Download insulin resistance of surgery

‫بسم هللا الرحمن الرحیم‬
Anesthesia & Diabetes
Dr Jarahzadeh(Intesivist)
DIABETES MELLITUS
Normal glucose physiology demonstrates a balance between
glucose utilization and endogenous production or dietary delivery
The liver is the primary source of endogenous glucose production
via glycogenolysis and gluconeogenesis.
Following a meal, plasma glucose increases, which stimulates an
increase in plasma insulin (maximum insulin level is reached
within 30 minutes) promoting glucose utilization.
Late in the postprandial period (2–4 hours after eating), the
plasma glucose concentration decreases to below the fasting level
before returning to preprandial values.
A transition from exogenous glucose delivery to endogenous
production then becomes necessary to maintain a normal plasma
glucose level. During the postabsorptive phase (4–8 hours after
eating) plasma glucose remains relatively stable with production
and utilization rates being equal. At this time, 75% of glucose
production results from hepatic glycogenolysis and 25% from
hepatic gluconeogenesis.
Approximately 70% to 80% of glucose released by the liver
is metabolized by insulin-insensitive tissues such as the
brain, gastrointestinal tract, and red blood cells.
During this time, diminished insulin secretion is
fundamental to the maintenance of a normal plasma
glucose concentration.
Hyperglycemia-producing hormones
(glucagon,epinephrine, growth hormone, cortisol)
Glucagon plays a primary role by stimulating
glycogenolysis, gluconeogenesis, and inhibiting glycolysis.
Epinephrine predominates when glucagon secretion is
deficient.
Neural glucoregulatory factors ( norepinephrine) and
glucose autoregulation also support glucose production.
Type 1 Diabetes
Five percent to 10% of all cases of diabetes are type 1. It is usually diagnosed
before the age of 40 years and is one of the most common chronic childhood
illnesses.
Type 1 diabetes is caused by a T cell–mediated autoimmune destruction of
beta cells of the pancreas.
The exact etiology is unknown, although environmental triggers such as viruses
(especially enteroviruses), dietary proteins, and drugs/chemicals may initiate the
autoimmune process in genetically susceptible hosts.
At least 80% to 90% of beta-cell function must be lost before hyperglycemia
occurs.
Patients demonstrate hyperglycemia over several days to weeks associated with
fatigue, weight loss, polyuria, polydipsia, blurring of vision, and signs of
intravascular volume depletion.
The diagnosis is based on the following symptoms: a random blood glucose
greater than 200 mg/dL and a hemoglobin (Hb) A1c level greater than 7.0%.
The presence of ketoacidosis indicates severe insulin deficiency and unrestrained
lipolysis. Beta-cell destruction is complete within 3 years of diagnosis in most
young children, with the process being slower in adults
Type 2 Diabetes
Type 2 diabetes is responsible for 90% of all cases of diabetes mellitus in the
world.. Type 2 diabetics are typically in the middle to older age group and
overweight,
It is estimated that most type 2 diabetics have had the disease for approximately
4 to 7 years before it is diagnosed.
Type 2 diabetes is characterized by relative beta-cell insufficiency and insulin
resistance.
There are three important defects in type 2 diabetes:
*increased rate of hepatic glucose release,
*impaired basal and stimulated insulin secretion
*inefficient use of glucose by peripheral tissues ( insulin resistance) .
Type 2 diabetes is characterized by insulin resistance in skeletal muscle,
adipose tissue, the liver. Insulin resistance is defined as a less-than-normal
biologic response to a given concentration of insulin.
Causes of insulin resistance include an abnormal insulin molecule,
circulating insulin antagonists including counterregulatory hormones, free fatty
acids, anti-insulin and insulin receptor antibodies and cytokines, and target tissue
defects at insulin receptors and/or postreceptor sites.
Metabolic syndrom
The metabolic syndrome or insulin-resistance syndrome is a
constellation of clinical and biochemical characteristics frequently
seen in patients with or at risk of type 2 diabetes.
Diagnostic criteria for diabetes mellitus
A normal fasting plasma glucose is 70 to 100 mg/dL.
Hyperglycemia not sufficient to meet the diagnostic criteria for diabetes is
classified as either impaired fasting glucose or impaired glucose tolerance,
depending on whether it is identified through a fasting plasma glucose or an oral
glucose tolerance
Any fasting glucose between 101 and 125 mg/dL is impaired fasting glucose.
the oral glucose tolerance test is recommended for diagnosis when glucose
values are equivocal.
The Hb A1c test provides a valuable assessment of long-term
glycemiccontrol.
Erythrocyte hemoglobin is nonenzymatically glycosylated by
glucose that freely crosses red blood cell membranes. The
percentage of hemoglobin molecules participating in this reaction is
proportional to the average plasma glucose concentration during
the preceding 60 to 90 days.
The normal range for Hb A1c is 4% to 6%. Increased risk of
microvascular and macrovascular disease begins at a Hb A1c of 6.5%.
Venous plasma or serum is the standard body fluid for glucose
determinations.
Arterial and capillary blood yield glucose values approximately 7%
higher than venous blood.
Whole blood determinations are usually 15% lower than plasma or
serum values.
Urine glucose is a poor diagnostic test since the renal glucose
threshold is not reached until the extracellular glucose
concentration exceeds 180 mg/dL. concentrations.
Treatment
The cornerstones of therapy for type 2 diabetes are
1-diet with weight loss
2- exercise therapy
3-the oral antidiabetic agents.
The initial decrease in fasting plasma glucose results from a decrease
in hepatic glycogen stores and a decline in glycogenolysis.
The decrease in adiposity improves hepatic and peripheral tissue
insulin sensitivity, enhances post receptor insulin action, and may
possibly increase insulin secretion.
Estimation of basal energy requirements and activity level
requirements plus additional adjustments for growing children,
pregnancy, lactation, infection, illness, and surgery are necessary.
Low-calorie diets (800–1500 kcal) and very low calorie diets (<800 kcal)
with limits on cholesterol raising fats and added sugars are used to
reduce body fat and decrease insulin resistance and to normalize
plasma glucose, lipids, and lipoproteins.
Oral Antidiabetic Agents
The four major classes of oral agents are the secretagogues
*sulfonylureas, meglitinides (Glibenclamid),which increase
insulin availability.
*biguanides (metformin), which suppress excessive hepatic
glucose release.
*Thiazolidinediones or glitazones (rosiglitazone pioglitazone),
which improve insulin sensitivity
*α-glucosidase inhibitors (acarbose, miglitol), which delay
gastrointestinal glucose absorption
These agents, either as monotherapy or in various combinations, are
used to maintain glucose control (fasting glucose, 90–130 mg/dL;
peak postprandial glucose( <180 mg/dL, Hb A1c <7%)in the initial
stages of the disease
Insulin
Insulin is necessary to manage all type 1 diabetics
and many type 2 diabetics .
In the United States, 30% of type 2 diabetics are
treated with insulin.
Conventional insulin therapy uses twice-daily
injections.
*Intensive insulin therapy uses three or more daily
injections or a continuous infusion.
The various forms of insulin include basal insulins,
which are intermediate acting (NPH, lente, lispro protamine,
aspart protamine) and administered twice daily
or long acting (ultralente and glargine) and administered once daily,
and insulins that are short acting (regular) or rapid acting
(lispro, aspart), which provide glycemic control at mealtimes
(prandial insulin).
Conventional insulin therapy usually requires twice-daily
injections of combinations of intermediate-acting and short-/rapidacting insulins such as Humulin 70/30 insulin (70% NPH, 30%
regular), Novolog 70/30 (70% insulin aspart protamine plus 30%
insulin aspart) or Humalog 75/25 (75% insulin lispro protamine plus
25% insulin lispro) .
For Humulin 70/30, injections are given 30 minutes before breakfast
and 30 minutes before dinner.
For Novalog 70/30 and Humalog 75/25, injections are given 5 to 15
minutes before breakfast and 5 to 15 minutes before dinner.
Twice-daily separate injections of NPH insulin and regular insulin or
NPH insulin and rapid-acting insulin (lispro, aspart) are another
conventional method of administration
Intensive insulin therapy uses three or four daily injections or a
continuous infusion with more frequent glucose monitoring.
Three daily injections includes NPH plus short-acting (regular) or rapid-acting
(lispro, aspart) insulin before breakfast, short-acting or rapid-acting insulin before
dinner, and NPH insulin at bedtime .
Four daily injections can include a single injection of NPH, lente, or insulin
glargine (Lantus) at bedtime plus short-acting or rapid-acting insulin before
breakfast, lunch, and dinner .A subcutaneous infusion pump uses regular or
rapid-acting insulin with a usual range of 0.5 to 2.0 units per hour.
A typical total daily basal dose of insulin equals weight (kg) × 0.3, with the
hourly rate obtained by dividing by 24.
Basal rates vary during a 24-hour period with
lower rates required at bedtime, higher rates between 3 and 9 AM and
intermediate rates during the day.
Premeal boluses may also be used, and insulin rates must be adjusted for
exercise.
Ideal glycemic goals for type 1 diabetics include the following: before
meals, 70 to 120 mg/dL; after meals, less than 150 mg/dL; at bedtime, 100
to 130 mg/dL; and at 3:00 AM more than 70 mg/dL.
For many type 2 diabetics,
early and aggressive initiation of insulin therapy has demonstrated beneficial
effects. Reports of remissions of type 2 diabetes with early intensive insulin
treatment suggests that it should be prescribed early rather than as a treatment of
last resort. Unlike oral agents, insulin has no upper dose limit and can be adjusted
over time to achieve near-normal glucose levels. Many type 2 diabetics require 0.6
to 1.0 U/kg per day. The amount of insulin needed is not related to the degree of
hyperglycemia but to body adiposity and other factors of insulin resistance. In
most studies, obese type 2 diabetics require significant daily doses (100–200
units) to achieve near-normal glycemia.
Fortunately, blood glucose levels for type 2 diabetics are much less labile than for
type 1 diabetics and adjustment of the dose is less necessary.
Insulin therapy is usually initiated with 10 to 15 units of intermediate-acting
insulin at bedtime with the dose being adjusted until fasting levels are
therapeutic, or, alternatively, administering long-acting insulin glargine in the
evening. If glucose levels remain elevated during the day, intermediate-acting
insulin is added in the morning with or without short- or rapid-acting insulin. Type
2 diabetics who benefit most from insulin therapy are those who demonstrate
catabolism with ketonuria, persistently elevated glucose levels despite oral
therapy, severe hypertriglyceridemia, uncontrolled weight loss or severe
dehydration with hyperglycemia, or the desire to maintain near-normal glycemia
or induce remission
Hypoglycemia is the most frequent and dangerous complication of insulin
. Approximately 30% of type 1 diabetics experience one or more severe
hypoglycemic attacks per year.
The incidence is three times higher in the intensive therapy group than the
conventional group.
The hypoglycemic effect can be exacerbated by simultaneous administration of
alcohol, sulfonylureas, biguanides, thiazolidinediones, angiotensinconverting enzyme (ACE) inhibitors, monoamine oxidase inhibitors, and
nonselective β-blockers.
β-Blockers may exacerbate hypoglycemia by inhibiting adipose tissue lipolysis,
which serves as an alternate fuel when patients become hypoglycemic.
Defective counterregulatory responses by glucagon and epinephrine to reduced
plasma glucose levels contribute to this complication.
Repetitive episodes of hypoglycemia, especially at night, results in hypoglycemia
unawareness where the patient does not respond with the appropriate autonomic
warning symptoms before neuroglycopenia.
The diagnosis in adults requires a plasma glucose level less than 50 mg/dL.
Symptoms are adrenergic (sweating, tachycardia, palpitations, restlessness,
pallor) and neuroglycopenic (fatigue, confusion, headache, somnolence,
convulsions, coma).
Treatment, if conscious, includes the administration of sugar in the form of sugar
cubes, glucose tablets or soft drinks, and, if unconscious, glucose 0.5 g/kg IV
or glucagon 0.5 to 1.0 mg IV, IM, or SC
Diabetic Ketoacidosis
Diabetic ketoacidosis (DKA) is a complication of decompensated
diabetes mellitus.
The signs and symptoms of DKA are primarily the result of
abnormalities in carbohydrate and fat metabolism.
Episodes of DKA occur more commonly in type 1 diabetics and are
precipitated by infection or acute illness (cerebrovascular accident,
myocardial infarction, acute pancreatitis)
High glucose levels exceed the threshold for renal tubular
absorption creating a significant osmotic diuresis with marked
hypovolemia
Hyperglycemic Hyperosmolar Syndrome
Hyperglycemic hyperosmolar syndrome (HHS) is characterized by severe
hyperglycemia, hyperosmolarity, and dehydration usually in elderly
(older than 60 years) type 2 diabetics who live alone, are socially isolated, and
experience an acute illness such as infection, myocardial infarction,
cerebrovascular accident, pancreatitis, intestinal obstruction, endocrinopathy,
renal failure, or a burn.
The patient presents with polyuria, polydipsia, hypovolemia,
hypotension, tachycardia, and organ hypoperfusion.
The early administration of large volumes of crystalloid fluids is necessary
to prevent this syndrome. Hyperosmolarity (>340 mOsm/L) is responsible
for an obtunded mental status or coma.
Patients may have some degree of metabolic acidosis but do not demonstrate
a ketosis.
Vascular occlusions secondary to
1-mesenteric artery thrombosis
2- low-flow states
3-DIC (Diffuse intravascular coagulation)
Glycemic Control
Controlled clinical trials and epidemiologic studies have analyzed
the relationship between the degree of glycemic control and the
incidence of microvascular and macrovascular complications.
Randomized, controlled clinical trials have unequivocally established
that strict control of glycemia can decrease the risk of
microangiopathic (nephropathy, peripheral neuropathy, retinopathy)
complications of diabetes.
Microvascular dysfunction is characterized by
Nonocclusive, microcirculatory impairment with vascular
permeability and impaired autoregulation of blood flow and
vascular tone.
Intensive glycemic control (near normal range) delays the onset and
slows progression of microvascular effects, demonstrating
significant improvements in all outcomes for all microvascular
complications.
The major morbidity and mortality from type 2 diabetes
is secondary to accelerated atherosclerosis, a multifactorial disease
process not solely due to hyperglycemia.
As a result, treatment must be directed at multiple risk factors in
addition to hyperglycemia such as hypertension, hyperlipidemia, and
smoking.
A growing number of epidemiologic studies have demonstrated an
association between the degree of glycemia and macrovascular
(cardiovascular, cerebrovascular, and peripheral vascular disease)
complications, but large randomized clinical trials have not
convincingly shown that macrovascular disease is affected by
glycemic control.
The macrovascular pathology is morphologically and functionally
similar to nondiabetics and is characterized by atherosclerotic
lesions of the coronary and peripheral arterial circulations.
Microvascular Complications
*Retinopathy
**Nephropathy
31
Visual Complications of Diabetes
Diabetic retinopathy can lead to blindnes
Education of client
*Check blood sugar
*Check blood pressure
*Regular eye exam with ophthalmologist
*Laser photocoagulation therapy
32
Management of Anesthesia
The goals of anesthetic management of the diabetic patient include
*preoperative evaluation.
*An in-depth understanding of the pathophysiology of diabetes and
the metabolic stress response.
*Asignificant knowledge and understanding of insulin, and possibly
collaboration with the patient’s internist/endocrinologist.
Management of Anesthesia
The stress response of surgery.
1-Activation of the sympathetic nervous system and release of catecholamines,
cortisol, and growth hormone may be sufficient to convert a well-controlled
diabetic to one with significant hyperglycemia and even ketoacidosis,
2-Reduction in insulin sensitivity (insulin resistance of surgery) in the periphery
The magnitude of surgery is very important, with major surgery creating
significant metabolic derangements and minor surgery demonstrating less risk.
The effects of chronic hyperglycemia (coronary artery disease, myocardial
infarction, congestive heart failure, peripheral vascular disease, hypertension,
cerebrovascular accident, chronic renal failure, infection, neuropathy) are
frequently present on preoperative evaluation and should be medically optimized
before proceeding,
The effects of acute hyperglycemia are also dangerous and must be
managed
Management of Anesthesia
Acute and chronic hyperglycemia appear to
Increase the risk of ischemic myocardial injury by decreasing coronary collateral
blood flow and coronary vasodilator reserve, impairing coronary microcirculation
and causing endothelial dysfunction.
Acute hyperglycemia causes
* Dehydration,
*Impaired wound healing,
*increased rate of infection,
*Worsening central nervous system/spinal cord injury with ischemia,
* Hyperviscosity with thrombogenesis.
Tight control of serum glucose in the perioperative period is important in
managing the consequences of acute and chronic hyperglycemia.
Management of Anesthesia
Preoperative Evaluation
The preoperative evaluation should emphasize
the cardiovascular, renal, neurologic, and musculoskeletal systems. A high index
of suspicion should exist for myocardial ischemia and infarction.
Silent ischemia is possible if an autonomic neuropathy is present.
Stress testing should be considered if a patient exhibits two or more cardiac risk
factors and is undergoing major surgery
β1-Antagonists should be used if coronary artery disease is present to decrease
morbidity and mortality perioperatively.
For renal disease, control of hypertension is a major priority, using ACE
inhibitors.
Meticulous attention to hydration status, avoiding nephrotoxins, and preserving
renal blood flow are also essential.
Management of Anesthesia
Preoperative Evaluation
The presence of an autonomic neuropathy
*Perioperative dysrhythmias.
*Intraoperative hypotension.
*Gastroparesis with possible aspiration.
* Hypoglycemia unawareness.
Preoperative evaluation of the musculoskeletal system
limited joint mobility of the neck (nonenzymatic glycosylation of
proteins and abnormal cross-linking of collagen). Firm, woody,
nonpitting edema of the posterior neck and upper back (scleredema of
diabetes) coupled with impaired joint mobility limits complete range
of motion of the neck and may render endotracheal intubation
difficult.(Atleto-occipital)
Management of Anesthesia
Insolin Thrapy
Management of insulin in the preoperative period depends on the
type of insulin that the patient takes and the timing of dosing .
*If a patient takes subcutaneous insulin each night at bedtime, two
thirds of this dose (NPH and regular) should be administered the
night before surgery and one half of the usual morning NPH dose
should be given on the day of surgery. The daily morning dose of
regular insulin should be held.
A 5% dextrose with 0.45% normal saline (D5 ½ NS) intravenous
infusion at 100 mL/hr should be initiated preoperatively.
If the patient uses an insulin pump, the overnight rate should be
decreased by 30% so that the patient receives 70% of the basal rate.
On the morning of surgery, the pump can be kept infusing at the
basal rate or discontinued and replaced with a continuous insulin
infusion at the same rate, or the patient can be given subcutaneous
Glargine and the pump discontinued in 60 to 90 minutes
Management of Anesthesia
Insolin Thrapy
If the patient uses glargine and lispro or aspart for daily glycemic control,
the patient should take two thirds of the glargine dose and the entire lispro or
aspart dose the night before surgery and hold all morning dosing.
Oral hypoglycemics should be discontinued 24 to 48 hours preoperatively.
The sulfonylureas should also be avoided during the entire perioperative period
since they block myocardial potassium ATP channels, which are responsible for
ischemia- and anesthetic-induced preconditioning.
Well-controlled type 2 diabetics do not require insulin for minor surgery.
Poorly controlled type 2 diabetics and all type 1 diabetics having minor surgery and
all diabetics having major surgery need insulin.
For major surgery, if the serum glucose is greater than 270 mg/dL preoperatively,
the surgery should be delayed while rapid control is achieved with intravenous
insulin.
If the serum glucose is greater than 400 mg/dL, the surgery should be postponed
and the metabolic state restabilized
Intraoperative Management
Two major goals are to minimize hyperglycemia and
avoid hypoglycemia.
Ideally, a continuous infusion of insulin should be
initiated at least 2 hours before surgery.
A sliding scale with short-acting, subcutaneous insulin
for glucose greater than 200 to 250 mg/dL is
ineffective and should not be used.
Intraoperative serum glucose levels should be
maintained between 120 and 180 mg/dL.
Levels above 200 mg/dL are likely to be detrimental in
the perioperative period,causing glycosuria and
dehydration and inhibiting phagocyte function and
wound healing.
Intraoperative Management
Typically, one unit of insulin lowers glucose approximately 25 to 30 •
mg/dL.
The initial hourly rate for a continuous insulin infusion is determined
by dividing the total daily insulin requirement by 24.
A typical rate is 0.02 U/kg per hour or 1.4 U/hr in a 70-kg patient.
An insulin infusion can be prepared by mixing 100 units of regular
insulin in 100 mL NS (1 U/mL).
Insulin infusion requirements are higher for CABG (0.06 U/kg per
hour),
patients receiving steroids (0.04 U/kg per hour),
patients with severe infection (0.04 U/kg per hour),
patients receiving hyperalimentation or vasopressor infusions. Insulin
infusions should be accompanied by an infusion of D5 ½ NS with 20
mEq KCl at 100 to 150 mL/hr to provide carbohydrate (at least 150
g/day) to inhibit hepatic glucose production and protein catabolism
Intraoperative Management
Serum glucose should be monitored every 1 hour and every 30
minutes for CABG or for patients with higher insulin requirements.
Spot urine glucose monitoring is not reliable, although the urine can
be tested for ketones if the glucose increases to more than 250
mg/dL. For serum glucose values less than 100 mg/dL, the D5 ½ NS
infusion rate should be 150 mL/hr;
for (100 to 150 mg/dL), it should be 75 mL/hr;
for (151 to 200 mg/dL), it should be 50 mL/hr,
for more than 200 mg/dL, a keep vein open (KVO) rate should be
used.
Hypoglycemia is defined as a serum glucose less than 50 mg/dL in
adults and 40 mg/dL in children.
Treatment consists of 50 mL of 50% dextrose (D50), which increases
the glucose 100 mg/dL or 2 mg/dL/mL
Emergency Surgery
Emergency surgery places diabetics at risk of developing DKA or HHS .
Surgery should be delayed for 4 to 6 hours to optimize the patient’s
metabolic status. DKA is more likely to develop in type 1 diabetics and is
usually precipitated by
Infection, gastrointestinal obstruction, or trauma in the surgical patient .
Patients present with hyperglycemia, hyperosmolarity, significant
dehydration, ketosis, and acidosis .
Treatment of DKA includes
large volumes of normal saline and insulin sulob nilusni nA .o.1 U/kg
followed by an infusion of 0.1 U/kg per hour is the initial prescription.
Serum glucose is monitored hourly derotinom era setylortcele dna ,
yreve2 hours era sticifed etahpsohp dna ,muisengam ,muissatoP .
.detnemucod si noitcudorp eniru nehw decalper
When serum glucose naht ssel ot sesaerced 250 mg/dL suonevartni ,
edulcni dluohs sdiulfdextrose. Insulin is continued until acidosis resolves .
Sodium bicarbonate is not routinely given and is reserved for cases
where the pH is less than 7.10
Emergency Surgery
HHS epyt detatilibed ,ylredle ni srucco yllausu 2 diabetics .
These patients present with greater metabolic derangements
than those with DKA and are severely dehydrated ∼ 7-10 L
< ralomsorepyh 320 mOsm/L), and hyperglycemic < 800-1000
mg/dL.
They may present with confusion, focal central nervous system
deficits, seizures, or coma. Surprisingly, electrolyte deficits
(K+,Mg2+( are less severe than in DKA.
Treatment
consists of larger volumes of normal saline and similar doses
of insulin compared to patients with DKA .
These patients are at significant risk of developing of larberec
amedeand therefore correction of serum glucose and
osmolarity should proceed gradually over a 12 to 24 hour
period
Postoperative Care
Aggressive insulin therapy in the intensive care unit (ICU)
has demonstrated significant benefit in morbidity and
mortality.
Patients receiving conventional insulin therapy (serum
glucose, 180–200 mg/dL) demonstrate significantly higher
rates of ICU mortality, in-hospital mortality and morbidity
including sepsis, renal failure, and anemia than patients
who were tightly controlled (80–110 mg/dL).
Possible reasons for improved outcome in the latter include
better neutrophil and macrophage function, beneficial
changes to mucosal/skin barriers, enhanced erythropoiesis,
reduced cholestasis, improved respiratory muscle function,
and decreased axonal degeneration.
Postoperative Care
The postoperative management of diabetics requires
meticulous monitoring of insulin requirements.
To determine the discharge dose,
the total insulin (long, intermediate, short, rapid acting)
dose for the most recent 24-hour period is calculated,
and 50% of the discharge dose is prescribed as long- or
intermediate-acting insulin and 50% as short- or rapidacting insulin.
If glargine is prescribed, it is usually given once at
bedtime.
If the patient takes intermediate-acting insulin twice
daily, then two thirds of the dose should be taken in
the morning and one third at bedtime.
THE
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