Peri-operative Hyperglycemia in Operation Theatre

1. PERIOPERATIVE
HYPERGLYCEMIA

2. CAUSES
• Diabetes mellitus
• Drugs
• Critical illness
• Stress
• Certain conditions associated with
hyperglycemia

4. • During the fasting state, normal subjects maintain plasma glucose
levels between 60 and 100mg/dl (3.3 to 5.5mM).
• The stress of surgery and anesthesia alters the finely regulated
balance between hepatic glucose production and glucose utilization
in peripheral tissues.
• An increase in the secretion of counterregulatory hormones
(catecholamines, cortisol, glucagon, and growth hormone) occurs,
causing excessive release of inflammatory cytokines including
tumor necrosis factor-α, interleukin-6, and interleukin-1β

5. • Surging catecholamines increase glucagon
secretion and inhibit insulin release by pancreatic
β cells
• Cortisol increases hepatic glucose production,
stimulates protein catabolism, and promotes
gluconeogenesis, resulting in elevated BG levels
• the increase in stress hormones leads to
enhanced lipolysis and high FFA concentrations.

6. STRESS

7. • Preoperative carbohydrate loading is becoming a more
frequent surgical practice because it may counteract the
state of insulin resistance that occurs due to stress and
starvation.
• The Enhanced Recovery After Surgery (ERAS) program
advocates carbohydrate-rich drinks up to 2h before surgery.
• This avoids the catabolic state associated with starvation
and has been demonstrated to increase insulin sensitivity
and decrease the risk of postoperative hyperglycemia.
• Particularly in patients undergoing major abdominal
surgery, carbohydrate loading has been associated with a
reduced hospital length of stay

8. Prevalence of Hyperglycemia and
Diabetes in Surgical Patients
• Perioperative hyperglycemia is reported in 20 to 40% of patients
undergoing general surgery and approximately 80% of patients
after cardiac surgery.
• However, 12 to 30% of patients who experience intra and/or
postoperative hyperglycemia do not have a history of diabetes
before surgery, a state often described as “stress hyperglycemia.”
Stress hyperglycemia typically resolves as the acute illness or
surgical stress abates
• Measurement of hemoglobin A1c (HbA1c) in patients with
hyperglycemia during hospitalization provides the opportunity to
differentiate patients with stress hyperglycemia from those with
diabetes who were previously undiagnosed.

9. • Crude incidence of mortality was 3 to 5% at 1 yr
in patients with preoperative BG between 60 and
100mg/dl (3.3 to 5.5mM) versus 12% in patients
with BG greater than 216mg/dl (12mM).
• Most patients with and without diabetes tolerate
fasting for several hours up to a few days without
increased risk of malnutrition or perioperative
complications.
• Nutritional support, with dextrose containing
solutions, is not indicated in diabetic patients
fasting for periods less than 24 to 48h.

10. • The metabolic needs for most hospitalized patients can
be supported by providing 25 to 35 calories /kg/day.
• Critically ill patients require decreased caloric intake
approximating 15 to 25 calories /kg/ day. A diet
between 1,800 and 2,000 callories/day is appropriate
for most patients.
• The postprandial rise in BG was reduced by 18 to
29mg/dl with these formulations, demonstrating
improved glucose control in diabetics.

11. Intra operative period
• Gandhi et al reported that for each
incremental change in intraoperative BG by
20mg/ dl (1.1mM) above 100mg/dl (5.5mM),
there was a 30% increase in occurrence of
adverse events including pulmonary and renal
complications and death.

14. Intraoperative Glycemic Management
The target perioperative BG level depends upon the ----
• duration of surgery,
• invasiveness of surgical procedure,
• type of anesthetic technique, and
• expected time to resume oral intake and
• routine antidiabetic therapy.
• The Endocrine Society and SAMBA recommend that intraoperative BG
levels be maintained less than 180 mg/dl
• Hyperglycemia (greater than 180 mg/dl, 10 mM) is treated with
subcutaneous rapid-acting insulin analogs or with an IV infusion of regular
insulin.
• When subcutaneous insulin is used in the preoperative
period or operating room to treat hyperglycemia, BG testing should occur
at least every 2 h.

16. Glucose Monitoring in the Perioperative
Period
• laboratory testing,
• blood gas analysis, and
• capillary point-of-care testing (POC).

17. CRITICAL ILLNESS
• Hyperglycemia is a common occurrence in the
intensive care unit (ICU) and is associated with
worse outcomes in both adults and children.
• This is compounded by the use of feeds,
fluids, and drugs that raise sugar levels
directly or are counter regulatory to insulin.

18. Mechanisms underlying hyperglycemia are
complex but include the following.
• Peripheral and hepatic insulin resistance.
• Enhanced hepatic and renal glucose
production.
• High glucose loads from feeds and
intravenous infusions.

19. • Hyperglycemia was reported as being present
in up to 68% of patients admitted to a medical
ICU.
• It is an independent predictor of death in
many acute settings, including acute
myocardial infarction, trauma, head injury,
and stroke.

20. • Postulated mechanisms by which hyperglycemia causes
harm include decreased cerebral blood flow, intracellular
acidosis, and low ATP levels; these may be similar to the
actions of hyperglycemia witnessed in diabetes mellitus.
• Hyperglycemia also produces a hypercoaguable state partly
through the increased expression of tissue factor, which is
both procoagulant and proinflammatory.
• hyperglycemia is associated with poor gut motility, a factor
that may be important in bacterial overgrowth and
translocation- This dysmotility may be in part due to the
inhibitory effects of hyperglycemia on vagal nerve activity
• The aggressive management of hyperglycemia in patients
reduced the incidence of critical illness polyneuropathy and
myopathy

21. • The American Diabetes Association (ADA)
provides hospital admission guidelines when
people exhibit hyperglycemia.
• Specifically, hospitalization is recommended
when DKA or HHS are present and when the
following are noted:
• hyperglycemia associated with volume depletion,
metabolic deterioration associated with
persistent refractory hyperglycemia, and
recurring fasting hyperglycemia > 300 mg/dl
refractory to outpatient therapy.

22. DRUGS

23. Antibiotics (Fluoroquinolones)
• Fluoroquinolones are the only class of antibiotics consistently
associated with the development of hyperglycemia. The most
commonly implicated fluoroquinolone is gatifloxacin---- it causes
both hyper and hypoglycemia
• hyperglycemia has been reported to occur with gatifloxacin within 5
days of initiation of therapy
• MOA- moa of hyperglycemia has not been precisely elucidated
• The proposed hypoglycemic mechanism involves binding of the
antibiotic to the pancreatic β-cell similar to the action of
sulfonylureas

24. β-blockers
• In people with diabetes, β-blockers such as
propranolol, metoprolol, and atenolol can result in
consistently elevated fasting blood glucose levels.
• carvedilol and nebivolol are not associated with the
development of hyperglycemia or new-onset diabetes
• MOA--β-blockers are thought to contribute to the
development of hyperglycemia by impairing the
release of insulin from the pancreatic β-cell.

25. Thiazide and Thiazide-Like Diuretics
• prescribed to control blood pressure in people with diabetes.
• Thiazide diuretics are known to promote hyperglycemia and in some cases
contribute to the new onset of diabetes
• MOA--The exact mechanism is unknown.
Postulated ---
• to worsening of insulin resistance,
• inhibition of glucose uptake, and
• decreased insulin release,
• down-regulate peroxisome proliferator-activated receptor gamma,
thereby decreasing insulin release
• activate the renin-angiotensin-aldosterone system, thus resulting in
elevated levels of aldosterone and resulting hyperglycemia.
Hydrochlorothiazide has been implicated in contributing to new-onset
diabetes in as few as 9–18 weeks of therapy initiation.

26. Second-Generation Antipsychotics
(SGAs)
• olanzapine and clozapine are most likely to increase
the risk of diabetes when used in people with
schizophrenia
• MOA-exact mechanism ---unknown.
• Postulated- antagonism at 5-HT receptors mainly
involving 5-HT2C ,
• antagonism at central histamine H1 receptors;
• development of insulin resistance through effects on
cellular glucose transporters;
• compromised insulin secretion; and
• alterations in leptin levels

27. CORTICOSTEROIDS
• It is well known and recognized that
glucocorticoid use in people with or without
diabetes results in hyperglycemia.
• The odds ratio for new-onset type 2 diabetes in
people treated with glucocorticoids ranges from
~1.5 to 2.5.
• MOA----Corticosteroids blunt the action of insulin
and promote hepatic gluconeogenesis
• corticosteroids primarily increase postprandial
blood glucose levels, whereas fasting levels are
unaffected or only mildly elevated

28. • Clore and Thurby-Hay propose a weight-based
dosing guideline using NPH insulin for treating
glucocorticoid-induced hyperglycemia associated
with tapering dosages of prednisone.
• This guideline suggests using 0.4 units/kg of NPH
for prednisone doses ≥ 40 mg/day, with the NPH
insulin dose being decreased by 0.1 unit/kg for
each 10 mg/day decrease in prednisone dose.

29. Calcineurin Inhibitors (CNIs)
• The CNIs cyclosporine, sirolimus, and tarcrolimus are
often used to avoid allograft rejection in
transplantation therapy.
• The sustained use of these agents results in post-
transplantation diabetes.
• The incidence of post-transplantation diabetes is
estimated to be 24% at 36 months post-transplant
• MOA--The postulated mechanism of hyperglycemia
results from inhibition of pancreatic islet β-cell
expansion promoted by calcineurin

30. Protease Inhibitors
• treatment of people with HIV and AIDS.
• INCIDENCE-occurs in 3–17% early in therapy or after
extensive and prolonged use.
• MOA--create a homeostatic stress response that decreases
insulin sensitivity, thereby promoting insulin resistance–
associated hyperglycemia.
• Ritonavir has been shown to directly inhibit glucose
transporter type 4 activity in vivo, accounting for its ability
to cause hyperglycemia.

31. CONDITIONS RELATED TO
HYPERGLYCEMIA
The following conditions can also cause hyperglycemia in
the absence of diabetes.
• 1) Dysfunction of the thyroid , adrenal---- cushing
syndrome, and pituitary glands
• 2) Numerous diseases of the pancreas- pancreatitis
• 3) Severe increases in blood glucose may be seen
in sepsis and certain infections

32. • 4) Intracranial diseases (frequently overlooked) can
also cause hyperglycemia.
Eg Encephalitis, brain tumors (especially those
located near the pituitary gland), brain bleeds,
and meningitis are prime examples.
5) Mild to high blood sugar levels are often seen in
convulsions and terminal stages of many diseases.
6. Acromegaly– increased GH—insulin resistance ---
hyperglycemia

33. ACUTE DISORDERS RELATED TO
SEVERE HYPERGLYCEMIA
• Individuals with type 1 or type 2 DM and
severe hyperglycemia(>16.7 mmol/L [300
mg/dL]) should be assessed for clinical
stability, including mentation and hydration.
• The physician should assess if the patient is
stable or if diabetic ketoacidosis or a
hyperglycemic hyperosmolar state should be
considered.

37. HYPERGLYCEMIC HYPEROSMOLAR
STATE
• TREATMENT-
• Volume depletion and hyperglycemia are prominent features of
both HHS and DKA.
• Fluid replacement should initially stabilize the hemodynamic status
of the patient (1–3 L of 0.9% normal saline over the first 2–3 h).
• If the serum sodium is >150 mmol/L (150 meq/L), 0.45% saline
should be used.
• hemodynamic stability achieved
• IV fluid administration is directed at reversing the free water deficit
using hypotonic fluids (0.45% saline initially, then 5% dextrose in
water [D5W]).

38. • reasonable regimen for HHS begins with an IV insulin bolus
of 0.1 unit/kg followed by IV insulin at a constant infusion
rate of 0.1 unit/kg per hr
serum glucose does not fall
• increase the insulin infusion rate by two fold.
• glucose should be added to IV fluid when the plasma
glucose falls to 13.9 mmol/L (250 mg/dL), and the insulin
infusion rate should be decreased to 0.05–0.1 unit/kg per
hour

39. The End