Abstract
In this chapter, the rare yet critical pediatric surgical procedure of pancreatectomy for hyperinsulinism is reviewed. The pathophysiology and diagnostic approach for congenital hyperinsulinism is discussed. The author covers the surgical interventions and their related complex anesthetic management in these patients, particularly with regards to maintenance of glucose homeostasis. The preoperative evaluation, anesthetic implications and regional anesthetic considerations are presented for this complex disease process.
An 18-day-old 4.3 kg female was admitted for evaluation of persistent hypoglycemia. The patient was born full term at 37 weeks 2/7 days. At one hour of life, the patient was listless and tremulous. Point of care glucose was noted to be <25 and the patient was treated and transferred to the NICU on a 20% dextrose infusion. Vital signs: Temp 37.2°C, RR 63, HR 138, BP 76/34.
What Is the Differential Diagnosis for Neonatal Hypoglycemia?
Acquired hyperinsulinism from diabetic mother
Beckwith–Wiedemann syndrome
Congenital hyperinsulinism
Fatty acid oxidation disorders
Glycogen storage disease
Growth hormone deficiency
Hypopituitarism
Inborn errors of metabolism
Ketotic hypoglycemia
Primary or central adrenal insufficiency
Type 1 diabetes mellitus
Exogenous insulin administration or other antidiabetic agents
Administration of beta blockers
What Are the Clinical Characteristics of Neonatal Hypoglycemia?
Hypoglycemia in newborns or young infants may be characterized by lethargy, feeding difficulty, hypothermia, sweating, respiratory distress, cyanosis, or apnea. However, seizures are often the presenting symptom.
What Is Congenital Hyperinsulinism?
Congenital hyperinsulinism (HI) is the most common hypoglycemic disorder in infants. It is a heterogeneous disorder of the pancreas consisting of two main types of histologic abnormalities of pancreatic structure: focal adenomatous hyperplasia and diffuse abnormality of the islet cells.
HI results from inappropriately high insulin secretion by the pancreatic B-cells. A failure to reduce pancreatic insulin secretion in the presence of hypoglycemia (serum glucose <60 mg/dL) is caused by structural or functional molecular abnormalities in the insulin secretory mechanism or glucose-sensing mechanism.
Increased insulin levels cause hepatic and skeletal muscle glycogenesis. Glycogenesis decreases the amount of free glucose in the bloodstream causing a suppression of free fatty acids (FFA) formation resulting in hypoglycemia.
What Is the Genetic Component of HI?
The congenital pancreatic abnormalities associated with HI are caused by genetic mutations on various genes that regulate insulin secretion. Although approximately 50% of HI cases have no known genetic abnormality, 11 genes have been identified in relation to pancreatic beta cells involved in insulin secretion regulation. The most common cause of HI is inactivating mutations in ABCC8 or KCNJ11 genes of the Na+/K+ ATP channel.
What Are the Two Types of HI?
There are two forms of HI, diffuse and focal. In diffuse HI, beta cells throughout the pancreas are affected, with nucleomegaly seen through the pancreas. In focal HI, a distinct area of beta cell adenomatosis is seen. Focal HI involves the combination of paternally inherited ABCC8 or KCN11 mutations along with the somatic loss of the maternal tumor suppressor genes on chromosome 11p 15.
What Is the Incidence of HI?
The estimated incidence of HI is 1/50,000 live births. However, in countries with substantial consanguinity incidences may be as high as 1/25,000.
What Is the Age of Presentation?
HI can present between birth and 18 months of age, with most cases diagnosed shortly after birth. Although rare, adult-onset cases have been documented.
What Is the Presentation of HI?
Patients present with hypoglycemia ranging from asymptomatic hypoglycemia noted on routine blood glucose monitoring, to life-threatening hypoglycemic coma or status epilepticus. Many are diagnosed by routine blood work, while others are diagnosed later when they present with hypoglycemia symptoms. The risk of severe hypoglycemia causing seizures and permanent brain damage is high. Some infants may be large for gestational age.
How Is the Diagnosis of HI Made?
Diagnostic criteria for HI include blood glucose <40 mg/dL, +/− detectable insulin, decrease in beta-hydroxybutyrate, decrease in free fatty acids, decrease in IGF-BP1, and positive glucagon response.
How Is Congenital Hyperinsulinism Managed?
First-line treatment is diazoxide, a benzothiazine derivative, which activates the SUR 1 subunit of the K+/ATP channel and opens the K/+ATP channel leading to a decrease in insulin. Diazoxide dose range is 5–15 mg/kg/day given orally twice a day. Side effects include hypertrichosis and fluid retention. Many neonates require diuretic therapy along with diazoxide. Pulmonary hypertension may occur in patients without adequate diuretic therapy.
Diazoxide is given as a 5-day trial (Figure 26.1). If diazoxide is not successful in maintaining a blood glucose >70 mg/dL during a 12 hour fast, it may suggest that the patient has a defect on the K+ ATP channel. A genetic workup should be initiated immediately.
