EMERGENCY MANAGEMENT OF DISORDERS OF CARBOHYDRATE METABOLISM

Disorders of carbohydrate metabolism represent a broad category of emergent and potentially

emergent conditions. Most are related to diabetes and associated complications. They may also occur
as a result of or be mimicked by drug or alcohol toxicity, multisystem trauma, head injury,
cardiovascular disease, cerebrovascular disease, and infection. Patients may present with coma or
altered mental status or look remarkably well clinically yet be on the brink of metabolic
decompensation. These disorders may be a challenge not only to diagnose early but also to treat in the
most severe cases. Often they are precipitated by underlying illness or injury. Early diagnosis and
effective treatment of these underlying entities is a crucial element in resolving the metabolic
decompensation.

DIABETIC KETOACIDOSIS

Essentials of Diagnosis
Signs and symptoms include fatigue, tachypnea (Kussmaul respiration), tachycardia, altered
mental status, abdominal pain, vomiting, polyuria, and polydipsia.
Arterial pH < 7.3, serum glucose = 250 mg/dL, and serum bicarbonate = 15 mEq/L.

General Considerations
Diabetic ketoacidosis (DKA) is the most common acute life-threatening complication
of diabetes. It is more commonly seen in type 1 diabetes but may occur rarely in type 2
diabetes. It is a result of insulin-producing cell failure in the islets of Langerhans located in the
pancreas. This results in insulin deficiency, which then shifts the normal metabolic processes from
using glucose for fuel to using lipids for fuel. Metabolic stress, most commonly from trauma or
infection, may accelerate this process. The result is osmotic diuresis from severe hyperglycemia
leading to dehydration, electrolyte loss, and metabolic acidosis, which results from a combination
of dehydration and the overproduction of ketone bodies from fat metabolism, primarily hydroxybutyrate and acetoacetate, which further acidify the blood. Eventually, hypovolemia leads to
inadequate blood flow to the kidneys and limits renal excretion of glucose. As serum osmolality rises
above 320 mOsm/L, lethargy and coma may ensue. If left untreated, severe metabolic acidosis from
DKA can lead to depression of cardiovascular function, severe hyperkalemia, and potentially lethal
cardiac dysrhythmias.

Clinical Findings
A. History
Determine if the patient has diabetes. Direct the history to ascertain potential precipitating causes of
DKA:

 Recent or current infection of any type (most common)

Injury or trauma
Acute coronary syndrome or myocardial infarction
Transient ischemic attack or stroke
Medications (corticosteroids, thiazides, or sympathomimetics)
Acute or acute-on-chronic pancreatitis
Alcohol or drug abuse
Psychosocial factors, such as depression or inability to afford medications, limiting compliance
Noncompliance with insulin regimen

B. Symptoms and Signs

Symptoms and signs include general fatigue and weakness, abdominal pain (be aware of
precipitating causes such as appendicitis, cholecystitis, pancreatitis, and pregnancy), and
Kussmaul respirations (rapid deep respirations attempting to compensate for acidosis) . Patients
may have a fruity or acetone-like smell to the breath. Other findings include polyuria, polydipsia, and
polyphagia (the body's attempt to compensate for inefficient use of fuel and water loss in
excreting glucose); nausea and vomiting (hemorrhagic gastritis occurs in 25% of patients); altered
mental status ranging from agitation to coma; hypothermia (may be fever equivalent; if present,
prognosis is poor).

C. Laboratory Findings
1. Key findingsKey laboratory features include serum glucose = 250 mg/dL, ketonuria (ketonemia
is unreliable unless -hydroxybutyrate is measured), serum bicarbonate = 15 mEq/L, and arterial
pH < 7.3 (venous pH has been shown to be a consistent, acceptable substitute for arterial pH). Limit
arterial blood gas analysis to patients in whom oxygenation or ventilation is a concern or when
diagnosis may be uncertain.
2. Serum potassiumSerum potassium is often elevated initially despite total body deficits estimated at
3-5 mEq/kg body weight. Additionally, potassium may be lost through vomiting or urinary losses.
Metabolic acidosis shifts potassium out of the cells and into the extracellular fluid space. Because
insulin therapy drives potassium back into the cells, serum potassium should be monitored every 2
hours during the first 8 hours of treatment. Low initial serum potassium (< 3.2 mEq/L) represents a
severe total body potassium deficit, and emergent repletion of potassium is essential to prevent lifethreatening cardiac dysrhythmias.

3. Serum sodiumSerum sodium is usually low from losses in the urine and vomitus coupled
with dilution effects of water being drawn out of the cells into the extracellular compartment by
hyperglycemia. This effect can be corrected by adding 1.8 mEq/L to the serum sodium concentration for
each 100 mg/dL the serum glucose concentration is above normal. Serum sodium may also be

artificially lowered by severe hypertriglyceridemia. Although sodium deficits may approach 7-10
mEq/kg, sodium repletion must proceed gradually to avoid cerebral edema, especially in children.

4. Serum phosphateSerum phosphate is usually normal or elevated despite deficits approaching 1

mmol/kg body weight. Routine phosphate repletion has not been shown to improve clinical outcomes in
DKA and is not indicated. There is significant potential to cause severe hypocalcemia, which may
manifest without the typical finding of tetany. Severe hypophosphatemia (< 1 mg/dL) may cause
skeletal, cardiac, and respiratory muscle depression; phosphate should be replaced in this
circumstance.

5. Other important laboratory findings

a. Anion gapAnion gap is useful to assess severity of acidosis and to follow progress of therapy. The
anion gap is obtained from the following formula:

Normal values are = 10. Effective serum osmolality may be estimated from the following formula:

Values of at least 320 mOsm/kg are associated with central nervous system involvement, usually
lethargy or coma. Below this value, other causes for lethargy or coma such as head injury,
subarachnoid hemorrhage, or cerebrovascular accident should be investigated. This value may also be
used to diagnose hyperglycemic hyperosmolar nonketotic syndrome (HHNS) or ingestions of ethanol or
other osmotically active substances such as ethylene glycol or other alcohols.

b. Serum ketonesStandard laboratory tests measure only acetoacetate. The primary ketone body
formed in DKA initially is -hydroxybutyrate, which is broken down into acetoacetate in the presence of
insulin. Serum ketones are not reliable as a diagnostic test because initially they may be reassuringly
negative even in a severely ill DKA patient. They are not useful to track therapy because in most cases
they will increase as the patient improves.

c. Blood urea nitrogen (BUN) and creatinineThese levels may be elevated because of severe
dehydration, even to the point at which acute tubular necrosis and renal failure occur. If these levels
are elevated on initial chemistries, be sure to establish urine output prior to initiating potassium
repletion.

d. ElectrocardiogramThe electrocardiogram (ECG) may reveal severe electrolyte disturbances or

diagnose cardiac ischemia or myocardial infarction, a common precipitating cause of DKA or HHNS in
older patients. History and physical examination should dictate whether to order cardiac enzymes.

Treatment & Disposition

Given the similar nature of treatment for DKA and HHNS, treatment and patient disposition for these
two entities are presented together in the discussion of HHNS, below.

HYPERGLYCEMIC HYPEROSMOLAR NONKETOTIC SYNDROME

Essentials of Diagnosis
Most symptoms relate to severe dehydration.
Kussmaul respirations and abdominal pain are unusual findings.
Absence of acidosis, small or absent serum ketones, and hyperglycemia usually = 600 mg/dL.

General Considerations
HHNS, formerly called hyperglycemic hyperosmolar nonketotic coma or hyperosmolar coma, is
differentiated from DKA in that patients with HHNS have enough insulin activity to prevent lipolysis
and ketogenesis. DKA often manifests suddenly over hours to a few days, whereas HHNS is more
insidious, developing over several days to weeks. Also, in mild or early DKA, mental status is
normal, whereas in HHNS, mental status is nearly always abnormal, ranging from confusion to
stupor or coma. HHNS occurs most commonly in older (> 65 years) patients who may or may not
have diagnosed diabetes and who are often residents in chronic care facilities. Symptoms of
hyperglycemia such as frequent urination may be attributed to aging, and the thirst response may be
depressed as normal physiology of aging or unrecognized secondary to dementia. Patients also may
not have or be given proper access to fluids.

Usually, a severe physiologic stressor, most commonly infection, is a precipitating cause.

Myocardial infarction, cerebrovascular accident, trauma, and drug effects or interactions may also
precipitate HHNS. Electrolyte deficits are similar in DKA and HHNS, and the free water loss is on the
order of 9 L in HHNS compared with an average water loss of 6 L in DKA.

Clinical Findings
A. History
Risk factors for HHNS include age of 65 years or older, residence in a chronic care facility or nursing
home, change in diabetes regimen, addition of medications that may elevate glucose levels (eg,
corticosteroids, thiazides, anticonvulsants, sympathomimetics), recent or current infection, and
dementia.

B. Symptoms and Signs

Symptoms and signs include polydipsia, polyuria, or polyphagia; generalized weakness; altered
mental status (clouded thinking to confusion to lethargy or coma); dry mucous membranes;
poor skin turgor; and delayed capillary refill. Kussmaul respiration is usually not present unless
metabolic acidosis from sepsis or hypoperfusion occurs.

Abdominal pain is not a typical finding in HHNS (in contrast to DKA); its presence merits aggressive
investigation for precipitating causes. Acute cholecystitis and appendicitis may be insidious and occur
atypically in elderly patients.

C. Laboratory Findings
1. Key laboratory findingsKey findings to diagnose HHNS and differentiate it from DKA include the
following:
Serum glucose is usually = 600 mg/dL.
Urine or serum ketones are small or absent (a small amount of ketone may be detected secondary to
starvation). Glucosuria is prominent.
Serum bicarbonate is usually > 15 mEq/L.
pH is usually > 7.30.
The anion gap may be variable depending on precipitating cause but is usually = 10
Effective serum osmolality is = 320 mOsm/kg.

2. Serum sodiumIn the early stages of HHNS, serum sodium findings are similar to those in patients
with DKA. Urinary losses and fluid shifts out of the cell and into the extracellular compartment create
hyponatremia usually in the 125-130 mg/dL range (remember to correct by adding 1.8 mg/dL for every
100 mg/dL glucose above normal). As water losses worsen, hypernatremia ensues and osmolality
rises, leading to progressive lethargy and coma.

3. Serum potassiumPotassium levels will most commonly be normal or low, unless renal failure is
present. An associated metabolic acidosis driving potassium out of the cells is usually not present in
HHNS.

4. Blood urea nitrogen and creatinineBUN is often markedly elevated. Gastrointestinal bleeding
may also elevate BUN, and this is a possible precipitating cause of HHNS in elderly patients.

5. Other studiesOther studies should be dictated by the history and physical examination findings, but
have a low threshold to obtain serial ECGs and cardiac enzymes to rule out cardiac ischemia or
myocardial infarction, computed tomography (CT) scan of the head to rule out cerebrovascular accident

or subdural hematoma, and rectal exam and nasogastric tube to look for gastrointestinal hemorrhage.
Order an abdominal CT scan or ultrasound to work up abdominal pain if the patient is stable enough to
leave the emergency department.

Treatment
Initial treatment for DKA and HHNS is similar. The various aspects of therapy should be initiated
concurrently whenever possible. Differences in therapy of DKA and HHNS are noted when appropriate.
Frequent reassessment of vital signs, mental status, and laboratory parameters are essential to
successful therapy of DKA and HHNS.

A. Resuscitation Issues
Assess the airway and consider obtaining arterial blood gases for any patient who appears not to be
oxygenating or ventilating properly or who is obtunded or comatose. Consider proceeding directly to
rapid-sequence intubation in patients who are unresponsive or who have depressed gag or swallow
reflexes. Avoid succinyl choline if hyperkalemia is suspected based on peaked T waves on ECG
or rhythm strip.
Oxygen therapy is indicated for all DKA or HHNS patients at flow rates adequate to maintain oxygen
saturation above 96% or PO2 = 70 mm Hg. Hypoxia should trigger an investigation for aspiration,
pneumonia, or pulmonary edema in the differential diagnosis of precipitating causes.

B. Fluid Therapy
Fluid therapy is dictated by 3 parameters: vital signs, corrected serum sodium, and serum glucose.
Overall fluid deficits approach 6-10 L in most patients, and daily maintenance fluid requirements must
also be considered. Multiple, preferably large-bore (= 18-gauge), intravenous lines are essential.
Central venous access should be strongly considered.

Hypotension should prompt a bolus of 1 L of 0.9% NaCl solution to restore blood pressure to at
least 90 mm Hg.

Caution: Assess patients for cardiogenic shock and renal failure before giving large volumes of
intravenous fluids. Reassess patients frequently for adequate urine output and absence of pulmonary
edema or congestive heart failure. Hemodynamic monitoring (Swan-Ganz) is indicated to facilitate fluid
management if cardiogenic shock is present. In the absence of hypotension, administer 1-1.5 L (~ 1520 mL/kg) normal saline in the first hour of therapy.

Using the serum sodium corrected for excess glucose:

 If serum sodium is high or normal, give 0.45% NaCl or half normal saline at a rate of 5-15 mL/kg for
the next liter of fluids.
If serum sodium is low, give 0.9% NaCl or normal saline for next liter of fluids at a rate of 5-15 mL/kg.
Once serum glucose reaches approximately 250 mg/dL, 5% dextrose in 0.45% NaCl is the fluid of
choice at a rate of 250 mL/h; or use 5% dextrose in normal saline if the corrected serum sodium
remains low.
Follow serum electrolytes, venous pH, BUN and creatinine, and glucose, and calculate the osmolality
frequently (every 2 hours in the first 8 hours) as measures of progress in therapy. The aim is a
decrease in serum osmolality of no more than ~ 3 mOsm/kg/h. Urine output may be unreliable while
glucose levels remain high secondary to osmotic diuresis. Once glucose levels approach normal, urine
output may be used to guide therapy; 30-50 cc/h is considered adequate.

C. Electrolyte Replacement
1. PotassiumPotassium repletion may commence once urine output is confirmed and should be
accomplished according to the following algorithm, with target levels of 4.0-5.0 mEq/L:
If serum potassium is 3.3 mEq/L or less, hold insulin therapy and give 40 mEq/h intravenously as
potassium chloride or as a mixture of two-thirds potassium chloride and one-third potassium phosphate
(~ 5 mmol) if serum phosphate is less than 1 mmol/L. If patient is not vomiting, potassium chloride, 2040 mEq, may also be given orally or by nasogastric tube. Assume a deficit of about 100 mEq potassium
for each 1 mEq/L below normal.
If serum potassium is 3.3-5.0 mEq/L, give 20-30 mEq potassium chloride in each liter of intravenous
fluid.
If serum potassium is 5.0 mEq/L or more, hold potassium repletion and recheck serum potassium in 2
hours.
Follow serum potassium every 2 hours during the first 8 hours of therapy.

D. Insulin Therapy
Insulin therapy for DKA and HHNS is generally accomplished intravenously using regular
human insulin. Subcutaneous insulin may be absorbed erratically in severely volume-depleted
patients. Begin therapy with a bolus of 0.1-0.15 U/kg body weight. In DKA this dose rapidly halts
lipolysis and further ketogenesis. In HHNS it helps in rapidly lowering very high serum glucose and
halting further water loss to osmotic diuresis. Start a continuous infusion at 0.1 U/kg body weight
per hour, and monitor capillary blood glucose hourly. If glucose is not decreasing at least 50-70
mg/dL/h, insulin dosage may be doubled hourly until this rate of decline is achieved. Hold insulin
therapy for any potassium level less than 3.3 mEq/L until repletion is undertaken and the level has risen
on recheck in 2 hours.
E. Sodium Bicarbonate Therapy
Sodium bicarbonate therapy is generally indicated only for severe cases of DKA (arterial pH < 6.9).
Bicarbonate therapy will seldom if ever be indicated for HHNS. At pH higher than 6.9, no benefit has

been proved in controlled trials on DKA outcomes, whereas studies have shown aggressive
bicarbonate therapy leading to increased rates of cerebral edema, especially in children. No controlled
data exist on bicarbonate therapy when pH is less than 6.9. Given the catastrophic potential of such
severe acidosis on cellular metabolism, bicarbonate therapy is indicated in these patients and is
accomplished by giving 100 mmol of NaHCO3 diluted in a 500-cc bag of 5% dextrose in water given
over 2 hours. This may be repeated every 2 hours until venous pH is greater than 7.0

F. Treatment of Suspected or Known Precipitating Causes

Infection is the most common precipitating cause of DKA and HHNS. Be sure to examine the patient's
entire skin surface for wounds and cellulitis. Obtain a urine pregnancy test and conduct a pelvic
examination in women of child-bearing age who have DKA to rule out pelvic inflammatory disease or
pregnancy as sources of physiologic stress. Analysis and cultures of all appropriate body fluids (blood,
sputum, urine, cerebrospinal fluid) should be obtained as dictated by the history and physical
examination or broadly in obtunded or comatose patients. Consider empiric administration of broadspectrum antibiotics until culture results are available. Treat other precipitating causes as they become
known, for example, cardiac catheterization and percutaneous transluminal coronary angioplasty for
myocardial infarction.

G. Flow Sheet
It is a good idea to organize vital signs, mental status findings, monitored laboratory values, intravenous
fluid therapy types and rates, insulin dosages, electrolyte repletion, urine output, and bicarbonate
administration (if any) into a flow sheet that can be included in the patient's chart.

Disposition
Patients with all but the mildest cases of DKA and all patients with HHNS should have cardiac
monitoring and a higher level of nursing care for at least 24 hours. Whether the patient goes to an
intermediate care or telemetry unit or the intensive care unit is based on severity of the case and
response to initial therapy as judged by the treating physician.

Kitabchi AE et al: Management of hyperglycemic crises in patients with diabetes mellitus. (Technical
Review). Diabetes Care 2001;24:131. [PMID: 11194218] (Definitive and extremely comprehensive
review on diagnosis and therapy of DKA and HHNS by the foremost authorities in these aspects of
endocrinology and diabetes care. Contains helpful therapeutic algorithms.)

HYPERGLYCEMIA WITHOUT KETOACIDOSIS OR UNRECOGNIZED TYPE 2 DIABETES

Hyperglycemia in the absence of metabolic decompensation (DKA or HHNS) is an increasingly

common finding in the emergency department. Obesity, pre-diabetes, and diabetes are epidemic in the
United States. Sedentary lifestyles and high-carbohydrate and high-fat diets have contributed to

the epidemic. Patients with diabetes may present with hyperglycemia from self-monitored blood
glucose, or they may have no history of diabetes. Patients without diabetes may present with symptoms
of hyperglycemia, most typically polydipsia, polyuria, fatigue, and blurred vision, or they may present
with one or more complications of unrecognized diabetes, such as ischemic heart disease, cerebral or
peripheral vascular disease, nonhealing wounds, or persistent or recurrent infections (especially of the
skin and genitourinary tract). Some patients present with unrelated complaints, and diabetes and
hyperglycemia are found incidentally. The astute emergency clinician should know the risk factors
for type 2 diabetes and recognize any of these symptomatic presentations as an indication to
investigate the possibility of hyperglycemia or unrecognized diabetes.
Clinical Findings
A. History
Risk factors for hyperglycemia and unrecognized type 2 diabetes are listed in Table 41-1.

B. Symptoms and Signs

Symptoms of hyperglycemia may include polydipsia, polyuria, polyphagia, weakness, fatigue,
headache, blurred vision, lightheadedness, or dizziness. When present, symptoms are generally mild to
moderate.

Superficial skin and skin structure infections (cellulitis, furuncles, abscesses, nonhealing wounds or
ulcers), urinary tract infections, candidal genital infections, malignant otitis externa, and rhinocerebral
mucormycosis all have epidemiologic associations to hyperglycemia and diabetes. Chronic
hyperglycemia impairs neutrophil function and other cellular immune responses. Glycosuria is
thought to contribute directly to urine bacterial colonization.

To excrete excess glucose, large volumes of water are lost, and the patient rapidly becomes
dehydrated if fluid intake is not keeping up. Symptoms may include weakness, dizziness, nearsyncope, and headache. Signs are sunken eyes, poor skin turgor, and poor capillary refill.

C. Laboratory Findings
Random serum glucose of greater than 200 mg/dL in the setting of symptoms of hyperglycemia or
metabolic decompensation (DKA or HHNS) or fasting serum glucose of greater than 126 mg/dL on
repeat occasions are both diagnostic of diabetes. Impaired fasting glucose is defined as a fasting
plasma glucose of 110- 126 mg/dL.
Glycosylated hemoglobin, or A1C, is increasingly available as a rapid assay, and the role of A1C
in diagnosing diabetes is evolving. Levels of 6.1% or more are about 80% sensitive in
diagnosing diabetes; levels of 7.0% or more are nearly always consistent with diabetes.

It is always prudent to assume that severe hyperglycemia (= 400 mg/dL) represents impending
decompensation. An underlying cause should be sought aggressively, most commonly infection, but
cardiac ischemia or myocardial infarction sometimes occur and an ECG plus cardiac enzymes may be
helpful. Lack of compliance with antidiabetic regimen or diet should always be exclusionary. Have a low
threshold in this setting to check electrolytes and BUN and creatinine to screen for metabolic
decompensation, severe electrolyte imbalance, and renal insufficiency.

Treatment
A growing body of literature suggests that hyperglycemia is a risk factor for adverse outcomes and that
tight glucose control is a strong component of therapy for nearly every acute illness or injury
experienced by diabetes patients. If hyperglycemia is mild (< 300 mg/dL), patients are not significantly
volume-depleted, no specific cause is identified, and medical follow-up is readily available, no specific
treatment is required other than to refer patients to primary care for diabetes testing (fasting plasma
glucose is preferred over oral glucose tolerance test) or for adjustment of antidiabetic regimen in
patients with known diabetes. When serum glucose is greater than 300 mg/dL, treatment is as follows:

A. Fluids
Normal saline or lactated Ringer's solution, 1 L given over 1 hour, may be adequate monotherapy for
hyperglycemia.
B. Insulin
Mildly volume-depleted patients may be given 0.1 U/kg regular human insulin or insulin lispro
(Humalog) or insulin aspart (Novolog) subcutaneously. Regular insulin at a dose of 0.1-0.15 U/kg
should be given intravenously to dehydrated patients because subcutaneous insulin absorption may be
erratic in these patients. Insulin may be rebolused intravenously if glucose does not decline by 50-75
mg/dL in the first hour.

C. Oral Hypoglycemic Agents

Oral hypoglycemic agents are generally not indicated for acute therapy of severe hyperglycemia,
but if a patient is newly diagnosed with diabetes, the emergency physician may wish to prescribe an
oral agent on discharge. Metformin, which inhibits fasting hepatic glucose production and promotes
weight loss, is the oral agent least likely to cause hypoglycemia. Metformin can be safely started at 500
mg orally once per day; the dosage can be increased by 500 mg/d each week until 500 mg 4 times a
day is reached. Metformin therapy may be initiated if serum creatinine levels are 1.4 mg/dL or lower.
Above this level, the patient is at risk for developing lactic acidosis. Sulfonylurea or insulin therapy is
best undertaken after the patient has received diabetes education and knows the symptoms of
hypoglycemia, how to treat them, and when to call for help. If adjusting an existing oral agent or insulin
dosage, it is a good rule of thumb not to increase insulin dosages by more than 10% or sulfonylurea
dosage by more than about 20%. Patients may also be taking insulin resistance-reduction agents such

as thiazolidinediones or agents that inhibit breakdown of complex carbohydrates in the small intestine,
such as a glucosidase inhibitors.

D. Treatment of Underlying Causes

Treat any underlying causes for hyperglycemia appropriately as they are discovered (eg, antibiotics for
urinary tract infection).

Disposition
Most patients with hyperglycemia in the absence of metabolic decompensation can be safely
discharged after thorough evaluation for underlying causes and therapy has reduced blood glucose to
less than 250-300 mg/dL. Patients with serious underlying causes or in whom hyperglycemia is
resistant to treatment should be hospitalized for further workup and treatment.

Expert Committee on the Diagnosis and Classification of Diabetes Mellitus: Report of the Expert
Committee on the Diagnosis and Classification of Diabetes Mellitus. Diabetes Care 2003;26(Suppl.
1):S5. [PMID:12502614] (Defines the various types of diabetes, their presentation, and diagnostic
criteria.)

Montori VM, Bistrian BR, McMahon MM: Hyperglycemia in acutely ill patients. JAMA 2002;288:2167.
[PMID: 12413377] (Outstanding brief review of the pathophysiology of hyperglycemia, its causes, and
the rationale and literature supporting aggressive blood glucose control in acutely ill patients.)

HYPOGLYCEMIA
Essentials of Diagnosis
Common signs and symptoms include irritability, diaphoresis, and tachycardia related to increased
circulating catecholamines.
As hypoglycemia progresses, neuroglycopenic effects range from focal neurologic deficits such as
diplopia and paresthesias to coma.
Always remember to check the fingerstick blood glucose on every patient presenting with altered
mental status or who appears to be acutely ill.

Causes
Hypoglycemia may occur for many reasons. Most commonly hypoglycemia results from an excess of
endogenous or exogenous insulin or oral hypoglycemic agents, such as sulfonylureas. Failure of other
organs that either produce glucose or mediate the production of glucose and glucose homeostasis may
also precipitate hypoglycemia.

A. Exogenous Insulin
In patients with known diabetes, hypoglycemia may occur as a result of the following:
Delay in eating after taking insulin, or general malnutrition or inadequate caloric intake from acute
nausea and vomiting or gastroparesis
Increased or unusual physical exertion
Increased physiologic stress resulting from illness (most commonly infection or sepsis), injury, or
emotional upset
Excessive dose of exogenous insulin (Note: Remember to check the patient's vision and confirm that
he or she can read the syringe appropriately.)
Variable absorption from injection site
Impaired counter-regulatory hormone axis (glucagon and epinephrine) secondary to autonomic failure
caused by iatrogenic (insulin therapy-related) hypoglycemia
Excessive insulin release produced by sulfonylurea drugs, especially in the presence of renal
insufficiency

 Alterations in therapeutic regimen, particularly increases in insulin or oral agent dosages or the
addition of new oral agents such as thiazolidinediones, which may reduce insulin resistance and
improve therapeutic action of endogenous or exogenous insulin

Rarely, insulin or sulfonylurea drugs have been given to nondiabetics with the intent to harm.
Comprehensive toxicology, insulin, and C-peptide levels can help diagnose these problems. C-peptide
is not present in manufactured insulin; therefore, a high insulin level without a correspondingly high Cpeptide level is diagnostic of insulin overdose.
B. Pancreatic Cell Tumor
Tumor of the insulin-secreting cells in the islets of Langerhans may cause refractory hypoglycemia
and even coma. C-peptide levels will elevate concurrently with insulin levels.

C. Alcohol
Excessive ethanol intake, especially without adequate caloric intake, may cause severe hypoglycemia.
Alcohol abuse depletes hepatic glycogen production and storage and also reduces NADH-mediated
gluconeogenesis. Caution: Administer thiamine, 100 mg, prior to giving large amounts of glucose to
alcoholic patients with hypoglycemia to avoid Wernicke encephalopathy.

D. Postprandial or Reactive Hypoglycemia

The intake of large amounts of calories in nondiabetics may produce enough excess insulin to induce
mildly symptomatic hypoglycemia. Seldom is the hypoglycemia severe enough or persistent enough to
cause decreased level of consciousness or coma.

Clinical Findings
A. History
Try to obtain history of diabetes from emergency medical services; family; or Medic Alert bracelet,
necklace, or wallet card. Emergency medical services or family may also be helpful in disclosing
alcohol use, recent caloric intake, alterations of medication regimen, and recent illness or injury.

B. Symptoms and Signs

Most early symptoms and signs are the result of increased catecholamine release (glucose usually
30-50 mg/dL): tachycardia, irritability, diaphoresis, paresthesias, hunger, decreased concentration.
Later or more severe symptoms and signs of neuroglycopenia (glucose usually < 30 mg/dL) include
confusion or bizarre behavior; visual disturbances (blurred vision, diplopia, hallucinations); hypothermia;
seizurelike activity (myoclonus, tremor) and even seizures; focal neurologic deficits similar to Todd
paralysis that resolve with glucose administration or remain transiently; and lethargy, syncope, or coma.

C. Laboratory Findings
The capillary or fingerstick glucose test is the most rapid diagnostic method to test blood glucose levels.
Because glucometers can become unreliable at readings less than 40 mg/dL, always try to draw a
serum or plasma sample for glucose before administration of glucose.

Search for ancillary causes of hypoglycemia such as infection or sepsis, myocardial infarction,
cerebrovascular accident, alcohol use, pregnancy, drug use (particularly stimulants), occult trauma,
depression (poor caloric intake or insulin or oral agent overdose), other endocrinopathies (Addison
disease, myxedema, thyrotoxicosis, pituitary insufficiency) as dictated by history and physical
examination, and, when appropriate or if history is not available, laboratory studies.

Treatment
A. Airway
Make sure the patient's tongue is not obstructing the airway and that the gag reflex and preferably the
ability to phonate and swallow are present.

B. Emergency Therapeutic Measures

1. Intravenous glucoseIf intravenous access is readily obtainable, administer 50 cc of 50% dextrose
in water (containing approximately 25 g of glucose, which is enough to resolve most
hypoglycemic episodes). Caution: Remember to give thiamine, 100 mg intravenously or
intramuscularly, to alcoholic patients prior to administration of glucose to prevent Wernicke
encephalopathy. Monitor the patient's mental status and recheck capillary blood glucose 30 minutes
after glucose administration. Repeat dosages of 50% glucose or even infusion of glucose glucosecontaining intravenous fluids (5-10%) may be necessary to maintain adequate blood glucose
levels. Neuroglycopenia (altered level of consciousness, seizurelike activity, focal neurologic deficits)
may take time to resolve completely; however, if abnormalities persist longer than 30 minutes after
glucose administration and hypoglycemia has not recurred, other causes should be investigated with a
head CT scan and appropriate laboratory studies.

2. Oral feedingAs soon as the patient regains consciousness, clear fruit juice (eg, apple, grape; 6 oz
= ~ 15 g glucose) is a good choice to maintain glucose levels, and if the patient has not eaten, a snack
or meal is appropriate.

3. GlucagonIf intravenous access is not readily available, 1 mg of glucagon may be given

intramuscularly. The response time is typically 10-15 minutes, and nausea and vomiting along with
overcorrection of glucose levels are common. Given that glucagon can be given intramuscularly, all
patients with insulin-treated diabetes (or their families) should carry and be familiar with the use of
glucagon emergency kits, which come with syringe, lyophilized glucagon, and diluent.

4. MonitoringConsider the duration of action of the insulin and/or oral agents taken by the patient.
Hourly capillary glucose checks should be taken until glucose levels are stable. Generally the patient
should be observed through the peak time of the longest-acting insulin, typically 30 minutes to 1 hour
after the dose with insulin lispro or insulin aspart, 2 hours with regular insulin, or 6 hours with NPH.
Insulin glargine has no peak activity and does not generally cause hypoglycemia by itself. Patients
taking long-acting insulins with peak activity, such as lente or ultralente, and patients taking sulfonylurea
oral agents should generally be observed for a day in the hospital.

Disposition
Indications for admission include persistent or recurrent hypoglycemia despite appropriate therapy,
hypoglycemia related to an oral agent or long-acting insulin, or serious ancillary cause (eg, severe
infection, persistent nausea and vomiting).

Conditions for discharge include availability of responsible adult to be with the patient for next 8-12
hours; ability to take oral fluids and food; medical follow-up available within 24-48 hours; and ability to
(and understanding of the need to) perform blood glucose checks, especially if changes are made in
the therapeutic regimen.

American Diabetes Association: Position Statement: Hospital admission guidelines for diabetes
mellitus. Diabetes Care 2003;26(Suppl. 1):S118. [PMID: 12502634] (American Diabetes Association
recommendations on when to admit patients with hypoglycemia.)

Cryer PE: Hypoglycaemia: the limiting factor in the glycaemic management of type I and type II
diabetes. Diabetologia 2002;45:937. [PMID: 12136392] (An excellent review of therapeutic
hypoglycemia and the counter-regulatory response, both normal and pathologic.)

McAulay V, Deary IJ, Frier BM: Symptoms of hypoglycaemia in people with diabetes. Diabet Med
2001;18:690. [PMID: 11606166] (Extensive review of literature on clinical presentation and
symptomatology in diabetes-related hypoglycemia.)

LACTIC ACIDOSIS

General Considerations
Lactic acidosis is a common complication of critical illness. It is defined as serum lactic acid
concentration greater than 5 mmol/L and arterial pH less than 7.35. Typically lactic acidosis results from
the metabolism of glucose in the presence of inadequate tissue oxygenation or inadequate disposal of
lactic acid by the liver. Severe acidosis can lead to impairment of cardiac contractility, increased
pulmonary vascular resistance, sensitization of the myocardium to dysrhythmias, hyperkalemia, and

inhibition of metabolism at the cellular or molecular level. The mortality rate is high, approaching 4060%.

Causes
Lactic acidosis may occur in any severe illness in which the combination of inadequate tissue
oxygenation, inadequate tissue perfusion, and inadequate lactic acid disposal is present. Common
underlying causes include the following:

Respiratory, hepatic, renal, or heart failure

Sepsis
Shock
Cancer, especially leukemias
Acute infarction of lung, bowel, or extremities
Severe abdominal or multisystem trauma
Alcohol, methanol, or ethylene glycol poisoning
Drugs: cocaine, metformin, isoniazid

Clinical Findings
Diagnostic efforts should focus on finding the underlying cause of the lactic acidosis. Treatment of the
underlying cause is crucial to recovery.

A. Symptoms and Signs

The clinical presentation varies according to the underlying illness or injury. Symptoms may include
hyperventilation, generalized weakness, abdominal pain, or hypotension. Often there is a general lack
of symptoms, especially in the early stages of the underlying pathology. As a result, diagnosis is
frequently difficult in the period when the underlying illness and the acidosis itself are most treatable. A
high index of suspicion is essential in older patients and in patients with the underlying illnesses
identified above.

B. Laboratory Findings
Laboratory findings include pH less than 7.35 and often less than 7.2; anion gap greater than 15
mEq/L; and lack of explanation of acidosis by other causessuch as salicylates; alcohol, methanol, or
ethylene glycol poisoning; or diabetic or alcoholic ketoacidosis. Hyperphosphatemia is a common
finding secondary to anaerobic glycolysis or cellular disruption. Samples collected for lactate should be

chilled immediately and centrifuged promptly to avoid continued lactic acid production by red and white
blood cells, which can distort results.

Treatment
Detailed attention to resuscitation issues is essential in improving outcome. Improving tissue
oxygenation through delivery of adequate oxygen through the lungs and adequate perfusion to carry
the oxygen to the tissues via the circulatory system is critical.

A. Oxygen
High flow rates are indicated. Consider rapid-sequence intubation, mechanical ventilation, or
noninvasive ventilation (eg, bilevel positive airway pressure) when arterial blood gas analysis indicates
that oxygenation or ventilation is inadequate.

B. Fluids BR>Rapid infusion of 1 L of 0.9% saline is indicated to restore intravascular volume.

Reassess the patient frequently to avoid volume overload in the setting of acute renal failure or
cardiogenic shock and circulatory failure.

C. Pressors
Avoid vasoconstrictive pressors such as norepinephrine and higher doses of active pressors such as
dopamine and dobutamine because they tend only to worsen tissue hypoxia. Low doses of dopamine
and dobutamine may improve cardiac output and renal blood flow and are worth trying.

D. Sodium Bicarbonate
The use of sodium bicarbonate is one of the most controversial issues in the treatment of metabolic
acidosis. The majority of data available suggest that at pH levels greater than 6.9, no benefit has been
shown supporting the administration of sodium bicarbonate, at least in the clinical settings of severe
metabolic acidosis resulting from DKA and sepsis. Significant risks of administering bicarbonate include
hypernatremia and hyperosmolality, volume overload, paradoxical increase of intracellular acidosis
secondary to excess carbon dioxide as a result of bicarbonate metabolism, and cerebral edema. If pH
is less than 6.9, especially if the patient is exhibiting one or more complications of severe acidosis as
listed above, consider administering 1-2 amps (~ 44 mEq/amp) diluted in 1 L of 5% dextrose in water or
0.2% saline infused over 2 hours. Reassess pH after allowing at least 2 hours for equilibration.

E. Treatment of Underlying Causes

Treatment of underlying causes may include revascularization therapy or balloon pump support in
patients with cardiogenic shock, antibiotics for suspected sepsis after appropriate culture material is

obtained, amputation or revascularization of ischemic extremities, removal or revascularization of

ischemic bowel, hemodialysis for renal failure, or removal of toxic components such as ethylene glycol
or methanol.

Disposition
The prognosis is grim, and mortality is high. Prompt identification and treatment of the underlying root
cause of lactic acidosis remains the best hope for a positive outcome.

Adrogue HJ, Madias NE: Management of life-threatening acid-base disorders. N Engl J Med
1998;338:26. [PMID: 9414329] (Excellent overview of pathophysiology of severe acidosis and the
management of several common causes.)

Forsythe SM, Schmidt GA: Sodium bicarbonate for the treatment of lactic acidosis. Chest
2000;117:260. [PMID: 10631227] (An intelligent debate on the rationale, or more accurately lack
thereof, for giving sodium bicarbonate as therapy for severe metabolic acidosis.)