By Craig Smollin, MD
Sodium bicarbonate administration is a suggested treatment modality for a variety of toxicologic and nontoxicologic conditions such as poisonings by tricyclic antidepressants, toxic alcohols, and salicylates, and other conditions such as hyperkalemia. The rationale for its use can be divided into several distinct categories, and its method of administration depends on its clinical indication.
A 28 year-old woman with a history of depression is brought to the emergency department approximately one hour after an overdose of amitriptyline. She is somnolent with a Glasgow coma score (GCS) of 8. Her blood pressure is 90 mm Hg by palpation and her heart rate is 110 beats/min. She undergoes immediate endotracheal intubation with moderate hyperventilation, and receives a 2 liters bolus of normal saline. Fifty grams of activated charcoal are instilled by NG tube into the stomach. An EKG shows sinus tachycardia with wide ventricular complexes (QRS interval > 160 msec) with a prominent R wave in lead aVR. Intravenous fluids and norepinephrine are administered for hypotension. Sodium bicarbonate is administered as a bolus of 1 mEq/kg and a repeat EKG reveals narrowing of the QRS complexes. However, ten minutes later the QRS abnormalities recur. Over the course of the next several hours, the patient receives ten ampules of sodium bicarbonate. Her arterial pH increases to greater than 7.50 but her QRS complexes remain narrow and she does not develop any more dysrhythmias. After 36 hours the patient is extubated and is awake and alert with resolution of hypotension. She is discharged to the psychiatry service.
- What are the indications for the use of sodium bicarbonate in toxicology?
- By what mechanism does sodium bicarbonate work?
- How should sodium bicarbonate be administered?
Drugs and toxins that act as sodium channel antagonists include agents listed in List 1. Together they comprise perhaps the largest group of cardiotoxic agents. These cardiotoxins are responsible for more fatal dysrhythmias annually than any other class of medications. In addition to use in treatment of poisonings with sodium channel blocking activity, sodium bicarbonate may also be used as adjunctive therapy in poisonings due to methanol, ethylene glycol, and salicylates.
List 1. Drugs with Na Channel Blocking Properties
- Tricyclic antidepressants
Dozens of fatal poisonings from toxic alcohols are reported to poison centers each year. Toxic alcohols such as ethylene glycol and its derivatives and methanol, are found in products like windshield washer fluids, brake fluids and antifreeze in automobiles, cleaning solutions around the house, and other industrial chemicals. Exposures are both accidental and intentional, with most life-threatening cases from self-harm gestures.
Salicylates are still one of the most common analgesics and anti-inflammatory agents found in medicine cabinets. While the possible association with Rye’s syndrome significantly reduced the utilization of aspirin in this country years ago, its presence has been rejuvenated as the drug’s cardio-protective activity has been realized. Fatal aspirin poisonings are still very commonly reported to poison control centers.
The role of sodium bicarbonate as an antidote depends on the specific indication. Its mechanisms as an antidote for sodium channel blocking drugs are incompletely understood. In vitro studies in human cardiac myocytes suggest that the bicarbonate component promotes dissociation of the tricyclic antidepressant imipramine from sodium channels at higher serum pH. Recent evidence suggests that the sodium component plays a more important role by helping to drive sodium through both blocked and unblocked channels. While the relative contribution of each mechanism is not completely understood, it is clear that the administration of sodium bicarbonate effectively narrows the QRS complex and leads to the resolution of dysrhythmias induced by drugs and toxins with sodium channel blocking properties.
Sodium bicarbonate may also be used to alkalinize the serum and urine to respectively minimize distribution and enhance elimination of some weak acids, such as salicylate, that exist in equilibrium between an ionized and unionized state. Because unionized species more readily cross cellular barriers and lead to increased toxicity, maintaining toxins in an ionized state is theoretically more desirable. Serum alkalinization may prevent distribution into the central nervous system. Urinary alkalinization will ionize the drug in the urine preventing resorption by the kidneys back into the blood, thus enhancing toxin elimination. This concept is often referred to as “ion trapping.”
Metabolism of toxic alcohols such as methanol and ethylene glycol can result in severe acidemia with pH values approaching 7 or less. In such instances, the severe acidemia may be an immediate threat to life by contributing to dysrhythmias and hemodynamic instability. While dialysis and the administration of the antidote fomepizole are primary treatment interventions in these cases, sodium bicarbonate administration should also be considered as temporizing, adjunctive treatment. In methanol poisoning, for example, maintaining normal serum pH is thought to be helpful in maintaining function of formate dehydrogenase to help metabolize formate.
Nebulized sodium bicarbonate has been used to treat pulmonary toxicity resulting from chlorine gas inhalation. When chlorine gas comes in contact with the mucosa of the respiratory tract, it forms hydrochloric acid that can result in pulmonary injury. Nebulized sodium bicarbonate may help to neutralize such acid production if given early after exposure. Although some toxicologists suggest an exothermic reaction may occur with this neutralization, this is somewhat controversial.
The clinical scenarios in which sodium bicarbonate may be utilized vary widely. Sodium channel blockade within cardiac myocytes may result in hypotension and dysrhythmias. The EKG can be an important indicator of the presence of sodium channel blocking drugs. Typical EKG findings include prolonged QRS duration, prolonged QT duration, or ventricular dysrhythmias. In addition, a late R wave in lead aVR will often be present, particularly in cases of TCA poisoning. Dysrhythmias may lead to syncope or sudden death but are often precipitated by convulsions. Because many agents with sodium channel blocking properties also have antimuscarinic effects, poisoned patients may also experience signs and symptoms in Table 2.
List 2. Signs and symptoms of antimuscarinic toxicity
- blurred vision due to mydriasis and inability to accommodate
- dry mouth and skin
- urinary retention
- flushing due to peripheral vasodilation
- hyperthermia due to inability to dissipate heat by producing and evaporating sweat
When bradycardia is present with toxicity from agents know to be both antimuscarinic and block sodium channels, this is an ominous sign suggestive of severe sodium channel blockade. Sodium bicarbonate should be considered and rapidly administered in this situation when other signs of sodium channel blockade such as increased QRS duration or hypotension are present.
Toxic alcohol poisoning most commonly presents with a metabolic acidosis and patients can appear intoxicated. Respiratory compensation with tachypnea may occur while the parent alcohols are metabolized to the respective organic acid metabolites.
Salicylate poisoning often presents with a mixed metabolic acidosis and respiratory alkalosis, due to the mixed effects of aspirin on the pulmonary system and cellular respiration. Patients with salicylate poisoning are often alkalemic on presentation with hyperventilation.
Patients presenting with ventricular dysrhythmias, wide QRS complexes, or severe hypotension should be suspected of poisoning by a sodium channel antagonist. Some of these agents, such as cocaine or diphenhydramine, may show up on rapid toxicology screening or gas chromatography confirmation, but this will only confirm presence of the drug. Laboratory test for serum concentrations to gauge the degree of toxicity will not be available for most of these agents.
Toxic alcohol poisoning can be suspected as part of the differential diagnosis of an elevated anion gap metabolic acidosis. Blood levels of methanol are more commonly available at hospital laboratories than ethylene glycol, but both are often “send-out” studies to reference laboratories requiring hours or days for results to return. Osmolal gap estimations between measured and calculated osmols may also assist in uncovering the presence of a toxic alcohol, but the absence of an osmolal gap should not be considered definitive evidence to completely rule out the presence of toxic alcohols, particularly ethylene glycol.
How is the osmolal gap caluculated?
Osmolal Gap = Measured Osmolality – Calculated Osmolality
Calculated Osmolality = 2Na + Glucose/18 + BUN/14 + Ethanol Concentration/4.6)
What is the “normal range” for the osmolal gap? Typically the osmolal gap is between 0 to10 but the range may be as wide as -5 to 15.
Salicylate concentrations are run by most hospital laboratories and results often return rapidly. The presence of a mixed acid-base disorder on blood gas analysis is often helpful in suggesting this diagnosis when a history is not available.
The dosage and administration of sodium bicarbonate depends on clinical indications. When sodium bicarbonate is administered for sodium channel antagonists, we recommend the use of intermittent boluses of 1-2 mEq/kg titrated to clinical effect (narrowing of the QRS interval and improvement of blood pressure). Generally, the target for serum pH is 7.4 – 7.5. While some have advocated the use of continuous sodium bicarbonate infusions, this has not been well studied.
For salicylates, we recommend the use of continuous infusions of sodium bicarbonate. It is important to remember that typically one ampule of sodium bicarbonate contains 44-50 mEq of sodium bicarbonate. A typical sodium bicarbonate solution needed for the treatment of salicylate poisoning would contain 3 ampules of sodium bicarbonate in D5W, infused at 200 mL/hour. Potassium supplementation is often also needed to help prevent hypokalemia resulting from intracellular shifting as serum pH rises, and to prevent paradoxical aciduria that can occur during exchange of potassium for hydrogen ions in the distal tubules of the kidney. Risks of continuous infusion include hypernatremia, hypokalemia, and fluid overload.
For treatment of toxic alcohol poisoning, sodium bicarbonate administration should be use in conjunction with dialysis to correct severe acid base disorders. Numerous ampules may be needed to correct the acidemia while dialysis is being initiated.
Discussion of case questions
- What are the indications for the use of sodium bicarbonate in toxicology, and by what mechanisms does it work?
The various uses and proposed mechanisms of action of sodium bicarbonate include:
- treatment of drug overdoses whereby the offending agent has sodium channel blocking properties;
- urinary and serum alkalinization to enhance the elimination of drugs by “ion trapping” and minimize drug distribution, respectively;
- promoting the solubility of drugs or toxins that may otherwise precipitate in the kidney resulting in renal failure; and
- neutralization of toxins that produce severe acidemia.
- How should sodium bicarbonate be administered?
Depending on the clinical scenario sodium bicarbonate can be administered as repeated intravenous boluses, a continuous intravenous infusion, or by hand-held nebulizer for cases of acid inhalation. Oral sodium bicarbonate should never be administered to patients with acid ingestions.