DESCRIPTION

• A metabolic acidosis (serum bicarbonate less than 24 mEq/L) may be associated with an increased anion gap.
• Anion gap is defined as the difference of measured cations and anions. Calculation: [serum sodium] - [serum chloride + serum bicarbonate] = anion gap.
• Normal anion gap is less than 16 mEq/L.

PATHOPHYSIOLOGY

• Blood is neutral in charge, with anions equaling cations. However, not all anions and cations are measured using standard laboratory tests. In a healthy, normal patient, the standard serum electrolyte panel appears to have an anion gap because there are more unmeasured anions than cations in the blood.
• In an increased anion gap metabolic acidosis, an anion (e.g., lactic acid), which is not measured in the electrolyte panel, accumulates in the blood. Serum bicarbonate decreases as it is consumed during neutralization of the acid thereby increasing the calculated anion gap above 16 mEq/L.

Section Outline:

• DESCRIPTION
• PATHOPHYSIOLOGY

DIFFERENTIAL DIAGNOSIS

Toxicologic Causes

• Further information on each poison is available in SECTION IV, CHEMICAL AND BIOLOGICAL AGENTS.
• MUDPILES is a mnemonic for common causes of increased anion gap metabolic acidosis:

Some authors include toluene and theophylline. Metabolic acidosis caused by toluene is often of nonanion gap type. Theophylline may produce mild anion gap without hypotension. Massive acetaminophen overdose may cause coma and metabolic acidosis.

Nontoxicologic Causes

Nontoxic causes of increased anion gap acidosis include any cause of acid accumulation. The most common cause is lactic acid arising from anaerobic glycolysis (ischemic tissue, hypoxia, severe agitation or seizure).

SIGNS AND SYMPTOMS

Associated physical signs may help reveal the poison involved when they occur in the setting of increased anion gap metabolic acidosis.

Vital Signs

Any cause of hypotension or hyperthermia may cause anion gap acidosis from lactic acid.

HEENT

• Blindness or blurred vision may indicate methanol poisoning.
• Unusual odors can identify cyanide (bitter almonds), hydrogen sulfide (rotten eggs), toluene (paint)

Dermatologic

• Diaphoresis is associated with beta-receptor agonist, stimulants.
• Eyanosis is caused by hypoxia or methemoglobinemia.
• Paint may indicate toluene abuse.

Cardiovascular

See SECTION II, Bradycardia Toxidrome, Tachycardia, and Ventricular Dysrhythmia chapters.

Pulmonary

Acidosis will cause compensatory tachypnea unless coingestant causes respiratory depression.

Gastrointestinal

• Vomiting is associated with acetaminophen, iron, salicylate, or theophylline intoxication.
• Hematemesis may indicate iron ingestion.

Hepatic

Hepatic damage may be caused by acetaminophen or salicylates and most causes of hyperthermia.

Renal

Renal damage is most likely caused by ethylene glycol, occasionally by acetaminophen or rhabdomyolysis.

Musculoskeletal

Rhabdomyolysis may be secondary to direct muscle injury, muscle compression during coma, excercise, agitation, beta-receptor agonists, seizures, or hyperthermic syndromes.

Neurologic

Toxicant-induced severe agitation or seizure may produce transient lactic acidosis.

PROCEDURES AND LABORATORY TESTS

See chapter on individual poisons for more detailed information.

Essential

Serum Electrolytes, Glucose, BUN, and Creatinine

• Hypokalemia may be caused by beta-receptor agonist, caffeine, or theophylline.
• Anion gap of 16 to 19 mEq/L should raise concern. Repeat anion gap determination in 2 hours to determine if worsening.
• Anion gap is greater than 19 mEq/L.
  • If possible cause is present (e.g., recent seizure), repeat anion gap determination in 1 to 2 hours and reevaluate.
  • If source of gap unclear or osmolal gap is elevated, test for serum lactate, serum methanol, ethlyene glycol levels, serum iron. Cyanide level may be needed rarely.
• Anion gap of greater than 30 mEq/L usually indicates lactic acidosis or ketoacidosis.

Serum Acetaminophen and Salicylate Levels

• Salicylate causes an increased anion gap acidosis.
• Severe acetaminophen poisoning (serum level greater than 800 µg/ml) may cause anion gap acidosis.

Recommended

• ECG and continuous cardiac monitoring are used in overdose setting to detect occult poisoning with cardiotoxic medication.
• Arterial blood gas with cooximetry is used to detect poisoning by carbon monoxide.
• Serum osmolality.
  • An elevated osmolal gap not accounted for by ethanol should initiate a workup for ethylene glycol or methanol.
  • Acetone also produces increased osmolal gap, but not an increased anion gap.
  • Due to variability in laboratories, a normal osmolal gap cannot be used to exclude the presence of methanol or ethylene glycol.
• Abdominal radiograph imaging may reveal radiopaque pills or material: bismuth subsalicylate, enteric coated tablets, iron sulfate, body packers.

Section Outline:

• DIFFERENTIAL DIAGNOSIS
  • Toxicologic Causes
  • Nontoxicologic Causes
• SIGNS AND SYMPTOMS
  • Vital Signs
  • HEENT
  • Dermatologic
  • Cardiovascular
  • Pulmonary
  • Gastrointestinal
  • Hepatic
  • Renal
  • Musculoskeletal
  • Neurologic
• PROCEDURES AND LABORATORY TESTS
  • Essential
  • Recommended

• Focus management on decontamination and supportive care while determining cause of acidosis. If identity of poison is known, see chapter on specific agent. Correct hypoxia and electrolytes as clinically indicated.
• Determine dose and time for all substances involved.

DECONTAMINATION

• The presence of an anion gap metabolic acidosis indicates that absorption and toxic effects are already present.
• Induction of emesis is not recommended unless the specific agent is known (iron, sustained-release preparation, salicylate).
• Gastric lavage should be performed in pediatric (tube size 24-32 French) or adult (tube size 36-42 French) patients for large ingestion presenting within 1 hour of ingestion or if serious effects are present.
• One dose of activated charcoal (1-2 g/kg) should be administered without a cathartic if a substantial ingestion has occurred within the previous few hours.

ANTIDOTES

• Administer antidotes for altered mental status: oxygen, thiamine, glucose, and naloxone. See chapter on specific toxicant for other appropriate antidotes.
• Ethanol. Often the diagnosis of increased anion gap acidosis will be delayed while waiting for a methanol or ethylene glycol level. It is often prudent to begin treatment with fomepizole or ethanol until poisoning with either of these substances can be excluded.
• The use of sodium bicarbonate (NaHCO₃) for treatment of lactic acidosis is not recommended because it is not well supported by current medical evidence.

Section Outline:

• DECONTAMINATION
• ANTIDOTES

PATIENT MONITORING

Serial evaluation of serum electrolytes and arterial blood gases is needed until diagnosis is established.

ADMISSION CRITERIA

All patients with persisent, unexplained, increased anion gap acidosis should be admitted.

Section Outline:

• PATIENT MONITORING
• ADMISSION CRITERIA

• False depression of pCO₂ and calculated bicarbonate on the arterial blood gas from excess heparin (insufficient filling of tubes).
• Failure to decontaminate patients who have unknown or inapparent ingestion.
• Failure to perform endotracheal intubation before aspiration or respiratory arrest occurs.
• Failure to repeat electrolytes and recalculate anion gap in a patient with acidosis and slightly elevated anion gap.
• Failure to maintain compensatory hyperventilation in an intubated patient with metabolic acidosis and compensatory respiratory alkalosis who is placed on mechanical respiration.

No code is available.

RECOMMENDED READING

Emmet M, Narins RG. Clinical use of the anion gap. Medicine 1977;56:38-54.

Author: Steven A. Seifert

Reviewer: Richard C. Dart