Continuing Education Activity

Sodium bicarbonate is a multifaceted medication that plays a crucial role in managing and treating diverse disease pathologies. This activity delves into the expansive applications of sodium bicarbonate, providing healthcare professionals with a nuanced understanding of its indications, mechanism of action, and contraindications. The program focuses on its pivotal role in treating conditions such as lactic acidosis and QRS prolongation, offering participants in-depth insights into therapeutic considerations, including dosing, toxicities, and relevant interactions. By examining sodium bicarbonate's adverse event profile, participants will be better equipped to ensure its effective utilization across a spectrum of clinical scenarios. This evidence-based activity aims to empower interprofessional healthcare team members with the essential knowledge to optimize sodium bicarbonate's potential to enhance patient outcomes.

Objectives:

• Identify clinical scenarios and biochemical abnormalities where sodium bicarbonate is indicated while considering evidence-based guidelines.

• Differentiate between FDA-approved and non-FDA-approved uses of sodium bicarbonate while understanding the clinical evidence supporting each application.

• Assess the effects of sodium bicarbonate while promptly evaluating for therapeutic responses and identifying any toxic changes or adverse reactions.

• Identify sodium bicarbonate therapy's indications, benefits, and potential risks while ensuring informed decision-making with patients.

Indications

Sodium bicarbonate is a chemical compound comprising sodium (Na⁺) and bicarbonate (HCO3^-), with numerous indications.

FDA-approved Indications

• Acute or chronic metabolic acidosis related to:
  • Severe renal disease
  • Uncontrolled diabetes
  • Severe primary lactic acidosis [1][2][3]
  • Circulatory insufficiency due to shock
  • Severe dehydration
  • Extracorporeal circulation of blood
  • Cardiac arrest
  • Drug toxicity
  • Barbiturates
  • Toxic alcohols [4]
  • Urine alkalization [5]
  • Severe diarrhea with HCO₃^- loss
• Urinary alkalinization
• Dyspepsia
  • Oral sodium bicarbonate is approved to relieve heartburn, acid indigestion, and upset stomach associated with these symptoms, and is available over the counter (eg, baking soda, effervescent granules).[6]

Non-FDA Approved Indication ("Off-label" uses)

• Nebulized sodium bicarbonate is an excellent option for treating chemical injuries from chlorine gas, especially within the pulmonary mucosa; it is believed that the inhaled gas neutralizes when it reacts with water and bicarbonate within the respiratory system.[7] 
• Tricyclic antidepressant overdose resulting in QRS prolongation [8]
• Cardiac conduction delays

Mechanism of Action

Bicarbonate is often a standard element of body fluids and is often regulated by the kidney via secretion or absorption methods to counter-regulate changes in serum pH. This action often leads to its second administration as it is known to alkalinize the urine, capable of changing precipitants in urine and providing a means of normalizing tubular acid concentration gradients to manage high fluctuations in serum acid-base status changes. This alkalization process enables compounds that would normally precipitate in the renal tubules in acidic conditions to be buffered within the renal tubule, thereby preventing mechanical or chemical damage while also providing increased efficiency within the kidney tubules to excrete acidified substances without disrupting the electrochemical gradient.[9][4]

Pharmacokinetics

After administration, intravenous sodium bicarbonate dissociates to form sodium (Na⁺) and bicarbonate (HCO₃^-) ions. Bicarbonate anions can consume hydrogen ions (H) and subsequently convert to carbonic acid (H₂CO₃). Carbonic acid subsequently converts to water (H₂O) and carbon dioxide (CO₂) for excretion from the lungs. The main therapeutic effect of intravenous sodium bicarbonate administration is increasing plasma bicarbonate levels, which buffer excess hydrogen ion (H⁺) concentration, raising serum pH to combat clinical manifestations of acidosis.

1. Absorption: Following oral administration, excess bicarbonate is absorbed, resulting in metabolic alkalosis and alkalinization of urine. IV administration results in complete bioavailability. 
2. Distribution: Sodium bicarbonate is widely distributed in the extracellular fluid.
3. Metabolism: Sodium bicarbonate has an unknown half-life.
4. Excretion: Bicarbonate is excreted in the urine; it is excreted and reabsorbed by the kidneys. Bicarbonate is also transported to the lungs and exhaled as carbon dioxide.

Administration

Dosage Forms and Strengths

NaHCO₃ comes in various forms, including oral tablets, IV injections, and IV infusions. Oral formulations are available via 325 mg powder and 650 mg oral tablets. One mEq NaHCO₃ is 84 mg. One gram of NaHCO₃ contains 11.9 mEq of sodium and bicarbonate ions. One 650 mg tablet of NaHCO₃ has 7.7 mEq of sodium and bicarbonate ions.

The 2 primary IV injection formulations of NaHCO₃ are:

• 7.5% concentration = 44.6 mEq NaHCO₃ in 50 mL. This concentration supplies 75 mg/mL of 0.9 mEq/mL each of sodium and bicarbonate.
• 8.4% concentration = 50 mEq in 50 mL. This concentration supplies 84 mg/mL of 1 mEq/mL for each sodium and bicarbonate. One ampoule of 50 mL contains 50 mEq sodium and 50 mEq bicarbonate to a total of 100 mEq/50 mL and corresponds to 2000 mOsm/L. This formulation is a hypertonic solution that can raise serum sodium concentration by attracting water to the extracellular areas from the intracellular space.
• A 4.2% and 5% solution are also available, though not as often used. 

NaHCO₃ IV infusions are available in the following formulations:

• 50 mEq, 75 mEq, 100 mEq NaHCO₃ in 1L of 0.45% NS, 0.45% NS+D5W, or D5W
• 50 mEq, 75 mEq, 100 mEq, and 150 mEq NaHCO₃ in 1L D5W or sterile water
• Bicarbonate tablets are available as 650 mg NaHCO₃, 25 to 50 mEq KHCO₃, 20 to 40 mEq KHCO₃-citric acid, and 20 to 50 mEq KHCO₃-KCl tablets.[10]

In patients with arrhythmias and cardiovascular instability, sodium bicarbonate can be administered to adults with 4 to 8-hour IV infusions. Each dose should be monitored and planned in a standard protocol to help evaluate the degree of response expected and predicted to understand the necessity to advance further infusions or withhold administration, given its fluid overloading effects. 

Adult Dosage

Acute metabolic acidosis: 2 to 5 mEq/kg/dose IV for a single dose; subsequent dosing based on patient response and acid-base status.

Chronic metabolic acidosis:

• Chronic renal failure: 1625 to 2925 mg/day orally divided every 4 to 6 hours; dose adjustments are based on serum HCO₃ levels.
• Distal renal tubular acidosis: 48 to 168 mg/kg/day orally divided every 4 to 6 hours; dose adjustments are based on serum HCO₃ levels.
• Proximal renal tubular acidosis: 420 to 840 mg/kg/day orally divided every 4 to 6 hours; dose adjustments are based on serum HCO₃ levels.

Lactic acidosis: Using sodium bicarbonate remains controversial but is an option if pH is below 7.[11]

Diabetic ketoacidosis: The use of sodium bicarbonate remains controversial in diabetic ketoacidosis since recovery outcomes are similar with or without NaHCO3. However, if the pH is below 7 after 1 hour of fluid administration, sodium bicarbonate is still recommended. Sodium bicarbonate should be given in hypotonic fluid every 2 hours until pH is 7 or higher.[12]

Salicylate overdose: 1 to 2 mEq/kg/dose IV for a single dose

Hyperkalemia: When patients with severe hyperkalemia (serum potassium level of more than 6 mEq/L or more than 5.5 mEq/L with arrhythmia or EKG changes) have metabolic acidosis, sodium bicarbonate should be administered. The dose needed is empirical and unpredictable. Initially, 150 mEq of sodium bicarbonate can be given in 1 liter of 5% dextrose over 4 hours. More can be provided if acidosis is not corrected with this regimen.[13] If there is a need to decrease serum potassium emergently, 50 mEq of NaHCO3 IV can be given over 5 minutes, followed by other methods of potassium reduction.

Urinary alkalinization: 975 to 1950 mg orally every 4 hours, starting with 3900 mg orally for a single dose

Dyspepsia: varies with age

• For those younger than 60: 650 to 2600 mg should be taken orally every 4 hours to a maximum of 15.6 g/d.
• Age 60 years and older: 650 to 1300 mg orally every 4 hours as needed to a maximum of 7.8 g/d.

Cardiac arrest: Currently, routine bicarbonate administration for cardiac arrest is no longer a recommendation. The agent should only be administered for cardiac arrest due to hyperkalemia, tricyclic antidepressant overdose, or metabolic acidosis.[14] Dosing is 1 mEq/kg per dose, repeated according to arterial blood gas measurements. Sodium bicarbonate should ideally be given after adequate alveolar ventilation and the initiation of cardiac compressions.

Specific Patient Population

• Hepatic impairment: Dosing in patients with hepatic impairment is undefined.
• Renal impairment: Dosing in renal impairment is undefined; however, clinicians should exercise caution as the drug may cause sodium retention. Dosing in dialysis is undefined.
• Pregnancy Considerations: Clinicians should weigh the risks and benefits when considering sodium bicarbonate during pregnancy, as comprehensive human data is unavailable. There is a potential risk of fluid retention based on the drug's mechanism.
• Breastfeeding Considerations: No human data are available to assess the risk of fetal harm or affecting milk production.
• Pediatric patients: Rapidly injecting (10 mL/min) of hypertonic sodium bicarbonate into neonates and children younger than 2 may cause hypernatremia, decreased cerebrospinal fluid pressure, and possible intracranial hemorrhage. The administration rate in pediatric patients should be limited to 8 mEq/kg/d. A 4.2% solution may be preferable for such slow administration. In emergent situations like cardiac arrest, the risk accompanying rapid infusion must be weighed against the potential for fatality due to acidosis.
• Older patients: Clinical studies of sodium bicarbonate have had insufficient numbers of subjects 65 and older to determine whether they respond differently than younger subjects. Additionally, reported clinical experience has not identified different responses between older and younger patients. Clinicians should generally exercise caution in dosing sodium bicarbonate in older patients, typically starting at the lower end of the dosing range.

Adverse Effects

Sodium bicarbonate can result in a multitude of adverse effects, including:

• Metabolic alkalosis
• Headache
• Muscle pain and twitching
• Nausea or vomiting
• Bradypnea
• Nervousness or restlessness
• Unpleasant taste
• Increased frequency of urination
• Tissue damage/necrosis secondary to extravasation [15][11]

Administration and extravasation of sodium bicarbonate have been known to cause chemical cellulitis due to its basic properties and have resulted in tissue necrosis, ischemia, and tissue death at administration sites. 

In significant dose administrations, it is known to increase edema and is more commonly noted in those with renal insufficiency, given its clearance via the kidneys. This increase in tissue edema appears to be due to an excess hyperosmolar state developed during the administration of sodium bicarbonate, resulting in fluid retention. This condition can be especially challenging to manage in those with underlying cardiovascular comorbidities, including those with heart failure and intravascular fluid management difficulties. 

Drug-Drug Interactions

Certain IV additives may be incompatible; norepinephrine and dobutamine are incompatible with sodium bicarbonate solution.

The addition of sodium bicarbonate to parenteral solutions containing calcium should be avoided, except in instances where compatibility has already been established. Sodium bicarbonate/calcium admixtures may result in precipitation or hazing. The injection should not be used if precipitate is present.

Due to its ability to buffer pH and influence acid-base shifts, sodium bicarbonate can also affect many drug-drug interactions, including fluoroquinolones such as levofloxacin and tetracyclines such as doxycycline and minocycline. These effects are often noted in oral preparations where both medications are taken orally and result in significantly decreased GI absorption due to compound structural alterations due to changes in pH in the GI lumen, such as NSAIDs, mesalamine, and also with extended-release formulations (eg, methylphenidate). 

Other interactions are due to the effects of sodium bicarbonate on increasing renal tubular pH, thereby increasing passive tubular reabsorption and increasing serum levels of medications such as dextroamphetamine and methamphetamine.

Contraindications

Due to rapid alkalotic effects, sodium bicarbonate is contraindicated in those with signs/symptoms or laboratory values indicating underlying metabolic or respiratory alkalosis due to the potential for exacerbation of symptoms. Another contraindication is for those who have hypersensitivity to sodium bicarbonate injections.[4][16]

Secondary to deionizing effects on metabolically active ionized serum calcium, sodium bicarbonate is contraindicated in patients with hypocalcemia. The administration of sodium bicarbonate can also exacerbate hypernatremia.

Rapid or high-dose administration of undiluted sodium bicarbonate may lead to decreased CSF pressure and intracranial hemorrhage, particularly in the pediatric population younger than 2.[17]

Monitoring

Clinicians should monitor serum electrolytes such as calcium, urinary pH, and when indicated, arterial blood gases. In metabolic acidosis, the acid-base balance should be monitored.[18]

Toxicity

Rapid administration of sodium bicarbonate may increase intravascular fluid volume, leading to acute pulmonary edema. Additionally, the medication must be administered judiciously in those with congestive heart failure, significant renal disease, or sodium retention due to exacerbation of sodium retention and edema.

Sodium bicarbonate administration in a rapid infusion or as large boluses can result in acute metabolic alkalosis, reducing serum ionized calcium. This acute shift in ionized calcium can result in tetany. The accompanying alkalosis is treatable with ammonium chloride. Hypocalcemia may be addressed with calcium gluconate. An addition of 0.9% NS infusion and potassium supplementation may also be indicated.[19][20]

Enhancing Healthcare Team Outcomes

Appropriate use of sodium bicarbonate and preventing its potential adverse effects require the involvement of the allied interprofessional team of healthcare professionals. When ordering sodium bicarbonate for a patient, the clinician, nursing team, and pharmacy team must recognize the indications for the medication and observe any toxicity or adverse effects from its administration. Clinicians need to ensure that sodium bicarbonate is the appropriate therapeutic choice. Nursing staff will either administer the drug for inpatients or give instructions for home administration for outpatient use and counsel regarding potential adverse events. Pharmacists will verify appropriate dosing, perform medication reconciliation checking for drug-drug interactions, and reinforce patient counseling points where applicable. 

Utilizing an interprofessional team approach to sodium bicarbonate therapy will increase the chances of therapeutic success while minimizing adverse events, resulting in better patient outcomes. Consistent clinical observation and recognition at the bedside consistently improve morbidity and mortality by reducing medication errors, medication-induced reactions, and adverse effects.