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CARDIOVASCULAR JOURNAL OF AFRICA • Volume 26, No 3, May/June 2015
138
AFRICA
Sodium bicarbonate is the first choice in the treatment of
TCA-induced cardiotoxicity.
4,5
There are several mechanism by
which NaHCO
3
treatment may confer beneficial effects. It may
increase serum sodium levels and reduce cardiac arrhythmias
resulting from the inhibition of sodium channels.
4,11
It may
reduce the alkaline pH of the serum concentration of the ionised
fraction of the drug that is responsible for cardiotoxicity.
20,26
In
addition, it may give rise to volume expansion.
4
Studies have shown that NaHCO
3
treatment reduces the
incidence of ventricular arrhythmias, prevents prolonged QRS
and QT intervals, and improves hypotension.
11,20
However,
the disadvantages of this treatment include volume overload,
hypokalaemia induced by alkalosis, and delay in the elimination
of the drug in an alkaline pH.
4
For this reason, it has been
suggested that hypertonic NaHCO
3
treatment should be used
only in the presence of severe cardiac findings.
6
Previous studies have frequently reported an association
between TCA poisoning and hyponatraemia.
24,27-29
Possible causes
of this situation are sodium loss due to vomiting or gastric
lavage, treatment with hypotonic fluids, or, most importantly,
inappropriate secretion of antidiuretic hormone due to critical
illness.
Our clinical observations of patients with amitriptyline
poisoning suggested that there might be a relationship between
hyponatraemia and the degree of poisoning, particularly with
regard to the presence of cardiac arrhythmias and seizures.
30
Therefore, in this study, we aimed to investigate whether HS
therapy initiated before the development of signs of systemic
toxicity would reduce the development of cardiotoxicity.
Hypertonic saline treatment is widely used for many
indications, especially in hypovolaemic and septic shock,
hyponatraemic encephalopathy and increased intracranial
pressure syndrome, and clinicians have a very high degree of
experience in this field.
31-34
Earlier experimental studies have
demonstrated the effects of the administration of HS in severe
TCA poisoning.
7-9
The main advantages of HS therapy are that
it is cheap and accessible, and it has therapeutic properties in
hyponatraemic, hypovolaemic or hypotensive patients.
In this study, the rats administered toxic doses of amitriptyline
developed severe cardiotoxicity that resulted in a prolonged QRS
and QTc duration on ECG, slower heart rates and even death.
The apparent relationship between the depth of hyponatraemia
and the clinical outcome led us to believe that sodium may be a
key player in the treatment.
In our study, the administration of HS or NaHCO
3
in the early
stage of poisoning seemed to delay and reduce the development
of toxicity. The effectiveness of both treatments was found to
be similar. Similar amounts of sodium (~ 3 mEq/kg) were given
to both groups. The group administered amitriptyline with
NaHCO
3
had borderline hyponatraemia. The cause of the more
significant hyponatraemia in the group treated with HS is not
clear. Further studies with different concentrations of sodium-
containing fluids are needed to evaluate this issue.
Interestingly, serum ionised calcium levels were higher in the
groups that received amitriptyline than in the control group in
our study. We did not study blood pH and other factors that
affect calcium metabolism. Therefore, the pathophysiological
basis of our findings is unclear. An additional limitation of
this study is that we did not study factors affecting calcium
metabolism and blood gases.
Conclusion
Amitriptyline poisoning is a common occurrence. Although
the majority of cases improve with supportive therapy, cardiac
complications may be life threatening in some cases. Although
prospective, controlled human studies are needed, the results of
this preliminary study suggest that amitriptyline poisoning leads
to hyponatraemia, and early HS or NaHCO
3
treatment may
reduce the development of cardiac toxicity. As HS treatment
does not affect serum levels of ionised calcium and potassium
or change the drug elimination time, it may be preferred to
NaHCO
3
therapy.
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