Publications by authors named "Fridtjof Heyerdahl"

45 Publications

Inhaled nitric oxide as temporary respiratory stabilization in patients with COVID-19 related respiratory failure (INOCOV): Study protocol for a randomized controlled trial.

Authors:
Jostein Skjalg Hagemo Arne Kristian Skulberg Marius Rehn Morten Valberg Maiju Pesonen Hans Julius Heimdal Fridtjof Heyerdahl

PLoS One 2022 27;17(5):e0268822. Epub 2022 May 27.

Faculty of Medicine, Institute of Clinical Medicine, University of Oslo, Oslo, Norway.

Background: In March 2020, WHO announced the COVID-19 a pandemic and a major global public health emergency. Mortality from COVID-19 is rapidly increasing globally, with acute respiratory failure as the predominant cause of death. Many patients experience severe hypoxia and life-threatening respiratory failure often requiring mechanical ventilation. To increase safety margins during emergency anaesthesia and rapid sequence intubation (RSI), patients are preoxygenated with a closed facemask with high-flow oxygen and positive end-expiratory pressure (PEEP). Due to the high shunt fraction of deoxygenated blood through the lungs frequently described in COVID-19 however, these measures may be insufficient to avoid harmful hypoxemia. Preoxygenation with inhaled nitric oxide (iNO) potentially reduces the shunt fraction and may thus allow for the necessary margins of safety during RSI.

Methods And Design: The INOCOV protocol describes a phase II pharmacological trial of inhaled nitric oxide (iNO) as an adjunct to standard of care with medical oxygen in initial airway and ventilation management of patients with known or suspected COVID-19 in acute respiratory failure. The trial is parallel two-arm, randomized, controlled, blinded trial. The primary outcome measure is the change in oxygen saturation (SpO2), and the null hypothesis is that there is no difference in the change in SpO2 following initiation of iNO.

Trial Registration: EudraCT number 2020-001656-18; WHO UTN: U1111-1250-1698. Protocol version: 2.0 (June 25th, 2021).
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0268822PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9140246PMC
May 2022

Clinical effect of ethanol co-use in patients with acute drug toxicity involving the use of central nervous system depressant recreational drugs.

Authors:
Eva-Carina Heier Florian Eyer Christian Rabe Stefanie Geith Paul I Dargan David M Wood Fridtjof Heyerdahl Alison M Dines Isabelle Giraudon Knut Erik Hovda Chris Yates Odd Martin Vallersnes Òscar Miró Matthias E Liechti Tobias Zellner

Eur J Emerg Med 2022 Aug 8;29(4):291-300. Epub 2022 Apr 8.

Division of Clinical Toxicology and Poison Control Centre Munich, Department of Internal Medicine II, TUM School of Medicine, Technical University of Munich, Germany.

Background And Importance: Patients who use recreational drugs frequently co-ingest ethanol, which is considered a central nervous system (CNS) depressant. The clinical relevance of this in acute toxicity involving other CNS depressants is not well described.

Objective: To assess the clinical impact of ethanol co-use in patients presenting to the emergency department (ED) with acute toxicity involving the use of CNS depressant drugs.

Design, Settings And Participants: A retrospective multicentre study using data from the Euro-DEN Plus database from January 2014 to December 2019.

Outcomes Measure And Analysis: Comparison of epidemiologic and clinical characteristics, ED and hospital management of patients with CNS depressant intoxication with or without ethanol co-use.

Main Results: Although 7644 (17.5%) of the 43 633 presentations were included, ethanol was co-ingested in 3811 (49.9%). In total 53.3% required medical treatment, 14 patients died. Patients with ethanol co-use more frequently presented with a Glasgow Coma Scale (GCS) ≤8 (34.1% vs. 22.4%; P   <  0.001), vomiting (8.1% vs. 4.6%; P   <  0.001), anxiety (12 % vs. 6.4%; P   <  0.001), agitation/aggression (22% vs. 14.7%; P   <  0.001), seizures (3.8% vs. 2.4%; P   <  0.001) and hypotension (7.5% vs. 4.6%; P   <  0.001). They more often required ambulance transport (85.5% vs. 76.5%; P   <  0.001), medical treatment (57.3% vs. 48.0%; P   <  0.001), hospitalization (27.7% vs. 18.9%; P   <  0.001), and admission to intensive care (12.2% vs. 4.0%; P   <  0.001). Subgroup analysis showed that GCS ≤8 was particularly common in patients who combined ethanol with opioids or gamma-hydroxybutyrate (GHB)/gamma-butyrolactone (GBL).

Conclusion: Co-use of ethanol with CNS-depressant drugs appears to increase the risk of adverse effects and is associated with a higher need for medical treatment, especially when ethanol is combined with opioids or GHB/GBL.
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http://dx.doi.org/10.1097/MEJ.0000000000000932DOI Listing
August 2022

Differences in clinical features associated with cannabis intoxication in presentations to European emergency departments according to patient age and sex.

Authors:
Yasmin Schmid Miguel Galicia Severin B Vogt Matthias E Liechti Guillermo Burillo-Putze Paul I Dargan Alison M Dines Isabelle Giraudon Fridtjof Heyerdahl Knut Erik Hovda David M Wood Christopher Yates Òscar Miró

Clin Toxicol (Phila) 2022 Apr 11:1-8. Epub 2022 Apr 11.

Emergency Department, Hospital Clínic, IDIBAPS, University of Barcelona, Barcelona, Catalonia, Spain.

Objective: To investigate if clinical features associated with acute cannabis intoxication in patients presenting to Emergency Departments for medical assistance differ according to patient age and sex.

Methods: We analysed presentations in the Euro-DEN Plus dataset from 2014 to 2019 in which cannabis was the only drug involved (except for alcohol), and age, sex and alcohol co-ingestion had been recorded. Age was considered as categorical (five groups; <20, 20-29, 30-39, 40-49 and ≥50 years), and sex as binary variable (male/female). We evaluated 12 key clinical features recorded during emergency department (ED) care. Risks of presenting with each of these clinical features according to patient age and sex were calculated by logistic regression models, and adjusted for sex, age and alcohol co-ingestion.

Results: 4,268 of 43,633 Euro-DEN presentations (9.8%) fulfilled the inclusion criteria (median age: 26 years (IQR = 20-34), 70% male, 52% co-ingested alcohol). The frequency of clinical features was: anxiety 28%, vomiting 24%, agitation 23%, palpitations 14%, reduced consciousness 13%, acute psychosis 9%, hallucinations 9%, chest pain 7%, headache 6%, hypotension 4%, hypertension 3% and seizures 2%. Patients younger than 20 years more frequently had vomiting (34.7% of cases), reduced consciousness (21.5%), and headache (10.8%); and less frequently acute psychosis (5.5%). Patients older than 49 years more often had hypotension (6.5%) and less frequently vomiting (20%), anxiety (14%), agitation (14%) and reduced consciousness (10%). Males more frequently presented with hypertension (3.7 vs. 1.5%; OR = 2.311, 95%CI = 1.299-3.816), psychosis (10.4 vs 6.3%; 1.948, 1.432-2.430), chest pain (8.1 vs 4.5%; 1.838, 1.390-2.430) and seizures (2.5 vs 1.4%; 1.805, 1.065-3.060), and less frequently with vomiting (21.8 vs 28.2%; 0.793, 0.677-0.930), anxiety (25.4 vs 32.3%; 0.655, 0.561-0.766) and hypotension (2.9 vs 5.8%; 0.485, 0.350-0.671).

Conclusions: The prevalence of some clinical features typically associated with acute cannabis intoxication differed according to age and sex. The causes for these differences should be further investigated in order to better understand the pathophysiology of cannabis-related acute toxicity, and they may be relevant particularly for developing prevention campaigns and for treatment in specific sex and/or age groups.
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http://dx.doi.org/10.1080/15563650.2022.2060116DOI Listing
April 2022

Comparison of intranasal and intramuscular naloxone in opioid overdoses managed by ambulance staff: a double-dummy, randomised, controlled trial.

Authors:
Arne Kristian Skulberg Ida Tylleskär Morten Valberg Anne-Cathrine Braarud Jostein Dale Fridtjof Heyerdahl Tore Skålhegg Jan Barstein Sindre Mellesmo Ola Dale

Addiction 2022 Jun 8;117(6):1658-1667. Epub 2022 Feb 8.

Department of Circulation and Medical Imaging, Norwegian University of Science and Technology, Trondheim, Norway.

Aims: To measure and evaluate clinical response to nasal naloxone in opioid overdoses in the pre-hospital environment.

Design: Randomised, controlled, double-dummy, blinded, non-inferiority trial, and conducted at two centres.

Setting: Participants were included by ambulance staff in Oslo and Trondheim, Norway, and treated at the place where the overdose occurred.

Participants: Men and women age above 18 years with miosis, rate of respiration ≤8/min, and Glasgow Coma Score <12/15 were included. Informed consent was obtained through a deferred-consent procedure.

Intervention And Comparator: A commercially available 1.4 mg/0.1 mL intranasal naloxone was compared with 0.8 mg/2 mL naloxone administered intramuscularly.

Measurements: The primary end-point was restoration of spontaneous respiration of ≥10 breaths/min within 10 minutes. Secondary outcomes included time to restoration of spontaneous respiration, recurrence of overdose within 12 hours and adverse events.

Findings: In total, 201 participants were analysed in the per-protocol population. Heroin was suspected in 196 cases. With 82% of the participants being men, 105 (97.2%) in the intramuscular group and 74 (79.6%) in the intranasal group returned to adequate spontaneous respiration within 10 minutes after one dose. The estimated risk difference was 17.5% (95% CI, 8.9%-26.1%) in favour of the intramuscular group. The risk of receiving additional naloxone was 19.4% (95% CI, 9.0%-29.7%) higher in the intranasal group. Adverse reactions were evenly distributed, except for drug withdrawal reactions, where the estimated risk difference was 6.8% (95% CI, 0.2%-13%) in favour of the intranasal group in a post hoc analysis.

Conclusion: Intranasal naloxone (1.4 mg/0.1 mL) was less efficient than 0.8 mg intramuscular naloxone for return to spontaneous breathing within 10 minutes in overdose patients in the pre-hospital environment when compared head-to-head. Intranasal naloxone at 1.4 mg/0.1 mL restored breathing in 80% of participants after one dose and had few mild adverse reactions.
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http://dx.doi.org/10.1111/add.15806DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9302677PMC
June 2022

Validation of the Decontamination of a Specialist Transport System for Patients with High Consequence Infectious Diseases.

Authors:
Claire Bailey Catherine Makison-Booth Jayne Farrant Alan Beswick John Chewins Michael Eimstad Fridtjof Heyerdahl Brian Crook

Microorganisms 2021 Dec 13;9(12). Epub 2021 Dec 13.

Health and Safety Executive Science Research Centre, Buxton SK17 9JN, UK.

When transferring highly infective patients to specialist hospitals, safe systems of work minimise the risk to healthcare staff. The EpiShuttle is a patient transport system that was developed to fit into an air ambulance. A validated decontamination procedure is required before the system can be adopted in the UK. Hydrogen peroxide (HO) vapour fumigation may offer better penetration of the inaccessible parts than the liquid disinfectant wiping that is currently suggested. To validate this, an EpiShuttle was fumigated in a sealed test chamber. Commercial bacterial spore indicators (BIs), alongside organic liquid suspensions and dried surface samples of MS2 bacteriophage (a safe virus surrogate), were placed in and around the EpiShuttle, for the purpose of evaluation. The complete kill of all of the BIs in the five test runs demonstrated the efficacy of the fumigation cycle. The log reduction of the MS2 that was dried on the coupons ranged from 2.66 to 4.50, but the log reduction of the MS2 that was in the organic liquids only ranged from 0.07 to 1.90, confirming the results of previous work. Fumigation with HO alone may offer insufficient inactivation of viruses in liquid droplets, therefore a combination of fumigation and disinfectant surface wiping was proposed. Initial fumigation reducing contamination with minimal intervention allows disinfectant wipe cleaning to be completed more safely, with a second fumigation step inactivating the residual pathogens.
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http://dx.doi.org/10.3390/microorganisms9122575DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8705707PMC
December 2021

Interhospital transport of critically ill patients: A prospective observational study of patient and transport characteristics.

Authors:
Helge Eiding Ulf E Kongsgaard Theresa M Olasveengen Fridtjof Heyerdahl

Acta Anaesthesiol Scand 2022 Feb 2;66(2):248-255. Epub 2021 Dec 2.

Department of Research and Development, Norwegian Air Ambulance Foundation, Oslo, Norway.

Background: The cohort of critically ill patients transported between Intensive Care Units (ICUs) in Norway has not been studied previously. The aim of this study was to describe the characteristics of patients and transports for different types of interhospital transfers and explore whether there were differences in morbidity and mortality between the different transfer categories and the general Norwegian ICU population.

Methods: All transports of critically ill adult patients transferred between two geographically different Intensive Care Units during a one-year period were registered. Patient and transport data were obtained from The Norwegian Intensive Care Registry, The Norwegian Cause of Death Registry, the hospital Electronic Patient Journal, the Air Ambulance Journal System, and the Emergency Medical Communication Centre database.

Results: 821 transports of 788 surgical and medical patients were enrolled. Simplified Acute Physiology Scores (SAPSII) were 43, 36 and 38 for urgent secondary transport, non-urgent secondary transport and return transfers, respectively. These were comparable to nationwide SAPSII scores that were 40 for university hospitals and 34 for local hospitals during the same time period. The return transfers had a median SOFA-score of 4.7 and 53% were mechanically ventilated. Only 33% of return transfers were performed by established teams.

Conclusion: Intensive care patients transferred between ICUs are as critically ill as the rest of the ICU population, with a similar morbidity and mortality. The return transfers of ICU-patients appear under-triaged compared to secondary transports in terms of allocated resources.
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http://dx.doi.org/10.1111/aas.14005DOI Listing
February 2022

Variation of drugs involved in acute drug toxicity presentations based on age and sex: an epidemiological approach based on European emergency departments.

Authors:
Òscar Miró William S Waring Paul I Dargan David M Wood Alison M Dines Christopher Yates Isabelle Giraudon Adrian Moughty Niall O'Connor Fridtjof Heyerdahl Knut E Hovda Odd M Vallersnes Raido Paasma Kristiina Pold Gesche Jürgens Bruno Megarbane Jacek S Anand Evangelia Liakoni Matthias Liechti Florian Eyer Sergej Zacharov Blazena Caganova Jeffrey Bonnici Julia Radenkova-Saeva Miguel Galicia

Clin Toxicol (Phila) 2021 Oct 16;59(10):896-904. Epub 2021 Mar 16.

Emergency Department, Hospital Clínic, IDIBAPS, Barcelona, Spain.

Objective: To analyse the relative percentage of acute recreational drug toxicity emergency department (ED) presentations involving the main drug groups according to age and sex and investigate different patterns based on sex and age strata.

Methods: We analysed all patients with acute recreational drug toxicity included by the Euro-DEN Plus dataset (22 EDs in 14 European countries) between October 2013 and December 2016 (39 months). Drugs were grouped as: opioids, cocaine, cannabis, amphetamines, gamma-hydroxybutyrate (GHB), hallucinogens, new psychoactive substances (NPS), benzodiazepines and ketamine. Descriptive data by age and sex are presented and compared among age/sex categories and among drug families.

Results: Of 17,371 patients were included during the 39-month period, 17,198 (99.0%) had taken at least one of the investigated drugs (median age: 31 years; 23.9% female; ethanol co-ingestion recorded in 41.5%, unknown in 31.2%; multiple drug use in 37.9%). Opioids (in 31.4% of patients) and amphetamines (23.3%) were the most frequently involved and hallucinogens (1.9%) and ketamine (1.7%) the least. Overall, female patients were younger than males, both in the whole cohort (median age 29 vs. 32 years;  < 0.001) and in all drug groups except benzodiazepines (median age 36 vs. 36 years;  = 0.83). The relative proportion of each drug group was different at every age strata and some patterns could be clearly described: cannabis, NPS and hallucinogens were the most common in patients <20 years; amphetamines, ketamine and cocaine in the 20- to 39-year group; GHB/GBL in the 30- to 39-year group; and opioids and benzodiazepines in patients ≥40 years. Ethanol and other drug co-ingestion was more frequent at middle-ages, and multidrug co-ingestion was more common in females than males.

Conclusion: Differences in the drugs involved in acute drug toxicity presentations according to age and sex may be relevant for developing drug-prevention and education programs for some particular subgroups of the population based on the increased risk of adverse events in specific sex and/or age strata.
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http://dx.doi.org/10.1080/15563650.2021.1884693DOI Listing
October 2021

Rhabdomyolysis related to acute recreational drug toxicity-A Euro-DEN study.

Authors:
Wojciech Waldman Piotr M Kabata Alison M Dines David M Wood Christopher Yates Fridtjof Heyerdahl Knut Erik Hovda Isabelle Giraudon Paul I Dargan Jacek Sein Anand

PLoS One 2021 11;16(3):e0246297. Epub 2021 Mar 11.

Department of Clinical Toxicology, Medical University of Gdansk, Gdansk, Poland.

Background: This study was conducted to retrospectively assess the relationships between: rhabdomyolysis (quantified by creatine kinase (CK) activity) and kidney injury (quantified by serum creatinine concentration), sex, age, body temperature on admission, presence of seizures, and agitation or aggression in patients presenting to the Emergency Department with acute recreational drug toxicity. We also investigated the association with the substances ingested.

Methods: All presentations to the 16 sentinel Euro-DEN centres in 10 European countries with acute recreational drug toxicity during the first year of the Euro-DEN study (October 2013 to September 2014) were considered. Cases that had abnormal CK activity recorded as part of routine clinical care were divided into 3 cohorts depending on peak CK activity. Cases with normal CK activity were included as a control group (4th cohort).

Results: Only 1,015 (18.4%) of the 5,529 Euro-DEN presentations had CK activity concentration recorded. Of this group 353 (34.8%) had also creatinine concentration measured. There were 375 (36.9%) with minor rhabdomyolysis, 69 (6.8%) with moderate rhabdomyolysis, and 24 (2.4%) with severe rhabdomyolysis; 547 (53.9%) were included in the control group. There was a positive correlation between CK activity and creatinine concentration (correlation coefficient r = 0.71, p<0.0001). There was no correlation between CK activity and body temperature at the time of presentation to the ED (correlation coefficient r = 0.07, p = 0.03). There was a positive correlation between CK activity and length of stay in the hospital (r = 0.31, p<0.001). There was no association between CK activity and the presence of seizures (p = 0.33) or agitation/aggression (p = 0.45), patients age (p = 0.4) or sex (p = 0.25). The 5 most common agents amongst patients presenting with rhabdomyolysis were: cocaine (n = 107; 22.9% presentations), amphetamine (76; 16.2%), cannabis (74; 15.8%), GHB/GBL (72; 15.4%) and heroin (67; 14.3%). The distribution of rhabdomyolysis in 5 most common drugs was (drug; patients with rhabdomyolysis, patients without rhabdomyolysis): cocaine (107, 122), cannabis (74, 117), GHB/GBL (72, 81), amphetamine (76, 66), heroin (67, 70).

Conclusions: Abnormal values of CK activity occurred in almost half (46.1%) of presentations to the Emergency Department with acute recreational drug toxicity in whom CK activity was measured; however, severe rhabdomyolysis is seen in only a small minority (2.4%). Those with rhabdomyolysis are at significantly higher risk of kidney injury and have a longer length of hospital stay.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0246297PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7951866PMC
August 2021

Impact of pregabalin co-use in patients presenting with acute heroin toxicity to the European Drug Emergencies Network Plus project.

Authors:
Craig Leaper Alison M Dines Paul I Dargan Chris Yates Knut Erik Hovda Fridtjof Heyerdahl Isabelle Giraudon David M Wood

Eur J Emerg Med 2021 04;28(2):144-146

Clinical Toxicology, Guy's and St Thomas' NHS Foundation Trust and King's Health Partners.

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http://dx.doi.org/10.1097/MEJ.0000000000000738DOI Listing
April 2021

NTNU intranasal naloxone trial (NINA-1) study protocol for a double-blind, double-dummy, non-inferiority randomised controlled trial comparing intranasal 1.4 mg to intramuscular 0.8 mg naloxone for prehospital use.

Authors:
Arne Kristian Skulberg Ida Tylleskär Anne-Cathrine Braarud Jostein Dale Fridtjof Heyerdahl Sindre Mellesmo Morten Valberg Ola Dale

BMJ Open 2020 11 12;10(11):e041556. Epub 2020 Nov 12.

Department of Circulation and Medical Imaging, Norwegian University of Science and Technology, Trondheim, Norway.

Introduction: Intranasal (IN) naloxone is widely used to treat opioid overdoses. The advantage of nasal administration compared with injection lies in its suitability for administration by lay people as it is needless. Approved formulations of nasal naloxone with bioavailability of approximately 50% have only undergone trials in healthy volunteers, while off-label nasal sprays with low bioavailability have been studied in patients. Randomised clinical trials are needed to investigate efficacy and safety of approved IN naloxone in patients suffering overdose. This study investigates whether the administration of 1.4 mg naloxone in 0.1 mL per dose is non-inferior to 0.8 mg intramuscular injection in patients treated for opioid overdose.

Methods And Analysis: Sponsor is the Norwegian University of Science and Technology. The study has been developed in collaboration with user representatives. The primary endpoint is the restoration of spontaneous respiration≥10 breaths/min based on a sample of 200 opioid overdose cases. Double-dummy design ensures blinding, which will be maintained until the database is locked.

Ethics And Dissemination: The study was approved by the Norwegian Medicines Agency and Regional Ethics Committees (REC: 2016/2000). It adheres to the Good Clinical Practice guidelines as set out by the International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use.Informed consent will be sought through a differentiated model. This allows for deferred consent after inclusion for patients who have regained the ability to consent. Patients who are unable to consent prior to discharge by emergency services are given written information and can withdraw at a later date in line with user recommendations. Metadata will be published in the Norwegian University of Science and Technology Open repository. Deidentified individual participant data will be made available to recipients conditional of data processor agreement being entered.

Trial Registration Numbers: EudraCT Registry (2016-004072-22) and Clinicaltrials.gov Registry (NCT03518021).
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http://dx.doi.org/10.1136/bmjopen-2020-041556DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7662429PMC
November 2020

Prehospital naloxone administration - what influences choice of dose and route of administration?

Authors:
Ida Tylleskar Linn Gjersing Lars Petter Bjørnsen Anne-Cathrine Braarud Fridtjof Heyerdahl Ola Dale Arne Kristian Skulberg

BMC Emerg Med 2020 09 5;20(1):71. Epub 2020 Sep 5.

Department of Circulation and Medical Imaging, Norwegian University of Science and Technology, NTNU, Trondheim, Norway.

Background: Amidst the ongoing opioid crisis there are debates regarding the optimal route of administration and dosages of naloxone. This applies both for lay people administration and emergency medical services, and in the development of new naloxone products. We examined the characteristics of naloxone administration, including predictors of dosages and multiple doses during patient treatment by emergency medical service staff in order to enlighten this debate.

Methods: This was a prospective observational study of patients administered naloxone by the Oslo City Center emergency medical service, Norway (2014-2018). Cases were linked to The National Cause of Death Registry. We investigated the route of administration and dosage of naloxone, clinical and demographic variables relating to initial naloxone dose and use of multiple naloxone doses and one-week mortality.

Results: Overall, 2215 cases were included, and the majority (91.9%) were administered intramuscular naloxone. Initial doses were 0.4 or 0.8 mg, and 15% of patients received multiple dosages. Unconscious patients or those in respiratory arrest were more likely to be treated with 0.8 mg naloxone and to receive multiple doses. The one-week mortality from drug-related deaths was 4.1 per 1000 episodes, with no deaths due to rebound opioid toxicity.

Conclusions: Intramuscular naloxone doses of 0.4 and 0.8 mg were effective and safe in the treatment of opioid overdose in the prehospital setting. Emergency medical staff appear to titrate naloxone based on clinical presentation.
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http://dx.doi.org/10.1186/s12873-020-00366-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7487505PMC
September 2020

MDMA-related presentations to the emergency departments of the European Drug Emergencies Network plus (Euro-DEN Plus) over the four-year period 2014-2017.

Authors:
Roberta Noseda Yasmin Schmid Irene Scholz Evangelia Liakoni Matthias E Liechti Paul I Dargan David M Wood Alison M Dines Christopher Yates Fridtjof Heyerdahl Knut E Hovda Isabelle Giraudon Alessandro Ceschi

Clin Toxicol (Phila) 2021 Feb 17;59(2):131-137. Epub 2020 Jul 17.

Division of Clinical Pharmacology and Toxicology, Institute of Pharmacological Sciences of Southern Switzerland, Ente Ospedaliero Cantonale, Lugano, Switzerland.

Context: 3,4-Methylenedioxymethamphetamine (MDMA) remains one of the most commonly used recreational drugs in Europe. Monitoring of Emergency Department (ED) presentations with acute toxicity associated with MDMA is important to determine trends in MDMA use and harms.

Methods: Data were extracted from the European Drug Emergencies Network (Euro-DEN) Plus database for all ED presentations with acute toxicity involving MDMA use, alone or in combination with other substances, between 1 January 2014 and 31 December 2017. Geographical distribution, time trends, patient demographics, clinical features, management and outcome were analysed.

Results: Out of 23,947 presentations, 2013 (8.4%) involved MDMA, used alone (88, 4.4%) or with other substances (1925, 95.6%). The proportion of MDMA presentations varied by country, from over 15% in France to less than 5% in Norway. For the 15 sentinel centres where data were available for all four years, MDMA-related presentations peaked in 2016 (10.4% 8.1% in 2015,  < 0.0001), thereafter decreasing in 2017 (8.2%,  = 0.0002). 1436 (71.3%) presentations involved males. Females were significantly younger than males (median 23 years, interquartile range, IQR, 20-27 years, median 25 years, IQR 21-30 years,  < 0.0001). Compared to presentations of acute toxicity with lone-use cocaine, presentations with lone-use MDMA occurred more frequently during the weekend (58.0% 43.9%,  = 0.02), were more frequently medically discharged directly from the ED (74.7% 62.4%,  = 0.03), and less frequently received sedation (43.5% 66.5%,  = 0.003).

Conclusions: This large multicentre series of MDMA presentations to EDs showed geographical variation and changes in time trends and in patient demographics. Triangulation with data from complementary sources including seizures, prevalence of use and wastewater analysis, will enable a greater understanding of the public health implications of MDMA use in Europe.
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http://dx.doi.org/10.1080/15563650.2020.1784914DOI Listing
February 2021

Acute toxicity related to misuse (nonmedical use) of tramadol: Experience of the European Drug Emergencies Network Plus.

Authors:
Kerry A Layne Paul I Dargan Alison M Dines Craig Leaper Christopher Yates Knut Erik Hovda Fridtjof Heyerdahl John R H Archer Isabelle Giraudon David M Wood

Br J Clin Pharmacol 2021 04 15;87(4):1668-1675. Epub 2020 Jul 15.

Clinical Toxicology, Guy's and St Thomas' NHS Foundation Trust and King's Health Partners, London, UK.

Following the development of the tramadol crisis currently affecting countries in the Middle East, and Africa, there has been increasing international interest in the regulation of tramadol. This study investigates the misuse of tramadol in patients presenting to emergency departments across Europe. Data from 32 emergency departments in 21 countries were extracted from the Euro-DEN Plus database for the 4-year period from 1 January 2014 to 31 December 2017. Of the reported 24,957 emergency department presentations, tramadol misuse was reported in 105 (0.4% presentations). Tramadol misuse was most common in Bratislava (Slovakia; n = 11, 7.5% of all presentations to this centre), Riga (Latvia; n = 4, 4.9%) and Munich (Germany; n = 17, 2.9%). On arrival, 14 (13.3%) of presentations were in coma/Glasgow coma score ≤ 8 and 9 of these had a respiratory rate <12 breaths/min. These presentations potentially pose a significant burden on emergency departments with a large proportion requiring admission to hospital for ongoing care.
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http://dx.doi.org/10.1111/bcp.14408DOI Listing
April 2021

Substance abuse-related admissions in a mixed Norwegian intensive care population.

Authors:
Karen Hunting Tollisen Marianne Bjerva Cathrine Lund Hadley Gry T Dahl Lisa Maria Högvall Leiv Sandvik Fridtjof Heyerdahl Dag Jacobsen

Acta Anaesthesiol Scand 2020 03 29;64(3):329-337. Epub 2019 Nov 29.

Faculty of Medicine, Institute of Clinical Medicine, University of Oslo, Oslo, Norway.

Background: Alcohol and drug abuse are potentially modifiable risk factors for critical illness. The aims of this study were to describe patients with substance abuse-related admissions (abbreviated SARA) in a mixed intensive care (ICU) population in Oslo, and to compare these patients with patients with non-SARA.

Methods: Cross-sectional prospective study of a mixed medical and surgical ICU-population in Oslo, Norway. Data were collected consecutively using a questionnaire, medical records, and toxicology results. SARA included admissions due to acute or chronic complications of alcohol or drug abuse, as well as substance abuse-related injuries.

Results: Of the 852 patients included, 168 (20%) had SARA; 102 (12%) alcohol-related and 66 (8%) drug-related. Male patients aged 18-39 had the highest proportion of SARA (47/97, 49%). Among the trauma patients, 69/182 (38%) were influenced by alcohol and drugs at the time of injury. Patients with SARA were significantly younger (median age 48 vs 66), had lower Charlson comorbidity index (mean 1.4 vs 2.5) and shorter length of stay (median days 2.4 vs 4.9), than non-SARA patients. Hospital mortality was similar when adjusting for age (OR 0.8, P = .27, non-SARA as reference).

Conclusion: Overall, one in five ICU admissions was associated with substance abuse. For male patients aged 18-39 this ratio was nearly half. More than one third of the trauma patients were influenced by alcohol or drugs at time of injury.
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http://dx.doi.org/10.1111/aas.13506DOI Listing
March 2020

Clinical relevance of ethanol coingestion in patients with GHB/GBL intoxication.

Authors:
Miguel Galicia Paul I Dargan Alison M Dines Christopher Yates Fridtjof Heyerdahl Knut Erik Hovda Isabella Giraudon David M Wood Òscar Miró

Toxicol Lett 2019 Oct 10;314:37-42. Epub 2019 Jul 10.

Emergency Department, Hospital Clínic, Barcelona, IDIBAPS, Barcelona, Spain; Medical School, University of Barcelona, Spain.

Objective: Ethanol intake can increase the sedative effects of gamma-hydroxybutyrate/gamma-butyrolactone (GHB/GBL), although the real clinical impact is unknown. We studied the clinical impact of the co-ingestion of ethanol in patients presenting to the Emergency Department (ED) with acute toxicity related to GHB/GBL use.

Method: We performed a secondary analysis of the Euro-DEN Plus Registry (14 countries, 22 EDs) which includes 17,371 consecutive patients presenting to the ED with acute recreational drug toxicity over 39 consecutive months (October 2013 - December 2016). We compared the epidemiological and clinical characteristics and ED management of patients identified as presenting with acute toxicity related to lone GHB/GBL (Group A) or GHB/GBL combined with ethanol (Group B) without other concomitant drugs.

Results: A total of 609 patients were included (age 32 (8) years; 116 women (19%); Group A: 183 patients and Group B: 426). The most common features were reduction in consciousness (defined as Glasgow Coma Score <13 points: 56.1%) and agitation/aggressiveness (33.6%). Those with ethanol co-ingestion were younger patients (Group A/B: 31.5/33.1 years, p = 0.029) and ethanol co-ingestion was associated with a lower frequency of bradycardia (23.5%/15.7%, p = 0.027) and more frequent arrival at the ED by ambulance (68.3/86.6%; p < 0.001), reduction in consciousness (58.9%/49.1%; p = 0.031), need for treatment in the ED (49.2%/60.4%; p = 0.011), use of sedatives (20.1%/12.8%; p = 0.034), admission to critical care units (22.4%/55.3%; p < 0.001), and longer hospital stay (stay longer than 6 h: 16.9%/28.4%; p = 0.003).

Conclusions: Co-ingestion of ethanol increases the adverse effects of patients intoxicated by GHB/GBL, leading to greater depression of consciousness, need for treatment, admission to the ICU and longer hospital stay.
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http://dx.doi.org/10.1016/j.toxlet.2019.07.001DOI Listing
October 2019

Gender differences in acute recreational drug toxicity: a case series from Oslo, Norway.

Authors:
Victoria Lykke Syse Mette Brekke Marit Mæhle Grimsrud Per Sverre Persett Fridtjof Heyerdahl Knut Erik Hovda Odd Martin Vallersnes

BMC Emerg Med 2019 04 29;19(1):29. Epub 2019 Apr 29.

Oslo Accident and Emergency Outpatient Clinic, Department of Emergency General Practice, City of Oslo Health Agency, Oslo, Norway.

Background: Female drug users report poorer physical and mental health than male drug users. We describe female and male patients treated for acute recreational drug toxicity, and look for gender differences in clinical state, treatment, and toxic agents taken.

Methods: Retrospective case series from a primary care emergency outpatient clinic and a hospital emergency department in Oslo, Norway. All patients treated for acute recreational drug toxicity from October 2013 through March 2015 were included, except patients with lone alcohol intoxication. Patients were grouped according to whether they had taken opioids or not, as a proxy differentiation between heavy drug users and party drug users. Data from the two clinical settings were analysed separately.

Results: In total, 2495 cases were included, 567 (22.7%) were women. Female patients were younger than males, median 31 vs 34 years (p < 0.001). On most comparisons of clinical variables there were no significant differences between genders. A larger proportion of females in the outpatient opioid group were hypotensive, 10.9% vs 3.9% (p < 0.001). Fewer females were intubated, none vs 21.1% (p = 0.019) in the hospital opioid group, and 6.4% vs 21.0% (p = 0.039) in the hospital non-opioid group. The proportion of gamma-hydroxybutyrate (GHB) poisoning was larger among females both at the outpatient clinic (14.4% vs 8.6%, p < 0.001) and at the hospital (60.3% vs 36.4%, p = 0.001), while the proportion of heroin poisoning was smaller among females at the outpatient clinic (37.1% vs 47.0%, p < 0.001).

Conclusion: One in four patients treated for acute recreational drug toxicity were women. Female patients were younger, had more frequently taken GHB and were less frequently intubated. Otherwise, the gender differences regarding clinical state and treatment were small. Although female drug users are known to report poorer health than males, we did not find that women had a more severe clinical course than men when presenting with overdose.
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http://dx.doi.org/10.1186/s12873-019-0244-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6489220PMC
April 2019

Seizures as a complication of recreational drug use: Analysis of the Euro-DEN Plus data-set.

Authors:
Caitlin E Wolfe David M Wood Alison Dines Benjamin P Whatley Christopher Yates Fridtjof Heyerdahl Knut Erik Hovda Isabelle Giraudon Paul I Dargan

Neurotoxicology 2019 07 8;73:183-187. Epub 2019 Apr 8.

Clinical Toxicology, Guy's and St Thomas' NHS Foundation Trust and King's Health Partners, London, UK; Clinical Toxicology, Faculty of Life Sciences and Medicine, King's College London, London, UK.

Seizures are a recognized and potentially serious complication of recreational drug use. This study examined a large international data set of presentations to Emergency Departments with acute recreational drug toxicity, the European Drug Emergencies Plus (Euro-DEN Plus) Network, to compare presentations with and without seizures and estimate incidence and associated drugs. Amongst 23,947 presentations between January 2014 and December 2017, there were 1013 (4.2%) with reported seizures. Clinical and demographic features were similar between individuals who had a seizure and those who did not, although rates of coma, cardiac arrest, intubation, intensive care admission, and death were significantly higher in those with seizures. There was a significant association between specific drugs and a higher seizure incidence, including fentanyl (odds ratio 2.63, 95% confidence interval 1.20-5.80), and synthetic cannabinoids (OR 2.90, 95% CI 2.19-3.84). Other drugs were associated with a lower seizure incidence, including heroin (OR 0.46, 95% CI 0.35-0.61), clonazepam (OR 0.22, 95% CI 0.06-0.91), and cannabis (OR 0.65, 95% CI 0.50-0.86). This substantiates observations that the synthetic cannabinoids as a group of novel psychoactive substances are clinically different in consequence of intoxication than cannabis, and that individuals who suffer a seizure in the context of recreational drug intoxication are likely to have worse outcomes overall. Utilising this information of what substances have a greater risk of seizures, could provide tailored harm reduction and education strategies to users to reduce the risk of seizures and their associated complications.
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http://dx.doi.org/10.1016/j.neuro.2019.04.003DOI Listing
July 2019

Epidemiology, clinical features and management of patients presenting to European emergency departments with acute cocaine toxicity: comparison between powder cocaine and crack cocaine cases.

Authors:
Òscar Miró Paul I Dargan David M Wood Alison M Dines Christopher Yates Fridtjof Heyerdahl Knut Erik Hovda Isabelle Giraudon Miguel Galicia

Clin Toxicol (Phila) 2019 Aug 30;57(8):718-726. Epub 2019 Jan 30.

Emergency Department , Hospital Clínic, Barcelona; IDIBAPS , Barcelona , Spain.

: To analyse the epidemiology, clinical picture and emergency department (ED) management of a large series of patients who presented to European EDs after cocaine consumption, comparing data from powder (C group) and crack (C group) consumers. : Between October 2013 and December 2016, the Euro-DEN Plus Registry recorded 17,371 consecutive acute recreational drug toxicity presentations to 22 EDs in 14 European countries. Epidemiological and demographic data, co-ingestion of alcohol and other drugs, clinical features, ED management and outcome (death) were analysed for cocaine cases, and comparison of clinical picture in C and C patients were performed adjusting for alcohol and other drug co-ingestion. : We included 3002 cases (C: 2600; C: 376; mixed consumption: 26): mean age 32(9) years, 23% female. The proportion of presentations involving cocaine varied significantly between countries (>30% in Malta, Spain, France, Denmark) and only centres in France, United Kingdom, Poland, Ireland and Malta recorded crack-related cases. Cocaine was frequently used with ethanol (74.3%, C>C) and other drugs (56.8%, C>C), the most frequent amphetamine (19.4%, C>C) and opioids (18.9%, C>C). C patients were more likely to have clinically significant episodes of hypotension (adjusted OR = 2.35; 95%CI = 1.42-3.89), and bradypnea (1.81; 1.03-3.16) and systolic blood pressure >180 mmHg on ED arrival (2.59; 1.28-5.25); while less likely anxiety (0.51; 0.38-0.70), chest pain (0.47; 0.31-0.70), palpitations (0.57; 0.38-0.84), vomiting (0.54; 0.32-0.90), and tachycardia on ED arrival (0.52; 0.39-0.67). Sedative drugs were given in 29.3%. The median length of hospital stay was 4:02 h, 22.1% patients were hospitalized, and 0.4% ( = 12) died. : Cocaine is commonly involved in European ED presentations with acute recreational drug toxicity, but there is variation across Europe not just in the involvement of cocaine but in the proportion related to powder versus crack. Some differences in clinical picture and ED management exist between powder cocaine and crack consumers.
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http://dx.doi.org/10.1080/15563650.2018.1549735DOI Listing
August 2019

Emergencies related to recreational drug abuse in Spain compared to emergencies attended in 3 European areas.

Authors:
Òscar Miró Christopher Yates Alison M Dines David M Wood Paul I Dargan Itxaso Galán Alba Jerez Jordi Puiguriguer W Stephen Waring Adrian Moughty Niall O'Connor Fridtjof Heyerdahl Knut E Hovda Odd M Vallersnes Raido Paasma Kristiina Põld Gesche Jürgens Bruno Megarbane Jacek S Anand Evangelia Liakoni Matthias Liechti Florian Eyer Sergej Zacharov Blazena Caganova Isabelle Giraudon Miguel Galicia

Emergencias 2018 Dic;30(6):385-394

Área de Urgencias, Hospital Clínic, Barcelona; Grupo de Investigación "Urgencias: Procesos y Patologías", IDIBAPS, Barcelona, España.

Objectives: To analyze epidemiologic, clinical, and care characteristics in cases in which patients came to 2 Spanish emergency departments (EDs) with symptoms caused by recreational drug abuse. To compare the characteristics with those reported for other areas of Europe.

Material And Methods: Secondary analysis of the registry of the European Drug Emergencies Network (Euro-DEN Plus), which collects cases in 14 European countries and 20 EDs. The registry included all patients attending EDs with symptoms of recreational drug abuse (excepting cases involving alcohol alone) over a period of 39 consecutive months (October 2013 to December 2016). We compared the cases from the 2 Spanish EDs (in Barcelona and Palma de Mallorca) to those from the 5 EDs in Ireland and the UK, 6 in northern Europe, and 7 in central Europe.

Results: A total of 17 104 patients' cases were included: Spain, 1186; UK and Ireland, 6653; northern Europe, 6097; and central Europe, 3168. Spain saw more emergencies related to cocaine (48.4%) and fewer related to opioids (12.4%) than the other areas. The Spanish patients were younger (32.2 years) on average than those in northern Europe and older than those in the UK and Ireland and central Europe. Fewer patients were women in Spain (21.9%) than in northern or central Europe. Fewer arrived in ambulances in Spain (70.0%) than in the UK and Ireland or northern Europe. The Spanish EDs recorded the temperature and respiratory frequency of fewer patients (29.8% and 30.3%, respectively). Clinical signs differed between geographical areas attributable to differences in drug-use patterns. In Spain, naloxone was used by fewer patients (9.6%) than in the UK and Ireland and northern Europe, and flumazenil was used by more patients (5.6%) than in other areas. Spain saw lower percentages of admissions (4.6%) and patients who left without an ED discharge (6.2%) in comparison with other areas. Mortality rates in the Spanish EDs (0.4%) and after discharge from them (0.7%) were higher than in northern Europe.

Conclusion: The characteristics of emergencies related to recreational drug abuse registered by the Spanish EDs were differed from those registered in other parts of Europe due to different patterns of drug use. We also detected differences between the Spanish and other European EDs with respect to examinations or tests performed, treatment given, and discharge disposition.
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July 2019

Ambulance-attended opioid overdoses: An examination into overdose locations and the role of a safe injection facility.

Authors:
Desiree Madah-Amiri Arne Kristian Skulberg Anne-Cathrine Braarud Ola Dale Fridtjof Heyerdahl Philipp Lobmaier Thomas Clausen

Subst Abus 2019 10;40(3):383-388. Epub 2018 Oct 10.

The Norwegian Centre for Addiction Research, The University of Oslo, Oslo, Norway.

: Although the United States and numerous other countries are amidst an opioid overdose crisis, access to safe injection facilities remains limited. We used prospective data from ambulance journals in Oslo, Norway, to describe the patterns, severity, and outcomes of opioid overdoses and compared these characteristics among various overdose locations. We also examined what role a safe injection facility may have had on these overdoses. Based on 48,825 ambulance calls, 1054 were for opioid overdoses from 465 individuals during 2014 and 2015. The rate of calls for overdoses was 1 out of 48 of the total ambulance calls. Males made up the majority of the sample ( = 368, 79%), and the median age was 35 (range: 18-96). Overdoses occurred in public locations ( = 530, 50.3%), the safe injection facility ( = 353, 33.5%), in private homes ( = 83, 7.9%), and other locations ( = 88, 8.3%). Patients from the safe injection facility and private homes had similarly severe initial clinical symptoms (Glasgow Coma Scale median =3 and respiratory frequency median =4 breaths per minute) when compared with other locations, yet the majority from the safe injection facility did not require further ambulance transport to the hospital ( = 302, 85.6%). Those overdosed in public locations (odds ratio [OR] = 1.66, 95% confidence interval [CI] = 1.17-2.35), and when the safe injection facility was closed (OR =1.4, 95% CI =1.04-1.89), were more likely to receive transport for further treatment. Our findings suggest that the opening hours at the safe injection facility and the overdose location may impact the likelihood of ambulance transport for further treatment.
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http://dx.doi.org/10.1080/08897077.2018.1485130DOI Listing
July 2020

Acute recreational drug toxicity: Comparison of self-reports and results of immunoassay and additional analytical methods in a multicenter European case series.

Authors:
Evangelia Liakoni Christopher Yates Alison M Dines Paul I Dargan Fridtjof Heyerdahl Knut Erik Hovda David M Wood Florian Eyer Matthias E Liechti

Medicine (Baltimore) 2018 02;97(5):e9784

Division of Clinical Pharmacology and Toxicology, Basel University Hospital and University of Basel, Basel, Switzerland Clinical Pharmacology and Toxicology, Department of General Internal Medicine, Inselspital, Bern University Hospital, University of Bern, Bern Clinical Toxicology Unit, Emergency Department, Hospital Universitari Son Espases, Research Institute of Health Sciences (IdISBa), Palma de Mallorca, Spain Clinical Toxicology, Guy's and St Thomas' NHS Foundation Trust and King's Health Partners Clinical Toxicology, Faculty of Life Sciences and Medicine, King's College London, London, UK The Norwegian CBRNe Centre of Medicine, Department of Acute Medicine, Oslo University Hospital, Oslo, Norway Department of Clinical Toxicology, Klinikum Rechts der Isar, Technical University of Munich, Munich, Germany.

The aim of the study was to compare self-reported and analytically confirmed substance use in cases of acute recreational drug toxicity.We performed a retrospective analysis of emergency department presentations of acute recreational drug toxicity over 2 years (October 2013 to September 2015) within the European Drug Emergencies Network Plus project.Among the 10,956 cases of acute recreational drug toxicity during the study period, 831 could be included. Between the self-reported substance use and the toxicological results, the highest agreement was found for heroin (86.1%) and cocaine (74.1%), whereas inhalants, poppers, and magic mushrooms were self-reported but not analytically detected. Cathinones and other new psychoactive substances (NPS) could be detected using additional analytical methods. Among cases with both immunoassay (IA) and confirmation with mass spectrometry (MS), the results were consistent for methadone (100%) and cocaine (95.5%) and less consistent for amphetamines (81.8%). In cases with a positive IA for amphetamines (n = 54), MS confirmed the presence of 3,4-methylenedioxymethamphetamine (MDMA), amphetamine, methamphetamine, and NPS in 37, 20, 10, and 6 cases, respectively, also revealing use of more than 1 substance in some cases. MS yielded positive results in 21 cases with a negative IA for amphetamines, including amphetamine, MDMA, methamphetamine, and NPS, in 14, 7, 2, and 2 cases, respectively.In conclusion, the highest agreement was found between self-reports and analytical findings for heroin and cocaine. The diagnosis of NPS use was mainly based on self-report. The IAs accurately identified methadone and cocaine, and MS had advantages for the detection of NPS and amphetamine derivatives.
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http://dx.doi.org/10.1097/MD.0000000000009784DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5805445PMC
February 2018

Manual ventilation and open suction procedures contribute to negative pressures in a mechanical lung model.

Authors:
Espen Rostrup Nakstad Helge Opdahl Fridtjof Heyerdahl Fredrik Borchsenius Ole Henning Skjønsberg

BMJ Open Respir Res 2017 8;4(1):e000176. Epub 2017 May 8.

Department of Pulmonary Medicine, Oslo University Hospital, Ullevaal, Norway.

Introduction: Removal of pulmonary secretions in mechanically ventilated patients usually requires suction with closed catheter systems or flexible bronchoscopes. Manual ventilation is occasionally performed during such procedures if clinicians suspect inadequate ventilation. Suctioning can also be performed with the ventilator entirely disconnected from the endotracheal tube (ETT). The aim of this study was to investigate if these two procedures generate negative airway pressures, which may contribute to atelectasis.

Methods: The effects of device insertion and suctioning in ETTs were examined in a mechanical lung model with a pressure transducer inserted distal to ETTs of 9 mm, 8 mm and 7 mm internal diameter (ID). A 16 Fr bronchoscope and 12, 14 and 16 Fr suction catheters were used at two different vacuum levels during manual ventilation and with the ETTs disconnected.

Results: During manual ventilation with ETTs of 9 mm, 8 mm and 7 mm ID, and bronchoscopic suctioning at moderate suction level, peak pressure (P) dropped from 23, 22 and 24.5 cm HO to 16, 16 and 15 cm HO, respectively. Maximum suction reduced P to 20, 17 and 11 cm HO, respectively, and the end-expiratory pressure fell from 5, 5.5 and 4.5 cm HO to -2, -6 and -17 cm HO. Suctioning through disconnected ETTs (open suction procedure) gave negative model airway pressures throughout the duration of the procedures.

Conclusions: Manual ventilation and open suction procedures induce negative end-expiratory pressure during endotracheal suctioning, which may have clinical implications in patients who need high PEEP (positive end-expiratory pressure).
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http://dx.doi.org/10.1136/bmjresp-2016-000176DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5501241PMC
May 2017

Intoxication by gamma hydroxybutyrate and related analogues: Clinical characteristics and comparison between pure intoxication and that combined with other substances of abuse.

Authors:
Òscar Miró Miguel Galicia Paul Dargan Alison M Dines Isabelle Giraudon Fridtjof Heyerdahl Knut E Hovda Christopher Yates David M Wood Evangelia Liakoni Matthias Liechti Gesche Jürgens Carsten Boe Pedersen Niall O'Connor Gerard Markey Adrian Moughty Christopher Lee Patrick O'Donohoe Jacek Sein Anand Jordi Puiguriguer Catalina Homar Florian Eyer Odd Martin Vallersnes Per Sverre Persett Lucie Chevillard Bruno Mégarbane Raido Paasma W Stephen Waring Kristiina Põld Christian Rabe

Toxicol Lett 2017 Aug 1;277:84-91. Epub 2017 Jun 1.

Department of Clinical Toxicology, Klinikum rechts der Isar, Technical University of Munich, Germany.

Objective: To study the profile of European gamma-hydroxybutyrate (GHB) and gammabutyrolactone (GBL) intoxication and analyse the differences in the clinical manifestations produced by intoxication by GHB/GBL alone and in combination with other substances of abuse.

Method: We prospectively collected data on all the patients attended in the Emergency Departments (ED) of the centres participating in the Euro-DEN network over 12 months (October 2013 to September 2014) with a primary presenting complaint of drug intoxication (excluding ethanol alone) and registered the epidemiological and clinical data and outcomes.

Results: We included 710 cases (83% males, mean age 31 years), representing 12.6% of the total cases attended for drug intoxication. Of these, 73.5% arrived at the ED by ambulance, predominantly during weekend, and 71.7% consumed GHB/GBL in combination with other substances of abuse, the most frequent additional agents being ethanol (50%), amphetamine derivatives (36%), cocaine (12%) and cannabis (8%). Among 15 clinical features pre-defined in the project database, the 3 most frequently identified were altered behaviour (39%), reduced consciousness (34%) and anxiety (14%). The severity ranged from mild cases requiring no treatment (308 cases, 43.4%) to severe cases requiring admission to intensive care (103 cases, 14.6%) and mechanical ventilation (49 cases, 6.9%). No deaths were reported. In comparison with only GHB/GBL consumption, patients consuming GHB/GBL with co-intoxicants presented more vomiting (15% vs. 3%, p<0.001) and cardiovascular symptoms (5.3% vs. 1.5%, p<0.05), a greater need for treatment (59.8% vs. 48.3%, p<0.01) and a longer ED stay (11.3% vs. 3.6% patients with ED stay >12h, p<0.01).

Conclusions: The profile of the typical GHB/GBL-intoxicated European is a young male, requiring care for altered behaviour and reduced level of consciousness, mainly during the weekend. The clinical features are more severe when GHB is consumed in combination with other substances of abuse.
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http://dx.doi.org/10.1016/j.toxlet.2017.05.030DOI Listing
August 2017

Underestimated impact of novel psychoactive substances: laboratory confirmation of recreational drug toxicity in Oslo, Norway.

Authors:
Odd Martin Vallersnes Per Sverre Persett Elisabeth Leere Øiestad Ritva Karinen Fridtjof Heyerdahl Knut Erik Hovda

Clin Toxicol (Phila) 2017 Aug 13;55(7):636-644. Epub 2017 Apr 13.

f The Norwegian CBRNe Centre of Medicine, Department of Acute Medicine , Oslo University Hospital , Oslo , Norway.

Context: Recreational drug toxicity is frequent. Availability of new psychoactive substances is steadily increasing. However, data with verified analyses from clinical settings are limited. To evaluate the impact of novel psychoactive substances (NPS) on recreational drug toxicity in Oslo, Norway, we analysed samples from a selection of patients.

Methods: All the patients presenting with recreational drug toxicity at the Oslo Accident and Emergency Outpatient Clinic (OAEOC) and at the Oslo University Hospital (OUH) were registered from April through September 2014. Oral fluid samples were collected at the OAEOC. Blood samples were collected at the OUH. The samples were screened using ultra-high performance liquid chromatography - tandem mass spectrometry (UHPLC-MS/MS).

Results: Nine hundred and sixty-four cases were included, 841 (87.2%) at the OAEOC and 123 (12.8%) at the OUH. A total of 55 oral fluid samples (OAEOC) and 103 blood samples (OUH) could be analysed. NPS were not clinically suspected in any of the screened cases. At the outpatient clinic, the most commonly found substances were clonazepam in 42/55 (76.4%) cases, amfetamines in 40/55 (72.7%) and heroin in 39/55 (70.9%). In seven (12.7%) cases NPS were detected: 4-methylamfetamine in three cases, dimethyltryptamine in two, methylone in one, and N,N-dimethyl-3,4-methylenedioxyamfetamine in one. Among the hospital patients, the most commonly found substances were clonazepam in 51/103 (49.5%) cases, amfetamines in 48/103 (46.6%), heroin in 31/103 (30.1%), and diazepam in 30/103 (29.1%). In five (4.9%) cases NPS were detected: JWH-210 in two cases, AM-2201 in two, and 5-EAPB in one.

Conclusion: NPS were clinically not suspected, though found in eight percent of cases. Still, the vast majority of patients treated for recreational drug toxicity in Oslo have taken classical drugs. Management of these patients should be based on their clinical condition. However, it is highly important to be alert to atypical presentations possibly resulting from unsuspected drugs.
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http://dx.doi.org/10.1080/15563650.2017.1312002DOI Listing
August 2017

Erratum to: Psychosis associated with acute recreational drug toxicity: a European case series.

Authors:
Odd Martin Vallersnes Alison M Dines David M Wood Christopher Yates Fridtjof Heyerdahl Knut Erik Hovda Isabelle Giraudon Paul I Dargan

BMC Psychiatry 2016 11 16;16(1):405. Epub 2016 Nov 16.

Clinical Toxicology, Guy's and St Thomas' NHS Foundation Trust and King's Health Partners, London, UK.

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http://dx.doi.org/10.1186/s12888-016-1066-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5112744PMC
November 2016

Psychosis associated with acute recreational drug toxicity: a European case series.

Authors:
Odd Martin Vallersnes Alison M Dines David M Wood Christopher Yates Fridtjof Heyerdahl Knut Erik Hovda Isabelle Giraudon Paul I Dargan

BMC Psychiatry 2016 08 18;16:293. Epub 2016 Aug 18.

Clinical Toxicology, Guy's and St Thomas' NHS Foundation Trust and King's Health Partners, London, UK.

Background: Psychosis can be associated with acute recreational drug and novel psychoactive substance (NPS) toxicity. However, there is limited data available on how common this is and which drugs are most frequently implicated. We describe a European case series of psychosis associated with acute recreational drug toxicity, and estimate the frequency of psychosis for different recreational drugs.

Methods: The European Drug Emergencies Network (Euro-DEN) collects data on presentations to Emergency Departments (EDs) with acute recreational drug and NPS toxicity at 16 centres in ten countries. Euro-DEN data from October 2013 through September 2014 was retrospectively searched, and cases with psychosis were included. The proportion of cases with psychosis per drug was calculated in the searched Euro-DEN dataset.

Results: Psychosis was present in 348 (6.3 %) of 5529 cases. The median (interquartile range) age was 29 (24-38) years, 276 (79.3 %) were male and 114 (32.8 %) were admitted to psychiatric ward. The drugs most commonly reported were cannabis in 90 (25.9 %) cases, amphetamine in 87 (25.0 %) and cocaine in 56 (16.1 %). More than one drug was taken in 189 (54.3 %) cases. Psychosis was frequent in those ED presentations involving tryptamines (4/7; 57.1 %), methylenedioxypyrovalerone (MDPV) (6/22; 27.3 %), methylphenidate (6/26; 23.1 %), lysergic acid diethylamide (LSD) (18/86; 20.9 %), psilocybe mushrooms (3/16; 18.8 %), synthetic cannabinoid receptor agonists (4/26; 15.4 %) and amphetamine (87/593; 14.7 %), but less common in those involving mephedrone (14/245; 5.7 %), methylenedioxymethamphetamine (MDMA) (20/461; 4.3 %) and methedrone (3/92; 3.3 %). Amphetamine was the most frequent drug associated with psychosis when only one agent was reported, with psychosis occurring in 32.4 % of these presentations.

Conclusion: The frequency of psychosis in acute recreational drug toxicity varies considerably between drugs, but is a major problem in amphetamine poisoning. In rapidly changing drug markets and patterns of use, the Euro-DEN sentinel network contributes to measuring the scale of drug-related harms in Europe beyond other more established indicators.
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http://dx.doi.org/10.1186/s12888-016-1002-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4990880PMC
August 2016

Psychosis associated with acute recreational drug toxicity: a European case series.

Authors:
Odd Martin Vallersnes Alison M Dines David M Wood Christopher Yates Fridtjof Heyerdahl Knut Erik Hovda Isabelle Giraudon Paul I Dargan

BMC Psychiatry 2016 08 18;16:293. Epub 2016 Aug 18.

Clinical Toxicology, Guy's and St Thomas' NHS Foundation Trust and King's Health Partners, London, UK.

Background: Psychosis can be associated with acute recreational drug and novel psychoactive substance (NPS) toxicity. However, there is limited data available on how common this is and which drugs are most frequently implicated. We describe a European case series of psychosis associated with acute recreational drug toxicity, and estimate the frequency of psychosis for different recreational drugs.

Methods: The European Drug Emergencies Network (Euro-DEN) collects data on presentations to Emergency Departments (EDs) with acute recreational drug and NPS toxicity at 16 centres in ten countries. Euro-DEN data from October 2013 through September 2014 was retrospectively searched, and cases with psychosis were included. The proportion of cases with psychosis per drug was calculated in the searched Euro-DEN dataset.

Results: Psychosis was present in 348 (6.3 %) of 5529 cases. The median (interquartile range) age was 29 (24-38) years, 276 (79.3 %) were male and 114 (32.8 %) were admitted to psychiatric ward. The drugs most commonly reported were cannabis in 90 (25.9 %) cases, amphetamine in 87 (25.0 %) and cocaine in 56 (16.1 %). More than one drug was taken in 189 (54.3 %) cases. Psychosis was frequent in those ED presentations involving tryptamines (4/7; 57.1 %), methylenedioxypyrovalerone (MDPV) (6/22; 27.3 %), methylphenidate (6/26; 23.1 %), lysergic acid diethylamide (LSD) (18/86; 20.9 %), psilocybe mushrooms (3/16; 18.8 %), synthetic cannabinoid receptor agonists (4/26; 15.4 %) and amphetamine (87/593; 14.7 %), but less common in those involving mephedrone (14/245; 5.7 %), methylenedioxymethamphetamine (MDMA) (20/461; 4.3 %) and methedrone (3/92; 3.3 %). Amphetamine was the most frequent drug associated with psychosis when only one agent was reported, with psychosis occurring in 32.4 % of these presentations.

Conclusion: The frequency of psychosis in acute recreational drug toxicity varies considerably between drugs, but is a major problem in amphetamine poisoning. In rapidly changing drug markets and patterns of use, the Euro-DEN sentinel network contributes to measuring the scale of drug-related harms in Europe beyond other more established indicators.
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http://dx.doi.org/10.1186/s12888-016-1002-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4990880PMC
August 2016

Psychosis associated with acute recreational drug toxicity: a European case series.

Authors:
Odd Martin Vallersnes Alison M Dines David M Wood Christopher Yates Fridtjof Heyerdahl Knut Erik Hovda Isabelle Giraudon Paul I Dargan

BMC Psychiatry 2016 08 18;16:293. Epub 2016 Aug 18.

Clinical Toxicology, Guy's and St Thomas' NHS Foundation Trust and King's Health Partners, London, UK.

Background: Psychosis can be associated with acute recreational drug and novel psychoactive substance (NPS) toxicity. However, there is limited data available on how common this is and which drugs are most frequently implicated. We describe a European case series of psychosis associated with acute recreational drug toxicity, and estimate the frequency of psychosis for different recreational drugs.

Methods: The European Drug Emergencies Network (Euro-DEN) collects data on presentations to Emergency Departments (EDs) with acute recreational drug and NPS toxicity at 16 centres in ten countries. Euro-DEN data from October 2013 through September 2014 was retrospectively searched, and cases with psychosis were included. The proportion of cases with psychosis per drug was calculated in the searched Euro-DEN dataset.

Results: Psychosis was present in 348 (6.3 %) of 5529 cases. The median (interquartile range) age was 29 (24-38) years, 276 (79.3 %) were male and 114 (32.8 %) were admitted to psychiatric ward. The drugs most commonly reported were cannabis in 90 (25.9 %) cases, amphetamine in 87 (25.0 %) and cocaine in 56 (16.1 %). More than one drug was taken in 189 (54.3 %) cases. Psychosis was frequent in those ED presentations involving tryptamines (4/7; 57.1 %), methylenedioxypyrovalerone (MDPV) (6/22; 27.3 %), methylphenidate (6/26; 23.1 %), lysergic acid diethylamide (LSD) (18/86; 20.9 %), psilocybe mushrooms (3/16; 18.8 %), synthetic cannabinoid receptor agonists (4/26; 15.4 %) and amphetamine (87/593; 14.7 %), but less common in those involving mephedrone (14/245; 5.7 %), methylenedioxymethamphetamine (MDMA) (20/461; 4.3 %) and methedrone (3/92; 3.3 %). Amphetamine was the most frequent drug associated with psychosis when only one agent was reported, with psychosis occurring in 32.4 % of these presentations.

Conclusion: The frequency of psychosis in acute recreational drug toxicity varies considerably between drugs, but is a major problem in amphetamine poisoning. In rapidly changing drug markets and patterns of use, the Euro-DEN sentinel network contributes to measuring the scale of drug-related harms in Europe beyond other more established indicators.
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http://dx.doi.org/10.1186/s12888-016-1002-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4990880PMC
August 2016

Can ventilator settings reduce the negative effects of endotracheal suctioning? Investigations in a mechanical lung model.

Authors:
Espen R Nakstad Helge Opdahl Fridtjof Heyerdahl Fredrik Borchsenius Ole H Skjønsberg

BMC Anesthesiol 2016 06 27;16(1):30. Epub 2016 Jun 27.

Department of Pulmonary Medicine, Oslo University Hospital, Ullevaal, Oslo, Norway.

Background: The insertion of suction devices through endotracheal tubes (ETTs) increases airway resistance and the subsequent suctioning may reduce airway pressures and facilitate atelectasis. The aim of this study was to investigate how airway pressures and tidal volumes change when different combinations of suction equipment and ETT sizes are used, and to what extent unfavorable effects can be ameliorated by choice of ventilator settings.

Methods: A mechanical ventilator was connected to a lung model by ETTs of 9 mm, 8 mm or 7 mm internal diameter (ID) with a pressure transducer inserted distal to the ETT. The effects of suction procedures with bronchoscope and closed catheter systems were investigated during pressure controlled ventilation (PCV) and volume controlled ventilation (VCV). In each mode, the effects of changes in inspiration:expiration (I:E) ratio, trigger sensitivity and suction pressure were examined.

Results: The variables that contributed most to negative model airway pressures and loss of tidal volume during suctioning were (in descending order); 1) Small-size ETTs (7-8 mm ID) combined with large diameter suction devices (14-16 Fr); 2) inverse I:E ratio ventilation (in VCV); 3) negative ventilator trigger sensitivity; and 4) strong suction pressure. The pressure changes observed distal to the ETTs were not identical to those detected by the ventilator.

Conclusions: Negative model airway pressure was induced by suctioning through small-size ETTs. The most extreme pressure and volume changes were ameliorated when conventional ventilator settings were used, such as PCV mode with short inspiration time and a trigger function sensitive to flow changes.
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http://dx.doi.org/10.1186/s12871-016-0196-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4924309PMC
June 2016

Acute recreational drug and new psychoactive substance toxicity in Europe: 12 months data collection from the European Drug Emergencies Network (Euro-DEN).

Authors:
Alison M Dines David M Wood Christopher Yates Fridtjof Heyerdahl Knut Erik Hovda Isabelle Giraudon Roumen Sedefov Paul I Dargan

Clin Toxicol (Phila) 2015 Nov;53(9):893-900

a Clinical Toxicology, Guy's and St Thomas' NHS Foundation Trust and King's Health Partners , London , UK.

Context: Despite the potential for recreational drugs and new psychoactive substances (NPSs) to cause significant morbidity and mortality, there is limited collection of systematic data on acute drug/NPS toxicity in Europe.

Objective: To report data on acute drug/NPS toxicity collected by a network of sentinel centres across Europe with a specialist clinical and research interest in the acute toxicity of recreational drugs and NPS to address this knowledge gap.

Methods: Sixteen sentinel centres in 10 European countries (Denmark, Estonia, France, Germany, Ireland, Norway, Poland, Spain, Switzerland and the UK) collected data on all acute drug toxicity presentations to their Emergency Rooms (ERs) for 12 months (October 2013-September 2014); information on the drug(s) involved in the presentations was on the basis of patient self-reporting.

Results: Data were collected on a total of 5529 presentations involving 8709 drugs (median (interquartile range [IQR]): 1 (1-2) drugs per presentation), a median of 0.3% of all ER attendances. Classical recreational drugs were most common (64.6%) followed by prescription drugs (26.5%) and NPS (5.6%). The 'top five' drugs recorded were heroin (1345 reports), cocaine (957), cannabis (904), GHB/GBL (711) and amphetamine (593). 69.5% of individuals went to hospital by ambulance (peak time between 19:00 and 02:00 at weekends); the median (IQR) age was 31 (24-39) years and 75.4% were male. Although serious clinical features were not seen in most presentations and 56.9% were medically discharged from the ER (median length of stay: 4.6 hours), a significant number (26.5%) was agitated, in 10.5% the GCS was 8 or less and 35 presented in cardiac arrest. There were 27 fatalities with opioids implicated in 13.

Conclusion: The Euro-DEN dataset provides a unique insight into the drugs involved in and clinical pattern of toxicity/outcome of acute recreational drug toxicity presentations to hospitals around Europe. This is complimentary to other indicators of drug-related harm and helps to build a fuller picture of the public health implications of drug use in Europe.
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http://dx.doi.org/10.3109/15563650.2015.1088157DOI Listing
November 2015
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