The INTOXICATE study: Methodology, experience and preliminary results of a prospective cohort study

doi:10.21203/rs.3.rs-4622968/v1

Download PDF

Research Article

The INTOXICATE study: Methodology, experience and preliminary results of a prospective cohort study

https://doi.org/10.21203/rs.3.rs-4622968/v1

This work is licensed under a CC BY 4.0 License

Journal Publication

published 27 Sep, 2024

Read the published version in Critical Care →

You are reading this latest preprint version

Background

No practice-based, multicenter database of poisoned patients admitted to intensive care units (ICUs) exists. The INTOXICATE study, endorsed by the ESICM and EAPCCT, aimed to collect detailed data on such patients. We hypothesized that the proportion of ICU intoxicated patients requiring genuine intensive care would be greater than previously reported.

Methods

Ethical approval was obtained for this multicenter, prospective study, and data-sharing contracts were signed. An electronic case report form was used to collect patient demographics, exposure, clinical features, investigations, treatment, and in-hospital mortality. The primary outcome was the proportion of patients who received mechanical ventilation and/or vasopressors in the first 24 h after ICU admission, and/or who died in the hospital. A one-proportion z test was used to test the difference in outcome in this study compared with the proportion of 6.5% previously observed in a large study.

Results

Seventy-eight ICUs, mainly from Europe, but also from Australia and the Eastern Mediterranean, participated. The median time to sign a data sharing agreement between a unit and the coordinating center was 17 months. A total of 2,275 patients were enrolled between November 2020 and June 2023. The median patient age was 41 years, 72% of whom were exposed to human drugs; neurological symptoms were the most common clinical feature (83% of admissions), and the ICU mortality rate was 3.7%. The observed proportion of patients with the primary outcome (requiring ICU treatment) was 40% versus 6.5% as previously mentioned (p-value < 0.001).

Conclusions

This study collected high-quality detailed clinical data from a large cohort of acutely intoxicated ICU patients. The proportion of intoxicated patients admitted to the ICU and requiring ICU treatment was much greater than previously mentioned. The challenges identified during the study setup and data collection will enable modifications of these processes for future data collection studies.

Trial registration

OSF registration ID: osf.io/7e5uy

Toxicology

Poisoning

Intensive Care Units

Critical Care Outcomes

Database Management Systems

Globally, human poisoning is an underrecognized and underreported major public health concern, with an estimated 84,278 deaths per year from unintentional poisoning [1] and more than 700,000 deaths per year from suicide [2, 3] worldwide in 2019. There are large disparities in mortality rates from both unintentional and intentional poisoning between and within continents and countries [1, 2]. The number of deaths and mortality rates due to intentional poisoning are greater than those due to unintentional poisoning. The global death rate from unintentional poisoning is 1.1 per 100,000 population and is decreasing worldwide [1]. The global age- standardized suicide mortality rate was 9 per 100 000 population in 2019 [2, 4]. However, “suicide” also includes methods of self-harm other than poisoning (e.g. hanging, shooting etc.). Worldwide mortality rates due to intentional poisoning are difficult to determine. In the USA, an intentional poisoning mortality rate of 1.93 per 100,000 population aged 15 years and older was reported for the period 2005–2016 [5]. In the United States of America (USA) and in Europe, intentional overdose deaths are no longer increasing due to the opioid crisis [6, 7]. The increase in the opioid-related overdose mortality rate was 7.8% between 2010 and 2018 in the USA compared with an average of 2.53% in European countries where an increase was observed [8]. However, there was wide variation between European countries, ranging from no increase/ a slight decrease to the largest increase in Scotland (+ 11.8%) [8]. A population-based study of national death records in the USA reported that the proportion of overdose deaths involving both fentanyl and stimulants increased from 0.6% (n = 235) in 2020 to 32.3% (34 429) in 2021 [9]. In Europe (including Norway and Turkey), between 7400 and 8300 deaths were attributed to opioids (often heroin, or opioid substitutes such as methadone and buprenorphine) in 2018 [10].

Hospital management of poisoning is based on appropriate general supportive and/or toxic-specific treatment. Patients with moderate or severe poisoning-related effects are likely to require Level 3 (intensive care units or ICUs) or Level 2 (high dependency unit or HDUs) care [11]. A serious effect is defined by the America’s Poison Centers (APC) as experiencing signs or symptoms that are life-threatening or result in significant permanent disability or disfigurement [12]. Examples of moderate or severe poisoning effects include severe acid-base disturbances, hyperpyrexia, confusion/agitation/aggression, treatment-unresponsive hypo- or hypertension and recurrent seizures. While information from poison information centers/services, along with that from individual treatment centers, is invaluable for providing epidemiological information and identifying emerging geographic and temporal trends in poisonings, it is not a sufficiently detailed source of information to understand the complexities of treatment and outcomes of patients admitted to the ICU following moderate/severe poisoning.

The majority of ICUs worldwide treat poisoned patients. Of the 785,141 patients aged 20 years or older who required treatment in a healthcare facility reported in the North American National Poison Data System (NPDS) in 2022, 113,620 (14.5%) had moderate effects and 31,520 (4%) had severe effects and were likely to require admission to an HDU or ICU [13].

The severity of poisoning depends on many factors, such as the type and dose of xenobiotics, patient characteristics (age, sex, comorbidities), clinical features at hospital presentation (level of consciousness, blood pressure, pulse rate, respiratory rate, temperature), time to treatment, poisoning circumstances (intentional or accidental; coingestions) and/or laboratory findings (electrolyte imbalances, coagulation abnormalities, renal function etc.) [14–22].

In addition to these predictors, the ICU mortality rate after poisoning also depends on the type of exposure, which differs between low- and middle-income countries and countries such as the USA, Australia or European countries. ICU mortality after acute poisoning therefore varies between continents and countries. High ICU mortality rates of 21.5% and 27.7% in ICU patients admitted for acute poisoning have been reported in Iran and China [23, 24], whereas ICU mortality in the USA, Australia or European ICUs is usually much lower, ranging from 0 to 6% depending on the study [13, 18, 25–34].

Previously published studies on the management and outcomes of ICU patients after acute poisoning have been relatively small single-center studies [27, 30, 31, 33, 35–37], sometimes including a few hundred patients, but still single-center and retrospective [25], sometimes not very recent [34], and lacking common methodology and definitions. A few studies were limited to one country [14, 38, 39]. The studies from Finland [14] and Sweden [39] were national studies, but lacked information on exposure or on treatment [38]. A more recent study was a multicenter study, but it used a North-American database and lacked the exact names, doses and routes of xenobiotics, as exposure was characterized only by APACHE IV categories [28].

Other studies were limited to developing or validating a prognostic model [18, 26, 29, 40]. There is no multinational database that collects information on severe poisoning in Europe and other continents. The INTOXICATE study aims to collect data on admissions to ICUs after acute poisoning in Europe and other continents to study the prognosis of these patients. In clinical medicine, prognosis is the prediction of future health outcomes for patients with a particular disease or health condition [41]. We hypothesized that the proportion of intoxicated ICU patients requiring intensive care would be greater than previously reported [18].

This was a prospective multicenter observational cohort study of patients admitted to ICUs after acute intoxication in Europe or other continents between 1st November 2020 and 30th June 2023.

Study registration and approval

The study protocol was available from November 2020 at toxicstudy.org. The study was registered prospectively with an Open Science Framework (OSF) (OSF registration ID: osf.io/7e5uy). The accredited Medical Research Ethics Committee of the University Medical Centre Utrecht (UMCU) did not consider the Dutch Medical Research Involving Human Subjects Act to be applicable to this study (ethics reference number: 20–495/C). All participating units provided either local research ethics committee approval or a waiver of consent. The original name was the "TOXIC-Europe study", but the name was changed to the INTOXICATE-study in October 2021 at the request of researchers involved in the Toxicology Investigators Consortium (ToxIC) run by the American College of Medical Toxicology, to avoid confusion.

Recruitment of intensive care units

The study was managed by a coordinating team supervising the national coordinators. In 2020, members of the European Association of Poison Centres and Clinical Toxicologists (EAPCCT) [42] and of the European Society of Intensive Care Medicine (ESICM) [43] were invited to participate in the INTOXICATE study. National coordinators were recruited to assist the coordinating team in recruiting ICUs and to assist them in obtaining the necessary approval in each country. All participating units had to follow the same procedure. A data-sharing contract had to be signed between the participating unit and the coordinating center, and the local investigator(s) had to provide information about their unit, and finally enroll patients. A list of collaborators is provided in the Acknowledgments section.

Patient selection

The patient inclusion criteria were adult patients (aged 18 years or older); patients admitted to the ICU from an emergency department, ambulance, or ward; intoxication (due to poisoning) as the main reason for ICU admission; patients who stayed in the ICU for four hours or more. The patient exclusion criteria were as follows: younger than 18 years; admitted to the ICU for another serious comorbidity (e.g., trauma from a car accident while intoxicated as the management, outcome and duration of admission were likely to be dictated by the comorbidity rather than intoxication); and an ICU stay shorter than four hours. An intoxication was defined as the occurrence of any toxic effect to humans following a single or repeated exposure to a mixture, natural or synthetic substance, available on the market or present in the environment. Pure ethanol intoxication was covered by the exposure definition. Before the study began, a sample size calculation indicated that at least 1879 patients would be needed. Details about the sample size calculation are provided in the Supplementary Material.

Consent

Informed consent

of the participating patients was either required or not, depending on the country and/or the unit. Local investigators reported only pseudoanonymized data. Patient confidentiality was maintained by deidentifying demographics(name, medical record number and date of birth).

Data collection

The data were collected first at the unit level and then at the patient level (Table 1). The data were entered into two study-specific databases (one for units and one for patients) developed in Castor EDC (Electronic Data Capture) [44]. Each patient and institution were identified by a code number generated by Castor EDC. Local investigators could access Castor through an account that required two-factor authentication (2FA). Local investigators entered their data into the database for patients identified as eligible, usually after hospital discharge. Data from Denmark were imported into Castor EDC in a single block (all patients from all Danish units at the same time) because Danish investigators collected patient data using the Redcap system; this made it easier for the Danish investigators to obtain the necessary institutional approval.

Table 1

Key data collected in the INTOXICATE study
Key data elements	Variables
Unit
	1. Type of hospital or institution
	2. Informed consent required or not for data collection?
	3. Unit type
	4. Which doctors write orders in the unit?
	5. Specialities of the unit
	6. Number of beds in the unit
	7. Number of admissions to the unit in the previous year
	8. Number of admissions for acute intoxication in the last year
Patient
Origin, dates and times
	1. Origin patient (ambulance/ED or ward or other ICU)
	2. Date and Time of Hospital admission (either ED or ward)
	3. Date and Time of ICU admission
	4. Date and Time of ICU discharge
	5. Date and Time of Hospital discharge
	6. Was a Poisons Information Center or a toxicologist contacted?
Patient characteristics
	1. ID patient number
	2. Age
	3. Sex
	4. Height
	5. Weight
	6. Comorbidities
	7. Second reason for ICU admission
Exposure
	1. Number of xenobiotics
	2. Reason of exposure (intentional or accidental)
	3. Time elapsed since the exposure
	4. Exposure category
	5. Name of exposure(s)
	6. Dose of exposure(s)
	7. Route of exposure
Clinical assessment
	1. Symptoms
	2. Location where the symptom(s) were observed
	3. Heart Rate at admission (most deviant)
	4. Systolic Blood Pressure at admission (most deviant)
	5. Diastolic Blood Pressure at admission (most deviant)
	6. Mean Arterial Pressure at admission (most deviant)
	7. Respiratory Rate at admission (most deviant)
	8. Body temperature at admission (most deviant)
	9. Glasgow Coma Score at admission
Lab
	1. International Normalized Ratio (INR)
	2. White blood count (WBC)
	3. Platelet count
	4. Hemoglobin
	5. Electrolytes
	6. Blood glucose
	7. Serum creatinine
	8. Urea
	9. Lactate
	10. Liver enzymes
	11. Total bilirubin
	12. Blood toxicology screen
	13. Urine toxicology screen
	14. Other
ECG
If ECG performed…	1. Performed or not
	2. Date and time
	3. QRS
	4. Heart rate on ECG
	5. QT time
	6. Abnormalities on the ECG
	7. Specify the abnormalities, if any
Treatment
Before ICU admission	1. Name treatment and location of administration
0–24 h in ICU	2. Name, route of administration, dose, duration
> 24 h in ICU	3. Name, route of administration, dose, duration
Complications and scores
	1. APACHE score if available
	2. SOFA score if available
	3. SAPS score if available
	4. Other score(s)
	5. Complication during the ICU stay
Outcome and follow-up
If patient deceased in hospital	1. Vital status at hospital discharge
	2. Destination after discharge
	3. Time elapsed between ICU admission and death
	4. Cause of death
	5. Withdrawal or withholding of treatment
If patient alive	6. Vital status 30 days after hospital discharge

[Insert Table 1 here]

The eCRF was divided into five sections: demographics, exposure, clinical feature, treatment, outcome and follow-up data (Table 1). The primary outcome reported in this article is the status at hospital discharge. The data entered by local investigators included only information that would have been collected as part of routine clinical care. Definitions of the variables were provided on the study website. Some questions had a ‘repeated format’, such as questions related to the patient’s exposure and treatments; for example, each treatment’s name, dose, route, and duration had to be entered. The eCRF was modified as little as possible over the years. Local investigators maintained their database at their site. In relation to this study, only the participating local investigators had access to the actual medical records of their own patients. To ensure complete case ascertainment, any missing or inconsistent data were identified at the end of the overall study data collection period and the local investigator was contacted to update/provide the data. The data were exported directly to R for further analysis.

The STROBE checklist was used in the preparation of this manuscript following the EQUATOR guidelines.

Data analysis

Participants with missing data were identified. Percentages were calculated for those with available data, and the denominator with missing data removed is reported throughout. The primary outcome was the proportion of patients who received mechanical ventilation and/or vasopressors in the first 24 h after ICU admission and/or who died in the hospital. A one-sample z test was used to test the difference in outcome in this study compared with the proportion of 6.5% previously observed in a large study [18]. All analyses were carried out in R studio version 2023.06.2 and R version 4.2.2. [45] for Windows.

Between November 2020 and June 2024, 237 units contacted us (Fig. 1), yet only 78 ICUs that met the inclusion criteria contributed data to the INTOXICATE study (Table 2).

Table 2

Location of the INTOXICATE intensive care units (ICUs) (N = 78)
City	Institution	Unit
Australia
Brisbane	Redcliffe Hospital	Intensive care unit
Austria
Salzburg	Paracelsus Medical University Salzburg	Medical intensive care unit
Belgium
Ghent	Ghent University Hospital	Intensive care unit
Brussels	Cliniques Universitaires St Luc	SIM/SIT
Ottignies	Clinique Saint Pierre Ottignies	Intensive care unit
Brugge	AZ Sint-Jan Brugge-Oostende AV	Intensieve zorgen
Charleroi	CHU Charleroi	Medico surgical ICU
Brunei Darussalam
Bandar Seri Begawan	Hospital RIPAS	Critical care medicine
Croatia
Split	University Hospital of Split	Internal medicine department, division of emergency and intensive medicine
Denmark
Copenhagen	Bispebjerg Hospital	Department of anaesthesia and intensive care
Herlev	Herlev Hospital	Afdeling for bedøvelse, operation og intensiv behandling
Roskilde	Zealand University Hospital	Intensive care unit I 12, Roskilde. dept. of anesthesiology
Køge	University Hospital Zealand - Køge	Intensive care unit, SUH Køge
Odense	OUH - Odense University Hospital	Department of intensive care
Viborg	Viborg Regional Hospital	Intensive care unit
Aalborg	Aalborg University Hospital	Anesthesia and intensive care department
Slagelse	Slagelse Hospital	Department of anaesthesia and intensive care
Egypt
Tanta	TANTA University Emergency Hospital	Emergency medicine and traumatology intensive care unit
Ismailia	Suez Canal University Hospitals (SCUH)	Department of anaesthesia and intensive care
Germany
Munich	Rechts der Isar Hospital	Toxikologische intensivstation
Essen	University Hospital Essen	Anästhesiologische intensivstation IT 2
Greece
Thessaloniki	Saint Paul (“Agios Pavlos”) General Hospital	Intensive care unit
Iraq
Najaf	Al-Sader Medical city Teaching Hospital	Intensive care unit
Italy
Milan	Humanitas Research Hospital	Department of anesthesiology and intensive care
Jordan
Amman	Jordan University Hospital, Amman	Medical intensive care unit
Amman	Islamic hospital	Surgical ICU
Amman	Amman Field Hospital	Intensive care unit
Lithuania
Vilnius	Republic Vilnius University hospital	Toxicology Centre
Netherlands
Utrecht	University Medical Center Utrecht	Department of intensive care medicine
Utrecht	Diakonessenhuis Utrecht	Intensive care unit
Enschede	Medisch Spectrum Twente	Intensive care center
Den Haag	Haaglanden Medisch centrum	Intensive care unit
Leeuwarden	Medisch Centrum Leeuwarden	Afdeling intensive care
Amsterdam	Onze Lieve Vrouwe Gasthuis (OLVG) hospital	Intensive care
Arnhem	Rijnstate Hospital	Intensive care unit
Maastricht	Maastricht University Medical Center+	Intensive care
Rotterdam	Franciscus Gasthuis & Vlietland	Afdeling intensive care
Amsterdam	Antoni van Leeuwenhoek ziekenhuis	Intensive care
Groningen	University Medical Center Groningen	Department of critical care
Rotterdam	Maasstad Hospital	Intensive care unit
Rotterdam	Ikazia Ziekenhuis	Intensive care unit
Deventer	Deventer Ziekenhuis	Intensive care unit
Portugal
Lisbon	Hospital S. Francisco Xavier Centro Hospitalar Lisboa Ocidental	Unidade de cuidados intensivos polivalente
Vila Nova de Gaia	Centro Hospitalar Vila Nova de Gaia	Serviço de medicina intensiva polivalente
Alentejano	Hospital do Litoral Alentejano	Serviço de medicina intensiva
Romania
Bucharest	Clinical Emergency Hospital Bucharest	Anesthesiology and intensive care - toxicology
Cluj	Clinical Emergency County Hospital Cluj-Napoca	Anaesthesia and intensive care I department
Spain
Valencia	Consorcio Hospital General Universitario	UCI anestesia
Santiago de Compostela	University Clinic Hospital of Santiago de Compostela	Intensive care unit, intensive care medicine department
Tortosa	Hospital Verge de la Cinta	Servicio de medicina intensiva
Zaragoza	Hospital Universitario Lozano-Blesa	Unidad de cuidado intensivos
Girona	Hospital Santa Caterina de Salt	Unidad de cuidados intensivos
Girona	Hospital Universitario Dr Josep Trueta	Unidad de cuidados intensivos
Octubre Madrid	Hospital Universitario 12 de Octubre	Trauma and emergency ICU. Intensive care medicine service
Valencia	IMED Hospital Valencia	UCI
Huesca	University San Jorge Hospital	Intensive care medicine
Granollers	Hospital General Granollers	Intensive care unit
Valladolid	Hospital Universitario Río Hortega	Servicio de medicina intensiva, unidad 1
Valladolid	Hospital Universitario Río Hortega	Servicio de medicina intensiva, unidad 2
Sudan
Khartoum-EastNile	East Nile (Sharg Alneel) Hospital	Intensive care unit
Sweden
Stockholm	South hospital	Intensive care unit
Stockholm	Capio St Görans hospital	Intensivvårdsavdelningen (IVA)
Lund	Skånes Universityhospital Lund	Intensivvårdsavdelning lund
Hudiksvalls	Hudiksvalls sjukhus	ICU Hudiksvall
Norrtälje	Norrtälje Hospital	Intensive care unit
Malmö	Skånes University Hospital, Malmö	Intensive care unit
Turkey
Istanbul - Kartal Dr. Lutfi Kirdar	Kartal Dr. Lutfi Kirdar Training and Research Hospital General	ICU
Ankara	Hacettepe University Faculty of Medicine, Ankara	Medical intensive care unit
Istanbul - Kanuni Sultan Suleyman	Kanuni Sultan Suleyman Education and Training Hospital	Anesthesiology intensive care unit (Reanimation)
Giresun	Giresun Eğitim Ve Araştırma Hastanesi	Reanimasyon 1 yoğun bakım
Sakarya	Sakarya University Faculty of Medicine	Department of internal medicine-intensive care unit
Trabzon	Karadeniz Technical University, Farabi Hospital	Anesthesia ICU-2
Kahramanmaraş	Kahramanmaraş Sütçü İmam Üniversitesi Tıp Fakültesi Sağlık Uygulama ve Eğitim Hastanesi	KSÜ anestezi yoğun bakim
Adana	Seyhan Public Hospital	Mixed-intensive care unit
Ankara	Ataturk Sanatorium Training and Research Hospital	General intensive care unit
United Kingdom
Nottingham	Nottingham University Hospitals NHS Trust	Intensive care unit
London	Guy’s and St Thomas’ NHS Foundation Trust	Intensive care unit
Cramlington	Northumbria Healthcare NHS foundation trust	Northumbria specialist emergency care hospital

[Insert Table 2 here]

Ethics and GDPR

In some countries, ethical approval and informed consent were considered at the national level (e.g. Belgium, Sweden or Denmark), but in other countries, they were considered at the level of the ICU (e.g. Spain). Informed consent was considered required or not required, depending on the country and/or unit; informed consent was required in 45 units (57%). In eight countries (38%), informed consent was required in all units in the respective countries, whereas in eight other countries, the situation was heterogeneous, with some units considering informed consent mandatory and others, not. In some non-European countries, the General Data Protection Regulation (GDPR) [46] did not apply (e.g. Egypt, Sudan, Iraq, Jordan).

Data-sharing agreements

There were also large differences across countries and institutions in the ease or difficulty of obtaining a data-sharing agreement signed by local competent authorities. Difficulties or delays in obtaining a contract acceptable to both parties (the ICU and the coordinating center) resulted in 66 potentially eligible units not participating in the study (Fig. 1). The median time to sign a data sharing agreement between a unit and the coordinating center was 17 (range 1 to 37) months.

[Insert Fig. 1 here]

Characteristics of intensive care units

Table 3 shows the characteristics of the units. The majority (62%) were university-affiliated ICUs. The size of ICUs was also usually less than 30 beds, and the number of admissions was usually less than 2000 per year per unit. Most units had fewer than 60 poisoning-related admissions in the year before the study. In the majority of ICUs, the doctors who wrote the orders (laboratory tests and medication prescriptions) were specialists in intensive care medicine (62%), and 42% of the units had physicians certified in medical toxicology.

Table 3

Characteristics of intensive care units (ICUs) (N = 78 units)
Parameter	N (%)
Institution/hospital type
University affiliated	49 (62)
Community teaching	22 (28)
Community nonteaching	6 (8)
Private sector – teaching hospital^a	1 (1)
Number of ICU beds
< 10	17 (22)
10–15	20 (25)
15–30	24 (30)
30–45	10 (13)
> 45	7 (9)
Total number of ICU admissions in the last year
< 500	18 (23)
500–1000	25 (32)
1000–2000	25 (32)
2000–3000	6 (8)
> 3000	4 (5)
ICU admissions related to poisoning last year
< 30	38 (48)
30–60	21 (27)
60–120	12 (15)
120–180	1 (1)
> 180	6 (8)
What kind of doctors write orders in the ICU?
Non-IC doctors can write orders	22 (28)
Only IC doctors write orders	49 (62)
Other doctors	5 (6)
Unknown	2 (3)
Specialties^a
Medical	71 (90)
Toxicological	33 (42)
Respiratory or pulmonary	61 (77)
Surgical	56 (71)
Trauma	44 (56)
Cardiothoracic surgery	15 (19)
Cardiac or coronary	25 (32)
Transplantation	13 (16)
Burns	6 (8)
Neurological and/or neurosurgical	40 (51)
Other^b	11 (14)
Informed consent needed
No	33 (42)
Yes	45 (57)
Notes:
^a Total greater than 80 because most ICUs have multiple specialties.
^b ‘Addiction care’ (n = 1); ‘ECMO’ or ‘renal disease’ (n = 2); ‘General’ or ‘mixed’ or ‘multidisciplinary’ or ‘no specialty’ (n = 5); ‘Obstetrics and gynecology’ (n = 1); ‘Oncology’ or ‘Palliative’ (n = 2).

[Insert Table 3 here]

Patient inclusion and patient characteristics

We predicted that there would be approximately 2000 eligible patients in Europe in one year. However, the COVID-19 pandemic hit almost immediately after the study was initiated, forcing us to extend the study by a further year and eight months. A total of 2,275 patients (Fig. 2a) were enrolled during this extended data collection period. The Netherlands was the largest contributor, followed by Denmark and Spain (Fig. 2b). At the beginning of the study, as shown in Fig. 2c, admissions were inversely correlated with pandemic pressure in the Netherlands. When more people were admitted to intensive care units for COVID-19, fewer poisoned patients were included in our observational study.

[Insert Fig. 2 here]

The median patient age was 41 years (range 18 to 96 years) and slightly more women were affected (53.2% women, 46.5% men, 0.3% non-binary, and < 0.001% missing) (Fig. 3). The most common comorbidities are shown in Table 4; fifty-eight percent of patients had a coexisting psychiatric illness, addiction and diabetes were the next most common comorbidities and only nineteen percent of patients had no comorbidities.

[Insert Fig. 3 here]

Table 4

Most common comorbidities in the 2,275 patients
Variables	N (%)
Psychiatric comorbidity
Other than addiction^a	1338 (59)
Addiction^b	511 (22)
Somatic comorbidity
Diabetes	227 (10)
Chronic obstructive pulmonary disease	126 (5.5)
Heart failure^c	67 (2.9)
Metabolic / endocrine disease	56 (2.5)
Chronic kidney disease	46 (2)
No comorbidity	426 (19)
Notes:

^a Including depression, borderline personality disorder, schizophrenia, bipolar disorders, eating disorders, posttraumatic stress disorder, anxiety and neurodevelopmental disorders including deficits in intellectual functioning.

^b Addiction as defined in the Diagnostic and Statistical Manual of Mental Disorders (5th ed.; DSM-5: American Psychiatric Association, 2013), including gambling or sex addiction.

^c Heart failure including cardiomyopathy, severe heart valve or coronary diseases with angina or symptoms at rest or minimal physical effort such as changing clothing and day-to-day care (New York Heart Association or NYHA Class VI).

Clinical features and exposure

Figure 4 provides an overview of some of the data available from the Intoxicate study. Neurological symptoms were the most common on admission (N = 1893, 83% of admissions), with the top three neurological symptoms being altered consciousness (N = 980 patients, 43% of admissions), coma (N = 747 patients, 33% of admissions), and agitation (N = 294 patients, 13% of admissions (Fig. 4a). The vast majority of the patients (72%) were exposed to human drugs, and almost a quarter were exposed to alcohol (Fig. 4b).

[Insert Fig. 4 here]

Primary outcome, treatments and in-hospital mortality

The observed proportion of patients with outcome (i.e. receiving mechanical ventilation and/or vasopressors in the first 24 h after ICU admission, and/or with in-hospital death) was 40% versus 6.5% as previously mentioned in [18] (p-value < 0.001). In addition to supportive care, treatment in the first 24 hours in the ICU consisted mainly of mechanical ventilation (36% of admissions), fluid resuscitation (with more than 1.5 L fluid in total) (27% of admissions), antidote treatment (21% of admissions), and vasopressors (20%) (Fig. 4c). The majority (95%) of patients survived to discharge from the hospital (Fig. 4d) with 3.7% dying in the ICU and 0.7% dying in the ward following discharge from the ICU.

The INTOXICATE study is a multicenter, international, prospective, observational study conducted in ICUs across Europe and beyond, providing a powerful cohort to address critical questions in ICU patients admitted after acute intoxication. Despite major obstacles, including the COVID-19 pandemic, we have met enrollment expectations and collected detailed data on exposure, symptoms, laboratory tests, ECGs, and treatments to study the prognosis of these patients. The proportion of intoxicated patients admitted to the ICU and requiring ICU treatment in this study was much greater than that previously reported in a large study [18].

We observed several unique features in the INTOXICATE cohort.

COVID-19 pandemic

First, enrollment was very slow at the beginning and was well below expectations in the first year. We planned to enroll approximately 2000 eligible patients within a year. However, the COVID-19 pandemic hit almost immediately, which had a rapid and dramatic impact on non-COVID-19 clinical research. All research efforts were redirected toward finding treatments for COVID-19, especially research conducted in intensive care units. Fewer poisoned patients were enrolled in our study as the pandemic pressure on intensive care units increased due to the COVID-19 pandemic. The first explanation seems quite obvious. In the participating ICUs, health care teams were overwhelmed by COVID-19 patients and lacked time, rendering research activities nonessential during the pandemic. An alternative explanation could be a decrease in severe intoxication. However, it is unclear whether there were fewer cases of poisoning during the COVID-19 pandemic, or whether the decrease in hospitalizations reflected a reduction in medical treatment, especially among self-poisoned individuals. The immediate consequence was that the INTOXICATE study, which was originally planned to run for one year, had to be extended to reach its predetermined sample size. This had major implications for research management, finance, and even research ethics.

Countries

Second, there was unequal enrollment between countries. Six countries accountted for more than 75% of the patients included (the Netherlands, Denmark, Spain, Sweden, Turkey and Belgium). Some relatively 'small countries' (e.g. Austria or Lithuania) included more patients than other 'large countries' ('small' or 'large' referring to the country’s population size). These proportions do not reflect the total population of these countries in Europe. On the other hand, there is no reason to believe that the treatment of a patient admitted to an intensive care unit after acute poisoning varies greatly between European countries or between Europe and Australia. Therefore, the 3.7% ICU mortality observed in the study seems to be a plausible estimate for European countries. Differences in exposure and inpatient care may be greater if the country is from another continent or has fewer resources.

The differences in patient care can also vary between types of units. University hospitals were overrepresented in our study. The overrepresentation of patients enrolled in university centers is likely to be a product of researcher interest, experience and research infrastructure, and interaction with clinical care logistics. We need to look at whether patients treated in university centers had more complex exposures and/or comorbidities.

General data protection regulation (GDPR) and informed consent

In May 2018, the European Union (EU) implemented the General Data Protection Regulation (GDPR), which aims to clarify, codify, and extend the data rights of individuals [46]. Although the regulation applies to observational studies based on patient data extracted from the healthcare system, the GDPR provides an exemption for research, such as when a study conducted by an academic institution is necessary for the performance of a task carried out in the public interest according to Article 6(1)(e) of the GDPR. In our study, we processed sensitive personal health data of ill people, a large proportion of whom were unable to provide informed consent (43% of patients had altered consciousness, and 33% were in a coma on admission to the ICU). We pseudonymized the data to ensure that the coordinating center could not reidentify the patients. Only local site investigators had direct access to patient records and could reidentify patients from their own institutions. However, the text of the GDPR has been interpreted differently by different European countries. Some institutions in the Netherlands, Spain, Portugal, Romania, Sweden or Turkey (35% of the ICUs and in 24% of the countries in this study) accepted the research exemption to the GDPR. In Denmark (8% of the ICUs), the inclusion of patients was carried out retrospectively by searching electronic health records, as the interpretation of the GDPR in Denmark requires informed consent prior to inclusion if the inclusion is carried out prospectively. In other countries (58% of the ICUs and 38% of the countries in this study), such as Austria, Belgium, Germany, and Lithuania, informed consent from patients prior to participation was considered mandatory at the national level. The Netherlands is one of the few countries that regulates proxy consent (e.g., consent by close relatives or legal representatives when it is not possible to obtain the patient’s informed consent due to his/her condition at the time of hospital admission) [47]. We thought that there would be consistency in the requirement for informed consent within an individual country, but this was not the case. Variations in the process and in the time needed to obtain ethical approval for observational studies have been reported to hamper the inclusion of patients in some European countries and possibly negatively influence the validity of the results [48]. For instance, most severely ill elderly patients were less often recruited for studies in ICUs where some form of active consent at admission was necessary from either the patient or surrogates. Hence the survival outcome was greater in this group [49].

We also observed that the process of signing a data-sharing agreement varied widely between ICUs and/or institutions. The legal department of the coordinating center provided a data sharing contract that had to be approved and signed by the other institutions involved in the study. Some national coordinators arranged for this to be done at the national level, while in other countries a contract had to be signed at the hospital and/or intensive care unit level. Due to the number of units that initially contacted us, it was not feasible to discuss the whole contract again with each unit. Attitudes toward legal issues relating to international research, or research in general, varied within and between European countries. Some countries were more strict, and observational research was conducted as strictly as interventional research. It sometimes took a long time to convince the legal department of some institutions that our study was observational and not interventional. In some cases, the process of reaching consensus between the legal departments took so long that the unit did not have time to enroll patients. Negotiations were stopped in some situations that dragged on without agreement between the legal departments.

In the UK, regulations have been simplified compared to those in other European countries. However, in almost all ICUs in the UK and some ICUs in Australia, researchers were accustomed to receiving financial compensation (or national funding) for their department, and as the INTOXICATE study was conducted without external sponsorship, some units declined to participate. On the other hand, some units sent us a signed contract very quickly, but it was sometimes difficult for us to assess whether the person signing the contract was authorized to do so. In these (rare) cases, we asked the national coordinator and our division managers for their opinions. All in all, agreeing with the contract documents significantly complicated and prolonged the time needed to enroll the originally planned sample size. A central European ethics approval could have helped. However, our experience is that central European Ethics approval does not exempt from a data sharing agreement, which is considered, negotiated and signed only at the institutional level in certain countries.

Proportion of intoxicated patients admitted to the ICU requiring intensive care

The proportion of intoxicated patients admitted to the ICU with the primary outcome (requiring mechanical ventilation and/or vasopressors or dying in the hospital) in this study was significantly greater than that previously reported in a Dutch study [18]. The proportion of patients with the primary outcome was 40% in this study versus 6.5% previously. The differences between the two studies are the design (prospective and international in this study; retrospective and national in the previous study) and the size of the study (2275 admissions in the INTOXICATE study versus 9679 in the previous study), but mainly the inclusion/exclusion criteria: patients who had received mechanical ventilation or cardiopulmonary resuscitation (CPR) were not excluded from the INTOXICATE study but were excluded from the previous study. We believe that the definition of “required ICU treatment” should be broader than the definition used in the previous study [18] by including also other ICU treatments such as e.g., the need for renal replacement therapy (RRT), active cooling, and oxygen supplementation with a FiO2 > 40%. However, to compare the proportions, we kept the same definition of ‘primary outcome’ in this study (including only mechanical ventilation and vasopressors) as in the Brandenburg study.

Experience with Castor EDC

In recent years, there has been no doubt that electronic data capture (EDC) has proven to be an effective method in terms of accuracy, integrity, timeliness and cost effectiveness. The Castor EDC was used in the INTOXICATE study because it is the only EDC system allowed in the coordinating center. This EDC system ensures GCP compliance and is secure through the two-factor authentication procedure. It took some time for some local investigators to understand how the EDC system -and the 2FA procedure- were working, but the Castor customer service always responded promptly. In our experience, the Castor EDC was especially helpful in creating an eCRF, monitoring the study, and exporting data.

The INTOXICATE study has been able to collect data on a large cohort of patients admitted to the ICU after acute intoxication, from intensive care units based mainly in Europe, with some additional units from other continents (including Australia and the Eastern Mediterranean region). The study was able to collect clinical information on patients recruited using standardized electronic data collection methods, and the study data were monitored for quality and completeness. The data collected include detailed information on the exposure, clinical features, investigations, treatments, and outcomes both at discharge and 30 days after ICU admission, which will allow further research into the prognosis of ICU patients following acute intoxication. The proportion of intoxicated patients admitted to the ICU and requiring ICU treatment was much greater than previously mentioned. The challenges identified during the study setup and data collection will enable modifications of these processes for future data collection studies.

APC	America's Poison Centers
DPIC	Dutch Poisons Information Centre
EAPCCT	European Association of Poison Centres and Clinical Toxicologists
eCRF	Electronic Case Report Form
ED	Emergency Department
EDC	Electronic Data Capture
ESICM	European Society of Intensive Care Medicine
GDPR	General Data Protection Regulation
HDU	High Dependency Unit
ICU	Intensive Care Unit
OSF	Open Science Framework

Ethics approval and consent to participate

Data collection was approved by the accredited Medical Research Ethics Committee of the University Medical Centre Utrecht, The Netherlands (ethics reference number: 20-495/C). All participating units provided either local research ethics committee approval or a waiver of consent. The study was registered prospectively with an Open Science Framework (OSF) (OSF registration ID: osf.io/7e5uy).

Consent for publication

Not applicable.

Availability of data and materials

The participants of the study did not give written consent for their personal data to be shared publicly, so supporting data are not available.

Competing interests

The authors declare that they have no competing interests.

Funding

None.

Authors’ contributions

SMZ and CCH performed the analysis, prepared the figures and wrote the manuscript. All the authors contributed to the data collection. All authors have thoroughly reviewed and approved the manuscript. DWdeL and CCH supervised the study.

Acknowledgements

INTOXICATE Study Investigators Group (collaborators): Christian Aage Wamberg, Hazim Ababneh, Eman Abdulwahed, Sefanja Achterberg, Entisar Ahmed Ali Alshareea, Aiman Al-Touny, Mahmoud Alali, Ali Najeh Al-Awwady, Amar Al-Jarrah, Maytham A. Al-Juaifari, Hazem Zuhair Hussain Alnatour, Khayry Al-Shami, Ahmed Altobal, Shimaa Ahmed Hamed Abdelrahman Al-Touny, Mahmut Arslan, Theodoros Aslanidis, Avinash Aujayeb, Munire Babayigit, Robertas Badaras, Stuart Baker, Patricia Barral Segade, Najat Ben Hasan, Dennis C.J.J. Bergmans, Yeliz Bilir, Muhannud Binnawara, Patrick Biston, Dirk P. Boer, Hans Christian Boesen, Hella F. Borggreve, Helene Brix, Thirsa Brommer, Nestor Bueno-Vidales, Isabel Canas-Pérez, Maxim P. Carlier, Alba Castellanos Esparraguera, Deniz Cekic, Mario Chico-Fernández, Lisbeth Christiansen, Cristian Cobilinschi, Luis Coelho, Catalin Constantinescu, Alexander D. Cornet, Elena Crescioli, Cristina Cuenca-Rubio, Paul I Dargan, Raluca Darie, Dylan W. de Lange, Francisco de Paula Delgado-Moya, Nicolas De Schryver, Bram Dewulf, Willem Dieperink, Patrick Druwé, Simon Dubler, Maree Duroux, Mohamed Elbahnasawy, Muhammed Elhadi, Ahmet Eroglu, Selin Eyüpoğlu, Raquel Feria Gil, Ana Silva Fernandes, Carolina Ferrer, Ana Ferrer Dufol, Sune Forsberg, Diego Franch-Llasat, Rik T. Gerritsen, Reem Ghmagh, Juliana Gonzalez Londoño, Christoffer Grant Sølling, Kjeld Gravgaard, Massimiliano Greco, Goncalo Guerreiro, Nicole Gustavsson, Seda Güzeldag, Burcin Halacli, Hytham K. S. Hamid, Philippe Hantson, Thijs T. W. van Herpt, Jantine van Holten, F. van der Horst, Aletta P.I. Houwink, Claudine C. Hunault, Malene Hvass Renner Block, Christian Jung, Stavri Karasiali, Mohamed Karghul, Ebru Kaya, Almu’atasim Khamees, Khalid Mahmood Khan Nafees, Justin Koh, Matty Koopmans, Vedran Kovacic, Gabija Laubner Sakalauskienė, Lenneke E. M. van Lelyveld-Haas, Elin Lindqvist, Meritxell Lladó Vilar, Mette Lolk, Beatriz Martín-Pérez, Eva Maria Mateo Rodríguez, Hélène P. Mattijsen, Ayman Meelad, Iris Miltenburg, Ahmed Mohamed Ibrahim Mohamed, Rui Moreno, Marwa Morgom, Mercedes Mucia-Anayaa, Mohamed Nassredin, Binti Haji Abd Rashid Nurhikmahtul Aqilah, Huub L. A. van den Oever, Evelien A. N. Oostdijk, Ozlem Ozkan Kuscu, Catarina Pacheco, Dorte Palmqvist, Despoina Papachristou, David Pérez-Torres, Cristina Petrişor, Michael Piagnerelli, Wouter Pijper, Christian Rabe, Țincu Radu, Megan Ratcliffe, Nanna Reiter, Richard Rezar, Ferran Roche-Campo, Emilio Rodriguez-Ruiz, Harm Roetert, J. Ruiz-Izquierdo, Ana Maria Ruiz Mena, Vusala Rzayeva, Nick van Sabben, Elfayadh Saidahmed, Gustaf Sandström, Kemal Tolga Saracoglu, Clemens Seelmaier, Nicolas Serck, Carlos Serón-Arbeloa, Susanne Stads, Louise Stenbryggen Herløv, Ayca Sultan Sahin, Josefine Thomsen, Radu Țincu, Arzu Topeli, Yen Tran, Bas van den Bogaard, Irma S. van den Hengel-Koot, Klaas Vanderbiest, Liam van Dielen, Abram L. van Duijn, Jolien Van Hecke, Klaus Vennick Marcussen, Marie Vergotten, Wytze Vermeijden, Ester Viktorsdottir, Peter H.J. van der Voort, Evert-Jan Wils, Xavier Wittebole, Esther Wolthuis, David M. Wood, Max Wretman, Hana B. Yahya, Cengizhan Yavuz, Selcuk Yaylaci, Begoña Zalba Etayo, Samanta M. Zwaag.

We would like to thank the European Society of Intensive Care Medicine (ESICM) and the European Association of Poison Centres and Clinical Toxicologists (EAPCCT) for supporting the study, and all the patients who participated in the study.

World Health Organization. Unintentional poisoning deaths: mortality rate from unintentional poisoning (per 100 000 population). 2024. https://data.who.int/indicators/i/84FD3DE. Accessed 5 May 2024.
World Health Organization. Suicide. 2023. https://www.who.int/news-room/fact-sheets/detail/suicide. Accessed 5 May 2024.
Fazel S, Runeson B. Suicide. N Engl J Med. 2020;382:266-74.
Ilic M, Ilic I. Worldwide suicide mortality trends (2000-2019): a joinpoint regression analysis. World J Psychiatry. 2022;12:1044-60.
Hempstead K, Phillips J. Divergence in recent trends in deaths from intentional and unintentional poisoning. Health Aff (Millwood). 2019;38:29-35.
Centers for Disease Control and Prevention (CDC). U.S. Overdose Deaths Decrease in 2023, First Time Since 2018. https://www.cdc.gov/nchs/pressroom/nchs_press_releases/2024/20240515.htm. Accessed 21 June 2024.
European Monitoring Centre for Drugs and Drug Addiction (EMCDDA). European drug report 2023: trends and developments. 2023. https://www.emcdda.europa.eu/publications/european-drug-report/2023_en. Accessed 5 May 2024.
Pierce M, Van Amsterdam J, Kalkman GA, Schellekens A, Van den Brink W. Is Europe facing an opioid crisis like the United States? An analysis of opioid use and related adverse effects in 19 European countries between 2010 and 2018. Eur Psychiatry. 2021;64:e47.
Friedman J, Shover CL. Charting the fourth wave: geographic, temporal, race/ethnicity and demographic trends in polysubstance fentanyl overdose deaths in the United States, 2010-2021. Addiction. 2023;118:2477-85.
European Monitoring Centre for Drugs and Drug Addiction (EMCDDA). Drug-related deaths and mortality in Europe. 2021. https://www.emcdda.europa.eu/publications/meeting-reports-and-conference-proceedings/drug-related-deaths-and-mortality-europe_en. Accessed 2 Jun 2024.
Brent J, Burkhart K, Dargan P, Hatten B, Megarbane B, Palmer R, et al. Critical care toxicology: diagnosis and management of the critically poisoned patient. 2nd ed. Cham: Springer; 2017.
Mowry JB, Spyker DA, Cantilena LR, Jr., McMillan N, Ford M. 2013 Annual report of the American association of poison control centers' national poison data system (NPDS): 31st annual report. Clin Toxicol (Phila). 2014;52:1032-283.
Gummin DD, Mowry JB, Beuhler MC, Spyker DA, Rivers LJ, Feldman R, et al. 2022 Annual report of the national poison data system^® (NPDS) from America's poison centers^®: 40th annual report. Clin Toxicol (Phila). 2023;61:717-939.
Liisanantti JH, Ohtonen P, Kiviniemi O, Laurila JJ, Ala-Kokko TI. Risk factors for prolonged intensive care unit stay and hospital mortality in acute drug-poisoned patients: an evaluation of the physiologic and laboratory parameters on admission. J Crit Care. 2011;26:160-5.
Yu JH, Weng YM, Chen KF, Chen SY, Lin CC. Triage vital signs predict in-hospital mortality among emergency department patients with acute poisoning: a case control study. BMC Health Serv Res. 2012;12:262-9.
Maignan M, Pommier P, Clot S, Saviuc P, Debaty G, Briot R, et al. Deliberate drug poisoning with slight symptoms on admission: are there predictive factors for intensive care unit referral? A three-year retrospective study. Basic Clin Pharmacol Toxicol. 2014;114:281-7.
Vallersnes OM, Jacobsen D, Ekeberg Ø, Brekke M. Outpatient treatment of acute poisoning by substances of abuse: a prospective observational cohort study. Scand J Trauma Resusc Emerg Med. 2016;24:76.
Brandenburg R, Brinkman S, De Keizer NF, Kesecioglu J, Meulenbelt J, De Lange DW. The need for ICU admission in intoxicated patients: a prediction model. Clin Toxicol (Phila). 2017;55:4-11.
Van den Oever HLA, Van Dam M, Van't Riet E, Jansman FGA. Clinical parameters that predict the need for medium or intensive care admission in intentional drug overdose patients: a retrospective cohort study. J Crit Care. 2017;37:156-61.
Lionte C, Sorodoc V, Jaba E, Botezat A. Development and validation of a risk-prediction nomogram for in-hospital mortality in adults poisoned with drugs and nonpharmaceutical agents: an observational study. Medicine (Baltimore). 2017;96:e6404.
Martín-Rodríguez F, López-Izquierdo R, Castro-Villamor MA, Martín-Conty JL, Herrero-Antón RM, Del Pozo-Vegas C, et al. A predictive model for serious adverse events in adults with acute poisoning in prehospital and hospital care. Aust Crit Care. 2021;34:209-16.
Han KS, Kim SJ, Lee EJ, Shin JH, Lee JS, Lee SW. Development and validation of new poisoning mortality score system for patients with acute poisoning at the emergency department. Crit Care. 2021;25:29.
Alizadeh AM, Hassanian-Moghaddam H, Shadnia S, Zamani N, Mehrpour O. Simplified acute physiology score II/acute physiology and chronic health evaluation II and prediction of the mortality and later development of complications in poisoned patients admitted to intensive care unit. Basic Clin Pharmacol Toxicol. 2014;115:297-300.
Jiang M, Wang J, Gu S, Cai N, Liu Y, Zhang Q, et al. Clinical features and prognosis analysis of the elderly and youth patients with acute severe poisoning. Zhonghua Wei Zhong Bing Ji Jiu Yi Xue. 2018;30:790-4.
Reisinger A, Rabensteiner J, Hackl G. Diagnosis of acute intoxications in critically ill patients: focus on biomarkers - part 1: epidemiology, methodology and general overview. Biomarkers. 2020;25:9-19.
Schmoll S, Heier EC, Böll R, Zellner T, Romanek K, Eyer F, et al. Independent validation of the Tanta University Risk Model for intensive care requirement in acutely poisoned adults. Clin Toxicol (Phila). 2023;61:266-9.
Kovacic V, Kvartuc L, Mikacic M, Jerkovic I, Begovic TI, Maras M, et al. Clinical and demographic features with outcome predictors of adult patients with acute intoxication admitted to a medical intensive care unit in the Mediterranean part of Croatia. Toxicol Res (Camb). 2023;12:626-34.
Rezar R, Jung C, Mamandipoor B, Seelmaier C, Felder TK, Lichtenauer M, et al. Management of intoxicated patients - a descriptive outcome analysis of 4,267 ICU patients. BMC Emerg Med. 2022;22:38.
Böll R, Romanek K, Schmoll S, Stich R, Ott A, Stenzel J, et al. Independent validation of the ICU requirement score in a cohort of acutely poisoned adults. Clin Toxicol (Phila). 2018;56:664-6.
Yaylaci S, Genc AB, Demir MV, Cinemre H, Tamer A. Retrospective evaluation of patients at follow-up with acute poisoning in Intensive Care Unit. Niger J Clin Pract. 2016;19:223-6.
McMahon A, Brohan J, Donnelly M, Fitzpatrick GJ. Characteristics of patients admitted to the intensive care unit following self-poisoning and their impact on resource utilisation. Ir J Med Sci. 2014;183:391-5.
Brandenburg R, Brinkman S, De Keizer NF, Meulenbelt J, De Lange DW. In-hospital mortality and long-term survival of patients with acute intoxication admitted to the ICU. Crit Care Med. 2014;42:1471-9.
Clark D, Murray DB, Ray D. Epidemiology and outcomes of patients admitted to critical care after self-poisoning. J Intensive Care Soc. 2011;12:268-73.
Henderson A, Wright M, Pond SM. Experience with 732 acute overdose patients admitted to an intensive care unit over six years. Med J Aust. 1993;158:28-30.
Banderas-Bravo ME, Arias-Verdú MD, Macías-Guarasa I, Aguilar-Alonso E, Castillo-Lorente E, Pérez-Costillas L, et al. Patients admitted to three Spanish intensive care units for poisoning: type of poisoning, mortality, and functioning of prognostic scores commonly used. Biomed Res Int. 2017;2017:5261264.
Athavale V, Green C, Lim KZ, Wong C, Tiruvoipati R. Characteristics and outcomes of patients with drug overdose requiring admission to intensive care unit. Australas Psychiatry. 2017;25:489-93.
Sulaj Z, Prifti E, Demiraj A, Strakosha A. Early clinical outcome of acute poisoning cases treated in intensive care unit. Med Arch. 2015;69:400-4.
Lindqvist E, Edman G, Hollenberg J, Nordberg P, Ösby U, Forsberg S. Intensive care admissions due to poisoning. Acta Anaesthesiol Scand. 2017;61:1296-304.
Lindqvist E, Edman G, Hollenberg J, Nordberg P, Forsberg S. Long-term mortality and cause of death for patients treated in intensive care units due to poisoning. Acta Anaesthesiol Scand. 2019;63:500-5.
El Gharbi F, El Bèze N, Jaffal K, Sutterlin L, Mora P, Malissin I, et al. Does the ICU requirement score allow the poisoned patient to be safely managed without admission to the intensive care unit? A validation cohort study. Clin Toxicol (Phila). 2022;60:298-303.
Riley RD, Van der Windt D, Croft P, Moons KGM. Prognosis research in healthcare. Oxford: Oxford University Press; 2019.
European Association of Poison Centres and Clinical Toxicologists (EAPCCT). https://www.eapcct.org. Accessed 21 June 2024.
European Society of Intensive Care Medicine (ESICM). https://www.esicm.org/. Accessed 21 June 2024.
Castor EDC. Electronic data capture solution. https://www.castoredc.com/electronic-data-capture-system/. Accessed 21 June 2024.
R Core Team. R: a language and environment for statistical computing, R Foundation for Statistical Computing. 2013. http://www.R-project.org/. Accessed 4 Jun 2024.
General Data Protection Regulation (GDPR). What is GDPR, the EU’s new data protection law? 2024. https://gdpr.eu/what-is-gdpr/. Accessed 21 June 2024.
Timmers M, Van Veen EB, Maas AIR, Kompanje EJO. Will the EU data protection regulation 2016/679 inhibit critical care research? Med Law Rev. 2019;27:59-78.
De Lange DW, Guidet B, Andersen FH, Artigas A, Bertolini G, Moreno R, et al. Huge variation in obtaining ethical permission for a non-interventional observational study in Europe. BMC Med Ethics. 2019;20:39.
Flaatten H, Guidet B, Jung C, Boumendil A, Leaver S, Szczeklik W, et al. Consent is a confounding factor in a prospective observational study of critically ill elderly patients. PLoS One. 2022;17:e0276386.

No competing interests reported.

6AdditionalFile.docx

Download PDF

Journal Publication

published 27 Sep, 2024

Read the published version in Critical Care →

Editorial decision: Revision requested
06 Jul, 2024
Reviews received at journal
05 Jul, 2024
Reviews received at journal
04 Jul, 2024
Reviewers agreed at journal
01 Jul, 2024
Reviewers agreed at journal
29 Jun, 2024
Reviewers agreed at journal
29 Jun, 2024
Reviewers invited by journal
28 Jun, 2024
Editor assigned by journal
25 Jun, 2024
Submission checks completed at journal
25 Jun, 2024
First submitted to journal
22 Jun, 2024

You are reading this latest preprint version

The INTOXICATE study: Methodology, experience and preliminary results of a prospective cohort study

Status:

Journal Publication

Version 1

Abstract

Background

Methods

Results

Conclusions

Trial registration

Figures

BACKGROUND

METHODS

Study registration and approval

Recruitment of intensive care units

Patient selection

Consent

Data collection

Data analysis

RESULTS

Ethics and GDPR

Data-sharing agreements

Characteristics of intensive care units

Patient inclusion and patient characteristics

Clinical features and exposure

Primary outcome, treatments and in-hospital mortality

DISCUSSION

COVID-19 pandemic

Countries

Proportion of intoxicated patients admitted to the ICU requiring intensive care

Experience with Castor EDC

CONCLUSIONS

Abbreviations

Declarations

References

Additional Declarations

Supplementary Files

Status:

Journal Publication

Version 1