Metabolic Acidosis Treatment & Management: Approach Considerations, Type 1 Renal Tubular Acidosis, Type 2 Renal Tubular Acidosis (2024)

Treatment of acute metabolic acidosis with alkali therapy is usually indicated to raise and maintain the plasma pH to greater than 7.20. In the following two circ*mstances 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.

In lactic acidosis and diabetic ketoacidosis, the organic anion can regenerate bicarbonate when the underlying disorder is corrected, and caution must be exercised in trying to correct the acidosis with bicarbonate therapy, unless the pH is less than 7.0-7.1.

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^-) × 0.5 × 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 anion gap 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 three ampules are added to 1 L of 5% dextrose in water.

Volume overload can be a consequence of alkali therapy. Loop diuretics can be used in these circ*mstances.

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 anion gap 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 kidnery impairment and must be avoided in the presence of hyperkalemia.

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.

In a 12-month controlled, randomized, interventional trial that included 30 kidney transplant patients with metabolic acidosis, correction of metabolic acidosis with potassium citrate was found to be effective and well tolerated, and was associated with improvements in bone quality, suggesting a beneficial effect of both alkali treatment and restoration of acid/base balance. The researchers concluded that potassium citrate may be superior to sodium bicarbonate, because it lacks volume effects and the obligatory calcium excretion associated with sodium administration. ^[18]

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

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Administration of an alkali is the mainstay of treatment for type 1 renal tubular acidosis (RTA). Adult patients should be given 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.

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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.

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Because hyperkalemia is central to the etiology of this disorder, ^[19] 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 kidney function declines further; eventually, the patient develops a high anion gap renal acidosis. Renal replacement therapy should be considered once the measures described fail to control hyperkalemia or acidosis.

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Treatment of chronic metabolic acidosis in persons with chronic kidney disease (CKD) 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.

Alkali treatment is suggested when the serum bicarbonate concentration falls below 22 mEq/L, as treatment may decrease muscle wasting, improve bone disease, and slow the progression of CKD. ^[20] In patients withstages 3b and 4 CKD, treatment ofmetabolicacidosiswith sodium bicarbonate has also been shown to significantly improve vascular endothelial function. ^[21] The target serum bicarbonate concentration is unclear, however; concentrations above 24 mEq/L have been tentatively linked with worsening of cardiovascular disease, which complicates treatment decisions. ^[22]

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.

The choice of sodium bicarbonate dose remains unclear, and there are concerns over adverse effects, most notably fluid retention, especially with higher doses. Consequently, Abramowitz and colleagues conducted a single-blinded pilot study in 20 adults with stages 3 and 4 CKD and mild metabolic acidosis. Participants were treated during successive 2-week periods with placebo followed by escalating doses of oral sodium bicarbonate at 2-week intervals (0.3, 0.6, and 1.0 mEq/d per kg ideal body weight). ^[23]

Sodium bicarbonate was well tolerated, even at high doses; produced a dose-dependent increase in serum bicarbonate; and was associated with an improvement in lower extremity muscle strength and reduced urinary nitrogen excretion. The authors caution, however, that the results require further study and confirmation from a large randomized placebo-controlled study. ^[23]

In older persons with CKD, existing evidence is insufficient to show whether any benefits of sodium bicarbonate therapy outweigh the adverse effects and treatment burden in this population, which may include fluid retention and blood pressure from the additional sodium load, as well as gastrointestinal side effects. Trials of bicarbonate therapy for older persons with CKD are currently in progress. ^[24]

Metabolic acidosis in patients with CKD can also be treated with dietary modification. Dietary acidreduction can be accomplished by limiting the intake of acid-producing foods such as animal protein and emphasizingbase-producing foods such as fruits and vegetables. ^[25]

In a year-long randomized study of 71 patients with stage 4 CKD, Goroya et al compared the effectiveness of daily oral sodium bicarbonate with that of base-producing fruits and vegetables for reduction of kidney injury and improvement of metabolic acidosis. Patients consuming fruits and vegetables dosed to reduce dietary acid by half had a reduction in kidney injury and improvement in metabolic acidosis comparable to that in the sodium bicarbonate group and did not experience hyperkalemia. ^[26]

The investigators note that study patients were selected to be at low risk for hyperkalemia and advise that caution should be exercised in prescribing fruits and vegetables in patients with very low estimated glomerular filtration rates. Nevertheless, Goroya et al concluded that treating metabolic acidosis in individuals with stage 4 CKD due to hypertensive nephropathy with fruits and vegetables appeared to be an effective kidney-protective adjunct. ^[26]

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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 diabetic ketoacidosis (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⁺.

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Correction of the underlying disorder is the mainstay of therapy. ^[27] 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.

Metformin-associated lactic acidosis (MALA) is treated with hemodialysis, bicarbonate therapy, and continuous renal replacement therapy (CRRT). ^{[27, 28]}

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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 acute kidney injury or severe central nervous system (CNS) depression is present.

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Treatment should be started promptly to prevent any neurologic sequelae.

Fomepizole (4-methylpyrazole; Antizol) 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, acute kidney injury, 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.

A study by Zakarov et al of 31 patients involved in a mass outbreak of methanol poisoning determined that correction of acidemia was accomplished more rapidly with intermittent hemodialysis (IHD) than with continuous renal replacement therapy (CRRT). HCO₃^- increased by 1 mmol/L in a mean of 12 ± 2 min with IHD versus 34 ± 8 min withr CRRT (P <  0.001), while arterial blood pH increased 0.01 in a mean of 7 ± 1 mins with IHD versus 11 ± 4 min with CRRT (p = 0.024). ^[28]

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Christie P Thomas, MBBS, FRCP, FASN, FAHA Professor, Department of Internal Medicine, Division of Nephrology, Departments of Pediatrics and Obstetrics and Gynecology, Medical Director, Kidney and Kidney/Pancreas Transplant Program, University of Iowa Hospitals and Clinics

Christie P Thomas, MBBS, FRCP, FASN, FAHA is a member of the following medical societies: American College of Physicians, American Heart Association, American Society of Nephrology, Royal College of Physicians

Disclosure: Nothing to disclose.

Khaled Hamawi, MD, MHA Director, Multi Organ Transplant Center, King Fahad Specialist Hospital, Dammam

Khaled Hamawi, MD, MHA is a member of the following medical societies: American Society of Transplantation, American Society of Nephrology

Disclosure: Nothing to disclose.

Francisco Talavera, PharmD, PhD Adjunct Assistant Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference

Disclosure: Received salary from Medscape for employment. for: Medscape.

Eleanor Lederer, MD, FASN Professor of Medicine, Chief, Nephrology Division, Director, Nephrology Training Program, Director, Metabolic Stone Clinic, Kidney Disease Program, University of Louisville School of Medicine; Consulting Staff, Louisville Veterans Affairs Hospital

Eleanor Lederer, MD, FASN is a member of the following medical societies: American Association for the Advancement of Science, American Society for Bone and Mineral Research, American Society of Nephrology, American Society of Transplantation, International Society of Nephrology, Kentucky Medical Association, National Kidney Foundation

Disclosure: Serve(d) as a director, officer, partner, employee, advisor, consultant or trustee for: American Society of Nephrology<br/>Received income in an amount equal to or greater than $250 from: Healthcare Quality Strategies, Inc.

Vecihi Batuman, MD, FASN Professor of Medicine, Section of Nephrology-Hypertension, Deming Department of Medicine, Tulane University School of Medicine

Vecihi Batuman, MD, FASN is a member of the following medical societies: American College of Physicians, American Society of Hypertension, American Society of Nephrology, Southern Society for Clinical Investigation

Disclosure: Nothing to disclose.

James W Lohr, MD Professor, Department of Internal Medicine, Division of Nephrology, Fellowship Program Director, University of Buffalo State University of New York School of Medicine and Biomedical Sciences

James W Lohr, MD is a member of the following medical societies: American College of Physicians, American Heart Association, American Society of Nephrology, Central Society for Clinical and Translational Research

Disclosure: Received research grant from: GSK<br/>Partner received salary from Alexion for employment.