Endocrine and Metabolic 2: Diabetic Ketoacidosis Portal
Introduction
DKA develops as a result of insufficient insulin activity and
increased counter-regulatory hormones which result in accumulation of ketones
(organic acids) and hyperglycemia. This hyperglycemia causes an osmotic
diuresis leading to volume contraction and sodium/potassium losses. DKA
is a serious complication with significant mortality for patients with
insulin-dependent diabetes mellitus. Under certain stressful conditions
(eg, MI or sepsis), even patients with non-insulin-dependent diabetes
may develop DKA. Furthermore, DKA may often be the initial
manifestation of diabetes, especially
in pediatric patients.1
Patient Assessment
History.
Patients with DKA as the initial manifestation of diabetes
often experience weight loss, polyuria, and polydipsia. Initial
complaints include nausea, weakness, vomiting, and abdominal pain,
(PEDS) particularly in children.1
The abdominal pain is usually vague
and non-localized but can mimic an acute abdomen. Often, symptoms have
progressed over several days. Other signs and symptoms are associated
with the concurrent disease/stress event(s) that precipitated the DKA
episode, such as infection (the most likely cause), cardiovascular
events, stroke, trauma, pregnancy, and other severe stresses. A
detailed history helps in managing this complex disorder.
Exam.
Patients with severe DKA may exhibit shock or altered level of
consciousness/coma. Clinically, the patient is usually severely
dehydrated; tachycardia is often present. Tachypnea/hyperventilation
(Kussmaul respirations—deep, gasping) may be due to respiratory
compensation for metabolic acidosis. Ketosis may cause acetone
halitosis (a fruity odor on the breath). Other signs will accompany the
associated conditions.
Diagnostic Studies.
An ECG is useful to identify MI if positive (a
negative or indeterminate ECG does not rule out MI) and to evaluate
severe hyperkalemia.2 (Vol III—END/M7 Disorders
of Electrolyte Concentration) Chest x-ray is necessary (if
just for a baseline) for
pulmonary assessment. Stat labs include ABGs, glucose, serum acetone,
electrolytes, and CO2. Other useful acute labs
include calcium,
magnesium, phosphorus, BUN, creatinine, CBC, and urinalysis.
Laboratory Findings.
DKA diagnostic triad criteria include:
hyperglycemia > 250 mg/dL, arterial pH <7.3 (metabolic
acidosis), and elevated plasma ketones and/or urinary ketones. Common
initial
electrolyte abnormalities include hyponatremia, hyperkalemia,
hypophosphatemia, and hypomagnesemia, and reveal an elevated anion gap.
(The anion gap is determined by subtracting the serum chloride and
serum bicarbonate concentrations from the serum sodium concentration,
and can be used to monitor treatment results. (Vol III—END/M6
Acid-Base) Osmolality should be measured and calculated (2
x sodium +
[glucose divided by 18]) if the patient is in a coma. If the coma is
because of the disease, levels are typically > 320 mOsm/kg H2O.3
If levels are less, search for another cause of coma. Have a low
threshold for obtaining a CT of the head. Note that elevated chemical
measurements may contribute to factitious levels of other elements:
high serum glucose and dilutional hyponatremia, high triglycerides and
factitious low glucose, high ketones and factitious creatinine
elevation. Serum urea nitrogen and creatinine are usually elevated.
Serum amylase is also frequently increased but usually unrelated to
abdominal pathology such as pancreatitis.
Disease Management
Management of the patient with DKA is two-fold: carefully
restoring homeostasis while aggressively searching for and treating the
precipitating cause(s).
I. Restoring homeostasis:
As therapy is begun, significant physiologic changes in hydration,
blood sugar, electrolytes, and acid-base balance occur in a short time
frame, affecting all organ systems. Therapy is dynamic, and it is easy
to overshoot/overcorrect on any one of the treatment parameters, to the
detriment of the patient’s clinical status. (See Treatment and
Complications, this portal.) Frequent
measurements and assessments are needed to gauge
treatment effects and further intervention. For these reasons, use flow
sheets to help monitor therapy closely until the patient stabilizes.
Homeostasis is generally achieved over 24 to 48 hours in adults (PEDS)
but longer in
children because of concerns of precipitating cerebral
edema. Simultaneously treat and monitor the following
areas of concern,
noting how changes in one parameter (fluid, insulin, glucose,
electrolytes, bicarbonate) influences treatment changes in the others.
Dehydration and Fluid
Replacement. If the patient is hypotensive, start
with isotonic IV fluids (NS or LR) without additives with a 1-liter
bolus. (If using NS, note that large amounts can cause hyperchloremic
acidosis.) If the adult patient is not hypotensive, has normal cardiac
function, and does not have renal failure, begin initial fluid
replacement at 1 L/hour over the initial hour, then at ½ - 1 L/hour
until the heart rate, BP, and urine flow (> 1 cc/kg/h) return to
normal levels and reflect adequate replacement. Once the patient is
hemodynamically stabilized, switch fluids to ½ NS at 200 to 500 mL/h.
The average fluid deficit in an adult with DKA is 3 to 6 L. PEDS:
Initial fluid 20
cc/kg NS over an hour or less (bolus if hypotensive);
then run at twice the maintenance rate until hemodynamically
stabilized; then switch to ½ NS at same rate. See text
that follows
about when to integrate dextrose, potassium, other electrolytes, and/or
bicarb at the appropriate time. Note that for the custom nature of
replacement therapy in DKA, several IVs of different composition and
rates may need to be utilized in the early stages of treatment. For
patients with renal and cardiovascular disease, a slower rate of fluid
replacement as well as closer monitoring is necessary.
(Vol III—Circ Skills 3 Central Venous Pressure Measurement)
Acidosis and Therapy.
The acidosis of DKA is metabolic with an
accompanying anion gap. Acidosis is significantly improved by
rehydration and insulin therapy, with ketone levels often correcting
over several hours as insulin promotes glucose metabolism. Generally, a
pH > 7.0 without clinical threats does not require bicarb
therapy. Rapid pH correction is not needed in most cases, and sodium
bicarbonate bolus
therapy is reserved only for life-threatening
acidemia (pH < 7.0 with clinical effects on critical organs).
Consider an IV infusion of sodium bicarbonate for acidosis with an
arterial pH < 7.1 in the presence of an arrhythmia, severe
hyperkalemia, shock, or coma. The American Diabetes Association (ADA)
recommendation for pH <7.0 is to administer 100 mmol sodium
bicarbonate (2 ampules of 8.4% sodium bicarbonate) added to 400 cc
sterile water (an isotonic solution) at a rate of 200 cc/hour for 2
hours until the pH > 7.0. Utilize ABGs to determine the pH
response to therapy: checking 60 minutes after the bicarb intervention
(described above) is the current recommendation.3,4
Monitoring the anion gap with electrolyte levels is the best indicator
of improvement, as the gap is a more reliable gauge of ketoacidosis
than subsequent serum ketone levels or glucose levels. (Ketonuria is
even less reliable than serum ketone measurement, and may be present
even after correction of the acidosis.)2
Should the patient not maintain respiratory compensation of their metabolic acidosis (because of a primary pulmonary problem or tiring out), intubate and ventilate to correct. Expect to maintain hyperventilation for the needed respiratory compensation. (Vol II—AIR SKILLS 1 Aids to Intubation; Vol III—AIR4 Ventilator Management, END/M6 Acid-Base) Suspect a concomitant lactic acidosis when the pH and anion gap do not improve with insulin therapy. Lactic acidosis is most commonly associated with shock, sepsis, or necrotizing inflammation. Bicarbonate therapy may be required if the lactic acidosis isn‘t responding to fluid replacement.
Hyperglycemia
and Insulin Therapy. A gradual decline in serum glucose
is desired with insulin therapy. Prime IV tubing before therapy because
insulin binds to the tubing. Do not give insulin until severe
hypokalemia has been treated (see below). Start adults with 0.1 U/kg of
regular insulin IV bolus (about 10 U). Then start a continuous IV
insulin infusion. One method is to mix 100 U of regular insulin in 100
cc NS (1 U/mL) and infuse at 0.1 to 0.2 U/kg/h for the first hour.
PEDS: For pediatric patients,
give 0.1 U/kg of regular insulin IV bolus
(do not give bolus if serum glucose < 500 mg/dL) and begin a
continuous IV insulin infusion at 0.1U/kg/h; adjust the rate based on
response to therapy. See cerebral edema concerns.
Measure serum glucose every 60 minutes and adjust insulin rate
according to the glucose levels. If the serum glucose hasn't decreased
by 50 mg/dL in the first hour, insulin resistance may be present. This
is treated by increasing the insulin dosage 50% to 100% each hour until
achieving a decline of serum glucose of at least 50 mg/L/h.
Continue with the infusion until the patient is able to eat and drink by mouth, the serum glucose is < 250 mg/dL, the serum bicarbonate level is > 15 mEq/L, and the anion gap is corrected. At this point, the insulin may be given SQ.
Dextrose
Administration. If the initial serum glucose is <
400
mg/dL and you have begun insulin therapy, add dextrose to IV fluids in
order to prevent hypoglycemia and monitor serum glucose frequently.
(Note: replacement dextrose may be just part of your total fluid rate
if the patient is undergoing large volume replacement; several IVs may
be needed to customize therapy.) Otherwise, as the serum glucose falls
into the < 300 mg/dL range
with your fluid and insulin treatment, change IV solutions to ones
containing either 5% or 10% dextrose. Maintaining serum glucose in the
200 to 250 or so mg/dL range is an appropriate goal while the patient
is receiving insulin IV.
Electrolyte Disorders and
Potassium Replacement. Because of
dehydration/hypertonicity and insulin deficiency, hyperkalemia may be
present initially, even though the patient has lost a significant
amount of potassium with diuresis. (As dehydration is corrected and
insulin drives extracellular potassium back into the cells, the
hypokalemic loss is unmasked.) If serum K+ is not immediately
available, perform an ECG to look for signs of hyperkalemia (peaked T
waves, prolonged PR intervals, diminished to absent P waves, QRS
widening, and depressed ST segments). If the hyperkalemia is life
threatening (cardiac toxicity, paralysis, values > 6.5 to 7
mEq), treat hyperkalemia with therapies that shift K+ into the cells:
calcium IV, insulin IV, albuterol nebs, and perhaps bicarb IV.
(Vol III—END/M7 Disorders of Electrolyte Concentration)
For most cases in which you have started fluid and insulin therapy, hyperkalemia can be observed with serial K levels every 1 hour X 2, holding off on K+ replacement therapy until levels are coming down into the normal range (< 5.5 mEq/L). At that time, add up to 40 mEq K+ per liter to the IV that is dedicated to K+ replacement. Total IV K+ rate should not exceed 40 mEq/h. The source of K+ is generally potassium chloride (KCL); combinations of KCL and potassium phosphate may be used in various ratios such as 50:50 or 2/3 KCL to 1/3 potassium phosphate, especially if there is hypophosphatemia. On the other hand, if the initial potassium is < or = 4.5 mEq, suspect severe K+ loss and begin replacement therapy as soon as it is established that the patient is making urine. (Remember: “no Pee = no K.”) This level of K+ loss may be life threatening and must be monitored closely with serum levels and ECGs as you are replacing it, using peripheral IV rates up to 40 mEq K+/h total. (Never give K+ IV push.) Note that several IVs may be needed to customize therapy, as the K+ rate requirement (up to 40 mEq/h) may be too limiting a factor for the initially large IV fluid rate requirements. For more stable situations, a more standard rate range is 10 to 20 mEq/h. Patients with renal failure need even closer monitoring of potassium levels with therapy.
If the patient has significant initial hypokalemia, begin
fluid and K+
replacement therapy, BUT hold insulin therapy until K+ is restored to
> 3.3 mEq/L in order to avoid adverse sequelae of hypokalemia:
arrest, arrhythmia, respiratory muscle weakness. PEDS: Oral/NG liquid
K+ replacement can supplement IV replacement therapy in severe cases of
hypokalemia.
Treatment and Complications
Avoiding rapid correction of metabolic abnormalities may be prudent,
trying to achieve gradual reduction of effective osmolarity over a 36-
to 48-hour period.1,5,6 Avoid over-correction of
DKA’s components,
which can lead to CHF, pulmonary edema, hypoglycemia, alkalosis,
hypokalemia, and cerebral edema. Cerebral edema is rare and (PEDS)
usually occurs in children. Those children at increased risk for
cerebral edema have low partial pressures of arterial carbon dioxide
and high serum BUN on initial testing or have received bicarbonate
treatment.1,6 Treat cerebral edema quickly, as
this may be a fatal
complication.
II. Precipitating Causes
of DKA
A common trap is to assume that all aspects of the DKA patient’s condition are because of the DKA. For instance, is the altered mental status due to the dehydration, acidosis, or hyperosmolar effects of DKA? Or, did a primary cranial/cerebrovascular event occur (such as a recent fall associated with a compromising subdural hemorrhage) that precipitated a DKA episode? Aggressive investigation is warranted for finding treatable precipitating causes for the DKA episode. Infection (the most likely cause) may be difficult to find in patients with diabetes. Note that patients with awesome diabetes can have silent myocardial infarctions (no pain and no ECG changes). So, if the patient is old enough to have atherosclerotic disease and their serial ECGs are indeterminate or normal, obtain serial cardiac enzymes over the acute treatment period. (Vol I—PATHWAY 1 Altered Level of Consciousness)
Monitoring Treatment Response in Diabetic Ketoacidosis
| Parameter | Suggested Frequency |
| Vital signs | Every 1/2 to 1 h until stable, then every 2 to 4 h |
| Temperature | On admission, then every 4 to 6 h |
| Mental status | On admission and frequently until mental status improves |
| Fluid input/output (I & O) | Every 1 to 2 h; decrease frequency when fluid balance improves |
| Blood glucose | >Every 1 h until blood glucose stabilizes, then every 2 to 4 h until IV insulin is stopped |
| ABGs | On admission and repeat as needed and/or 20 to 30 minutes after an acid-base therapy intervention |
| Serum potassium and electrolytes | On admission and every 1 to 2 h after therapy begins until stable; then every 2 to 8 hours until DKA has resolved |
| Serum magnesium, calcium, BUN, creatinine, phosphate | On admission and every 4 hours if levels are abnormal |
| >Electrocardiogram | On admission and repeated as indicated and/or per protocol |
| Serial cardiac enzymes | On admission (if ACS is possible) as per protocol |
References
- Piva JP, Czepielewskii M, Garcia PC, Machado D. Current perspectives for treating children with diabetic ketoacidosis. J Pediatr (Rio J). 2007;83(5 suppl); S119-127.
- Kitabchi AE, Haerian H, Rose BD.
Treatment of diabetic ketoacidosis and hyperosmolar hyperglycemic state
in adults. UpToDate Online 16.1. Available at
http://www.uptodate.com/online/content/topic.do?topicKey=diabetes/
25334&selectedTitle=1~150&source=search_result. Accessed May 30, 2008. - Kitabchi AE, Umpierrez GE, Murphy MB, Kreisberg RA. Hyperglycemic crises in adult patients with diabetes: a consensus statement from the American Diabetes Association. Diabetes Care. 2006;29:2739-2748.
- Trachtenbarg DE. Diabetic ketoacidosis. Am Fam Physician. 2005;71:1705-1714.
- Bohn D, Daneman D. Diabetic ketoacidosis and cerebral edema. Curr Opin Pediatr. 2002;14:287-291.
- Glaser N, Barnett P, McCaslin I, et al. Risk factors for cerebral edema in children with diabetic ketoacidosis. The Pediatric Emergency Medicine Collaborative Research Committee of the American Academy of Pediatrics. N Engl J Med. 2001; 25;344:264-269.