Knut Erik Hovda

Methanol outbreak in Norway 2002-2004: epidemiology, clinical features and prognostic signs

Objectives.  Knowledge on methanol poisoning does mainly come from clinical studies. We therefore report epidemiological, clinical and prognostic features from the large methanol outbreak in Norway in 2002–2004 where the new antidote fomepizole was the primary antidote in use.

Methanol mass poisoning in Estonia: Outbreak in 154 patients

Background. Knowledge of methanol toxicity is based on human data from case series and larger outbreaks. In many of these cases, however, diagnosis was not verified by methanol determinations. We present epidemiological and clinical data from one of the largest methanol outbreaks in which all patients had detectable serum methanol levels. Methods. Retrospective case series study of hospital and forensic charts from the five hospitals where patients were treated. Results. Of the 147 patients admitted with suspected methanol poisoning, the diagnosis was confirmed in 111, of whom 25 (23 %) died. In addition, 43 patients died outside the hospital, giving a total of 154 patients and a death toll of 68 (44 %). Outcome was related to the degree of metabolic acidosis, serum methanol concentration, coma upon admission, and the patients ability to hyperventilate. Patients were treated with bicarbonate (85 %), ethanol (87 %), hemodialysis (71 %), and mechanical ventilation (61%) according to clinical features and blood gases, since serum methanol concentrations were analyzed retrospectively. Twenty patients (18 %) survived with permanent sequelae, 18 suffered from impaired vision, and 3 developed permanent brain damage. Discussion. Given limited resources, triage and use age of tertiary care centers allowed a small community hospital to treat a high number of methanol-poisoned patients. Critical resources were ventilators and dialyzing machines, whereas stores of antidote (ethanol) and bicarbonate were sufficient. Many patients were mechanically ventilated by hand and treated with bicarbonate and ethanol during transport to tertiary care centers for hemodialysis.

Anion and osmolal gaps in the diagnosis of methanol poisoning: clinical study in 28 patients

Objective To evaluate anion and osmolal gaps as diagnostic tools in methanol poisoning.Design and setting Clinical observational study.Patients and methods In a recent methanol outbreak, the initial triage and treatment decisions in 28 patients were based mainly upon the values of the osmolal and anion gaps on admission. Methanol and formate levels were later compared to these gaps by linear regression analysis.Results The correlation between the osmolal gaps and serum methanol concentrations on admission was linear (y = 1.03x+12.71, R2 = 0.94). The anion gaps correlated well with the serum formate concentrations (y = 1.12x+13.82, R2 = 0.86). Both gaps were elevated in 24 of the 28 subjects upon admission. Three patients had an osmolal gap within the reference area (because of low serum methanol), but elevated anion gap because of formate accumulation. One patient with probable concomitant ethanol ingestion had a high osmolal gap and a normal anion gap.Conclusion Osmolal and anion gaps are useful in the diagnosis and triage of methanol-exposed subjects. Confounders are low serum methanol and concomitant ethanol ingestion.

Methanol poisoning and long term sequelae – a six years follow-up after a large methanol outbreak

BackgroundMass poisonings with methanol are rare but occur regularly both in developed and in developing countries. Data from the poisoning episodes are often published, but follow-up-data is scarce. We therefore conducted a six year follow-up study after the large methanol outbreak in Estonia in September 2001.MethodsSurviving victims from the outbreak were contacted and invited to an interview and a clinical evaluation by an ophthalmologist and a physician. The patients that failed to respond were searched for in the Estonian Register of Population and through their General Practitioner.ResultsDuring the outbreak in 2001, 86/111 hospitalized patients survived: 66 without sequelae (Group I) and 20 with sequelae (Group II). Six years later, 26/86 were dead, 33/86 could not be tracked down, and so only 27/86 of these were followed up and examined: 22/66 of the patients in Group I, and 5/20 in Group II were found and examined. From Group I, 8/22 were identified with new neurological impairment and 8/22 with new visual disturbances after discharge. From Group II, visual disturbances (n = 4) and neurological impairment (n = 3) were still present in all patients. Among the 26 dead, 19 were from Group I, and seven were from Group II. Alcohol intoxication was the most frequent cause of death (7/26).ConclusionAll sequelae were still present six years after the initial poisoning suggesting that these were irreversible damages. On follow-up, apparently new neurological and visual complications were identified in 36% and 36%, respectively. 35% of the patients initially discharged with sequelae and 29% discharged without were dead six years later; 27% of them from alcohol intoxication.

Acute poisonings treated in hospitals in Oslo : A one-year prospective study (I): Pattern of poisoning

Objectives. Prospective design is mandatory to study pattern of poisoning and suicidal intention of patients. Material and Methods. Prospective cross-sectional multi-center study of all patients contacting health care services because of acute poisoning during one year in Oslo, irrespective of intention. Data on the adult hospitalized patients (≥16 years) are presented here. Results. Of a total of 3,775 such adult contacts (3,025 episodes), there were 947 (31 %) hospitalizations; annual incidence 1.9 (per 1,000) in males and 2.1 in females. Median age was 36 years (range 16–89); 54% females. Benzodiazepines (18%), ethanol (17%), paracetamol (12%), opioids (7%), and gamma hydroxybutyric acid (GHB) (7%) were most frequently taken. Patients stated suicidal intention in 29% of the admissions; physicians in 10%. Conclusion. Benzodiazepines and ethanol were the most common agents, but newer illicit drugs were frequent, especially GHB. Males often took ethanol and drugs of abuse; females often used prescription drugs with suicidal intention.

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

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.

Repetition of acute poisoning in Oslo: 1-year prospective study.

BACKGROUND The repetition of acute poisoning occurs frequently. The intention may change between episodes and many poisonings are treated outside the hospital setting. Few studies have taken this into account. AIMS To quantify the repetition frequency regardless of the level of health care or the intention behind the poisoning, and to identify possible risk factors for repetition. METHOD A prospective multicentre study of all acute poisonings in Oslo treated in hospital, at an out-patient clinic or by the ambulance service. Repetition was estimated using Kaplan-Meier calculations, and predictive factors were identified using Cox regression analysis. RESULTS The estimated 1-year repetition rate was 30% (95% CI 24-35). Independent predictors of repetition were middle age (30-49 years), poisoning with opiates or sedatives, unemployment or living on social welfare, a previous suicide attempt, and a history of psychiatric treatment. Intention was not a significant predictor. CONCLUSIONS Repetition of acute poisoning is high, irrespective of the level of healthcare and the intention behind the poisoning.

Methanol and Formate Kinetics During Treatment with Fomepizole

Objective. Methanol is metabolized by a1cohol dehydrogenase to formaldehyde, and further to formic acid, which is responsible for the toxicity in methanol poisoning. Fomepizole (4-methylpyrazole) is a potent competitive inhibitor of a1cohol dehydrogenase and is used as an antidote to treat methanol poisonings. We report serum methanol kinetics in eight patients treated with bicarbonate and fomepizole only. Methods. Prospective case series study of eight patients with methanol poisoning, who were selected to fomepizole and bicarbonate treatment only because of moderate metabolic acidosis. Three of the patients were later dialyzed, because of high serum methanol concentrations and very slow methanol elimination. Results. Upon admission the median pH was 7.27 (range 7.12–7.50), median base deficit was 15 mmol/L (5–22 mmol/L) and median serum methanol was 20.4 mmol/L (65 mg/dL) (range 8.4–140.6 mmol/L). The kinetics of methanol during fomepizole treatment in six patients was best described by a first-order elimination one-compartment model. The mean correlation coefficient (R2) describing the first-order elimination model in all eight patients was 0.95 (range 0.90–0.99). The mean plasma half-life (t½) of methanol during fomepizole treatment was 52 h (range 22–87); the higher the serum methanol, the longer the T½. Mean half-life of serum formate was 2.6 h, when methanol metabolism was assumed blocked by fomepizole and no folinic acid was given. This rapid formate elimination in nonacidotic patients may be explained by high renal excretion of formate. Conclusion. Based on our data, methanol-poisoned patients with moderate metabolic acidosis and methanol levels up to 19 mmol/L (60 mg/L) may safely be treated with bicarbonate and fomepizole only, without dialysis.

Czech mass methanol outbreak 2012: Epidemiology, challenges and clinical features

Abstract Objectives. Methanol poisonings occur frequently globally, but reports of larger outbreaks where complete clinical and laboratory data are reported remain scarce. The objective of the present study was to report the data from the mass methanol poisoning in the Czech Republic in 2012 addressing the general epidemiology, treatment, and outcomes, and to present a protocol for the use of fomepizole ensuring that the antidote was provided to the most severely poisoned patients in the critical phase. Methods. A combined prospective and retrospective case series study of 121 patients with confirmed methanol poisoning. Results. From a total of 121 intoxicated subjects, 20 died outside the hospital and 101 were hospitalized. Among them, 60 survived without, and 20 with visual/CNS sequelae, whereas 21 patients died. The total and hospital mortality rates were 34% and 21%, respectively. Multivariate regression analysis found pH < 7.0 (OR 0.04 (0.01–0.16), p < 0.001), negative serum ethanol (OR 0.08 (0.02–0.37), p < 0.001), and coma on admission (OR 29.4 (10.2–84.6), p < 0.001) to be the only independent parameters predicting death. Continuous hemodialysis was used more often than intermittent hemodialysis, but there was no significant difference in mortality rate between the two [29% (n = 45) vs 17% (n = 30), p = 0.23]. Due to limited stockpiles of fomepizole, ethanol was administered more often; no difference in mortality rate was found between the two [16% (n = 70) vs. 24% (n = 21), p = 0.39]. The effect of folate administration both on the mortality rate and on the probability of visual sequelae was not significant (both p > 0.05). Conclusions. Severity of metabolic acidosis, state of consciousness, and serum ethanol on admission were the only significant parameters associated with mortality. The type of dialysis or antidote did not appear to affect mortality. Recommendations that were issued for hospital triage of fomepizole administration allowed conservation of valuable antidote in this massive poisoning outbreak for those patients most in need.

Intermittent hemodialysis is superior to continuous veno-venous hemodialysis/hemodiafiltration to eliminate methanol and formate during treatment for methanol poisoning

During an outbreak of methanol poisonings in the Czech Republic in 2012, we were able to study methanol and formate elimination half-lives during intermittent hemodialysis (IHD) and continuous veno-venous hemodialysis/hemodiafiltration (CVVHD/HDF) and the relative impact of dialysate and blood flow rates on elimination. Data were obtained from 11 IHD and 13 CVVHD/HDF patients. Serum methanol and formate concentrations were measured by gas chromatography and an enzymatic method. The groups were relatively comparable, but the CVVHD/HDF group was significantly more acidotic (mean pH 6.9 vs. 7.1 IHD). The mean elimination half-life of methanol was 3.7 and formate 1.6 h with IHD, versus 8.1 and 3.6 h, respectively, with CVVHD/HDF (both significant). The 54% greater reduction in methanol and 56% reduction in formate elimination half-life during IHD resulted from the higher blood and dialysate flow rates. Increased blood and dialysate flow on the CVVHD/HDF also increased elimination significantly. Thus, IHD is superior to CVVHD/HDF for more rapid methanol and formate elimination, and if CVVHD/HDF is the only treatment available then elimination is greater with greater blood and dialysate flow rates.