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CALL US...TM
The
Official Newsletter of the
Volume 5, Number 1.
Spring, 2007
The Use of Sodium Bicarbonate in
Medical Toxicology
Introduction
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.
Case presentation
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
Questions
1. What are the indications for the use of
sodium bicarbonate in toxicology?
2. By what mechanism does sodium bicarbonate
work?
3. How should sodium bicarbonate be
administered?
Epidemiology
Drugs and toxins that act as sodium
channel antagonists include agents listed in Table 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.
Table 1.
Drugs with Na Channel Blocking Properties
Tricyclic antidepressants
Cocaine
Propranolol
Diphenhydramine
Propoxyphene
Phenothiazines
Chloroquine
Quinine
Quinindine
Procainamide
Disopyramide
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
Pathophysiology
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.
Clinical presentation
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.
Table 2.
Signs and symptoms of antimuscarinic toxicity
1.
blurred vision
due to mydriasis and inability to accommodate
2.
dry mouth and
skin
3.
tachycardia
4.
ileus
5.
urinary
retention
6.
flushing due to
peripheral vasodilation
7.
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.
Diagnosis
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.
Treatment
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
1. 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: (1) treatment of drug overdoses
whereby the offending agent has sodium channel blocking properties; (2) urinary
and serum alkalinization to enhance the elimination
of drugs by “ion trapping” and minimize drug distribution, respectively;
(3) promoting the solubility of drugs or toxins that may otherwise precipitate
in the kidney resulting in renal failure; and (4) neutralization of toxins that
produce severe acidemia.
2. 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.
Consultation assistance
Consultation with a specialist in poison information or with a medical toxicologist can be obtained free of charge by calling the California Poison Control System at 1-800-411-8080.
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