Hyperglycemic Emergencies

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Hyperglycemic Emergencies

• Thomas Repas D.O.
• Diabetes, Endocrinology and Nutrition Center,
  Affinity Medical Group, Neenah, Wisconsin
• Member, Inpatient Diabetes Management Committee,
  St. Elizabeths Hospital, Appleton, WI
• Member, Diabetes Advisory Group, Wisconsin
  Diabetes Prevention and Control Program

Website www.endocrinology-online.com
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U.S. Total Costs of Diabetes, 2002
Diabetes Care 26(3)917-932, 2003
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Acute Complications of Diabetes

• Acute
• Poor wound healing
• Infections
• Vascular insufficiency
• Other
• Hyperglycemic Emergencies
• Diabetic Ketoacidosis (DKA)
• Hyperosmolar Hyperglycemic Syndrome (HHS)

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Consequences of Poor Hospital Glycemic Control

• Several studies show diabetes increases morbidity
  and mortality for myocardial infarction, coronary
  bypass surgery, and stroke. More specifically,
  when glucoses are elevated there may be
• Fluid and electrolyte abnormalities secondary to
  osmotic diuresis
• Decreased WBC function
• Delayed gastric emptying
• Increased surgical complications including
• Relative risk for "serious" postoperative
  nosocomial infections increased by a factor of
  5.7 when glucose gt220 mg/dl
• Relative odds of wound infection increased to
  1.17 with glucoses were 207-227 and 1.78-1.86
  when glucoses were gt253.
• Delayed hospital discharge
• Double the mortality risk in patients admitted
  with a stroke

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Intervention Studies Evidence That Improving
Glucose Control Improves Outcome

• Improved WBC function
• Perioperative insulin infusion improves
  neutrophil phagocytic activity to 75 of baseline
  activity compared to only 47 in a control group
• Decreased postoperative mortality
• Diabetes team followed patients and controlled
  glucoses using perioperative IV insulin infusion
  and algorithm based SQ premeal insulin. Mortality
  of diabetic patients undergoing CABG in 1993-1996
  was reduced to level of nondiabetics. Nationally,
  diabetic patients had 50 higher mortality
• Decreased infections
• Perioperative intravenous insulin infusion
  designed to keep glucoses lt200 mg/dl reduces the
  risk of wound infection in diabetics after open
  heart operations. Incidence of Deep Wound
  Infections decreased from 2.4 to 1.5
• Decreased length of stay
• Use of an inpatient diabetes consultation service
  decreased length of stay by 56

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Importance of Excellent Glycemic Control

• In a surgical ICU, 1548 patients were randomized
  to intensive vs. conventional therapy
• Intensive IV insulin to maintain BG 80 110
  mg/dl
• Conventional begin IV insulin if BG gt 215 with
  goal of 180 200
• Risk reduction in ICU mortality was 42
• Overall in hospital mortality reduced 34
• Greatest benefits were seen in patients with
  multiorgan failure and sepsis
• Also reduced duration of mechanical ventilation,
  acute renal failure, and need for transfusion

Van de Berghe G, et al. Intensive Insulin Therapy
in Critically ill Patients. N Engl J Med.
20013451359-1367.
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Cardiovascular RiskMortality After MI Reduced by
Insulin Therapy in the DIGAMI Study
IV Insulin 48 hours, then
4 injections daily
All Subjects
.7
.7
Low-risk and Not Previously on Insulin
(N 620)
(N 272)
.6
.6
Risk reduction (51)
Risk reduction (28)
.5
.5
P .011
P .0004
.4
.4
.3
.3
.2
.2
.1
.1
0
0
0
1
2
3
4
5
0
1
2
3
4
5
Years of Follow-up
Years of Follow-up
Malmberg, et al. BMJ. 19973141512-1515.
6-11
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Common Errors in Inpatient Diabetes Management

• Admission orders
• Overly high glycemic targets
• Lack of therapeutic adjustment
• Overutilization of sliding scales
• Underutilization of IV insulin

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Hyperglycemic Emergencies
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Hyperglycemic Emergencies

• Diabetic Ketoacidosis (DKA)
• Occurs in type 1s
• May or may not occur with other illness
• Typically younger patients
• Mortality lt5 under optimal management
• Hyperosmolar Hyperglycemic Syndrome (HHS)
• Occurs in type 2s
• Often occurs with other concurrent illness
• Typically older patients
• Mortality 15

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Precipitating Factors

• Infection (Pneumonia and UTI most common)
• Previously undiagnosed diabetes
• Inadequate insulin treatment
• Noncompliance with therapy
• Unknown or other causes

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Symptoms and Clinical Findings

• Diabetic Ketoacidosis can present rapidly
  (lt24hrs)
• nausea vomiting (most common symptom)
• fruity (acetone) breath odor
• abdominal pain (but always rule out other
  pathology also)
• Kussmaul breathing (rapid and deep inspiration)
• HHS often more insidious in presentation
  (develops over several days)
• May have polyuria, polydipsia, and weight loss
  for days before diagnosis.
• More likely to have mental status changes or even
  coma, and/or seizures or other focal neurologic
  findings.
• Both DKA HHS can have evidence of dehydration
  such as poor skin turgor, dry oral mucosa,
  hypotension

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Diagnostic Criteria

• DKA HHS
• Plasma Glucose gt250 gt600
• Arterial pH lt7.3 gt7.3
• Serum Bicarb lt15 gt15
• Ketones Positive None or small
• Serum Osmolality Varies gt320
• Anion Gap gt10 lt12
• Mental Status Varies Stupor/coma

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• Anion Gap
• A.G.(Na) - (Cl- HCO3-)
• Normal 7 to 9 mEq/l

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Serum osmolality2measured Na
glucose/18Normal2855
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• Corrected Sodium
• For each 100 mg/dl glucose gt100 mg/dl, add 1.6
  mEq to sodium value for corrected serum sodium
  value

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Other Causes of Metabolic Acidosis

• Alcoholic Ketoacidosis
• Starvation Ketoacidosis
• Lactic Acidosis
• Chronic Renal Failure
• Drug induced
• Salicylate, Methanol, Ethylene Glycol,
  Paraldehyde

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Therapeutic Goals

• Improving circulatory volume and tissue perfusion
• Decreasing serum glucose and plasma osmolality
  towards normal
• Clearing of urine and serum of ketones at a
  steady rate
• Correcting electrolyte imbalances
• Identifying and treating precipitating factors

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Patient Outcomes Neurologic status

• Hyperosmolarity can be associated with mental
  status changes, stupor or coma
• The presence of such mental status changes
  without hyperosmolarity requires consideration of
  other causes
• Cerebral edema is a rare, but serious
  complication with high mortality (gt70).
• Consider cerebral edema when
• Lethargy with deterioration of mental status
• Decrease in arousal
• Headache
• Seizures
• Other Incontinence, pupillary changes,
  bradycardia, respiratory arrest

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Patient Outcomes Fluid electrolyte balance

• During therapy for DKA or HHS, blood should be
  drawn every 24 h for determination of serum
  electrolytes, blood urea nitrogen, creatinine,
  osmolality, and venous pH (for DKA).
• Frequently, repeat arterial blood gases are
  unnecessary venous pH (which is usually 0.03
  units lower than arterial pH) and/or anion gap
  can be followed to monitor resolution of
  acidosis.

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Patient Outcomes Fluid electrolyte balance

• Fluid replacement should correct estimated
  deficits within the first 24 h.
• The induced change in serum osmolality should
  not exceed 3 mOsm kg1 H2O h1
• In patients with renal or cardiac compromise,
  monitoring of serum osmolality and frequent
  assessment of cardiac, renal, and mental status
  must be performed during fluid resuscitation to
  avoid iatrogenic fluid overload.

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• Calculating Fluid Deficit
• BWD (L) 0.6 (weight kg) (measured Na 140)
• 140

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Patient Outcomes Blood Glucose

• Blood Glucose must be monitored every 1 to 2
  hours during treatment
• Goal is to decrease plasma glucose concentration
  at a rate of 5075 mg dl1 h1

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Patient Outcomes Ketones

• Ketonemia typically takes longer to clear than
  hyperglycemia.
• Direct measurement of ß-OHB in the blood is the
  preferred method for monitoring DKA. The
  nitroprusside method only measures acetoacetic
  acid and acetone.
• However, ß-OHB, the strongest and most prevalent
  acid in DKA, is not measured by the nitroprusside
  method.
• During therapy, ß-OHB is converted to acetoacetic
  acid, which may lead the clinician to believe
  that ketosis has worsened.
• Therefore, assessments of urinary or serum ketone
  levels by the nitroprusside method should not be
  used as an indicator of response to therapy.

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Patient Outcomes Hemodynamic status

• Successful progress with fluid replacement is
  judged by hemodynamic monitoring (improvement in
  blood pressure), measurement of fluid
  input/output, and clinical examination.

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Patient Outcomes Identifying and treating
precipitating factors

• It is essential to identify and treat
  precipitating factors
• Chest x-rays, urinalysis, blood cultures and
  other studies should be obtained where
  appropriate

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Therapeutic Interventions

• Replacement of Fluids and electrolytes
• Insulin Therapy
• Potassium
• Phosphate
• Bicarbonate

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Replacement of Fluids and electrolytes

• Initial fluid therapy is directed toward
  expansion of the intravascular and extravascular
  volume and restoration of renal perfusion.
• In the absence of cardiac compromise, isotonic
  saline (0.9 NaCl) is infused at a rate of 1520
  ml kg1 body wt h1 or greater during the 1st
  hour ( 11.5 l in the average adult).
• Subsequent choice for fluid replacement depends
  on the state of hydration, serum electrolyte
  levels, and urinary output.
• In general, 0.45 NaCl infused at 414 ml kg1
  h1 is appropriate if the corrected serum
  sodium is normal or elevated 0.9 NaCl at a
  similar rate is appropriate if corrected serum
  sodium is low.

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Insulin Therapy

• Unless the episode of DKA is mild, regular
  insulin by continuous intravenous infusion is the
  treatment of choice.
• In adult patients an intravenous bolus of
  regular insulin at 0.15 units/kg body wt,
  followed by a continuous infusion of regular
  insulin at a dose of 0.1 unit kg1 h1 (57
  units/h in adults), should be administered.
• An initial insulin bolus is not recommended in
  pediatric patients a continuous insulin infusion
  of regular insulin at a dose of 0.1 unit kg1
  h1 may be started in these patients.

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Insulin Therapy

• If plasma glucose does not fall by 50 mg/dl from
  the initial value in the 1st hour, check
  hydration status if acceptable, the insulin
  infusion may be doubled every hour until a steady
  glucose decline between 50 and 75 mg/h is
  achieved.
• When the plasma glucose reaches 250 mg/dl in DKA
  or 300 mg/dl in HHS, it may be possible to
  decrease the insulin infusion rate to 0.050.1
  unit kg1 h1 (36 units/h), and dextrose
  (510) may be added to the intravenous fluids.
• Thereafter, the rate of insulin administration or
  the concentration of dextrose may need to be
  adjusted to maintain the above glucose values
  until acidosis in DKA or mental obtundation and
  hyperosmolarity in HHS are resolved.

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Potassium

• Despite total-body potassium depletion, mild to
  moderate hyperkalemia is not uncommon in patients
  with hyperglycemic crises.
• To prevent hypokalemia, potassium replacement is
  initiated after serum levels fall below 5.5
  mEq/l, assuming the presence of adequate urine
  output.
• Generally, 2030 mEq potassium (2/3 KCl and 1/3
  KPO4) in each liter of infusion fluid is
  sufficient to maintain a serum potassium
  concentration within the normal range of 45
  mEq/l.
• Rarely, DKA patients may present with
  hypokalemia. In such cases, potassium replacement
  should begin with fluid therapy, and insulin
  treatment should be delayed until potassium
  concentration is restored to gt3.3 mEq/l to avoid
  arrhythmias or cardiac arrest and respiratory
  muscle weakness.

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Phosphate

• Despite whole-body phosphate deficits in DKA,
  serum phosphate is often normal or increased at
  presentation.
• Phosphate concentration decreases with insulin
  therapy.
• Studies have failed to show any beneficial effect
  of phosphate replacement on the outcome in DKA
  and overzealous phosphate therapy can cause
  severe hypocalcemia.
• However, to avoid complications, careful
  phosphate replacement may sometimes be indicated
  in patients with cardiac dysfunction, anemia, or
  respiratory depression and in those with serum
  phosphate concentration lt1.0 mg/dl.
• When needed, 2030 mEq/l potassium phosphate can
  be added to replacement fluids.

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Bicarbonate

• Bicarbonate use in DKA remains controversial
• At a pH gt7.0, reestablishing insulin activity
  blocks lipolysis and resolves ketoacidosis
  without any added bicarbonate.
• Studies have failed to show either beneficial or
  deleterious changes in morbidity or mortality
  with bicarbonate therapy in DKA patients with pH
  between 6.9 and 7.1
• No studies concerning the use of bicarbonate in
  DKA with pH values lt6.9 have been reported.

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Bicarbonate

• Because severe acidosis may cause adverse
  vascular complications, it is a consensus for
  adult patients with a pH lt6.9, 100 mmol sodium
  bicarbonate be added to 400 ml sterile water and
  given at a rate of 200 ml/h.
• In patients with a pH of 6.97.0, 50 mmol sodium
  bicarbonate is diluted in 200 ml sterile water
  and infused at a rate of 200 ml/h.
• Thereafter, pH should be assessed every 2 h until
  the pH rises to 7.0, and treatment should be
  repeated every 2 h if necessary.
• No bicarbonate is necessary if pH is gt7.0.

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Bicarbonate

• In the pediatric patient, there are no well
  designed studies in patients with pH lt6.9.
• If the pH remains lt7.0 after the initial hour of
  hydration, it seems prudent to administer 12
  mEq/kg sodium bicarbonate over the course of 1 h.
  
• No bicarbonate therapy is required if pH is 7.0

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Complications of Therapy

• Hypoglycemia
• Hypokalemia
• Cerebral Edema
• Acute Respiratory Distress Syndrome
• Hyperchloremic metabolic acidosis

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Hypoglycemia

• Before of the advent or low dose insulin
  protocols, this occurred in as many as 25 of
  patients
• Close monitoring of BGs, decreasing IV insulin
  rate when BG improves and adding dextrose to IV
  fluids when BG lt 250 all can reduce risks of
  hypoglycemia

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Hypokalemia

• Insulin therapy, correction of acidosis, and
  volume expansion decrease serum potassium
  concentration.
• Labs should be ordered every 2 to 4 hours to
  closely monitor this.
• To prevent hypokalemia, potassium replacement is
  initiated after serum levels fall below 5.5
  mEq/l,

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Cerebral Edema

• Cerebral edema is a rare, but serious
  complication with high mortality (gt70).
• It is more common in children, especially those
  with newly diagnosed diabetes
• Consider cerebral edema when
• Lethargy with deterioration of mental status
• Decrease in arousal
• Headache
• Seizures
• Other Incontinence, pupillary changes,
  bradycardia, respiratory arrest
• Prevention measures include
• gradual replacement of sodium and water deficits
  in patients who are hyperosmolar
• addition of dextrose to the hydrating solution
  once blood glucose reaches 250 mg/dl.

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Prevention of DKA HHS

• Hyperglycemic emergencies are often preventable
  through better access to medical care, proper
  education, and effective communication
• Sick day management should be reviewed with all
  patients periodically, including
• When to call health care provider
• BG goals and when/how to use additional short
  acting insulin
• Means to address fever treat infection
• Initiating easily digestible liquid diet with
  carbs and electrolytes
• Advise to never stop insulin
• Instruction for family members and caregivers
• Consultation by a dedicated diabetic education
  team prior to discharge from hospital are useful
  for instruction of self management skills