Principal characteristics of patients acutely poisoned by ethanol in the region of Belgrade (Serbia)

Background/Aim. Acute intoxication by ethanol constitutes a significant part of the acute pathology caused by toxic chemicals, which require medical care in specialized health care institutions. The aim of the study was to determine some principal characteristics of the patients treated after acute ethanol poisoning, such as: participation in the total number of patients treated after acute poisoning by all chemical agents, age, sex, severity of poisoning and capacities for ambulatory or hospital treatment. Methods. A five-year retrospective case study was conducted on 20,891 acute poisoned patients, of which 10,731 were treated after acute ethanol poisoning during the period 2011?2015. All the subjects satisfied the diagnostic criteria of poisoning according to the World Health Organization International Classification of Diseases-10 and standardized Poison Severity Score scale. Results. Monitored parameters were analyzed in 10,731 patients acutely poisoned by ethanol, and their average number during one study year was 2146.2 ? 437.95. The average number of treated patients due to poisoning by ethanol (51.47 ? 2.86%) was statistically significantly higher than that of other causes of acute poisoning (p < 0.001). The majority of poisoned patients were men, aged 19 to 65 years, with mild to moderate symptoms of acute ethanol intoxication. The highest number of patients poisoned by ethanol had Poison Severity Score 1 (70.25 ? 5.04%, p < 0.001). Very few acute poisoned with ethanol required hospital treatment (1.05%). Anticipated number of patients acutely poisoned by ethanol had high percentage of increase for the period 2016?2020 (slightly more than 20%), which is worrying, primarily due to their high absolute number. Conclusion. Acute alcohol poisoning represents a significant part of the pathology in the total number of patients treated due to acute poisoning with various chemical substances. The results of this analysis showed that certain populations are particularly vulnerable to abuse of alcohol to the level requiring health care (male population, age 19?65 years). Only a small number of patients (1% of all patients treated for acute alcohol poisoning) required clinical treatment. The obtained data provided the basis for a more targeted preventive action in certain population groups, as well as the adequate planning of professional medical staff engagement, material, spatial and other capacities. These data, also, provided the basis for additional detailed social, economic, health and other researches in this area as well as a more detailed registration of this type of poisoning and establishing a monitoring system and database.


Introduction
The development of science, technology and industry leads to the development and production a lot of new chemicals and their broad use create the possibility for potential acute poisoning, which represent one of the important causes of morbidity and mortality in many countries 1.According to the available data, around 355.000 persons dies in the world every year, as a result of the unintentional poisoning 2 .Causes of poisoning, gender and age structure, severity of poisoning, as well as the outcome of treatment are specific and different between local regions within countries, as well as between the countries and regions all over the world 3 -11 .More precise data can be obtained only in those countries that have developed health information system and the exact records of illnesses and causes of death.Acute intoxications by chemical substances are very important in terms of the organization of care for emergency cases in Serbia 12 -15 .As a part of the emergency pathology, patients who required medical treatment and observation after acute intoxication caused by different chemical substances participate with about 8% of the total number of treated patients in the Center of the Emergency Care of the Military Medical Academy in Belgrade.
Ethanol, ethyl alcohol or alcohol, is one of the most frequently used substances of abuse all over the world.There are many reasons for that and among the most important ones are: easy availability, low price, certain types of customs, aggressive advertisements, limited legal sanctions, etc. Excessive and frequently use of alcohol often leads to the emergence of alcoholism, as well as many health and social problems 16,17 .About two thirds of adult population in the United States of America (USA) consumed alcohol drinks, and about 10% of them in the case-history have excessive alcohol consumption.A particular area of concern is the fact that a certain number of thеse acute intoxication has death as a final outcome 18.According to the World Health Organization (WHO) data around 208 million people were consumed alcohol during the year 2010 that is about 4.10 % of all world population aged over 15 years 19,20 .Also, according to the WHO data, Serbia is at a very high, 12 th place, with registered 12.6 liters of consumed alcoholic beverages per capita during one year in population older than 15 years.Ethanol is very often cause of acute intoxication which requires an urgent care in the health care institutions.
Assessment of the frequency of the acute ethanol intoxication, gender and age of poisoned patients, severity of poisoning, as well as level of the therapeutic measurements are not fully investigated, but they are of great importance for preventive work and capacity planning (material, human resources, spatial and other capacities) necessary for medical treatment.
The aim of this study was to estimate the frequency of ethanol intoxication and to assess the basic characteristics of the patients treated due to acute ethanol poisoning including age, gender, severity of poisoning and modality of treatment.These results may be important for further prospective investigation and adequate preventive intervention in certain age and gender population, as well as for necessary staff and hospital capacities planning.

Study design
This study was done in the National Poison Control Centre (NPCC), Military Medical Academy (MMA), Belgrade, Serbia, which usually provides medical treatment for 4,000 to 4,500 acutely poisoned patients per year.
A five-year retrospective study was done in a period from 2011 to 2015.It included the patiensts admitted to the emergency unit due to suspected poisoning.All poisoning cases were classified according to WHO's International Classification of Diseases-10 (ICD-10) 21 .The medical records were reviewed for all patients acute ethanol intoxication (10731 cases).They were provided with the necessary initial diagnostic procedures at the admission (hystory, physical examination, electocardiogram, vital signs, laboratory and toxicological tests, and in some specific situations, with other diagnostic procedures -Xray, computed tomography, etc.) and therapy treatments.
In accordance with their age, patients were divided into the following groups: 1 st group: ≤ 18 years, 2 nd group: 19 -40 years, 3 rd group: 41 -65 years, 4 rt group: > 65 years and 5 th group: patients with undetermined age.

Poison severity score
For determining the severity of the poisoning the standardized Poison Severity Score (PSS) was used: PSS 0 -no symptoms and signs related to poisoning; PSS 1 -mild or spontaneously resolving symptoms; PSS 2 -moderate, pronounced or prolonged symptoms, PSS 3 -severe or life-threatening symptoms and PSS 4 -with lethal outcome 22, 23.

Ethical approval
According to the Medicines and Medical Devices Agency of Serbia on Researches Involving Human Subjects retrospective research/patient file research does not fall under the scope of the Ministry of Health, Republic of Serbia.Therefore, ethical approval by the institutional medical ethical review board (the Ethics Committee of the Military Medical Academy) was not needed.
This research has been performed in accordance with the ethical standards laid down in the 1964 Declaration of Helsinki and its later amendments.

Informed consent
For this type of study formal informed consent is not required.

Statistical analysis
The complete statistic data processing was performed in the IBM SPSS Statistics 19.0 computer program (IBM, USA, 2011).All continuous variables are represented in the form of the mean (χ) ± standard deviations (SD), while the categorical variables are represented with the percentage of certain category frequency.For categorical variables the statistical significance of differences was examined by chi-square (χ 2 ) test.Ratios between variables were tested by Pearson correlation coefficient.All the analyses were evaluated at the level of statistical significance of p < 0.05.Health forecasting, as a novel area of forecasting, is a valuable tool for predicting future health events or situations such as demands for health services and healthcare needs.For purpose of our study, exponential smoothing (dampened trend) method was chosen for number of patient's time series prediction.

Results
In a period from year 2011 to 2015, 20891 patients intoxicated by different types of chemical agents were treated (average number per year was 4178.8 ± 606.51) including 10731 treated after acute ethanol poisoning (2146.2± 437.95 per year).The share of ethanol intoxication in the total number of patients did not differ significantly over the observed years, the average was 51.47 ± 2.86%.Their number was statistical significantly higher (p < 0.001) in comparison to the other poisoned patients (Table 1).

Table 1 (near here)
The number of patient intoxitaed by ethanol was in significant positive correlation with the number of patient poisoned by abuse drugs (r = 0.956; p < 0.05).There was no correlation with the of patients poisoned by prescribed drugs (r = -0.641;n.s.) (Figure 1).

Figure 1 (near here)
Generally, the frequency of intoxication was greater in male than in fimale population due to high prevalence of ethanol poisoning.In the male population is evident slight increasing trend of patients who were treated after intixication by ethanol, as well as by other agents.The increase in the number of patients treated after acute alcohol poisoning was higher than the number of patients treated after poisoning with other agents (p < 0.001) (Figure 2a).In the female population is evident statistically significant increase of acute ethanol poisonings in comparison with the number of treated patients after poisoning by other chemicals (p < 0.001) (Figure 2b).Most of patients intoxicated by ethanol were aged from 19 to 40 years (44.03 ± 7.09%), and their number was significantly higher in comparison with other age groups of poisoned patients (p < 0.001).The total number of the patient poisoned by ethanol was significantly lower in the following groups: group ≤ 18 years (13 08 ± 1 94%), group > 65 years (5.16 ± 2.32%) and a group of unknown age (2.49 ± 1.76%), respectively.On the Figure 3 were shown a reduction in the number of patients aged from 19 to 40 years during 2014, and then, in 2015, theirs significant growth.In the group of patients aged from 41 to 65 years, the reduction of the number of poisonings in 2013 year, while in 2014 and 2015 year a significant increasing in the number of patients poisoned by ethanol was registered.In the group of patients poisoned by other chemicals, the average number of treated patients was as follows: in the group of ≤ 18 years 10 12 ± 1 80%, in the group of 19 -40 years 47.43 ± 3.93%, in the group of 41 -65 years 34.04 ± 3.02%, in the group of more than 65 years 6.81 ± 0.81% and in the group in which was not precisely determined by the age 1.61 ± 1.01%.Comparison of age distribution between acute intoxication by ethanol and by other chemicals, revealed a statistically significant difference (p < 0.001) only in the group of the patients aged 41 to 65 years during 2014 and 2015 year.

Figure 4 (near here)
The average number of patients hospitalized for acute ethanol intoxication (after initial treatment in the Emergency room) was 1.05 ± 0.62% and it was significantly lower in comparison with poisoning by all other groups of agents (p < 0.001).During the entire period of the study, a significant increase in the trend of hospitalized patients after acute ethanol poisoning was observed in 2014.Of the total number of hospitalization per year due to acute poisoning, ethanol was the reason in only 0.35 ± 0.17% (p < 0.001).
The number of patients treated for acute ethanol poisoning had shown the trend of increasing, so that at the end of the observation period it was higher than the number of patients poisoned by all other chemicals.With intention to predict future health trends and health trends and healthcare needs, exponential smoothing (dampened trend) method was used.Table 2 shows the predicted number of poisonings by type of causal agents.It is evident that the largest increase is registered in the category of poisoning by substances of abuse, followed by ethanol.The minimal growth trend is registered in the categories of corrosives and vapours, while in other categories declining trend was registered.
Graphical presentation of registered cases of poisoning by categories (for the period from 2011 to 2015), as well as the projected trends for the same categories of agents (for the period from 2016 to 2020) are shown in Figure 5.

Discussion
Ethanol is the most common psychoactive substance used by adolescents and adults in the Serbia 24 -26 and is one of the most commonly abused substances in the world 27 .Excessive and uncontrolled consumption of ethanol greatly increases the risk of trauma, especially trauma due to motor vehicle collisions or violent crimes.Excessive consumption of ethanol results in serious health and social consequences such as acute drunkenness, chronic alcoholism and dependence with all its consequences.Alcohol causes 1.8 million deaths (3.2% of total) and a loss of 58.3 million (4% of total) of Disability-Adjusted Life Years (DALY) [2].Unintentional injuries alone account for about one third of the 1.8 million deaths, while neuro-psychiatric conditions account for close to 40% of the 58.3 million DALYs.The burden is not equally distributed among the countries.In Europe alone, alcohol consumption was responsible for many deaths among young people 28 .
In the paper Meropol SB et al. in which the relationship between alcohol abuse injuries in a population of adolescents who have been treated in the emergency department has been investigated.The highest percentage of positive ethanol test results in a group of 295 treated young patients was found at the urban trauma center, where 15% of total subjects and 22% of subjects aged 17 through 21 tested positive 29 .
Also, in the Clinic for Emergency in Oslo (Oslo study) 2343 adult patients have been treated after overdose by substances of abuse during one-year period, and 55.10% (1291) of these patients were treated after acute ethanol poisoning 30 .In our study, the average number of treated patients after acute ethanol poisoning in comparation to the total number of all treated patients after acute poisonings was 51.47%.In Oslo study, more than 89.00 % of all patients were treated after excessive consumption of ethanol, drugs, as well as substances of abuse.In our study, share of patients with acute intoxication by drugs, substances of abuse and ethanol was almost equal -89.43%.Comparing the total numbers of poisoning reported by Oslo study with those treated in our centre, and taking in account the number of Oslo inhabitants of 900.000 and Belgrade of about 1.660.000, the incidence was almost the same -0,26% and 0.25%, respectively.
By comparing gender representation in both studies, the results are as follows: in our study the relationship between the male and female patients treated for acute ethanol poisoning was 77.40% male and 22.60% female and in Oslo study 68.29% were males and 31.71%were females 30 .We can conclude that sex representation is also very similar in both studies -the male subjects are more often treated for acute ethanol poisoning.
Oslo study used different criteria for classification by age.Patients were divided into three groups: group I ≤ 25 years, group II 26 -50 years and group III > 50 years.In this study over than 52% of treated patients were in the group of 26 -50 years old 30 .In our study, the highest number of the treated patients after acute ethanol poisonings have been observed in the group of age from 19 to 40 years (44.03%) and the group of age from 41 to 65 years (35.47%).In both studies is evident that this is a working population, which specifically indicates the possible socio-economic implications and the need for more active prevention work in these population groups.
The severity of poisoning was assessed by the different criteria: Glasgow coma score in Oslo study and PSS in our study.Both studies showed that most of the treated patients did not had severe clinical signs of poisoning.The first study shoved that most of treated patients (85.19%) were in the group with Glasgow coma score of 10 -15.Our study showed that in a population acutely poisoned by ethanol 77.43% of patients were in the groups with PSS score ≤ 1 Due to the different criteria which define used scores it was difficult to perform accurate comparison, but it is evident that in both studies, the proportion of patients with mild to moderate level was high.
In accordance with severity of poisoning, only 1.05 % of our patients intoxicated by ethanol, after initial treatment in Emergency department requered additional hospital treatment.At the same time, this group of patients who required stationary treatment after acute ethanol poisoning in the group of all poisoned and treated patients was only 0.35 ± 0.17%.This data is very important for the planning of adequate spatial capacities primarily in emergence service, as well as the planning and scheduling of engagement of staff.
Another important planning factor is estimated number of patients in the future.Our forecast for the period 2016 -2020 indicates the highest increase of poisoning by substances of abuse (about 40%).However, predicted increase of slightly more than 20%, for acute ethanol intoxicants, may represent the greatest burden for emergency due to high absolute number of patients (Table 2).

Conclusion
Acute alcohol poisoning represents a significant part of the pathology in the total number of patients treated for acute poisoning by various chemical substances.The results of this analysis have shown that certain populations are particularly vulnerable to abuse of alcohol to the level requiring health care (male population, age 19 -65 years).Most of patients had mild signs and symptoms of poisoning and required only supportive and symptomatic treatment in the emergency room.
The presented data provide the basis for a more targeted preventive action in certain population groups, as well as the adequate planning of professional medical staff, material, spatial and other capacities.Given the potential impact of excessive alcohol consumption on the national health, along with the monitoring of chronic alcohol abuse, more detailed data on acute ethanol intoxication should be obtained.Enhancement of the monitoring system and database should enable the dissemination of data and information on trends in alcohol consumption, actual epidemiological situation regarding alcohol drinking, including alcohol-related mortality and possible details of health policy responses.Online First June 2018.

Fig. 1 -Fig. 2 -Fig. 3 -Fig. 4 -Fig. 5 -
Fig. 1 -Correlation of the total number of patients poisoned by alcohol and drugs, or drugs of abuse in the period from year 2011 to 2015