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Acute poisoning with benzodiazepines and other hypnotics: Etiologic cause, sex/age distribution and clinical outcome

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Petko Marinov at Medical University of Varna
Petko Marinov
Snezha Zlateva
Snezha Zlateva
Snezha Zlateva
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Georgi Bonchev
Georgi Bonchev
Georgi Bonchev
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Dobri Ivanov at Medical University of Varna
Dobri Ivanov
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Abstract

Purpose: Poisoning with drugs occupies a leading position among the causes of acute intoxications. Etiological distribution of medicated poisoning in different countries, even if they are adjacent, is different. In the most studies, it was reported that the highest incidence of poisoning is with benzodiazepines or other psychoactive drugs. A retrospective analysis of acute poisoning with benzodiazepines and other hypnotic drugs in the Varna region for 25 years period – from 1991 to 2015 was carried out. Material and Methods: The number of patients who received hospital treatment after poisoning with benzodiazepines is 1741, and those with other hypnotics is 293, representing respectively 26.37% and 4.44% of all drug intoxications. Results: The share of poisoning with benzodiazepines and hypnotics compared to all acute intoxications is 11.66%. They are more common in women – 1566 (77%). Men are 468 (23%), the ratio of men to women was 3.34:1. The largest number of intoxications is in the age group up to 24 years - 1123 (55.2%), and only 4.1% of patients over 60 years. Intentional suicide attempts are 1896 (93.2%). Death is registered in 8 (0.4%) patients. � 2016, Medical University - Varna. All rights reserved.
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/ J of IMAB. 2016, vol. 22, issue 4/ http://www.journal-imab-bg.org 1371
ACUTE POISONING WITH BENZODIAZEPINES
AND OTHER HYPNOTICS: ETIOLOGIC CAUSE,
SEX/AGE DISTRIBUTION AND CLINICAL
OUTCOME
Petko Marinov1,4, Snezha Zlateva1,4, Georgi Bonchev1, Dobri Ivanov2, Kaloyan
Georgiev3, Yulichka Sabeva4, Marieta Yovcheva1
1) Clinic for Intensive Treatment of Acute Intoxications and Toxicoallergies,
Naval Hospital – Varna, Military Medical Academy, Bulgaria
2) Department of Biology, Faculty of Pharmacy, Medical University - Varna,
Bulgaria
3) Department of Pharmaceutical Technologies, Faculty of Pharmacy, Medical
University - Varna, Bulgaria
4) Department of Pharmacology, Toxicology and Pharmacotherapy, Faculty of
Pharmacy, Medical University - Varna, Bulgaria
Journal of IMAB - Annual Proceeding (Scientific Papers) 2016, vol. 22, issue 4
Journal of IMAB
ISSN: 1312-773X
http://www.journal-imab-bg.org
ABSTRACT
Purpose: Poisoning with drugs occupies a leading
position among the causes of acute intoxications.
Etiological distribution of medicated poisoning in different
countries, even if they are adjacent, is different. In the most
studies, it was reported that the highest incidence of poi-
soning is with benzodiazepines or other psychoactive drugs.
A retrospective analysis of acute poisoning with benzo-
diazepines and other hypnotic drugs in the Varna region for
25 years period – from 1991 to 2015 was carried out.
Material and Methods: The number of patients
who received hospital treatment after poisoning with
benzodiazepines is 1741, and those with other hypnotics
is 293, representing respectively 26.37% and 4.44% of all
drug intoxications.
Results: The share of poisoning with
benzodiazepines and hypnotics compared to all acute
intoxications is 11.66%. They are more common in women
– 1566 (77%). Men are 468 (23%), the ratio of men to women
was 3.34:1. The largest number of intoxications is in the age
group up to 24 years - 1123 (55.2%), and only 4.1% of pa-
tients over 60 years. Intentional suicide attempts are 1896
(93.2%). Death is registered in 8 (0.4%) patients.
Key words: benzodiazepines, hypnotics, drug poi-
soning
INTRODUCTION
Acute poisonings are a serious social and health
problem throughout the world and are a major cause of hos-
pitalization in emergency and intensive care [1]. The drugs
are the most common etiological factor for hospitalization
due to poisoning [2, 3]. The incidence of drug intoxication
varies widely between countries – from 13.8% [4] to 88.2%
[5]. A number of studies have shown that the highest frequen-
cies are the poisonings with psychoactive drugs [6 - 10] or
benzodiazepines [11 - 16].
In this regard, we aim to investigate poisoning with
benzodiazepines and hypnotic drugs in the Varna region for
25 years (1991-2015 years), defining their frequency dynam-
ics during the period, the etiological structure, mortality, and
demographic characteristics – breakdown by gender and age.
MATERIALS AND METHODS
Patients
The objects of the study were 2034 patients with
acute poisonings with benzodiazepines and hypnotics, who
received treatment in the Clinic of Toxicology of Military
Medical Academy Varna/Bulgaria for the period 1991-2015.
The study was retrospective. It has analyzed the stories of
illness, personal outpatient cards, and the accepted treatment
of poisoned patients and medico-legal reports autopsies of
the deceased patients. The hypnotics are divided into bar-
biturates and non-barbituric compounds. The diagnosis was
based on history, clinical symptoms and was confirmed by
demonstration of the medication and/or their metabolites in
blood and urine of patients.
Statistical Analysis
A descriptive analysis was used for assessment of
the results of the study.
RESULTS AND DISCUSSION
During the period 1991-2015, in the Clinic of Toxi-
cology were hospitalized 6601 patients with acute drug
poisonings. Acute intoxication with benzodiazepines and
other hypnotic medications were 2034 (30.8%). Their share
compared to all poisoning is 11.66%. Poisonings with
benzodiazepines were 1741 (26.37%). Barbiturate
intoxications were 120 (1.98%), poisonings with non-barbi-
turic hypnotic compounds were 173 (2.62%). The drugs are
the most common etiological cause of hospital admissions
due to poisoning [3, 5, 6, 11, 17, 18, 19]. We find a signifi-
cant difference in the absolute number of poisonings with
https://doi.org/10.5272/jimab.2016224.1371
1372 http://www.journal-imab-bg.org / J of IMAB. 2016, vol. 22, issue 4/
benzodiazepines and hypnotic pills and their share in all
acute intoxications during the studied period (Tabl. 1).
Poisoning with benzodiazepines occupies the first
position as frequency among medicated intoxication while
poisoning with hypnotic drugs is considerably rarer. Fol-
lowing the dynamics of intoxication with benzodiazepines
and other hypnotics, it has established a tendency to re-
duce their absolute numbers in the second half of the pe-
riod. Their share is the highest during the first 5 years and
then it declines. The absolute number of intoxications with
benzodiazepines has decreased 7.5 times in 2015 compared
to those in 1991. Similar results were observed with hyp-
notic drugs.
In our study medication poisonings occurred sig-
nificantly more often in women – 1566 (77%) than in men
– 468 (23%). The ratio female:male were 3.34:1. We estab-
lished the greater frequency of drug intoxication in women,
also confirmed by studies in other countries, including Bul-
garia neighbors [8, 12, 17, 18, 20]. The analysis of the dis-
tribution of drug intoxication by age shows that the most
Tabl. 1. Absolute and relative share of poisonings with benzodiazepines and other hypnotics
Year Total count Poisonings with benzodiazepines Poisonings with other hypnotics
of poisonings Count Percent Count Percent
1991 906 174 19.2 30 3.3
1992 892 133 14.9 23 2.6
1993 884 146 16.5 26 2.9
1994 885 145 16.4 32 3.6
1995 879 144 16.4 27 3.1
1996 797 113 14.2 18 2.2
1997 773 91 11.8 29 3.7
1998 883 100 11.3 21 2.4
1999 801 96 12.0 17 2.1
2000 617 65 10.5 11 1.8
2001 508 41 8.1 5 1.0
2002 593 29 4.9 5 0.8
2003 506 26 5.1 5 1.0
2004 633 26 4.1 5 0.8
2005 525 21 4.0 4 0.8
2006 674 33 4.9 5 0.7
2007 708 46 6.5 1 0.1
2008 829 56 6.7 2 0.2
2009 798 59 7.4 2 0.25
2010 656 37 5.6 0 0.0
2011 553 43 8.0 5 0.9
2012 590 31 5.2 7 1.2
2013 529 30 5.7 5 0.9
2014 484 33 6.8 5 1.0
2015 546 23 4.2 4 0.7
Total 17438 1741 9.98 293 1.68
affected age group is up to 24 years – 1123 cases (55.2%)
(Tabl. 2).
Tabl. 2. Frequency distribution of poisonings with
benzodiazepines and other hypnotic drugs by age
Age Patients Percent
up to 24 1123 55.2
25 - 44 694 34.1
45 - 60 134 6.6
over 60 83 4.1
The majority of poisonings with drugs - 89.3% were
in patients up to 44 years and only 4.1% are in people be-
yond working age. Extremely high frequency of poison-
ing with benzodiazepines and hypnotic drugs at the young
age implies a slight leakage of such intoxication and a
/ J of IMAB. 2016, vol. 22, issue 4/ http://www.journal-imab-bg.org 1373
cation. All these combined with the availability and severe
comorbidities lead to more severe course of poisoning and
adverse outcome.
CONCLUSIONS
Poisonings with benzodiazepines and hypnotic drugs
are 30.8% compared to all medication poisonings and
11.66% of all acute intoxications. The most of them
(93.2%) are a result of suicide attempts. Benzodiazepines
occupy the leading position as a reason for hospitalization
due to drug poisoning. Poisonings with benzodiazepines
and hypnotics are more common in females and in younger
age. Lethality in intoxications with benzodiazepines and
hypnotic drugs were 0.4%.
more favorable outcome from them. In a number of studies
was reported that the greater the incidence of poisoning is
in the age up to 30 years [2, 3, 9, 11, 12, 17, 19]. Young
women are the highest risk group for poisonings with medi-
cations [5, 6, 18].
Poisonings with benzodiazepines and hypnotic drugs
were a mostly result of suicide attempts - 1896 (93.2%).
Fatalities were registered in 8 (0.4%) patients of mean age
73.5 years. In two patients the cause of death is intoxica-
tion with phenobarbital. In the remaining 6 patients
benzodiazepines are poisoning the cause of death. All 8
patients were elderly. Slower metabolism of drugs and their
highly elongated plasma half-life leads to more prolonged
suppression of consciousness and the protraction of intoxi-
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Address for correspondence:
Georgi Bonchev, PhD, Head, Laboratory of Analytycal Toxicology
Military Medical Academy, Naval Hospital – Varna
3, Chr. Smirnenski Str., 9010 Varna, Bulgaria
E-mail: toxilab.varna@abv.bg
Please cite this article as: Marinov P, Zlateva S, Bonchev G, Ivanov D, Georgiev K, Sabeva Y, Yovcheva M. Acute poi-
soning with benzodiazepines and other hypnotics: etiologic cause, sex/age distribution and clinical outcome. J of IMAB.
2016 Oct-Dec;22(4):1371-1374. DOI: https://doi.org/10.5272/jimab.2016224.1371
Received: 07/09/2016; Published online: 10/11/2016
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  • Aug 2013
  • CLIN TOXICOL
Introduction: Large, prospective pre-hospital studies of acute poisonings are scarce. We present the epidemiology of the pre-hospital poisonings, the treatment given, the complications of the poisoning itself and the treatment, predictors for hospitalization, and the safety of the present approach in a large industrial Russian city. Methods: Data were collected from March 2009 to March 2010. All adult (≥ 16 years) acute poisonings in the city of Yekaterinburg, Russia were included. The prospective cohort inclusion of data included age, gender, simple clinical features (including consciousness, respiratory status, circulatory status, convulsions, etc.), main toxic agent, reason why poisoning was suspected, treatment given, and outcome. Multivariate logistic regression analysis was used to identify the factors associated with hospitalization of the patients. Results: In total, 1795/2536 patients (71%) were brought to hospitals, 736/2536 (29%) were discharged by the ambulance, and 5/2536 (0.2%) died on scene. The most frequent main agents were opioids (25%), ethanol (9%), benzodiazepines (8%), corrosive substances (7%), carbon monoxide (5%), and neuroleptics (5%). Pre-hospital treatment was given to 73% of patients; 3% were intubated, and antidotes were given in 27% (naloxone 24%, atropine 2%, and flumazenil 0.2%). Gastric lavage was performed in 34%, but only 20% within the first hour after ingestion; 49% had a Glasgow Coma Scale (GCS)< 15, but only 6% of them were intubated in the ambulance. Activated charcoal was given to two patients, both with a GCS = 15. A suicidal behavior was the strongest predictor for hospitalization. Conclusion: This study reveals current practice differing from the common treatment practice in most places, especially concerning the use of gastric lavage. Whether the current practice led to an increased morbidity and mortality is uncertain, but it justifies the need for thorough evaluation of clinical practice. These findings highlight the importance of studies like the present to improve diagnostics, triage, and treatment in acute poisonings.
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Epidemiology of acute drug poisoning in a tertiary center from Iasi County, Romania
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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.
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The relationship of demographic and etiological characteristics with mortality in acutely poisoned patients admitted to intensive care unit
Article
  • Mar 2009
Aim: To evaluate the relationship of demographic, and etiological elnirecteristirs with mortality in acutely poisoned patients admitted to the intensive care unit (1CU). Material and Melhodş: Medical records of poisoned patients admitted to the ICU between January 2002 and July 2005 were reviewed retrospectively. Demographic data [age, sex, Glascow coma scale (CCS) on admission, APACHE II score], eliological data, and clinical outcome [length of stay (LOS) in the ICU, duration of mechanical ventilation, and the ICU mortality] were analyzed. Results: They were 121 poisoning patients (66 females and 55 males), and mean age was 38,15+14,34 years. GCS and APACHE II were 8,47+4,10 and 15,80±8,74 respectively. Toxic substances involved were, in descending order, organophosphates (45,5 %), tricyclic anlidepressant (% 14,8), multiple drugs (% 14,8), methanol (% 9), different types of drugs (% 10,7), food (% 3,3), and carbon monoxide (% 1,6). The overall mortality rale was 15.7 %, and toxic agents caused the highest fatality rates were methanol and organophosphate (54,5 % and % 21,7, respectively). Young female were more poisoned with tricy-lic antideprcssant and multiple drugs. Age, APACHE II, LOS in the ICU, and duration of mechanical ventilation were significantly higher in patients poisoned by methanol, while GCS was lower than other groups. Also, in nonsurvived patients age, APACHE II, and duration of mechanical ventilation were higher than survived patients, while GCS was lower than survived group. Conclusion: Age, GCS, APACHE II score, and the type of toxie substances may be a determinant for mortality in poisoned patients. While most of the poisonings were due to organophosphates, tricyclic antidepressant and multiple drugs were the most commonly ingested agents by young female.
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In-Hospital Mortality and Long-Term Survival of Patients With Acute Intoxication Admitted to the ICU
Article
  • Feb 2014
To assess in-hospital and long-term mortality of Dutch ICU patients admitted with an acute intoxication. Cohort of ICU admissions from a national ICU registry linked to records from an insurance claims database. Eighty-one ICUs (85% of all Dutch ICUs). Seven thousand three hundred thirty-one admissions between January 1, 2008, and October 1, 2011. None. Kaplan-Meier curves were used to compare the unadjusted mortality of the total intoxicated population and for specific intoxication subgroups based on the Acute Physiology and Chronic Health Evaluation IV reasons for admission: 1) alcohol(s), 2) analgesics, 3) antidepressants, 4) street drugs, 5) sedatives, 6) poisoning (carbon monoxide, arsenic, or cyanide), 7) other toxins, and 8) combinations. The case-mix adjusted mortality was assessed by the odds ratio adjusted for age, gender, severity of illness, intubation status, recurrent intoxication, and several comorbidities. The ICU mortality was 1.2%, and the in-hospital mortality was 2.1%. The mortality 1, 3, 6, 12, and 24 months after ICU admission was 2.8%, 4.1%, 5.2%, 6.5%, and 9.3%, respectively. Street drugs had the highest mortality 2 years after ICU admission (12.3%); a combination of different intoxications had the lowest (6.3%). The adjusted observed mortality showed that intoxications with street drugs and "other toxins" have a significant higher mortality 1 month after ICU admission (odds ratioadj = 1.63 and odds ratioadj= 1.73, respectively). Intoxications with alcohol or antidepressants have a significant lower mortality 1 month after ICU admission (odds ratioadj = 0.50 and odds ratioadj = 0.46, respectively). These differences were not found in the adjusted mortality 3 months upward of ICU admission. Overall, the mortality 2 years after ICU admission is relatively low compared with other ICU admissions. The first 3 months after ICU admission there is a difference in mortality between the subgroups, not thereafter. Still, the difference between the in-hospital mortality and the mortality after 2 years is substantial.
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