Preop PBLD 2: Preoperative and Perioperative Glucose Management

Instructor Version

Authors

Debra D. Pulley, MD
Washington University School of Medicine in St. Louis, Department of Anesthesiology

Deborah C. Richman, MBChB, FFA (SA)

Stony Brook School of Medicine, Department of Anesthesiology

Disclosures: None

Learning Objectives:

Upon completion of this learning activity, participants will be able to:

• Describe the pathophysiology of diabetes mellitus types 1 and 2

• Recognize the different types of diabetic medications
• Name the perioperative risks of poor glycemic control and identify patients who should
have blood glucose optimization prior to surgery
• Apply the principles learned to determine appropriate preoperative patient instructions

Case 1: A 71 year-old male presents to the preoperative clinic in preparation for a left total
hip replacement. First thing he tells the nurse is that he is worried about his sugar level.

1) Why is glucose important and how is it regulated in the body?

• Glucose is an important source of energy and is regulated primarily by hormones

produced in islet cells of the pancreas (insulin from beta-cells and glucagon from
alpha-cells). Abnormal glucose levels can have significant consequences on organs and
tissues.
 • Glucose swings are metabolically stressful, lead to catecholamine surges, and are pro-
inflammatory. DM can be construed as an inflammatory disease with associated
accelerated macro- and micro-vascular and aging effects.

2) What does insulin do?

• Insulin regulates fuel storage and regulation.

o In carbohydrate metabolism, insulin increases the uptake of glucose by striated
muscle and adipose tissue. It increases glycolysis (the breakdown of glucose). It
also increases the rate of glycogen synthesis and decreases the rate of glycogen
breakdown in the liver, muscle and adipose tissue.
o In lipid metabolism, insulin promotes the synthesis of fatty acids in the liver and
inhibits the breakdown of fat in adipose tissue.
o In protein metabolism, insulin stimulates the uptake of some amino acids into cells,
increases the rate of protein synthesis in muscle, adipose tissue, liver, and other
tissues, and decreases the rate of protein degradation in muscle.
o Other effects, insulin can increase the permeability of potassium, phosphate, and
magnesium ions into cells.

3) The patient reports he has diabetes. How common is diabetes mellitus (DM) in the US
and what percentage is type 1 (DM-1) and type 2 (DM-2)?

• DM is common in the US with an incidence of over 10% of adults with the vast majority
DM-2 (90-95% of cases of DM are type 2).

4) What is the pathophysiology of diabetes mellitus type 1 and 2?

• DM-1 is an absolute deficiency of insulin production in beta islet cells of the pancreas.
Type 1A is due to destruction of beta cells from autoantibodies. Type 1B is due to
destruction of beta cells from other causes than autoimmune.
• DM-2 develops when there is a relative deficiency of insulin (i.e., insulin production in
the pancreas cannot keep up with increased insulin resistance in the periphery (muscle,
fat and liver cells) leading to hyperglycemia). The etiology of insulin resistance can be
complicated and not clear but can involve excess weight, physical inactivity, genetics,
 hormones, steroid use, medications, older age, obstructive sleep apnea, and cigarette
smoking. Chronic inflammation can also lead to beta-cell loss.

5) The patient was diagnosed 10 years ago with DM-2. He has been on metformin for years
but linagliptin and empagliflozin were added over the last two years. How do you treat
DM type 2 and why do you think his treatment was changed over the past two years?

• Treatment is based on the response to an individual’s glycemic control. Initial

treatment of DM-2 usually includes lifestyle modifications – low carbohydrate diet and
exercise – with the addition of metformin. Based on the patient’s response, additional
medications may be added (insulin or non-insulin). Table 1 lists different types of
noninsulin medications along with the mechanism of action and Table 2 lists insulin
preparations. In this patient, the addition of linagliptin and empagliflozin was most
likely done because of inadequate glucose control on metformin alone.

Table One – Antidiabetic Medications (Non-Insulin)

DOS – Day of surgery

Drug class Generic Name (Trade Mechanism of Patient Preoperative

Names) Action Instruction
Alpha acarbose (Precose) Decreases Do not take on DOS
glucosidase miglitol (Glyset) digestion of
inhibitors carbohydrates
Amylin pramlintide(SymlinPen) Assists insulin in Do not take on DOS
analogues controlling post-
prandial glucose
levels
Biguanides metformin (Glucophage) Prevents the Do not take on DOS
production of (hold up to 48 hours
glucose in the for more extensive
liver, improving surgeries, in renal
sensitivity to insufficiency and
insulin, and dehydration if
reducing concerned about
absorption of metformin associated
glucose by the GI lactic acidosis)
tract
Dipeptidyl alogliptin (Nesina) Prevents incretin Do not take on DOS
peptidase - 4 linagliptin (Tradjenta) hormones from
(DDP-4) saxagliptin (Onglyza) being destroyed
 inhibitors sitagliptin(Januvia)
Glucagon-like albiglutide (Tanzeum) Mimics incretin Do not take on DOS
peptide - 1 (GLP- dulaglutide (Trulicity) hormone
1) analogues exenatide (Byetta)
liraglutide (Victoza)
Meglitinides nateglinide (Starlix) Stimulates the Do not take on DOS
repaglinide (Prandin) production of
insulin by beta
cells of the
pancreas
Sodium/glucose canagliflozin (Invokana) Prevents kidneys Do not take on DOS
cotransporter 2 dapagliflozin (Farxiga) from reabsorbing (Hold 3 days before
(SGLT2) empagliflozin (Jardiance) glucose back into surgery if concerned
inhibitors the blood about euglycemic
DKA).
Sulphonylureas glimepiride (Amaryl) Stimulates the Do not take on DOS
glipizide (Glucotrol) production of
glyburide (DiaBeta) insulin by beta
tolbutaine (Orinase) cells of the
pancreas
Thiazolidinidione pioglitazone (Actose) Reduces the Do not take on DOS
s rosiglitazone (Avandia) body’s resistance
to insulin

Table 2 – Insulin Preparations

DOS – Day of surgery

Type of Insulin Generic Name (Trade Name) Patient’s Perioperative Instructions

Long-acting Insulin glargine (Lantus 100 u/mL) If take in evening, administer 80% PM
insulin Insulin glargine (Toujeo 300 u/mL) dose the evening before surgery. If take
Insulin degludec (Tresiba) in morning, administer 75% on DOS.
Determir (Levemir) Check glucose levels prior to arrival.
(Hx of frequent hypoglycemia – consider
50% of dose)
Intermediate- NPH insulin/isophane insulin If take in the evening, administer 75%
acting insulin (Novolin N, Humulin N) PM dose the evening before surgery. If
Lente take in the morning, administer 75% on
Ultralente DOS. Check glucose levels prior to
arrival.
Short and Regular insulin (Novolin R, On DOS, hold all scheduled short/rapid
rapid-acting Humulin R) acting insulin doses normally take with
insulin Insulin lispro (Humalog 100 or 200 meals.
u/mL))
Insulin aspart (NovoLog)
Insulin glulisine (Apidra)
Combination 70/30 (Novolin 70/30, Humulin Do not take any combination insulin
insulin 70/30 DOS. Substitute an intermediate-acting
50/50 (Humulin 50/50) (NPH) and administer 50% of morning
75/25 (Humalog 75/25) dose on DOS or can be done on arrival.
Check glucose levels prior to arrival.
Insulin pump Short and rapid-acting insulins On DOS, keep at basal rate and check
glucose levels prior to arrival.
V-Go Insulin Short and rapid-acting insulins On DOS remove device and give 30%
Delivery Device (Insulin lispro or aspart) basal 24-hour rate as NPH SQ (or can be
done on arrival).
Inhaled insulin Regular insulin On DOS, hold all scheduled short/rapid
acting insulin doses normally take with
meals.

6) The nurse checks the patient’s blood glucose level and tells the patient his level is 200
mg/dL. The patient is relieved that it is not higher. What are the signs and symptoms of
hypoglycemia and hyperglycemia?

• Signs and symptoms of hypoglycemia include sweating, fatigue, dizziness, shakiness,

nervousness/anxiety, hunger, weakness, blurred vision, elevated heart rate, confusion,
seizures, coma, and eventually death.
• Signs and symptoms of hyperglycemia include frequent urination, increased thirst,
blurred vision, fatigue, and headache. If hyperglycemia progresses, it will lead to more
serious signs and symptoms of ketoacidosis or hyperosmolar coma, such as fruity
breath, dry mouth, nausea/vomiting, abdominal pain, shortness of breath, weakness,
confusion, coma, and eventually death.

7) Since this patient has had DM-2 for a long time, what comorbidities might you expect him
to have?

• Long-term complications of DM include hypertension, cardiovascular disease (CAD,

PAD, CVA), retinopathy, nephropathy, peripheral neuropathy, autonomic neuropathy
(dominant sympathetic system, abnormal baroreceptor responsiveness, gastroparesis,
diarrhea, impotence, urinary retention, abnormal sweating, inability to perceive
 hypoglycemia), and musculoskeletal effects (glycosylation of joints and ligaments
especially in the cervical spine).

8) How do you evaluate this patient in the preoperative clinic?

• Perform a complete history and physical examination to identify any sequelae from
DM especially effects on the cardiovascular system and risk for episodes of
hypoglycemia, hyperosmolar hyperglycemic states, or ketoacidosis. In addition,
obtain/review recent labs including fasting blood sugar levels, HbA1c, and BMP to
assess glycemic control and potential nephropathy. Obtain an ECG since this is not a
low risk surgery and the patient has a diagnosis of DM.

9) The patient states he rarely does any physical activity because of severe arthritis in his
knees. He lives in a one-story home and is not sure if he could climb one-flight of stairs
(because of knee pain). Would you recommend any preoperative cardiac testing? Why or
why not?

• Recommend further cardiac testing based on the ACC/AHA guidelines (such as:
symptoms concerning for acute coronary syndrome, cardiac risk ≥ 1% with poor or
unknown functional capacity and that further testing will impact decision making or
perioperative care).

10) How would you manage this patient’s metformin, linagliptin, and empagliflozin
perioperatively? Is there any evidence to support your approach?

• Metformin is a biguanide. This group of drugs, especially phenformin and buformin,

has been associated with lactic acidosis which can have significant morbidity and
mortality. The risk of metformin associated lactic acidosis (MALA) is lower than the
earlier used biguanides with an incidence reported between 3-47 per 100,000 patient-
years (Diabetes Obes Metab. 2017 Nov;19(11):1499-1501. doi: 10.1111/dom.12994.
Epub 2017 Jun 9). There is no published data on incidence in the perioperative period.
Risk factors for MALA include renal dysfunction, liver dysfunction, alcoholism, and
states of decreased tissue perfusion. Although there are no absolute guidelines, most
would advise to hold metformin the morning of surgery for low risk surgeries. For
more invasive and extensive procedures, especially in patients with pre-existing renal
 disease and/or expected fluid shifts and dehydration, it may be prudent to hold
metformin for up to 48 hours. It can be restarted postoperatively after checking
creatinine and adjusting the dose as necessary. However, this is controversial, with a
recent report suggesting it may be safe to continue in procedures/surgeries without
kidney or liver injury, or shock (British Journal of Anaesthesia 113 (6): 906–9 (2014)
Advance Access publication 30 July 2014. doi:10.1093/bja/aeu259 and BMC
Pharmacology and Toxicology (2017) 18:38 doi: 10.1186/s40360-017-0145-6)
• Linagliptin is a DPP IV inhibitor and it may be taken the morning of surgery.
• Empagliflozin is an SGL2 inhibitor and most would advise not to take the day of
surgery. However, there have been reports of euglycemic diabetic ketoacidosis with
these agents. Fasting, dehydration, and active infection have been shown to increase
the risk. In 2018, the Australian Diabetes Society issued an alert and recommendations
to stop these medications 3 days prior to surgery
(.https://diabetessociety.com.au/.../2018_ALERT-
ADS_SGLT2i_PerioperativeKetoacid...).
• Once he is admitted postoperatively, the ADA recommends that all admitted patients
are managed with insulin and no oral agents are to be given.
• Insulin doses are given to cover
o Basal needs – daily long-acting based on expected insulin needs (assess age, BMI,
renal function, comorbidities and type of diabetes.)
o Prandial bolus of short-acting insulin according to assessment of need above and
planned carbohydrate intake for the meal.
o And add correction factor of short-acting insulin based on his blood glucose prior to
meal.

11) The patient’s HbA1c today is 12.8%. Does he have good glycemic control?

• HbA1c is a very useful blood test to help diagnose and treat DM. The test measures
the amount of glycated hemoglobin in red blood cells. Red blood cells have a lifespan
of about 120 days so the amount of glycated hemoglobin gives an overview of glucose
control over a period of weeks/months. The higher the HbA1c, the worse the degree of
hyperglycemia has been (see Table 3). The American Diabetes Association
recommends a goal of 7.0% in order to minimize long-term complications of DM,
however, in some patients, this goal may be less aggressive.
 Table 3 – HbA1c to eAG Conversion

HbA1c % eAG mg/dl

6.0 126
6.5 140
7.0 154
7.5 169
8.0 183
8.5 197
9.0 212
9.5 226
10.0 240
10.5 255
11.0 269
11.5 283
12.0 298
12.5 312
13.0 326

eAG – estimated average glucose,

eAG = 28.7 x HbA1c- 46.7

12) How does anesthesia and surgery affect glucose levels?

• In general, glucose levels increase during anesthesia and surgery. Stress can occur
from surgery (bowel prep, tissue trauma, inflammation, pain) and anesthesia (fasting,
tracheal intubation, inadequate anesthesia) leading to increased sympathetic nerve
activity, increased circulating catabolic hormones (NE, Epi, GH, cortisol) and decreased
insulin secretion leading to increased glucose production and decreased glucose
utilization thereby increasing glucose levels. Volatile anesthetics reduce insulin
secretion and can increase glucose levels. Steroid medications (hydrocortisone,
dexamethasone) increase glucose levels. Insulin preparations decrease glucose levels.
Hyperglycemia can also lead to insulin resistance.

13) How would you counsel this patient regarding perioperative risks of poor glycemic
control?
 • Hyperglycemia can lead to increased risk of perioperative infection, cardiovascular
morbidity, and mortality. In addition, severe hypoglycemia can cause serious morbidity
and mortality. Poor preoperative glycemic control is a risk factor for difficulty with
perioperative glycemic control.

14) Would you postpone surgery in this patient? Why or why not?

• There is no consensus on an absolute HbA1c or glucose level to postpone surgery.

Factors influencing any decision include risk of the surgery, risk of delaying surgery,
cause of poor glycemic control, and surgeon/patient preferences, etc. It is best to have
institutional guidelines. Due to the markedly elevated HbA1c, the risk of hip infection,
and elective nature of the surgery, the best course of action would be to postpone the
surgery and refer the patient back to his primary care physician or endocrinologist.

15) Would your management change if this patient were having urgent/emergent surgery?

• If the patient is ketotic, if possible, any surgery should be delayed. Otherwise, it would
be prudent to closely follow glucose levels closely preoperatively (either by admitting
the patient to the hospital prior to surgery or as an outpatient) to try to achieve better
glycemic control. A fructosamine level (glycated albumin), if available, will indicate
more recent glycemic control (1-3 weeks) than HbA1c. Poor glycemic control
preoperatively leads to poor glycemic control both intraoperatively and
postoperatively. Since the patient’s HbA1c is markedly elevated, intraoperatively,
insulin will most likely need to be administered and to help manage glucose levels
postoperatively an endocrinology consult would be advisable.

16) The patient returns to the clinic 12 months later to have his other hip replaced. His HbA1c
is 8.3%. He is now on 20 units of glargine insulin at nighttime. What are your patient
instructions for his insulin?

• For long-acting insulin given once a day at night, the patient should take only 80% of
the insulin the night before surgery (see Table 2). If there is a history of recent or
frequent hypoglycemic episodes recommend taking only 50% of the nighttime dose.
17) What glucose levels are recommended perioperatively? What is the evidence?

• The optimal target range of glucose levels has not been determined and if available, it
is best to follow an institutional policy. In 2012, a Cochrane Database Systemic Review
of previous studies comparing “intensive” vs “conventional” control in patients
undergoing surgery showed no benefit with “intensive” treatment. In addition, there
were increased episodes of hypoglycemia in the “intensive” treatment group. For
hospitalized patients, the 2018 ADA recommendation is that “insulin therapy should be
initiated for treatment of persistent hyperglycemia starting at a threshold ≥180 mg/dL
(10.0 mmol/L). Once insulin therapy is started, a target glucose range of 140–180
mg/dL (7.8–10.0 mmol/L) is recommended for the majority of critically ill patients and
noncritically ill patients. More stringent goals, such as 110–140 mg/dL (6.1–7.8
mmol/L), may be appropriate for selected patients if this can be achieved without
significant hypoglycemia.”

If time permits - OPTIONAL CASES

Case 2: 45-year-old female with PMH significant for obesity presents to the preoperative
clinic in preparation for a hysteroscopy and D&C for excessive uterine bleeding one week
from today. The History and Physical Exam are otherwise unremarkable.

18) The surgeon ordered a CBC and a BMP and the results show a random glucose of 200
g/dL. What does this mean?

• This patient may have DM. Approximately 25% of adults in the US who have DM do
not know it. As a person ages, the incidence of DM increases with about 1 in 4 US
adults over the age of 65 years have DM. Any lab test should be repeated before a
diagnosis is made.
• The ADA criteria for DM include a) HbA1c ≥ 6.5%, b) fasting plasma glucose 126
mg/dL, or 3) 2 hour plasma glucose ≥ 200 mg/dL after an oral glucose tolerance test,
or a random plasma glucose ≥ 200 mg/dL in a patient with classic symptoms of
hyperglycemia (polyphagia, polyuria, or polydipsia) or hyperglycemic crisis (diabetic
ketoacidosis/hyperosmolar hyperglycemic syndrome).

19) What is prediabetes?

 • Prediabetes is when glucose levels are higher than normal but not high enough to be
classified as diabetes (HbA1c 5.7 – 6.4).

20) What is metabolic syndrome?

• Metabolic syndrome is a group of risk factors that lead to a greater risk for
cardiovascular disease and diabetes. The 5 parameters include abdominal obesity,
high triglyceride, low HDL, hypertension, and elevated fasting glucose levels.

21) How do you proceed with this patient?

• Contact the patient’s PCP to see if there has been any previous testing performed. Ask
the patient if she was fasting prior to her blood test. Discuss with her, the health
implications of the blood sugar level and the importance to discuss this with her PCP.
Discuss with both the patient and the surgeon if it is urgent to proceed with the
procedure. It is not clear from one random glucose level of 200 whether or not this
patient has DM. Repeat testing should be done such as repeat glucose or HbA1C, but
keep in mind that iron-deficiency anemia can increase HbA1c levels. Even if a repeat
test indicates the patient does have DM, as long as the patient is not ketotic nor
dehydrated, with a low risk surgery such as a D & C, it is reasonable to proceed with
the original planned surgery date keeping in mind that the patient will need to be
reevaluated for dehydration and ketosis on the day of surgery.

22) The patient states she has an aunt who has DM and asks you what she can do to prevent
diabetes.

• Lose weight, be more physically active, and eat healthier foods, specifically to avoid
simple sugars and limit carbohydrates. You recommend a visit with a nutritionist.

23) What glucose on the morning of surgery would cause you to cancel the case?

• There is no consensus as to an actual blood glucose level that should be canceled.

Hydration status and the presence of ketones should be assessed for. If not ketotic nor
dehydrated, the surgery can proceed as planned and glucose should be brought under
control with short acting insulin.
Case 3: A 22 year-old female with history of diabetes type 1 treated with an insulin pump
presents to the preoperative clinic in preparation for removal of hardware from her right
upper extremity.

24) What labs would you get for this patient in the clinic and what are your preoperative
instructions for the pump in the perioperative period?

• Suggest obtaining a BMP and an HbA1c. No other labs unless indicated by the history
or physical exam. Instruct her to continue her insulin pump on a setting for when she
is not eating (basal or nighttime infusion) until the morning of surgery with frequent
checks of her glucose levels. Patients with DM-1 need insulin, stopping the insulin
pump prior to surgery may cause the patient to become ketotic. Immediately before
the surgery or when in a hospitalized setting, the patient’s pump may be stopped and
other routes of insulin started (intravenous or subcutaneous).

25) The patient relates previous issues with hypoglycemia. Discuss how you would address
her concerns.

• Talk with her surgeon to make the patient the first case of the day. Instruct the patient
to check her glucose levels frequently, and if low, instruct her to take sugar water or
apple juice and caution her against taking non-clear liquids such as orange juice with
pulp.

26) If this patient is going to have a colon resection instead, would you change anything?

• ERAS protocols for colon resection include carbohydrate loading. Emphasize the need
to check her blood glucose levels. If her surgeon requests a bowel prep, advise her to
get insulin pump instructions from her endocrinologist; the combination of history of
hypoglycemia and altered nutrient intake over a 24-48 hour period would be best
managed by an experienced specialist.

Case 4: A 35 year-old male with meningioma presents to the preoperative clinic in

preparation for resection of the meningioma.
27) The patient was recently started on dexamethasone while in the hospital a few weeks
ago. How do you proceed?

• Steroids such as dexamethasone can increase glucose levels and lead to steroid
induced hyperglycemia. Check a glucose level and HbA1c to see what effect the steroid
has had on his glucose level.

28) The patient reports that when he was in the hospital a few weeks ago, he had an allergic
reaction to insulin. Is there anything you would do prior to his surgery?

• Yes. Hypersensitivity reactions can occur to various components/contaminants of

insulin preparations or to the insulin itself. It was more common with porcine or
bovine insulins, but hypersensitivity reactions to recombinant human insulin have been
documented. Ask the patient what insulin preparation he had received, what his
reaction was, and how it was treated. Obtain the records from the hospitalization
when the episode occurred. Consider a formal consultation to an allergist and an
endocrinologist if it is not clear what to do if the patient needs a glucose lowering drug
while in the hospital.

References and Suggested Reading

1. American Diabetes Association Professional website: www.professional.diabetes.org

2. Centers for Disease Control and Prevention website
www.cdc.gov/diabetes/home/index.html
3. Clinical Diabetes 2009 Oct; 27(4): 160-163. https://doi.org/10.2337/diaclin.27.4.160
4. National Diabetes Education Initiative website www.ndei.org/MediaKit/index.aspx.html
5. Standards of Medical Care in Diabetes—2018. Diabetes Care 2018 Jan; 41(Supplement
1)
6. Miller JD, Richman DC. Preoperative Evaluation of Patients with Diabetes Mellitus, In
Anesthesiology Clinics, Volume 34, Issue 1, 2016, Pages 155-169, ISSN 1932-2275, ISBN
9780323442299, https://doi.org/10.1016/j.anclin.2015.10.008.