Metabolic Acidosis Treatment & Management

Treatment of acute metabolic acidosis by alkali therapy is usually indicated to raise and maintain the plasma pH to greater than 7.20. In the following 2 circumstances this is particularly important.

When the serum pH is below 7.20, a continued fall in the serum HCO₃^- level may result in a significant drop in pH. This is especially true when the PCO₂ is close to the lower limit of compensation, which, in an otherwise healthy young individual is approximately 15 mm Hg. With increasing age and other complicating illnesses, the limit of compensation is likely to be less. A further small drop in HCO₃^- at this point thus is not matched by a corresponding fall in PaCO₂, and rapid decompensation can occur. For example, in a patient with metabolic acidosis with a serum HCO₃^- level of 9 mEq/L and a maximally compensated PCO₂ of 20 mm Hg, a drop in the serum HCO₃^- level to 7 mEq/L results in a change in pH from 7.28 to 7.16.

A second situation in which HCO₃^- correction should be considered is in well-compensated metabolic acidosis with impending respiratory failure. As metabolic acidosis continues in some patients, the increased ventilatory drive to lower the PaCO₂ may not be sustainable because of respiratory muscle fatigue. In this situation, a PaCO₂ that starts to rise may change the plasma pH dramatically even without a significant further fall in HCO₃^-. For example, in a patient with metabolic acidosis with a serum HCO₃^- level of 15 and a compensated PaCO₂ of 27 mm Hg, a rise in PaCO₂ to 37 mm Hg results in a change in pH from 7.33 to 7.20. A further rise of the PaCO₂ to 43 mm Hg drops the pH to 7.14. All of this would have occurred while the serum HCO₃^- level remained at 15 mEq/L.

Sodium bicarbonate (NaHCO₃) is the agent most commonly used to correct metabolic acidosis. The HCO₃^- deficit can be calculated by using the following equation:

HCO₃^- deficit = deficit/L (desired serum HCO₃^- - measured HCO₃^-) x 0.5 x body weight (volume of distribution for HCO₃^-)

This provides a crude estimate of the amount of HCO₃^- that must be administered to correct the metabolic acidosis; the serum HCO₃^- level or pH should be reassessed frequently.

HCO₃^- can be administered intravenously to raise the serum HCO₃^- level adequately to increase the pH to greater than 7.20. Further correction depends on the individual situation and may not be indicated if the underlying process is treatable or the patient is asymptomatic. This is especially true in certain forms of metabolic acidosis. For example, in high-AG acidosis secondary to accumulation of organic acids, lactate, and ketones, these anions are eventually metabolized to HCO₃^-. When the underlying disorder is treated, the serum pH corrects; thus, caution should be exercised in these patients when providing alkali to raise the pH much higher than 7.20, because an overshoot alkalosis may occur.

To minimize the risk of hypernatremia and hyperosmolality, two 50-mL ampules of 8.4% NaHCO₃ (containing 50 mEq each) are added to 1 L of 0.25 normal saline or 3 ampules are added to 1 L of 5% dextrose in water.

Volume overload can be a consequence of alkali therapy, and loop diuretics can be used in these circumstances.

Another consequence of treatment with NaHCO₃ is a rise in PaCO₂. This can become a very important factor in patients who have reduced ventilatory reserve.

In high-AG acidosis secondary to accumulation of organic acids, lactate, and ketones, these anions are eventually metabolized to HCO₃^-. When the underlying disorder is treated, the serum pH corrects; thus, caution should be exercised in these patients when providing alkali to raise the pH much higher than 7.20, because an overshoot alkalosis may occur.

Potassium citrate can be useful when the acidosis is accompanied by hypokalemia but should be used cautiously in the presence of renal impairment and must be avoided in the presence of hyperkalemia.

Carbicarb has an equimolar concentration of NaHCO₃^- and sodium carbonate. Because carbonate is a stronger base, it buffers H⁺ in preference to HCO₃^-, resulting in the generation of HCO₃^- rather than CO₂. This drug is not available in the United States.

THAM is a sodium-free alkalizing solution containing 0.3N tromethamine. It buffers acids and limits the generation of CO₂ and has been used in some clinical situations to treat severe metabolic acidosis. Major adverse effects include hyperkalemia and hypoglycemia, and the drug should not be used in patients with oliguria or poor renal function. This drug is not used widely in the United States.

Oral NaHCO₃ can be administered in some acute metabolic acidemic states in which correction of metabolic acidosis is unlikely to occur without exogenous alkali administration.

Oral alkali administration is the preferred route of therapy in persons with chronic metabolic acidosis. The most common alkali forms for oral therapy include NaHCO₃ tablets. These are available in 325 and 650 mg strengths (1 g of NaHCO₃ is equal to 11.5 mEq of HCO₃^-).

Citrate salts are available in a variety of formulations, as mixtures of citric acid with sodium citrate and/or potassium citrate. These solutions generally contain 1-2 mEq of HCO₃^- per mL. Potassium citrate is useful when the acidosis is accompanied by hypokalemia but should be used cautiously in persons with renal impairment and must be avoided in those with hyperkalemia.

Go to Pediatric Metabolic Acidosis and Emergent Management of Metabolic Acidosis for complete information on these topics.

Administration of an alkali is the mainstay of treatment for Type 1 RTA. Adult patients should be administered the amount required to buffer the daily acid load from the diet. This is usually approximately 1-3 mEq/kg/d and can be administered in any form, although the preferred form is as potassium citrate. Correction of acidosis usually corrects the hypokalemia, but K⁺ supplements may be necessary.

Correcting this form of acidosis with alkali is difficult because a substantial proportion of the administered HCO₃^- is excreted in the urine, and large amounts are needed to correct the acidosis (10-30 mEq/kg/d). Potassium is also required when administering HCO₃^-. Correction is essential in children for normal growth, while in adults aggressive correction to a normal level may not be required. Thiazide diuretics can be administered to induce diuresis and mild volume depletion, which, in turn, raises the proximal tubule threshold for HCO₃^- wasting.

Patients with type 2 RTA typically have hypokalemia and increased urinary K⁺ wasting. Administration of alkali in those patients leads to more HCO₃^- wasting and can worsen hypokalemia unless K⁺ is replaced simultaneously.

Because hyperkalemia is central to the etiology of this disorder, a major treatment goal is to lower the serum K⁺ level. This can be achieved by placing the patient on a low-K⁺ diet (1 mEq/kg K⁺/d) and by withdrawal of drugs that can cause hyperkalemia (eg, angiotensin-converting enzyme [ACE] inhibitors, nonsteroidal anti-inflammatory drugs). Loop diuretics can be helpful in reducing serum potassium levels as long as the patient is not hypovolemic.

In resistant cases, fludrocortisone, a synthetic mineralocorticoid, can be used to increase K⁺ secretion, but this may increase Na⁺ retention. Alkali therapy is not usually required, because, in many patients, the mild degree of acidosis is corrected by achieving normokalemia. Hyperkalemia and acidosis worsen as renal function declines further; eventually, the patient develops a high-AG renal acidosis. Renal replacement therapy should be considered once the measures described fail to control hyperkalemia or acidosis.

Treatment of chronic metabolic acidosis in persons with renal failure is indicated because it can help to prevent bone loss that can progress to osteopenia or osteoporosis. In children, growth retardation can occur.

In addition, treatment slows the progression of hyperparathyroidism and helps to reduce the high-protein catabolic state associated with uremic acidosis, which leads to loss of muscle mass and malnutrition.

NaHCO₃ is the most frequently used agent. It is administered in an amount necessary to keep the serum HCO₃^- level greater than 20 mEq/L. The average requirement is approximately 1-2 mEq/kg/d. Sodium citrate should be avoided if the patient is taking aluminum as a phosphate binder, because citrate increases aluminum absorption and, hence, the risk for aluminum toxicity.

Starvation and alcohol use resulting in acidosis is treated with intravenous glucose, which is administered to stimulate insulin secretion and stop lipolysis and ketosis.

For DKA, insulin is administered, usually intravenously, to facilitate cellular uptake of glucose, reduce gluconeogenesis, and halt lipolysis and production of ketone bodies. In addition, normal saline is administered to restore extracellular volume; potassium and phosphate replacement also may be necessary. The acidosis is corrected partly by the metabolism of ketones to HCO₃^-, partly by increased H⁺ secretion by the collecting duct, and partly by H⁺ excretion as NH₄⁺.

Correction of the underlying disorder is the mainstay of therapy. In patients with tissue hypoxia, restoration of tissue perfusion is essential.

The role of alkali therapy is controversial; some authors recommend raising the serum pH to 7.20 when possible. Some evidence suggests, however, that HCO₃^- therapy produces only a transient increase in the serum HCO₃^- level and that this can lead to intracellular acidosis and worsening of lactic acidosis. Furthermore, large amounts of NaHCO₃ are commonly required, and volume overload and hypernatremia can occur. In such situations, hemodialysis or continuous venovenous hemofiltration can be used to correct the metabolic abnormalities.

If the process leading to lactic acidosis is corrected, lactic acid can be used again by the liver to produce HCO₃^- on an equimolar basis. This is important, because rebound alkalosis can occur if the patient has received an excessive amount of alkali during the acidemia.

Alkali therapy is an important component of therapy in salicylate overdose for several reasons. Correcting the acidemia decreases the amount of salicylate crossing the blood-brain barrier. Care should be exercised to avoid inducing or worsening the alkalosis that may be present.

Increasing urine pH increases the excreted salicylate. Alkaline diuresis can be initiated by intravenous NaHCO₃ administration or by acetazolamide therapy. The goal is to maintain the urine pH at greater than 7.5 until the salicylate level falls below 30-50 mg/dL.

Multiple dosing of activated charcoal at 0.25-1 g/kg every 2-4 hours can also be used to increase the excretion of salicylate.

In acute intoxication, hemodialysis should be considered when the blood level is greater than 80 mg/dL or when renal failure or severe central nervous system (CNS) depression is present.

Treatment should be started promptly to prevent any neurologic sequelae.

4-methylpyrazole (fomepizole) is a potent inhibitor of alcohol dehydrogenase and is now the preferred therapy, although it is much more expensive than ethanol. Fomepizole is given as a loading dose and continued over several doses until toxin levels decline substantially. Fomepizole levels do not need to be monitored.

Ethanol competes for alcohol dehydrogenase and can be used as an alternative to fomepizole. It is administered orally or intravenously to saturate alcohol dehydrogenase, to which it has a higher affinity, thus inhibiting metabolism of methanol or ethylene glycol to its toxic metabolites. The blood ethanol level should be maintained at 100-150 mg/dL.

HCO₃^- therapy can be administered to correct severe acidosis, but large amounts of HCO₃^- may be required and fluid overload can compromise therapy.

Patients with methanol overdose should receive folate to enhance the metabolism of formic acid. Patients with ethylene glycol overdose should receive thiamine and pyridoxine.

Hemodialysis should be considered in any patient with significant metabolic acidosis, renal failure, visual symptoms, a high blood toxin level, or a suspected large overdose. Hemodialysis is effective in clearing methanol and ethylene glycol, as well as their toxic metabolites; in correcting the acidosis; and in restoring extracellular volume.