eMedicine Specialties > Nephrology > Acid-Base, Fluid, and Electrolyte Disorders
Hyperchloremic Acidosis: Treatment & Medication
Updated: Jul 30, 2009
- Overview
- Differential Diagnoses & Workup
- Treatment & Medication
- Follow-up
Treatment
Medical Care
- Treatment of GI causes of hyperchloremic acidosis is aimed at the underlying cause and includes (1) administration of saline solutions to repair the volume losses and (2) early administration of potassium.
- Treatment of acidosis with bicarbonate-containing solutions is accompanied by potassium replacement to avoid severe hypokalemia, with its possible associated cardiac arrhythmias and muscular paralysis due to the introduction of potassium into the cells.
- Patients with chronic acidosis secondary to diarrhea benefit from long-term therapy with sodium and potassium citrate solutions.
- For hyperchloremic acidosis (ie, RTA), once an underlying disease entity has been identified, specific therapy is needed to control the primary problem. Therapy for the hyperchloremic acidosis itself is still needed. Depending on the type of RTA, the goals of therapy are to decrease the rate of progressive renal insufficiency by preventing nephrocalcinosis and nephrolithiasis; to neutralize metabolic bone disease; and, in children, to improve growth.
- In cases of pRTA, multitherapy with large quantities of alkali, vitamin D, and potassium supplementation is required.
- The usual range of bicarbonate administration is 5-15 mEq/kg/d, and the administration must be accompanied or preceded by the administration of large amounts of potassium.
- pRTA can be difficult to treat because alkali administration results in prompt and marked bicarbonaturia and potassium wasting.
- The use of diuretics to induce extracellular volume depletion that enhances proximal tubular bicarbonate reabsorption can be effective but is usually accompanied by worsening of the hypokalemia. Thus, diuretics must be used with caution, and they require additional potassium or the addition of potassium-sparing agents.
- In hypokalemic dRTA, treatment consists of long-term alkali administration in amounts sufficient to counterbalance endogenous acid production and any bicarbonaturia that may be present.
- Fortunately, the alkali requirements of these patients are minimal compared with the requirements needed to treat patients with pRTA. A daily dose of 1-2 mEq/kg of NaHCO3 is usually sufficient in most cases and can be provided in the form of sodium citrate solution (ie, Shohl Solution), which is well tolerated because it causes less abdominal distention and aerophagia than bicarbonate.
- Providing bicarbonate via citrate salts that are metabolized to bicarbonate in the liver provides the additional advantage of exogenous citrate from the portion escaping hepatic metabolism.
- Potassium supplements are indicated in the presence of hypokalemia. Hypokalemia can be severe, and patients can be symptomatic. Spironolactone can be used to maintain normokalemia.
- Corrective alkali therapy results in normal growth in children with dRTA if therapy is started early.
- Hypercalciuria, nephrolithiasis, and nephrocalcinosis are also prevented when alkali therapy is started in the early stages of dRTA.
- With hyperkalemic dRTA, entities amenable to intervention, such as obstructive uropathy, must be identified.
- In general, distal sodium delivery is increased if patients increase ingestion of dietary salt, taking into account that many of these patients have concomitant cardiorenal compromise.
- Fluid overload can be overcome with the addition of furosemide to a high-salt diet. This combination encourages distal delivery of sodium by rendering the collecting tubule impermeable to chloride, and it increases the exchange of sodium for hydrogen and potassium.
- Mineralocorticoid therapy (ie, fludrocortisone in daily doses of 0.1-0.2 mg) is sometimes useful for aldosterone deficiency, but take care to combine mineralocorticoid therapy with diuretics in order to prevent heart failure.
- Foods with a high potassium content and drugs that may aggravate hyperkalemia (eg, ACE inhibitors, potassium-sparing diuretics, beta-blockers) must be avoided.
- Cation-exchange resins (eg, sodium polystyrene sulfonate [Kayexalate], alkalinizing salts) can be helpful in controlling hyperkalemia.
- In many instances, careful evaluation of iatrogenic offenders (eg, beta-blockers, ACE inhibitors) can explain persistently high potassium levels in the absence of moderate-to-severe renal failure.
Medication
The goals of pharmacotherapy are to correct the acidosis, to reduce morbidity, and to prevent complications.
Alkalinizing agents
Used as gastric, systemic, and urinary alkalinizers and have been used in treatment of acidosis resulting from metabolic and respiratory causes, including diarrhea, kidney disturbances, shock, and diabetic coma.
Sodium bicarbonate (Neut)
Indicated for treatment of metabolic acidosis. Increases renal clearance of acidic drugs.
Adult
Use following formula if blood gas values and pH measurements are available to estimate dose: HCO3 - (mEq) = 0.5 X weight (kg) X [24 - serum HCO3 - (mEq/L)]
Formula has many limitations, but practitioner can roughly determine amount of bicarbonate required and subsequently titrate against pH and AG
Pediatric
Administer as in adults
Urinary alkalinization, induced by increased NaHCO3 concentrations, may cause decreased levels of lithium, tetracyclines, chlorpropamide, methotrexate, and salicylates; increases levels of amphetamines, pseudoephedrine, flecainide, anorexiants, mecamylamine, ephedrine, quinidine, and quinine
Alkalosis, hypernatremia, severe pulmonary edema, hypocalcemia, abdominal pain of unknown origin
Pregnancy
C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus
Precautions
Use only to treat documented metabolic acidosis and hyperkalemia-induced cardiac arrest; routine use in cardiac arrest not recommended; can cause alkalosis, decreased plasma potassium, hypocalcemia, and hypernatremia; caution in electrolyte imbalances (eg, CHF, cirrhosis, edema, corticosteroid use, renal failure); when administering, avoid extravasation because can cause tissue necrosis; rapid administration in neonates or children <2 y has led to hypernatremia, decreased CSF pressure, and intracranial hemorrhage
Sodium citrate (Bicitra, Modified Shohl Solution)
Treats metabolic acidosis and used as alkalinizing agent when long-term maintenance of alkaline urine is desirable.
Adult
15-30 mL sodium citrate and citric acid solution containing 500 mg sodium citrate and 334 mg of citric acid/5 mL PO tid
Pediatric
Infants and children: 2-3 mEq/kg/d sodium citrate and citric acid solution containing 500 mg sodium citrate and 334 mg citric acid/5 mL PO divided tid/qid (1 mEq sodium and 1 mEq bicarbonate/mL)
Decreases therapeutic levels of lithium, chlorpropamide, methotrexate, tetracyclines, and salicylates because of urinary alkalinization; increases toxicity of amphetamines, ephedrine, pseudoephedrine, aluminum hydroxide, quinine, and quinidine because of urinary alkalinization
Severe renal insufficiency, patients requiring sodium-restricted diet
Pregnancy
C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus
Precautions
Conversion to bicarbonate may be impaired in patients who have hepatic failure, are in shock, or are severely ill
Electrolytes
Used to correct disturbances in fluid and electrolyte homoeostasis or acid-base balance and to reestablish osmotic equilibrium of specific ions.
Potassium chloride (Klor-Con, K-Dur, Micro-K, Kaochlor, Cena-K, Gen-K)
Essential for transmission of nerve impulses, contraction of cardiac muscle, maintenance of intracellular tonicity, skeletal and smooth muscle function, and maintenance of normal renal function. Gradual potassium depletion occurs via renal excretion, through GI loss, or because of low intake. Depletion usually results from diuretic therapy, primary or secondary hyperaldosteronism, diabetic ketoacidosis, severe diarrhea (if associated with vomiting), or inadequate replacement during prolonged parenteral nutrition. Potassium depletion sufficient to cause 1-mEq/L decrease in serum potassium requires loss of approximately 100-200 mEq of potassium from total body store.
Adult
Asymptomatic patients: 20 mEq PO tid/qid
Symptomatic patient with cardiac arrhythmia, respiratory failure, or CHF: 20-40 mEq in 500 mL NS given 50-60 mL/h IV until symptoms are controlled, then switch to PO KCl
Pediatric
1 mEq/kg IV over 1-2 h initially and then prn based on frequently obtained laboratory values; not to exceed 3 mEq/kg/d
Concurrent use with ACE inhibitors may result in elevated serum potassium concentrations; potassium-sparing diuretics and potassium-containing salt substitutes can produce severe hyperkalemia; in patients taking digoxin, hypokalemia may result in digoxin toxicity; caution if discontinuing potassium administration in patients maintained on digoxin
Hyperkalemia, renal failure, conditions in which potassium retention is present, oliguria or azotemia, crush syndrome, severe hemolytic reactions, anuria, adrenocortical insufficiency
Pregnancy
A - Fetal risk not revealed in controlled studies in humans
Precautions
Do not infuse rapidly, must dilute prior to infusion; high potassium plasma concentrations may cause death from cardiac depression, arrhythmias, or arrest; plasma levels do not necessarily reflect tissue levels; monitor potassium replacement therapy whenever possible by continuous or serial ECG; when concentration >40 mEq/L infused, local pain and phlebitis may follow
Diuretics
Used to overcome fluid overload. Increase distal delivery of sodium by rendering collecting tubule impermeable to chloride and increase exchange of sodium for hydrogen and potassium.
Furosemide (Lasix)
Increases water excretion by interfering with chloride-binding cotransport system, which, in turn, inhibits sodium and chloride reabsorption in ascending loop of Henle and distal renal tubule. Dose must be individualized to patient.
Adult
20-80 mg/d PO/IV/IM; titrate up to 600 mg/d for severe edematous states; depending on response, administer at increments of 20-40 mg, no sooner than 6-8 h after previous dose, until desired diuresis occurs
Pediatric
1-2 mg/kg/dose PO; not to exceed 6 mg/kg/dose; do not administer more often than q6h; 1 mg/kg IV/IM slowly under close supervision; not to exceed 6 mg/kg; titrate PO/IV/IM administration in increments of 1 mg/kg/dose until satisfactory effect is achieved
Metformin decreases concentrations; interferes with hypoglycemic effect of antidiabetic agents; prolongs effect of neuromuscular blockers; potentiates effects of ganglionic blockers and peripheral adrenergic blockers; auditory toxicity appears to be increased with coadministration of aminoglycosides, varying degrees of hearing loss may occur; anticoagulant activity of warfarin may be enhanced; increases plasma lithium levels and toxicity; enhances potential for digoxin toxicity secondary to hypokalemia
Documented hypersensitivity, coma, anuria, state of severe electrolyte depletion
Pregnancy
C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus
Precautions
Perform frequent serum electrolyte, carbon dioxide, glucose, creatinine, uric acid, calcium, and BUN determinations during first few months of therapy and periodically thereafter; cross-sensitivity to sulfonamides
Mineralocorticoids
May be useful for aldosterone deficiency. Combine with sodium loading and diuretics to prevent heart failure.
Fludrocortisone (Florinef)
Promotes increased sodium reabsorption and potassium loss in renal distal tubules.
Adult
0.1-0.2 mg/d PO; not to exceed 1 mg/d PO
Pediatric
Not established; administer under supervision of pediatric subspecialist
Antagonizes effects of anticholinergics; rifampin, hydantoins, and barbiturates decrease salicylate levels
Documented hypersensitivity, systemic fungal infections
Pregnancy
C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus
Precautions
Taper dose gradually when therapy is discontinued; caution in Addison disease, potassium loss, and sodium retention
Vitamin D supplements
Fat-soluble vitamin that promotes absorption of calcium and phosphorus in the small intestine. Also promotes renal tubule phosphate resorption.
Calcitriol (Calcijex, Rocaltrol)
Active form of vitamin D. Used in pRTA as multitherapy with large quantities of alkali and potassium supplementation.
Adult
0.25 mcg/d PO; increase at 4- to 8-wk intervals by 0.25 mcg prn
Pediatric
Initial: 15 ng/kg/d PO
Maintenance: 5-40 ng/kg/d PO
Cholestyramine and colestipol decrease absorption; possible increased calcitriol effects with concomitant magnesium-containing antacids and thiazide diuretics
Documented hypersensitivity, hypercalcemia, malabsorption syndrome
Pregnancy
C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus
Precautions
Maintain adequate fluid intake; discontinue if serum calcium increased outside reference range
More on Hyperchloremic Acidosis |
| Overview: Hyperchloremic Acidosis |
| Differential Diagnoses & Workup: Hyperchloremic Acidosis |
 Treatment & Medication: Hyperchloremic Acidosis |
| Follow-up: Hyperchloremic Acidosis |
| References |
| Further Reading |
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References
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Davenport A. Potential adverse effects of replacing high volume hemofiltration exchanges on electrolyte balance and acid-base status using the current commercially available replacement solutions in patients with acute renal failure. Int J Artif Organs. Jan 2008;31(1):3-5. [Medline].
Blake-Palmer KG, Karet FE. Cellular physiology of the renal H+ATPase. Curr Opin Nephrol Hypertens. Jun 24 2009;[Medline].
Basic DT, Hadzi-Djokic J, Ignjatovic I. The history of urinary diversion. Acta Chir Iugosl. 2007;54(4):9-17. [Medline].
Grünfeld JP, Rossier BC. Lithium nephrotoxicity revisited. Nat Rev Nephrol. May 2009;5(5):270-6. [Medline].
Batlle D, Kurtzman NA. Distal renal tubular acidosis: pathogenesis and classification. Am J Kidney Dis. May 1982;1(6):328-44. [Medline].
Burton DR. Metabolic acidosis. In: Clinical Physiology of Acid-Base and Electrolyte Disorders. 4th ed. New York, NY: McGraw-Hill; 1994:. 540-604.
DuBose TD Jr. Hyperkalemic hyperchloremic metabolic acidosis: pathophysiologic insights. Kidney Int. Feb 1997;51(2):591-602. [Medline].
Garella S, Salem MM. Clinical acid-base disorders. In: Oxford Textbook of Clinical Nephrology. 2nd ed. Oxford, UK: Oxford University Press; 1998:. 313-26.
Lash JP, Arruda JA. Laboratory evaluation of renal tubular acidosis. Clin Lab Med. Mar 1993;13(1):117-29. [Medline].
Rothstein M, Obialo C, Hruska KA. Renal tubular acidosis. Endocrinol Metab Clin North Am. Dec 1990;19(4):869-87. [Medline].
Walmsley RN, White GH. Normal "anion gap" (hyperchloremic) acidosis. Clin Chem. Feb 1985;31(2):309-13. [Medline].
Further Reading
Clinical guidelines:
Metabolic acidosis and growth in children. Caring for Australasians with Renal Impairment - Disease Specific Society. 2005 Dec. 3 pages. NGC:006105
Clinical trials:
Genetic Study of Nephrolithiasis in Gouty Diathesis
Keywords
hyperchloremic acidosis, acidosis, metabolic acidosis, renal acidosis, renal tubular, renal acidosis, metabolic acidosis anion gap, renal tubular acidosis, anion gap, AG acidosis, nonanion gap acidosis, normal anion gap acidosis, low plasma bicarbonate, low bicarbonate concentration, chronic metabolic acidosis, bicarbonate-wasting acidosis, hyperchloremic metabolic acidosis, proximal renal tubular acidosis, pRTA, distal renal tubular acidosis, dRTA, hypokalemic distal renal tubular acidosis, RTA type I, type I RTA, hyperkalemic distal renal tubular acidosis, RTA type IV, type IV RTA, classic distal tubular acidosis, uremic acidosis, gastrointestinal bicarbonate loss, bicarbonaturia, bicarbonate wasting, potassium wasting, hypokalemia
