Publications by authors named "Knut Erik Hovda"

56 Publications

Substances, poisonings and A&E clinics.

Authors:
Knut Erik Hovda

Tidsskr Nor Laegeforen 2021 05 3;141(7). Epub 2021 May 3.

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http://dx.doi.org/10.4045/tidsskr.21.0133DOI Listing
May 2021

Formate test for bedside diagnosis of methanol poisoning.

Basic Clin Pharmacol Toxicol 2021 Jul 12;129(1):86-88. Epub 2021 May 12.

Department of Acute Medicine, Oslo University Hospital, Oslo, Norway.

Methanol poisoning kills thousands of people every year and remains a diagnostic challenge, especially where the resources are scarce, but also in high-income countries worldwide. We are in the course of developing a bedside strip to detect formate - the toxic metabolite of methanol. We hereby present the first clinical methanol case where formate was detected bedside from a drop of blood: The patient, a 61-year-old male, was admitted with a suspect methanol poisoning and severe metabolic acidosis. The test strip was positive after 3 minutes. Sodium bicarbonate (500 mmol/L), fomepizole, dialysis and folinic acid were given based on the positive test. The diagnosis was some hours later confirmed by GC-MS, showing a methanol concentration of 62 mmol/L (200 mg/dL) and a formate concentration of 19 mmol/L. Implementation of this technology into routine clinical use can potentially offer an opportunity for a step change in the management of methanol poisoning.
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http://dx.doi.org/10.1111/bcpt.13597DOI Listing
July 2021

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

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
March 2021

A survey of the antidote preparedness in Norwegian hospitals.

Eur J Hosp Pharm 2021 Jan 22. Epub 2021 Jan 22.

Norwegian National Unit for CBRNE Medicine, Department of Acute Medicine, Oslo University Hospital, Oslo, Norway.

Objectives: Antidotes are an important part of the emergency preparedness in hospitals. In the case of a major chemical accident or a fire, large quantities of antidotes may be needed within a short period of time. For time-critical antidotes it is therefore necessary that they be immediately available. We wanted to evaluate the antidote preparedness in Norwegian hospitals as regards the national recommendations and compare this with other international guidelines.

Methods: A digital survey was sent to the 50 hospitals in Norway that treat acute poisonings. Of these, four hospitals are categorised as regional hospitals, 15 as large hospitals and 31 as small hospitals. Each hospital was asked which antidotes they stockpiled from a list of 35 antidotes. The financial costs (low, moderate, high) were added to an established efficacy scale to illustrate the cost-effectiveness of the different antidotes.

Results: The response rate was 100%. Eleven of fifty (22%) hospitals stockpiled all antidotes recommended for their hospital size. All four regional hospitals had all the recommended antidotes. Large hospitals which were not regional hospitals had the least availability of antidotes, and only one large hospital stockpiled all antidotes recommended for this hospital size.

Conclusions: We found varying compliance with the national recommendations for antidote storage in hospitals. To strengthen antidote preparedness, we recommend standardised European guidelines to support national guidelines.
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http://dx.doi.org/10.1136/ejhpharm-2020-002544DOI Listing
January 2021

Ventilatory support for hypoxaemic intensive care patients with COVID-19.

Tidsskr Nor Laegeforen 2020 08 8;140(11). Epub 2020 Jul 8.

Background: COVID-19 pneumonia can result in severe hypoxaemic respiratory failure that requires intensive medical care. We wished to describe COVID-19 intensive care patients who were treated with and without invasive ventilatory support.

Material And Method: The material was retrieved from the local quality register and comprises data on patients with COVID-19 admitted to the intensive care department at Oslo University Hospital Ullevål from 5 March-28 May 2020. The patients were categorised in three groups on the basis of the treatment they received for respiratory failure (oxygen alone, supplemental non-invasive ventilation (NIV), and intubation/ventilator) and described using descriptive statistics.

Results: Of 165 hospitalised COVID-19 patients, a total of 26 (16 %) were treated in our intensive care department. Four of them had do-not-resuscitate-orders and were excluded. The 22 patients included in this study had an average age of 56 years (range 25 to 78 years); 17 (77 %) were men. Eleven patients received ventilator treatment, seven oxygen by mask, and four supplemental NIV. In the ventilator group, as of 28 May 2020 two had died, and the remainder had been discharged alive from the intensive care department, with one remaining hospitalised on a ward. All patients treated with oxygen and NIV were alive and had been discharged from hospital.

Interpretation: For many patients with COVID-19 respiratory failure and need for intensive care, increased oxygen and NIV are sufficient, but the need for intubation must be continuously assessed. More than 90 % of actively treated intensive care patients survived.
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http://dx.doi.org/10.4045/tidsskr.20.0445DOI Listing
August 2020

Double trouble: methanol outbreak in the wake of the COVID-19 pandemic in Iran-a cross-sectional assessment.

Crit Care 2020 07 9;24(1):402. Epub 2020 Jul 9.

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

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http://dx.doi.org/10.1186/s13054-020-03140-wDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7344025PMC
July 2020

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

Br J Clin Pharmacol 2021 Apr 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

Fatal liver failure after therapeutic doses of paracetamol in a patient with Duchenne muscular dystrophy and atypical pharmacogenetic profile of drug-metabolizing enzymes.

Basic Clin Pharmacol Toxicol 2020 Jul 5;127(1):47-51. Epub 2020 Feb 5.

Norwegian National Unit for CBRNE Medicine, Department of Acute Medicine, Oslo University Hospital, Oslo, Norway.

Paracetamol has a good safety profile, but pharmacogenetic differences in drug-metabolizing enzymes may have an impact on its risk of hepatotoxicity. We present a case of fatal acute liver failure (ALF) after therapeutic doses of paracetamol in a patient with Duchenne muscular dystrophy, where pharmacogenetic screening was conducted. This 30-year-old man was electively admitted for a tracheostomy. A total of 14.5 g paracetamol was given over four days. He developed a severe ALF and died 11 days after admission. Pharmacogenetic screening showed absent CYP2D6 metabolism and increased CYP1A2 activity, which may have increased the formation of toxic intermediate metabolite, N-acetyl-p-benzo-quinone imine (NAPQI). He also had decreased function of UGT2B15, which increases the amount of paracetamol available for metabolism to NAPQI. Having a reduced muscle mass and thus a reduced glutathione levels to detoxify produced NAPQI may add to the risk of toxicity. This case may indicate that pharmacogenetic variability is of potential relevance for the risk of paracetamol-induced hepatotoxicity in patients with neuromuscular diseases. Further studies should investigate if pharmacogenetic screening could be a tool to detect potentially increased risk of hepatotoxicity in these patients at therapeutic doses of paracetamol and hence provide information for selection of analgesic treatment.
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http://dx.doi.org/10.1111/bcpt.13389DOI Listing
July 2020

Consensus statements on the approach to patients in a methanol poisoning outbreak.

Clin Toxicol (Phila) 2019 12 22;57(12):1129-1136. Epub 2019 Jul 22.

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

Methanol poisoning is an important cause of mortality and morbidity worldwide. Although it often occurs as smaller sporadic events, epidemic outbreaks are not uncommon due to the illicit manufacture and sale of alcoholic beverages. We aimed to define methanol poisoning outbreak (MPO), outline an approach to triaging an MPO, and define criteria for prioritizing antidotes, extracorporeal elimination treatments (i.e., dialysis), and indications for transferring patients in the context of an MPO. We convened a group of experts from across the world to explore geographical, socio-cultural and clinical considerations in the management of an MPO. The experts answered specific open-ended questions based on themes aligned to the goals of this project. This project used a modified Delphi process. The discussion continued until there was condensation of themes. We defined MPO as a sudden increase in the number of cases of methanol poisoning during a short period of time above what is normally expected in the population in that specific geographic area. Prompt initiation of an antidote is necessary in MPOs. Scarce hemodialysis resources require triage to identify patients most likely to benefit from this treatment. The sickest patients should not be transferred unless the time for transfer is very short. Transporting extracorporeal treatment equipment and antidotes may be more efficient. We have developed consensus statements on the response to a methanol poisoning outbreak. These can be used in any country and will be most effective when they are discussed by health authorities and clinicians prior to an outbreak.
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http://dx.doi.org/10.1080/15563650.2019.1636992DOI Listing
December 2019

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

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

Methanol content in homemade alcohol from a province in North Vietnam.

Drug Alcohol Rev 2019 07 16;38(5):537-542. Epub 2019 May 16.

Norwegian National Unit for CBRNE Medicine, Department of Acute Medicine, Oslo University Hospital, Oslo, Norway.

Introduction And Aims: Methanol poisonings pose a major risk especially where illegal alcohol is consumed. The source of the methanol in the drinks are debated. We aimed to evaluate whether home distillation of alcohol made from rice was capable of producing toxic amounts of methanol.

Design And Methods: Twenty households with homemade alcohol production in Phu Tho province in Vietnam were included in this pilot study. We followed the whole production process and an alcohol sample from each household was analysed for methanol content.

Results: 17 (85%) of the samples contained detectable levels of methanol. The median concentration was 9 mg/L (range 2-37 mg/L). To develop clinical symptoms of methanol poisoning from the sample with the highest concentration would require drinking more than 424 L.

Discussion And Conclusions: Homemade alcohol from rice did not contain sufficient amount of methanol to cause toxicity in our study. This supports the theory of methanol being added to ethanol post production for economical purposes as the main source of mass poisonings.
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http://dx.doi.org/10.1111/dar.12937DOI Listing
July 2019

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

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.

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.

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

Poor Identification of Emergency Department Acute Recreational Drug Toxicity Presentations Using Routine Hospital Coding Systems: the Experience in Denmark, Switzerland and the UK.

J Med Toxicol 2019 04 2;15(2):112-120. Epub 2019 Jan 2.

Clinical Toxicology, Guy's and St Thomas' NHS Foundation Trust and King's Health Partners, St Thomas' Hospital, 3rd Floor, Block C, South Wing, Westminster Bridge Road, London, SE1 7EH, UK.

Background: Understanding emergency department and healthcare utilisation related to acute recreational drug toxicity (ARDT) generally relies on nationally collated data based on ICD-10 coding. Previous UK studies have shown this poorly captures the true ARDT burden. The aim of this study was to investigate whether this is also the case elsewhere in Europe.

Methods: The Euro-DEN Plus database was interrogated for all presentations 1st July to 31st December 2015 to the EDs in (i) St Thomas' Hospital, London, UK; (ii) Universitätsspital Basel, Basel, Switzerland; and (iii) Zealand University Hospital, Roskilde, Denmark. Comparison of the drug(s) involved in the presentation with the ICD-10 codes applied to those presentations was undertaken to determine the proportion of cases where the primary/subsequent ICD-10 code(s) were ARDT related.

Results: There were 619 presentations over the 6-month period. Two hundred thirteen (34.4%) of those presentations were coded; 89.7% had a primary/subsequent ARDT-related ICD-10 code. One hundred percent of presentations to Roskilde had a primary ARDT ICD-10 code compared to 9.6% and 18.9% in Basel and London respectively. Overall, only 8.5% of the coded presentations had codes that captured all of the drugs that were involved in that presentation.

Conclusions: While the majority of primary and secondary codes applied related to ARDT, often they did not identify the actual drug(s) involved. This was due to both inconsistencies in the ICD-10 codes applied and lack of ICD-10 codes for the drugs/NPS. Further work and education is needed to improve consistency of use of current ICD-10 and future potential ICD-11 coding systems.
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http://dx.doi.org/10.1007/s13181-018-0687-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6440929PMC
April 2019

The Hypothesis of Circulus Hypoxicus and Its Clinical Relevance in Patients With Methanol Poisoning - An Observational Study of 35 Patients.

Basic Clin Pharmacol Toxicol 2018 Dec 23;123(6):749-755. Epub 2018 Jul 23.

Department of Acute Medicine, Division of Medicine, Oslo University Hospital, Oslo, Norway.

Methanol mass poisoning is a global problem with high fatality rates and often severe sequelae in survivors. Patients typically present late to the hospital with severe metabolic acidosis followed by a rapid deterioration in their clinical status. The hypothesis 'Circulus hypoxicus' describes the metabolic acidosis following methanol poisoning as a self-enhancing hypoxic circle responsible for methanol toxicity. We wanted to test the validity of this hypothesis by an observational study based on 35 patients from the methanol outbreaks in Norway (2004) and the Czech Republic (2012). Comprehensive laboratory values, including S(serum)-methanol, S-formate, S-lactate, arterial blood gases, anion and osmolal gaps, were used in the calculations. Laboratory values and calculated gaps were compared to each other using linear regression. S-lactate and S-formate correlated better with the increased base deficit and anion gap than did S-formate alone. Base deficit rose to about 20 mmol/L and S-formate rose to 12 mmol/L prior to a significant rise in S-lactate - most likely caused by formate inhibition of mitochondrial respiration (type B lactacidosis). The further rise in S-lactate was not linear to S-formate most likely due to the self-enhancing pathophysiology, but may also be associated with hypotension in critically ill patients and variable ethanol drinking habits. Our study suggests that the primary metabolic acidosis leads to a secondary lactic acidosis mainly due to the toxic effects of formate. The following decline in pH will further increase this toxicity. As such, a vicious and self-enhancing acidotic circle may explain the pathophysiology in methanol poisoning, namely the 'Circulus hypoxicus'.
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http://dx.doi.org/10.1111/bcpt.13074DOI Listing
December 2018

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

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

Intermittent versus continuous renal replacement therapy in acute methanol poisoning: comparison of clinical effectiveness in mass poisoning outbreaks.

Ann Intensive Care 2017 Dec 20;7(1):77. Epub 2017 Jul 20.

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

Background: Intermittent hemodialysis (IHD) is the modality of choice in the extracorporeal treatment (ECTR) of acute methanol poisoning. However, the comparative clinical effectiveness of intermittent versus continuous modalities (CRRT) is unknown. During an outbreak of mass methanol poisoning, we therefore studied the effect of IHD versus CRRT on mortality and the prevalence of visual/central nervous system (CNS) sequelae in survivors.

Methods: The study was designed as prospective observational cohort study. Patients hospitalized with a diagnosis of acute methanol poisoning were identified for the study. Exploratory factor analysis and multivariate logistic regression were applied to determine the effect of ECTR modality on the outcome.

Results: Data were obtained from 41 patients treated with IHD and 40 patients with CRRT. The follow-up time in survivors was two years. Both groups of patients were comparable by age, time to presentation, laboratory data, clinical features, and other treatment applied. The CRRT group was more acidemic (arterial blood pH 6.96 ± 0.08 vs. 7.17 ± 0.07; p < 0.001) and more severely poisoned (25/40 vs. 9/41 patients with Glasgow Coma Scale (GCS) ≤ 8; p < 0.001). The median intensive care unit length of stay (4 (range 1-16) days vs. 4 (1-22) days; p = 0.703) and the number of patients with complications during the treatment (11/41 vs. 13/40 patients; p = 0.576) did not differ between the groups. The mortality was higher in the CRRT group (15/40 vs. 5/41; p = 0.008). The number of survivors without sequelae of poisoning was higher in the IHD group (23/41 vs. 10/40; p = 0.004). There was a significant association of ECTR modality with both mortality and the number of survivors with visual and CNS sequelae of poisoning, but this association was not present after adjustment for arterial blood pH and GCS on admission (all p > 0.05).

Conclusions: In spite of the faster correction of the acidosis and the quicker removal of the toxic metabolite in intermittent dialysis, we did not find significant differences in the treatment outcomes between the two groups after adjusting for the degree of acidemia and the severity of poisoning on admission. These findings support the strategy of "use what you have" in situations with large outbreaks and limited dialysis capacity.
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http://dx.doi.org/10.1186/s13613-017-0300-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5519513PMC
December 2017

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

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

Reply to "Letter in response to efficiency of acidemia correction on intermittent versus continuous hemodialysis in acute methanol poisoning".

Clin Toxicol (Phila) 2017 04;55(4):306-307

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

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http://dx.doi.org/10.1080/15563650.2017.1284338DOI Listing
April 2017

Efficiency of acidemia correction on intermittent versus continuous hemodialysis in acute methanol poisoning.

Clin Toxicol (Phila) 2017 Feb 7;55(2):123-132. Epub 2016 Nov 7.

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

Context: Acidemia is a marker of prognosis in methanol poisoning, as well as compounding formate-induced cytotoxicity. Prompt correction of acidemia is a key treatment of methanol toxicity and methods to optimize this are poorly defined.

Objective: We studied the efficiency of acidemia correction by intermittent hemodialysis (IHD) and continuous renal replacement therapy (CRRT) in a mass outbreak of methanol poisoning.

Methods: The study was designed as observational cohort study. The mean time for an increase of 1 mmol/L HCO, 0.01 unit arterial blood pH, and the total time for correction of HCO were determined in IHD- and CRRT-treated patients.

Results: Data were obtained from 18 patients treated with IHD and 13 patients treated with CRRT. At baseline, CRRT group was more acidemic than IHD group (mean arterial pH 6.79 ± 0.10 versus 7.05 ± 0.10; p = 0.001). No association was found between the rate of acidemia correction and age, weight, serum methanol, lactate, formate, and glucose on admission. The time to HCO correction correlated with arterial blood pH (r= -0.511; p = 0.003) and creatinine (r = 0.415; p = 0.020). There was association between the time to HCO correction and dialysate/effluent and blood flow rates (r= -0.738; p < 0.001 and r= -0.602; p < 0.001, correspondingly). The mean time for HCO to increase by 1 mmol/L was 12 ± 2 min for IHD versus 34 ± 8 min for CRRT (p < 0.001), and the mean time for arterial blood pH to increase 0.01 was 7 ± 1 mins for IHD versus 11 ± 4 min for CRRT (p = 0.024). The mean increase in HCO was 5.67 ± 0.90 mmol/L/h for IHD versus 2.17 ± 0.74 mmol/L/h for CRRT (p < 0.001).

Conclusions: Our study supports the superiority of IHD over CRRT in terms of the rate of acidemia correction.
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http://dx.doi.org/10.1080/15563650.2016.1250901DOI Listing
February 2017

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

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

The Methanol Poisoning Outbreaks in Libya 2013 and Kenya 2014.

PLoS One 2016 31;11(3):e0152676. Epub 2016 Mar 31.

Médecins Sans Frontières, Oslo, Norway.

Background: Outbreaks of methanol poisoning occur frequently on a global basis, affecting poor and vulnerable populations. Knowledge regarding methanol is limited, likely many cases and even outbreaks go unnoticed, with patients dying unnecessarily. We describe findings from the first three large outbreaks of methanol poisoning where Médecins Sans Frontières (MSF) responded, and evaluate the benefits of a possible future collaboration between local health authorities, a Non-Governmental Organisation and international expertise.

Methods: Retrospective study of three major methanol outbreaks in Libya (2013) and Kenya (May and July 2014). Data were collected from MSF field personnel, local health personnel, hospital files, and media reports.

Findings: In Tripoli, Libya, over 1,000 patients were poisoned with a reported case fatality rate of 10% (101/1,066). In Kenya, two outbreaks resulted in approximately 341 and 126 patients, with case fatality rates of 29% (100/341) and 21% (26/126), respectively. MSF launched an emergency team with international experts, medications and equipment, however, the outbreaks were resolving by the time of arrival.

Interpretation: Recognition of an outbreak of methanol poisoning and diagnosis seem to be the most challenging tasks, with significant delay from time of first presentations to public health warnings being issued. In spite of the rapid response from an emergency team, the outbreaks were nearly concluded by the time of arrival. A major impact on the outcome was not seen, but large educational trainings were conducted to increase awareness and knowledge about methanol poisoning. Based on this training, MSF was able to send a local emergency team during the second outbreak, supporting that such an approach could improve outcomes. Basic training, simplified treatment protocols, point-of-care diagnostic tools, and early support when needed, are likely the most important components to impact the consequences of methanol poisoning outbreaks in these challenging contexts.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0152676PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4816302PMC
August 2016

Use of Out-of-Hospital Ethanol Administration to Improve Outcome in Mass Methanol Outbreaks.

Ann Emerg Med 2016 07 11;68(1):52-61. Epub 2016 Feb 11.

Norwegian CBRNe Center of Medicine, Department of Acute Medicine, Oslo University Hospital, Oslo, Norway.

Study Objective: Methanol poisoning outbreaks are a global public health issue, with delayed treatment causing poor outcomes. Out-of-hospital ethanol administration may improve outcome, but the difficulty of conducting research in outbreaks has meant that its effects have never been assessed. We study the effect of out-of-hospital ethanol in patients treated during a methanol outbreak in the Czech Republic between 2012 and 2014.

Methods: This was an observational case-series study of 100 hospitalized patients with confirmed methanol poisoning. Out-of-hospital ethanol as a "first aid antidote" was administered by paramedic or medical staff before the confirmation of diagnosis to 30 patients; 70 patients did not receive out-of-hospital ethanol from the staff (12 patients self-administered ethanol shortly before presentation).

Results: The state of consciousness at first contact with paramedic or medical staff, delay to admission, and serum methanol concentration were similar among groups. The median serum ethanol level on admission in the patients with out-of-hospital administration by paramedic or medical staff was 84.3 mg/dL (interquartile range 32.7 to 129.5 mg/dL). No patients with positive serum ethanol level on admission died compared with 21 with negative serum ethanol level (0% versus 36.2%). Patients receiving out-of-hospital ethanol survived without visual and central nervous system sequelae more often than those not receiving it (90.5% versus 19.0%). A positive association was present between out-of-hospital ethanol administration by paramedic or medical staff, serum ethanol concentration on admission, and both total survival and survival without sequelae of poisoning.

Conclusion: We found a positive association between out-of-hospital ethanol administration and improved clinical outcome. During mass methanol outbreaks, conscious adults with suspected poisoning should be considered for administration of out-of-hospital ethanol to reduce morbidity and mortality.
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http://dx.doi.org/10.1016/j.annemergmed.2016.01.010DOI Listing
July 2016

A young woman who drank Strep test reagents.

Tidsskr Nor Laegeforen 2015 Dec 1;135(22):2067-70. Epub 2015 Dec 1.

Nasjonal behandlingstjeneste for CBRNe-medisin og Akuttmedisinsk avdeling Oslo universitetssykehus, Ullevål.

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http://dx.doi.org/10.4045/tidsskr.15.0190DOI Listing
December 2015

Antidotes for poisoning by alcohols that form toxic metabolites.

Br J Clin Pharmacol 2016 Mar 4;81(3):505-15. Epub 2016 Jan 4.

The Norwegian CBRNe Centre of Medicine, Department of Acute Medicine, Division of Medicine, Oslo University Hospital, NO-0424, Oslo, Norway.

The alcohols, methanol, ethylene glycol and diethylene glycol, have many features in common, the most important of which is the fact that the compounds themselves are relatively non-toxic but are metabolized, initially by alcohol dehydrogenase, to various toxic intermediates. These compounds are readily available worldwide in commercial products as well as in homemade alcoholic beverages, both of which lead to most of the poisoning cases, from either unintentional or intentional ingestion. Although relatively infrequent in overall occurrence, poisonings by metabolically-toxic alcohols do unfortunately occur in outbreaks and can result in severe morbidity and mortality. These poisonings have traditionally been treated with ethanol since it competes for the active site of alcohol dehydrogenase and decreases the formation of toxic metabolites. Although ethanol can be effective in these poisonings, there are substantial practical problems with its use and so fomepizole, a potent competitive inhibitor of alcohol dehydrogenase, was developed for a hopefully better treatment for metabolically-toxic alcohol poisonings. Fomepizole has few side effects and is easy to use in practice and it may obviate the need for haemodialysis in some, but not all, patients. Hence, fomepizole has largely replaced ethanol as the toxic alcohol antidote in many countries. Nevertheless, ethanol remains an important alternative because access to fomepizole can be limited, the cost may appear excessive, or the physician may prefer ethanol due to experience.
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http://dx.doi.org/10.1111/bcp.12824DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4767193PMC
March 2016