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|Subject: DIABETIC KETOACIDOSIS Wed Feb 01, 2012 3:09 am|| |
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Diabetic ketoacidosis (DKA) is a state
of absolute or relative insulin deficiency aggravated by ensuing hyperglycemia,dehydration, and acidosis-producing derangements in intermediary metabolism.
The most common causes are underlying infection, disruption of insulintreatment, and new onset of diabetes. DKA typically is characterized by
hyperglycemia over 300 mg/dL, low bicarbonate (<15 mEq/L), and acidosis (pH<7.30) with ketonemia and ketonuria. Pathophysiology:
Many of the underlying
pathophysiologic disturbances in DKA are directly measurable by the clinician and need to be followed throughout the course of treatment. Close attention to
clinical lab data allows the emergency physician not only to track the underlying acidosis and hyperglycemia but also to prevent common potentially lethal complications such as hypoglycemia, hyponatremia, and hypokalemia. The absence of insulin, theprimary anabolic hormone, means that tissues such as muscle, fat, and liver do
not take up glucose. Counterregulatory hormones, such as glucagon, growth hormone, and catecholamines, enhance triglyceride breakdown into free fatty
acids and gluconeogenesis, which is the main cause for the elevation in serum glucose in DKA. Beta-oxidation of these free fatty acids leads to increased
formation of ketone bodies. Overall, metabolism in DKA shifts from the normal fed state characterized by carbohydrate metabolism to a fasting state
characterized by fat metabolism. Secondary consequences of the primary metabolic derangements in DKA include an ensuing metabolic acidosis as the ketone bodies produced by beta-oxidation of free fatty acids deplete extracellular and cellular acid buffers. The hyperglycemia-induced osmotic
diuresis depletes sodium, potassium, phosphates, and water as well as ketones and glucose. Commonly, the total body water deficit is 10%, and the potassium
deficit is 5 mEq per kg of body weight. The total body potassium deficit may be
masked by the acidosis, which sustains an increased serum potassium level. The potassium level can drop precipitously once rehydration and insulin treatment start. Urinary loss of ketoanions with brisk diuresis and intact renal function also may lead to a component of hyperchloremic metabolic acidosis. Frequency:
Mortality/Morbidity: With modern fluid management, the mortality rate of DKA is about 2% per episode. Before the discovery of insulin
- In the US: DKA is seen primarily in patients
with type 1 (insulin-dependent) diabetes. The incidence is roughly 2/100
patient years of diabetes, with about 3% of type 1 diabetic patients
initially presenting with DKA. It can occur in type 2
(non–insulin-dependent) diabetic patients as well.
in 1922, the mortality rate was 100%. Sex: No predilection exists.
Age: DKA tends to occur in individuals
younger than 19 years, the more brittle type 1 diabetic patients, but may occur
in diabetic patients of any age.
| CLINICAL |
- Classic symptoms of hyperglycemia
- Anorexia or increased appetite
- Symptoms of associated infections and conditions
- Ketotic breath (fruity, with acetone smell)
- The most common scenarios are underlying or
concomitant infection (40%), missed insulin treatments (25%), and newly
diagnosed, previously unknown diabetes (15%). Other associated causes make
up roughly 20% in the various series.
- Urinary tract infections (UTIs) are the single most
common infection associated with DKA, but many other associated illnesses
need to be considered as well.
- Cerebrovascular accident
- Complicated pregnancy
| DIFFERENTIALS |
Hyperglycemic Nonketotic Coma
Urinary Tract Infection,
Urinary Tract Infection,
Other Problems to be
Acute hypoglycemia coma
| WORKUP |
- Glucose: Levels may be as low as 250 mg/dL. The
clinician can do a fingerstick glucose while waiting for the serum
- Sodium: The osmotic effect of hyperglycemia moves
extravascular water to the intravascular space. For each 100 mg/dL of
glucose over 100 mg/dL, the serum sodium is lowered by approximately 1.6
mEq/L. When glucose levels fall, the serum sodium will rise by a
- Potassium: This needs to be checked frequently, as
values drop very rapidly with treatment. An ECG may be used to assess the
cardiac effects of extremes in potassium levels.
- Bicarbonate: Use in conjunction with the anion gap
to assess degree of acidosis.
- Complete blood count (CBC): High WBC counts (>15
x 109/L) or marked left shift suggest underlying bacterial
- Arterial blood gases (ABG): pH is often <7.3.
Venous pH may be used for repeat pH measurements.
- Ketones: The Acetest and Ketostix products measure
blood and urine acetone and acetoacetic acid. They do not measure the more
common ketone body, beta-hydroxybutyrate, so the patient may have
paradoxical worsening as the latter is converted into the former during
treatment. Specific testing for beta-hydroxybutyrate can be performed by
- Urinalysis (UA): Look for glycosuria and urine
ketosis. Use to detect underlying UTI.
- Osmolality: Measured as 2(Na+) (mEq/L) +
glucose (mg/dL)/18 + BUN(mg/dL)/2.8. Patients with DKA who are in a coma
typically have osmolalities >330 mOsm/kg H20. If the
osmolality is less than this in a comatose patient, search for another
cause of obtundation.
- Phosphorous: If the patient is at risk for
hypophosphatemia (eg, poor nutritional status, chronic alcoholism), then
serum phosphorous should be determined.
- Hyperamylasemia may be seen even in the absence of
- Anion gap is higher than normal.
- Repeat labs are critical. Potassium needs to be
checked every 1-2 hours during initial treatment. Glucose and other
electrolytes should be checked every 2 hours or so during initial
aggressive volume, glucose, and electrolyte management. If the initial
phosphorous was low, it should be monitored every 4 hours during therapy.
- Be aware that high serum glucose levels may lead to
dilutional hyponatremia; high triglyceride levels may lead to factitious
low glucose; and high levels of ketone bodies may lead to factitious
elevation of creatinine.
- Chest x-ray (CXR): Rule out pulmonary infection.
- CT scan: The threshold should be low for obtaining a
head CT scan in children with DKA who have altered mental status, as this
may be caused by cerebral edema.
- Telemetry: Consider telemetry to monitor for
ischemia and hypokalemia effects.
- Electrocardiogram (ECG): DKA may be precipitated by
a cardiac event, and the physiological disturbances of DKA may cause
- Intubation and airway management should be
considered for coma (especially if the patient is hypoventilating or
unable to protect the airway) or for cerebral edema.
- Nasogastric tube should be considered to prevent
aspiration if the patient is comatose.
Prehospital Care: Isotonic saline solution should be
| TREATMENT |
given as a bolus up to 1 L, depending on the patient's vital signs and other
indicators of hypovolemia. Emergency Department
extreme vigilance for any concomitant process such as infection,
cerebrovascular accident (CVA), MI, sepsis, or deep venous thrombosis (DVT).
- Fluid resuscitation is a critical part of treating
DKA. Intravenous (IV) solutions replace extravascular and intravascular
fluids and electrolyte losses. They also dilute both the glucose level and
the levels of circulating counterregulatory hormones. Insulin is needed to
help switch from a catabolic to an anabolic state, with uptake of glucose
in tissues and the reduction of gluconeogenesis as well as free fatty acid
and ketone production.
- Administer 1 L of isotonic
saline (or more if needed for significant hypovolemia) in the first hour.
Further isotonic saline should be administered at a rate appropriate to
maintain adequate blood pressure and pulse, urinary output, and mental
status. If a patient is severely dehydrated and significant fluid
resuscitation is needed, switching to a balanced electrolyte solution
(such as Normosol-R, in which some of the chloride in isotonic saline is
replaced with acetate) may help to avoid the development of a hyperchloremic
- After initial stabilization with
isotonic saline, switch to half-normal saline at 200-1000 mL/h
(half-normal saline matches losses due to osmotic diuresis).
- Add 20-40 mEq/L of KCl to each
liter of fluid once K+ is under 5.5 mEq/L.
- Can give potassium as follows:
two thirds as KCl, one third as KPO4.
- Bicarbonate typically is not replaced, although some
physicians do so when pH <7. Administration of bicarbonate has been
correlated with cerebral edema in children.
- Phosphate and magnesium replacements typically are
not needed, since levels correct when patient resumes eating.
- Use data flow sheets to monitor timing of labs and
Treatment of ketoacidosis
| MEDICATION |
should aim at correcting dehydration, reversing the acidosis and ketosis,
reducing plasma glucose concentration to normal, replenishing electrolyte and
volume losses, and identifying the underlying cause.
Please see specific chapters for dosing regimens.Drug
These agents lower plasma glucose and ketone levels.
| Insulin |
(Humulin, Humalog, and Novolin) -- In addition to lowering glucose levels and
preventing further ketone production, insulin stimulates cellular uptake of
potassium within 20-30 min. Glucose should be administered along with insulin
to prevent hypoglycemia once glucose levels are lowered to 200 mg/dL. Monitor
blood glucose levels frequently.
Regular insulin is used to reduce blood glucose levels in DKA.
| Loading |
dose: 0.1-0.15 U/kg IV bolus (note that some consider this optional)
Maintenance ED doses: 0.1 U/kg/h IV infusion, typically 5-7 U/h
| Administer |
as in adults
| Documented |
hypersensitivity, hypoglycemia; profound hypokalemia
| Not |
a clinical concern in the treatment of DKA in the ED
| B |
- Usually safe but benefits must outweigh the risks.
| Monitor |
glucose and institute D5 isotonic saline with 3-7 U/h insulin IV/IM/SC once
serum glucose reaches 200 mg/dL to prevent iatrogenic hypoglycemia
Category: Mineral solutions
-- These solutions
replenish mineral deficiencies.
| Potassium |
chloride -- Potassium deficits are high in DKA even with paradoxically high K+
due to acidotic state, which shifts H+ into cells and K+
out of cells into blood. Monitor potassium q1-2 h initially. Repletion with
potassium phosphate often thought unnecessary, although some recommend giving
potassium phosphate to replete both of these electrolytes.
| 20-40 |
mEq/L of KCl to each liter of fluid once K+ is <5.5 mEq/L; give
two thirds as KCl and one third as KPO4+
| Administer |
as in adults
| Hyperkalemia, |
renal failure, conditions associated with potassium retention, oliguria or
azotemia, crush syndrome, severe hemolytic reactions, anuria, and
| Concurrent |
ACE inhibitors may elevate serum potassium concentrations; potassium-sparing
diuretics and potassium-containing salt substitutes can produce severe
hyperkalemia; in patients taking digoxin, hypokalemia may result in digoxin
toxicity; caution if discontinuing potassium administration in patients
maintained on digoxin
| A |
- Safe in pregnancy
| In |
patients with elevated potassium initially, hold until K+ <5.5
mEq/L—should happen rapidly with saline/insulin treatment; can check ECG to
assess effects of elevated potassium if in doubt, but mildly elevated
potassium levels may not produce ECG changes
| FOLLOW-UP |
- Admit to ICU or floors depending on clinical status.
Patients undergoing continuous insulin require frequent monitoring, which
is best done in the ICU.
- Ocsionally, patients with mild acidosis and
fluid/electrolyte deficits can be stabilized adequately in the ED if very
close follow-up can be arranged.
- Typically, patients with DKA are admitted.
- Complications of associated illnesses, including
sepsis and diffuse ischemic processes, are possible.
- The leading cause of DKA mortality in children is
cerebral edema, which occurs 4-12 hours into treatment. Recent research by
Glaser et al indicated that cerebral edema occurs in 1% of children with
DKA, with a mortality rate of 21% and neurologic sequelae in another 21%
- Cerebral edema begins with mental
status changes and is believed to be due partially to "idiogenic
osmoles," which have stabilized brain cells from shrinking while the
DKA was developing. The risk of cerebral edema is related to the severity
and duration of DKA. It is often associated with ongoing hyponatremia.
Cerebral edema is correlated with the administration of bicarbonate.
Concerns about the role of overaggressive or overly hypotonic fluid
resuscitation as a cause of the edema have been raised in the past.
- Cerebral edema is a complication
that affects primarily children.
- Hypokalemia is a complication that is precipitated
by failing to rapidly address the total body potassium deficit brought out
by rehydration and insulin treatment, which not only reduce acidosis but
directly facilitate potassium reentry into the cell
- Hypoglycemia may result from inadequate monitoring
of glucose levels during insulin therapy.
- Acute pulmonary edema potentially is related to
aggressive or excessive fluid therapy.
- Acute gastric dilatation
- Erosive gastritis
- Late hypoglycemia
- Respiratory distress
- DKA accounts for 14% of all hospital admissions of
patients with diabetes and 16% of all diabetes-related fatalities.
- The overall mortality rate is 2% or less currently.
- In children younger than 10 years, DKA causes 70% of
- Control blood glucose carefully.
- Monitor glucose particularly closely during
infection, trauma, and other periods of stress.
| MISCELLANEOUS |
- Failure to consider other coexisting illnesses, such
as pelvic or rectal abscess, pneumonia, and silent MI
- Failure to evaluate for other causes of coma if
osmolality is relatively normal
- A fetal mortality rate as high
as 30% is associated with DKA. The rate is as high as 60% in DKA with
- Fetal death typically occurs in
women with overt diabetes, but it may occur with gestational diabetes.
- Children: Be alert to headache and altered mental
status (eg, decreased alertness) since these are signs of impending
| BIBLIOGRAPHY |
- Bell DS, Alele J: Diabetic ketoacidosis: Why early
detection and aggressive treatment are crucial. Postgraduate Medicine
1997; 101: 193-8, 203-4[Medline].
- Brandenburg MA, Dire DJ: Comparison of arterial and
venous blood gas values in the initial emergency department evaluation of
patients with diabetic ketoacidosis. Ann Emerg Med 1998; 31(4):
- Glaser N, Barnett P, McCaslin I: Risk Factors for
Cerebral Edema in Children with Diabetic Ketoacidosis. NEJM 2001; 344:
- Green SM, Rothrock SG, Ho JD, et al: Failure of
adjunctive bicarbonate to improve outcome in severe pediatric diabetic
ketoacidosis. Ann Emerg Med 1998; 31: 41-8[Medline].
- Grimberg A, Cerri RW, Satin-Smith M: The "two
bag system" for variable intravenous dextrose and fluid
administration: benefits in diabetic ketoacidosis management. J Pediatr
1999 Mar; 134(3): 376-8[Medline].
- Kitabchi AE, Wall BM: Diabetic ketoacidosis. Med
Clin North Am 1995 Jan; 79(1): 9-37[Medline].
- Klekamp J, Churchwell KB: Diabetic ketoacidosis in
children: initial clinical assessment and treatment. Pediatr Ann 1996 Jul;
- Marinac JS, Mesa L: Using a severity of illness
scoring system to assess intensive care unit admissions for diabetic
ketoacidosis. Crit Care Med 2000 Jul; 28(7): 2238-41[Medline].
- Umpierrez GE, Khajavi M, Kitabchi AE: Review:
Diabetic ketoacidosis and hyperglycemic hyperosmolar nonketotic syndrome.
Am J Med Sci 1996; 311: 225-33[Medline].
- Warner EA, Greene GS, Buchsbaum MS: Diabetic
ketoacidosis associated with cocaine use. Arch Intern Med 1998; 158 (16):
- Westphal SA: The occurrence of diabetic ketoacidosis
in non-insulin-dependent diabetes and newly diagnosed diabetic adults. Am
J Med 1996; 101: 19-24[Medline].
- Whiteman VE, Homko CJ, Reece EA: Management of
hypoglycemia and diabetic ketoacidosis in pregnancy. Obstet Gynecol Clin
North Am 1996; 23: 87-107[Medline].