe the peri-operative course of this condition in a neonate who presented with recurrent hypoglycemic episodes.

CASE REPORT

An 8-day-old male neonate with frequent episodes of non ketotic hypoglycemia and seizures, despite 15 mg/kg/min glucose infusion rate, was admitted to neonatal intensive care. The biochemical and urinary analysis was carried out to rule out other metabolic and endocrinal conditions. Persistent hyperinsulinemic hypoglycemia of infancy (PHHI) was diagnosed from inappropriate plasma insulin: Cortisol ratio (74.4 IU/ml: 16 g/dl) and elevated serum insulin levels.

Positron emission tomography computed tomography (CT) scan (18 F-DOPA) revealed diffuse increased radiotracer uptake in body and tail of the pancreas [Figure 1].

Figure 1

(a-c) Positron emission tomography/computed tomography suggestive of diffuse variant of nesidioblastosis

The neonate was managed with intravenous (IV) 10% dextrose (15 mg/kg/min) to maintain blood glucose of more than 60 mg/dl. Two hourly feed through a nasogastric tube, oral diazoxide 24 mg t.i.d., and hydroclorthiazide (25 mg on an alternate day) were given.

The patient was scheduled for near total pancreatectomy due to the persistence of symptoms in spite of aggressive medical management. Prior to surgery, the baby was kept fasting for 3 h, IV, infusion of 10% dextrose with all other drugs was continued till the morning of surgery. In the operation room, 24-gauge IV cannula was secured in the right upper limb. Anesthesia was induced with fentanyl 2 µg/kg, propofol 1 mg/kg, atracurium 0.5 mg/kg and airway was secured with 3 mm uncuffed tube, and oral packing was carried out. Monitoring included an electrocardiogram, noninvasive blood pressure, pulse oximetry, capnography, temperature, and urine output. Anesthesia was maintained with oxygen and nitrous oxide (60:40), sevoflurane 1 to 1.5%, and intermittent atracurium.

Ringer lactate 10 ml/kg/h was used as replacement fluid and 10% dextrose infusion was kept going from 40 to 50 ml/h to keep blood sugar between 100 and 200 mg/dl. Intra-operative blood loss was 70 ml for which 75 ml of blood was given. The case lasted for 4 h. Urine output was 20 ml. Intra-operative hemodynamic parameters were stable, and the procedure was uneventful. Residual neuromuscular blockade was reversed with glycopyrrolate 0.02 mg/kg and neostigmine 0.07 mg/kg. The child was extubated and shifted to the neonatal intensive care unit. Immediately after removing the pancreas [Figure 2], 10% dextrose infusion was stopped due to anticipated hyperglycemia but by the conclusion of surgery, blood sugar came down to 80 mg/dl. Therefore 10% dextrose (20 ml/h) was started at the time of shifting and blood sugar was stabilized between 80 and 100 mg/dl. Histopathological examination of specimen confirmed the diagnosis of PHHI. Postsurgery oral diazoxide and hydrochlorthiazide had to be added to attain sustained euglycemia (at a lower dose and glucose infusion was avoided). On follow-up examination, he was euglycemia with persistent seizures (electroencephalography: Focal epileptic discharges from occipital lobe), and poor head growth. Magnetic resonance imaging showed encephalomalacia of the left cerebellum. At 1 year, the baby had a developmental age of about 7–8 months pointing toward neurological sequelae of hypoglycemia.

Figure 2

Intra-operative image showing pancreas (solid arrow) lifted off the splenic vein (hollow arrow)

DISCUSSION

PHHI is a common cause of persistent hypoglycemia in this age group.[3] It is more common in areas of consanguinity like an Arabian peninsula, where the incidence may be as high as one in 2500 births,[3] but the incidence in general population is 1/50,000 live births. The putative cause is a defect in the pancreatic adenosine triphosphate sensitive potassium channel beta cells leading to hyperinsulinemia. In infancy, hyperinsulinism is the most common cause of recurrent and persistent hypoglycemia.[4] Other causes can be adrenal insufficiency, infant of a diabetic mother, growth hormone deficiency, multiple endocrine neoplasia, intrauterine growth retardation, inborn error of metabolism, small for gestational age.[5] To rule out the aforementioned causes serum metabolic screens, pH, lactate, ammonia, amino acids, urinary ketones, reducing substance, serum cortisol, and growth hormone levels were carried out but were found to be normal.

The serum glucose level of <60 mg/dl, nonketotic hypoglycemia in association with elevated insulin levels (>10 IU/ml), insulin glucose ratio from 0.4 to 2.7 (normal <0.3), sustained glucose requirement in excess of 10 mg/kg/min are confirmatory finding of PHHI.[6]

In this neonate case, glucose requirement was 15 mg/kg/min, and insulin levels were elevated. Optimization of blood glucose level prior to surgery is necessary to avoid adverse effects of hypoglycemia.

Timely nasogastric feeds, dextrose infusion, and drugs such as diazoxide, octreotide, etc., play an important role in blood glucose level optimization.[7]

Intra-operatively, our aim was to maintain normoglycemia to mild hyperglycemia and avoid fluid shifts of major surgery. We maintained the child with sevoflurane because other inhalation agents depress insulin release and promote glucose intolerance.[89]

Our second concern was to avoid hypoglycemia during surgery. Therefore continuous infusion of 10% dextrose was carried out to keep blood sugar level above 60 mg/dl. Rebound hyperglycemia can occur after pancreatic mass excision, but it is transient and resolves spontaneously. We also experienced hyperglycemia after pancreatic excision (180 mg/dl), therefore we had stopped dextrose 10% infusion but at the conclusion of surgery, the child was hypoglycemic (80 mg/dl).

Another concern is when glucose is supplemented with boluses of high concentration dextrose containing fluid, blood glucose level can exceed the renal threshold for glucose, causing glycosuria and osmotic diuresis. But it did not happen in our case as we had not given a very high concentration of dextrose. Hence, it is preferred to use the dextrose containing fluid as maintenance and Ringer lactate as replacement fluids.

The increased solution can cause volume over load in neonates. The maximum concentration of glucose that can be given through peripheral line is D 12.5%. Utmost care should be taken not to use dextrose 25% or dextrose 50% IV as this creates rebound hypoglycemia and hyperosmolarity in an infant who are hyperinsulinemic.[5]

In summary, pancreatectomy in PHHI is a semi emergency surgery that is performed to protect the brain. It is a safe procedure. The main challenge to the anesthetist is fluid management, to maintain normoglycemia and hemodynamic stability. In our case, the less than satisfactory outcome was because the baby had incurred multiple hypoglycemic episodes leading to brain damage even before he was referred to our hospital. This mandates early referral to a tertiary care center.