Peri-operative Glycemic Control
The challenge of peri-operative glycemic control
Surgery and general anesthesia frequently lead to imbalances in glucose control, both intra-operatively and in the peri-operative period. These imbalances can occur in diabetic and non-diabetic patients and involve a complex relationship between patient factors such as baseline glucose control and underlying comorbidities and surgical/operative factors such as procedure complexity and type of anesthesia. The post-operative period brings additional challenges such as unpredictability in nutritional intake, hyperalimentation, and later, post-surgical complications such as sepsis.
Peri-operative hyperglycemia has been identified as a risk factor for morbidity and mortality. Intensive insulin therapy (IIT) has been shown to decrease post-operative infection rates and improve mortality in cardiac surgery patients. However, IIT has also been linked to increased incidence of severe hypoglycemia and related adverse events. Furthermore, the generalizability of specific blood glucose targets over a wide patient population is unclear; initial research showing improved outcomes with IIT in cardiac surgery patients has not played out in other patient groups.
The Hospitalist physician deals with peri-operative glycemic management in several settings. In the pre-operative clinic the Hospitalist must assess the surgical suitability of patients with disorders of glucose control. Patients with baseline diabetes have increased incidence of post-operative morbidity and mortality largely due to increased cardiovascular complications and poor wound healing. Also in the pre-operative setting, the Hospitalist is expected to formulate a plan for management of glucose control in the days leading up to surgery.
In the inpatient peri-operative setting, the Hospitalist must develop a management plan that maximizes normoglycemia while minimizing risk of hypoglycemia. The Hospitalist must also be adept in adjusting the plan to unpredictable post-operative courses as well as managing any complications of hyper- or hypoglycemia. Finally, the Hospitalist must be able to recommend a plan for glucose management as the patient is transitioned back to the outpatient setting.
Pathophysiology of Hyperglycemia
Surgical stress, anesthesia and critical illness cause increase of counter-regulatory hormones including cortisol, glucagon, epinephrine and growth hormone. Pro-inflammatory cytokines such as interleukin 6, interleukin 8 and tumor necrosis factor alpha are also upregulated. Together this neuro-endocrine response heads to upregulation of hepatic gluconeogenesis, glycogenolysis, lypolysis and protein catabolism as well as decreased peripheral glucose utilization and insulin resistance.
While the hyperglycemia response to stress may be adaptive in some respects, there are many deleterious effects, including impaired nitric oxide generation with resulting impaired vasodilation, decreased complement function, increased endothelial cell adhesion molecules, increased cytokine levels and impaired neutrophil chemotaxis and phagocytosis. In turn, pro-inflammatory cytokines lead to further peripheral glucose resistance thereby perpetuating hyperglycemia. This ultimately results in a pro-inflammatory state, hypercoagulability and increased risk of infection.
The magnitude of this response is determined by the presence of underlying disorders of glucose control, the type of anesthesia used (general anesthesia leads to a much bigger neuroendocrine response than neuro-axial), and the specifics of the surgery (on-pump cardiobypass procedures, for example, lead to particularly high rates of insulin resistance).
Insulin administration ameliorates some of the neuroendocrine response by stimulating peripheral glucose uptake and reducing endothelial cell activation. This benefit is thought related to the end result of normoglycemia rather than direct effects of insulin itself.
II. Identify the Goal Behavior.
General goals for peri-operative glycemic management
Goals for hospitalist management of peri-operative glucose control include the following:
Assess baseline glycemic control.
Identify and anticipate patient specific risk factors for peri-operative glucose imbalance.
Formulate a plan for diabetic medication management in the days leading to surgery.
Peri-operative and early post-operative:
Structure a plan for peri-operative glucose control that is tailored to the individual patient setting with attention to patient, operative, anesthetic and anticipated post-operative factors. This plan should strike a balance between adequate glucose control and minimized risk of hypoglycemia with general goals being:
Maintenance of fluid and electrolyte balance
Prevention of ketoacidosis
Avoidance of marked hyperglycemia
Avoidance of hypoglycemia
Manage post-operative complications of peri-operative hyper- and hypoglycemia.
Transition back to outpatient regimen.
Arrange for adequate patient education on nutrition and glucose management as needed.
Arrange any needed followup in the outpatient setting.
Specific glycemic targets
There is considerable controversy over optimal blood glucose targets. Studies have shown that intensive insulin therapy (IIT) is associated with improved outcomes in the post-cardiac surgery SICU (surgical intensive care unit) population, but such benefits have not played out in other settings and IIT is clearly associated with increased incidence of hypoglycemia. There is little data to guide specific glucose targets in post-surgical ward patients or the ambulatory surgery setting.
In general, available guidelines agree that relative normoglycemia should be the goal for most patient populations with target random glucose levels <180-200 milligrams/deciliter (mg/dL) if such levels can be achieved safely.
III. Describe a Step-by-Step approach/method to this problem.
The pre-op consultation
The Hospitalist management of peri-operative glucose control starts in the pre-op clinic. The pre-op assessment should include the following:
Assessment of operative risk. The diabetic population is at increased risk for multiple co-morbidities that may contribute to operative risk. Careful attention must be paid to any underlying cardiac, renal, electrolyte and hematologic abnormalities. Cardiac and renal diseases are particularly common; an electrocardiogram (EKG) is indicated even in the absence of symptoms to evaluate for underlying “silent” ischemia, and baseline kidney function should be checked.
Assessment of baseline glucose control. Glycosylated hemoglobin (HbA1C) should be checked in all diabetics if it has not been checked within the prior 3 months. This value will help guide peri-operative management and help determine the adequacy of the patient’s outpatient regimen for use in the inpatient setting. A history of typical daily blood glucose values (including timing of high and low values) is particularly important in patients with diabetes that is difficult to control. Type I diabetics with brittle diabetes and wide fluctuations in outpatient blood glucose levels may need to be managed with conservative inpatient glycemic targets to avoid hypoglycemia.
Long term diabetic control and surgical outcomes
The significance of baseline glucose control in operative outcomes needs further study, but there is evidence that patients with higher pre-operative HbA1C have increased post-operative infections in non-cardiac surgery, and increased 5-year mortality following cardiac surgery compared to diabetic patients with better pre-operative control. There is insufficient data to recommend a level of HbA1C above which elective surgery should be postponed; this is a decision that must take place after considering the specifics of the individual situation, including:
A detailed history of diabetes therapy. This includes information on the type of insulin, dose, timing and frequency of administration.
A detailed history of prior diabetic complications. This should include history of low blood glucose including the frequency, timing and awareness of hypoglycemic episodes and prior episodes of diabetic ketoacidosis (DKA).
The characteristics of the surgery. This includes the timing of the procedure, how long the patient must be NPO (nil per os or without food) before and after the procedure, duration and complexity of the procedure and type of anesthesia (general or neuro-axial).
Hyperglycemia in the immediate pre-op setting
Moderate hyperglycemia in the immediate pre-operative setting may be due to inappropriate discontinuation of diabetic medications and/or pre-operative stress, particularly in patients with good long-term control. In this situation, as long as there is no significant dehydration or electrolyte/acid-base disturbance it may be safe to proceed, but the specifics of the individual situation need to be considered.
Perioperative management strategies by specific situation
Patients with diet controlled type II diabetes:
Typically patients with type II diabetes that is adequately diet controlled in the outpatient setting require little peri-operative therapy. Glucose levels should be monitored every 6 hours by fingerstick (or before meals/bedtime [QAC/HS] if eating). Short-acting (aspart, lispro) insulin can be used as needed. For patients in this category who have persistently elevated blood glucose (ie>200 mg/dL), low-dose basal insulin (5-10 units at bedtime) can be added. If there is evidence for good baseline control with low pre-operative HbA1C, the post-operative hyperglycemia is likely related to the acute surgical stress; most patients in this category do not require insulin on discharge.
Patients with type II diabetes maintained on oral medications:
Oral diabetes medications can be dangerous in the peri-operative setting with unpredictable nutritional intake and the possibility of pre-operative changes in renal, hepatic and cardiac function. As such, patients should be instructed to hold all oral diabetic agents on the morning of surgery.
For patients who are undergoing minor procedures, who are not critically ill and for whom oral agents afforded good outpatient control, oral diabetic agents may be resumed post-operatively IF adequate oral intake has been established. For such patients, corrective insulin sliding scale is typically adequate control until they are able to resume oral medications, and it can be used in addition to orals after they have been restarted. For patients in this category who have persistently elevated blood glucose post-operatively (i.e., >200 mg/dL), low dose basal insulin (5-10 units at bedtime) can be added. If there is evidence for good baseline control with low pre-operative HbA1C, the post-operative hyperglycemia is likely related to the acute surgical stress; most patients in this category do not require insulin on discharge and will do fine on their oral medications.
Information on specific oral diabetic agents
Sulfonylureas (glyburide, glipizide, chlorpropamide, glimeperide): Sulfonylureas are insulin secretagogues and can lead to hypoglycemia in patients with inadequate oral intake. They should be held whenever a patient is NPO and resumed only once oral intake is adequate.
Alpha-glucosidase inhibitors (acarbose, miglitol): Alpha-glucosidase inhibitors inhibit the upper gastrointestinal enzymes (alpha-glucosidases) that convert complex polysaccharides to monosaccharides, thereby slowing the absorption of glucose. They are ineffective when a patient is NPO.
Metformin: Metformin inhibits hepatic gluconeogenesis and enhances peripheral glucose utilization. It has been linked to lactic acidosis, with increased risk in settings of renal, hepatic or cardiac failure, or any setting of potential hemodynamic instability. Patients should be instructed to hold this medication on the morning of surgery and it should not be restarted post-operatively until adequate PO is ensured AND renal, hepatic and cardiac function are stable and adequate. If there is the possibility that the patient will require an iodinated contrast study post-operatively, metformin should be held given the risk of contrast-induced changes in renal function.
Thiazolidinediones (rosiglitazone, pioglitazone): Thiazolidinediones act on muscle, liver and adipose tissue to decrease glucose production and increase glucose utilization through mediation of PPAR-gamma (peroxisome proliferator-activated receptor). This class of drugs has been associated with fluid retention and precipitation or worsening of cardiac failure. Patients should be instructed to hold these medications on the morning of surgery. Such medications should not be resumed post-operatively if there are concerns about cardiac or liver function, particularly in patients who have received large amounts of intra-operative fluids.
Dipeptidyl-IV (DPP-IV) Inhibitors (sitagliptin, linagliptin): DPP-IV inhibitors inhibit dipeptidyl peptidase IV, an enzyme that deactivates glucagon-like peptide-1. While these agents do not cause hypoglycemia, they do decrease gastric motility and can thereby cause problems with diet resumption post-operatively. They should be held the morning of surgery and not resumed post-operatively until enteral intake and bowel function are clearly established.
Patients with type I or insulin dependent type II diabetes
Peri-operative management of Type 1 and insulin dependent type II diabetics is formulated through an understanding of baseline glucose control, anticipated timing, length and duration of the procedure and anticipated complexity of the post-operative course.
All patients should have a baseline assessment of diabetic needs. This is best done in the pre-op clinic setting and includes HbA1C measurement, assessment of insulin sensitivity or resistance, and assessment of risk for hypoglycemia. See above under “The pre-op consultation” for further details.
For procedures that are neither long nor complex most patients can continue with subcutaneous insulin peri-operatively. In general, all insulin dependent diabetics should be maintained on intermediate or long acting insulin for basal control and short acting insulin for prandial and corrective coverage. The so-called “insulin sliding scale” alone is virtually never adequate in this patient population. A patient’s basal metabolic needs utilize approximately one-half of his or her total daily requirements even when NPO, thus patients should continue with basal insulin (with some dose adjustment) even when not eating. This is particularly important for Type I diabetics who ALWAYS require basal insulin to prevent ketosis.
PRE-OP: Patients should be instructed to take their basal insulin as routine on the evening (QH) prior to surgery. For patients on long-acting insulin (glargine or detemir), consideration can be given to switching to twice daily intermediate acting insulin (NPH) in the 1-2 days prior to surgery (1:1 conversion of total daily insulin dose). Theoretically this may minimize the risk of hypoglycemia on the morning of surgery as compared with the long-acting regimen, however, there are no studies comparing the two approaches. For patients that are at increased risk for morning hypoglycemia (either due to tight baseline control with history of low morning glucose levels or due to insulin sensitivity with unpredictable glucose levels), the evening dose of long or intermediate insulin should be reduced.
DAY OF SURGERY: Day of surgery regimens are formulated based on the timing and complexity of the procedure.
Minor early morning procedures with anticipation that the patient may have delay in breakfast but generally stick to usual meal plan:
Morning insulin should be delayed until after the surgery and then administered as usual before eating.
Short procedures later in the day for which breakfast and/or lunch will be skipped
Hold all short acting prandial insulin.
Place patients on low dose glucose infusion while NPO (e.g., Dextrose 5% 1/2 normal saline at 75 milliter/hour [mL/hr] ).
Follow fingersticks every 6 hours and use short acting correcting sliding scale for as needed treatment of hyperglycemia.
For patients who take once daily basal insulin (i.e., QAM dosing only) with or without prandial coverage throughout the day, hold prandial coverage and administer one-half to two-thirds of the basal dose.
For patients who take twice daily basal coverage (i.e., Twice a day glargine or two or three times a day NPH) with or without prandial coverage throughout the day, hold prandial insulin and administer one-third to one-half the morning basal dose. This is in anticipation that the patient will receive their typical PM dosing after the surgery.
Patients on subcutaneous insulin pump should be maintained on typical basal infusion rate.
Long and complicated procedures
These procedures require on intravenous insulin infusion with concomitant potassium infusion to avoid insulin induced hyperkalemia. Combined insulin+potassium+glucose solutions are available.
POST-OP:In general patients can resume their pre-operative diabetic regimens once they have resumed eating, assuming the pre-op regimen was providing adequate glucose control.
For patients on intravenous insulin infusion, the infusion should be continued until the patient is tolerating oral nutrition. At this point the patient can be converted back to a subcutaneous regimen.
For patients who received subcutaneous insulin on the morning of surgery, they may continue on the same subcutaneous insulin regimen post-operatively, however, the dextrose 5% (D5) infusion should be continued until the patient is tolerating orals.
Prandial insulin should be used cautiously in the early post-operative setting as patients may experience nausea and difficulty resuming diet. Patients are put at risk for hypoglycemia if they receive prandial insulin in anticipation of a meal they are subsequently unable to tolerate. If there is any concern that a patient may not tolerate his or her meal, the prandial insulin can be held until immediately after the patient eats.
Transition from intravenous insulin to subcutaneous regimen
Intravenous insulin can be transitioned to subcutaneous when:
The patient is tolerating orals.
The patient’s requirement is less than 1 unit per hour for several hours.
The patient’s 24H insulin requirements have stabilized. If the glucose has been stable for 6-8 hours, the 24H requirements can be extrapolated.
The transition from intravenous to subcutaneous insulin is best done at mealtime or bedtime. This approach is more compatible with mealtime insulin administration and provides a smoother transition to subcutaneous regimens.
The total subcutaneous dose is 50% of the total 24H intravenous dose. The total subcutaneous dose is then divided as 50% for the total basal dose and 50% for the total prandial dose. The basal insulin is then further divided 2-3 times daily for intermediate insulin (NPH) or 1-2 times daily for long acting (glargine or detemir). The mealtime dose is decided appropriately for the meals consumed with attention to any difficulty with enteral intake. Corrective insulin sliding scale can be used additionally so that the total regimen includes basal + prandial + corrective.
In general, dose adjustments should be made if blood glucose levels are over 200 mg/dL or less than 100 mg/dL without obvious cause, for example, unnecessary dextrose containing fluids or a skipped meal. For patients on both basal and prandial insulin the ratio of total basal to prandial insulin should be maintained at approximately 1:1.
If long-acting glargine or detemir is used, dose adjustments should be made on basis of fasting morning glucose level. If NPH is used, the adjustment should be made on either the morning fasting or fasting pre-dinner value. If the patient is requiring high doses of corrective insulin, this may be incorporated into the basal dose adjustment.
Type I diabetics: additional considerations
Type I diabetics ALWAYS require basal insulin to prevent ketosis. Moderately elevated blood glucose levels (> 200 mg/dL) may be the onset of ketoacidosis in some patients. On the other hand, Type I diabetics are insulin sensitive and at high risk for hypoglycemia. They typically require much less overall insulin than patients with Type II diabetes. If using short acting corrective and/or prandial insulin via sliding scale, they should be placed on the lowest dosing algorithm.
For any Type I diabetic who has so-called “brittle” diabetes with fluctuating blood sugars and/or frequent hypoglycemia, intra-operative IV insulin should be used even for simple procedures. As these patients are at high risk for complication, the treating physician should have a low threshold for obtaining an endocrine consultation on all Type I diabetic patients in the peri-operative setting.
Patients often receive “stress dose” steroids peri-operatively. Steroids can lead to worsening of pre-existing diabetes and/or steroid-induced diabetes, although the severity of the response can be unpredictable. Fortunately, it is uncommon for treatment with steroids to lead to ketosis. In general, for patients on high dose steroids a 2-3 fold increase in insulin is required. All patients receiving steroids post-operatively should have blood glucose monitored. For patients with only modest elevation in blood glucose (<200 mg/dL) an insulin sliding scale may be sufficient coverage. For others with higher glucose levels, a basal regimen with once or twice daily glargine or detemir in addition to corrective insulin may be required. This strategy should be avoided in patients with anticipated rapid steroid taper.
Patients on continuous tube feeds are typically managed on basal insulin with corrective short acting insulin every 6 hours. Basal insulin usually needs to be given multiple times per day – every 23 hours for glargine or detemir and every 8 hours for NPH. If tube feeds are interrupted for any reason, the equivalent amount of carbohydrate (typically dextrose 10% saline) needs to be infused immediately to prevent hypoglycemia.
The late post-operative phase and the transition back to the outpatient regimen.
Many patients with good baseline glycemic control and uncomplicated hospital courses are easily transitioned back into the outpatient setting. For those patients who had poor outpatient control, the inpatient resources of diabetic educators and nutritionists should be utilized. Discharge regimens, if different from prior outpatient regimens should be simplified depending on the capacity of the patient.
For patients who have had typically good control requiring little insulin in the hospital (i.e., < 20-30 units per day) oral medications on discharge may be sufficient. Patients requiring higher doses of insulin in the hospital should be continued on insulin as outpatients. For patients with newly diagnosed hyperglycemia in the hospital, many may not need ongoing therapy after they have recovered from their acute illness. Follow-up for any patient with a new or changed regimen should be within 1-2 weeks.
IV. Common Pitfalls.
Common pitfalls of the Hospitalist physician in the peri-operative glucose management include the following:
Failure to continue basal insulin when patient is NPO. Often hospitalists will hold all insulin in patients who are NPO. If dosed correctly, basal insulin covers the patient’s basal metabolic needs independent of oral intake and should be continued (though dose adjusted) on the morning of most procedures. For further information see section above titled “Patients with Type I or insulin dependent Type II diabetes.”
Inappropriate use of insulin sliding scale. Insulin sliding scales are often problematic if used as the sole method of insulin delivery. They delay insulin administration until hyperglycemia occurs and may lead to wide fluctuations in glucose. They should NEVER be used as sole therapy in Type I diabetes (ketosis can occur before hyperglycemia) and the majority of insulin dependent type II diabetics.
Overly aggressive control. For the majority of post-surgical patients, glucose management should be targeted to avoid complications of hypoglycemia and marked hyperglycemia. Intensive insulin therapy (variable definitions but generally BG <110-140 mg/dL) has been shown to be beneficial only in post-cardiac surgery SICU patients and is universally associated with higher incidence of hypoglycemia.
V. National Standards, Core Indicators and Quality Measures.
No national standards/benchmarks established yet.
VI. What's the Evidence?
Buhleitner, AM, Martinez-Alonso, M, Hernandez, M. “Perioperative glycemic control for diabetic patients undergoing surgery”. Cochrane Database Syst Rev. 2012.
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- I. Problem/Challenge.
- II. Identify the Goal Behavior.
- III. Describe a Step-by-Step approach/method to this problem.
- The pre-op consultation
- Long term diabetic control and surgical outcomes
- Hyperglycemia in the immediate pre-op setting
- Perioperative management strategies by specific situation
- Information on specific oral diabetic agents
- Patients with type I or insulin dependent type II diabetes
- Transition from intravenous insulin to subcutaneous regimen
- Insulin adjustment
- Type I diabetics: additional considerations
- Peri-operative steroids
- The late post-operative phase and the transition back to the outpatient regimen.
- IV. Common Pitfalls.
- V. National Standards, Core Indicators and Quality Measures.