Michael P. Kefer
HYPOGLYCEMIA
EPIDEMIOLOGY
Patients with diabetes mellitus, alcoholism, sepsis, adrenal insufficiency, or malnutrition are at risk for hypoglycemia.
Hypoglycemia occurs most commonly in diabetics treated with insulin or sulfonylureas (chlorpropa-mide, glyburide, glipizide). It is less common with the glinides (repaglinide, nateglinide) and unlikely from monotherapy with the α-glucosidase inhibitors (acarbose, miglitol), the glitazones (rosiglitazone, pioglitazone), and the biguanide, metformin.
PATHOPHYSIOLOGY
Glucose is the main energy source of the brain. Severe hypoglycemia can cause brain damage or death.
Serum glucose is dependent on the balance between insulin and the counter-regulatory hormones: epinephrine, glucagon, cortisol, and growth hormone. Excess insulin, either relative or absolute, will result in decreased glucose production and utilization.
CLINICAL FEATURES
Typical symptoms of hypoglycemia include sweating, shakiness, anxiety, nausea, dizziness, confusion, blurred vision, headache, and lethargy.
Typical signs include diaphoresis, tachycardia, and almost any neurologic finding, ranging from altered mental status or tremor to focal neurologic deficit or seizure.
DIAGNOSIS AND DIFFERENTIAL
Diagnosis is based on a low serum glucose level in conjunction with the clinical features that resolve with treatment.
Differential diagnosis is wide due to the nonspecific features. It can be misdiagnosed as a primary neurologic, psychiatric, or cardiovascular condition (Table 131-1).
TABLE 131-1 Differential Diagnosis of some Drugs Used in tuberculosis (adults)*
Stroke
Transient ischemic attack
Seizure disorder
Traumatic head injury
Brain tumor
Narcolepsy
Multiple sclerosis
Psychosis
Sympathomimetic drug ingestion
Hysteria
Altered sleep patterns and nightmares
Depression
EMERGENCY DEPARTMENT CARE AND DISPOSITION
Glucose is administered orally in mild cases.
Advanced cases are treated with 50% dextrose 50 mL intravenously (IV).
Continuous infusion of 10% dextrose solution may be required to maintain the serum glucose level above 100 milligrams/dL.
If no IV access is obtained, give glucagon 1 milligram intramuscularly (IM) or subcutaneously (SC).
Sulfonylureas can cause refractory hypoglycemia that may respond to octreotide 50 to 100 micrograms SC. Subsequent dosing every 6 hours or continuous infusion of 125 micrograms/h may be required.
Check blood glucose every 30 minutes initially to monitor for rebound hypoglycemia.
Factors considered in determining disposition include the patient’s response to treatment, etiology of hypoglycemia, existing comorbid conditions, and social situation.
Most diabetics with insulin reactions respond rapidly to treatment. They can be discharged with instructions to continue oral intake of carbohydrates and to closely monitor their fingerstick glucose level.
Admission guidelines are listed in Table 131-2.
TABLE 131-2 Disposition/Guidelines for Hospital Admission
DIABETIC KETOACIDOSIS
EPIDEMIOLOGY
Diabetic ketoacidosis (DKA) occurs predominantly in type 1 insulin-dependent diabetics, but may occur in type 2 non-insulin-dependent diabetics.
Table 131-3 lists important causes of DKA.
TABLE 131-3 Important Causes of Diabetic Ketoacidosis
Omission or reduced daily insulin injections
Dislodgement/occlusion of insulin pump catheter
Infection
Pregnancy
Hyperthyroidi sm
Substance abuse (cocaine)
Medications: steroids, thiazides, antipsychotics, sympathomimetics
Heat-related illness
Cerebrovascular accident
GI hemorrhage
Myocardial infarction
Pulmonary embolism
Pancreatitis
Major trauma
Surgery
PATHOPHYSIOLOGY
DKA results from a relative insulin deficiency and counter-regulatory hormone excess, resulting in cellular starvation.
Insulin acts on the liver to promote glucose storage as glycogen, on adipose tissue to promote storage of triglycerides, and on skeletal muscle to promote protein synthesis.
Although serum glucose levels are high, in the absence of insulin, cells cannot use glucose as fuel.
The counter-regulatory hormones epinephrine, gluca-gon, cortisol, and growth hormone have the opposite effect of insulin. Glycogenolysis releases glucose stores. Proteolysis and lipolysis result in release of amino acids and glycerol, respectively, for gluconeo-genesis to synthesize more glucose.
Free fatty acids are metabolized in the liver to the ketone bodies β-hydroxybutyrate, acetoacetate, and acetone. However, these also are unavailable for use as fuel by cells in the absence of insulin.
Hyperglycemia causes an osmotic diuresis with volume depletion and electrolyte loss.
Ketonemia results in a high anion gap metabolic aci-dosis with myocardial depression, vasodilation, and compensatory hyperpnea (Kussmaul respiration).
CLINICAL FEATURES
Clinical manifestations are directly related to metabolic derangements.
Dehydration, hypotension, and tachycardia result from osmotic diuresis.
Ketonemia causes a metabolic acidosis with myocardial depression, vasodilation, and compensatory Kussmaul respiration. Nausea, vomiting, and abdominal pain are common.
Acetone excretion via the lungs causes the characteristic fruity odor of the breath.
Inappropriate normothermia may occur, so infection must be considered even in the absence of fever.
DIAGNOSIS AND DIFFERENTIAL
Diagnosis of DKA is based on the clinical presentation and laboratory values of a serum glucose >250 milligrams/dL, serum bicarbonate <15 mEq/L, pH <7.3, and moderate ketonemia.
β-Hydroxybutyrate is the reduced form of acetoacetate. In DKA, reduction of acetoacetate to β-hydroxybutyrate is favored. As a result, in advanced cases, acetoacetate levels are low and β-hydroxybutyrate levels are high.
If the nitroprusside test is used to detect serum or urine ketones, results may be falsely low or negative because this test detects acetoacetate and not β-hydroxybutyrate.
Sodium, chloride, calcium, phosphorus, and magnesium levels may be low from osmotic diuresis.
Pseudohyponatremia is common: for each 100 milligrams/dL increase in the glucose level, there is a 1.6 mEq/L decrease in sodium.
Serum potassium may be low (from osmotic diuresis and vomiting), normal, or high (from acidosis since acidosis drives potassium out of cells). The patient who is acidotic with a normal or low potassium level has a marked depletion of total body potassium.
Laboratory investigation includes serum pH, glucose, electrolytes, blood urea nitrogen, creatinine, phosphorus, magnesium, complete blood count, urinalysis, pregnancy if indicated, electrocardiogram, and chest radiograph to assess the severity of DKA and search for the underlying cause. When ordering serum pH, consider that venous pH correlates closely with arterial pH and avoids the pain and risk of arterial puncture.
Differential diagnosis includes other causes of an anion gap metabolic acidosis (Table 131-4). Hypoglycemia and hyperosmolar hyperglycemic state should also be considered.
EMERGENCY DEPARTMENT CARE AND DISPOSITION
The goal of treatment is to correct hypovolemia, ketonemia, acidosis, and electrolyte abnormalities, and treat the underlying cause (Fig. 131-1).
Bicarbonate therapy remains controversial as to when the benefits of correcting the effects of acidosis (vasodilation, central nervous system and myocardial depression, hyperkalemia) outweigh the risks of bicarbonate treatment (paradoxical cerebrospinal fluid acidosis, hypokalemia, impaired oxyhemoglobin dissociation, rebound alkalosis, sodium overload). It may be of benefit to treat severe acidosis (pH <6.9). It is indicated to treat severe hyperkalemia
Monitor serum glucose, anion gap, potassium, and bicarbonate hourly until recovery is well established.
Note that if monitoring ketones with the nitroprusside test, there will be a paradoxical increase in levels as the undetectable β-hydroxybutyrate is converted back to acetoacetate during recovery.
Cerebral edema is a complication of treatment and occurs predominantly in children. It tends to develop 4 to 12 hours into treatment and manifests as a deterioration in neurologic status. Treat with mannitol 1 gram/kg before the diagnosis is confirmed by computed tomography.
Cerebral edema has been associated with rapid correction of sodium, glucose, and hypovolemia.
TABLE 131-4 Differential Diagnosis for Diabetic Ketoacidosis
FIG. 131-1. Timeline for the typical adult patient with suspected diabetic ketoacidosis. ABG = arterial blood gas; AG = anion gap, BS = blood sugar; CBC = complete blood count; chemistries = sodium, potassium, chloride, CO2content, blood urea nitrogen, creati-nine; DKA = diabetic ketoacidosis; NS = normal saline; STAT = immediately; TKO = IV infusion just to keep the venous access patent.
HYPEROSMOLAR HYPERGLYCEMIC STATE
EPIDEMIOLOGY
Hyperosmolar hyperglycemic state (HHS) is distinguished from DKA by the absence of significant ketosis.
HHS occurs in poorly controlled type 2 diabetics. It is a relatively common presentation of new-onset type 2 diabetes. Precipitating factors are the same as for DKA (Table 131-3).
PATHOPHYSIOLOGY
HHS develops as a result of (1) insulin resistance, deficiency, or both; (2) increased hepatic gluconeogenesis and glycogenolysis; and (3) osmotic diuresis and dehydration.
As serum glucose increases, the osmotic gradient pulls intracellular fluid into the intravascular space. Glucosuria also ensues resulting in an osmotic diuresis causing volume depletion.
CLINICAL FEATURES
The typical patient is elderly with type 2 diabetes, presents with complaints of weakness or mental status changes, and has preexisting renal or heart disease. Because metabolic changes progress slowly, symptoms often signal advanced HHS.
Physical examination reveals signs of dehydration with orthostasis, dry skin and mucous membranes, and altered mental status. Focal deficits and seizures may occur.
Kussmaul respiration and the smell of acetone on the breath are not present due to lack of significant ketosis.
DIAGNOSIS AND DIFFERENTIAL
The diagnosis is based on clinical and laboratory findings.
Defining laboratory criteria are serum glucose >600 milligrams/dL, calculated serum osmolality >315 mOsm/kg, serum bicarbonate >15 mEq/L, and pH >7.3. Ketosis is absent or mild.
Sodium, potassium, chloride, calcium, phosphorus, and magnesium levels may be low from osmotic diuresis. Pseudohyponatremia is common.
EMERGENCY DEPARTMENT CARE AND DISPOSITION
The goal of treatment is to correct hypovolemia and electrolyte abnormalities and treat the underlying cause (Fig. 131-2).
Admission guidelines are listed in Table 131-2.
FIG. 131-2. Protocol for the management of severely ill adult patients with hyperosmolar hyperglycemic state (HHS). Diagnostic criteria for HHS: blood glucose >600 milligrams/dL, arterial pH >7.3, bicarbonate >15 mEq/L, mild ketonuria or ketonemia, and effective serum osmolahty >320 mOsm/kg of water. *Concentrations of K+ ≥20 mEq/L should be administered via central line. History and physical examination, appropriate ancillary studies. D5½NS = 5% dextrose in half normal saline; HHS = hyperosmolar hyperglycemic state; NS = normal saline.
DIABETIC FOOT ULCERS
These are classified and managed as non-limb-threatening, limb-threatening, or life-threatening (Table 131-5).
Antibiotic treatment is tailored accordingly (Table 131-6).
TABLE 131-5 Clinical Practice Pathways for Diabetic Foot Ulcer and Infection
TABLE 131-6. Antimicrobial Therapy in Infected Diabetes-Related Lower Extremity Ulcers
For further reading in Tintinalli’s Emergency Medicine: A Comprehensive Study Guide, 7th ed., see Chapter 218, “Type 1 Diabetes Mellitus,” by Nikhil Goyal and Adam B. Schlichting; Chapter 219, “Type 2 Diabetes Mellitus,” by Mohammad Jalili; Chapter 220, “Diabetic Ketoacidosis,” by Michael E. Chansky and Cary Lubkin; and Chapter 222, “Hyperosmolar Hyperglycemic State,” by Charles S. Graffeo