Acidosis

Basics

Description

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 of a 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:

  • Reduction in serum pH from decreased plasma [HCO3−] or elevated [H+] levels
  • Primarily caused by:
    • Increased acid formation
    • Decreased acid excretion
    • Loss of bicarbonate
  • Metabolic acidosis is clinically evaluated by dividing into 2 main groups:
    • High anion gap metabolic acidosis (HAGMA):
      • Bicarbonate reduced through buffering of added strong acid
      • Anion gap (AG) is increased due to retention of the unmeasured anion from the titrated strong acid
    • Normal anion gap metabolic acidosis (NAGMA):
      • Kidneys fail to reabsorb or regenerate bicarbonate
      • Losses of bicarbonate from GI tract (ie, diarrhea)
      • Ingestion or infusion of substances that release hydrochloric acid
      • Lack of anion gap results from increased in H+ and Cl− OR decreased HCO3− with increased Cl−

Etiology

  • Respiratory acidosis:
    • Inhibition of respiratory center:
      • Cardiac arrest
      • Drugs (sedatives, opiates, benzodiazepines, etc.)
      • Meningitis/encephalitis
      • CNS lesions (mass, stroke)
      • Oxygen therapy
    • Impaired gas exchange:
      • Pulmonary edema
      • Acute respiratory distress syndrome
      • Asthma/COPD
      • Pneumonia
      • Interstitial lung disease
      • Pulmonary contusion
    • Neuromuscular disease:
      • Diaphragmatic paralysis
      • Guillain–Barré syndrome
      • Myasthenia gravis
      • Muscular dystrophy
      • Spinal cord injury
      • Hypokalemia/hypophosphatemia
      • Multiple sclerosis
      • Amyotrophic lateral sclerosis
    • Obstructive:
      • Congenital lesions (laryngomalacia)
      • Obstructive sleep apnea
      • Obesity hypoventilation syndrome
      • Foreign body aspiration
      • Vascular ring
      • Infectious (epiglottitis, croup, abscess)
  • Metabolic acidosis:
    • HAGMA (Mnemonic—A CAT PILES MUD):
      • Alcohol ketoacidosis
      • Carbon monoxide or cyanide
      • Aspirin
      • Toluene
      • Paraldehyde, propylene glycol, phenformin
      • Iron/isoniazid
      • Lactic acidosis
      • Ethylene glycol, ethanol
      • Starvation, salicylates
      • Methanol, metformin
      • Uremia
      • Diabetic ketoacidosis
    • Increased osmolar gap (Mnemonic—ME DIE):
      • Methanol
      • Ethylene glycol
      • Diuretics (mannitol; no acidosis)
      • Isopropyl alcohol (no acidosis)
      • Ethanol
    • NAGMA (Mnemonic—HARD UP):
      • Hyperalimentation
      • Acetazolamide
      • Rental tubular acidosis (RTA), early renal failure
        Type I RTA—defect in H+ secretion at the distal tubule
        Type II RTA—defect in bicarbonate reabsorption at the proximal tubule
        Type IV RTA—results from hypoaldosteronism or defect in distal tubule’s response to aldosterone resulting in decreased Na+ absorption in combination with decreased H+ and K+ secretion
      • Diarrhea, diuretics, dilutional acidosis
      • Ureteroenterostomy
      • Pancreatic fistula

Diagnosis

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
  • Blood gas (ABG/VBG):
    • pH <7.35
    • PCO2
      • Increases in primary respiratory acidosis
      • Decreases in metabolic acidosis secondary to compensation (immediate)
    • HCO3−
      • Decreases in primary metabolic acidosis
      • Increases in respiratory acidosis secondary to compensation (delayed)
    • PaO2
  • Negative inspiratory force (NIF)
    • Obtain when concerned for respiratory muscle weakness
    • NIF ≤20 cm H2O: poor prognosis, consider ventilatory support
  • Calculate anion gap:
    • Na+ − (HCO3– + Cl–)
    • Normal range = 7 ± 4 mEq/L
      • Previous teaching was 12 ± 4 mEq/L
      • The new range accounts for increase in measured chloride secondary to improved laboratory instrumentation
    • 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 also affects the concentration of chloride and bicarbonate
    • Anion gap >25 mEq/L is seen only with:
      • Lactic acidosis
      • Ketoacidosis
      • Toxin-associated acidosis
  • Calculate the degree of respiratory compensation:
    • PaCO2 = 1.5[HCO3–] + 8 ± 2 (Winter Formula)
    • If PaCO2 inappropriately high, patient has a concomitant respiratory acidosis, and/or inadequate compensation
  • Calculate the delta gap (∆Gap):
    • ∆Gap = ∆AG – ∆HCO3–
      • ∆AG = AG – 12
      • ∆HCO3– = 24 – [HCO3–]
    • Evaluates for pure HAGMA or mixed acid–base disorders
      • For every 1-point increase in anion gap, HCO3– should decrease by ∼1 mEq/L in simple acid–base disorder
      • If the ∆Gap ≠ 0 ± 6, it signifies a mixed acid–base disorder
    • Interpretation of ∆Gap:
      • HCO3– decrease ≈ AG increase (∆Gap of 0 ± 6): AG acidosis only
      • HCO3– decrease > AG increase (∆Gap of ≤−6): NAGMA and/or respiratory alkalosis
      • HCO3– decrease < AG increase (∆Gap of ≥6): metabolic alkalosis and/or respiratory acidosis

Diagnostic Tests And Interpretation

Labs

  • ABG/VBG: See interpretation above
    • Obvious benefit is less patient discomfort and ease in acquiring a VBG sample
    • VBG 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 osmolarity = 2 × Na + glucose/18 + BUN/2.8 + ETOH/4.6
  • Osmolar gap = difference between calculated osmolarity and measured osmolality:
    • Normal = 10 ± 6 mOsm/L
    • Elevated osmolar gap may indicate toxic alcohol as etiology of acidosis (>25 mOsm/L is strongly suggestive)
    • 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

Imaging

CXR:

  • May identify cardiomyopathy, CHF, pulmonary edema
  • Underlying pneumonia

Diagnostic Procedures/Surgery

ECG:

  • May identify regional wall motion abnormalities or valvular dysfunction
  • Evaluate for conduction disturbances

Differential Diagnosis

  • HAGMA: Mnemonic A CAT PILES MUD
  • Increased osmolar gap: Mnemonic ME DIE
  • NAGMA: Mnemonic HARD UP

Treatment

Initial Stabilization/Therapy

Airway, breathing, and circulation (ABCs):

  • Consider intubation:
    • Severe metabolic acidosis with progressive/potential weakening of respiratory compensation
    • NIF ≤20 cm H2O
    • Contraindicated or failed noninvasive mechanical ventilation
  • Naloxone, D50W (or point of care glucose), 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
    • Discontinue offending agents
    • Correct electrolyte abnormalities
  • IV fluids:
    • Rehydrate with 0.9% normal saline if patient hypovolemic
  • Sodium bicarbonate:
    • There is limited utility and should only be considered in specific case:
      • Increase elimination of toxic agent (ie, salicylates)
      • Counteract effects of toxic agents that block cardiac Na+ channels (ie, Tricyclic Antidepressants)
  • Fomepizole:
    • Antagonist of alcohol dehydrogenase preventing formation of toxic metabolites
    • Has no affected on already formed toxic metabolites
    • Ethanol can also be used
  • Pyridoxine:
    • Treats acute isoniazid toxicity
    • Dose (g) = Isoniazid ingestion (g)
      • Max dose is 5 g in adults and 70 mg/kg in pediatrics
  • Dialyze (Mnemonic – AEIOU)
    • Acidosis
    • Electrolyte disturbance
    • Intoxication (eg, ethanol, ethylene glycol, isopropyl alcohol, methanol, lithium, salicylates)
    • Fluid overload
    • Uremia

Medication

  • Dextrose: D50W 1 amp (50 mL or 25 g); (peds: D25W 2–4 mL/kg) IV
  • Naloxone (Narcan): 2 mg (peds: 0.1 mg/kg) IV/IM initial dose
  • Thiamine (vitamin B1): 100 mg (peds: 50 mg) IV/IM
  • Sodium bicarb:
    • Bolus: 1–2 mEq/kg IV bolus
    • Infusion: 100–150 mEq added to 1 L 5% dextrose at rate 200–300 mL/hr
    • Peds: 1–2 mEq/kg slow IV bolus with infusion of 20 mL/kg/hr in 5% dextrose or 45% saline
  • Fomepizole:
    • Loading dose: 15 mg/kg in 100 mL of 0.9% saline or 5% dextrose IV over 30 min
    • Maintenance dose: 10 mg/kg in 100 mL of 0.9% saline or 5% dextrose IV over 30 min every 12 hr for 4 doses
    • Subsequent dose: 15 mg/kg in 100 mL of 0.9% saline or 5% dextrose IV over 30 min every 12 hr until toxic ethylene glycol levels are <20 mg/dL

Follow-Up

Disposition

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

  • Mnemonics such as A CAT PILES MUD are helpful, but are not all encompassing
    • Cocaine, amphetamines, valproic acid are a few other toxins that increase AG
    • Halides, lithium, polymyxin are drugs that decrease AG
  • 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:
    • Normal pH with abnormal pCO2 or HCO3−
    • HCO3− and pCO2 move in opposite directions
    • pH changes in the direction opposite of expected from a known primary disorder

Additional Readings

  1. Antonogiannaki EM, Mitrouska I, Amargianitakis V, Georgopoulos D. Evaluation of acid-base status in patients admitted to ED-physicochemical vs traditional approaches. Am J Emer Med. 2015;33(3):378–382.
  2. Arena A, Miller E. Respiratory acid-base disorders. Emerg Med Clin North Am. 2023;41(4):863–875.  [PMID:37758429]
  3. Judge B. Metabolic acidosis. Emerg Med Clin North Am. 2022;40(2):251–264
  4. Lents S, Ackil D. Metabolic acid-base disorders. Emerg Med Clin North Am. 2023;41(4):849–862.
  5. Mofenson H, Caraccio T, McGuigan M, Greensher J. Medical toxicology. In: Kellerman RD, ed. Conn’s Current Therapy. 2024; 1425–1479.
  6. Rice M, Ismail B, Pillow MT. Approach to metabolic acidosis in the emergency department. Emerg Med Clin North Am. 2014;32(2):403–420.  [PMID:24766940]
  7. Sanghavi SF, Swenson ER. Arterial blood gases and acid-base regulation. Semin Respir Crit Care Med. 2023;44(5):612–626.  [PMID:37369215]
  8. Wiener SW. Toxicologic acid-base disorders. Emerg Med Clin North Am. 2014;32(1):149–165.  [PMID:24275173]

See Also (Topic, Algorithm, Electronic Media Element)

Alkalosis

Authors

Matthew T. Robinson

Catherine D. Parker

Tarrin K. Casey