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Abstract

The aim of this retrospective epidemiological study was to investigate the demographical, etiological and clinical characteristics of acute drug poisonings in Iasi County, Romania. All patients were referred and admitted in the Toxicology Clinic of “Sf. Ioan” Emergency Clinic Hospital Iasi, Romania. Between 2003 and 2009, 811 cases of acute drug poisonings were recorded, counting for 28.43% from the total number of poisonings. The majority of these poisonings resulted in mild (51.94%) and medium (28.35%) clinical forms, while 19.71% were coma situations. In all, 63.51% of patients originated from urban areas, 39.94% were unemployed and the patients were predominantly women (66.46%). A high percentage (97.27%) were suicide attempts, using only one type of drug (65.88%) and the 21–30 years group (29.8%) records the highest incidence, for both women and men. The most frequently involved drugs were benzodiazepines 13.69%, anticonvulsive drugs 8.63%, barbiturates 8.51% and cardiovascular drugs 5.92%. Drugs combinations were recorded in 32.92% of cases and 1.2% were combinations between drugs and other substances. Mortality was the outcome in 0.3% of the total registered number of acute drug poisonings. This study underlines that in order to provide a proper management of these situations, a Regional Poison Information Center is absolutely necessary.

Keywords

epidemiology poisonings drug toxicology clinical toxicology

Introduction

Acute poisonings are common situations in the emergency departments all around the world and involve high medical attention and significant costs.

Poisoning with pharmaceutical products is ubiquitous, as we can see in the reports originating from very different countries.^1–11

In 2008, acute drug poisonings were found to be the first cause of acute poisoning in USA. In top 25 substance categories associated with the largest number of fatalities, the first five positions were occupied by drugs poisonings.¹

There are many differences with respect to the pattern and cause of acute poisoning between geographical regions, even within the same country, and there is a constant need for new information in this field, in order to develop educational and prevention programs.¹²

Few epidemiological studies exist in Romania, concerning acute poisoning and to our knowledge no study on acute drug poisoning epidemiology in this region has been previously published in an international medical journal. Our aim was to provide a detailed screening on aspects of the pattern of drug poisoning in our region and to compare our experience with the data reported by the researchers from other countries. The final envisaged end point was to identify the risk factors for drug poisoning.

Iasi is one of the oldest cities in Romania, an important economic, political and cultural center in the North-Eastern region of Romania. Iasi County is the second most populous county in Romania, with an estimated population of about 850,000 inhabitants.

Our Internal Medicine and Toxicology Department represents the place where all the poisoning cases from Iasi County are referred and it is the tertiary center for the North-Eastern region of Romania.

In our country, there is no poison control center for the surveillance and management of poisoning situations, the patients being referred to regional hospitals such as “Sf. Ioan” Emergency Clinic Hospital of Iasi.

Methods

We reviewed retrospectively the medical charts of all patients with acute drug poisoning who were admitted in our department between January 2003 and December 2009. The selection of cases was based on the patient’s diagnosis on discharge and was accomplished through analysis of all the medical records of the patients hospitalized in our Internal Medicine and Toxicology Department, for the last 7 years.

A number of five physicians participating in the study abstracted the charts using a standardized data collection form, in a Microsoft Excel spreadsheet. This collection form was designed for this purpose and included the following variables: demographical characteristics including age, gender, occupation, residence (rural or urban area) and type of exposure (intentional or accidental); drug category; clinical form of poisoning (mild, medium, coma); number of pills; provenience of the drug (prescribed by the family physician, family members and pharmacy); the time between the poisoning and the admission to the hospital; previous history of poisoning; history of psychiatric disease; blood alcohol levels; length of hospital stay and clinical outcome. When the information was not available, it was classified as unknown. The abstractors were trained in data abstraction by the principal investigator. Inter-rater reliability was calculated by using 42 (6 per year) medical charts. All five abstractors reviewed the entire set of randomly selected medical charts. Inter-rater agreement was assessed by using κ analysis.¹³ The inter-rater reliability was assessed after the finalization of the medical records abstraction.

Patients who did not require admission to the toxicology department and were discharged from the emergency unit were not included in this study. Also, the adverse reactions, the drugs secondary effects and chronic poisonings were excluded.

The drugs were classified as benzodiazepines, barbiturates, neuroleptics, anticonvulsants, antidepressants, cardiovascular drugs, acetaminophen, nonsteroidal anti-inflammatory drugs (NSAIDs) and nonopioid analgesics, antibiotics, hypoglycemiant drugs, opioids, tuberculostatics, other medications (vitamins, antithyroid drugs, iron compounds, etc.) and unknown.

The database thus created was analyzed using SPSS for Windows 18.0. In the statistical analysis, the chi-square test for comparing nominal variables was used when proportions were analyzed for significant differences. For numeric variables, means were compared using ANOVA one-way analysis of variance, followed by Bonferroni post hoc test. Differences are considered statistically significant when p values are under 0.05.¹⁴

Results

Between 2003 and 2009, a number of 2852 cases of acute poisonings were recorded in our clinic, and among those, drug poisonings represented 28.43% (811 cases). The highest numbers of drug poisoning cases were hospitalized in 2005, up to a total of 170 cases (Figure 1).

Figure 1.

Incidence of acute poisoning between 2003 and 2009.

The majority of the poisonings were voluntary (97.27%), for suicidal purposes. More than half of the patients (65.88%) used only one drug, while in 32.92% of the poisonings the patients took a form of polymedication. The poisonings were a mixture of drugs with non-medicinal substances in only a few of the recorded cases (10 patients): seven cases that associated small amounts of corrosive substances, one cannabis and two pesticide compounds.

The most frequently involved drugs were the benzodiazepines (13.69%), followed by anticonvulsants (8.63%), barbiturates (8.51%) and cardiovascular medication (5.92%; Figure 2).

Figure 2.

Categories of drugs involved in acute drug poisonings between 2003 and 2009.

From the total number of drug poisonings, the highest incidence was recorded in women 66.46% (Table 1), 39.94% patients were unemployed, 35.78% had undergraduate education and 19.11% were retirees. The lowest incidence of drug poisonings was observed in the group with graduate education (5.17%). The majority (61.67%) of the patients came from urban areas.

Table 1.

Distribution of acute drug poisoning in gender groups

Category	Cases No.	Gender (%)
Category	Cases No.	Men	Women
Polymedication	267	32.6	67.4^a
Benzodiazepines	111	41.4	58.6^a
Anticonvulsants	70	45.7	54.3^a
Barbiturates	69	23.2	76.8^a
Cardiovascular drugs	48	29.2	70.8^a
Other	41	29.3	70.7^a
Neuroleptics	31	22.6	77.4^a
NSAIDs and nonopioid analgesics	24	37.5	62.5^a
Antidepressants	22	22.4	77.3^a
Tuberculostatics	15	40	60^a
Antibiotics	11	9.1	90.9^a
Acetaminophen	10	20	80^a
Drugs and other substances	10	60	40
Hypoglycemiant drugs	7	28.6	71.4^a
Opioids	5	20	80^a
Unknown drugs	70	37.1	62.9^a
Total	811

NSAIDs: nonsteroidal anti-inflammatory drugs.

^a The difference is significant at the 0.05 level.

The 21–30 years age group had the biggest incidence, 29.8%, while patients over 70 years old, 3%, were less frequently hospitalized for drug poisonings (24 cases; Table 2).

Table 2.

Distribution of acute drug poisoning in age groups

Category	Age							Cases No.
Category	18–20	21–30	31–40	41–50	51–60	61–70	>70	Cases No.
Polymedication	49	81	63	23	31	14	6	267
Benzodiazepines	12	34	26	18	12	4	5	111
Anticonvulsants	8	22	25	10	5	–	–	70
Barbiturates	9	20	19	14	3	2	2	69
Cardiovascular drugs	6	14	10	5	8	2	3	48
Others	11	12	6	3	4	1	4	41
Neuroleptics	6	8	7	5	1	3	1	31
NSAIDs and nonopioid analgesics	3	6	11	2	1	1	–	24
Antidepressants	3	7	6	5	–	1	–	22
Tuberculostatics	4	7	3	1	–	–	–	15
Antibiotics	2	7	–	2	–	–	–	11
Acetaminophen	3	2	2	2	1	–	–	10
Drugs and other substances	2	–	4	2	1	1	–	10
Hypoglycemiant agents	2	1	2	1	1	–	–	7
Opioids	4	1	–	–	–	–	–	5
Unknown drugs	8	20	17	11	4	7	3	70
Total	132	242	201	104	72	36	24	811

The number of pills ingested varied highly, with an average of 33.87 ± 33.63, frequently from personal medication prescribed by the personal physician (41.15%), from family (37.69%) or bought directly from the pharmacy (21.16%).

Most of the cases had mild (51.94%) or medium clinical manifestations (28.35%). Coma was recorded in only 19.71% of the cases. More women manifested severe clinical forms than men (p 0.013). Also, higher frequency of severe clinical forms was observed in patients without history of psychiatric diseases (p 0.006) and blood alcohol levels over 150 mg/dl (p < 0.001).

A previous psychiatric report was present in 13.81% of the cases. For a total of 77.8% of patients, this was the first attempt, 11.7% patients had history of two suicide attempts and 10.5% had records for more than two. A higher rate of repeated attempts was accompanied by cases with two or more medicines involved (p 0.035), and repeated attempts were more frequent for 31–40 age group (p 0.023), urban areas (p 0.001), patients with psychiatric history (p < 0.001) and unemployed patients (p 0.037), using their own medication for the suicidal attempt (p 0.042). The lowest frequency of repeated suicide attempts was recorded for the groups with graduate education or over 60 years old, while for patients over 70 years only one previous suicidal attempt was recorded.

Alcohol intake was more frequent in men (27.2% had levels over 50 mg/dl) than in women (17.4% had levels over 50 mg/dl). Higher levels of blood alcohol were registered in men: 17.1% of men compared with 11.2% of women had blood alcohol levels over 150 mg/dl (p 0.014; Table 3).

Table 3.

Distribution of blood alcohol levels in gender groups

Blood alcohol	Cases No.	Percentage in men group	Percentage in women group
0–10 mg/dl	338	43.9%	40.6%
50–150 mg/dl	61	10.1%	6.2%
150–300 mg/dl	83	14.0%	8.4%
>300 mg/dl	23	3.1%	2.8%
Testing not recommended	306	28.9%	42%
Total	811

On average, the cases arrived in the clinic at 6.42 ± 7.80 hours from ingestion. The raised value of standard deviation indicates the higher variability of the parameter in our group. The patients were hospitalized for 3.12 ± 2.39 days, the longest hospitalization period being registered for neuroleptics poisoning, 4.04 ± 3.41 days. From all patients, 20% were admitted in the intensive care unit.

In the majority of cases, the patients were released with a referral towards a psychiatric consult (82.16%). There were registered cases of release on request (14.96%), against the doctors' recommendations and warnings about possible complications.

In only two of the patients surveyed the outcome was the death (one with barbiturates and one associating barbiturates with phenothiazines), representing 0.3% of the cases. Both patients were men, from urban areas, between 31-40 years old, on the first attempt, which associated alcohol intake. In both patients blood alcohol levels were higher than 300 mg/dl.

The inter-rater score for categorical variables varied between 0.92 and 1, expressing a good inter-rater reliability.

Discussion

During the 7-year period we have recorded, there were researched a number of 811 cases of acute drug poisoning, counting for 28.43% from the total number of acute poisonings.

Consistent with the data from the majority of the studies from different countries,^{3,4,8,11,12,15–19} attempting suicide was the most common cause of poisoning.

There are considerable variations in the substances implicated in acute poisonings in different countries. In studies conducted in Poland, Spain, Taiwan, Turkey (Ankara, Istanbul, Mersin), Malaysia, Oman and different regions from Iran, the most common agent involved in acute poisoning were drugs, with variable sizes, between 42.7% in Spain and 89.34% in Western Iran from the total number of poisonings.^{3,5,6,12,15–17,20–23}

In the Romanian region we surveyed, the 28.43% drug poisonings is a result that aligns us with reports from Zimbabwe (30.4%), India (New Delhi 18.8%) and Thailand (19%), where the top leader in poisonings are the organophosphorus compounds.^24–27

The results of our study showed that the benzodiazepine group occupies the first place in acute drug poisonings, comparable with reports from Spain, Japan, Poland, different regions from Iran.^2,3,12,19,20 Report from The American Association of Poison Control Centers, studies from North England, Paris/France, Turkey, Malaysia and Oman have shown that the most common agents involved were the analgesics.^{1,6,17,21,23,28,29} In other reports, antidepressants or barbiturates were declared the most common drug poisoning agent.^4,30

In our region, the frequency of analgesics poisoning follows psychotropic and cardiovascular drug poisonings.

Benzodiazepines remain a constant leader in this Romanian region, displaying the highest percentage in a previous study accomplished in our clinic between 1991 and 2003, where from the 16,579 cases of acute poisonings recorded, 29.8% were drug poisoning, and from these the benzodiazepines represented 30%.³¹

More than half of the patients (65.88%) used only one drug, similar with other studies from Barcelona/Spain, Tabriz/Iran, Sari City/Iran, Istanbul/Turkey.^3,4,12,32

The highest incidence was recorded in young adults (21–30 years of age), situation also reported by investigators from Iran and developing countries.^{3,5,8,17,33,34}

A slight predominance in women was observed, the male-to-female ratio 1:1.9. Comparable findings have also been reported in several studies conducted in Iran, Taiwan, Turkey and Hong Kong^{3,5,6,12,15,16,18,33} but differs from epidemiological studies from the western part of Iran and India, where the poisonings are more frequent in men, possibly due to the religious characteristics in these regions, reasons actually mentioned by the authors.^25,26,35

Psychiatric disorders marked the history of 13.81% of the patients, percentage that is lower when compared with other studies (38.9% in a Spanish multicenter study).²

When compared with the psychiatric history, the increased percentage of repeated suicide attempts (22.2%) tends to show that patients did not undergo psychiatric consultation after discharge from the hospital.

Following the change that took place in the early 2000s in drug prescription regulations, in Romania psychotropic drugs are now released from pharmacies only based on medical prescription. This explains the significantly small percentage in which psychotropic drugs originating from pharmacies were used as a means of suicide.

Considering that a big proportion of the psychotropic drugs encountered in poisonings came from personal medication, we conclude that these patients had no records in a psychiatric care unit. The necessary prescription used to acquire these drugs was most probably prescribed by the family physician for sleep disturbances or minor anxiety disorders.^16,29,30

The profile for a patient with multiple suicidal attempts in our study is woman, 31–40 years old, unemployed, residing in urban areas, with a history of psychiatric disease, using her personal medication to suicide. Patients over 70 years old do not have previous repeated suicide attempts and the group of patients with graduate education displays the lowest frequency for suicide attempts by drug poisoning.

In our study, there is a delay between the ingestion and the admission time, similar with the reports from Izmir/Turkey, Helsinki/Finland and Hong Kong.^16,36,37 In contrast, in England the mean interval is 2 hours, in Tikur Anbessa/Ethiopia is 3 hours, and in a report from Spain 34.2% of patients come in the first 2 hours.^2,29,30 In our country, the delay is probably the result of the fact that mild forms of poisoning are treated first at home with a traditional antidote (milk, lemon).

Our study emphasizes the predominance of mild or medium intensity clinical forms. These usually associated a small number of pills ingested, young age, and required a reduced number of hospitalization days. Our results are in agreement with data reported by of Lapatto-Reiniluoto O. et al. in a Finish study.³⁷ In most of these cases, the suicidal act of a patient with an instable emotional profile is usually an attempt to engage the attention of the entourage and not a veritable lethal act.

We have to note the increased use of alcohol, concomitant with a blood alcohol content higher than 150 mg/dl, fact also reported in studies from Finland, where two thirds of the poisonings involved alcohol, and from Taiwan where concomitant use of alcohol was recorded for 62.4% of the observed patients.^5,37

Our patients were hospitalized in average for 3.12 ± 2.39 days, while the average hospital stay reported in literature was 1.5 days in studies from North Eastern England and Western Iran, 3.02 ± 2.8 days in Tabriz/Iran and 4 days in Karnataka/India.^8,12,26,29

It is to be remarked the reduced mortality recorded by our study. There were only two death cases and these associated a psychotropic drug poisoning with high amounts of alcohol intake (blood alcohol >300 mg/dl); the alcohol potentiated their effect. This decreased mortality rate was described in epidemiological studies accomplished in Japan in 1996 (12 cases of death from a total of 1188 acute drug poisonings, also related with benzodiazepines or barbiturates intake) or Northern Iran in 2008 (3 deaths from benzodiazepines poisonings in a total of 1598 cases of acute drug poisonings).^3,19 The fatal outcome was registered in our group in men, like in another study from Belgium, with male to female ratio of 9:1.³⁸

The reasonably high inter-rater reliability suggests that the study did not result in substantial investigator bias.

Conclusion

Sedative and hypnotic drugs occupied a preferred position in the top of drugs used in suicide attempts in our region. This emphasizes the necessity for a better stipulated algorithm under which these drugs are prescribed and released from pharmacies. We should avoid prescribing such medicines when it is not absolutely necessary and try to prevent an accumulation of pharmaceuticals disposable for suicidal purpose at patient’s home.

Based upon the high number of patients that resort to repeated suicide attempts, it becomes clear that a coordinated effort to integrate the intervention of a toxicology expert with a psychiatrist is necessary.³⁹

Considering the long delay between the moment of the ingestion and the time of the arrival in the toxicology clinic, we conclude that a better continuous medical education on this subject is necessary, tailored on targeting an early admittance of poisoning patients in a medical unit.⁴⁰

The current research entailed certain limits, the fundamental problems being that it was a hospital-based study and the population under 18 years of age was not included.

Yet, through the significant numbers of patients considered, over a 7 years span, we believe that our research provided significant information concerning the pattern of acute drug poisonings in North-Eastern Romania. The information we recorded tends to show that the highest risk profile for acute drug poisoning is young, unemployed, woman and the most frequently involved drugs are benzodiazepines.

These data underline that, in order to provide a proper management of drug poisonings, a Regional Poison Information Center is absolutely necessary.

Footnotes

This research received no specific grant from any funding agency in the public, commercial, or not-for-profit sectors.

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