Hyperglycemia

Description

Hyperglycemia (>180–200 mg/dL) is common in diabetics as well as critically ill patients without diabetes. It can result from
- Insulin deficiency
- Insulin receptor resistance
- Excess of glucagon
- Glucose over-administration
Stress-induced hyperglycemia compared to diabetic hyperglycemia has been reported to increase the length of hospital stay and in-hospital mortality.

Epidemiology

Prevalence

Approximately 23 million patients have diabetes.
Type 2 diabetes is seen in ~12.9% of people older than 20 years of age.

Morbidity

Diabetes is associated with a higher risk of acute myocardial infarction, stroke, and heart failure

Mortality

Three-fold increase in mortality in patients with hyperglycemia following acute myocardial infarction.
Poor outcome has been observed in non-diabetic patients with acute stroke and stress-induced hyperglycemia.

Etiology/Risk Factors

Underlying diabetes mellitus (DM)
Inadequate insulin dosing in diabetics
Concurrent medical illness: Stroke, acute myocardial infarction, trauma, sepsis, hypoxia
Medication side effect
Obesity

Physiology/Pathophysiology

In healthy individuals, the blood glucose level is closely regulated by insulin production, hepatic glucose uptake, and production.
Insulin actions include
- Increased transport of glucose, potassium, and amino acids into cells
- Protein synthesis
- Glycogen synthesis
- Inhibition of gluconeogenesis
Counterregulatory hormones (cortisol, catecholamine, growth hormone) decrease peripheral glucose uptake, inhibit hepatic glucose uptake, and increase hepatic gluconeogenesis and glycogenolysis.
Hyperglycemia
- Insulin deficiency (or insulin resistant states) can result in fat catabolism and increased formation of acetyl CoA. Acetyl CoA will then form ketone bodies.
- Immune function. Impairs phagocytic function (adherence and chemotaxis) of neutrophils and monocytes. Believed to be secondary to elevated cytosolic calcium in polymorphonuclear (PMN) leukocytes that result in reduced ATP synthesis as well as reduced superoxide formation in leukocytes.
- Fluid balance. Glycosuria promotes dehydration and various electrolyte imbalances. It can cause serum hypertonicity and acidosis.
- Cardiovascular system. Hyperglycemia can increase systolic and diastolic BP, prolong the QTc, and elevate catecholamine levels. Hyperglycemia can increase platelet activation and adhesion, leading to thrombosis; as well as inflammatory markers such as TNF, IL-6, and IL-18. Studies have also demonstrated that it affects ischemic preconditioning of the heart and reduced coronary collateral blood flow.
- Central nervous system (CNS). The penumbra area that surrounds the ischemic zone in the brain is at increased risk for further infarction in hyperglycemic states because of the ensuing acidosis and high lactate levels. High levels of lactate can damage astrocytes, endothelial cells, and neurons.
Glycemic control. Studies have yielded varying results.
- In critically ill surgical patients, tight glycemic control using intensive insulin therapy (between 80 and 110 mg/dL) has shown improved outcomes.
- However, subsequent studies in the medical intensive care unit (ICU) have failed to show similar benefits in all patients and more hypoglycemic episodes observed in patients with more than 3 days of hospital stay.
- Furthermore, glucose variability has been shown to be more important than maintaining the glucose level in a certain range. Fluctuation of blood glucose can cause increased apoptosis, cytokine expression, and oxidative stress markers.

Prevantative Measures

Surgical and anesthetic techniques that can minimize hyperglycemia responses:

Minimally invasive surgery. The stress of surgery can reduce insulin sensitivity and the release of counterregulatory hormones that can cause hyperglycemia.
Avoid hypovolemia which can trigger a hyperosmolar hyperglycemic nonketotic (HHNK) state (severe hyperglycemia often >600 mg/dL, hyperosmolarity often >320 mOsm/kg, glycosuria with worsening hypovolemia, and central nervous system depression). Dehydration combined with baseline impaired insulin production can further decrease insulin levels and worsen hyperglycemia (compared to diabetic ketoacidosis, HHNK has sufficient levels of insulin to prevent lipolysis and ketone production).
Prevent nausea and vomiting (can lead to hypovolemia and electrolyte imbalances). Identify patients at risk and avoid drugs with emetic properties (if possible) and administer prophylactic treatment.
Appropriate pain relief management to reduce the stress of surgery
Neuraxial blockade. General anesthesia can result in a greater release of stress hormones compared to local or epidural anesthesia. Volatile anesthetic agents can inhibit insulin release and increase hepatic glucose output.

Diagnosis ⬆ ⬇

Preoperative blood sugar testing in all diabetics.
Intraoperative blood sugar testing should be considered in brittle diabetics and critically ill patients.
Postoperative blood sugar testing is typically performed in all diabetics in the recovery room. Cases that are short in duration, ambulatory, minimal stress, and/or performed with sedation may not require repeat testing in the recovery room (e.g., cataract, skin biopsies, etc).

Differential Diagnosis

Inaccurate monitor results

Treatment ⬆ ⬇

A multidisciplinary approach involving the anesthesia provider, surgeon, endocrinologist, intensivist, cardiologist, and dietitian may be necessary to minimize the perioperative morbidity and mortality in diabetic patients.
Preoperatively, blood glucose should be adequately controlled as per American Diabetes Association (ADA) recommendations.
- HbA1C should ideally be <7%
- Preprandial glucose between 90 and 130 mg/dL
- Postprandial glucose <180 mg/dL
Schedule elective cases for diabetic patients early in the day.
On the day before surgery
- Oral hypoglycemic drugs should be dosed normally
- Long or intermediate acting insulin can be given in usual doses while taking a normal diet. Evening or night doses are normally decreased to avoid hypoglycemia on the day of surgery.
- While NPO, order blood sugar checks frequently. If hypoglycemic, treat with 15–20 gm of glucose. Options include clear liquids, in the form of sugary drinks and fruit juices, sodas, or electrolyte solutions.
On the morning of the surgery
- Hold oral hypoglycemic agents to prevent reactive hypoglycemia
- Withhold short-acting insulin, but insulin pumps can be maintained at basal rate
- Intermediate insulin may be given according to the following formula: Fraction = [(Dosing interval in hours) – (Hours of fast during interval)]/Dosing interval in hours. for example, a patient is scheduled for hernioplasty. He will be eating normally at 10 am after minimally invasive anesthesia.
  - If he takes 24 U NPH daily at 7 am, then the fraction of intermediate insulin to give is (24 – 3)/24 = 7/8. Thus, at 7 am, he will receive 7/8th of his morning dose or 21 U of NPH.
  - If he takes 24 U of NPH twice a day at 7 am and 7 pm, then the fraction of insulin to give is (12 – 3)/12 = 3/4. Thus, at 7 am, he will receive 3/4th of his morning dose or 18 U of NPH.
for cases later in the day
- Maintain a basal rate for patients on insulin pump
- Consider advising that the patient takes a fraction of the intermediate acting insulin according to the formula above.
- Consider allowing a small/light early snack such as toast (center-dependent).
Intraoperatively
- Insulin-dependent diabetics: Consider administering an insulin infusion starting at 0.02 U/kg/h (100 U of insulin is mixed with 100 mL of IV fluid to yield a concentration of 1 U/mL) with a separate D5% or D5NS drip at 100–125 mL/h, for adult patients. Subsequent titration should be based upon the desired glucose target.
- Alternatively, for insulin-dependent diabetics undergoing short procedures or minor surgeries, or noninsulin-dependent diabetics, scheduled glucose testing may be performed and treated as needed.
- Correction of hyperglycemia may be performed with correction doses of ultra short-acting insulin; 1–4 U IV typically decreases blood sugar by 50 mg/dL.
Recovery room or on the inpatient ward. While the patient is NPO, sliding scale insulin dosing is commonly performed. When oral intake has resumed, oral medications may be restarted alongside a sliding scale regimen. In insulin dependent diabetics, regular insulin dosing may be restarted alongside a sliding scale regimen.
In the ICU
- Some studies have documented decreased morbidity and mortality with normalization of blood glucose within a range of 140–150 mg/dL.
- Type 1 diabetic patients require basal amounts of insulin.
- Type 2 diabetic patients: Withhold all oral hypoglycemia agents to prevent reactive hypoglycemia. Patients with renal disease are at increased risk of lactic acidosis if treated with biguanides.
- Initiate a sliding scale insulin infusion with a basal longer acting preparation to provide more consistent glucose control.
- Subcutaneous insulin administration during critical illness may be unpredictable.
Transition from the intensive care to general care with basal-bolus insulin has been shown to demonstrate superior glycemic control. Ideally, the transition should take place either before leaving the ICU or shortly thereafter. Several techniques have been described and are often institution or practitioner specific.
- The starting dose for subcutaneous insulin should be 50–80% of the total IV insulin dose over the last 24 hours; it may be given daily or divided into twice daily dosing as a long-acting insulin analog (insulin detemir or insulin glargine). for example, if 72 U of IV insulin have been administered over 24 hours, then the subcutaneous insulin dosing would range from 36 to 58 U (QD or BID).
  - Alternatively, the Miami 4/12 formula can be utilized. Dosage of basal insulin = body weight (kg)/4. for example, a patient who weighs 72 kg needs 72/4 = 18 U of basal insulin. Dosage of bolus insulin = body weight (kg)/12. for example, a patient who weighs 72 kg needs 72/4 = 6 U of rapid-acting insulin before a meal.
  - The first dose of long-acting insulin should be given 2–3 hours and the short-acting insulin 1–2 hours before stopping an insulin infusion.

Follow-Up ⬆ ⬇

Patients, who were diagnosed as stress-induced hyperglycemia, requiring intensive insulin therapy or not known to be diabetic before, need outpatient follow-up to confirm the diagnosis of DM in an unstressed state.
Long-standing and uncontrolled diabetes can cause a myriad of intraoperative events:
- Difficult intubation due to joint rigidity seen in Type 1 DM.
- Risk of aspiration due to gastroparesis
- Wide hemodynamic disturbances during induction

References ⬆ ⬇

Cowie CC , Rust KF , ford ES , et al. Full accounting of diabetes and pre-diabetes in the U.S. population in 1988–1994 and 2005–2006. Diabetes Care. 2009;32(2):287–294.
Fahy BG , Sheehy AM , Coursin DB. Glucose control in the intensive care unit. Crit Care Med. 2009;37(5):1769–1776.
Lipshutz AK , Gropper MA. Perioperative glycemic control: An evidence-based review. Anesthesiology. 2009;110(2):408–421.
American Diabetes Association . Diagnosis and classification of diabetes mellitus. Diabetes Care. 2005;28(Suppl 1):S37–42.
Marik PE. Glycemic control in critically ill patients: What to do post NICE-SUGAR?World J Gastrointest Surg. 2009;1(1):3–5.
Raju TA , Torjman MC , Goldberg ME. Perioperative blood glucose monitoring in the general surgical population. J Diabetes Sci Technol. 2009;3(6):1282–1287.
Vann MA. Perioperative management of ambulatory surgical patients with diabetes mellitus. Curr Opin Anaesthesiol. 2009;22(6):718–724.

section name header

Basics ⬇

Prevalence

Morbidity

Mortality

Diagnosis ⬆ ⬇

Treatment ⬆ ⬇

Follow-Up ⬆ ⬇

References ⬆ ⬇

Additional Reading ⬆ ⬇

Codes ⬆ ⬇

Clinical Pearls ⬆ ⬇

Author(s) ⬆