Document 6429783

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Document 6429783

EMERGENCY MEDICINE
PRACTICE
.
EMPRACTICE NET
A N E V I D E N C E - B A S E D A P P ROAC H T O E M E RG E N C Y M E D I C I N E
February 2004
Diabetic Emergencies:
Diagnosis And Management
Of Hyperglycemic Disorders
Volume 6, Number 2
Author
Charles Stewart, MD, FACEP
Colorado Springs, CO.
2:20 a.m.: Prehospital personnel call with a case of vomiting and altered mental
status in a 9-year-old girl. The child’s mother found her unconscious in bed in a pool of
vomit. The child’s mother notes that the child had been vomiting earlier but had
consumed clear liquids for supper. She also notes that her child had recently started a
diet and was doing exceptionally well at her planned weight loss; she also comments
that for the past two days, her daughter kept a pitcher of water at the bedside and would
wake frequently and drink. The child felt that the extra water was helping her weight
loss program. The paramedics note that the child’s respiratory rate is 50, she has a heart
rate of 128, and her bedside glucose test measures “HHH” on their glucometer. They’ve
been unable to obtain intravenous access in this child.
D
Peer Reviewers
Catherine A. Marco, MD, FACEP
Associate Professor, Department of Surgery,
Medical College of Ohio; Attending
Physician, St. Vincent Mercy Medical Center,
Toledo, OH.
Amal Mattu, MD
Director, Emergency Medicine Residency,
University of Maryland School of Medicine,
Baltimore, MD.
IABETES is a chronic disease that requires long-term medical attention.
As many as 5%-6% of the United States population have either diagnosed
or undiagnosed diabetes.1
Diabetic emergencies are common in patients with diabetes, and the effects
can be devastating. Hypoglycemia and hyperglycemia represent two extremes
in the emergency presentations of the diabetic patient. This edition of Emergency
Medicine Practice reviews the acute management of two of the most serious
hyperglycemic disorders—diabetic ketoacidosis (DKA) and hyperglycemic
hyperosmolar syndrome (HHS)—and the controversy that surrounds the
management of these diseases.
Over 100,000 cases of DKA, 5000 cases of diabetic coma, and 10,000 cases of
hyperosmolar coma were recorded in the United States between 1989 and 1991.2
DKA is the most common cause of diabetes-related death in childhood and is a
significant cause of mortality in adults.101 There is considerable overlap—about
one-fifth to one-third of patients with otherwise classic DKA will also have
hyperosmolarity. About one-half to three-fourths of patients with uncontrolled
diabetes will have an osmolarity of 320 mOsm or more.3
Despite the plethora of guidelines and protocols, all with meticulous
details of fluid and electrolyte replacement and insulin therapy, the mortality of
diabetic emergencies has remained unchanged for the past 10 years.111 However,
Associate Editor
San Gabriel Valley Medical
Center, San Gabriel, CA.
Andy Jagoda, MD, FACEP, ViceChair of Academic Affairs,
Department of Emergency
Medicine; Residency Program
Director; Director, International
Studies Program, Mount Sinai
School of Medicine, New York, NY.
Francis M. Fesmire, MD, FACEP,
Director, Heart-Stroke Center,
Erlanger Medical Center;
Assistant Professor of Medicine,
UT College of Medicine,
Chattanooga, TN.
Editorial Board
Valerio Gai, MD, Professor and
Chair, Department of Emergency
Medicine, University of Turin,
Italy.
Judith C. Brillman, MD, Associate
Professor, Department of
Emergency Medicine, The
University of New Mexico Health
Sciences Center School of
Medicine, Albuquerque, NM.
W. Richard Bukata, MD, Clinical
Professor, Emergency Medicine,
Los Angeles County/USC Medical
Center, Los Angeles, CA; Medical
Director, Emergency Department,
Michael J. Gerardi, MD, FAAP, FACEP,
Clinical Assistant Professor,
Medicine, University of Medicine
and Dentistry of New Jersey;
Director, Pediatric Emergency
Medicine, Children’s Medical
Center, Atlantic Health System;
Medicine, Morristown
Memorial Hospital.
Michael A. Gibbs, MD, FACEP, Chief,
Medicine, Maine Medical Center,
Portland, ME.
Gregory L. Henry, MD, FACEP,
CEO, Medical Practice Risk
Assessment, Inc., Ann Arbor,
MI; Clinical Professor, Department
of Emergency Medicine,
University of Michigan Medical
School, Ann Arbor, MI; Past
President, ACEP.
Jerome R. Hoffman, MA, MD, FACEP,
Professor of Medicine/
Emergency Medicine, UCLA
School of Medicine; Attending
Physician, UCLA Emergency
Medicine Center; Co-Director, The
Doctoring Program, UCLA School
of Medicine, Los Angeles, CA.
Francis P. Kohrs, MD, MSPH, Lifelong
Medical Care, Berkeley, CA.
CME Objectives
Upon completing this article, you should be
able to:
1. discuss the pathophysiology and risk factors for
diabetes and related hyperglycemic complications;
2. describe the signs and symptoms of hyperglycemic
emergencies such as diabetic ketoacidosis and
hyperglycemic hyperosmolar syndrome;
3. explain ways to target the history, physical
examination, and laboratory studies in order to
identify potentially lethal complications of diabetes
such as diabetic ketoacidosis and hyperglycemic
hyperosmolar syndrome; and
4. discuss complications of diabetic ketoacidosis and
hyperglycemic hyperosmolar syndrome, such as coexisting infection and/or other illnesses, including
cerebral edema.
Date of original release: February 1, 2004.
Date of most recent review: January 9, 2004.
See “Physician CME Information” on back page.
Michael S. Radeos, MD, MPH,
Attending Physician, Department
of Emergency Medicine, Lincoln
Medical and Mental Health
Center, Bronx, NY; Assistant
Professor in Emergency Medicine,
Weill College of Medicine, Cornell
University, New York, NY.
Steven G. Rothrock, MD, FACEP,
FAAP, Associate Professor
University of Florida; Orlando
Regional Medical Center; Medical
Director of Orange County
Emergency Medical Service,
Orlando, FL.
Alfred Sacchetti, MD, FACEP,
Research Director, Our Lady of
Lourdes Medical Center, Camden,
NJ; Assistant Clinical Professor
Thomas Jefferson University,
Philadelphia, PA.
Corey M. Slovis, MD, FACP, FACEP,
Professor of Emergency Medicine
and Chairman, Department of
Emergency Medicine, Vanderbilt
University Medical Center;
Medical Director, Metro Nashville
EMS, Nashville, TN.
Mark Smith, MD, Chairman,
Medicine, Washington Hospital
Center and Georgetown
University School of Medicine,
Washington, DC.
Charles Stewart, MD, FACEP,
Colorado Springs, CO.
Thomas E. Terndrup, MD, Professor
and Chair, Department of
Emergency Medicine, University
of Alabama at Birmingham,
Birmingham, AL.
COPYRIGHTED MATERIAL—DO NOT PHOTOCOPY OR DISTRIBUTE ELECTRONICALLY WITHOUT WRITTEN CONSENT OF EB PRACTICE, LLC
level greater than 140 mg/dL (7.8 mmol/L) or an oral
glucose tolerance test greater than 200 mg/dL (11.1
mmol/L). As a practical point to emergency physicians,
any measured glucose > 200 mg/dL should be
considered diagnostic of diabetes (unless it has been
drawn from the same venous runoff as currently infusing
glucose solutions!).
with continued emphasis on the timely and appropriate
identification and management of diabetic emergencies,
hopefully this trend may change.
Critical Appraisal Of The Literature
Since the literature on diabetic hyperglycemic emergencies
is fairly mature, there are a number of review articles that
cover basic management of hyperglycemic emergencies.4
The 2003 American Diabetes Association review presents
that group’s latest consensus recommendations.4 The
substance of these recommendations has been covered in
detail in this article.
The state of the literature concerning some key
discussions made in this article is summarized as follows.
Use of insulin by intravenous infusion is well-supported by appropriately conducted randomized, controlled
trials that have adequate power. Meta-analysis of the data
further supports this conclusion. Use of insulin by other
routes has supportive evidence from well-conducted
studies. These studies are older, but nonetheless valid.
Use of fluid replacement in DKA in both adults and
children, use of fluid replacement in HHS in adults, and use
of electrolyte replacement in both DKA and HHS in adults
and DKA in children, as noted in this text and in the clinical
pathways, are well-supported by well-designed trials that
have adequate power. Meta-analysis of the data further
supports the conclusions.
Bicarbonate therapy is not well-supported, and there is
conflicting evidence in the literature. The weight of the
evidence appears to support use of bicarbonate in patients
with pH levels less than 7.0, but this recommendation may
change with better evidence.
Use of phosphate replacement has shown no evidence
of clinical benefit to the vast majority of patients with DKA
and is not recommended. Replacement of phosphate may
be of some benefit in patients who have cardiac dysfunction
or respiratory depression. Replacement of phosphate when
phosphate is lower than 1.0 is indicated and is wellsupported by appropriately conducted randomized,
controlled trials that have adequate power.
Cerebral edema associated with DKA has only a
limited number of studies that present somewhat conflicting
results, resulting in different recommendations for therapy.
Currently, the strength of evidence cannot conclusively
support one recommendation over another. The best advice
for the emergency practitioner is to be wary of this condition in all diabetic patients who have an alteration of
consciousness and hyperglycemia.
Normal Glucose Physiology
Maintenance of blood glucose homeostasis is of paramount
importance to the survival of the human body. The brain
requires 75% of the glucose circulating in the blood. Both
elevated and reduced levels of blood glucose trigger
hormonal responses to restore glucose homeostasis. Low
blood glucose triggers the release of glucagon from pancreatic alpha cells. High blood glucose triggers the release of
insulin from pancreatic beta cells. Additional signals,
adrenocorticotropic hormone (ACTH) and growth hormone
released from the pituitary, increase blood glucose levels by
inhibition of glucose uptake by extrahepatic tissues.
Glucocorticoids also act to increase blood glucose levels by
inhibition of glucose uptake. Cortisol is secreted by the
adrenal cortex in response to the increased ACTH levels.
The adrenal medullary hormone, epinephrine, stimulates
the production of glucose by activation of glycogenolysis in
response to stress.
Insulin
Pathophysiology
Insulin is initially synthesized in the form of proinsulin. In
this form, the alpha and beta chains of active insulin are
linked by a third polypeptide chain, called the connecting
peptide (c-peptide for short). For every molecule of insulin
produced, one molecule of c-peptide is also produced.
Levels of c-peptide can be measured and used as an
indicator of insulin production in cases where insulin has
been injected and mixed with insulin produced by the body.
The c-peptide test can also be used to assess if high blood
sugar is due to reduced insulin production (as in type I
diabetes) or to reduced glucose intake by the cells (as in type
II diabetes). There is little or no c-peptide in the blood of
type I diabetics, and c-peptide levels in type II diabetics can
be reduced or normal. Normal serum concentrations of cpeptide range from 0.5-3.0 nanograms per milliliter.
Insulin levels can also be measured. The primary
clinical utility of insulin measurement is in the evaluation of
patients with fasting hypoglycemia, rather than diabetes.
Insulin levels are inappropriately elevated by insulinsecreting tumors.9 They may also be useful in predicting
susceptibility to the development of type II diabetes,
although c-peptide has largely supplanted direct insulin
measurements for this role.
Diabetes
Epidemiology And Etiology
The broad, sweeping term “diabetes” is used to describe a
group of diseases consisting of different errors or faults in
metabolic processes that culminate in high blood sugar.
While the implications, treatment, and short-term complications seen with these various diseases can be quite different,
they are all classified as diabetes.
The current definition of diabetes is a fasting glucose
Previously, diabetes was classified as either insulindependent or non-insulin-dependent. The disease was often
further separated into juvenile onset or adult onset.
However, these terms are not only passé, but they may be
quite inaccurate. Knowledge about diabetes mellitus and its
management has steadily increased since the discovery of
insulin in 1921. The emergency physician should be aware
Emergency Medicine Practice
2
www.empractice.net • February 2004
Latent Autoimmune Diabetes Of Adults
To further complicate the picture, in older people, type I
diabetes does not present as it does in childhood. When
clinical type I diabetes develops in people over the age of 15,
beta cell function is preserved much longer. This translates
into about 70% of the older type I diabetics having relatively
high c-peptide levels after two years of the disease.11 When
diabetes is diagnosed before age 15, only about 10% of the
patients will have normal c-peptide levels after two years.113
The process is much slower and may be, in the early
phases, indistinguishable from type II diabetes.12 The clinical
presentation is often not catastrophic and may occur over
years or months. These older patients with type I diabetes
may have more insulin secretory capacity and may do well
on oral agents at first.
While the various autoantibody measurements that can
define a type I diabetic are beyond the scope of this article,
about 5% of adults diagnosed with type II diabetes have
positive autoantibodies.12 This puts them into a group
known as latent autoimmune diabetes of adults (LADA).
LADA patients all require insulin therapy eventually, and
this therapy is often started early in the disease process. In
the older literature, LADA cases were described as type II
diabetes that “converted” to type I diabetes—when, in fact,
the LADA patients had type I diabetes all along.
Type I Diabetes
Type I diabetes is due to absolute insulin deficiency. These
patients will have a lifetime dependence on exogenous
insulin. The overall incidence of insulin-dependent diabetes
is about 15 cases per 100,000 people per year. (About 50,000
are diagnosed with type I diabetes each year.) An estimated
three of every 1000 children will develop insulin-dependent
diabetes by the age of 20.112
Type I diabetes is primarily a disease of Caucasians.
The worldwide incidence is highest in Finland and Sardinia
and lowest in Asians and blacks. Type I diabetes is more
frequently diagnosed in the winter months. (The reason
for this is not known.) Interestingly, twins affected by
type I diabetes are often discordant in the development
of the disease.10
One of the most exciting findings of the past 10 years
about diabetes is that most (about 95%) of type I diabetes is
the result of a genetic defect of the immune system,
exacerbated by environmental factors.10 The autoimmune
destruction of the beta cells of the pancreas results in the
inability to produce insulin. Inheritance of type I diabetes is
carried in genes of the major histocompatibility complex
(the human leukocyte antigen system). Eventually, this line
of research may make it possible to identify all patients who
are susceptible to diabetes by a simple blood test. Indeed,
this research may lead to a vaccine using the insulin B chain
8-24 peptides to prevent type I diabetes.10
It is currently thought that islet cells damaged by a
virus produce a membrane antigen that may stimulate a
response by T killer cells of the immune system in the
genetically susceptible patient. The T killer cells misidentify
the beta cell as foreign and destroy it. As the beta cells in the
pancreas are destroyed, the remaining beta cells must
increase their metabolism and, thus, the turnover of
membrane antigen in order to keep up with insulin
demands. More membrane antigen means that more T
killer cells are activated and, hence, more islet cell
destruction. This sets up a vicious cycle that ends in the
destruction of the entire beta cell mass and the symptoms
of clinical diabetes.
This chronic destructive process involves humoral and
cellular components that are detectable in the peripheral
blood months, or even years, before the onset of clinical
diabetes. Throughout this long “pre-diabetic” period,
metabolic changes including a decrease in insulin secretion
with altered glucose tolerance develop at variable rates,
leading to full-blown diabetes.
Early recognition of diabetes and adequate supplemental insulin may reverse this process and prevent the immune
response.10 This preservation and possible recovery of the
beta cell mass is thought to be the basis of the “honeymoon”
period seen after insulin is started in the patient with newonset type I diabetes. Early identification and adequate
treatment with insulin may initiate, sustain, and even
February 2004 • www.empractice.net
Medications For Type I Diabetes
The FDA approved insulin in 1939.13 Early insulin preparations were crude extractions from the pancreases of pigs or
cows. These preparations were purified, but they still
contained a number of additional substances such as
proinsulin, insulin derivatives, and other active peptides
found in the pancreas. Since then, purer forms of insulin
with various time profiles of action have been developed.14
(See Table 1 on page 4.)
Type II Diabetes
Typical type II diabetes is a heterogeneous glucose disorder
found most often in patients over 40 years of age and
associated with a family history of diabetes. Type II diabetes
is usually characterized by a resistance to the patient’s own
insulin that may or may not be coupled with a defect in
insulin secretion of varying severity. These defects lead to an
increase in the liver’s production of glucose and subsequent
fasting hyperglycemia.
Type II diabetes is increasing in incidence as the
population ages and becomes more affluent. The major risk
factor for type II diabetes appears to be obesity—and
obesity has become an epidemic in the United States for all
ethnic subtypes.15 Obesity is associated with insulin
resistance, which worsens diabetes in any case. If the type II
diabetic loses weight and adheres to a strict diet, often no
medication at all is required.
DKA is uncommon in the type II diabetic, since the
majority of these patients have some insulin secretion. The
type II diabetic patient is often considered to require insulin
for control but not to be “insulin-dependent.”
Although type II diabetes was formerly considered to
3
extend this partial remission.
that some of the recent developments in diabetes
care include further separation and identification of
these disparate disease processes that can cause a high
blood sugar.
seen by the emergency physician. (See Table 2 on page 5.)
Oral medications work by causing the pancreas to
make more insulin, by making the tissues more sensitive to
the effects of insulin, by decreasing hepatic output of
glucose, or by decreasing absorption of glucose from the
gut. No single medication uses all four mechanisms, but
most will have one or more effects.
A new, cutting-edge drug, exenatide, actually causes
the pancreas to produce more islet cells and hence produce
more natural insulin.32
be a disease of people older than 40, emergency physicians
are seeing increasing numbers of patients in their 20s or 30s
with type II diabetes. It is seen more frequently in younger
people in association with childhood obesity.16,17 Type II
diabetes is even found in adolescents. (These patients have
the slow clinical course of type II diabetics without the
development of DKA.)
High blood sugars in type II diabetics can be associated
with obesity, high blood pressure, renal failure, and
accelerated coronary artery disease. Prolonged hyperglycemia will increase the rate of development of all of these
diseases.18 Prolonged high blood sugars will also reduce the
effect of insulin (insulin resistance) and decrease the
secretion of insulin (glucose toxicity).19 When the pancreas
quits making insulin, then the type II diabetic needs insulin
as much as the type I diabetic.20 (As noted, these patients
often will secrete enough insulin to stave off ketoacidosis,
but not enough to prevent profound hyperglycemia.)
Secondary Diabetes
Severe pancreatic disorders, including pancreatic cancer,
chronic pancreatitis, hemachromatosis, and cystic fibrosis,
can lead to insulin deficiency and subsequent diabetes.
Since the pancreatic tissue in these individuals is destroyed,
these patients clinically resemble type I diabetics and
require insulin.
Other patients may have diseases or hormonal
syndromes that interfere with insulin secretion (such as
pheochromocytoma) or insulin use (such as acromegaly,
Cushing’s syndrome, and pheochromocytoma). These cases
more closely resemble type II diabetes.
Several common medications can impair the body’s use
of insulin and produce diabetes. The most commonly seen is
probably associated with glucocorticosteroids such as
methylprednisolone or prednisone. Treatment for high
blood pressure (furosemide, clonidine, and thiazide
diuretics), other drugs with hormonal activity (oral contraceptives, thyroid hormone, and progestins), and the antiinflammatory drug indomethacin can also cause or exacerbate diabetes. Numerous other drugs can impair glucose
absorption, such as haloperidol, lithium, phenothiazines,
tricyclic antidepressants, isoniazid, nicotinic acid, heparin,
and cimetidine.
Drug-induced diabetes may or may not require
insulin and may simply resolve after the drug is stopped.
Drug-induced diabetes may resemble either type I or
type II diabetes.
Maturity Onset Diabetes Of The Young
Maturity onset diabetes of the young (MODY) is a
familial form of type II diabetes that was described as
a separate entity from type II diabetes by many researchers.21-24 MODY represents a very small subset of type II
diabetes. It is estimated that only 1%-5% of all type II
diabetics may have MODY.21-24
A typical MODY patient has a diagnosis of diabetes
that is not type I diabetes, is less than 25 years old, and has a
positive family history with a dominant mode of inheritance. These patients are often lean and do not appear to be
insulin-resistant. There are several types that have been
identified and classified by the type of genetic defect
involved. A monogenic defect in insulin secretion is
responsible for all forms of MODY, and genetic tests can
confirm the clinical suspicion.25-31
Medications For Type II Diabetes
Oral medications for the treatment of type II diabetes have
been around since the 1950s. Recently, there has been a
marked increase in the number and kinds of drugs that are
Continued on page 6
Table 1. Types Of Insulin And Times Of Onset/Peak.
Insulin
Onset Of Action
Peak Action
Duration Of Action
Humalog
10 minutes
1 hour
4 hours
Regular
30 minutes
2-5 hours
8 hours
NPH
90 minutes
4-12 hours
22-24 hours
Lente
2.5 hours
6-12 hours
24 hours
Ultralente
4 hours
8-18 hours
30 hours
70/30 blend (70% NPH, 30% regular)
30 minutes
2-12 hours
24 hours
50/50 blend (50% regular, 50% NPH)
30 minutes
2-6 hours
24 hours
• While Humalog, Regular, and 50/50 blend have sharp and
definable peaks, the long-acting Lente insulins have a slow
onset, long flat peaks, and a very slow rate of decline.
• Lente insulins should never be combined with NPH insulin.
(The chemicals in the NPH insulin turn the Lente insulin
into an approximation of fast-acting Regular insulin.)
• There are several insulins not charted above. Buffered
insulins from Lilly and Novo Nordisk and a special U-400
insulin from Hoechst of Germany are designed for use in
insulin pumps.
Source: Derived from data furnished by Eli Lilly and Novo Nordisk
Pharmaceuticals in their product information.
4
Sulfonylureas
Sulfonylureas have been available in the
United States for 40 years. They lower blood
glucose mainly by stimulating the pancreas
to produce more insulin. To a lesser degree,
this action increases the use of glucose in the
peripheral tissues and reduces the hepatic
glucose output. For these pills to work, the
patient’s pancreas must still be making
insulin.
Acetohexamide
Available generically? Yes
Brand name: Dymelor
Duration of action: Intermediate
Dosage: 1 or 2 times a day
Chlorpropamide
Brand name: Diabinese
Duration of action: Long
Dosage: Daily
Comments: With this sulfonylurea in
particular: Patient who drink alcohol may
develop a tingling in the neck and arms, red
eyes, and flushed face. Hypoglycemia is a
real problem with overdoses, as this drug is
eliminated slowly. In children, a single pill
may be lethal.
Glimepiride
Available generically? No
Brand name: Amaryl
Duration of action: Long
Dosage: Daily
Comments: Similar to other sulfonylureas, but
may have fewer side effects.
Glipizide
Brand name: Glucotrol, Glucotrol XL
Duration of action: Intermediate-and longacting formulas
Comments: Appears to be more effective
when taken before meals.
Glyburide
Brand names: Diabeta, Micronase, Glynase
PresTab
Comments: Intermediate in duration, but
effects may last entire day. Glynase PresTab
is new and more readily absorbed than the
other preparations.
Tolazamide
Brand name: Tolinase
Tolbutamide
Brand name: Orinase
Duration of action: Short
Comments: May be a good choice if the
patient has kidney problems. Relatively
short half-life, so the risk of hypoglycemia is
lower than with some of the other
sulfonylureas.
Repaglinide
Dosage: Three times a day
Comments: Repaglinide is chemically not a
sulfonylurea, but has a similar action. This
drug causes a rapid and short-lived release
of insulin. The effects go away quickly.
Biguanides
Metformin lowers blood glucose mainly by
keeping the liver from releasing too much
glucose. It also increases the glucose use in
peripheral tissues by a small amount.
Metformin may also decrease intestinal
glucose absorption somewhat. In contrast to
sulfonylureas, metformin doesn’t raise insulin
levels, so under ordinary circumstances, it
doesn’t cause hypoglycemia. Hypoglycemia
may occur if metformin is taken with insulin, a
sulfonylurea, or an excessive amount of
alcohol.
Metformin
Brand name: Glucophage
Comments: Under usual circumstances,
doesn’t cause hypoglycemia. Doesn’t
promote weight gain. May cause low B12
levels. Patients will often complain of
gastrointestinal side-effects. In very rare
cases, especially if kidney disease is present,
can produce lactic acidosis, a serious
complication. Can be used alone or with a
sulfonylurea. This is the preferred agent for
the obese patient.
Alpha-Glucosidase Inhibitors
Acarbose is an alpha-glucosidase inhibitor
that blocks the digestion of starches. This
slows down the rise of glucose in the blood
after eating. It may also prove useful for
people who have insulin-dependent diabetes,
when they use it with their usual insulin
doses. This drug doesn’t have any other
effects on sugar metabolism.
Acarbose
Brand name: Precose
Dosage: 3 times a day, with main meals
Comments: Doesn’t cause hypoglycemia or
weight gain. Side effects include gas,
bloating, and diarrhea. Causes no serious
side effects. May cause rise in liver function
tests. This drug should be taken with the
first mouthful of each meal. If a dose is
missed, there is no advantage to taking it
later.
5
Miglitol
Brand name: Glyset
Dosage: 3 times a day with meals
Comments: Gastrointestinal side-effects are
quite common.
Thiazolidinediones
These drugs reduce resistance to insulin in
the tissues. The drugs have no effect on the
secretion of insulin. They are often known as
“insulin sensitizers.” Thiazolidinediones also
decrease the production of glucose by the
liver, but only modestly. As an added
beneficial effect, thiazolidinediones will lower
triglycerides and HDL levels.
Troglitazone
Brand name: Rezulin
Duration of action: No longer available
Dosage: n/a
Comments: Associated with liver abnormalities that caused several fatalities. This drug
is no longer available.
Rosiglitazone
Brand name: Avandia
Comments: Lowers insulin resistance.
Pioglitazone
Brand name: Actos
Comments: Lowers insulin resistance.
Exenatide
This new and experimental drug can improve
blood sugar control in type II diabetes. These
actions include stimulating the body’s ability
to produce insulin in response to elevated
levels of blood glucose, inhibiting the release
of glucagon following meals and slowing the
rate at which nutrients are absorbed into the
bloodstream. It has the added benefit of not
affecting body weight or cholesterol.
(Kolterman, O, Buse J, Fineman M, et al.
Synthetic exendin-4 (exenatide) significantly
reduces postprandial and fasting glucose in
subjects with type II diabetes. J Clin Endocrinol
Metab 2003;88(7):3082-3089.)
Exenatide
Brand name: Investigative new drug only
Comments: Increases the number of insulinproducing cells in the pancreas in animal
studies. Increases the secretion of insulin
resulting from elevated sugars. Inhibits the
release of glucagon following meals and
slows the rate at which nutrients are
absorbed into the bloodstream.
Adapted from: Stewart CE. New trends in
diabetes management. EMS Magazine 2001
Nov;30:80.
Table 2. Oral Medications For The Treatment Of Type II Diabetes.
Continued from page 4
very long differential for altered mental status. Since these
patients may have complex medical histories and
comorbidities, this evaluation should not stop at the first
disease encountered.
Not all patients with ketoacidosis have DKA.
The differential diagnosis for the patient who has a
known history of diabetes and presents with the findings
of DKA includes:
• HHS
• Alcoholic ketoacidosis
• Starvation
• Sepsis
• Lactic acidosis
• Uremia
Gestational Diabetes
Gestational diabetes is glucose intolerance during pregnancy. About 4% of all pregnancies are complicated by
gestational diabetes.114 Mothers with gestational diabetes
have higher rates of cesarean delivery and chronic hypertension.114 Their children may have macrosomia, hypoglycemia,
hypocalcemia, and hyperbilirubinemia. (A complete
discussion of gestational diabetes is beyond the scope of
this review.)
Impaired Glucose Tolerance
An impaired glucose tolerance is defined as a fasting
glucose of greater than 110 mg/dL (6.1 mmol/L) but less
than 140 mg/dL.115,116 It is also defined as a patient who has
a glucose tolerance test with ranges between 140 mg/dL (7.8
mmol/L) and 199 mg/dL.115,116 Impaired glucose tolerance
was formerly known as borderline, chemical, or latent
diabetes.115,116 (Impaired glucose tolerance and its implications are not covered in this review.)
Starvation ketosis and alcoholic ketoacidosis are
excluded by the clinical history and by a plasma glucose
that ranges from mildly elevated (rarely ≥ 250 mg/dL) to
frank hypoglycemia. In addition, although alcoholic
ketoacidosis can result in profound acidosis, the serum
bicarbonate concentration in starvation ketosis is usually
less pronounced than in DKA.
Differential Diagnosis: Hyperglycemic
Complications Of Diabetes
Diabetic Ketoacidosis
DKA and HHS are the most lethal hyperglycemic complications of diabetes. Patients may present with some combination of hyperglycemia, altered mental status, and dehydration. Significantly, both can be associated with coexisting
medical conditions that may obfuscate the clinical encounter, and both can be associated with a patient’s initial
presentation of diabetes. The history, physical examination,
and laboratory studies must therefore be tailored to detect
DKA, HHS, and any possible coexisting illnesses. (See also
Table 3 and Table 4 on page 7.)
The basic underlying mechanism for both DKA and
HHS is a reduction in the net effective action of circulating
insulin coupled with a concomitant elevation of
counterregulatory hormones, such as glucagon, catecholamines, cortisol, and growth hormone.
The differential diagnosis for the patient who has no
history of diabetes and is found in a coma starts with the
The pathology of DKA is due to the inability of the cells to
take up and use glucose when insulin is not present. Insulin
is the most significant hormone of blood glucose regulation.
It increases the ability of the cell to take in glucose and
stimulates the manufacture of glycogen.
DKA can be caused by either an absolute or relative
deficiency of insulin and is exacerbated by the concomitant
increase in the insulin counter-regulatory hormones:
glucagon, epinephrine, cortisol, and growth hormone. In
DKA, the classic triad of hyperglycemia, ketosis, and
acidosis is present. The counter-regulatory hormones
further shift metabolism toward hyperglycemia, acidosis,
and ketosis.
DKA is characterized by hyperglycemia with glucose
over 250 mg/dL, although it has been recently recognized
that some patients may present with only mild hyperglycemia, but with marked ketoacidosis (notably pregnant
Table 3. Comparison Of Diabetic Ketoacidosis And Hyperglycemic Hyperosmolar Syndrome.
Ketoacidosis
Hyperglycemic Hyperosmolar Syndrome
Profound
Minimal or none
Glucose
~250-600 mg/dL
Often >900 mg/dL
HCO3
< 15 mEq/L
> 15 mEq/L
Osmolarity
300-325 mOsm
Often > 350 mOsm
Age
Young
Elderly
Onset
Acute; over hours to days
Chronic; over days to weeks
Associated diseases
Common
Common
Seizures
Very rare
Common
Coma
Rare
Common
Insulin levels
Very low to none
May be normal
Mortality
0%-10% (depends on underlying conditions)
20%-40%
Dehydration
Severe
Profound
6
hypertriglyceridemia (found in as many as 50% of
patients with DKA).34,35 This extreme hypertriglyceridemia
can cause the blood sugar, sodium, and bicarbonate to be
factitiously lowered.36
Blood glucose levels will rise above the renal threshold
for glucose reabsorption, so an osmotic diuresis occurs, as
discussed below.
Acidosis
Insulin inhibits the lipolytic action of cortisol and growth
hormone. A deficiency of insulin will increase the circulating
levels of fatty acids. These fatty acids are metabolized by
alternative metabolic pathways. The breakdown products of
the alternative metabolic pathways cause the characteristic
acetone byproducts and a resultant metabolic acidosis. The
acidosis of DKA is mostly due to the ketoacids, although
excess fatty acids and lactic acid (produced by poor tissue
perfusion) also contribute to the lowered pH. These
increased ketoacids include acetone, beta-hydroxybutyric
acid, and acetoacetic acid, although the major derangement
in DKA is an increased level of beta-hydroxybutyric acid
rather than acetone or acetoacetate (on the order of 10:1).115
Hyperglycemia
The main counter-regulatory hormones (glucagon, cortisol,
catecholamines, and growth hormones) are increased
because the cells can’t use the available glucose. Increased
hepatic glucose production and decreased peripheral
uptake of glucose are major causes of the hyperglycemia
seen in diabetes.
In the absence of insulin, glucagon becomes the
primary driving hormone for hepatic carbohydrate
metabolism. Glucagon stimulates the release of glucose
from the liver by gluconeogenesis and glycogenolysis.
Liver glycogen stores are broken down into sugar and
released into the bloodstream. Deficiency of insulin and
concomitant increases in glucagon will enhance the liver
production of glucose by breakdown of fat and protein. The
fatty acid oxidation leads to ketone body formation and
inhibits the conversion of acetyl CoA, by acetyl CoA
carboxylase, to malonyl CoA, which is the first intermediate
in the lipogenesis pathway. This inhibition means that fatty
acids are unable to enter the citric acid cycle and move
instead into the mitochondria, where they are oxidized and
further ketone bodies (acetoacetate and betahydroxybutyrate) are formed.33
At the same time, peripheral uptake of glucose is
impaired by both lack of insulin and excess of glucagon,
so the excess glucose accumulates in the bloodstream.
Insulin deficiency alone, or in combination with the
insulin counter-regulatory hormone increases will
increase protein breakdown, providing amino acids
for increased gluconeogenesis.
Poorly controlled diabetes may result in
Volume Depletion
The kidney plays an important role in the development of
DKA. The normal renal threshold for glucose reabsorption
is greater than 240 mg/dL.37 When the patient is wellhydrated and normal kidney function is maintained, the
serum glucose level is maintained at about 240 mg/dL by
spillage into the urine.
The osmotic diuresis results in significant volume
depletion unless the patient drinks copious amounts of
fluids. When hypovolemia occurs, the glomerular filtration
rate falls and the hyperglycemia is exacerbated. The diuresis
also leads to significant urinary losses of potassium,
sodium, phosphate, chloride, and magnesium ions.
Epidemiology
HHS has a mean age of onset in the seventh decade of life.115
Males are affected slightly less often than females.115
Residents of nursing facilities who are both elderly and
Table 4. Diagnostic Criteria For Diabetic Ketoacidosis And Hyperglycemic
Hyperosmolar Syndrome.
Mild DKA
Moderate DKA
Severe DKA
HHS
Plasma glucose (mg/dL)
>250
>250
>250
>600
Arterial pH
7.25–7.30
7.00–7.24
<7.00
>7.30
15–18
10 to <15
<10
>15
Urine ketones
Positive
Positive
Positive
Small
Serum ketones*
Positive
Positive
Positive
Small
Variable
Variable
Variable
>320
>10
>12
>12
<12
Alert
Alert/drowsy
Stupor/coma
Stupor/coma
Serum bicarbonate (mEq/L)
*
Effective serum osmolality (mOsm/kg)
Anion gap
†
‡
Alteration in sensoria or mental obtundation
*
Nitroprusside reaction method
† Calculation: 2[measured Na (mEq/L)] + glucose (mg/dL)/18
‡ Calculation: (Na+) - (Cl- + HCO3-) (mEq/L)—see text for details
7
women).115 Typically, patients will be overtly acidotic with
pH levels less than 7.35, low serum bicarbonate (commonly
under 15 mmol/L), and positive serum ketones. (If a patient
presents with a marked ketosis, but a glucose under 250
mg/dL, the physician should consider the possibility that
the ketosis is related to another cause such as alcoholic
ketosis, rather than DKA.)
Insulin must be administered to correct the underlying
metabolic abnormalities.
demented are at the highest risk.115 (Oral hydration may be
impaired by dementia and immobility.) Estimates of
incidence are 1 out of every 1000 hospital admissions and a
frequency of 17.5 per 100,000.38
This is a very lethal disease; mortality rates as high as
12%-46% have been recorded.39,40 Wachtel et al found an
increasing mortality associated with increasing age—10%
among those less than 75 years, 19% in those 75-84 years
old, and 35% among those older than 85 years.41 The
mortality rate also increases with higher levels of serum
osmolality. Most deaths caused by HHS occur within the
first 1-2 days.39-41
the kidney is unable to excrete the increased sugar load.
If the patient is unable to drink due to either incapacity
or confusion, the patient also will develop hyperosmolar
hyperglycemia. The patient may be unable to ingest liquids
due to restraints, chemical sedation, coma, nausea or
vomiting, diarrhea, or because they are not given fluids by a
caretaker. The patient may also have been given inadequate
free water from hyperosmolar feedings such as Ensure.
Metabolic abnormalities leading to the pathogenesis of
HHS are similar to those that occur in DKA. Lack of ketosis
in HHS is thought to represent the combination of three
major effects: 1) insulin is available—even if not in sufficient
quantities to prevent hypoglycemia; 2) lower levels of
insulin counter-regulatory hormone levels; and 3) relative
inhibition of lipolysis that result in lower levels of free fatty
acids for the body to process to ketone bodies.38,42,43
Pathogenesis
The initiating event in HHS is an osmotic diuresis due to a
high glucose level. The presence of glucose in the urine
impairs the kidneys’ ability to concentrate the urine and
thus causes increased water losses. If these losses are not
replaced, hypovolemia, intra- and extracellular dehydration,
and hyperosmolarity develop. Fluid losses in HHS are
considerable and may be as much as 10% of the patient’s
body weight.115
If the fluid intake is adequate and glomerular filtration
is maintained, the renal loss of sugar prevents further rise in
osmolarity. When the patient has kidney disease or develops renal insufficiency due to intravascular volume
depletion and subsequent decreased glomerular filtration,
Prehospital Care
Prehospital care of the patient with a hyperglycemic diabetic
emergency is primarily supportive. Ideally, providers
should have access to blood glucose measurement devices.
These strips or meters will frequently measure as “high”
and not give an accurate number when attempting to
measure the serum glucose of a patient with a glucose over
400 mg/dL.
Depending on transport time, an intravenous line
should be started and normal saline given as a bolus of up
to 1 liter in the average-sized adult. All of the patient’s
medications should be identified and brought to the ED.
Table 5. Signs And Symptoms Of
Hyperglycemic Emergencies.
Hyperglycemia
Emergency Department Management
Acidosis
Initial Stabilization
• Polyuria—This may be
• Hyperventilation—This is
seen as nocturia or
due to the metabolic
enuresis in a previously
acidosis. The patient may
continent child.
have peri-oral and limb
• Polydipsia—This may be
paresthesias. Acidosis may
quite extreme; the
be mistaken for hypervenpatient may report that
tilation syndrome.
he or she will set a large
• Altered mental status—
glass of water or other
This can vary from lethargy
liquid at the bedside
to coma.
when going to bed.
Cerebral Edema
• Polyphagia
• Decreasing sensoria
• Weight loss—This may
be quite dramatic due to • Sudden and severe
headache
the breakdown of
• Incontinence
protein and fat stores.
• Vomiting
• Fatigue and weakness—
• Combativeness, disorientaThese are common
tion, agitation
presenting symptoms.
• Change in vital signs
• Abdominal pain—The
(hypothermia, hypotension,
abdominal pain is of
hypertension, tachycardia,
uncertain cause or may
bradycardia, gasping
be due to pancreatitis or
respirations, periods of
another disease that
apnea)
precipitated the DKA.
• Ophthalmoplegia
Note that DKA is often
• Pupillary changes
mistaken for gastroen• Papilledema
teritis.
• Posturing, seizures
• Nausea and vomiting
Initial stabilization of the patient with a hyperglycemic
diabetic emergency consists of ensuring that an appropriate
airway is secured and/or protected, ensuring that the
patient has an intravenous line, and verifying the serum
glucose concentration. Following these initial stabilizations,
the patient evaluation should commence with history,
examination, and laboratory evaluation.
History
A thorough history should be obtained, documenting the
patient’s chief complaint, duration, and associated symptoms. In the review of systems, be sure to focus on possible
precipitants—particularly ones which may complicate the
treatment and/or increase mortality, such as infection,
stroke, and myocardial infarction.
Some high-yield questions that may help streamline the
history include the following:
1. Are any symptoms consistent with hyperglycemia,
acidosis, or cerebral edema present?
See Table 5.
2. Does the patient have diabetes? If so, has the patient had
prior episodes of DKA or HHS?
The most common association with hyperglycemic emergencies is, of course, a prior history of diabetes. Unfortunately, as many as 20%-30% of cases of DKA may be the
initial presentation of previously undiagnosed diabetes.117
8
3. Is there an associated infection?
An infection—including pneumonia, urinary tract infection,
or sepsis—is the most common precipitating factor of both
DKA and HHS.44-47 The physician must search diligently in
these patients for a focus of infection such as sinusitis,
middle ear infections, prostatitis, perirectal abscess, or
infected decubiti. Rectal and pelvic examinations are
important parts of the evaluation if the patient has no
obvious focus of infection identified.
4. Is there another associated illness?
Associated medical illnesses are commonly present in HHS.
These may include:
• Cerebrovascular accidents (both stroke and intracranial
hemorrhage)
• Myocardial infarction
• Acute pancreatitis
• Pulmonary embolus
• Mesenteric thrombosis
• Renal failure
• Heat stroke and heat stress
• Gastrointestinal hemorrhage
• Hypothermia
• Alcohol consumption or cocaine use
6. What other medications has the patient been taking?
Drugs such as sympathomimetics, pentamidine, thiazides,
phenytoin, and calcium-channel blocker agents can
precipitate diabetes and DKA.48 As noted earlier, corticosteroids can not only precipitate diabetes, they can alter the
glucose tolerance of normal patients.
The use of drugs and therapies that are known to cause
hyperglycemia may precipitate HHS. These include
azathioprine, beta-blocking agents, cimetidine, diazoxide,
diuretics, glycerol, phenothiazines, calcium-channel
blocking agents, phenytoin, and steroids.50-56 Initiation of
total parenteral nutrition (parenteral hyperalimentation) is
commonly implicated as a precipitating factor, but this is not
usually seen in the ED.57
Furthermore, trauma, febrile illnesses, or even psychological turmoil may elevate the counter-regulatory hormones (glucagon, epinephrine, growth hormone, and
cortisol) and precipitate DKA. Other precipitating diseases
include alcohol abuse and pancreatitis. In older patients, the
stress of myocardial infarction or stroke can precipitate
DKA. The stress of pregnancy may also precipitate DKA in
diabetic patients.
Steroid excess due to exogenous steroid administration
or endogenous production of steroids (Cushing’s syndrome)
is a common precipitating factor of DKA. Excess of counterregulatory hormones, such as is found in pheochromocytoma, may cause DKA. Thyrotoxicosis and hyperthyroidism
can precipitate DKA.
Physical Examination
The physical examination for cases of suspected DKA or
HHS is essentially the same. In such cases, be sure to
carefully assess vital signs. Also, check and document the
patient’s weight, extent of dehydration, level of consciousness, whether Kussmaul respirations are present, and be
sure to evaluate for the possibility of infection.
Certain physical findings can help determine whether
the patient has DKA, HHS, or both.
5. Has the patient been receiving adequate insulin?
Thorough questioning may be necessary in order to
evaluate this issue adequately. Failure to take insulin is the
most common cause of recurrent DKA, particularly in
Physical Findings In Both Diabetic Ketoacidosis And
Uniformly, the patient will be dehydrated. The typical
9
adolescents.5 The patient may also run out of insulin, have a
calibration error in the injection device, use the wrong
concentration or type of insulin, or inadvertently inject an
inadequate dose of insulin. Underinsurance may mean that
the patient can’t afford insulin or that funds were diverted
to other uses (e.g., syringes).5 A change of diet or exercise
may also mean that the insulin administered is inadequate.
In young patients with type I diabetes, psychological
problems complicated by eating disorders may be a
contributing factor in up to 20% of cases of recurrent
ketoacidosis.5,48 Factors that decrease compliance in the
young include fear of weight gain, fear of hypoglycemia,
rebellion, and the stress of chronic disease.48
Noncompliance with insulin or other drugs is one of
the most commonly cited precipitating factors for HHS.38
The noncompliant adult diabetic may have repeated
episodes of HHS. Noncompliance may be due to psychiatric
disorders, neglect/abuse, onset of dementia, or inability to
purchase medications or obtain refills.38 Each of these causes
should be explored in the patient who presents with
recurrent HHS and considered carefully in a patient with
new HHS.
It is also important to note that patients may skip
insulin when ill. Insulin must always be administered
during illness, even when eating is markedly diminished.
Infection induces insulin resistance and may require
increased or supplemental doses of insulin. Failing to
increase insulin during periods of illness may contribute to
an increased incidence of DKA during this period of stress.49
The blood sugar level and the presence of ketones help to
determine the optimal supplemental insulin dosage.
When DKA occurs as the initial presentation in the new
diabetic, the symptoms are often gradual in onset with
progressive dehydration and slowly developing ketosis. The
stress and symptoms of another illness may both mask the
onset of the DKA and precipitate the entire process.
In the established diabetic, DKA can develop quite
rapidly. This may occur during an illness or when insulin
therapy has been forgotten, deliberately omitted, or
disrupted. When this happens, the ketoacidosis may
predominate, and DKA may present with only a modest
elevation of the blood glucose (250 mg/dL).
DKA most often occurs in patients with type I diabetes,
although it may occur in patients with type II diabetes.118 In
one series, 13% of cases of DKA occurred in patients over 60
years of age and 31% of mixed DKA and HHS cases were in
patients over the age of 60.44
are generated in adipose tissue, are increased during
DKA.59 These prostaglandins decrease peripheral vascular
resistance and may cause tachycardia, hypotension,
nausea, vomiting, and abdominal pain. The same
symptoms occur when PGI2 is infused over several
hours into normal humans.
The abdominal pain associated with diabetes is
disconcerting, since it may be from either DKA or from a
pathologic process that caused the crisis, such as pyelonephritis, appendicitis, or pancreatitis.48 Indeed, in some
patients with DKA, surgeons have been asked to evaluate
the patient for intra-abdominal pathology before the
diagnosis of DKA is made.
The respiratory rate may be normal or somewhat
rapid. If the patient is carefully examined, the rapid, deep
breathing typical of Kussmaul respirations is often found.
If Kussmaul respirations are present, serum CO2 is likely
to be less than 10 mEq/L. A fruity odor to the breath, due
to the acetone and ketone bodies associated with DKA, is
often reported.60
Lethargy is common, and some patients will present
in a coma. Mental status changes may occur in DKA and
may be the result of DKA or may be due to an underlying
process that caused the patient to develop DKA. If a mental
status change is present, it is imperative to find the cause.
Coma may result from the hyperosmolality associated
with DKA. A calculated osmolality greater than 320
mOsm/L is often associated with coma.61,62 Calculated
or measured values below this level would not explain a
coma, and another cause such as meningitis or stroke
should be pursued. The clinician should also be wary of
cerebral edema associated with DKA, as described later in
this article.
Up to 25% of patients with DKA have emesis,
which may be coffee-ground in appearance and guaiacpositive.47 Endoscopy has shown this to be the result of
hemorrhagic gastritis.48
deficit in body water is 20%-25%, which is about 12% of the
patient’s total body weight.58 The physical examination may
reflect this profound dehydration. The mucous membranes
may be quite dry. Skin turgor may be decreased, but this
may be difficult to evaluate in the elderly patient. The
patient’s eyes may be sunken.
Tachycardia and hypotension may be present. The
pulse may be weak and thready. Use of beta-blockers must
be taken into consideration when evaluating the vital signs.
If infection is present, the patient may be febrile; however,
those patients who are immunocompromised or septic may
be normothermic or even hypothermic.48
Abdominal pain or tenderness, nausea and vomiting,
lack of bowel sounds, and ileus may be found in many
patients with uncontrolled diabetes. These same findings
may also be due to an intra-abdominal process that caused
the patient to decompensate. This is not uncommon in the
elderly. The development of findings due to decompensation of the diabetes follows the onset of symptoms rather
than precedes it. The symptoms should improve markedly
after the patient’s elevated blood sugar and dehydration are
properly treated.
Physical Findings In Diabetic Ketoacidosis
The physical signs of DKA can be quite variable. Typical
signs include fatigue, malaise, thirst, polyuria, reduced
skin elasticity (poor skin turgor), dry mucous membranes,
hypotension, and tachycardia from the volume deficits.
Protracted vomiting may markedly increase the water
loss. Some water loss may also occur due to the compensatory hyperventilation from the metabolic acidosis (Kussmaul respiration).
The patient may note weight loss if there is a long
onset. As the patient becomes more ill, he or she will begin
to vomit and may complain of abdominal pain.
The exact cause of the abdominal pain associated
with DKA is not known. Prostaglandins I2 and E2, which
Cost- And Time-Effective Strategies For Hyperglycemic Disorders
1. Check the glucose in children, even if the chief complaint
does not appear to relate to diabetes.
A major impact that the emergency physician can make is
to ensure that no child with new-onset diabetes is missed.
Since the original presenting symptom often masquerades
as gastroenteritis, abdominal pain, or is concomitant with
another illness, the emergency physician’s best strategy is
to ensure that a glucose measurement is always obtained.
other samples can both save time and costs. Use of a
bedside glucose measurement on all patients who require
an IV for hydration can both rapidly and inexpensively
ensure that the vast majority of DKA patients will not be
missed. Use of bedside glucose measurements on all
patients with alteration of consciousness is both
appropriate and will rapidly identify those who have hypoor hyperglycemia as either contributing or primary causes
of the alteration of consciousness.
2. Dipstick the urine in all patients with vomiting.
Since glucose is spilled into the urine when the blood
sugar exceeds about 200 mg/dL, the easiest cost- and
time-saving measure is to simply dipstick the urine and
ensure that there is no significant sugar in the urine in
patients with vomiting.
4. In many cases, phosphate replacement is unnecessary
and can be potentially harmful.
Use of phosphate replacement in diabetes has shown no
benefit on clinical outcome in the majority of patients with
DKA. Overzealous use of phosphate can cause severe
hypocalcemia. Unless the patient has a phosphate of less
than 1.0 mg/dL, the clinician can decrease costs by
omitting this mineral in intravenous fluids used in DKA. ▲
3. Bedside glucose measurements are fast, inexpensive, and
relay clinically relevant information.
Bedside glucose measurements done from fingerstick or
10
DKA. The findings are somewhat different, however. On
presentation, the patient with HHS has glucosuria and no or
minimal ketonuria and ketonemia. A mild metabolic
acidosis may be present in these patients.
Laboratory criteria used to diagnose DKA include a
glucose level greater than 250 mg/dL, a pH less than 7.35, a
serum bicarbonate of 12-15 mEq/dL, a high anion gap, and
positive ketones. (Occasionally DKA can occur with a
normal glucose level when there is vomiting, reduced intake
of carbohydrate, and continued insulin therapy.) (See also
Table 6.)
HHS is characterized by a marked hyperglycemia (plasma
glucose is often greater than 600 mg/dL with
hyperosmolarity (serum osmolarity is often greater than 350
mOsm, dehydration, and a relative lack of insulin. Ketosis
may be present but is not a significant feature. The presence
of some ketonuria or mild ketonemia does not preclude the
diagnosis. This syndrome may also be called hyperosmolar
hyperglycemic nonketotic coma or hyperosmolar
nonacidotic diabetes.
The patient may have one of several presentations, each
of which should prompt the clinician’s consideration of the
possibility of HHS. The onset of HHS is more insidious than
that of DKA. The patient with hyperosmolar syndrome
often has no history of diabetes or may have a mild type II
disease, treated with diet or oral antidiabetic agents. Rarely
will HHS present in a young patient with type I diabetes. As
in other endocrine emergencies, patients with HHS often do
not present with specific signs and symptoms suggesting a
metabolic disorder.
Initial features of HHS include fatigue, blurred vision,
polydipsia, muscle cramps, and weight loss. The increased
osmotic load of the high glucose may lead to decreased
visual acuity with distance vision and paradoxical improvement of near vision. The patient may also complain of
muscle cramps, nausea, vomiting, or abdominal pain.
Unfortunately, many patients with HHS present with more
advanced symptoms. The typical patient is elderly, volumedepleted, and comatose or with an altered mental status.115
While the patient with HHS often has an altered mental
status, he or she may be alert.3,46 Indeed, the name was
changed from hyperosmolar nonketotic coma to HHS
because frank coma is present in less than 10% of cases.113
Patients with HHS often present with neurologic
abnormalities that are rarely seen in the patient with DKA.63
In HHS, mental obtundation and coma are more frequent
because the majority of patients, by definition, are
hyperosmolar. These abnormalities include seizures,
transient hemiparesis, movement disorders, and other focal
neurologic findings. Seizures are seen in up to 25% of
patients and can be either generalized or focal.64-66
The unwary examiner may erroneously pin the
diagnosis of stroke on the patient with HHS due to the
obtundation associated with hyperosmolarity. Likewise, of
course, coma should not be attributed to hyperosmolality
when the osmolality is less than 320 mOsm/kg.
Others who may develop HHS include patients who
have been given massive glucose loads—such as in
hyperalimentation, patients with significant renal disease
and diabetes, and elderly patients who have been newly
started on oral antidiabetic drugs.
The patient often has another disease process to
confuse the initial picture. Meticulous attention will be
needed to treat both the metabolic disturbance and the
precipitating factors.
Serum Glucose
A serum glucose determination should always be obtained,
but most management can be done with bedside glucose
testing. Suspect DKA when the glucose is greater than
250 mg/dL.48 However, normoglycemia may be seen in
patients who received insulin before being seen in the ED,
were fasting, or who have impaired gluconeogenesis from
liver failure.
Electrolytes
The massive diuresis may contribute significantly to the
electrolyte abnormalities seen in DKA. Free water, sodium,
potassium, magnesium, and phosphate are excreted into the
urine along with the glucose. Ketoacids act as nonresorbable
ions in the kidney and are excreted as potassium and
sodium salts. Because urine contains about 70-80 mEq/L of
cations, most of which are sodium and potassium, massive
total body deficiencies in sodium and potassium may result.
Despite this urinary potassium loss and total body
deficits of potassium, most patients will have an elevated
potassium at initial laboratory evaluation.47 This is due to
the lack of insulin, acidosis, and the increased osmolality.
Loss of insulin will cause a shift in intracellular potassium
into the serum. Acidosis and movement of water from the
intracellular space to the extracellular space will further
move potassium into the extracellular fluid.
The sodium should be corrected for the high glucose
seen in the patient with HHS. The effects of a very
elevated glucose on the sodium may be greater than the
usual correction. There is some controversy about the
method of correction to be used.113 See Table 6 for the
usually accepted correction.
When the patient has severe acidosis, the differential
diagnosis should consider DKA, lactic acidosis, and other
Continued on page 15
Table 6. Useful Calculations In Diabetic
Ketoacidosis.
The anion gap:
Na+ -(Cl- + HCO3-)
Correction of serum sodium:
Corrected Na+ = Na+ + 1.6 * [(glucose in mg/dL) – 100] / 100
Calculation of effective serum osmolality:
2[Na+ + K+ ] + [glucose in mg/dL]/18
Diagnostic Studies
Total body water deficit:
0.6 x weight x [1-140/serum sodium]
The diagnostic work-up for HHS is identical to that for
11
Physical Findings In Hyperglycemic
Hyperosmolar Syndrome
Presumptive diagnosis of diabetic ketoacidosis
ED encounter:
Laboratory findings:
• ECG if age greater than 20
• Chest radiograph and cultures as
appropriate
• Start IV fluids 15-20 mL/kg/hour
• History and physical examination
• Laboratory tests, serum pH, CBC, UA,
BUN, creatinine, electrolytes
•
•
•
•
Blood glucose > 250 mg/dL
pH < 7.3
Serum HCO3 < 15 mEq/L
Moderate ketonuria and ketonemia
Evaluate volume status and potassium (Class I)
➤
➤
➤
Insulin
IV fluids
Potassium
➤
➤
• Administer regular insulin IV 0.15 U/
kg as IV bolus (this is controversial)
(Class indeterminate)
• Administer regular insulin IV 0.1 U/
kg/hour as IV drip (Class I)
Hypovolemic shock?
YES
➤
➤
➤
➤
➤
Switch to 0.45%
sodium chloride
solution (Class II)
Continue 0.9%
sodium chloride
solution (Class II)
➤
➤
K < 3.3 mEq/L
• Hold insulin
• Give K (40 mEq in adults) per
hour until K > 3.3 mEq/L
(Class II)
➤
* ICU bed may not be
necessary if adequate
monitoring is
available in a lesser
unit—depends on
hospital capabilities
➤
➤
➤
➤
• Continue insulin
infusion (Class I)
• Add glucose 5%
to IV (Class I)
• Continue to
monitor
electrolytes or
glucose every 2
hours until
patient is stable
(Class I)
• Search diligently
for precipitating
cause (Class
indeterminate)
• Admit to ICU*
(Class indeterminate)
Continue insulin
infusion (Class I)
➤
➤
➤
Low
sodium
NO
K 3.3-5.5 mEq/L
• Give 20-30 mEq to keep serum
potassium at about 4-5 mEq/L
(Class II)
Normal or
elevated sodium
Continue insulin infusion until serum
glucose reaches 250 mg/dL (Class I)
YES
➤
Evaluate corrected sodium
Double insulin infusion hourly
until serum glucose drops 50-70
mg/dL (Class indeterminate)
Serum glucose under 250 mg/dL?
NO
➤
NO
K > 5.5 mEq/L
• Hold K
• Check K every 2 hours
(Class II)
➤
➤
YES
➤
• Hemodynamic monitoring
(Class I)
• Administer 0.9% sodium
chloride 20-40 mL/kg
(Class I)
• Re-evaluate volume status
Did the blood glucose fall
by 50-70 mg/dL in the first hour?
➤
Clinical Pathway: Treatment Of Diabetic Ketoacidosis
Monitor serum glucose, potassium, sodium, and bicarbonate every 1-2 hours for
at least 18 hours (Class II)
If serum glucose falls under 250 mg/dL:
•
•
•
•
•
Continue insulin infusion (Class I)
Add glucose 5% to IV (Class I)
Continue to monitor chem 7 every 2 hours until patient is stable (Class II)
Search diligently for precipitating cause (Class indeterminate)
Admit to ICU* (Class indeterminate)
The evidence for recommendations is graded using the following scale. For complete definitions, see back page. Class
I: Definitely recommended. Definitive, excellent evidence provides support. Class II: Acceptable and useful. Good
evidence provides support. Class III: May be acceptable, possibly useful. Fair-to-good evidence provides support.
Indeterminate: Continuing area of research.
This clinical pathway is intended to supplement, rather than substitute for, professional judgment and may be
changed depending upon a patient’s individual needs. Failure to comply with this pathway does not represent a
breach of the standard of care.
Copyright ©2004 EB Practice, LLC. 1-800-249-5770. No part of this publication may be reproduced in any format without written consent of EB Practice, LLC.
12
Presumptive diagnosis of
hyerpglycemic hyperosmolar syndrome
Continued from previous column
YES
➤
NO
➤
• Add glucose 5% to IV
(Class I)
• Lower serum glucose
slowly to normal,
decreasing the insulin
infusion as needed
(Class I)
• Replace remaining
estimated fluid deficit
over the next 24-48
hours (Class II)
Establish invasive monitoring (Class I)
➤
➤
Administer normal saline at 250 mL/hour (Class II)
➤
Adequate urine output established?*
YES
Monitor serum
glucose, potassium,
bicarbonate every
1-2 hours for at
least 18 hours
(Class II)
NO
➤
➤
• Add KCl (40 mEq/L) and
potassium phosphate
(Class II)
• Administer insulin bolus
5-10 units IV regular and
then insulin infusion at
5-10 units per hour
(Class II)
• Monitor serum glucose,
potassium, bicarbonate
every 1-2 hours for at
least 18 hours (Class I)
Continue insulin
infusion (Class I)
➤
➤
YES
➤
Evidence of cardiac decompensation?
Continue insulin infusion
(Class I)
NO
➤
➤
Administer 1-2 liters of normal saline solution (Class I)
➤
➤
Serum glucose under 300 mg/dL?
Reassess volume
status of patient
(Class I)
➤
Go to top of next column
* Note: If the patient continues to have inadequate urine output despite adequate volume replenishment, assume that renal
failure is present: Use insulin and decrease the IV fluid rates (Class indeterminate)
The evidence for recommendations is graded using the following scale. For complete definitions, see back page. Class I: Definitely
recommended. Definitive, excellent evidence provides support. Class II: Acceptable and useful. Good evidence provides support. Class III:
May be acceptable, possibly useful. Fair-to-good evidence provides support. Indeterminate: Continuing area of research.
This clinical pathway is intended to supplement, rather than substitute for, professional judgment and may be changed depending
upon a patient’s individual needs. Failure to comply with this pathway does not represent a breach of the standard of care.
Copyright ©2004 EB Practice, LLC. 1-800-249-5770. No part of this publication may be reproduced in any format
without written consent of EB Practice, LLC.
13
Clinical Pathway: Treatment Of
Ten Pitfalls To Avoid
1. “The little girl did really well during therapy for DKA,
and the glucose returned to normal before I could
arrange a bed in the ICU. I arranged for a floor admission
for overnight. How could I predict that she’d develop
cerebral edema?”
The patient with DKA always deserves to be admitted
and carefully watched. The responsible clinician should
admit the patient with DKA to a unit where neurologic
status and vital signs can be monitored frequently and
the blood or fingerstick glucose can be measured hourly.
A diabetic flow sheet is quite helpful in the management
of these patients.
ketones may become positive later in the disease
process. In this patient, the development of “positive
ketones” could signify improvement if other laboratory
values and clinical signs are improving.
6. “The blood sugar dropped to 30 while the patient was
waiting for a bed in the ICU. The ED was too busy for
serial examinations.”
The patient in DKA is a critical patient who deserves high
priority. By any method of administration, insulin may
produce hypoglycemia. With low-dose insulin therapy
and adequate volume replenishment, the drop in blood
glucose is predictable and may be easily observed with
adequate monitoring. This complication should not
occur. As the blood glucose approaches 300 mg/dL,
exogenous glucose should be added, either
intravenously or orally (if the patient is awake). As
exogenous sugar is added, insulin will still need to be
given, but the dosage and rate of administration may
have to be adjusted.
2. “I told the family that that their elderly grandmother
had another stroke! She had two prior strokes by the
medical records and was a stable, diet-controlled
diabetic. How was I to know that this time was
different?”
HHS often presents as an alteration of consciousness,
and a cerebrovascular accident may precipitate the
illness. Unfortunately, bedridden patients may also not
be able to get adequate fluids, which also can precipitate
the syndrome.
7. “She really looked quite dehydrated, her BUN was 45,
and her CO2 was 12, so I just let a couple of liters of
normal saline with bicarbonate run in wide open.”
The incidence of cerebral edema in DKA may be related
to the administration of bicarbonate rather than the
speed of fluid replenishment, so bicarbonate should be
avoided if at all possible.
3. “The patient was admitted in DKA; there was no reason
to suspect that he had an MI.”
Myocardial infarction elevates catecholamines, which
can precipitate DKA. Any patient with DKA who is
clinically at risk for a myocardial infarction should be
evaluated for myocardial ischemia. Patients with an
infarction or congestive heart failure may require a
central line.
8. “I thought that 8-year-old boy only had
gastroenteritis.”
DKA often presents initially as an upset stomach. You don’t
have to look for acetone in every patient with
gastroenteritis, but you should check serum glucose. Many
previously undiagnosed patients are seen in physicians’
offices or EDs before they become critically ill. Checking
the sugar may be life-saving in these patients.
4. “I knew that the patient’s renal status was marginal,
but she still appeared quite dehydrated. How was I
to predict the rapid onset of congestive heart failure in
this patient?”
The patient with DKA and renal failure may be very
difficult to manage. Fluid losses will have been smaller
than those seen in DKA patients with normal renal
function, and fluid replacement must be done much
more slowly. Therapeutic emphasis is on insulin per se,
careful monitoring of potassium, and consideration of
dialysis. Rapid fluid administration may lead to
congestive heart failure. The patient with both renal
failure and DKA may require central monitoring to
prevent pulmonary edema.
9. “She was an elderly type II diabetic who recovered
quite promptly from the blood sugar of 32, so I gave her
a meal and let her go home.”
The diabetic patient on oral hypoglycemic agents who
becomes hypoglycemic should be evaluated carefully.
The half-life of the oral hypoglycemic agents is often
long and may be unpredictable. Admission is generally
recommended for these patients, since hypoglycemia is
likely to recur.
5. “I knew that the patient had diabetes, and I found a
urinary tract infection. The blood sugar was 450 and
I didn’t think to get an arterial blood gas when the
serum ketones were negative. How was I to know that
this was DKA?”
Sepsis, accumulation of lactate, and poor tissue
perfusion prevent the formation of acetoacetate. Betahydroxybutyrate—a ketoacid that does not react in the
nitroprusside test—is preferentially formed. The very ill
diabetic with hyperglycemia and an anion gap acidosis
should be treated for DKA. A nitroprusside test for
10. “The blood sugar was only 240—how could he
have had DKA?”
Most patients with DKA present with glucose levels
greater than 300 mg/dL, but occasionally patients
may have lower glucose levels or even normal glucose
levels. Normal glucose may be seen when the patient
has had insulin before presentation, reduced food
intake, or impaired gluconeogenesis (as with liver
failure or severe alcohol abuse). Markedly increased
triglycerides may foil the lab, so be wary if the serum is
very lipemic. ▲
14
The forces governing the movement of water are both
hydrostatic and osmotic pressures. The osmotic pressures
greatly exceed hydrostatic pressures in the body.
Osmotic pressure is a property of solutions that
depends on the number of osmotically active molecules in
solution. It does not depend on the ionic charge, the size of
the molecule, or the chemical properties of the molecule.
One gram-molecular weight (1 mole) of a compound is also
termed 1 osmole (osmol or Osm). Most biological concentrations are expressed in milliosmolar (mOsm) or
microosmolar (µOsm) concentrations. Ionized molecules
such as sodium chloride will dissociate in solution, and each
ion exerts its own osmotic force. (This means that 1 mOsm
of NaCl exerts 2 mOsm of osmotic pressure.) Osmolality is
the expression of this quantity of osmotically active particles
per 1000 grams of water or solvent. The more common term,
osmolarity, expresses the number of osmotically active
particles per liter of solvent. The difference between
osmolarity and osmolality is due to protein and fat, which
comprise about 6%-8% of the solutes in plasma.
Hyperosmolality in diabetes is largely due to
hyperglycemia.
non-HHS disease processes. Vomiting or the concomitant
use of a thiazide diuretic can cause a metabolic alkalosis that
can mask the severity of the acidosis. This situation might
be found if the combined anion gap and the measured
HCO3 are greater than expected.
Complete Blood Count
The complete blood count often shows a leukocytosis. This
may be in part due to the hemoconcentration from dehydration. White blood cell counts of 20,000 cells/mm3 are not
uncommon. If the patient has an elevated band count
(bandemia) on peripheral smear, then an infectious process
is likely.67
Serum pH
An arterial blood gas or venous gas should be sent early in
the evaluation of the patient considered to have DKA.68,69
(The correlation between arterial and venous pH is quite
close, and the two can be used interchangably for the
evaluation of DKA patients.) This will help determine the
degree of acidosis and bicarbonate loss. When the pH is less
than 7.35 and a low HCO3- is found, then the diagnosis of
DKA should be seriously considered.
Lumbar Puncture
Lumbar puncture is indicated in patients with an acute
alteration of consciousness and clinical features suggestive
of possible central nervous system infection.
Blood Urea Nitrogen And Creatinine
The patient will often have some elevation of the blood urea
nitrogen due to dehydration. The clinician should carefully
consider the possibility of chronic renal failure. The patient
with both diabetes and renal failure may be quite difficult to
manage. Fluid losses may be smaller than when the patient
has normal renal function, and fluid replacement must be
much more conservative. Therapeutic emphasis will switch
to insulin, careful monitoring of potassium, and consideration of dialysis.
Hemoglobin A1c Determination
Glycosylated hemoglobin measurement is not needed for
the emergent management of the patient’s diabetes. The
hemoglobin A1c will give the clinician some idea of the
duration or degree of control of the patient’s diabetes prior
to the emergency.
Treatment
Urinalysis And Urine Culture
Successful treatment of both DKA and HHS includes
correction of the dehydration and hyperglycemia, resolution
and anticipation of the electrolyte abnormalities, identification of precipitating or comorbid illnesses. (See also the
Clinical Pathways on page 12 and page 13.)
Infection is quite common as a precipitating factor.
Pneumonia, urinary infections, and sepsis are the most
common etiologies. This high incidence of infection in HHS
patients has led to a recommendation for early empiric
antibiotic therapy, even if no source is identified.41,70 This is
controversial; others recommend waiting for definitive
evidence since both fever and leukocytosis can also be
precipitated by other factors.71
The current mortality rate of DKA is about 2%-5%.72
Without insulin therapy, the mortality rate of DKA is 100%.
Remember that the underlying pathology may be the
reason for mortality in the patient with HHS. Re-evaluate
the patient for infection, myocardial infarction, and underlying diseases. Early mortality in HHS is more likely to be
caused by sepsis, shock, or an underlying illness.
The most common complications of DKA and HHS
include hypoglycemia due to overtreatment with insulin,
hypokalemia due to insulin administration in the potas-
Check the urine on every patient who presents with a
possible diagnosis of DKA in order to identify possible
urosepsis causing the DKA. Likewise, in females of childbearing age, a urine pregnancy test is equally important.
Serum Ketones
Serum ketone testing may not correlate with the degree of
ketoacidosis. Beta-hydroxybutyric acid is the major ketoacid
produced in DKA. It does not react with nitroprusside, so
urine or blood testing for ketones may be negative or only
slightly positive.
During the treatment of DKA, beta-hydroxybutyric
acid will be converted to acetoacetic acid. The resultant
increase in acetoacetic acid may make the serum or urine
testing for ketones more positive, despite clinical improvement and an increasing pH and decreasing anion gap.
While some literature has suggested that urine ketones can
be used to rule out DKA, serum ketones are more accurate
and should be used instead.
Serum Osmolality
Because biological membranes are readily permeable to
water molecules, there is a continuing movement or
exchange of water between various fluid compartments.
15
Continued from page 11
monitoring of mental status, which may be the first
indication of cerebral edema in the diabetic patient.
sium-depleted patient and treatment of acidosis with
bicarbonate, and hyperglycemia due to interruption of
intravenous insulin before coverage with other forms of
insulin has been established.
Insulin
Replacing insulin reverses the mobilization of free fatty
acid and the hepatic production of glucose and ketoacids.
Insulin treats the ketosis and the acidosis as well as the
hyperglycemia. Insulin can be given intravenously or
intramuscularly. Some physicians advocate preceding the
infusion with a bolus of insulin; however, this has no
physiologic advantage.
Continuous intravenous insulin infusion has several
advantages over intramuscular insulin.113 Smaller insulin
doses are needed for clinical efficacy when given intravenously. An insulin drip gives therapeutic plasma insulin
levels with a smooth correction and flexibility to increase or
decrease the dose easily. A common intravenous insulin
administration regimen is continuous infusion of 0.1 units
per kilogram per hour (about 6-8 units per hour in the
average adult). If the insulin infusion is connected through a
separate line or through a “piggy-back” connection, the
infusion can be regulated separately from the rate of fluid
administration.
An alternative method of dosing would be to give an
equivalent dose of rapid-acting insulin intramuscularly
every hour. Since vasoconstriction decreases medication
absorption in hypotensive patients, this method is less than
optimal in the critically ill patient.
Subcutaneous insulin is not recommended during
the treatment of any critically ill patient. In these
potentially hypotensive and/or dehydrated patients,
the absorption from subcutaneous tissues may be inadequate or unpredictable.
Research indicates that bolus administration of insulin
may not be the best possible therapy for the patient.113 Bolus
insulin causes plasma insulin levels to rise within minutes
to over 3000 microunits per milliliter. This level far exceeds
physiological levels of insulin. Potassium levels are significantly reduced when these boluses of insulin are used. This
could be a clinical problem if the patient is hypokalemic
before insulin is given.
The endpoint for continuous insulin infusion should be
resolution of hyperketonemia (3-hydroxybutyrate < 0.5
mmol/L) rather than the normalization of blood sugar.73 To
prevent the recurrence of DKA, the patient should resume
his or her usual subcutaneous dose of insulin before the
insulin infusion is stopped. The insulin drip should not be
considered as part of fluid replacement calculations.
The glucose level can be anticipated to fall by 50-100
mg/dL (2.5-5.0 mmol/L) per hour.74 The initial rate of
decrease may be more rapid as the renal function improves
with improved hydration. When the glucose level reaches
250 mg/dL (12.5 mmol/L), the possibility of hypoglycemia
should be anticipated. When the patient’s glucose level
reaches 250 mg/dL, the rate of infusion of insulin should be
cut in half to decrease the possibility of hypoglycemia. In
some patients, D5 normal saline or even D10 normal sailine
may be used to prevent hypoglycemia and allow intrave-
The specific treatment goals of the patient with DKA are:
1. Improve tissue perfusion and correct hypovolemia
2. Decrease the serum glucose
3. Reverse acidosis and ketonemia
4. Correct electrolyte imbalances
5. Treat the disease process that precipitated the patient’s
DKA (if present)
This is not a rigid treatment protocol but a guideline.
Each aspect of each case must be assessed individually and
reassessed frequently.
Fluids
Rehydration is the most important intervention in the
therapy of DKA; however, the optimal fluid management
for DKA is uncertain. The practitioner is faced with a patient
who is often dehydrated, yet rapid fluid administration may
predispose the patient to lethal complications.
If the patient is hypotensive, administer a bolus of 1-2
liters of normal saline (0.9%) over the first hour (pediatric
dose, 20-40 mL/kg). If hypotension persists, then give
another bolus. If the patient is normotensive, then use 0.9%
saline at 1000 cc per hour. Subsequent choice of fluids
depends on the state of hydration, serum electrolytes, and
the urinary output. When giving this much fluid to older
patients, pulmonary edema is a real possibility. The patient’s
lung sounds should be carefully monitored. If the patient
has renal failure or has a history of congestive heart failure,
then invasive monitoring with Swan catheters may be an
appropriate step. This is a clinical judgment.
In general, normal saline (0.9%) infused at 4-14 mL/
kg/hour is appropriate if the corrected serum sodium is
normal or elevated.113 Once renal function is ensured, the
infusion should include 20-30 mEq/L of potassium until the
patient is stable and can tolerate oral intake.
Provide maintenance fluids and electrolytes evenly
over the first 24 hours. Deficit fluids are usually replaced in
a bi-level fashion: One half of the deficit is replaced over the
first eight hours, and the other half of the deficit is replaced
over the next 16 hours.113
Successful fluid replacement is judged by hemodynamic stability, measurement of fluid input/output, and
clinical examination of the patient. Overhydration is a
concern when treating children with DKA, adults with
compromised renal or cardiac function, and elderly patients
with incipient congestive heart failure.
In patients with renal or cardiac insufficiency, monitoring of cardiac, renal, and mental status must be diligently
performed during the fluid resuscitation to avoid an
iatrogenic fluid overload.
In pediatric patients, the need for volume expansion
must be balanced with the risk of cerebral edema, as
discussed later in this article. Therapy must include
16
disappearance of the P wave, and widening of the QRS
complex. (Remember that the T waves usually peak if the
serum potassium is over 6 mEq/L.) Hypertonicity, deficit of
insulin, and acidosis can combine to cause extracellular
hyperkalemia. In reality, the patient has lost total body
potassium, but the lack of insulin and acidosis can
mobilize remaining intracellular potassium into the
extracellular fluid. An ECG may show these signs of
hyper- or hypokalemia before the electrolyte determination
has returned.
Multiple algorithms are described in the literature for
the replacement of potassium during therapy of DKA. The
most important part of any such algorithm is adequate
monitoring of the electrolytes during the process. If the
serum potassium is less than 5.0 mEq/L and there is a recent
history of urination, and/or the ECG has no peaked T
waves, then potassium can be started safely. Before any
potassium is given, kidney function and adequate urine
output must be established.
Bicarbonate
In DKA, calcium, magnesium, and phosphate are also
deficient. The prevalence and clinical need for replacement
of these electrolytes are not universally accepted.
Phosphate, Magnesium, And Calcium
The use of bicarbonate is not recommended for DKA.
Bicarbonate is used to treat metabolic acidosis. The rationale
for the use of bicarbonate in DKA is based on the assumption that the acidosis may contribute to morbidity in these
patients.75,76 This ignores the issue in the patient with DKA
that the appropriate treatment for ketoacidosis is not
bicarbonate, but insulin. Use of bicarbonate merely masks
the ketoacidosis. Studies of cerebral edema (outlined later in
this article) show that there is an increased risk of cerebral
edema when bicarbonate is used. Given all of these factors,
bicarbonate can’t be recommended for patients in DKA.
The American Diabetes Association guidelines suggest
the use of bicarbonate when the pH is below 6.9.6 There are
no prospective, randomized studies concerning the use of
bicarbonate in DKA in either children or adults. The support
for this part of these American Diabetes Association
guidelines, therefore, is incredibly weak.
Phosphate
Whole body phosphate deficits in DKA are substantial.
Despite this, several small studies have not shown any clear
benefit to phosphate replacement in DKA.78-80 Excessive
phosphate replacement may cause hypocalcemia and softtissue metastatic calcifications.
The clinical manifestations of severe hypophosphatemia are diverse. Alterations in the function of skeletal
and smooth muscles can lead to rhabdomyolysis, ileus,
respiratory failure, and cardiac dysfunction. Decrease in
intracellular adenosine triphosphate can result in hemolysis,
thrombocytopenia, and impaired phagocytosis. Patients also
may demonstrate metabolic encephalopathy, progressing
from irritability to coma. Indications for the clinical repletion of phosphate include left ventricular dysfunction or
failure to clear mental confusion despite improvement in
circulating volume, hyperosmolarity, and acidosis.
If the patient’s phosphate level is less than 1.0
mg/dL or if one of the above indications for phosphate
therapy is present, then give 30-60 mM of phosphate over
a 24-hour period. Obtain phosphate levels before the start
of treatment, after an infusion, and at 24 and 48 hours
into treatment.
Potassium
The major electrolyte lost during DKA is potassium. The
total body potassium deficit ranges from 300-1000 mEq total
body deficit for an adult.77 Hypokalemia is a potentially
lethal complication of DKA. The patient may have a mildly
elevated potassium level upon initial evaluation and still
have a tremendous total potassium deficit. Much potassium
is lost as the potassium salts of ketoacidosis.
Continued potassium losses are the rule during the
treatment of the patient with normal renal function and
DKA. Resolution of acidosis and concomitant administration of insulin will force the remaining extracellular
potassium into the cells. The clinician should anticipate the
massive shift of potassium carried into the cells with insulin
and the endogenous glucose loading. Insulin therapy
should not be started until the potassium level is known, in
order to prevent lethal hypokalemia.113
The electrocardiogram should be evaluated for the
signs of hyperkalemia, such as tall peaked T waves,
Magnesium
The kidney is the primary organ responsible for magnesium
homeostasis. Under normal conditions, 15% of filtered
magnesium is reabsorbed in the proximal tubule through an
active transcellular process, 60%-70% is reabsorbed passively in the thick ascending limb of the loop of Henle
driven by transepithelial voltage, and 10% is reabsorbed in
the distal tubule.119 Because magnesium reabsorption is
proportional to urine volume and flow, volume expansion
or osmotic diuresis can lead to magnesium wasting.
17
nous infusion of insulin until the subcutaneous administration of insulin is resumed.113
If the patient’s glucose is falling steadily, the anion gap
is decreasing, and the pH is improving, then the insulin
infusion is appropriate. If the glucose level does not fall in
the presence of adequate hydration and urine output, then
the patient may have insulin resistance. In this case, the
insulin dose can be doubled each hour where there is no
decrease. This insulin resistance should remind the clinician
that the patient may have sepsis, occult infection (e.g.,
endocarditis, perirectal abscess, prostatitis, or sinusitis, to
name a few), myocardial infarction, or an intra-abdominal
illness that precipitated the crisis. A few patients may have a
primary insulin resistance. The serum glucose level may
decline more rapidly in the older patient, so carefully
monitor glucose levels in these patients.
This insulin administration regimen is only a guideline.
Consider the patient’s previously injected long-acting
insulin, concurrent stress (such as a myocardial infarction),
or the concurrent administration of steroids.
may accompany the administration of insulin as potassium
is forced into the cells with insulin and sugar. (This is now
quite rare since patients are now treated with lower-dose
continuous insulin infusion rather than large boluses of
insulin.113) The clinician must follow serum potassium levels
frequently and administer a minimum of 10 mEq per hour
of potassium chloride. Severe hypokalemia is often correlated with frequent emesis, nasogastric suction, or the use of
thiazide diuretic agents. As with DKA, do not initiate
potassium replacement until it has been confirmed by the
laboratory and adequate urine output has been established.
Hypokalemia is often accompanied by hypomagnesemia. Again, the initial serum levels of magnesium
and phosphate are typically normal or elevated when
the disease process is diagnosed and may fall with
insulin administration.
Significant magnesium depletion usually is associated
with hypocalcemia and hypokalemia, since they have the
similar mechanisms.
Clinical manifestations of hypomagnesemia are
nonspecific and include weakness, dizziness, tremors,
cramps, paresthesias, and seizures.81 Severe hypomagnesemia can lead to both atrial and ventricular
arrhythmias. If the patient has a magnesium level of less
than 1.8 mEq/L or has tetany, then magnesium sulfate may
be started as 5 grams in 500 mL of normal saline administered over five hours.
Calcium
If the patient has symptomatic hypocalcemia, then 10-20 mL
(1-2 grams) of 10% calcium gluconate may be given
intravenously over 10 minutes.
Hyperosmolar Hyperglycemic Syndrome
Careful Monitoring
Adequate management of HHS requires fluid replacement;
this is the first priority of treatment. HHS patients are often
about 25% dehydrated and may require 9-12 liters of fluid
replenishment. Unfortunately, many patients with this
disease cannot tolerate either the disease or the treatment
required. Careful monitoring during this fluid therapy is
crucial, because people with hyperosmolar coma may have
compromised cardiovascular function.
Most patients can be treated with normal saline at 5001000 cc per hour until the blood pressure is normal and the
patient has good urine output. The clinician should plan on
replacing about 50% of the fluid deficit in the first 12 hours
and the remaining 50% in the subsequent 24-36 hours.113
Controversy also abounds about the proper choice of
rehydration fluid in HHS. Normal saline replaces the
intracellular volume more quickly but also increases the
possibility of fluid overload. It may provoke adult respiratory distress syndrome, particularly in patients with
potential cardiac and respiratory compromise. Hypotonic
fluids such as half-normal saline (0.45%) may be more
effective in replacing the lost free water, but risk too rapid
correction of hyponatremia with subsequent pontine
myelinonecrolysis. (Severe hypertonicity is associated with
large sodium deficits and hypovolemic shock.40,82)
An appropriate compromise is an initial fluid replacement of one liter of normal saline and then switching to half
normal saline when urine output is adequate.
Insulin, while not present in quantities sufficient to
prevent hyperglycemia, is usually present in patients with
HHS and may serve to prevent the formation of ketone
bodies. Relative insulin deficiency is exacerbated by the
patient’s dehydration. Insulin therapy is not as important as
it is in DKA. Indeed, the use of too much insulin, given too
rapidly, may cause vascular collapse as glucose and water
are moved into the cells and out of the volume-depleted
intravascular space. As in the patient with DKA, once the
glucose drops to 250 mg/dL, the patient must receive
dextrose in the intravenous fluids.
Although patients are generally not hypokalemic by
initial measurement of serum potassium, the total body
deficit may be quite high as in DKA. Lethal hypokalemia
The sicker the patient, the more frequently he or she should
be monitored. Do not wait for results to come back before
sending the next set of tests. The following parameters
should be monitored and recorded on a flow sheet:
• Glucose—every 1-2 hours by fingerstick (confirmed by
laboratory correlation when indicated)
• Basic metabolic profile for anion gap and serum
potassium—at the onset of treatment, at one and two
hours after the onset of treatment, and at two- to fourhour intervals until the patient is substantially better
• Arterial or venous pH—follow as indicated to monitor
clinical status
• Insulin dose and route of administration—every hour
• IV fluids—every hour
• Urine output—every hour
Special Circumstances
Pulmonary Edema And Adult Respiratory
Distress Syndrome
Cardiogenic and non-cardiogenic pulmonary edema can
occur in association with the treatment of DKA. These
complications more often are noted during the ICU stay, but
they may be found by the emergency physician. Excessive
fluid replacement may cause pulmonary edema even when
the cardiac function is normal. These patients should have
continuous pulse oximeter monitoring. Avoiding overzealous fluid administration should prevent cases related to
decreased colloid osmotic pressure.
Adult respiratory distress syndrome is a rare but
potentially fatal complication of the treatment of DKA.83,84 A
patient who has an increased alveolar-to-arterial oxygen
gradient on arterial blood gas or who presents with rales
may have an increased risk of adult respiratory distress
syndrome. This rare complication appears to result from an
increased capillary membrane permeability and is consequently more difficult to prevent. Treatment requires a
delicate balance between adequate rehydration and fluid
restriction needed for the treatment of the pulmonary
edema. These patients require invasive hemodynamic
monitoring and intensive pulmonary therapy.
18
diabetic patients.88,89 It is almost always a disease of children;
over 95% of cases in the largest reported series occurred
under the age of 20, and one-third of cases occurred
under the age of 5 years.88 One-fourth of the children
affected die from this complication. When cerebral edema
does occur in adults, it is quite similar in presentation to
the pediatric disease.
After initial improvement of clinical, biochemical, and
central nervous system signs in a patient with DKA, the
patient develops increasing irritability, central nervous
system depression, seizures, and coma. Cerebral edema
complicating DKA generally occurs in children who seem to
be metabolically returning to normal about 3-12 hours after
the onset of therapy.6,7
The risk factors for cerebral edema are incompletely
defined. Recent work shows that children who have a low
CO2 and a high blood urea nitrogen and then are treated
with bicarbonate are at increased risk for cerebral edema.8,90
Children who had a smaller increase in serum sodium
during therapy were also at more risk of cerebral edema.
The highest risk was found with the use of bicarbonate and
a low CO2.
The initial serum glucose and the rate of change in the
serum glucose were not associated with the development of
cerebral edema in this study. The traditional dogma has
been that these values are related to cerebral edema;
however, this appears to be completely unsubstantiated by
this study.
Previous investigations of cerebral edema in children
with DKA implicated a younger age, a new onset of the
disease,91 and a rapid rate of fluid administration as factors
associated with cerebral edema.88,92 In these studies, children
with cerebral edema were not compared with controls.
Why does it occur in children and not adults? There is
no clear answer. Some speculate that it may relate to
relatively greater brain volume, more rapid changes in
plasma osmolarity, lack of sex steroids, less developed
mechanisms for brain cell volume regulation, a difference in
taurine or other osmolyte metabolism, a difference in bloodbrain barrier efficiency, or unidentified causes.89
Why does cerebral edema with the treatment of
DKA occur at all? The pathogenesis remains an enigma.
There are a number of hypotheses attempting to explain
the development of cerebral edema, none of which are
entirely satisfactory and have remained unproven.8,93-106
The mechanisms that lead to the development of cerebral
edema in DKA probably involve a complex interaction of
many of these hypothetical mechanisms. How they relate
to fluid and electrolyte balance during the treatment of
DKA is also not known. Much more study is needed to
answer these questions.
DKA is a hypercoagulable state. The factors that precipitate
thrombosis include the hypercoagulability in the DKA
patient, stasis, and endothelial damage.85,86 The severe
dehydration and immobility that occur in DKA also
decrease perfusion of vital organs and promote stasis and
hypercoagulability.
Vascular occlusions (such as myocardial infarction,
cerebrovascular accidents, and mesenteric artery occlusions)
are important complications of both DKA and HHS.113
Predisposing factors include dehydration with resultant
increased viscosity, and preexisting coagulation abnormalities. With aggressive rehydration of the patient, the
expected incidence of these complications can be reduced
to about 2%.113
Rhabdomyolysis
Subclinical rhabdomyolysis, possibly owing to shrinkage of
muscle cells and impaired glucose use, is a common finding
in patients with HHS (and to a lesser degree with DKA), but
secondary acute renal failure is extremely rare.113 Many
patients do not develop myoglobinuria; thus, monitoring
serum creatinine phosphokinase levels is the most sensitive
way to screen for this potentially serious complication.
Acute Gastric Dilatation
Acute gastric dilatation is a relatively uncommon but
potentially lethal problem. If the patient is distended, then
other causes of intra-abdominal pathology must be sought
first. A nasogastric tube will make the diagnosis and serve
as therapy if the patient continues to vomit.
Electrolyte Disorders
Treatment for DKA can cause life-threatening, predictable,
and avoidable acute complications such as hypokalemia,
hyponatremia, and fluid overload. These are common yet
preventable complications of the treatment of diabetic
emergencies.
Hyperchloremic Metabolic Acidosis
Hyperchloremic metabolic acidosis with a normal anion gap
often persists after the resolution of ketonemia. This acidosis
has no adverse clinical effects and is gradually corrected
over the subsequent 24-48 hours by enhanced renal acid
excretion.87 Hyperchloremia can be aggravated by excessive
chloride administration during the rehydration phase.
Seizures
Seizures associated with HHS are often resistant to typical
antiseizure medications.120 Phenytoin may further exacerbate the HHS.120 The emergency physician should be
aware of this problem with seizure control and proceed
to alternative agents such as barbiturates if benzodiazepines
are not effective.
Management Of Cerebral Edema
Cerebral Edema—A Pediatric Problem
Children with the biochemical features of cerebral edema
should be monitored carefully during therapy. If any sign of
neurologic deterioration is noted, hyperosmolar therapy
should be readily available and neurologic consultation
sought. Two of the risk factors identified in the study by
Cerebral edema is the most feared complication of DKA and
may have driven many of the changes in the management
of DKA over the past few decades.
Cerebral edema occurs in about 1% of DKA cases and is
the most common cause of diabetes-related death in young
19
Vascular Complications
Summary
Glaser et al were blood urea nitrogen and CO2 at presentation, which can’t be altered by ED therapy. However, the
third risk factor—bicarbonate administration—is directly
within the realm of ED care. Bicarbonate is associated with
several risks, including cerebral edema, and should be
avoided if possible.
Initial therapy of cerebral edema should be the use of
mannitol as an osmotic diuretic to lower the intracranial
pressure. Recent studies show that for maximum effect,
mannitol should be given within 5-10 minutes of the initial
deterioration in neurologic function.107,108
A more favorable outcome has been reported when
intracranial pressure monitoring is used in addition to
mannitol.109 The role of dexamethasone and diuretics has
not been established.
DKA and HHS are among the most lethal complications of
diabetes. Furthermore, they can occur with other serious
comorbid illnesses or infection—or as the patient’s initial
presentation of diabetes. With the growing incidence
diabetes, it is all the more necessary for the prompt identification and effective management of these complications to
be a part of every emergency physician’s armamentarium.
The major complications related to the treatment of
DKA and HHS include hypoglycemia, hypokalemia, and,
rarely, cerebral edema. The use of low-dose insulin regimens, potassium replacement early in management, the
addition of glucose to intravenous solutions, and attentive
monitoring of therapeutic response should significantly
reduce these complications. ▲
HHS And Cerebral Edema
References
Cerebral edema is generally not seen in adults with HHS.
Because undertreatment of HHS carries an increased risk for
mortality, rapid correction of hyperosmolarity to an effective
serum osmolarity under 320 mOsm/L and correction of the
glucose to about 250-300 mg/dL is the goal of early
therapy.110 This approach differs from the one used to correct
hyperosmolarity in DKA.
Evidence-based medicine requires a critical appraisal of the
literature based upon study methodology and number of
subjects. Not all references are equally robust. The findings
of a large, prospective, randomized, and blinded trial
should carry more weight than a case report.
To help the reader judge the strength of each reference,
pertinent information about the study, such as the type of
study and the number of patients in the study, will be
included in bold type following the reference, where
available. In addition, the most informative references cited
in the paper, as determined by the authors, will be noted by
an asterisk (*) next to the number of the reference.
Cutting Edge
There are many exciting developments in the management
of the diabetic patient that have not been covered in this
article. Inhaled delivery of insulin is in the final stages of
field testing.121 Gene therapy for some of the variants
of diabetes is in planning stages.122 Insulin pumps that
measure the glucose and deliver the exact dose—an
artificial pancreas—are under development.123 This device
would make DKA much less common, as the patient would
not be able to forget or misread the delivered dose of
insulin. Sick days and exercise doses of insulin would be
automatically compensated.
1.
2.
3.*
Disposition
4.
The patient with DKA or HHS requires hospital admission
to a unit where the patient’s neurologic status and vital
signs can be monitored frequently and blood glucose (or
fingerstick glucose) can be measured hourly.
Severely decompensated diabetes should be managed
in the ICU. Admit the patient to the ICU if:
• the patient has hemodynamic instability;
• the patient is unable to defend the airway (this patient
should be promptly intubated);
• the patient is obtunded (this patient should also be
promptly intubated);
• abdominal distention, acute abdominal signs, or
symptoms suggestive of acute gastric dilatation are
present (surgical consultation should be considered for
these patients);
• insulin infusions cannot be administered on the ward;
• monitoring cannot be provided on the ward; or
• the patient has a co-morbid disease such as sepsis,
myocardial infarction, or trauma.
5.*
6.
7.
8.
9.
10.
11.
20
No authors listed. Diabetes: 1991 vital statistics. Alexandria, VA:
American Diabetes Association; 1991. (Statistical compilation)
Fishbein H, Palumbo PJ. Acute metabolic complications in diabetes. In:
Diabetes in America. Washington, DC, NIH Publication No. 95-1468,
283-291. (Statistical compilation)
Carroll P, Matz R. Uncontrolled diabetes mellitus in adults: experience
in treating diabetic ketoacidosis and hyperosmolar nonketotic coma
with low-dose insulin and a uniform treatment regimen. Diabetes Care
1983 Nov-Dec;6(6):579-585. (Retrospective; 275 cases)
Kitabchi AE, Umpierrez GE, Murphy MB; American Diabetes
Association. Hyperglycemic crises in patients with diabetes mellitus.
Diabetes Care 2003 Jan;26 Suppl 1:S109-S117. (Review)
Rewers A, Chase HP, Mackenzie T, et al. Predictors of acute complications in children with type I diabetes. JAMA 2002 May 15;287(19):25112518. (Prospective cohort over four years; 1243 patients)
Bratton SL, Krane EJ. Diabetic ketoacidosis: pathophysiology,
management and complications. J Intensive Care Med 1992;7:199-211.
(Review)
Krane EJ, Rockoff MA, Wallman JK, et al. Subclinical brain swelling in
children during treatment of diabetic ketoacidosis. N Engl J Med 1985
May 2;312(18):1147-1151. (Convenience sampling; 6 children—shows
that even asymptomatic children may have signs of cerebral edema
on CT scan)
Glaser N, Barnett P, McCaslin I, et al; Pediatric Emergency Medicine
Collaborative Research Committee of the American Academy of
Pediatrics. 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 Jan 25;344(4):264-269. (Retrospective, case-control; 61
children)
Boden G. Glucagonomas and insulinomas. Gastroenterol Clin North Am
1989 Dec;18(4):831-845. (Review)
Kukreja A, Maclaren NK. Autoimmunity and diabetes. J Clin
Endocrinol Metab 1999 Dec;84(12):4371-4378. (Review)
Decochez K, Keymeulen B, Somers G, et al; Belgian Diabetes Registry.
Use of an islet cell antibody assay to identify type I diabetic patients
with rapid decrease in C-peptide levels after clinical onset. Belgian
13.
14.
15.
16.*
17.
18.
19.*
20.
21.
22.
23.
24.
25.
26.
27.*
28.
29.
30.
31.
32.
33.
34.*
35.
36.
37.
38.
39.
21
12.
North Am 1995 Jan;79(1):39-52. (Review)
Khardori R, Soler NG. Hyperosmolar hyperglycemic nonketotic
syndrome. Report of 22 cases and brief review. Am J Med 1984
Nov;77(5):899-904. (Review, case report)
40. Arieff AI, Carroll HJ. Nonketotic hyperosmolar coma with hyperglycemia: clinical features, pathophysiology, renal function, acid-base
balance, plasma-cerebrospinal fluid equilibria and the effects of
therapy in 37 cases. Medicine (Baltimore) 1972 Mar;51(2):73-94.
(Retrospective; 37 cases)
41. Wachtel TJ, Silliman RA, Lamberton P. Prognostic factors in the
diabetic hyperosmolar state. J Am Geriatr Soc 1987 Aug;35(8):737-741.
(Retrospective; 135 patients)
42. Lorber D. Nonketotic hypertonicity in diabetes mellitus. Med Clin
43. Umpierrez GE, Khajavi M, Kitabchi AE. Review: diabetic ketoacidosis
and hyperglycemic hyperosmolar nonketotic syndrome. Am J Med Sci
1996 May;311(5):225-233. (Review)
44. Wachtel TJ, Tetu-Mouradjian LM, Goldman DL, et al. Hyperosmolarity
and acidosis in diabetes mellitus: a three-year experience in Rhode
Island. J Gen Intern Med 1991 Nov-Dec;6(6):495-502. (Retrospective; 613
patients)
45. Ellemann K, Soerensen JN, Pedersen L, et al. Epidemiology and
treatment of diabetic ketoacidosis in a community population. Diabetes
Care 1984 Nov-Dec;7(6):528-532. (Epidemiological statistical review)
46. Umpierrez GE, Kelly JP, Navarrete JE, et al. Hyperglycemic crises in
urban blacks. Arch Intern Med 1997 Mar 24;157(6):669-675. (Prospective; 144 patients)
47. Kitabchi AE, Umpierrez GE, Murphy MB, et al. Management of
hyperglycemic crises in patients with diabetes. Diabetes Care 2001
Jan;24(1):131-153. (Review)
48.* No authors listed. American Diabetes Association. Position statement:
hyperglycemic crises in patients with diabetes mellitus. Diabetes Care
2002;25:S100-S108. (Consensus statement, review)
49. Laffel L. Sick-day management in type I diabetes. Endocrinol Metab Clin
North Am 2000 Dec;29(4):707-723. (Review)
50. Bress P, DeFronzo RA. Drugs and diabetes. Diabetes Rev 1994;2:53-84.
(Review)
51. Harrison BD, Rutter TW, Taylor RT. Severe non-ketotic hyperglycaemic
pre-coma in a hypertensive patient receiving diazoxide. Lancet 1972
Sep 16;2(7777):599-600. (Review, case report)
52. Ahmad S. Diltiazem and hyperglycemia-coma. J Am Coll Cardiol 1985
Aug;6(2):494. (Letter, case report)
53. Fonseca V, Phear DN. Hyperosmolar non-ketotic diabetic syndrome
precipitated by treatment with diuretics. Br Med J (Clin Res Ed) 1982 Jan
2;284(6308):36-37. (Case report)
54. Hollis WC. Aggravation of diabetes mellitus during treatment with
chlorothiazide. JAMA 1961 Jun 17;176:947-949. (Case report)
55. Podolsky S, Pattavina CG. Hyperosmolar nonketotic diabetic coma: a
complication of propranolol therapy. Metabolism 1973 May;22(5):685693. (Case report)
56. Hiler B. Hyperglycemia and glycosuria following chlorpromazine
therapy. JAMA 1956;162:1651-1652. (Case report)
57. Sypniewski E Jr, Mirtallo JM, Schneider PJ. Hyperosmolar, hyperglycemic, nonketotic coma in a patient receiving home total parenteral
nutrient therapy. Clin Pharm 1987 Jan;6(1):69-73. (Case report)
58. Ennis ED, Stachl EJ, Kreisberg RA. The hyperosmolar hyperglycemic
syndrome. Diabetes Rev 1994;2:115-126. (Review)
59. Axelrod L. Insulin, prostaglandins, and the pathogenesis of
hypertension. Diabetes 1991 Oct;40(10):1223-1227. (Review)
60. Axelrod L. Diabetic ketoacidosis. Endocrinologist 1992;2:375-383.
(Review)
61. Fulop M, Tannenbaum H, Dreyer N. Ketotic hyperosmolar coma.
Lancet 1973 Sep 22;2(7830):635-639. (Retrospective; 70 cases)
62. Arieff AI, Carroll HJ. Cerebral edema and depression of sensorium in
nonketotic hyperosmolar coma. Diabetes 1974 Jun;23(6):525-531.
(Retrospective; 53 cases)
63. Morres CA, Dire DJ. Movement disorders as a manifestation of
nonketotic hyperglycemia. J Emerg Med 1989 Jul-Aug;7(4):359-364.
(Review, case report; 2 patients)
64. Lorber D. Nonketotic hypertonicity in diabetes mellitus. Med Clin
65. Harden CL, Rosenbaum DH, Daras M. Hyperglycemia presenting
with occipital seizures. Epilepsia 1991 Mar-Apr;32(2):215-220. (Case
report)
66. Duncan MB, Jabbari B, Rosenberg ML. Gaze-evoked visual seizures in
nonketotic hyperglycemia. Epilepsia 1991 Mar-Apr;32(2):221-224. (Case
report)
67. Slovis CM, Mork VG, Slovis RJ, et al. Diabetic ketoacidosis and
Diabetes Registry. Diabetes Care 2000 Aug;23(8):1072-1078. (Case
series; 172 patients)
Leslie RD, Pozzilli P. Type I diabetes masquerading as type II diabetes.
Possible implications for prevention and treatment. Diabetes Care 1994
Oct;17(10):1214-1219. (Review)
Bliss M. The Discovery of Insulin. Chicago: University of Chicago Press;
1982:112-113. (Historical reference)
White JR Jr, Campbell RK, Hirsch I. Insulin analogues: new agents for
improving glycemic control. Postgrad Med 1997 Feb;101(2):58-60, 63-65,
70. (Review)
Crawford PB, Story M, Wang MC, et al. Ethnic issues in the epidemiology of childhood obesity. Pediatr Clin North Am 2001 Aug;48(4):855878. (Review)
No authors listed. Type II diabetes in children and adolescents.
American Diabetes Association. Diabetes Care 2000 Mar;23(3):381-389.
(Practice guideline, consensus statement)
Fagot-Campagna A, Pettitt DJ, Engelgau MM, et al. Type II diabetes
among North American children and adolescents: an epidemiologic
review and a public health perspective. J Pediatr 2000 May;136(5):664672. (Multicase review)
Edelman SV. Importance of glucose control. Med Clin North Am 1998
Jul;82(4):665-687. (Review)
Le Roith D, Zick Y. Recent advances in our understanding of insulin
action and insulin resistance. Diabetes Care 2001 Mar;24(3):588-597.
(Review)
Buse JB. The use of insulin alone and in combination with oral agents
in type II diabetes. Prim Care 1999 Dec;26(4):931-950. (Review)
Fajans SS, Floyd JC Jr, Pek S, et al. The course of asymptomatic
diabetes in young people, as determined by levels of blood glucose
and plasma insulin. Trans Assoc Am Physicians 1969;82:211-224.
(Historical review)
Fajans SS, Floyd JC Jr, Conn JW, et al. The course of asymptomatic
diabetes of children, adolescents, and young adults. Adv Metab Disord
1970;1:Suppl 1:377. (Historical review)
Tattersall RB, Fajans SS. A difference between the inheritance of
classical juvenile-onset and maturity-onset type diabetes of young
people. Diabetes 1975 Jan;24(1):44-53. (Historical review)
Tattersall RB. Mild familial diabetes with dominant inheritance. Q J
Med 1974 Apr;43(170):339-357. (Historical review)
Fajans SS. Scope and heterogeneous nature of MODY. Diabetes Care
1990 Jan;13(1):49-64. (Review)
Hattersley AT. Maturity-onset diabetes of the young: clinical
heterogeneity explained by genetic heterogeneity. Diabet Med 1998
Jan;15(1):15-24. (Review)
Froguel P. Glucokinase and MODY: from the gene to the disease.
Diabet Med 1996 Sep;13(9 Suppl 6):S96-S97. (Review)
Fajans SS, Bell GI, Polonsky KS. Molecular mechanisms and clinical
pathophysiology of maturity-onset diabetes of the young. N Engl J Med
2001 Sep 27;345(13):971-980. (Review)
Byrne MM, Sturis J, Fajans SS, et al. Altered insulin secretory responses
to glucose in subjects with a mutation in the MODY1 gene on
chromosome 20. Diabetes 1995 Jun;44(6):699-704. (Case-control; 10
patients)
Byrne MM, Sturis J, Clement K, et al. Insulin secretory abnormalities in
subjects with hyperglycemia due to glucokinase mutations. J Clin
Invest 1994 Mar;93(3):1120-1130. (Case control; 6 patients)
Byrne MM, Sturis J, Menzel S, et al. Altered insulin secretory responses
to glucose in diabetic and nondiabetic subjects with mutations in the
diabetes susceptibility gene MODY3 on chromosome 12. Diabetes 1996
Nov;45(11):1503-1510. (Case control; 18 patients)
Kolterman OG, Buse JB, Fineman MS, et al. Synthetic exendin-4
(exenatide) significantly reduces postprandial and fasting plasma
glucose in subjects with type II diabetes. J Clin Endocrinol Metab 2003
Jul;88(7):3082-3089. (Controlled clinical trial [Phase III]; 37 patients)
Fleckman AM. Diabetic ketoacidosis. Endocrinol Metab Clin North Am
1993 Jun;22(2):181-207. (Review)
Kitabchi AE, Murphy MB. Diabetic ketoacidosis and hyperosmolar
hyperglycemic nonketotic coma. Med Clin North Am 1988
Nov;72(6):1545-1563. (Review)
Bagdade JD, Porte D Jr, Bierman EL. Diabetic lipemia. A form of
acquired fat-induced lipemia. N Engl J Med 1967 Feb 23;276(8):427-433.
(Review, case report)
Rumbak MJ, Hughes TA, Kitabchi AE. Pseudonormoglycemia in
diabetic ketoacidosis with elevated triglycerides. Am J Emerg Med 1991
Jan;9(1):61-63. (Case report)
Rose BD. Proximal tubule. In: Rose BD. Clinical Physiology of Acid-Base
and Electrolyte Disorders. New York: McGraw-Hill; 1989:102. (Review)
Lorber D. Nonketotic hypertonicity in diabetes mellitus. Med Clin
infection: leukocyte count and differential as early predictors of serious
infection. Am J Emerg Med 1987 Jan;5(1):1-5. (Retrospective; 153
patients)
68. 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 Apr;31(4):459-465.
(Retrospective; 38 patients with 44 episodes of DKA)
69. Gokel Y, Paydas S, Koseoglu Z, et al. Comparison of blood gas and
acid-base measurements in arterial and venous blood samples in
patients with uremic acidosis and diabetic ketoacidosis in the
emergency room. Am J Nephrol 2000 Jul-Aug;20(4):319-323. (Retrospective; 100 uremic patients, 21 diabetic patients, and 31 normal controls
with a total of 152 venous and arterial samples)
70. Small M, Alzaid A, MacCuish AC. Diabetic hyperosmolar non-ketotic
decompensation. Q J Med 1988 Mar;66(251):251-257. (Retrospective; 22
patients)
71. Levine SN, Sanson TH. Treatment of hyperglycaemic hyperosmolar
non-ketotic syndrome. Drugs 1989 Sep;38(3):462-472. (Review)
72. Scibilia J, Finegold D, Dorman J, et al. Why do children with diabetes
die? Acta Endocrinol Suppl (Copenh) 1986;279:326-333. (Retrospective;
55 cases)
73.* Wiggam MI, O’Kane MJ, Harper R, et al. Treatment of diabetic
ketoacidosis using normalization of blood 3-hydroxybutyrate
concentration as the endpoint of emergency management. A
randomized controlled study. Diabetes Care 1997 Sep;20(9):1347-1352.
(Randomized, controlled trial; 22 adult patients [11 in each study
arm])
74. Kitabchi AE, Young R, Sacks H, et al. Diabetic ketoacidosis: reappraisal
of therapeutic approach. Annu Rev Med 1979;30:339-357. (Review)
75. Morris LR, Murphy MB, Kitabchi AE. Bicarbonate therapy in severe
diabetic ketoacidosis. Ann Intern Med 1986 Dec;105(6):836-840.
(Randomized, controlled trial; 21 adult patients)
76. Viallon A, Zeni F, Lafond P, et al. Does bicarbonate therapy improve
the management of severe diabetic ketoacidosis? Crit Care Med 1999
Dec;27(12):2690-2693. (Retrospective; 39 patients)
77. Van Gaal L, De Leeuwen I, Beaker J. Serum potassium levels in
untreated diabetic ketoacidosis. Diabetoliga 1981;21:338A. (Retrospective; 22 cases)
78. Fisher JN, Kitabchi AE. A randomized study of phosphate therapy in
the treatment of diabetic ketoacidosis. J Clin Endocrinol Metab 1983
Jul;57(1):177-180. (Randomized, controlled trial; 30 patients)
79. Wilson HK, Keuer SP, Lea AS, et al. Phosphate therapy in diabetic
ketoacidosis. Arch Intern Med 1982 Mar;142(3):517-520. (Randomized,
controlled trial; 44 patients)
80. Zipf WB, Bacon GE, Spencer ML, et al. Hypocalcemia, hypomagnesemia, and transient hypoparathyroidism during therapy with
potassium phosphate in diabetic ketoacidosis. Diabetes Care 1979 MayJun;2(3):265-268. (Case report)
81. Bell DR, Woods RL, Levi JA. cis-Diamminedichloroplatinum-induced
hypomagnesemia and renal magnesium wasting. Eur J Cancer Clin
Oncol 1985 Mar;21(3):287-290. (Prospective; 50 patients; describes
symptoms of hypomagnesemia well)
82. Pinies JA, Cairo G, Gaztambide S, et al. Course and prognosis of 132
patients with diabetic non ketotic hyperosmolar state. Diabetes Metab
1994 Jan-Feb;20(1):43-48. (Retrospective; 132 cases)
83. Carroll P, Matz R. Adult respiratory distress syndrome complicating
severely uncontrolled diabetes mellitus: report of nine cases and a
review of the literature. Diabetes Care 1982 Nov-Dec;5(6):574-580. (Case
report; 9 patients)
84. Oh MS, Carroll HJ, Uribarri J. Mechanism of normochloremic and
hyperchloremic acidosis in diabetic ketoacidosis. Nephron 1990;54(1):16. (Review)
85. Kitches CS. Concepts of hypercoagulability: A review of its development, clinical application, and recent progress. Semin Thromb Hemostas
1985;11:293-315. (Review)
86. Lavis VR, D’Souza D, Brown SD. Decompensated diabetes. New
features of an old problem. Circulation 1994 Dec;90(6):3108-3112.
(Review, clinical conference)
87. DeFronzo RA, Matsuda M, Barret EJ. Diabetic ketoacidosis A
combined metabolic-nephrologic approach to therapy. Diabetes Rev
1994;2:209-238. (Review)
88. Rosenbloom AL. Intracerebral crises during treatment of diabetic
ketoacidosis. Diabetes Care 1990 Jan;13(1):22-33. (Retrospective; 69
cases)
89. Edge JA. Cerebral oedema during treatment of diabetic ketoacidosis:
are we any nearer finding a cause? Diabetes Metab Res Rev 2000 SepOct;16(5):316-324. (Review)
90. Mahoney CP, Vlcek BW, DelAguila M. Risk factors for developing
91.*
92.
93.
94.
95.
96.
97.
98.*
99.
100.
101.
102.
103.
104.
105.
106.
107.
108.
109.
110.
111.
112.
113.*
114.
115.
22
brain herniation during diabetic ketoacidosis. Pediatr Neurol 1999
Oct;21(4):721-727. (Retrospective; 153 children)
Edge JA, Hawkins MM, Winter DL, et al. The risk and outcome of
cerebral oedema developing during diabetic ketoacidosis. Arch Dis
Child 2001 Jul;85(1):16-22. (Prospective, population-based statistical
study; 20 children with DKA and cerebral edema)
Duck SC, Wyatt DT. Factors associated with brain herniation in the
treatment of diabetic ketoacidosis. J Pediatr 1988 Jul;113(1 Pt 1):10-14.
(Retrospective [33 cases]; case report [9 cases])
Arieff AI, Kleeman CR. Studies on mechanisms of cerebral edema in
diabetic comas. Effects of hyperglycemia and rapid lowering of plasma
glucose in normal rabbits. J Clin Invest 1973 Mar;52(3):571-583.
(Animal study)
Arieff AI, Kleeman CR. Cerebral edema in diabetic comas. II. Effects of
hyperosmolality, hyperglycemia and insulin in diabetic rabbits. J Clin
Endocrinol Metab 1974 Jun;38(6):1057-1067. (Animal study)
Rother KI, Schwenk WF 2nd. Effect of rehydration fluid with 75
mmol/L of sodium on serum sodium concentration and serum
osmolality in young patients with diabetic ketoacidosis. Mayo Clin Proc
1994 Dec;69(12):1149-1153. (Retrospective; 18 episodes)
Felner EI, White PC. Improving management of diabetic ketoacidosis
in children. Pediatrics 2001 Sep;108(3):735-740. (Retrospective; 520
patients)
Rosenbloom AL. Cerebral edema in diabetic ketoacidosis. J Clin
Endocrinol Metab 2000;85:508-509. (Editorial, case report; 2 cases)
Rutledge J, Couch R. Initial fluid management of diabetic ketoacidosis
in children. Am J Emerg Med 2000 Oct;18(6):658-660. (Retrospective; 49
cases of DKA in 37 patients)
Glasgow AM. Devastating cerebral edema in diabetic ketoacidosis
before therapy. Diabetes Care 1991 Jan;14(1):77-78. (Letter, case report)
Couch RM, Acott PD, Wong GW. Early onset fatal cerebral edema in
diabetic ketoacidosis. Diabetes Care 1991 Jan;14(1):78-79. (Letter, case
report)
Edge JA, Ford-Adams ME, Dunger DB. Causes of death in children
with insulin dependent diabetes 1990-96. Arch Dis Child 1999
Oct;81(4):318-323. (Retrospective; 83 deaths caused by diabetes)
Clements RS Jr, Blumenthal SA, Morrison AD, et al. Increased
cerebrospinal fluid pressure during therapy for diabetic acidosis. Trans
Assoc Am Physicians 1971;84:102-112. (Case report)
Fein IA, Rachow EC, Sprung CL, et al. Relation of colloid osmotic
pressure to arterial hypoxemia and cerebral edema during crystalloid
volume loading of patients with diabetic ketoacidosis. Ann Intern Med
1982 May;96(5):570-575. (Prospective; 18 patients)
Hoffman WH, Pluta RM, Fisher AQ, et al. Transcranial Doppler
ultrasound assessment of intracranial hemodynamics in children with
diabetic ketoacidosis. J Clin Ultrasound 1995 Nov-Dec;23(9):517-523.
(Convenience sample)
Hoffman WH, Steinhart CM, el Gammal T, et al. Cranial CT in children
and adolescents with diabetic ketoacidosis. AJNR Am J Neuroradiol
1988 Jul-Aug;9(4):733-739. (Convenience sample; 9 patients)
Hoffman WH, Casanova MF, Bauza JA, et al. Computer analysis of
magnetic resonance imaging of the brain in children and adolescents
after treatment of diabetic ketoacidosis. J Diabetes Complications 1999
Jul-Aug;13(4):176-181. (Convenience sample; 6 patients)
Duck SC, Kohler E. Cerebral edema in diabetic ketoacidosis. J Pediatr
1981 Apr;98(4):674-676. (Letter)
Franklin B, Liu J, Ginsberg-Fellner F. Cerebral edema and ophthalmoplegia reversed by mannitol in a new case of insulin-dependent
diabetes mellitus. Pediatrics 1982 Jan;69(1):87-90. (Case report)
Wood EG, Go-Wingkun J, Luisiri A, et al. Symptomatic cerebral
swelling complicating diabetic ketoacidosis documented by
intraventricular pressure monitoring: survival without neurologic
sequela. Pediatr Emerg Care 1990 Dec;6(4):285-288. (Case report)
Matz R. Management of the hyperosmolar hyperglycemic syndrome.
Am Fam Physician 1999 Oct 1;60(5):1468-1476. (Review)
Inward CD, Chambers TL. Fluid management in diabetic ketoacidosis.
Arch Dis Child 2002 Jun;86(6):443-444. (Review)
LaPorte RE, Matsushima M, Chang Y-F. Prevalence and incidence of
insulin dependent diabetes. http://diabetes.niddk.nih.gov/dm/
pubs/America/pdf/chapter3.pdf. (Statistical analysis)
Magee MF, Bhatt BA. Management of decompensated diabetes.
Diabetic ketoacidosis and hyperglycemic hyperosmolar syndrome. Crit
Care Clin 2001 Jan;17(1):75-106. (Review)
U.S. preventative services task force. Screening for gestational diabetes:
Recommendations and rationale. http://www.ahcpr.gov/clinic/
3rduspstf/gdmrr.pdf. (Consensus practice guidelines)
Delaney MF, Zisman A, Kettyle WM. Diabetic ketoacidosis and
hyperglycemic hyperosmolar nonketotic syndrome. Endocrinol Metab
23. Ketoacidosis:
a. is profound in DKA but is minimal in HHS.
b. is profound in HHS but is minimal in DKA.
c. is profound in both DKA and HHS.
d. rarely occurs except in severe cases of DKA.
24. Dehydration:
a. is severe in DKA but is minimal in HHS.
b. is severe in HHS but is minimal in DKA.
c. is severe in both DKA and HHS.
d. rarely occurs in hyperglycemic disorders.
25. Neurologic symptoms such as seizures and coma:
a. are common in DKA but rare in HHS.
b. are common in HHS but rare in DKA.
c. are common in both DKA and HHS.
d. rarely occur in hyperglycemic disorders.
Physician CME Questions
26. Which of the following is not a common sign/
symptom of hyperglycemia?
a. Nervousness/perspiration
b. Polyuria
c. Polydipsia
d. Fatigue and weakness
17. Type I diabetes results from a decreased secretion
of insulin, and type II diabetes results from
insulin resistance.
a. True
b. False
18. Latent autoimmune diabetes of adults:
a. presents very similarly to the way diabetes
presents in children.
b. has a rapid onset.
c. can often be managed on oral agents at first, but all
patients will eventually require insulin therapy.
d. is a form of type II diabetes.
27. Hyperglycemic emergencies:
a. rarely occur in patients with previously undiagnosed diabetes.
b. are associated with very low morbidity.
c. often occur in conjunction with other illnesses
or infection.
d. rarely require hospital admission.
19. Prolonged hyperglycemia in the type II diabetic can
cause all of the following except:
a. obesity.
b. type I diabetes.
c. high blood pressure.
d. renal failure.
28. Which of the following medications is not known to
cause or complicate diabetes?
a. Glucocorticosteroids (methylprednisolone,
prednisone)
b. NSAIDs
c. High blood pressure medications (furosemide,
clonidine, and thiazide diuretics)
d. Drugs with hormonal activity (oral contraceptives,
thyroid hormone, and progestins)
20. Oral medications for type II diabetes work by:
a. causing the pancreas to make more insulin.
b. making the tissues more sensitive to the effects
of insulin.
c. decreasing hepatic output of glucose.
d. decreasing absorption of glucose from the gut.
e. any of the above.
29. Which of the following factors may prevent a patient
from receiving adequate insulin?
a. Lack of funds to buy insulin, syringes, etc.
b. Psychological problems, including eating disorders
or dementia
c. Recent changes in diet or exercise
d. Recent illness, especially if the patient is unable to
eat normally
e. Any of the above
21. Which of the following is not known to cause
diabetes?
a. Pancreatic disorders, including pancreatic
cancer, chronic pancreatitis, hemachromatosis,
and cystic fibrosis
b. Pregnancy
c. Use of glucocorticosteroids such as methylprednisolone or prednisone
d. Vegetarianism
30. Laboratory findings of a glucose level greater
than 250 mg/dL, a pH less than 7.35, a serum
bicarbonate of 12-15 mEq/L, a high anion gap, and
positive ketones suggest:
a. DKA.
b. HHS.
c. both DKA and HHS.
d. neither DKA nor HHS.
22. DKA most frequently occurs in the elderly, while
HHS most frequently occurs in children.
a. True
b. False
23
Clin North Am 2000 Dec;29(4):683-705, V. (Review)
116.* No authors listed. Standards of medical care in diabetes. Diabetes Care
2004 Jan;27(Suppl 1):S15-S35. (Position statement, clinical guideline)
117. White NH. Diabetic ketoacidosis in children. Endocrinol Metab Clin
North Am 2000 Dec;29(4):657-682. (Review)
118.* Adler E, Paauw D. Medical myths involving diabetes. Prim Care 2003
Sep;30(3):607-618. (Review)
119. Kapoor M, Chan GZ. Fluid and electrolyte abnormalities. Crit Care Clin
2001 Jul;17(3):503-529. (Review)
120. Trence DL, Hirsch IB. Hyperglycemic crises in diabetes mellitus type 2.
Endocrinol Metab Clin North Am 2001 Dec;30(4):817-831. (Review)
121. No authors listed. Inhaled insulin could become a reality soon. Diabetes
Monitor http://www.diabetesmonitor.com/inhaledi.htm. (News
release of phase III trials)
122. No authors listed. VA researchers develop potential gene therapy for
diabetes. VA Research and Development http://www1.va.gov/resdev/
highlights/diabetes.htm. (News release of animal studies)
123. Gano S. Artificial pancreas. Energy Science News http://www.pnl.gov/
energyscience/06-01/ws.htm. (News release)
Physician CME Information
31. DKA treatment goals are to improve tissue perfusion
and correct hypovolemia; decrease the serum glucose;
reverse acidosis and ketonemia; correct electrolyte
imbalances; and treat coexisting disease.
a. True
b. False
This CME enduring material is sponsored by Mount Sinai School of Medicine and
has been planned and implemented in accordance with the Essentials and
Standards of the Accreditation Council for Continuing Medical Education. Credit
may be obtained by reading each issue and completing the printed post-tests
administered in December and June or online single-issue post-tests
administered at www.empractice.net.
Target Audience: This enduring material is designed for emergency medicine
physicians.
32. Cerebral edema:
a. is almost always a disease of adults and rarely
occurs in children.
b. is more common in patients who have a low CO2, a
high blood urea nitrogen, and who are then treated
with bicarbonate.
c. rarely requires a neurologic consult.
d. is common among adults with HHS.
Needs Assessment: The need for this educational activity was determined by a
survey of medical staff, including the editorial board of this publication; review
of morbidity and mortality data from the CDC, AHA, NCHS, and ACEP; and
evaluation of prior activities for emergency physicians.
Date of Original Release: This issue of Emergency Medicine Practice was published
February 1, 2004. This activity is eligible for CME credit through February 1,
2007. The latest review of this material was January 9, 2004.
Discussion of Investigational Information: As part of the newsletter, faculty may
be presenting investigational information about pharmaceutical products that
is outside Food and Drug Administration approved labeling. Information
presented as part of this activity is intended solely as continuing medical
education and is not intended to promote off-label use of any pharmaceutical
product. Disclosure of Off-Label Usage: This issue of Emergency Medicine Practice
discusses no off-label use of any pharmaceutical product.
Coming in Future Issues:
Acute Coronary Syndromes • Gastrointestinal Hemorrhage •
Deep Venous Thrombosis
Faculty Disclosure: In compliance with all ACCME Essentials, Standards, and
Guidelines, all faculty for this CME activity were asked to complete a full
disclosure statement. The information received is as follows: Dr. Stewart, Dr.
Marco, and Dr. Mattu report no significant financial interest or other relationship
with the manufacturer(s) of any commercial product(s) discussed in this
educational presentation.
Class Of Evidence Definitions
Each action in the clinical pathways section of Emergency Medicine Practice
receives an alpha-numerical score based on the following definitions.
Class I
• Always acceptable, safe
• Definitely useful
• Proven in both efficacy and
effectiveness
Level of Evidence:
• One or more large prospective
studies are present (with
rare exceptions)
• High-quality meta-analyses
• Study results consistently
positive and compelling
Class II
• Safe, acceptable
• Probably useful
Level of Evidence:
• Generally higher levels
of evidence
• Non-randomized or retrospective studies: historic, cohort, or
case-control studies
• Less robust RCTs
• Results consistently positive
Class III
• May be acceptable
• Possibly useful
• Considered optional or
alternative treatments
Level of Evidence:
• Generally lower or intermediate
levels of evidence
• Case series, animal studies,
consensus panels
• Occasionally positive results
Accreditation: Mount Sinai School of Medicine is accredited by the Accreditation
Council for Continuing Medical Education to sponsor continuing medical
education for physicians.
Indeterminate
• Continuing area of research
• No recommendations until
further research
Credit Designation: Mount Sinai School of Medicine designates this educational
activity for up to 4 hours of Category 1 credit toward the AMA Physician’s
Recognition Award. Each physician should claim only those hours of credit
actually spent in the educational activity. Emergency Medicine Practice is approved
by the American College of Emergency Physicians for 48 hours of ACEP Category
1 credit (per annual subscription). Emergency Medicine Practice has been reviewed
and is acceptable for up to 48 Prescribed credit hours by the American Academy
of Family Physicians. Emergency Medicine Practice has been approved for 48
Category 2-B credit hours by the American Osteopathic Association.
Level of Evidence:
• Evidence not available
• Higher studies in progress
• Results inconsistent,
contradictory
• Results not compelling
Earning Credit: Two Convenient Methods
Significantly modified from: The
Emergency Cardiovascular Care
Committees of the American Heart
Association and representatives
from the resuscitation councils of
ILCOR: How to Develop EvidenceBased Guidelines for Emergency
Cardiac Care: Quality of Evidence
and Classes of Recommendations;
also: Anonymous. Guidelines for
cardiopulmonary resuscitation and
emergency cardiac care. Emergency
Cardiac Care Committee and
Subcommittees, American Heart
Association. Part IX. Ensuring
effectiveness of community-wide
emergency cardiac care. JAMA
1992;268(16):2289-2295.
• Print Subscription Semester Program: Paid subscribers with current and
valid licenses in the United States who read all CME articles during each
Emergency Medicine Practice six-month testing period, complete the posttest and the CME Evaluation Form distributed with the December and June
issues, and return it according to the published instructions are eligible for
up to 4 hours of Category 1 credit toward the AMA Physician’s Recognition
Award (PRA) for each issue. You must complete both the post-test and CME
Evaluation Form to receive credit. Results will be kept confidential. CME
certificates will be delivered to each participant scoring higher than 70%.
• Online Single-Issue Program: Paid subscribers with current and valid
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article and complete the online post-test and CME Evaluation Form at
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both the post-test and CME Evaluation Form to receive credit. Results will
be kept confidential. CME certificates may be printed directly from the Web
site to each participant scoring higher than 70%.
Emergency Medicine Practice is not affiliated with any pharmaceutical firm or medical device manufacturer.
President and CEO: Robert Williford. Publisher: Heidi Frost. Research Editors: Ben Abella, MD, University of Chicago; Richard Kwun, MD, Mount Sinai School of Medicine.
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