Hypoglycemia is defined as a serum glucose <70 mg/dL.
Tight glucose control has been shown to improve outcomes in critically ill patients; however, hypoglycemia is the most common complication of insulin therapy and has more immediate and direct deleterious effects.
Additionally, severely ill, elderly patients, and neonates have an increased susceptibility to the deleterious effects of hypoglycemia (permanent neurologic damage and death).
Epidemiology
Incidence
Rare in persons not treated for diabetes.
Severe hypoglycemia (episodes per 100 patients/year)
Type 1 diabetic: 11.5
Type 2 diabetic treated with oral hypoglycemic agents: 0.05
Type 2 diabetes treated with insulin: 11.8
Elderly patients: 2
Neonates: 15 per 1,000 live birth; higher incidence in large-for-gestational age, preterm, and intrauterine growth restricted (IUGR) infants, as well as those born to diabetic mothers.
Morbidity
Increased when intensive insulin therapy (IIT) in the medical intensive care unit (ICU) is implemented; particularly in patients with renal or hepatic failure.
Etiology/Risk Factors
Iatrogenic hypoglycemia
Overdose of insulin or other antidiabetic drug ingestion.
Decreased exogenous glucose intake (missed meals/snack or after overnight fasting).
Alcohol ingestion
Side effect of certain drugs: Haloperidol, pentamidine, quinine, and nonselective beta-blockers.
Severe illness
Tumors: Pancreatic islet cell adenoma or carcinoma, hepatoma, and sarcoma
Adrenal insufficiency
Autoimmune processes
Increased sensitivity to insulin following exercise, weight loss, or due to insulin sensitizers.
Renal failure: Decreased clearance of insulin
Neonates
Preterm delivery
Transient hypoglycemia of the newborn
IUGR
Sepsis
Hypothermia
Birth asphyxia
Inborn errors of metabolism
Hepatic enzyme deficiencies
Transplacental exposure to maternal hypoglycemic medications
Elderly: Frail, polypharmacy, and multiple hospital admissions.
Physiology/Pathophysiology
Glucose is a principal energy substrate for the body; for the brain, it is the sole energy substrate.
Glucose is synthesized from gluconeogenesis (from the metabolism of pyruvate, lactate, glycerol, and glucogenic amino acids) and glycogenolysis that results from the breakdown of glycogen.
In normal glucose homeostasis, blood glucose levels are tightly regulated by insulin, glucagon, epinephrine, and cortisol. The liver is the principal storage site for glucose in the form of glycogen.
A decrease in blood glucose level will cause
Drops in endogenous insulin production
Release of epinephrine, glucagon, growth hormone, and cortisol that act as counterregulatory hormones.
An increase in hepatic glucose production
A decrease in peripheral utilization of glucose
Neurogenic and neuroglycopenic symptoms
Diabetes
Type 1, or insulin-dependent, diabetics have reduced or absent insulin secretion. In addition, they have an impaired release of counterregulatory hormones such as glucagon and epinephrine.
In type 2 diabetes, patients are capable of generating and secreting insulin, but peripheral tissues are resistant to its effects. There is a lower risk of hypoglycemia compared to type 1 diabetes, potentially due to the sustained ability to secrete counterregulatory hormones.
Exogenous insulin administration and oral antihyperglycemic medications (e.g., sulfonylureas) can cause iatrogenic hypoglycemia.
Neonatal hypoglycemia can cause seizure and permanent brain damage. The brain utilizes glucose as the sole substrate of energy. In the rapidly growing neonatal brain, cerebral consumption comprises nearly 90% of their total glucose consumption; however, neonates are susceptible to hypoglycemia due to
Inadequate hepatic glycogen reserve
Immaturity of the liver in synthesizing glucose (hepatic gluconeogenesis).
Relative hyperinsulinism in infants of diabetic mother
Inherited disorders of metabolism
Impaired release of counterregulatory hormones
Evidence is suggesting that the benefits of tight glucose control may be outweighed by the potential harm of hypoglycemia.
The ACCORD trial revealed that intensive glucose control in patients with type 2 diabetes mellitus (HBA1C <6%) is associated with increased mortality and no reduction in adverse cardiovascular events.
The NICE SUGAR study revealed that in the ICU patients treated with IIT had increased mortality. IIT was defined as a blood glucose aim of 81106 g/dL; the conventional group was defined as a blood glucose aim of <180 g/dL.
Several studies report that maintaining a stable glucose level is equally important to the absolute glucose values. Fluctuations in glucose control lead to oxidative stress that cause macrovascular complications.
Cardiac surgical patients, particularly those requiring prolonged intensive care admissions, are an exception; they show a clear benefit from strict glycemic control.
Prevantative Measures
Diabetics. Preoperative assessment of glucose control, type and dose of medications, frequency of hypoglycemia, and current HBA1C level is needed.
On the day before surgery
Oral medications are usually dosed normally
Long or intermediate-acting insulin can be taken in usual doses while on a normal diet. Evening of night doses are normally decreased.
If hypoglycemic while NPO, treat with 1520 gm of glucose. Options include clear liquids, in the form of sugary drinks and fruit juices, sodas, or electrolyte solutions.
Blood sugar checks should be done frequently when NPO.
On the morning of surgery
In type 2 diabetics, oral medications and short-acting injectables should be withheld.
Insulin pumps should be maintained at a basal rate and short-acting insulin should be withheld.
for morning cases, hold intermediate-acting insulin or give a percentage of the dose calculated as below:
Fraction = [(dosing interval in hours) (hours of fast during interval)]/(dosing interval in hours)
for cases later in the day, maintain a basal rate for patients on an insulin pump and for patients on intermediate insulin, give a percentage of the dose based on the formula above.
In the recover room or hospital ward, resume oral hypoglycemic agents and insulin with food.
Hyperglycemia in the perioperative period. Correction doses of ultra short-acting insulin: 14 U IV typically decreases blood sugar by 50 mg/dL.
Diagnosis⬆⬇
Signs and symptoms are the result of:
Adrenergic excess; diaphoresis, tachycardia, palpitations, or tremulousness/shakiness.
Neuroglycopenia; headache, confusion, mental sluggishness, seizures, or coma
In anesthetized patients all symptoms may be masked; unexplained tachycardia can sometimes present. Blood glucose monitoring is confirmatory.
In awake patients
Severe hypoglycemia: Requires the presence of another person to actively administer carbohydrates, glucagon, or other treatments. It does not require documentation of the plasma glucose level. Symptoms resolve after restoring normal blood glucose.
Documented symptomatic hypoglycemia: The presence of hypoglycemic symptoms along with a documented blood glucose <70 mg/dL.
Asymptomatic hypoglycemia: Absence of hypoglycemic symptoms but documented blood glucose <70 mg/dL.
Probable symptomatic hypoglycemia: Presence of hypoglycemic symptoms with unknown blood glucose level.
Relative hypoglycemia: Presence of hypoglycemic symptoms but blood glucose level >70 mg/dL.
Whipple's triad: Hypoglycemic symptoms, symptoms relieved after glucose intake, and documented low blood glucose level.
Women respond less strongly to hypoglycemia than men.
Differential Diagnosis
Seizure
Vasovagal attack
Cardiac arrhythmia
Panic attack
Treatment⬆⬇
Fully conscious patient
Oral glucose (1520 g), sucrose or sugar containing fluid, orange juice, or a piece of fruit.
Ensure adequate subsequent food intake to prevent recurrence.
Impaired consciousness
Administer Dextrose 50% 2550 mL IV until there is a return of consciousness or normal blood glucose level. Then start a Dextrose 5% (D5W) or Dextrose 10% (D10W) infusion and titrate to effect.
In severe hypoglycemia, glucagon 1 mg IV may be administered. In patients without IV access, glucagon IM or SQ may be given.
Symptomatic infants
D10W 2 mL/kg IV bolus, followed by an infusion rate of 68 mg/kg/min. To achieve this rate:
D5W: IV rate (in mL/hr) = 8.4 × body weight (kg)
D10W: IV rate (in mL/hr) = 4.2 × body weight (kg)
Anesthetized patient
Administer Dextrose 50% 2550 mL IV, followed by repeat testing and careful observation with possible infusion. If glucose levels remain low, repeat the bolus and consider starting an infusion.
Follow-Up⬆⬇
Anesthetic management should aim to minimize the stress response during the intraoperative and postoperative period. Consider adequate pain relief and prophylaxis for nausea and vomiting.
Dexamethasone can elevate blood glucose for several hours, with a maximum blood glucose noted 120 minutes after dosing.
Autonomic neuropathy can cause swings in hemodynamic response during induction.
References⬆⬇
ZammittNN, FrierBM.Hypoglycemia in type 2 diabetes. Diabetes Care. 2005;28:29482961.
CryerPE.Management of hyperglycemia in type 2 diabetes: A consensus algorithm for the initiation and adjustment of therapy: A consensus statement from the American Diabetes Association and the European Association for the Study of Diabetes. Diabetes Care. 2007;30(1):190192.
Workgroup on Hypoglycemia, American Diabetes Association. Defining and reporting hypoglycemia in diabetes: A report from the American Diabetes Association Workgroup on Hypoglycemia. Diabetes Care. 2005;28(5):12451249.
GabrielyI, ShamoonH.Hypoglycemia in diabetes: Common, often unrecognized. Cleve Clin J Med. 2004;71(4):335342.
WintergerstKA, BuckinghamB, GandrudL, et al.Association of hypoglycemia, hyperglycemia, and glucose variability with morbidity and death in the pediatric intensive care unit. Pediatrics. 2006;118(1):173179.
NICE-SUGAR Study Investigators, FinferS, ChittockDR, et al.Intensive versus conventional glucose control in critically ill patients. N Engl J Med. 2009;360(13):12831297.
VannMA.Perioperative management of ambulatory surgical patients with DM. Curr Opin Anaesthesiol. 2009;22(6):718724.
Additional Reading⬆⬇
JoshiGP, ChungF, VannMA, et al.; Society for Ambulatory Anesthesia. Society for Ambulatory Anesthesia consensus statement on perioperative blood glucose management in diabetic patients undergoing ambulatory surgery. Anesth Analg. 2010;111(6):13781387.
MoghissiES, KorytkowskiMT, DinardoM, et al.American Association of Clinical Endocrinologists and American Diabetes Association consensus statement on inpatient glycemic control. Diabetes Care. 2009;32:11191131.
The DCCT Research Group: Hypoglycemia in the Diabetes Control and Complications Trial. Diabetes. 1997;46:271286.
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