METABOLIC ACIDOSIS
DEFINITION
A fall in serum bicarbonate concentration to below 24 mmol/L (mEq/L)
(normal range: 24 to 28 mmol/L). It is usually, but not always,
associated with low blood pH (normal range: 7.35 to 7.45).
Metabolic acidosis is produced by four basic mechanisms:
Loss of bicarbonate
Diarrhoea
Renal tubular acidosis
Gain of hydrogen ions (exogenous or endogenous)
Ingestion of acid
Ingestion of material with acidic metabolites
Ketoacidosis
Lactic acidosis
Failure to excrete daily acid load
Renal failure
Dilution of extracellular bicarbonate
TOXIC CAUSES
Metabolic acidosis may be a major presenting feature of ethylene
glycol, methanol or salicylate poisoning.
Other agents associated with metabolic acidosis include:
Acids
Ammonium chloride
Ibuprofen
Formaldehyde
Paraldehyde
Valproic acid
Agents causing lactic acidosis
Acetaminophen
Biguanides (metformin, phenformin)
Carbon monoxide
Chloramphenicol
Cocaine
Cyanide
Ethanol
Fructose
Hydrogen sulphide
Iron
Isoniazid
Nalidixic acid
Sodium nitroprusside
Strychnine
Agents causing methaemoglobinaemia
Agents causing renal tubular acidosis
Amphotericin
Amiloride
Angiotensin-converting enzyme inhibitors
Beta blockers
Carbonic anhydrase inhibitors (acetazolamide)
Cyclamates
Cyclosporin
Heavy metals
Lithium
Non-steroidal antiinflammatories
Toluene
Triamterene
Spironolactone
Vitamin D
It should be noted that any toxin may produce metabolic acidosis if
toxicity is complicated by hypoxia, hypotension or renal failure.
NON-TOXIC CAUSES
Diabetic ketoacidosis
GI alkali loss (diarrhoea, ileo- or colostomy, pancreatic fistula)
Lactic acidosis
Renal failure
Renal tubular acidosis
Uro-intestinal fistula
CLINICAL FEATURES
In mild metabolic acidosis, the clinical features are those of the
underlying intoxication.
More severe acidosis (pH < 7.2, bicarbonate < 13 mmol/L),
irrespective of the underlying cause, may directly produce
cardiovascular, respiratory, CNS and gastrointestinal effects.
Myocardial contractility is impaired and this may progress to
circulatory shock. Respiration becomes abnormally deep and then more
frequent (Kussmaul breathing). CNS depression progresses to coma.
Abdominal pain and nausea may be present. Hyperkalaemia is a
potentially life-threatening complication of acidosis.
DIFFERENTIAL DIAGNOSIS
Hyperventilation syndrome
Respiratory acidosis
(However, following interpretation of arterial blood gases, there is
no differential diagnosis.)
RELEVANT INVESTIGATIONS
Arterial blood gases
Essential to establish diagnosis.
Blood sugar
Chest X-ray
ECG
Liver function tests
Serum electrolytes
Calculation of the anion gap ( [Na+] þ [Cl-] þ [HCO3-] ) is
useful in defining the diagnosis. It represents unmeasured serum
anions and the normal range is 12 ± 4 mEq/L. Most cases of
exogenous poisoning (acetazolamide and ammonium chloride are
exceptions) are associated with an elevated anion gap as are
renal failure, ketoacidosis and lactic acidosis.
Serum lactate
Serum osmolality
Specific toxin concentrations, especially ethylene glycol, methanol
and salicylate
Serum urea and creatinine
TREATMENT
Treatment is directed towards the underlying cause of the metabolic
acidosis. Certain intoxications may require specific antidotal
therapy (e.g. pyridoxine for isoniazid, ethanol or fomepizole for
methanol or ethylene glycol) or haemodialysis (e.g. ethylene glycol,
methanol, salicylate). Where toxin-induced metabolic acidosis is a
complication of renal failure, haemodialysis may be indicated.
The indications for the administration of sodium bicarbonate are
controversial except in methanol poisoning where it should be
vigorously administered in doses sufficient to normalise the serum pH.
Sodium bicarbonate may be useful in other cases of severe toxic
metabolic acidosis in order to maintain an arterial pH of 7.2 and
avoid adverse haemodynamic effects. A typical initial dose is 1 to 2
mmol/kg in isotonic glucose (5%) or hypotonic saline (0.45%) by slow
intravenous infusion. The blood pH should not be corrected to above
7.2 (plasma bicarbonate 10 mmol/L). The dose of sodium bicarbonate
required may be roughly calculated using the following formula: mmol
of sodium bicarbonate required = (mmol/L plasma bicarbonate desired -
mmol/L observed) × 40% of body weight.
Patients with salicylate poisoning should receive sufficient
bicarbonate to raise their pH to greater than 7.4 as lower serum pH
enhances salicylate penetration into tissues. Alkalinization also
promotes urinary salicylate elimination.
If ethanol or fomepizole are not given as antidotes in methanol or
ethylene glycol poisoning, continued production of organic acids may
produce a so-called "bicarbonate-resistant acidosis". In these
situations, a larger amount of bicarbonate than indicated above will
need to be administered. Potential complications of sodium
bicarbonate administration include volume overload (especially in
patients with impaired renal or cardiac function), hypernatraemia,
hypokalaemia, hypocalcaemia and alkalosis. Rapid elevation of blood
sodium, even just to normal level, may induce demyelination of
subcortical brain structures.
CLINICAL COURSE & MONITORING
Mental status, blood pressure, cardiac rhythm, urine output, blood
gases and serum electrolytes must be monitored.
In most cases of toxin-induced metabolic acidosis, appropriate
supportive care including fluid resuscitation, control of seizures,
and correction of hypoxia will be associated with resolution of the
acidosis. In those intoxications requiring specific antidotes or
methods of enhanced elimination, the acidosis will worsen unless the
appropriate therapies are instituted.
LONG-TERM COMPLICATIONS
Metabolic acidosis due to poisoning is of itself rarely associated
with sequelae. Brain damage may result from acute complications such
as cardiac arrest or from excessive sodium bicarbonate administration.
AUTHOR(S)/REVIEWERS
Author: Janusz Szajewski, MD, Warsaw Poisons Control Centre,
Szpital Praski, Pl. Weteranow 4, 03-701 Warszawa,
Poland.
Reviewers: Rio de Janeiro 9/97: J.N. Bernstein, E. Birtanov,
R. Fernando, H. Hentschel, T.J. Meredith, Y. Ostapenko,
P. Pelclova, C.P. Snook, J. Szajewski.
Geneva 8/98, D. Jacobsen, L. Murray, J Pronczuk.
Birmingham 3/99: T. Meredith, L. Murray, A. Nantel,
J. Szajewski.