Respiratory acidosis.
  • Reduced pH owing to alveolar hypoventilation with elevated PaCO2
  • Defined as PaCO2 >45 mm Hg or higher than expected for calculated respiratory compensation for metabolic acidosis
  • Divided into 3 broad categories:
    • Primary failure in CNS drive to ventilate:
      • Sleep apnea
      • Anesthesia
      • Sedative overdose
    • Primary failure in transport of CO2 from alveolar space:
      • COPD
      • Myasthenic crisis
      • Severe hypokalemia
      • Guillain–Barré syndrome
    • Primary failure in transport of CO2 from tissue to alveoli:
      • Severe heart failure/pulmonary edema
Metabolic acidosis
  • Process that reduces serum pH by decreasing plasma bicarbonate levels
  • Primarily caused by:
    • Accumulation of a strong acid through ingestion or metabolism
    • Loss of bicarbonate from the body
  • Metabolic acidosis is clinically evaluated by dividing into 2 main groups:
    • Elevated anion gap metabolic acidosis:
      • Bicarbonate reduced through buffering of added strong acid
      • Anion gap is increased due to retention of the unmeasured anion from the titrated strong acid.
    • Normal anion gap metabolic acidosis due to:
      • Kidneys fail to reabsorb or regenerate bicarbonate.
      • Losses of bicarbonate from GI tract (diarrhea)
      • Ingestion or infusion of substances that release hydrochloric acid
    • No anion gap is observed owing to the absence of any unmeasured anion of a titrated acid and secondary chloride retention with HCO3 loss.


  • Respiratory acidosis:
    • Inhibition of respiratory center:
      • Cardiac arrest
      • Drugs (opiates, benzodiazepines, etc.)
      • Meningitis/encephalitis
      • CNS lesions (mass, CVA)
    • Impaired gas exchange:
      • Pulmonary edema
      • Asthma/COPD
      • Pneumonia
      • Interstitial lung disease
      • Obesity
      • Pulmonary contusion
    • Neuromuscular disease:
      • Diaphragmatic paralysis
      • Guillain–Barré syndrome
      • Myasthenia gravis
      • Muscular dystrophy
      • Spinal cord injury
      • Hypokalemia/hypophosphatemia
      • MS
    • Obstructive:
      • Congenital lesions (laryngomalacia)
      • Foreign body aspiration
      • Vascular ring
      • Infectious (epiglottitis, croup, abscess)
  • Anion gap acidosis: Mnemonic A CAT PILES MUD:
    • Alcohol ketoacidosis
    • Carbon monoxide or cyanide
    • Aspirin
    • Toluene
    • Paraldehyde
    • Iron/isoniazid
    • Lactic acidosis
    • Ethylene glycol
    • Starvation
    • Methanol
    • Uremia
    • Diabetic ketoacidosis
  • Increased osmolar gap: Mnemonic ME DIE:
    • Methanol
    • Ethylene glycol
    • Diuretics (mannitol; no acidosis)
    • Isopropyl alcohol (no acidosis)
    • Ethanol
  • Nonanion gap metabolic acidosis:
    • GI losses of bicarbonate:
      • Diarrhea
      • Villous adenoma
      • Removal of small bowel, pancreatic or biliary secretions
      • Tube drainage
      • Small bowel/pancreatic fistula
    • Anion exchange resins (i.e., cholestyramine)
    • Ingestion of calcium chloride or magnesium chloride
    • Type I renal tubular acidosis (distal): Hypokalemic hyperchloremic metabolic acidosis:
      • Decreased ability to secrete hydrogen
      • Serum HCO3 <15 mEq/L when untreated
      • Potassium low
      • Renal stones common
    • Type II renal tubular acidosis (proximal): Hypokalemic hyperchloremic metabolic acidosis:
      • Decreased proximal reabsorption of HCO3
      • Acidosis limited by reabsorptive capacity of proximal tubule for HCO3
      • Serum HCO3 typically 14–18 mEq/L
      • Low/normal potassium
    • Type IV renal tubular acidosis (hypoaldosteronism): Hyperkalemic hyperchloremic acidosis:
      • Aldosterone deficiency or resistance causing decreased H+ secretion
      • Serum bicarb >15 mEq/L
      • Normal/elevated potassium
    • Carbonic anhydrase inhibitors
    • Tubulointerstitial renal disease
    • Hypoaldosteronism
    • Addition of hydrochloric acid such as:
      • Ammonium chloride
      • Arginine hydrogen chloride
      • Lysine hydrogen chloride


Signs and Symptoms

  • Nonspecific findings
  • Vital signs:
    • Tachypnea or Kussmaul respirations with metabolic acidosis
    • Hypoventilation with respiratory acidosis
    • Tachycardia
  • Somnolence
  • Confusion
  • Altered mental status (CO2 narcosis)
  • Myocardial conduction and contraction disturbances (dysrhythmias)

Essential Workup

  • Electrolytes, BUN, creatinine, and glucose:
    • Decreased bicarbonate with metabolic acidosis
    • Hyperkalemia and hypercalcemia with severe metabolic acidosis
  • Arterial blood gases:
    • pH
    • CO2 retention in respiratory acidosis
    • CO level
Check the degree of compensation by calculating the expected values and comparing them to the observed laboratory values as follows:
  • Respiratory acidosis:
    • Acute: Expected HCO3 increased by 1 mEq/L for every 10 mm Hg increase in PaCO2
    • Chronic: Expected HCO3 increased by 4 mEq/L for every 10 mm Hg increase in PaCO2
  • Calculate anion gap: Na+ – (HCO3 + Cl):
    • Correct anion gap for hypoalbuminemia:
      • For every 1 g/dL decrease in albumin (from 4 g/dL), add 2.5 points to calculated anion gap.
    • Do not correct sodium concentration when calculating the anion gap in the setting of marked hyperglycemia because hyperglycemia affects the concentration of chloride and bicarbonate, as well as sodium.
    • Normal range = 5 – 12 ± 3 mEq/L
    • Anion gap >25 mEq/L is seen only with:
      • Lactic acidosis
      • Ketoacidosis
      • Toxin-associated acidosis
  • Calculate the degree of compensation:
    • Expected PaCO2 = 1.5[HCO3] + 8
    • If PaCO2 inappropriately high, patient has a concomitant respiratory acidosis and/or inadequate compensation.
  • Evaluate the delta gap (ΔGap):
    • For every 1-point increase in anion gap, HCO3 should decrease by ∼1 mEq/L in simple acid–base disorder.
    • As the volumes of distribution of the unmeasured anions and serum HCO3 are not in unity, a ΔGap > 6 signifies a mixed acid–base disorder
  • Evaluate ΔGap by comparing the change in the anion gap (ΔAG) with the change in the HCO3 (ΔHCO3) from normal:
    • If ΔAG > ΔHCO3, then patient has a concomitant metabolic alkalosis.
    • If ΔHCO3 > ΔAG, then patient has concomitant nonanion gap acidosis.

Diagnostic Tests and Interpretation

  • ABG: See interpretation above.
  • VBG:
    • Obvious benefit is less patient discomfort and ease in acquiring sample
    • pH varies by <0.04 units when compared to arterial sampling.
    • Correlation between venous pCO2 lacking
    • Limited role in screening for hypercapnia. pCO2 >45 mm Hg is sensitive (but not specific) for detection of arterial pCO2 > 50 mm Hg in hemodynamically stable patients
    • Useful in simple acid–base disorders
  • Urinalysis for glucose and ketones
  • Measure serum osmolality:
    • Calculated serum osmolality = 2 Na + glucose/18 + BUN/2.8
  • Osmolar gap = difference between calculated and measured osmolality:
    • Normal = <10
    • Elevated osmolar gap may indicate toxic alcohol as etiology of acidosis.
    • Absence of an osmolar gap should never be used to rule out toxic ingestions:
      • Osmolar gap imprecisely defined
      • Delayed presentations may have normal gap
      • Large variance in gap among normal patients
  • Toxicology screen:
    • Methanol, ethylene glycol, ethanol, and isopropyl alcohol if increased osmolality gap
    • Aspirin or iron levels for suspected ingestion
  • Co-oximetry for CO exposure
  • Serum ketones or β-hydroxybutyrate level
  • Serum lactate

  • May identify cardiomyopathy or CHF
  • Underlying pneumonia

Diagnostic Procedures/Other
  • May identify regional wall motion abnormalities or valvular dysfunction
  • Evaluate for conduction disturbances

Differential Diagnosis

  • Anion gap acidosis:
    • Mnemonic A CATPILES MUD
  • Increased osmolar gap:
    • Mnemonic ME DIE


Initial Stabilization/Therapy

Airway, breathing, and circulation (ABCs):
  • Early intubation for severe metabolic acidosis with progressive/potential weakening of respiratory compensation
  • Naloxone, D50W (or Accu-Chek), and thiamine if mental status altered

Ed Treatment/Procedures

  • Respiratory acidosis:
    • Treat underlying disorder
    • Provide ventilatory support for worsening hypercapnia
    • Identify and correct aggravating factors (pneumonia) in chronic hypercapnia.
  • Metabolic acidosis:
    • Identify if concurrent osmolar gap.
    • Treat underlying disorder:
      • Diabetic ketoacidosis
      • Lactic acidosis
      • Alcohol ketoacidosis
      • Ingestion
    • Correct electrolyte abnormalities.
  • IV fluids:
    • Rehydrate with 0.9% normal saline if patient hypovolemic.
    • Consider hemodialysis


  • Dextrose: D50W 1 amp (50 mL or 25 g); (peds: D25W 4 mL/kg) IV
  • Naloxone (Narcan): 2 mg (peds: 0.1 mg/kg) IV or IM initial dose
  • Thiamine (vitamin B1): 100 mg (peds: 50 mg) IV or IM

Ongoing Care


Admission Criteria
Consider ICU admission if:
  • pH <7.1
  • Altered mental status
  • Respiratory acidosis
  • Hemodynamic instability
  • Dysrhythmias
  • Electrolyte abnormalities

Discharge Criteria
Resolving or resolved anion gap metabolic acidosis

Pearls and Pitfalls

  • Failure to appreciate acidosis in mixed acid–base disorders
  • Failure to appreciate inadequate respiratory compensation for metabolic acidosis and need for ventilatory support
  • Clues to the presence of a mixed acid–base disorder are normal pH with abnormal PCO2 or HCO3, when the HCO3 and PCO2 move in opposite directions, or when the pH changes in the direction opposite that expected from a known primary disorder.

Additional Reading

  • Ayers C, Dixon P. Simple Acid-Base Tutorial. J Parenter Enteral Nutr. 2012;36(1):18–23.
  • Kellum JA. Determinants of plasma acid-base balance. Crit Care Clin. 2005;21(2):329–346.  [PMID:15781166]
  • Robinson MT, Heffner AC. Acid base disorders. In: Adams J ed. Emergency Medicine. Philadelphia, PA: Elsevier; 2012.
  • Whittier WL, Rutecki GW. Primer on clinical acid-base problem solving. Dis Mon. 2004;50:122.  [PMID:15069420]

See Also




276.2 Acidosis




  • 51387008 Acidosis (disorder)
  • 12326000 Respiratory acidosis (disorder)
  • 59455009 Metabolic acidosis (disorder)


Matthew T. Robinson

© Wolters Kluwer Health Lippincott Williams & Wilkins

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