Cardiovascular Journal of Africa: Vol 26 No 3 (May/June 2015)

CARDIOVASCULAR JOURNAL OF AFRICA • Volume 26, No 3, May/June 2015

134

AFRICA

Can empirical hypertonic saline or sodium bicarbonate

treatment prevent the development of cardiotoxicity

during serious amitriptyline poisoning?

Experimental research

Muhammet Sukru Paksu, Halit Zengin, Fatih Ilkaya, Sule Paksu, Hasan Guzel, Durmus Ucar,

Adem Uzun, Hasan Alacam, Latif Duran, Naci Murat, Ahmet Guzel

Abstract

Objective:

The aim of this experimental study was to investi-

gate whether hypertonic saline or sodium bicarbonate admin-

istration prevented the development of cardiotoxicity in rats

that received toxic doses of amitriptyline.

Method:

Thirty-six Sprague Dawley rats were used in the

study. The animals were divided into six groups. Group 1

received toxic doses of i.p. amitriptyline. Groups 2 and 3

toxic doses of i.p. amitriptyline, plus i.v. sodium bicarbonate

and i.v. hypertonic saline, respectively. Group 4 received only

i.v. sodium bicarbonate, group 5 received only i.v. hyper-

tonic saline, and group 6 was the control. Electrocardiography

was recorded in all rats for a maximum of 60 minutes. Blood

samples were obtained to measure the serum levels of sodium

and ionised calcium.

Results:

The survival time was shorter in group 1. In this

group, the animals’ heart rates also decreased over time, and

their QRS and QTc intervals were significantly prolonged.

Groups 2 and 3 showed less severe changes in their ECGs and

the rats survived for a longer period. The effects of sodium

bicarbonate or hypertonic saline treatments on reducing the

development of cardiotoxicity were similar. The serum sodi-

um levels decreased in all the amitriptyline-applied groups.

Reduction of serum sodium level was most pronounced in

group 1.

Conclusion:

Empirical treatment with sodium bicarbonate or

hypertonic saline can reduce the development of cardiotoxic-

ity during amitriptyline intoxication. As hypertonic saline has

no adverse effects on drug elimination, it should be consid-

ered as an alternative to sodium bicarbonate therapy.

Keywords:

amitriptyline, poisoning, cardiotoxicity, sodium bicar-

bonate, hypertonic saline

Submitted 3/12/13, accepted 27/1/15

Published online 5/5/15

Cardiovasc J Afr

2015;

: 134–139

www.cvja.co.za

DOI: 10.5830/CVJA-2015-014

Tricyclic antidepressant (TCA) drugs are commonly used to

treat many neuropsychiatric diseases.

Amitriptyline is the most

commonly prescribed antidepressant, and it is a frequent cause

of toxicity in drug overdoses. TCA overdose primarily affects the

neurological, cardiovascular and respiratory systems.

1,2

Blockage of the rapid sodium channels is responsible for

drug-induced cardiotoxicity, which clinically manifests as PR,

QT and QRS prolongation, ventricular or supraventricular

arrhythmias, hypotension and heart failure.

1,3

Sodiumbicarbonate

(NaHCO

) administration is the most widely accepted treatment

to reduce amitriptyline-induced cardiotoxicity.

2,4,5

However,

at an alkaline pH, the volume distribution of amitriptyline

expands, and the elimination time is longer. Therefore, NaHCO

treatment is suggested only in the presence of cardiac findings.

Hypertonic saline (HS) administration has been shown to be

useful, particularly when cardiotoxicity is accompanied by

hypotension.

7-9

There is always a need for a medication to prevent

cardiotoxicity that will save patients’ lives, especially when toxic

Paediatric Intensive Care Unit, Faculty of Medicine,

Ondokuz Mayis University, Samsun, Turkey

Muhammet Sukru Paksu, MD

Department of Cardiology, Faculty of Medicine, Ondokuz

Mayis University, Samsun, Turkey

Halit Zengin, MD,

drhzengin@yahoo.com.tr

Adem Uzun, MD

Department of Pharmacology, Faculty of Medicine,

Ondokuz Mayis University, Samsun, Turkey

Fatih Ilkaya, MD

Hasan Guzel, MD

Department of Paediatrics, Faculty of Medicine, Ondokuz

Mayis University, Samsun, Turkey

Sule Paksu, MD

Department of Physiology, Faculty of Medicine, Ondokuz

Mayis University, Samsun, Turkey

Durmus Ucar, MD

Department of Biochemistry, Faculty of Medicine, Ondokuz

Mayis University, Samsun, Turkey

Hasan Alacam, MD

Department of Emergency Medicine, Faculty of Medicine,

Ondokuz Mayis University, Samsun, Turkey

Latif Duran, MD

Department of Industrial Engineering, Faculty of

Engineering, Ondokuz Mayis University, Samsun, Turkey

Naci Murat, MD

Department of Paediatric Emergency, Faculty of Medicine,

Ondokuz Mayis University, Samsun, Turkey

Ahmet Guzel, MD