Transcript Type 2 Diabetes - Endocrinology

Hyperglycemic
Emergencies
Thomas Repas D.O.
Diabetes, Endocrinology and Nutrition Center, Affinity Medical Group, Neenah, Wisconsin
Member, Inpatient Diabetes Management Committee, St. Elizabeth’s Hospital, Appleton, WI
Member, Diabetes Advisory Group, Wisconsin Diabetes Prevention and Control Program
Website: www.endocrinology-online.com
U.S. Total Costs of Diabetes, 2002
Emergency Care
$2.1 (2%)
$132 Billion
Inpatient
Hospital
$54.2 (41%)
Lost Productivity
$39.8 (27%)
Outpatient
Hospital
$20.1(3%)
Office Visits
$10 (8%)
Insulin and
Supplies
$6.9 (5%)
Other Medication
$5 (4%)
Home Healthcare
$3.9 (3%)
Oral Medication
$5.5 (4%)
Diabetes Care 26(3):917-932, 2003
Acute Complications of Diabetes
• Acute
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Poor wound healing
Infections
Vascular insufficiency
Other
• Hyperglycemic Emergencies
– Diabetic Ketoacidosis (DKA)
– Hyperosmolar Hyperglycemic Syndrome (HHS)
Consequences of Poor Hospital Glycemic Control
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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:
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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 >220 mg/dl
– Relative odds of wound infection increased to 1.17 with glucoses were 207-227 and
1.78-1.86 when glucoses were >253.
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Delayed hospital discharge
Double the mortality risk in patients admitted with a stroke
Intervention Studies: Evidence That Improving
Glucose Control Improves Outcome
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Improved WBC function
– Perioperative insulin infusion improves neutrophil phagocytic activity to 75% of
baseline activity compared to only 47% in a control group
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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
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Decreased infections
– Perioperative intravenous insulin infusion designed to keep glucoses <200 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%
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Decreased length of stay
– Use of an inpatient diabetes consultation service decreased length of stay by 56%
Importance of Excellent Glycemic Control
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– Intensive = IV insulin to maintain
BG 80 – 110 mg/dl
– Conventional = begin IV insulin if
BG > 215 with goal of 180 – 200
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In a surgical ICU, 1548 patients were
randomized to intensive vs.
conventional therapy
Conventional
Therapy
Intensive
Therapy
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ICU Mortality
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. 2001;345:1359-1367.
Cardiovascular Risk
Mortality After MI Reduced by Insulin Therapy in the DIGAMI Study
Standard treatment
IV Insulin 48 hours, then 4 injections daily
.7
All Subjects
.7
.6
(N = 620)
Risk reduction (28%)
P = .011
.6
.5
.4
.3
.3
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.2
.1
.1
0
0
1
2
3
4
Years of Follow-up
(N = 272)
Risk reduction (51%)
P = .0004
.5
.4
0
Low-risk and Not Previously on Insulin
5
0
1
2
3
4
Years of Follow-up
5
Malmberg, et al. BMJ. 1997;314:1512-1515.
6-11
Common Errors in Inpatient Diabetes Management
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Admission orders
Overly high glycemic targets
Lack of therapeutic adjustment
Overutilization of “sliding scales”
Underutilization of IV insulin
Hyperglycemic Emergencies
Hyperglycemic Emergencies
• Diabetic Ketoacidosis (DKA)
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Occurs in type 1’s
May or may not occur with other illness
Typically younger patients
Mortality <5 % under optimal management
• Hyperosmolar Hyperglycemic Syndrome (HHS)
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Occurs in type 2’s
Often occurs with other concurrent illness
Typically older patients
Mortality ~ 15%
Precipitating Factors
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Infection (Pneumonia and UTI most common)
Previously undiagnosed diabetes
Inadequate insulin treatment
Noncompliance with therapy
Unknown or other causes
Symptoms and Clinical Findings
• Diabetic Ketoacidosis: can present rapidly (<24hrs)
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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
Diagnostic Criteria
Plasma Glucose
Arterial pH
Serum Bicarb
Ketones
Serum Osmolality
Anion Gap
Mental Status
DKA
HHS
>250
<7.3
<15
Positive
Varies
>10
Varies
>600
>7.3
>15
None or small
>320
<12
Stupor/coma
Anion Gap
A.G.=(Na+) - (Cl- + HCO3-)
Normal= 7 to 9 mEq/l
Serum osmolality
2[measured Na] + glucose/18
Normal=285+5
Corrected Sodium
For each 100 mg/dl glucose >100 mg/dl, add 1.6
mEq to sodium value for corrected serum
sodium value
Other Causes of Metabolic Acidosis
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Alcoholic Ketoacidosis
Starvation Ketoacidosis
Lactic Acidosis
Chronic Renal Failure
Drug induced
– Salicylate, Methanol, Ethylene Glycol, Paraldehyde
Therapeutic Goals
1.
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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
Patient Outcomes: Neurologic status
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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 (>70%).
Consider cerebral edema when:
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Lethargy with deterioration of mental status
Decrease in arousal
Headache
Seizures
Other: Incontinence, pupillary changes, bradycardia, respiratory arrest
Patient Outcomes: Fluid & electrolyte
balance
• During therapy for DKA or HHS, blood should be drawn every
2–4 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.
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 · kg–1 H2O · h–1
• 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.
Calculating Fluid
Deficit
BWD (L) = 0.6 (weight kg) ([measured Na] – 140)
140
Patient Outcomes:
Blood Glucose
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Blood Glucose must be monitored every 1 to 2
hours during treatment
Goal is to decrease plasma glucose concentration
at a rate of 50–75 mg · dl–1 · h–1
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.
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.
Patient Outcomes: Identifying and treating
precipitating factors
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It is essential to identify and treat precipitating
factors
Chest x-rays, urinalysis, blood cultures and other
studies should be obtained where appropriate
Therapeutic Interventions
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Replacement of Fluids and electrolytes
Insulin Therapy
Potassium
Phosphate
Bicarbonate
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 15–20 ml · kg–1 body wt · h–1 or greater during
the 1st hour ( 1–1.5 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 4–14 ml · kg–1 · h–1 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.
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 · kg–1 · h–1 (5–7 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 · kg–1 · h–1 may be started in these patients.
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 0.05–
0.1 unit · kg–1 · h–1 (3–6 units/h), and dextrose (5–10%) 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.
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, 20–30 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 4–5 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 >3.3 mEq/l to avoid arrhythmias or cardiac arrest and respiratory
muscle weakness.
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 <1.0 mg/dl.
• When needed, 20–30 mEq/l potassium phosphate can be added to
replacement fluids.
Bicarbonate
• Bicarbonate use in DKA remains controversial
• At a pH >7.0, 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 <6.9 have been reported.
Bicarbonate
• Because severe acidosis may cause adverse vascular
complications, it is a consensus for adult patients with a pH
<6.9, 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 6.9–7.0, 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 >7.0.
Bicarbonate
• In the pediatric patient, there are no well designed
studies in patients with pH <6.9.
• If the pH remains <7.0 after the initial hour of
hydration, it seems prudent to administer 1–2
mEq/kg sodium bicarbonate over the course of 1 h.
• No bicarbonate therapy is required if pH is 7.0
Complications of Therapy
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Hypoglycemia
Hypokalemia
Cerebral Edema
Acute Respiratory Distress Syndrome
Hyperchloremic metabolic acidosis
Hypoglycemia
• Before of the advent or low dose insulin protocols,
this occurred in as many as 25% of patients
• Close monitoring of BG’s, decreasing IV insulin rate
when BG improves and adding dextrose to IV fluids
when BG < 250 all can reduce risks of hypoglycemia
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,
Cerebral Edema
• Cerebral edema is a rare, but serious complication with high
mortality (>70%).
• It is more common in children, especially those with newly
diagnosed diabetes
• Consider cerebral edema when:
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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.
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:
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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