Diabetes mellitus

Diabetes mellitus

Anesthetic relevance	High
Anesthetic management	Preoperative HgA1c value Preoperative glucose value Preoperative medication adjustment Insulin administration Post-operative glucose
Specialty	Endocrine
Signs and symptoms	Excessive thirst Polyuria Polydypsia Glucosuria Peripheral neuropathy Ocular degeneration Cardiovascular disease
Diagnosis	HgA1c Fasting glucose
Treatment	Oral anti-hyperglycemics Exogenous insulin administration
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Editor rating	Unrated
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Diabetes is an endocrine, metabolic disorder marked by high levels of blood glucose. Three classifications of diabetics exist:

1. Type 1 Diabetes, where an immune mediated destruction of pancreatic beta cells occurs causing a total reduction in endogenous insulin and thus causing hyperglycemia
2. Type II Diabetes, where patients experience increasing insulin resistance for the level of endogenous insulin thus causing hyperglycemia
3. Gestational Diabetes in which hyperglycemia occurs in the second or third trimester of pregnancy.

The diagnosis of diabetes is made based on fasting blood glucose levels and hemoglobin A1c levels. The diabetic population in the United States is both increasing in incidence and prevalence within the last decade. This disease affects multiple organ systems that have anesthetic implications including cardiovascular health, renal disease, peripheral neurologic function, and gastrointestinal emptying requiring preoperative optimization and intraoperative control.

Cystic fibrosis patients have an acquired form of diabetes as the most common co-morbidity of cystic fibrosis (20% of adolescents and 40-50% of adults).

Anesthetic implications

Preoperative optimization

• No overt indications for case cancellations for poorly controlled diabetes except if patients are in diabetes ketoacidosis (DKA) or hyperosmolar osmotic non-ketotic crisis (HONK)
• Postoperative blood glucose greater than 140 mg/dL is found in as many as 40% of patient undergoing non-cardiac surgery and almost 25% of those patients demonstrate a blood glucose greater than 180 mg/dL during the operative and immediate post-operative period
• Data shows mixed reduction of mortality with good blood glucose control in surgical patients, but a reduction in surgical site infection risk
• Consider case delay alongside surgery team if BG > 250 mg/dL and case is elective and a prothesis or synthetic biofilm will be inserted into the patient during surgery (i.e. prothesis, intraocular lens, joint replacement, graft, etc).
• Obtain pre-operative HgA1c if one has not been obtained via primary care in last 3 months prior to surgery
  • If HgA1c > 8.0 - evidence shows greater incidence of post-operative hyperglycemia during patient recovery

Pre-operative medication adjustments:

Drug Class	Medication	Day before Surgery	Day of surgery	Notes
DPP-4 inhibitors	Sitagliptin/Saxagliptin lidagliptin/linagliptin	Take	Take
Alpha-glucosidase inhibitors	Acarbose/Miglitol	Take	Do not take
Sulfonylureas	Glipizide/glyburide	Take	Do not take
SGLT-2 inhbitors	dapagliflozin/canagliflozin empagliflozin	Hold 3 days prior to surgery	Do not take	Can cause euglycemic DKA if not stopped in advance of surgery
SGLT-2 inhibitors	ertugliflozin	Hold 4 days prior to surgery	Do not take	Can cause euglycemic DKA if not stopped in advance of surgery
Biguanides	metformin/Metformin ER	Take	+/- take	Hold if patient has renal/hepatic insufficiency, COPD or CHF or if team anticipates potential for AKI or hepatic shock during case
GLP-1 agonist	exenatide/exenatide ER	Take	Do not take
GLP-1 agonist	dulaglutide	Take	Do not take
GLP-1 agonist	semaglutide	Take	Do not take
GLP-1 agonist	liraglutide	Take	Do not take
Amylin mimetics	pramlintide	Take	Do not take
Long acting insulin	Glargine/detemir/degludec	Take 80% of dose	Take 80% of dose	Coordinate with patient's endocrinologist
U-500 insulin		Take usual dose	Take 50% of dose	Coordinate with patient's endocrinologist
70/30 insulin		Take usual dose	Change to NPH and give 50% of dose	Coordinate with patient's endocrinologist
70/25 insulin		Take usual dose	Change to NPH and give 50% of dose	Coordinate with patient's endocrinologist
50/50 insulin		Take usual dose	Change to NPH and give 50% of dose	Coordinate with patient's endocrinologist
NPH insulin		Take usual dose	Take 50% of dose	Coordinate with patient's endocrinologist
Prandial insulin		Take usual mealtime dose	Do not take	Coordinate with patient's endocrinologist
Insulin pump			Set at 80% basal rate	Coordinate with patient's endocrinologist

Intraoperative management

Institutional practices may vary, however the general principle is to perform close monitoring and maintain euglycemia. Stanford intraoperative glycemic care guidelines recommend targeting a blood glucose of 140-180 during surgery. An interval of q2h is appropriate if the patient's blood glucose remains within this range. Sugars between 70-140 warrant closer q1h monitoring, and any sugar below 70 in most adult patients necessitates treatment with a dextrose bolus (e.g. 12.5 g of D50) with subsequent q15 min glucose checks.

For patients with hyperglycemia >180, the duration of surgery and level of critical illness can guide whether intermittent subcutaneous insulin vs continuous insulin infusion is appropriate for intraoperative management. Subcutaneous insulin (e.g. Humalog a.k.a. Lispro) is delivered every 2-3 hours based on a sliding scale (cannot be delivered more frequently due to the time to peak effect of insulin and risk of dose stacking). Continuous insulin infusions are generally titrated every hour with at minimum a rate of 0.5 units/hour running unless glucose levels fall below 100 mg/dL. Subcutaneous insulin management is not appropriate for patients with poor perfusion or those who have no change in glucose after 2 attempted doses.

Postoperative management

Continue sliding scale/insulin pump management post-operatively.

Related surgical considerations

Certain factors can predispose patients to being either insulin-sensitive or insulin-resistant intra-operatively. Factors that are associated with insulin-sensitivity include: new diagnosis; age >70 years old; BMI <25 kg/m2, eGFR <45 mL/min. Factors that are associated with insulin-resistance include: BMI >35 kg/m2; home TDD >80 units; steroids >20 mg prednisone/day.

Pathophysiology

Correctional dosing of insulin is based off of a patients total daily dose (TDD). This may already be known based off of a patients home regimen. For patients whose TDD is unknown, an adult's TDD can be approximated as 0.4U/kg/day.

From a patient's TDD, an insulin sensitivity factor (ISF) can be calculated that provides a patient's corrective dosing (i.e. the expected drop in glucose if a patient is given 1U of rapid-acting insulin).

ISF = 1800/TDD

As an example, a patient with a TDD of 48U will have an ISF of 37.5 (which can be rounded to 40). Therefore, one possible corrective dosing regimen could be 1U for every 40 >180 (assuming target glucose of 180).

Signs and symptoms

Intra-operatively, hypoglycemia can lead to cardiac arrhythmia and hemodynamic instability. Hyperglycemia has been shown to increase adverse post-surgical outcomes including surgical site infections, delayed wound healing, and increased length of stay.

Diagnosis

Diagnosis of diabetes can be made by a variety of ways:

1. Fasting plasma glucose ≥ 126mg/dL
2. Two-hour plasma glucose ≥ 200mg/dL
3. A1C ≥ 6.5 prior to initiating anti-hyperglycemic medications

Treatment

Medication

Humalog (Lispro) is a rapid-acting agent commonly used in sliding scale regimens. It's onset occurs in <15 minutes. Its peak occurs in 30-90 minutes. Duration is generally between 3-5 hours (which is why dosing is performed no more frequently than every 2-3 hours).

Long acting agents include glargine (Basaglar/Lantus) and are typically dosed once a day in the evening as part of a home insulin regimen.

Epidemiology

The diabetic population in the United States is both increasing in incidence and prevalence within the last decade. According to the 2017 National Diabetes Statistics Report from the Center for Disease Control (CDC), 10.5% of the U.S. population has diabetes with an estimated 21.4% of those who have the disease are still not diagnosed.