Treatment of Metabolic Acidosis – When to use Bicarbonate

The decision whether to give bicarbonate (HCO₃^–) for metabolic acidosis can be confusing.

In some conditions, such as lactic acidosis, bicarbonate has not been shown to be beneficial, may be harmful, and is reserved for very severe acidosis.

In other conditions such as Chronic Kidney Disease (CKD) treatment with alkali is recommended to achieve a normal serum total CO2.  Not treating may be associated with increased risk of progression, bone disease and malnutrition.

Framework for when to give bicarbonate

One can learn the specific guidelines for each condition.  However, an understanding of the pathophysiologic cause of the acidosis is a useful determinant.

• If the metabolic acidosis is caused by acid generation (organic acidosis), HCO₃^– administration is reserved for severe life threatening acidosis.
• If the metabolic acidosis is caused by HCO₃^– loss from the body (or lack of HCO₃^–  generation by the kidney), the acidosis should be corrected with HCO₃^–  (or an alkali equivalent).

Organic Acidosis

In organic acidosis, a bicarbonate equivalent is generated (typically lactate or a ketone).  When this occurs a HCO₃^– anion is consumed.  In these cases treatment is guided at treating the underlying pathologic process.  When this occurs HCO₃^– will be regenerated.

• In general an organic acidosis is associated with an elevated anion gap
• IV HCO₃^– may be harmful in these cases
• Treatment with intravenous HCO₃^– is only recommended for severe acidemia

Lactic Acidosis

• The main treatment of lactic acidosis is restoration of tissue perfusion.
• Recommendations are to reserve treatment with IV bicarbonate unless the pH is < 7.1 – 7.2.
• HCO₃^– is given more liberally if there is associated Acute Kidney Injury, to target a pH > 7.3 as this may help to decrease the need for dialysis in this context.

This study showed that using HCO₃^–  for a pH < 7.2 to achieve target a pH > 7.3 did not reduce mortality except if there was Acute Kidney Injury (AKI)

Sodium bicarbonate therapy for patients with severe metabolic acidaemia in the intensive care unit (BICAR-ICU): a multicentre, open-label, randomised controlled, phase 3 trial – Archive ouverte HAL

Diabetic Ketoacidosis

• The main treatment in DKA is insulin.
• Recommendations are to reserve HCO₃^– unless the acidemia is severe enough to affect cardiac contractility (pH < 6.9).
• Since the organic anion (ketone) is a HCO₃^– equivalent, reversal of the ketoacidosis will result in HCO₃^– Too liberal administration of HCO₃^– may result in a metabolic alkalosis when this occurs.

This study did not show a benefit of HCO₃^–  with an initial pH of 6.9 – 7.14

Bicarbonate Therapy in Severe Diabetic Ketoacidosis | Annals of Internal Medicine

How can treatment with bicarbonate be harmful?

The  administration of IV HCO₃^–  in lactic or ketoacidosis can be harmful – why is this?

• Worsen intracellular acidosis

When IV HCO3^– is given  some of it is converted to CO2 by the following biochemical process.

HCO₃^– + H⁺  ⇄  H2CO₃  ⇄  H₂0 + CO₂

CO₂ can diffuse across the cell membrane faster than HCO₃^–. So paradoxically giving HCO₃^– in this situation can worsen intracellular acidosis.

The increase in CO₂ production can be an issue in mixed acidosis.  If there is a respiratory component to acidosis the patient may not be able to ventilate the increased CO₂ that is generated.  In this situation the respiratory component of the acidosis may worsen.

• Worsen ionized calcium

Ionized calcium is pH dependent.  Administration of HCO₃^– can lower ionized calcium.  This may adversely affect cardiac function or even cause seizures.

When IV bicarbonate is necessary

IV HCO₃^– can be given as amps pushed or in an IV drip.  Although amps may need to be administered in an emergent situation, I prefer giving as IVF for 2 reasons.

• Amps of HCO₃^– are hypertonic. This may cause hypernatremia/hypertonicity.
• Pushing amps of HCO₃^–  can more rapidly lower ionized calcium which may cause complications in a patient who is already hypocalcemic.

Isotonic  IV HCO3^– infusions are:

• D5W with 150 milliequivalents (3 amps) NaHCO₃/ Liter
• ½ NS with 75 milliequivalents (1 ½ amps) NaHCO₃/ Liter

Dialysis

What about dialysis?  How does dialysis correct acidosis?

• Dialysis replaces HCO₃^–
• HCO₃^– in the dialysate diffuses down the concentration gradient into the blood.
• Dialysis does not correct acidosis by the removal of lactate. Although lactate is removed by dialysis, this is a HCO₃^– It is the associated H⁺ that causes the acidosis.

What is the benefit of replacing HCO₃^–  with dialysis vs giving IV HCO₃^– ?

• With dialysis HCO₃^– can be administered without volume.  It can be given in a euvolemic or even hypovolemic manner.  Giving HCO₃^–   IV requires volume which may be problematic in an oliguric patient with Acute Kidney Injury (AKI).

Non Organic (Mineral) Acidosis

Acidosis can also be caused by a loss of HCO₃^–  from the body.  This can be:

• Non renal – Typically gastrointestinal losses in diarrhea
• Neobladder (or bladder augmentation). The neobladder is created using colon tissue.  This gastrointestinal mucosa allows for electrolyte (HCO₃^– ) secretion.
• Renal – Type 2 (proximal) Renal Tubular Acidosis (RTA). In this condition there is impaired HCO₃^– reabsorption in the proximal tubule.

Metabolic acidosis can also be caused by the kidney failing to excrete acid (H⁺).  For every H⁺ the kidney excretes a HCO₃^– anion is generated which is reabsorbed into the body.

The majority of renal acid (H⁺) excretion is in the form of ammonium NH₄⁺.

• Intercalated cells of the distal nephron secrete H⁺.
• H⁺ combines with ammonia (NH₃) to form ammonium (NH₄⁺).
• Ammonium (NH₄⁺) is excreted in the urine.

How does H⁺ excretion result in HCO3^– generation? By the following biochemical reaction.

HCO₃^– + H⁺  ⇄  H₂CO₃  ⇄  H₂0 + CO₂

• For every H⁺ excreted a HCO₃^– is generated.
• This HCO₃^– is returned to the circulation.
• The lack of HCO₃^– generation is equivalent to a HCO₃^–

Chronic Kidney Disease

In CKD the goal is to keep the HCO₃^– normal > 22 mEq/L

Prevalence of acidosis in CKD

• Stage 2 – 7%
• Stage 3 – 13%
• Stage 4 – 37%

In CKD (and Renal Tubular Acidosis RTA) chronic acidosis can result in:

• Bone disease/ decreased bone mineral density. Bone components serve as a buffer to the acidosis.
• Muscle Wasting
• Adverse cardiovascular outcomes
• Progression of CKD

In the initial stages of CKD the anion gap will be normal.  In later stages it increases due to retention of phosphate and sulfate along with other anions.

Treatment can be with sodium bicarbonate or sodium citrate.  Citrate is metabolized to bicarbonate.

Summary

Metabolic acidosis can be caused by increased acid generation (i.e. lactate), HCO₃^–  loss from the body (i.e. diarrhea) or lack of renal acid excretion (i.e. CKD) resulting in decreased HCO₃^– generation.

In general if the acidosis is caused by a loss of HCO₃^–  from the body or impaired HCO₃^–  generation treatment with alkali to target a normal bicarbonate is indicated.  If the acidosis is caused by increased production of an organic anion, treatment with HCO₃^–  is reserved for severe life threatening acidemia while the underlying cause is treated.