INTRODUCTION:

The 2017 update of the Global Burden of Disease found that approximately 72,400 people deaths worldwide could be attributed to poisoning, intentional or accidental (1). While this statistic alone demonstrates the peril, studies place poisoning as the cause of 2.4% of all patients presenting to the Emergency Department (ED) and upto 6% of all Intensive Care Unit (ICU) admissions (2-4).

Income status is a factor that pervades the epidemiology of poisoning cases. A study on the population of China found that more than three-quarters of the poisoning related deaths reported over 10 years were of people living in rural areas (5). The Global Health Observatory (GHO) believes that problems with reporting in low- and middle- income countries may actually lead to the worldwide mortality being underestimated (6).

It is important, then, to keep in mind that Pakistan is a developing country. The majority of data on poisoning comes from scattered case series, and deals with the general demographics of presenting cases. A 2016 study conducted at a tertiary care hospital in Pakistan, found that 46.1% of adult poisoning cases had suicidal intent (7). However it was limited by location and fees structure to the upper class. Data on poisoning mortality, especially of people of lower socioeconomic status is lacking. The first step towards reducing the morbidity and mortality of poisoning in this country is to fully understand it. A number of non-governmental organizations (NGOs) ,for example, are known to exist for the purpose of reducing the burden of poisons, and there is great potential for benefit by having more knowledge available (8). The goal of this paper is to combine the obtained social and demographic data with information available in the literature, and to present it in an actionable form.

METHODOLOGY:

Our study consisted of a total of 204 cases of fatalities caused by poisons in patients aged 13 and above who reported to the emergency department of the National Poison Control Centre (NPCC) between 29/05/13 and 10/09/2019. The NPCC is a wing of the Jinnah Postgraduate Medical Centre, a government-operated tertiary-care hospital in one of the country’s major cities. The institute receives cases from a large part of the city itself as well as cases from the rural areas surrounding the city. Being government-operated it mostly takes cases of middle- or lower-socioeconomic class patients, as the majority of upper-class patients prefer private hospitals. In addition, the NPCC also picks up cases from smaller hospitals that do not have the facilities available to manage patients once a diagnosis of poisoning has been made. Cases of poisoning by accident, suicide and homicide were included however animal bites and food poisoning were not considered.

The data was retrospectively retrieved manually by going through existing patient case records. On admission to the emergency department, details of the patient are recorded, as well as a brief history of poisoning, and a simple assessment of the patient’s status. Where patients are referred from other hospitals the patient’s details and all information of clinical significance is transcribed onto the hospital’s own records. If an adult patient expires, the case is handed over to the office of the resident medico-legal officer, where it is reviewed and all pertinent documents are stored away as physical records. Because cases of patients of age

Ethical approval was received by the Institutional Review Board of JPMC. The patient case data was used as a component of this study, however all personal details pertaining to the patients were removed prior to descriptive analysis, to ensure anonymity of individuals.

The poisoning cases were analyzed on the basis of age, gender, marital status, occupation, type of poison used (organophosphates, corrosives, heavy metals etc.), interventions done (gastric lavage, activated charcoal, antidotes etc.), cause of death (cardiopulmonary arrest, renal failure etc.) and the approximate interval between onset of symptoms and death. The patients were divided into 5 categories on the basis of age: 13-18 years, 19-24 years, 25-44 years, 45-64 years and 65 or greater. The poisons were classified on the frequency of which they were used in different age groups and the cases in which the causing agent could not be determined were classified under ‘unidentified’.

Data analysis was done using IBM’s Statistical Package for the Social Sciences 20.0 (SPSS 20, IBM, Armonk, NY, USA). Descriptive statistics such as percentages and frequencies were used to report numerical values. Chi-square test was used to find associations between qualitative values, with p of

RESULTS

A total of 204 deceased patient medical records were included in the study, of which 137 (67.2%) were males and 67 (32.8%) were females. The mean age of the patients was 29.20 ± 13.04 years, and 102 (50%) were married.

Most of the poisoning cases occurred from organophosphate consumption, mainly through the ingestion of rat killer (30.9%), Typhon (23.5%), and insecticides (10.3%). Other substances that contributed to patient mortality included heroin/opioids, corrosives, heavy metals, paraphenylenediamine, cocaine, and antidepressants. (Table 1)

Cardiopulmonary arrest was the main cause of death amongst patients (n-202, 99%), and 2 patients died of acute kidney injury. The mean interval between onset of symptoms and death, i.e. the time for which resuscitation was attempted was 13.07 ± 1.71 minutes. 11.8% of patients died within 10 minutes and a further 44.1% within 15 minutes. Only 2% of patients were alive after 30 minutes.

Most of the recorded occupations belonged to students and housewives, with the unemployed, private employees, labourers and salesmen making up the rest of the record. A significant association was seen between occupation and poison consumed (p=0.048). Heroin/ Opioids were most commonly used amongst the unemployed (n=5, 2.5%), as compared to other occupations. Paraphenylenediamine, found in hair dye, was most commonly used amongst housewives (n=4, 2%). Organophosphates were the main choice of poison within all of the occupation groups. (Figure 1)

Participants were categorized by age, according to Medical Subject Headings (MeSH), into adolescents (ages 13 to 18 years, n=50), young adults (ages 19 to 24 years, n=44), adults (ages 25 to 44 years, n=80) middle-aged adults (ages 45-64 years, n=26), and older adults (aged older than 65 years, n=4). A significant association was found between age and the poison consumed (p = 0.005). Organophosphates were the main choice of poison amongst all age groups. Heroin and corrosives were mainly used by adults and the middle-aged group. (Table 2)

A significant association was found between poison class and gender (p < 0.001). Organophosphate use was the highest amongst both groups. Heroin/ Opioid poisoning was much more common in men (n=21, 10.3%) than women (n=1, 0.5%), whereas women were more likely to die of paraphenylenediamine poisoning than men. There were no cases of antidepressant or cocaine poisoning amongst women. (Table 3)

Atropine was the treatment used for most cases (n=59, 28.9%), corresponding to the high number or organophosphate poisoning cases. Atropine was also administered in one case of heroin and one case of antidepressant poisoning. For two other cases of organophosphate poisoning, epinephrine and metoclopramide were administered. Ipratropium Bromide (Atrovent) nebulizer was given in cases of heroin/ opioid poisoning and a tracheostomy was performed in one case of paraphenylenediamine poisoning. For most of the cases, however, treatment was nonspecific (n=135, 66.2%).

DISCUSSION

In our study we observed that the personal characteristics of the deceased closely resembled those reported in the literature concerning poisoning in other countries. More than two-thirds of patients of acute poisoning were found to be men, a statistic demonstrated in both Poland (9) and Iran (10). Unlike the sex of the patients, however, age has not been consistent among studies; a paper in Turkey (11) found the majority of patients to be below 25, while China (5) found the elderly to be the most at risk. While this may be partially explained due to cultural differences, it does indicate that poisons potentially pose a threat to all demographics. Our own study lends to this, reporting a mean age of 29 years, albeit with a high variance.

The substance most commonly used amongst all age groups was found to be the organophosphates. This is no surprise, the insidious presence of organophosphates as a poison has been apparent across the Asian subcontinent for decades, with studies in both India and Pakistan finding it to be among the more widely used substances for either suicidal or homicidal intent at different points in time (12-16). Pakistan, in particular, suffers due the widespread use of organophosphate compounds in common household items. One noteworthy finding was the use of Dichlorvos (2,2-dichlorovinyl dimethyl phosphate), an organophosphate commonly used as part of the pesticide ‘Typhon’. It was implicated in 48 cases, accounting for nearly a quarter of all deaths, possibly because of its rapid-acting and highly toxic profile (17).

One previous study in Pakistan found an abuse of drugs, therapeutic or recreational, to be the most common reason for mortality due to poisoning, rather than organophosphates (18). While our study does not support that finding, it was found to be the second most common cause, with a total of 29 cases being caused by either drugs of abuse or by an overdose of therapeutic drugs, although the latter was a small contributor. Interestingly, the identity of the patients diagnosed with a heroin overdose was not established, as they did not present with an acquaintance, but rather were brought to the hospital by an onlooker. This may suggest that the number of cases observed does not represent the actual burden as it is dependent on someone being present to report the overdose.

Of the remaining cases, the only standout substances were Methanol and Paraphenyldiamine (PPD), being used in 8 and in 7 cases, respectively. Alcohol intoxication being of low incidence is worth noting, especially when compared to developed countries, where it is often one of the more commonly reported causes of poisoning (9,19). This disparity may be because the distribution of alcohol as liquor is largely restricted in Pakistan, and cases of methanol toxicity are usually linked to methanol being consumed as a contaminant of drinking alcohol. The finding may also be due to the largely Muslim area in which the hospital is situated; higher incidences of methanol poisoning in areas of Pakistan with larger Christian demographics have been documented (20). PPD is a curious substance. It is used mostly as a cheap hair dye, and so there is scant mention of it as a poison except in developing countries (21). It has previously been documented as a cause of suicidal poisoning among women in Pakistan (22), a finding that our study may attest to, with the majority of cases being among housewives.

One peculiar observation in our study was a total lack of cases of Aluminum Phosphide (AP) poisoning. AP poisoning was labeled as the second commonest cause among unintentional injuries in a national health survey of Pakistan (23).  A case study conducted in a tertiary care hospital in Lahore showed that AP poisoning was not only one of the most common but also one of the most fatal with a mortality rate of 70% and another study reported a mortality rate of 55-90% (24). The incidence of AP poisoning has increased greatly in recent years due to its easy accessibility and low cost. Most of the available literature on AP poisoning in Pakistan is based in Punjab with scarce documented reports in Karachi. This may show an important relationship between social and environmental factors such as the provincial region and the variation in types of poisons used.

In terms of management, all cases of suspected poisoning were subjected to an immediate gastric lavage. Where enough information was present, either by a clinical history or by the patient's symptoms, to reach a diagnosis, substance-specific treatment was started. Interestingly atropine the treatment for OP poisoning was only administered to a quarter of the patients, even though OP poisoning accounted for more than half of all the deaths. This can perhaps be due to an inability to quickly identify symptoms and formulate a treatment plan, or a reluctance to administer it for fear of exacerbating the patient’s condition when the offending substance remains undetermined.

The management of OP poisoning has been discussed extensively in the open literature, and while there exist a wide  the current accepted protocol asks for the use of atropine, diazepam, and an oxime in the treatment of an acute case (25). However, the use of oximes, particularly that of Pralidoxime (PAM), has been a subject of much controversy. A recent meta-analysis (26) determined that there was no benefit to the inclusion of pralidoxime in the treatment of OP poisonings, but an RCT performed in 2016 found that, if administered in a dosage adjusted according to different parameters rather than a fixed dose, pralidoxime can be a lifesaving drug (27). Despite the controversy, however, pralidoxime still finds itself used in treatment of acute OP poisoning. Interestingly, while the use of atropine was noted for certain cases of OP poisoning, no record was found indicating the usage of pralidoxime in the cases found for our study.

On expiry, the mechanism of death for the vast majority of patients was noted down only as a cardiopulmonary event. While not incorrect, the approach is rather reductive, as the particular modes of action of the different poisons vary. For example, OP poisoning causes death by inducing a paralysis of the muscles of respiration, as well as the brain’s respiratory center (25). Two cases, however, featured kidney injury so severe that it was considered directly responsible for the patient’s demise. One of these was notably due to PPD poisoning, while the other was an unidentified poison.

LIMITATIONS

Some limitations to this study include the study design, being retrospective in nature. The low sample size and the fact that data was obtained from only one center, despite it being centrally placed, detract from the power of the analyses. Children under the age of 13 were not included in the study, as cases of poisoning in this age groups are not processed by medicolegal officers.  We were unable to collect data on the reason for the poisoning, that is, whether the poisoning was done accidentally or intentionally. This information is an essential tool for analysing demographic data within the study itself as well as with other studies in the literature. In addition, data on the time since poisoning was difficult to attain for the majority of cases due to factors such as an insufficient clinical history, or patients that had been transferred from the poorly-equipped local healthcare facilities not having an accompanying history. Another limitation of the study is that the records did not contain socioeconomic data on the patients. That being said, the general population that visits SMC is from the low to middle class. Since we did not exclude patients based on history of exposure, drug addicts may also be included in the sample. We analysed the poisons and their associated epidemology without a previously decided on criteria i.e. on a post hoc basis, so poisons other than the ones menioned are not included in the study. Finally, although the cause of death is fully confirmed by a formal autopsy in all cases, we were unable to access the records and individually parse them for information that may have been of interests.

CONCLUSION

Poisoning is a serious threat to all demographics. The mortality can by and large be attributed to substances that can be easily obtained and are widely used. This perhaps indicates a gap in safety measures, and calls for tighter regulation standards. Moreover, since the majority of cases were associated with OP poisoning, treatment standards should be looked into and updated wherever possible to be able to better handle it. Current medical research suggests a treatment regimen supplementing the use of atropine with oximes and diazepam (22), and hospitals should look to adopting if not already done.

Conflict of interests: None to be declared.

Funding and support: None.