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Diabetic ketoacidosis in pregnancy
Mary Anne Carroll, MD; Edward R. Yeomans, MD
Objective: The development of diabetic ketoacidosis in pregnancy is a medical emergency, requiring treatment in an intensive
care setting. Both the mother and the fetus are at risk for
significant morbidity and mortality. Physiologic changes unique to
pregnancy provide a background for the development of diabetic
ketoacidosis. An understanding of these physiologic changes
assists in the management of the two patients being treated.
Treatment of the patient with diabetic ketoacidosis includes insulin therapy and careful fluid management; recommendations
for management are presented.
F
ortunately for obstetricians
and intensivists, the vast majority of women who become
pregnant are both young and
healthy. Of the relatively small percentage of pregnant women with pregestational medical complications, an even
smaller group will experience what we
would call a medical emergency, that is, a
condition that poses an immediate threat
to the life of mother, fetus, or both. Diabetic ketoacidosis (DKA) is such an entity. Once diagnosed, the first order written by the admitting physician should be
“Admit to ICU.”
In our review of this important subject, we will attempt to present useful
information to two groups of readers: a)
physiologic changes unique to pregnancy
for the medical intensivist, because these
changes affect management; and b) a
“cookbook” algorithm of medical management for the obstetrician who may
have to provide emergency care before
consulting an intensivist. Again, fortunately for us, the incidence of DKA in
pregnancy has declined substantively
over the years, and so has the perinatal
mortality (Table 1) (1–5). However, the
From the Department of Obstetrics, Gynecology
and Reproductive Science, University of Texas Health
Science Center-Houston, Houston, TX.
The authors have no financial or ethical conflict of
interest regarding the contents of this submission.
Copyright © 2005 by the Society of Critical Care
Medicine and Lippincott Williams & Wilkins
DOI: 10.1097/01.CCM.0000183164.69315.13
Crit Care Med 2005 Vol. 33, No. 10 (Suppl.)
Patients: Pregnant women, either with preexisting diabetes or
with diabetes diagnosed during pregnancy.
Conclusions: Prompt recognition of the clinical manifestations
of diabetic ketoacidosis, followed by appropriate, timely treatment will optimize outcome for the pregnant woman and her
fetus. (Crit Care Med 2005; 33[Suppl.]:S347–S353)
KEY WORDS: diabetic ketoacidosis; pregnancy; anion gap; osmotic diuresis; ketone bodies; acidosis; dehydration; nitroprusside test; insulin
importance of providing prompt, effective
medical care is unaltered or perhaps even
increased, due to the unrealistic expectation for a perfect outcome for all pregnancies.
creases with advancing gestation. Insulin
dose adjustments may not keep pace with
increasing requirements, a fact that may
explain the higher incidence of DKA in
the second and third trimesters of pregnancy (9).
Adaptation to Pregnancy
A detailed account of physiologic
changes induced by pregnancy is presented elsewhere in this supplement.
Here we review only a few pertinent facts.
The acid-base state of pregnancy is a
compensated respiratory alkalosis. Normal pH is 7.43, PCO2 is 30 mm Hg, and
bicarbonate is 19 –20 mEq/L. The drop in
bicarbonate occurs to compensate for the
primary respiratory alkalosis. This reduction in buffering capacity renders the
pregnant woman more susceptible to
metabolic acidosis, particularly DKA.
Normal pregnancy is a diabetogenic
state, marked by relative insulin resistance, enhanced lipolysis, elevated free
fatty acids, and ketogenesis (6). Ketone
bodies can be demonstrated in the serum
and urine of normal pregnant women
throughout the antepartum period (7).
Several hormones produced in pregnancy, including human placental lactogen, progesterone, and cortisol, impair
the action of maternal insulin and contribute to this diabetogenic state. Insulinase, of placental origin, further depletes
maternal insulin (8). For these reasons,
insulin production by the pancreas is
augmented during normal pregnancy. If
the woman is a known diabetic, the requirement for exogenous insulin also in-
Pathophysiology
An overview of the complex pathophysiologic process leading to DKA is
provided in Figure 1 (10).
DKA results from inadequate insulin
action and a failure of glucose utilization
at the cellular level. With insulin deficiency, the cell is unable to use glucose as
an energy substrate. Insulin counterregulatory hormones are released in response to this metabolic condition; glucagon, catecholamines, cortisol, and
growth hormone act on insulin-sensitive
tissues to facilitate the production of alternative substrates for cellular metabolism, using carbohydrates, proteins, and
lipids.
Muscle, adipose tissue, and liver are the
insulin-sensitive tissues that respond to
both the decrease in insulin as well as the
increase in counterregulatory hormones
seen in DKA. Decreasing glucose utilization
in muscle results in hyperglycemia. Additionally, protein catabolism provides free
amino acids for gluconeogenesis.
In adipose tissue, the combination of
decreased insulin and increased counterregulatory hormones results in the activation of hormone-sensitive lipase. This
enzyme acts on triglycerides stored in the
adipocyte, releasing free fatty acids in
S347
Table 1. Incidence of diabetic ketoacidosis in pregnancy
Lufkin et al. (1)
Kilvert et al. (2)
Montoro et al. (3)
Chauhan et al. (4)
Cullen et al. (5)
Time Interval
Incidence, % (No.)
Perinatal Mortality
Rate, % (No.)
1950–1979
1971–1990
1972–1987
1976–1981
1986–1991
1985–1995
7.9 (18/228)
1.7 (11/635)
3.9 (22/560)
22
3
2 (11/520)
27.8 (5/18)
22
35 (7/20)
35
10
9 (1/11)
large quantities, which undergo oxidation in the liver to form ketone bodies.
Hepatocytes respond to the insulin deficiency and high levels of glucagon by
increasing hepatic glucose production.
Hyperglycemia results from the increase
in gluconeogenesis and glycogenolysis in
the liver and a decrease in glucose utilization in peripheral tissues (10 –12).
Ketone bodies (acetoacetate, 3-␤hydroxybutyrate and acetone) are produced in the liver from the oxidation of
fatty acids, under the influence of an elevated glucagon/insulin ratio (12). ␤-hydroxybutyrate production is selectively
accelerated in DKA, to a ratio of up to
10:1 compared with acetoacetate (7). Acetone is produced by spontaneous decarboxylation of acetoacetate (12) and is
present in DKA in much lower concentration than either ␤-hydroxybutyrate or
acetoacetate. It is highly fat soluble and is
excreted slowly via the lungs. Acetone
production is clinically apparent as a
fruity odor on the breath.
In the laboratory, the conventional test
for the presence of ketone bodies is the
nitroprusside test. This test only detects
acetoacetate in serum and urine. Given that
␤-hydroxybutyrate is present in three to
ten times greater concentration and that it
is metabolized to acetoacetate, the measurement of serum ketones using the nitroprusside reaction may greatly underestimate the degree of ketonemia present in
the patient. Quantitative testing for ␤-hydroxybutyrate is available and should be
considered if there is concern for a falsenegative nitroprusside result (7).
Ketone bodies are organic acids that
completely dissociate at physiologic pH
and are neutralized by bicarbonate (7). In
high concentrations (as seen in DKA),
they contribute a large hydrogen ion pool
that consumes the normal buffering capacity of serum and tissue, leading to
metabolic acidosis with a high anion gap.
The kidney plays an important role in
the pathogenesis of DKA. Glucose resorption in the tubules of the kidney is effecS348
tive up to a threshold of ⵑ240 mg/dL,
designated Tm (tubular maximum), beyond which glucosuria is evident (13).
Glucose is an osmotically active substance. With increasing hyperglycemia,
an osmotic diuresis ensues, leading to
dehydration, hypovolemia, hyperosmolality, and electrolyte depletion. Further
depletion of electrolytes occurs because
ketoacid anions are first coupled to sodium and potassium salts, which are then
excreted (7). Left untreated, worsening
acidosis, electrolyte abnormalities, and
hypovolemia can have multiple-system
effects, including cardiac dysfunction, altered vascular tone, poor tissue perfusion, and diminished renal function, leading to shock, coma, and death.
Clinical Presentation
Armed with an understanding of altered pregnancy physiology and pathophysiology of DKA from the preceding
two sections, the clinician is now prepared to encounter a pregnant woman
with DKA. Typical presenting features are
shown in Table 2.
Patients with diabetic ketoacidosis
classically present with a triad of concurrent abnormalities, which constitute an
acronym: D ⫽ dehydration; K ⫽ ketosis;
A ⫽ acidosis (metabolic). Although
marked hyperglycemia is often detected
as well, DKA is occasionally diagnosed
with only mild elevations in serum glucose (10). This is especially true in pregnant women who develop DKA (5, 6).
Careful history taking, physical examination, and laboratory evaluation may reveal many of the diagnostic features listed
in Table 2 (6, 11, 12, 14).
Various triggers of DKA in pregnancy
have been reported in the literature (3,
6). In a 15-yr series of consecutive cases
of DKA in pregnancy, Montoro et al. (3)
found that cessation of insulin therapy in
pregnancy was the precipitating factor for
DKA in 40% of cases, infection initiated
20% of cases, and 30% of women had
previously undiagnosed diabetes until
they presented with diabetic ketoacidosis
(15, 16).
Later in this review, we will present a
case of a pregnant woman whose first
manifestation of diabetes was DKA. The
diagnosis of DKA is less likely to be considered in nondiabetics (15). In addition
to Montoro’s three categories, certain obstetrical interventions like ␤-mimetic tocolytic agents and corticosteroids to enhance fetal lung maturity have been
reported to trigger DKA (17, 18). Finally,
ketoacidosis has been reported as a complication of the use of a subcutaneous
insulin infusion pump; however, this risk
appears to be small (19, 20).
The impact of DKA on pregnancy can
be artificially separated into maternal
concerns and fetal concerns. In reality,
both patients are affected simultaneously.
Maternal Concerns
In the same way that DKA represents
an acute emergency in the nonpregnant
individual, it poses an immediate threat
to maternal well-being. Severe dehydration can lead to hypotension, acidosis can
cause organ dysfunction, and electrolyte
imbalance can cause cardiac arrhythmias. Prompt initiation of treatment can
correct all of the metabolic derangements.
Fetal Concerns
Maternal hyperglycemia results in fetal hyperglycemia and fetal osmotic diuresis. The fetus can also become acidotic
from ketoacids that cross the placenta.
Acidemia decreases uterine blood flow,
reduces tissue perfusion, and leads to decreased oxygenation of the fetoplacental
unit. Furthermore, a leftward shift of the
maternal oxy-hemoglobin dissociation
curve with decreased 2,3-diphosphoglycerate increases hemoglobin affinity for
oxygen, decreasing fetal oxygen delivery
(9, 21, 22).
Ketoacids dissociate into hydrogen
ions and organic anions, both of which
are transported across the placenta. Thus,
with increasing maternal ketonemia, fetal metabolic acidosis may develop.
Because the fetus is not directly accessible, inferences regarding fetal status are
often made from the external recording
of the fetal heart rate. Often, decreased or
absent variability, absent accelerations,
and late decelerations are observed on
external fetal heart rate tracings with deCrit Care Med 2005 Vol. 33, No. 10 (Suppl.)
Figure 1. Pathophysiologic process leading to diabetic ketoacidosis.
compensated maternal DKA. Doppler ultrasound has also been used to look at
blood flow in fetal vessels with DKA (23).
Crit Care Med 2005 Vol. 33, No. 10 (Suppl.)
Transient fetal blood flow redistribution
was demonstrated in the umbilical and
middle cerebral arteries, as measured by
pulsatility index. Reversal of the abnormal flow was demonstrated after treatment of the maternal DKA. Hagay et al.
S349
Table 2. Diagnosis of diabetic ketoacidosis (DKA)
Signs and Symptoms
Malaise
Dehydration
Polyuria
Polydipsia
Nausea
Vomiting
Abdominal pain
Ileus
Fruity breath odor
a
Hypotension
Tachycardia
Tachypnea
Hyperventilation
(Kussmaul respiration)
Drowsiness
Mental status change
Lethargy
Coma
Shock
Labs
Hyperglycemia (⬎250 mg/dL)a
Acidosis (arterial pH ⬍ 7.3)
Anion gap (⬎12 mEq/L)
Low bicarbonate (⬍15 mEq/L)
Elevated base deficit (base deficit ⬎4 mEq/L)
Ketonemia (ⱖ1:2 dilution)
Treatment
In pregnancy, DKA can manifest at lower blood glucose values (may be as low as 180 mg/dL).
(24) similarly describe improvements in
the fetal heart rate tracing following
treatment of maternal DKA.
Immediate delivery in response to the
presence of nonreassuring fetal monitoring is therefore not indicated, until the
maternal metabolic condition is corrected. Intervention for fetal indications
should be reserved for fetal compromise
persisting after maternal resuscitation.
Emergency cesarean delivery in the setting of decompensated DKA could further
worsen the maternal condition (21, 23,
24).
A single episode of DKA poses considerable risk to the fetus. Several retrospective studies have reported a perinatal
mortality rate of 9 –35% (1–5). Early recognition and prompt treatment of DKA
might well avoid adverse fetal outcome. A
recent case of DKA in pregnancy that was
not optimally managed resulted in a fetal
death.
Case
A 23-yr-old woman gravida 3, para 2 at
31 wks gestation presented to the Obstetrical Service with complaint of “feeling
weak” and “throwing up” for 3 days duration. The patient complained of extreme thirst, nausea, and abdominal pain.
She was not known to be diabetic; she
denied the development of gestational diabetes in either of her two previous pregnancies. On exam, she was noted to have
dry mucous membranes, heart rate of
128 beats/min, and respiratory rate of 26
breaths/min. Her weight was 104 kg, and
blood pressure was mildly elevated (169/
87), which was attributed to agitation.
Her oral temperature was 100.3°C. She
was noted to be tolerating oral fluid intake. Ultrasound examination of the fetus
confirmed cardiac activity. A finger-stick
blood glucose measurement was initially
read as “too high to calculate,” followed
S350
This case illustrates delayed recognition of the clinical manifestations of
DKA. Had a timely diagnosis been made,
appropriate fluid and insulin therapy
could have been instituted, with correction of the maternal metabolic disturbances, and perhaps the fetal death would
have been prevented.
by a measured finger-stick value of ⬎600
mg%. Initial laboratory work confirmed
hyperglycemia (serum glucose of 836 mg/
dL), an anion gap of 23, bicarbonate of 15
mmol/L, blood urea nitrogen of 8, and
creatinine of 1.8 mg/dL; urinalysis was
positive for glucose (3⫹) and leukocytes.
Urine and serum ketones were negative.
Several attempts were made to obtain an
arterial blood gas, but all were unsuccessful. The patient was admitted with a diagnosis of pyelonephritis and hyperglycemia.
Five hours after admission to labor
and delivery triage, intravenous fluid and
insulin treatment were started. In the
first hour, the patient received 500 mL of
normal saline and 5 units of regular insulin intravenously. Blood glucose (by
finger-stick) values remained ⬎600 mg%
for the next 3 hrs, and the anion gap
remained elevated at 20 during this time.
Normal saline was maintained at 500
mL/hr over this time interval, along with
5 units of intravenous regular insulin administered hourly.
For each of the next 6 hrs, the patient
received 10 units of regular insulin.
Blood glucose values remained in the
range of 375– 440 mg/dL. The patient remained tachycardic (125 beats/min), and
urine output was recorded at ⵑ100 mL/
hr. The intravenous fluid was changed to
0.45% saline, at a rate of 100 mL/hr over
this time period. Potassium chloride was
added to intravenous fluids to correct a
serum potassium of 3.1 mmol/L.
The fetus was monitored by an external fetal heart rate monitor, with a baseline fetal heart rate ranging from 125 to
140 beats/min. Notably, this was the same
as the mother’s pulse. Ten hours after
admission, after difficulty in obtaining a
continuous fetal heart rate tracing, ultrasound confirmed an intrauterine fetal demise.
A careful search for the presence of
infection is required for every patient presenting in DKA. Infection has been demonstrated to reduce the rate of glucose
utilization by 50% (28). The presence of
bands on a differential is more telling of
infection, as an elevated white blood cell
count may be the result of dehydration,
rather than infection. Common sites of
infection include the urinary tract, lungs,
soft tissue, sinuses, skin, and teeth.
Prompt treatment of infection with appropriate antibiotic coverage will assist in
glucose control. Other precipitating
causes of DKA are referenced earlier (17–
20).
We now present our recommendations for treatment of DKA. An algorithmic approach is outlined in Figure 2,
focusing on the treatment of the fetus,
maternal acidosis and dehydration, and
the elucidation and treatment of underlying causes of DKA. This is followed by
recommendations for therapy in a “cookbook” form, detailing fluid administration, insulin therapy, and electrolyte replacement (Table 3).
For the interested reader, we conclude
this section with a rationale for our recommendations for treatment of DKA, including pertinent calculations discussed
throughout the text (Table 4). Treatment
of the pregnant woman with DKA does
not differ from the nonpregnant patient.
The goals of DKA management are as
follows:
1. Improve circulating volume and tissue perfusion.
2. Decrease serum glucose.
3. Clear the serum and urine of ketoacids (correcting acidosis).
4. Correct electrolyte imbalances.
5. Treat initiating causes of DKA.
6. Monitor therapeutic response in the
mother and fetus.
These goals will be met with volume
replacement, insulin therapy, replacement of electrolytes, and treatment of the
underlying causes of DKA (10, 14).
Fluid Therapy. Volume replacement
should be vigorous and sustained to corCrit Care Med 2005 Vol. 33, No. 10 (Suppl.)
•
•
•
•
Admit to obstetric intensive care unit (or equivalent).
Begin monitoring vital signs, pulse oximetry, strict intake and output, patient weight.
Labs: arterial blood gas, serum glucose, serum ketones, serum electrolytes, anion gap, urine analysis, urine culture, urine ketones.
Fetal monitoring if viable gestational age.
Start a bedside flowsheet.
Figure 2. Algorithm for treatment of diabetic ketoacidosis. ABG, arterial blood gas; UA, urine analysis; CXR, chest radiograph; IV, intravenous; NS, normal
saline.
rect dehydration, replete circulating volume, decrease serum glucose concentration, restore renal function, and,
importantly, prevent a recurrence of acidosis. The major cause of fluid loss in
DKA is osmotic diuresis. Isotonic fluid
(0.9% normal saline) should be used for
initial fluid replacement. Isotonic fluid
has been demonstrated to replete the extracellular fluid compartment and corCrit Care Med 2005 Vol. 33, No. 10 (Suppl.)
rect circulating plasma volume most effectively (11).
Insulin Therapy. Insulin is the mainstay of treatment, correcting the hyperglycemia, acidosis, and the overproduction of ketones that occur in DKA.
Continuous insulin infusion of regular
(short-acting) insulin is the preferred
method of delivery. Intramuscular administration of insulin leads to a delay in
response to treatment due to the impaired absorption of insulin in the setting
of volume depletion and acidosis (11).
Intravenous insulin therapy should be
maintained until after the first dose of
subcutaneous insulin is administered, to
prevent a recurrence of ketoacidosis. Several protocols describe the subcutaneous
administration of insulin after an episode
of DKA (11, 25).
S351
Table 3. Recommendations for therapy
Electrolyte Replacement
Fluid therapy
Estimate fluid deficit of ⬃100 mL/kg body weight.
Correct 75% of estimated fluid deficit over first 24 hrs.
Record intake and output hourly.
Initial 24 hrs:
Use isotonic saline (0.9% NS)
First hour Give 1 L NS
Second hour Give 0.5–1 L NS
Third hour Give 0.5 L NS
Thereafter (24 hrs) Give 0.25 L/hr 0.45% NS until 75% deficit corrected
Calculate corrected Na⫹ during fluid administration.
Monitor serum Na⫹ and Cl⫺; adjust IV fluids if hypernatremia or hyperchloremia.
Continue hydration for 24–48 hrs, until anion gap and acidosis have corrected and volume
deficit is replaced.
Insulin therapy
Give 0.1 units/kg bolus regular insulin IV, then 0.1 units/kg/hr IV continuous infusion by pump.
Mix 50 units of regular insulin in 500 mL of NS (10 mL ⫽ 1 unit).
Flush IV tubing prior to infusing, as insulin binding to tubing occurs.
Monitor serum glucose every 1–2 hrs.
If serum glucose is not decreased by 20% within first 2 hrs, double insulin infusion rate.
Aim for a decrease in serum glucose of 60–75 mg/dL/hr.
With blood glucose at 250 mg/dL, add dextrose to IV fluids, to avoid hypoglycemia (maintain
insulin rate).
Monitor serum ketones every 2 hrs.
Continue insulin therapy until bicarbonate and anion gap normalize.
After full resolution of ketosis, maintain insulin drip until after the first subcutaneous dose of
insulin is administered.
Electrolyte replacement
Monitor serum electrolytes every 2–4 hrs
Potassium
Potassium chloride is most often given for replacement; occasionally potassium phosphate
or acetate is used.
Anticipate deficit of 5–10 mEq/kg.
With replacement, maintain adequate urine output (0.5 mL/kg/hr).
Maintain serum K⫹ level at 4–5 mEq/L.
Suggested protocol using serum K⫹:
⬎5 mEq/L No treatment
4–5 mEq/L 20 mEq/L replacement
3–4 mEq/L 30–40 mEq/L replacement
ⱕ3 mEq/L 40–60 mEq/L replacement
Phosphate
Replacement not normally required.
If serum phosphate ⬍1.0 mg/dL or if cardiac dysfunction or obtundation, replace using
potassium phosphate.
Bicarbonate
Replacement is usually not necessary.
Potassium. Potassium replacement is
indicated after fluid replacement and insulin have been initiated. The most rapid
changes in potassium occur in the first
few hours of treatment (26). Insulin mediates the shift in K⫹ ion from the extracellular to intracellular space, along with
glucose. With correction of acidosis, K⫹
ions are further shifted into the intracellular fluid. Losses of potassium also occur
with continued osmotic diuresis and as
ketone bodies are excreted by the kidney
as potassium salts. The development of
significant hypokalemia can precipitate
life-threatening arrhythmias (11); close
attention to serum electrolytes and potassium replacement is essential to the effective treatment of DKA.
On the average, a potassium deficit of
5–10 mEq/kg body weight occurs (11,
12). Various guidelines are described for
potassium replacement (12, 25, 27).
Maintenance of serum K ⫹ levels at
4 –5mEq/L will prevent hypokalemia and
the associated cardiac arrhythmias. Potassium chloride is most often used for
replacement, at a maximum rate of 40
mEq/hr. Potassium phosphate may also
be used for replacement, if concomitant
hypophosphatemia is present or with the
development of hyperchloremic acidosis.
Phosphate, Magnesium, and Calcium.
Inorganic cations are also deficient in
DKA; however, the need for replacement
of these electrolytes is debated. Studies
do not demonstrate the benefit of replacement of these cations (26). As mentioned, potassium phosphate can be used
for potassium replacement, if phosphate
levels are ⬍1.0 mg/dL (decrease dose of
KCl accordingly). Replacement has also
been recommended for patients with left
ventricular dysfunction or with obtundation of mental status that has not responded after the initial treatment of
DKA (27).
Bicarbonate. The use of bicarbonate to
correct acidosis has been the subject of
study and controversy (22, 26). The metabolism of ketone bodies via the citric
acid cycle acts to rapidly regenerate bicarbonate levels. Studies demonstrate
that bicarbonate administration has not
proven beneficial in the treatment of DKA
and its use may be associated with risk,
including a paradoxical central nervous
system acidosis, hypokalemia, hypertonicity, and the development of cerebral
edema (22, 26). Treatment of DKA with
bicarbonate delays the correction of ke-
NS, normal saline; IV, intravenous.
Table 4. Calculations
● Anion gap ⫽ [Na ⫺ (Cl ⫹ HCO3)]: normal value 12 mEq/L ⫾ 2
Anion gap measures the difference between unmeasured anions and unmeasured cations.
An increased anion gap reflects the presence of a metabolic acidosis, if renal failure is not present.
● Serum osmolality (mOsm/L) ⫽ [2(Na ⫹ K) ⫹ (glucose/18) ⫹ (BUN/2.8)]
Normal value ⫽ 290 ⫾ 5
Serum osmolality is elevated less in DKA (300–330 mOsm/L) than in nonketotic hyperosmolar
coma (⬎350 mOsm/L). The difference in serum glucose accounts for almost the entire difference
in osmolality.
● Corrected serum sodium (mEq/L) ⫽ measured Na ⫹ {([plasma glucose (mg/dL)] ⫺ 100)/100}
⫻ 1.6
Normal range ⬃ 135–145 mEq/L
Hyperglycemia dilutes plasma Na by 1.6 mEq/L for every 100 mg/dL increase in glucose.
An elevated value indicates marked dehydration; below the range suggests too rapid administration
of fluids.
● Total body water deficit ⫽ {[0.6 ⫻ body weight (kg)] ⫹ [1 ⫺ (140/serum Na)]}
BUN, blood urea nitrogen; DKA, diabetic ketoacidosis.
S352
Crit Care Med 2005 Vol. 33, No. 10 (Suppl.)
tonemia (22). Further studies are needed
to assess the benefits and risks of bicarbonate administration when pH is ⬍6.9
or in cases complicated by cardiac dysfunction, sepsis, or shock (10).
REFERENCES
1. Lufkin ES, Nelson RL, Hill LM, et al: An
analysis of diabetic pregnancies at Mayo
Clinic, 1950 –79. Diabet Care 1984;
7:539 –547
2. Kilvert JA, Nicholson HO, Wright AD. Ketoacidosis in diabetic pregnancy Diabet Med
1993; 10:278 –281
3. Montoro MN, Myers VP, Mestman JH, et al:
Outcome of pregnancy in diabetic ketoacidosis. Am J Perinatol 1993; 10:17–20
4. Chauhan SP, Perry KG, McLaughlin BN, et
al: Diabetic ketoacidosis complicating pregnancy. J Perinatol 1996; 16:173–175
5. Cullen MT, Reece EA, Homko CJ, et al: The
changing presentations of diabetic ketoacidosis during pregnancy. Am J Perinatol
1996; 13:449 – 451
6. ACOG Practice Bulletin No. 60. Pregestational Diabetes Mellitus. Obstet Gynecol
2005; 105:675– 685
7. Laffel L: Ketone bodies: A review of physiology, pathophysiology, and application of
monitoring to diabetes. Diab Metab Res Rev
1999; 15:412– 426
8. Ogata ES. Carbohydrate homeostasis. In:
Neonatology Pathophysiology and Management of the Newborn. Avery GB, Fletcher
MA, MacDonald MG (Eds). Philadelphia, Lippincott Williams & Wilkins, 1999
Crit Care Med 2005 Vol. 33, No. 10 (Suppl.)
9. Ramin K: Diabetic ketoacidosis in pregnancy.
Obstet Gynec Clin NA 1999; 26:481– 488
10. White NH: Management of diabetic ketoacidosis. Rev Endocr Metab Dis 2003;
4:343–353
11. Kitabchi AE, Umpierrez GE, Murphy MB et
al: Management of hyperglycemic crises in
patients with diabetes. Diabet Care 2001; 24:
131–153
12. Foster DW, Mc Garry JD: The metabolic derangements and treatment of diabetic ketoacidosis. N Engl J Med 1983; 809:159 –169
13. Rose BD. Proximal tubule. In: Clinical Physiology of Acid-Base and Electrolyte Disorders. Rose BD (Ed). New York, McGraw-Hill,
1989, p 43–54
14. Moore TR: Diabetes in pregnancy. In: Maternal Fetal Medicine Principles and Practice.
Fifth Edition. Creasy RK, Resnik R, Iams JD
(Eds). Philadelphia, Saunders (Elsevier),
2004, pp 1023–1063
15. Sills IN, Rappaport R: New onset IDDM presenting with diabetic ketoacidosis in a pregnant adolescent. Diabet Care 1994; 17:
904 –905
16. Kamalakannan D, Baskar V, Barton DM, et al:
Diabetic ketoacidosis in pregnancy. Postgrad
Med 2003; 79:699 –714
17. Bernstein IM, Catalano PM: Ketoacidosis in
pregnancy associated with the parenteral administration of terbutaline and betamethasone. A case report. J Reprod Med 1990; 35:
818 – 820
18. Bedalov A, Balasubramanyam B: Glucocorticoid-induced ketoacidosis in gestational diabetes: Sequela of the acute treatment of preterm labor. Diabet Care 1997; 20:922–924
19. Gabbe SG, Holing E, Temple P, et al: Benefits, risks, costs, and patient satisfaction as-
20.
21.
22.
23.
24.
25.
26.
27.
28.
sociated with insulin pump therapy for the
pregnancy complicated by type I diabetes
mellitus. Am J Obstet Gynecol 2000; 182:
1283–1291
Lindenbaum C, Menzin A, Ludmir J: Diabetic
ketoacidosis in pregnancy resulting from insulin pump failure. A CASE report. J Reprod
Med 1993; 38:306 –308
Chauhan SP, Perry KG: Management of
diabetic ketoacidosis in the obstetric patient. Obstet Gynecol Clin N Am 1995; 22:
143–155
Rodgers BD, Rodgers DE: Clinical variables
associated with diabetic ketoacidosis during
pregnancy. J Repro Med 1991; 36:797– 800
Takahashi Y, Kawabata I, Shinohara A, et al:
Transient fetal blood flow redistribution induced by maternal diabetic ketoacidosis diagnosed by Doppler ultrasonography. Prenat
Diagn 2000; 20:524 –525
Hagay ZJ, Weissman A, Lurie S, et al: Reversal of fetal distress following intensive treatment of maternal diabetic ketoacidosis. Am J
Perinatol 1994; 11:430 – 432
Foley MR: Diabetic ketoacidosis in pregnancy
In: Obstetric Intensive Care Manual. Second
Edition. Foley MR, Strong TH, Garite TJ
(Eds). New York, McGraw-Hill, 2004
Adrogue HJ, Madias NE: Management of lifethreatening acid-base disorders. N Engl
J Med 1998; 1:26 –33
Magee MF, Bhatt BA: Management of decompensated diabetes. Crit Care Clin 2001; 17:
75–106
Hagay ZJ: Diabetic ketoacidosis in pregnancy: Etiology, pathophysiology, and management. Clin Obstet Gynecol 1994; 37:
39 – 49
S353
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