Preop mgmt of diabetes meds in pts undergoing surgery

For patients with type 2 diabetes, suggest giving at least 50% of a long-acting insulin the morning of surgery. Or advise giving about 75%....
Abdelwahab Ward, BS Pharm, PharmD

Overview

The goal is to help prevent the blood glucose seesaw. Consider these strategies, but be aware, evidence is lacking for the best preoperative glucose targets or protocols for diabetes medications. Continue to recommend avoiding tight blood glucose control around surgery to limit hypoglycemia. Generally aim to keep glucose below 180 mg/dL or lean toward less than 200 mg/dL for patients with hypoglycemic risks.

NPS-adv

Periop. management of diabetes medications

Non-insulin medications

Advise holding most non-insulin diabetes medications the morning of surgery. Dispel the myth that metformin needs to be held longer. But consider holding empagliflozin (Jardiance) or other SGLT2 inhibitors starting the day BEFORE surgery due to ketoacidosis risk. Be aware, it may be okay to continue DPP-4 inhibitors or GLP-1 agonists. Limited evidence suggests these are safe around some surgeries and suggest restarting non-insulin medications once normal oral intake resumes.

Insulin

For patients with type 2 diabetes, suggest giving at least 50% of a long-acting insulin the morning of surgery. Or advise giving about 75% of a long-acting dose scheduled the evening before. In patients with type 1 diabetes, recommend continuing the long-acting insulin. But consider decreasing the dose if there are risks, such as frequent hypoglycemia or a basal dose more than 60% of their daily insulin dose.

For all diabetes patients, expect IV insulin infusions for longer or more complex surgeries, such as a coronary artery bypass graft (CABG). After surgery, recommend restarting stable patients on their home insulin regimen. For patients with limited oral intake, advise starting with about 75% of their long-acting dose. If insulin-naive patients come out of surgery on an insulin infusion, suggest switching to a long-acting insulin or stopping insulin if blood glucose is well controlled on a low infusion rate. Advise caution if insulin-naive patients are sent home on insulin. If insulin is needed, verify the patient is willing and able to get early follow-up after discharge. And ensure education is provided.

Table (1) Perioperative management of diabetes medications in hospitalized patients undergoing surgery
OPTIONS FOR MANAGING GLUCOSE CONTROL BEFORE AND AFTER SURGERY
Drug or Drug Class Pertinent Information or Suggested Approach
Metformin Concern: surgery- or contrast media-associated renal insults may put patient at risk of lactic acidosis.

Generally hold the morning of surgery. Consider continuing for minimally invasive surgery if no contrast media will be administered.

Restart when eating and drinking normally. For inpatients, consider waiting at least 48 to 72 hours post-operation, and no further tests or procedures are scheduled. If eGFR < 45 mL/min, hold until renal function normalizes.

If the patient has received iodinated contrast media, hold/resume metformin per institution protocol. American College of Radiology guideline suggest holding metformin for 48 hours post-imaging with non-gadolinium contrast media in patients with severe renal impairment or undergoing arterial studies that might cause emboli to the renal arteries.
Sulfonylureas and meglitinides (e.g. glyburide, repaglinide) Concern: potential for hypoglycemia in fasting patient.

Hold the morning of surgery. If surgery is in the afternoon, a meglitinide could be taken in the morning if patient eats breakfast.

Restart post-operation when patient is stable and eating regularly, and no further tests or procedures are scheduled.
SGLT2 Inhibitors (canagliflozin, dapagliflozin, empagliflozin, ertugliflozin) Concern: euglycemic ketoacidosis and dehydration in surgery patients.

U.S. labeling recommends stopping at least 3 days prior to surgery (at least 4 days for ertugliflozin).

Monitor and appropriately manage glucose after discontinuation. Be aware that although about two-thirds of ketoacidosis cases associated with SGLT2 inhibitors occur at a glucose ≥ 250 mg/dL, it can happen at lower levels too. Suspect ketoacidosis in the event of symptoms such as shortness of breath, nausea, vomiting, or fatigue. Note that urine ketones may not test high.

Post-operation, the home regimen can generally be resumed when patient is stable and eating and drinking regularly, no further tests or procedures are scheduled, and any other risk factors for ketoacidosis have resolved (e.g. urinary tract or other infection, renal impairment).
DPP-4 Inhibitors (alogliptin, linagliptin, saxagliptin, sitagliptin) Patients are typically advised to hold DPP-4 inhibitors on the morning of surgery. However, these agents are relatively safe in this setting. Some experts suggest continuing.

Sitagliptin alone or in combination with basal insulin provides glycemic control similar to that of basal-bolus insulin without increasing the risk of hypoglycemia or prolonging hospital stay.

Ensure dose is adjusted for renal function.

If held, restart with oral intake.
Thiazolidinediones (pioglitazone) Concern: edema and heart failure.

Generally hold the morning of surgery. Consider continuing for minimally invasive surgery.

If held, restart with oral intake.
Acarbose Hold if patient is not eating regular meals because the mechanism of action is inhibition of dietary carbohydrate breakdown in the intestine. If surgery is in the afternoon, it could be taken in the morning if the patient eats breakfast.

Post-operation, the home regimen can generally be resumed when patient is stable and eating regularly, and no further tests or procedures are scheduled.
GLP-1 Inhibitor (dulaglutide, exenatide, liraglutide, lixisenatide, semaglutide) Concern: gastrointestinal side effects post-op due to delayed gastric emptying.

Consider administering per usual. Liraglutide has been initiated prior to elective surgery for perioperative glucose control. Avoid in gastrointestinal surgeries.
INSULIN:
  • For elective surgery, try to schedule insulin-treated patients first to reduce glucose excursion and allow early oral intake.
  • Intensive glucose control (i.e., near-normal target) should be avoided perioperatively due to the risk of hypoglycemia.
  • Consider a glucose target of ≤ 180 mg/dL (10 mmol/L), or even up to 200 mg/dL (11.1 mmol/L).
  • Avoid sliding scale regimen.
  • Post-operation, ERAS protocols promote normal oral intake, which in turn allows patients to resume their home meds, thus reducing risk of harm. If oral intake is insufficient, reduce insulin doses accordingly. Consider a 20% to 25% reduction for safety.
Insulin Pertinent Information or Suggested Approach
Basal insulin (e.g., glargine, detemir, degludec, NPH) Evening before surgery:
  • Usual dose the night before surgery, especially if patient has type 1 diabetes. Or
  • Reduce nighttime dose (by 20% to 30% for type 2 patients; by 10% to 20% for type 1 patients), especially for patients who have a history of nocturnal or morning hypoglycemia, or those with tight control.
Morning of surgery:
  • Type 1:
    • Give usual dose of morning basal insulin.
    • Consider reducing dose by 50% if patient has a history of hypoglycemia with prolonged fasting; has frequent hypoglycemia (especially at night or early morning) has overnight glucose drops of > 40 mg/dL (2.2 mmol/L); needs a bedtime snack to avoid hypoglycemia; or takes a high basal dose (e.g. > 60% of total daily insulin dose). Or
  • Type 2:
    • NPH: consider giving 50% of the usual morning dose.
    • Other basal insulins: consider giving 50%, or as much as 60% to 80% of the usual morning dose.
General considerations:
  • Dose reduction may be especially prudent if patient’s surgery is scheduled for later in the day.
  • It is imperative that patients with type 1 diabetes continue their basal insulin to prevent ketoacidosis.
Premixed insulin Patient can take usual dose the evening before surgery, but omit pre-mix dose the morning of surgery.

The morning of surgery, give 50% of the basal component as NPH or, if blood glucose is > 200 mg/dL (11.1 mmol/L), 50% of the usual morning dose of premix can be given.
Prandial insulin Omit bolus doses while patient is NPO.
Insulin pump Consider use of protocols that allow patients to self-manage pump when appropriate, for patient safety and satisfaction.

The following is sample guidance based on the anticipated duration of the surgery.
  • At arrival/admission:
    • Document type of pump, type of insulin (designate U-100 vs. U-500), and insulin dose (basal rate, carbohydrate to insulin ratio, insulin sensitivity factor). Do this at the pre-op visit, if applicable. Enter in electronic medical record in a place accessible to all caregivers.
    • Consult endocrinology. Do this at pre-op visit, if applicable.
    • Confirm basal rate with patient. Keep pump on basal setting or consider a 10% to 20% reduction (ADA: 20% to 40% reduction).
    • Check insertion site for swelling or leaking. Document date of insertion.
    • Check glucose using point-of-care testing. Treat symptomatic hypoglycemia or glucose ≤ 70 mg/dL (3.9 mmol/L) by stopping pump and giving 12.5 to 25 mL of D50W intravenously. Re-check in five minutes.
  • For non-cardiac procedures lasting < 1 hour (and perhaps up to 2 hours) (inclusive of pre-operative sedation, procedure, and recovery):
    • Pre-operation, if glucose is above target, patient can self-treat per usual (assuming sedatives have not yet been given). If pre-op blood glucose is > 300 mg/dL, consider switching to intravenous insulin infusion, and check for problems with pump or infusion site.
    • Continue basal rate for most patients. If MRI, x-ray, or defibrillation anticipated, disconnect pump and secure outside operating room.
    • Do not use pump intraoperatively if patients may become hemodynamically unstable, or infusion site is close to surgical field. In these cases, switch to intravenous insulin infusion.
  • For non-cardiac procedures lasting one to three hours (inclusive of pre-op sedation, procedure, and recovery):
    • Pre-operation, if glucose is within target range, patient can self-administer (assuming sedatives have not yet been administered) one hour’s worth of basal insulin as a bolus. Hold bolus if glucose ≤ 110 mg/dL (6.1 mmol/L). If above glucose target, patient can self-treat per usual.
    • Disconnect pump and secure outside operating room.
    • If pre-op blood glucose is > 300 mg/dL (16.6 mmol/L), major blood loss is anticipated, or fluid or temperature shifts are anticipated, consider intravenous insulin infusion (see dosing, below).
    • Post-operation, check glucose before re-connecting pump.
  • For non-cardiac procedures lasting > 3 hours (inclusive of pre-operative sedation, procedure, and recovery):
    • Disconnect pump.
    • Start intravenous insulin infusion within one hour of stopping pump.
    • If pump basal rate was < 1 unit/hour, start insulin infusion at 0.5 unit/hour. If pump basal rate was > 1 unit/hour, start insulin infusion at 2/3 the pump basal rate.
    • Follow institution’s insulin infusion algorithm for adjustments.
    • Post-operative management depends upon whether the patient is stable, and competent to manage pump and record carbohydrate intake.
      • If patient is stable and competent, start insulin pump within 30 minutes of stopping intravenous insulin infusion.
      • If patient is not stable and competent, continue as per intraoperative management, or switch to basal subcutaneous insulin. Continue infusion for one to two hours after administration of basal subcutaneous insulin.
TREATMENT OF PERIOPERATIVE GLUCOSE EXCURSIONS
Target Intensive glucose control (i.e. near-normal target) should be avoided perioperatively due to the risk of hypoglycemia. Consider a target of ≤ 180 mg/dL (10 mmol/L), or even 200 mg/dL (11.1 mmol/L).

Post-cardiac surgery, glucose target is 100 to 150 mg/dL (5.5 to 8.3 mmol/L) for the first three days.
Test Check blood glucose every four to six hours while NPO. Consider checking blood glucose every one to two hours for patients on continuous intravenous insulin or who are critically ill.
Treat In critical care areas, cardiac surgery, prolonged surgery in patients with type 1 diabetes, or very high glucose levels, use an intravenous insulin infusion per institutional protocol.

For other post-op patients, consider basal insulin if patient is not restarted on their oral diabetes medications.
  • Example: patients requiring only oral agents at home could be switched to basal insulin 0.25 units/kg once daily, reduced to 0.15 units/kg/day if ≥ 70 years of age or SCr ≥ 2 mg/dL (176.8 umol/L).Treat excursions above target or pre-meal glucose > 140 mg/dL (7.8 mmol/L) with rapid-acting or regular insulin.Do not give any pre-op boluses unless glucose > 200 mg/dL (11.1 mmol/L) AND >3 hours pre-operation.

Do not use sliding scale insulin.
TRANSITION FROM INPATIENT INSULIN REGIMEN TO HOME REGIMEN (i.e. preparation for discharge)
Insulin infusion to subcutaneous insulin The following is sample guidance based on ADA standards and published protocols:
  • Give first dose of basal insulin two to four hours before intravenous insulin is discontinued. Consider a dose equal to 60% to 80% of the daily infusion dose (daily infusions dose = requirement in the last six to eight hours extrapolated to 24 hours). Give the remainder as prandial insulin, if applicable.
    • Also take into consideration the patient’s home insulin regimen, if applicable. Reduce the patient’s home total daily dose by 20% to 25% and give as basal insulin if the patient is NPO or has limited caloric intake. Alternatively, start 0.3 to 0.5 units/kg/day (total daily insulin dose), with 50% given as basal.
    • If the patient was not on home insulin, and using ≤ 1 unit/hour with glucose running <140 mg/dL (7.8 mmol/L), consider stopping insulin. For patients needing higher doses and/or glucose levels are running > 140 mg/dL (7.8 mmol/L), provide basal insulin as above.
  • Monitor glucose at least four times daily, and provide subcutaneous corrective coverage (not sliding scale) if needed.
Switching back to oral antidiabetic agents. Try to get patients switched back to oral agents at least one to two days before discharge.
SPECIAL POPULATION OR SITUATION
Clinical Situation Pertinent Information
Emergency surgery No short-acting bolus before surgery.

Check blood glucose every 30 to 60 minutes during surgery.

Start intravenous insulin infusion if glucose > 200 mg/dL (11.1 mmol/L).
Long or complex surgery Insulin infusion, especially for type 1 diabetes, coronary artery bypass grafting, or severe hyperglycemia. Check glucose every one to two hours.

Alternatively, give rapid-acting insulin every two hours as needed to control glucose.
Carbohydrate loading As part of ERAS protocols, patients with diabetes often receive a carbohydrate-containing beverage a few hours before surgery. However, there is little safety and efficacy data for this practice in patients with diabetes. There are anecdotal reports of surgical cancellations due to this practice.

Until more data is available, experts suggest that diabetes patients not receive these drinks.

NPS-adv

References

  1. Simha, V. and Shah, P. (2019). Perioperative Glucose Control in Patients With Diabetes Undergoing Elective Surgery. JAMA, 321(4), p.399.
  2. Duggan, E.W., Carlson, K. and Umpierrez, G.E. (2017). Perioperative Hyperglycemia Management. Anesthesiology, 126(3), pp.547–560.
  3. Diabetes Care in the Hospital: Standards of Medical Care in Diabetes—2019. (2018). Diabetes Care, 42(Supplement 1), pp.S173–S181.
Abdelwahab Ward, BS Pharm, PharmD