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ORIGINAL ARTICLE
Year : 2014  |  Volume : 27  |  Issue : 2  |  Page : 260-268

Clinical study of poisoned cases by some drugs admitted to the menoufia poisoning control center over 1 year (2011), with a focus on ECG changes


Department of Forensic Medicine and Clinical Toxicology, Faculty of Medicine, Menoufia University, Menoufia, Egypt

Date of Submission07-Apr-2013
Date of Acceptance24-Aug-2013
Date of Web Publication26-Sep-2014

Correspondence Address:
Nagwa Mahmoud Habib
MBBCH, Forensic Medicine and Clinical Toxicology Department, Faculty of Medicine, Menoufia University, Sameh Mubark Street, Shebin Al-Kom, Menoufia
Egypt
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/1110-2098.141671

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  Abstract 

Objective
The aim of this work was to study ECG changes in cases of poisoning by digoxin, theophylline, and antidepressant overdose that were admitted to Menoufia Poisoning Control Center (MPCC) in 2011, with a focus on evaluation of ECG changes in correlation with both arterial blood gases and electrolyte changes, together with clinical manifestations.
Background
Numerous drugs can cause ECG changes and lead to cardiac dysrhythmias, and the diagnoses and subsequent management of patients with ECG changes following poisonings can be a challenge for even the most experienced physician. Digoxin toxicity often presents with gastrointestinal side effects, cardiac dysrhythmias, and neurological effects. Overdoses of antidepressants are common and deadly, and sudden cardiovascular deterioration is the hallmark of toxicity. Theophylline overdose can lead to neurotoxicity and cardiac toxicity associated with life-threatening dysrhythmias.
Patients and methods
In this study, patients who had overdosed on digitalis, theophylline, and antidepressants admitted to MPCC in 2011 were included. Clinical data, serum electrolytes, arterial blood gas changes, and ECG changes were assessed.
Results
A total of 77 patients were studied. Most patients in the study were females in the age group of 20 to less than 40 years, and they outnumbered males in both suicidal and accidental modes. Theophylline overdose cases were the most common, followed by antidepressants and then digoxin overdose. A significant relation was found between the type of drug overdose and clinical manifestations, wherein vomiting occurred most frequently with digoxin overdose. Convulsions occurred only in cases of overdose with antidepressants. Hypokalemia was more evident in cases of overdose with antidepressants. In terms of ECG changes, sinus bradycardia and ST segment depression were found only in digoxin overdose cases. Sinus tachycardia occurred most frequently in theophylline overdose cases. A highly significant relation was found between potassium (K + ) blood-level and ECG changes such as sinus tachycardia and ST segment depression. A significant relation was found between metabolic acidosis and a wide QRS complex. No case fatality was recorded in this study.
Conclusion
Drug overdose is a major and longstanding source of morbidity worldwide. Digitalis overdose manifested as sinus bradycardia and ST segment depression. Theophylline overdose manifested as sinus tachycardia and antidepressant overdose cases were characterized by sinus tachycardia and a wide QRS complex.


How to cite this article:
Hammad SA, Amin SA, El-Seidy AM, Habib NM. Clinical study of poisoned cases by some drugs admitted to the menoufia poisoning control center over 1 year (2011), with a focus on ECG changes. Menoufia Med J 2014;27:260-8

How to cite this URL:
Hammad SA, Amin SA, El-Seidy AM, Habib NM. Clinical study of poisoned cases by some drugs admitted to the menoufia poisoning control center over 1 year (2011), with a focus on ECG changes. Menoufia Med J [serial online] 2014 [cited 2020 Feb 26];27:260-8. Available from: http://www.mmj.eg.net/text.asp?2014/27/2/260/141671


  Introduction Top


In the context of prescription medicines, a therapeutic dose is an amount of a substance that is generally accepted as safe for the majority of the population and usually results in a desired therapeutic effect, with few and/or mild side effects [1]. The word 'overdose' implies that there is a common safe dosage and usage for the drug; therefore, the term is commonly only applied to drugs, not poison [2]. Numerous drugs can cause ECG changes and lead to cardiac dysrhythmias. Drug-induced changes and abnormalities on ECG are common, and the diagnoses and subsequent management of patients presenting ECG changes following poisonings can be a challenge for even the most experienced physician [3].

In the setting of drug overdose or of a toxic exposure, ECG abnormalities, especially dysrhythmias, are produced by three mechanisms: abnormal impulse formation, abnormal impulse conduction, and triggered activity. Factors contributing toward ECG changes are hypotension, hypoxia, acid-base, and electrolyte imbalances [4].

Digoxin and digitoxin are the oral preparations of cardiac glycosides. Both exert a positive inotropic effect on cardiac muscle by directly binding to the membrane sodium-potassium ATPase pump and impairing active transport of these ions. Digoxin toxicity often presents with gastrointestinal (GIT) side effects. Others include cardiac dysrhythmias and neurological effects [5].

Antidepressants have been shown to be highly effective treatments for depression; paradoxically, to achieve compliance, a dangerous drug may be prescribed, providing the patient ready access to a potential method of suicide [6]. Introduced in the 1950s, tricyclic antidepressants (TCAs) were the mainstay of antidepressant therapy for a long period [7]. Overdoses of these drugs are common and deadly; sudden cardiovascular deterioration is the hallmark of toxicity. Seizures and the ensuing academia may markedly worsen the clinical situation [8].

Although theophylline has lost its popularity in the last 20 years, it is still an effective drug commonly prescribed in the management of bronchial asthma and chronic obstructive pulmonary disease. Its narrow therapeutic range, erratic absorption, wide individual variations in elimination rate, and side effects even at low serum theophylline levels discouraged many clinicians from using theophylline preparations [9]. The occurrence of adverse effects with theophylline, even at levels in the therapeutic range, and the severity of its effects in acute and chronic overdoses are notable [10]. Theophylline overdose can lead to neurotoxicity and cardiac toxicity associated with life-threatening dysrhythmias [11].

The aim of this work was to study ECG changes in cases of poisoning by digoxin, theophylline, and antidepressant overdose admitted to Menoufia Poisoning Control Center (MPCC) in 2011, with a focus on evaluation of ECG changes in correlation with both arterial blood gases (ABGs) and electrolyte changes together with clinical manifestations.


  Patients and methods Top


In this study, patients who overdosed on digitalis, theophylline, and antidepressants admitted to MPCC in the period from 1 January 2011 to 31 December 2011 were included. A total of 77 patients were studied.

The demographic and clinical data from their medical records were collected.

Blood pressure, heart rate, serum electrolytes, and ABG changes were compared with age-specific norms [12].

At least one ECG for each patient was available for inclusion in the study.

The studied cases were classified according to the poison severity score (PSS), which is a four-scale grading as follows: 0, none; 1, minor; 2, moderate; 3, severe; and 4, fatal. PSS was determined at the time of initial assessment and following recovery using examination findings including the Glasgow coma score, pupil size, convulsion, respiratory rate, pulse rate, blood pressure, body temperature, ECG findings, pain assessment, and laboratory presentations (serum glucose, potassium, sodium, pH, and bicarbonate in ABG) [13].

Statistical analysis

  1. Descriptive statistics: as percentage, mean (X), and SD.
  2. Analytic statistics: as c2 -test, Fisher's exact test, and analysis of variance (F) test, with a level of significance as follows: P value less than 0.05, significant; P value less than 0.001, highly significant; and P value more than 0.05, nonsignificant.



  Results Top


A total of 77 patients were studied: 44 cases of theophylline overdose, 24 cases of antidepressant overdose, and nine cases of digoxin overdose.

[Figure 1] shows the sex distribution in age groups in drug poisoning cases admitted to MPCC during the period of the study. It was found that females outnumbered males in the age groups of 10 to less than 20 years, 20 to less than 40 years, and 40 years and older. The percent of males was higher in the age group of less than 5 years (50%).
Figure 1:

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[Table 1] shows that there was a significant relation between mode of exposure and sex (P < 0.05), wherein the highest percent of females was found in the categories of both suicidal and accidental modes, 89.3 and 52.4%, respectively.
Table 1: Relation between mode of exposure and sex of the cases studied

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[Table 2] shows the significant relation between the type of drug overdose and clinical manifestations. In digoxin overdose cases, 88.9% had vomiting (P < 0.001) and 11.1% had loss of consciousness (P < 0.05).
Table 2: Relation between clinical symptoms and type of drug overdose

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In theophylline overdose cases, 72.7% had vomiting and 2.3% had loss of consciousness. 20.8% of antidepressant overdose cases had vomiting, 20.8% had loss of consciousness, and 12.5% had convulsions (P < 0.05).

[Table 3] shows a highly significant relation (P < 0.001) between severity grades of the cases studied according to PSS and the type of drug overdose. In digitalis overdose cases, 38.1% were of moderate and severe grades, whereas only 9.1% were of 'none' grade.
Table 3: Relation between severity grades of the cases studied according to poison severity score and the type of drug overdose

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Among theophylline overdose cases, 68.9% were of the minor grade, 45.5% were of the 'none' grade, and 38.1% were of moderate and severe grades.

Most of the antidepressant overdose cases had a 'none' grade score, representing 45.5%, and 31.1% of the cases were of the minor grade. The lowest percent included cases of moderate and severe grades, representing 23.8%.

In terms of ECG changes in the cases studied, [Table 4] shows the relation between the type of drug overdose and different ECG changes, which was significant.
Table 4: Relation between ECG changes in the cases studied and the type of drug overdose

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In digoxin overdose cases, 77.8% presented with sinus bradycardia (P < 0.001) [Figure 2], 66.7% had ST segment depression (P < 0.001), 33.3% had extrasystole (P < 0.05), 33.3% had first-degree heart block (P < 0.05), and 11.1% had complete heart block (P < 0.05).
Figure 2:

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Among the theophylline overdose cases, 70.5% had sinus tachycardia (P < 0.001) [Figure 3], 9.1% had extrasystole, 4.5% had first-degree heart block (P < 0.05), and 2.3% had a wide QRS complex (P < 0.001).
Figure 3:

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Among antidepressant overdose cases, 45.8% had sinus tachycardia (P < 0.001), 33.3% had a wide QRS complex (P < 0.001), 12.5% had first-degree heart block (P < 0.05), and only 4.2% had extrasystole (P < 0.05)

[Table 5] shows that there was a significant relation between K + serum level and type of drug overdose (P < 0.05), wherein hypokalemia was observed in cases of antidepressant overdose (25%) followed by theophylline overdose cases (18.2%). There was a statistical significance in the percent of cases with hyperkalemia caused by digitalis overdose (22.2%) and theophylline overdose (2.3%).
Table 5: Relation between the type of drug overdose in the cases studied and serum electrolyte changes

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According to the relation between K + blood-level and different ECG changes, [Table 6] shows that there was a statistically significant relation (P < 0.001) regarding rise in serum K in different ECG changes. Hyperkalemia was evident in 66.7% of cases of atrial fibrillation (AF) and the same percent was found in cases with ST segment depression. Hyperkalemia was also found in 33.3% of sinus bradycardia cases and in 33.3% of extrasystole cases.
Table 6: Relation between potassium blood-level changes and different ECG changes

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Hypokalemia was found in 85.7% of cases with sinus tachycardia (P < 0.05), in 28.6% of cases with extrasystole, in 28.6% of cases with a wide QRS complex, and in 28.6% of cases of first-degree heart block. The lowest percent of hypokalemia (21.4%) was found in cases of AF.

[Table 7] shows a significant relation between metabolic acidosis and a wide QRS complex (P < 0.05). Metabolic acidosis was a disorder found in 42.9% of cases with a wide QRS complex.
Table 7: Relation between pH changes because of metabolic acidosis and different ECG changes

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  Discussion Top


Drug overdose is a major and longstanding source of morbidity and mortality worldwide [1]. Drug overdose is one of the easiest methods of suicide attempts [14].

The present study found that most of the cases were females, with a predominance in the age group (20 to <40 years), and a sex discrepancy in terms of suicide attempts was obvious in our results compared with the literature [15], explained that the predominance of females could be because of lower education levels, a lower rate of employment, and suppression of personal freedom by parents, which were similar to the findings of the current study. Suicidal attempts could be explained by impulsive suicides that are generally motivated by anger, the desire to get even, the wish to frighten or punish others, or the need to avoid intense shame [14]. Also, oppressive attitudes of the husband toward the wife, marriage at a young age, and being a housewife (not working) influence suicide attempts by women [16].

These results are in agreement with those of Yasan et al. [17], who found that higher suicide attempt rates were observed in females compared with males.

In contrast to the results of this study, Garg and Verma [18] found that the majority of cases were male victims of suicidal attempts. This difference may be because of different sociocultural characteristics and backgrounds in these studies.

On studying clinical manifestations and ECG changes in the patients in the present study and their relation with the type of drug overdose, it was significant.

The digitalis overdose group

The clinical presentations included vomiting and disturbed consciousness level. GIT manifestations of digitalis intoxication are attributed to local irritation and chemoreceptor stimulation in the area postmera of the medulla [19]. None of the cases developed convulsions; this may be attributed to the fact that digitalis is mainly a cardiotoxic agent. This result was in agreement with that of Ashraf [20], who reported that digoxin toxicity often presents with GIT side effects and cardiac dysrhythmias.

In contrast, Eichhorn and Gheorghiade [21] reported that the most commonly observed symptoms of digoxin intoxication include lethargy and loss of consciousness.

ECG changes in this group included sinus bradycardia, extrasystole, ST segment depression, first-degree heart block, and complete heart block. Dysrhythmias caused by digitalis overdose can be explained by the simultaneous manifestation of increased automaticity and depressed AV conduction [19]. These results were similar to those reported by Reilly and Stawicki [22].

Theophylline overdose cases

Vomiting and loss of consciousness were the main complaints in this group of patients. GIT symptoms of theophylline overdose can be attributed to catecholamine-induced gastric acid secretion [23]. The central nervous system (CNS) manifestations in cases of theophylline overdose are mediated by blocking adenosine receptors with an increase in seizure threshold [23]. This was similar to the result reported by Altaie et al. [24].

None of the cases in this group developed convulsions. This result was not in agreement with that of Boison [25], who reported that seizures are potentially severe or fatal complications of theophylline therapy.

The difference in the results of this study in comparison with the literature may be because of the inaccuracy of the estimated dose (32.5% of the patients in the study reported a history of an unknown ingested dose) as the drug was not prospectively administered and the information on dose relied on data obtained from a witness, parent, or the patient. The proconvulsant and convulsant effects of methylxanthines are generally dependant on the dose and the mode of application [26].

Sinus tachycardia was evident in 70.5% of the cases; extrasystole and a wide QRS complex were observed in fewer numbers of patients. These ECG changes can be attributed to increased plasma levels of epinephrine and norepinephrine secondary to theophylline toxicity [23].

The results of the current study are in agreement with those of Yin et al. [27], who found that levels of theophylline above therapeutic levels can cause arrhythmia, coma, heartburn, and tachycardia, and even respiratory arrest and cardiac arrest.

Antidepressant overdose cases

Among antidepressants overdose cases, 20.8% developed vomiting. Vomiting can be attributed to the anticholinergic effects of TCA [28]. This result was not in agreement with that of White et al. [29], who reported that GIT manifestations were remarkably absent with TCA.

In terms of CNS manifestations in antidepressant overdose cases, 20.8% had loss of consciousness and 12.5% had convulsions. These manifestations can be attributed to the anticholinergic blockade by antidepressants [30], blockade of the g-aminobutyric acid receptor by TCA, and reduced cerebral perfusion secondary to systemic hypotension [31]. TCA also leads to CNS sedation [29].

These results were in agreement with those of Mills [32], who reported that coma, confusion, lethargy, seizures, and agitation were most common in TCA overdose cases.

The most frequent ECG change was sinus tachycardia, followed by a wide QRS complex. The least frequent ECG change was first-degree heart block.

Sinus tachycardia in TCA overdose cases can be attributed to anticholinergic activity and/or inhibition of norepinephrine uptake [32]. Conduction delays (prolonged PR interval, QRS complex) are because of 'quinidine-like' effects on myocardial membranes [30]. Arrhythmias can be arise because of the fact that both TCA and selective serotonin reuptake inhibitors have calcium-channel blocking activity in cardiac myocytes and antagonize voltage-gated ion channels [33]. Like TCA, selective serotonin reuptake inhibitors and serotonin norepinephrine reuptake inhibitors appear to have effects on cardiac conduction and negative inotropic effects [34].

These results were in agreement with those of Caksen et al. [35], who found that sinus tachycardia, long QRS, and nonspecific ST-T changes are the most common dysrhythmias in symptomatic cases.

Potassium disorders are common and may precipitate cardiac arrhythmias or cardiopulmonary arrest [36]. This was evident in the current study, where K blood-level changes showed a significant relation with different ECG changes.

In terms of hyperkalemia (which was observed in 22.2% of digitalis overdose cases), these results were in agreement with those of El-Sherif and Turitto [37], who reported that ECG changes of hyperkalemia include first-degree AV block and ST segment depression. Garth [38] also reported hyperkalemia after digoxin overdose, which could be attributed to digoxin blockage of Na + -K + ATPase diffusely throughout the body and the resultant leak of potassium from its intracellular milieu into extracellular spaces, with the resultant cardiac dysrhythmias.

However, Bandyopadhyay and Banerjee [39] reported that ECG changes because of hyperkalemia are not always present and the relation between ECG changes and serum potassium will vary among patients. They also reported that even in severe hyperkalemia, only minimal changes may be seen on the ECG.

Hypokalemia was evident in 25% of antidepressant overdose cases and 18.2% of theophylline overdose cases, along with the occurrence of sinus tachycardia, extrasystole, a wide QRS complex, first-degree heart block, and AF. The results of the current study were similar to those obtained by Glancy et al. [40], who reported that hypokalemia can predispose to VT or VF, long QT syndrome, and torsade de pointes.

On studying acid-base disorders in the present study, metabolic acidosis was found in 42.9% of cases with a wide QRS complex; the latter occurred most frequently in antidepressant overdose cases. This result was in agreement with that of Liebelt et al. [41], who reported that hypoxia and acidosis increase cardiac excitability directly, increasing the risk of arrhythmias and cardiac arrests. Also, Charles and Heilman [42] added that the presence of metabolic disturbances, such as hypocalcemia, hyponatremia, and acidemia, may exacerbate the effects of hyperkalemia, with subsequent serious arrhythmias.


  Conclusion Top


There are numerous drugs that can cause, on overdose, ECG changes, even in patients without a history of cardiac pathology. Digoxin toxicity often presents with GIT side effects, cardiac dysrhythmias, mainly sinus bradycardia, and variable degrees of heart block. Antidepressant overdoses are common, and severe toxicity marked by ECG and hemodynamic changes such as hypotension and wide-complex tachycardia should be treated aggressively to maximize survival. In theophylline intoxication, the theophylline toxidrome manifestation can present as an overlap with other drug toxicities, as the clinical features are nonspecific, and include nausea, vomiting, and sinus and supraventricular tachycardia.


  Acknowledgements Top


Conflicts of interest

There are no conflicts of interest.

 
  References Top

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37.El-Sherif N, Turitto G. Electrolyte disorders and arrythmogenesis. Cardiol J 2011; 18:233-245.  Back to cited text no. 37
    
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39.Bandyopadhyay S, Banerjee S. Severe hyperkalaemia with normal electrocardiogram. Int J Clin Pract 2001; 55:486-487.  Back to cited text no. 39
    
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41.Liebelt EL, Francis PD, Woolf AD. ECG lead aVR versus QRS interval in predicting seizures and arrhythmias in acute tricyclic antidepressant toxicity. Ann Emerg Med 1995; 26:195-201.  Back to cited text no. 41
    
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    Figures

  [Figure 1], [Figure 2], [Figure 3]
 
 
    Tables

  [Table 1], [Table 2], [Table 3], [Table 4], [Table 5], [Table 6], [Table 7]



 

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