A Nationwide Register‐Based Survey of Baclofen Toxicity

To study the use and misuse (poisonings) of baclofen in the time period of 2007–2012 and to evaluate the severity and clinical symptoms of poisonings including ingested baclofen. The National Patient Register (NPR) was searched for admissions due to baclofen poisonings from 2007 to 2012. The search was conducted with ICD‐10 codes for poisoning, self‐harm and suicide, and coupled with the baclofen ATC code. All enquiries about baclofen to the Danish Poison Information Centre (DPIC) in the same period were evaluated. Demographic and clinical data were extracted, and the poisonings were classified according to the Poison Severity Score. The number of baclofen poisonings did not increase from 2007 to 2012. Thirty‐eight admissions with baclofen poisoning were registered at the NPR; however, only one‐third of the reviewed DPIC cases were registered at the NPR with the correct coding. In the group of severely poisoned patients (PSS 3), three patients had only ingested baclofen (mean 2000 mg; SD 500 mg) and eight patients had ingested baclofen together with alcohol or psychotropic drugs (mean 900 mg; SD 641 mg). All patients presented with deep coma and respiratory depression. Additionally, seizures and cardiovascular events (mild hypo‐ or hypertension and bradycardia) occurred. There is a substantial degree of underreporting of baclofen poisonings in Denmark. Symptoms of baclofen poisoning progress very fast, and toxicity was observed even with doses as low as 150 mg. We therefore recommend that observation and treatment of these patients should be carried out in an intermediate‐ or intensive care unit. The most important treatment is the maintenance of a protected airway and respiration.     

Comparative Drug Dose and Drug Combinations in Patients that Present to Hospital Due to Self‐Poisoning

Self‐poisoning is a common reason for acute presentation to hospital. Commonly involved drugs have been reported, but few data exist concerning the different combinations of agents or comparative doses ingested. The present study sought to better characterise the typical patterns of drug overdose that may present via the emergency department. Consecutive adults ≥16 years of age that presented to York Hospital owing to self‐poisoning were studied for 2010–2011 inclusive. The primary outcome measure was reported dose, expressed as a multiple of the defined daily dose (DDD) to allow comparison between different agents. There were 1024 patients, including 622 women (60.7%), and median age was 32 years (range, 16 to 92 years). Overdose in men was associated with a higher overall quantity of drugs: arithmetic mean of 20 DDD multiples (95% CI, 15–26) versus 13 (11–15), p = 0.001. Overdose involved a single agent only in 538 patients (52.5%). The mean paracetamol dose was 4.0 (95% CI, 3.7–4.3) DDD multiples; the doses of antidepressants (19.4, 17.0–21.7, p < 0.0001) and benzodiazepines (18.0, 12.8–23.2, p < 0.0001) were comparatively higher. The types of agents involved in self‐poisoning and common combinations of agents are characterised. Psychotropic medications were ingested in comparatively larger quantities than analgesic agents and had worse clinical outcome. Further work is required to understand the factors that determine the quantity of drug ingested in patients at risk of drug overdose so as to minimise the risk of significant toxicity.     

Acute CO Poisoning is Associated with Impaired Fibrinolysis and Increased Thrombin Generation

Carbon monoxide (CO) poisoning is a leading cause of unintentional poisoning deaths in many countries. In ex vivo studies, CO released from carbon monoxide‐releasing molecules has been shown to attenuate fibrinolysis via increased alpha‐2‐antiplasmin activity. Hypofibrinolysis is associated with coronary ischaemia, which is also commonly observed in CO poisoning. We examined fibrin clot properties in acutely poisoned CO patients. Ex vivo plasma fibrin clot permeability, turbidimetry and efficiency of fibrinolysis were investigated in 48 patients and controls matched for age and sex. CO‐poisoned patients had 11.6% longer clot lysis time than the controls (p < 0.0001). No intergroup differences in clot permeability or turbidimetric variables were observed. Plasma tissue‐type plasminogen antigen (tPA), plasminogen activator inhibitor‐1 (PAI‐1) antigen and activity and F1.2 prothrombin fragments were higher in the patients than in the controls (all p < 0.0001). Plasma tPA activity was lower in the CO‐poisoned group. Multiple linear regression showed that a thrombin generation marker, F1.2, is the strongest predictor of clot lysis time, followed by PAI‐1 activity and carboxyhaemoglobin levels. In conclusion, this report is the first to demonstrate that acute CO poisoning in human beings is linked to increased thrombin generation and impaired fibrinolysis, which might contribute to ischaemic complications.     

Levothyroxine Poisoning – Symptoms and Clinical Outcome

Levothyroxine (LT), T4, poisoning is rarely associated with a severe outcome. However, cases with significant complications have been reported. The aim of this study was to identify factors associated with symptoms of poisoning including late‐onset symptoms. All enquiries to the Danish Poison Information Centre (DPIC) concerning LT poisoning between March 2007 and September 2012 were reviewed and the following parameters were recorded: age, dose, time from ingestion, multiple drug intake and symptoms. To evaluate the frequency of late‐onset symptoms, a subgroup of patients without initial symptoms were contacted. A total of 181 patients were registered (112 children). Ingested LT dose ranged from 10 to 9000 mcg (median 275 mcg). A total of 29 of 181 (16%) patients were symptomatic at the time of enquiry, and there was no difference in ingested LT dose between asymptomatic and symptomatic patients, neither in children nor in adults (age 16–92 years) (p < 0.68 and p < 0.47, respectively). In total, 153 of 181 (85%) patients did not have symptoms of poisoning at the time of enquiry; however, in 9 of 21 (43%) patients, we were able to contact, late‐onset symptoms existed. In none of the cases, hospital contact was needed and there were no reports of long‐term sequelae. Acute LT poisoning often follows a benign course. The occurrence of symptoms appears not to be dose dependent. Late‐onset symptoms seem to be common. However, all symptoms resolved spontaneously without need of medical care.     

Baclofen and Alcohol‐Dependent Patients: A Real Risk of Severe Self‐Poisoning

Baclofen is often prescribed in high doses to fight cravings experienced by alcohol‐dependent patients. Such an increase in the availability of baclofen is concerning. This study aimed to determine the change in number and profile of self‐poisoning with baclofen over time, as baclofen has become increasingly popular, in order to describe the severity of self‐poisoning with baclofen and to focus on co‐existing alcohol use disorders, and psychiatric illnesses determine predictors of severity. This was a retrospective study of self‐poisoning with baclofen as reported by the western France Poison Control Center (PCC), which represents a population of more than 12 million people from January 2008 to March 2014. One hundred and eleven cases of self‐poisoning with baclofen were reported to the western France PCC (62 males and 49 females; average age 39 ± 12). Poisoning severities were as follows: ‘null’ (nine cases), ‘minor’ (37 cases), ‘moderate’ (19 cases) and ‘high’ (46 cases, including four deaths). The most frequently reported symptoms were neurological (45%) and cardiovascular (27%). The severity was significantly associated with psychiatric disorders (OR = 2.9; p = 0.03). Baclofen, prescribed in high doses, may lead to severe poisoning, particularly in patients with psychiatric illnesses. Authorities should put forward a new policy for prescribing the drug as a treatment for alcohol dependence.     

Do Serotonin Reuptake Inhibitors Worsen Outcome of Patients Referred to the Emergency Department for Deliberate Multi‐drug Exposure?

Incidence of poisonings with serotonin reuptake inhibitors (SRIs) is growing. SRI toxicity is considered low, but its actual impact in multi‐drug poisonings remains unclear. Our objective was to evaluate the consequences of SRI exposure in patients referred to the emergency department (ED) for deliberate multi‐drug exposure. Patients admitted for multi‐drug exposure involving at least one SRI were matched with patients who did not ingest any SRI, according to age, gender, type of drug and ingested doses. Features of serotonin syndrome according to Sternbach's criteria and Hunter's serotonin toxicity criteria were evaluated from records. In 4 years, 148 SRI‐exposed patients were included and compared to 296 matched controls. The SRIs mainly involved were escitalopram (22%), venlafaxine (20%), fluoxetine (19%), citalopram (15%) and paroxetine (11%). Serotonin syndrome was diagnosed in one patient, but actually occurred in five SRI‐exposed patients based on the retrospective evaluation of records. Twenty patients (14%) exhibited one or more serotonin syndrome criteria. At least two of 11 of Sternbach's criteria and two of nine of Hunter's serotonin toxicity criteria were missing in each chart. Using a conditional logistic regression analysis, seizures (p = 0.04) and serotonin syndrome (p = 0.01 based on Sternbach's criteria and p = 0.004 based on Hunter's serotonin toxicity criteria) more frequently occurred in SRI‐exposed patients. Requirement for mechanical ventilation was significantly increased (p = 0.03), although admission to the intensive care unit was not. In multi‐drug‐poisoned patients admitted to the ED, exposure to SRIs significantly increases the risk of seizures and requirement for mechanically ventilation. Diagnosis of serotonin syndrome remains insufficient justifying improved training.     

N‐acetylcysteine in Acute Organophosphorus Pesticide Poisoning: A Randomized,Clinical Trial

Organophosphorus poisoning is a major global health problem with hundreds of thousands of deaths each year. Research interest in N‐acetylcysteine has grown among increasing evidence of the role of oxidative stress in organophosphorus poisoning. We aimed to assess the safety and efficacy of N‐acetylcysteine as an adjuvant treatment in patients with acute organophosphorus poisoning. This was a randomized, controlled, parallel‐group trial on 30 patients suffering from acute organophosphorus poisoning, who were admitted to the Poison Control Center of Tanta University Emergency Hospital, Tanta, Egypt, between April and September 2014. Interventions included oral N‐acetylcysteine (600 mg three times daily for 3 days) as an added treatment to the conventional measures versus only the conventional treatment. Outcome measures included mortality, total dose of atropine administered, duration of hospitalization and the need for ICU admission and/or mechanical ventilation. A total of 46 patients were screened and 30 were randomized. No significant difference was found between both groups regarding demographic characteristics and the nature or severity of baseline clinical manifestations. No major adverse effects to N‐acetylcysteine therapy were reported. Malondialdehyde significantly decreased and reduced glutathione significantly increased only in the NAC‐treated patients. The patients on NAC therapy required less atropine doses than those who received only the conventional treatment; however, the length of hospital stay showed no significant difference between both groups. The study concluded that the use of N‐acetylcysteine as an added treatment was apparently safe, and it reduced atropine requirements in patients with acute organophosphorus pesticide poisoning.     

Deliberate Drug Poisoning with Slight Symptoms on Admission: Are there Predictive Factors for Intensive Care Unit Referral? A three‐year Retrospective Study

Deliberate drug poisoning leads to 1% of emergency department (ED) admissions. Even if most patients do not exhibit any significant complication, 5% need to be referred to an intensive care unit (ICU). Emergency physicians should distinguish between low‐ and high‐acuity poisoned patients at an early stage to avoid excess morbidity. Our aim was to identify ICU transfer factors in deliberately self‐poisoned patients without life‐threatening symptoms on admission. We performed a 3‐year retrospective observational study in a university hospital. Patients over 18 years of age with a diagnosis of deliberate drug poisoning were included. Clinical and toxicological data were analysed with univariate tests between groups (ED stay versus ICU transfer). Factors associated with ICU admission were then included in a logistic regression analysis. Two thousand five hundred and sixty‐five patients were included. 63.2% were women, and median age was 40 (28–49). 142 patients (5.5%) were transferred to ICU. Cardiac drugs [adjusted OR (aOR) = 19.81; 95% confidence interval (95% CI): 7.93–49.50], neuroleptics (aOR = 2.78; 95% CI: 1.55–4.97) and meprobamate (aOR = 2.71; 95% CI: 1.27–5.81) ingestions were significantly linked to ICU admission. A presumed toxic dose ingestion (aOR = 2.27; 95% CI: 1.28–4.02), number of ingested tablets (aOR = 1.01; 95% CI: 1.01–1.02 for each tablet) and delay between ingestion and ED arrival <2 hr (aOR = 2.85; 95%CI: 1.62–5.03) were also factors for ICU referral. The Glasgow Coma Scale was the only clinical feature associated with ICU admission (aOR = 1.57; 95% CI: 1.44–1.70 for each point loss). These results suggest that emergency physicians should pay particular attention to toxicological data on ED admission to distinguish between low‐ and high‐acuity self‐poisoned patients.     

Simplified Acute Physiology Score II/Acute Physiology and Chronic Health Evaluation II and Prediction of the Mortality and Later Development of Complications in Poisoned Patients Admitted to Intensive Care Unit

We aimed to determine the acute physiology and chronic health evaluation (APACHE) II and simplified acute physiology score (SAPS) II in poisoned patients admitted to the poisoning ICU and compare them to see which is a more sensitive and specific system for prognostication of the mortality and complications in these patients. Between February 2013 and July 2013, all patients referring to our centre with any poisoning mandating ICU admission were prospectively included. On ICU arrival, a questionnaire containing the demographic data, parameters of the APACHE II and SAPS II scores, the sum of the scores, complications during the stay and the patients' final outcome (compete recovery versus death) was filled for every single patient. A total of 195 patients were evaluated. Forty‐two patients (21.5%) died. Mean SAPS and APACHE scores were 41 ± 16 and 15 ± 6, respectively. Mean SAPS and APACHE scores were significantly different between the survivors and non‐survivors. Both scores could successfully prognosticate the development of the complications (p = 0.07 and 0.013, respectively). APACHE II was a better score in prediction of both mortality and later complications in the setting of poisoning ICU. APACHE >22 has a good specificity in determining the mortality and development of further complications in poisoned patients admitted to the medical toxicology ICUs. SAPS II score >59 and >43 can predict the risk of mortality and later complications in these patients, as well.     

Cyclopeptide mushroom poisoning: A retrospective series of 204 patients

Cyclopeptide mushroom poisoning is responsible for 90%–95% of deaths from macrofungi ingestion. The main objectives of this study are to describe cases of cyclopeptide mushroom poisoning and to determine risk factors that may influence the severity/mortality of poisoned patients. We included all cases of amatoxin toxicity reported to two French Poison Centers from 2013 through 2019. We compared the severity with the Poison Severity Score (PSS) and the outcomes of patients using simple logistic regression and multinomial logistic regression. We included 204 cases of amatoxin toxicity. More than three-quarters developed an increase in AST and/or ALT (78.1%), and over half developed a decrease in prothrombin ratio (<70%: 53%) and/or Factor V (<70%: 54%). One-third developed an acute renal injury (AKI). Twelve patients (5.9%) developed post-poisoning sequelae (persistent kidney injury more than 1 month after ingestion and liver transplant). Five patients (2.5%) received a liver transplant, and nine died (4.4%). The mean time to onset of digestive disorders was shorter in PSS2 and PSS3–4 patients (10.9 ± 3.9/11.3 ± 6.3 h) than in PSS1 patients (14 ± 6.5 h; p < 0.05). Patients who died or developed post-poisoning sequelae had more frequent cardiovascular comorbidities compared with recovered patients (60.0% versus 29.5%; p < 0.01).     

Prognostic Factors in Acute Aluminium Phosphide Poisoning: A Risk‐Prediction Nomogram Approach

Aluminium phosphide (AlP) is a toxic agent associated with a high mortality rate following acute exposure from various routes. The aim of this study was to determine the clinical and laboratory findings useful for predicting the medical outcome of AlP‐poisoned patients using established scoring systems. This is a prospective study of AlP‐poisoned patients from 2010 to 2015 in Ardabil, Iran. All patients that presented with a confirmed diagnosis of acute AlP poisoning in the study interval were included in the study. Clinical and laboratory data, using Acute Physiology and Chronic Health Evaluation II (APACHE II), Sequential Organ Failure Assessment (SOFA) and Simplified Acute Physiology Score II (SAPS II) scoring systems, were compared for their predictive value in determining differences between survived and non‐survived patients. Univariate analysis (Mann–Whitney or t‐test), multiple logistic regression analysis, receiver operating characteristic (ROC) curve analysis and the Pearson correlation test were performed using STATA/SE 13.0 and the Nomolog Software . A total of 68 AlP‐poisoned patients with confirmed acute AlP poisoning were included for evaluation. Of these, 36 were non‐survived. Multiple logistic regression analysis was performed using parameters and values derived from patient clinical and laboratory data, and revealed that four factors were significant for predicting mortality: Glasgow coma score (GCS); systolic blood pressure (SBP); urinary output (UOP); and serum HCO₃. A four‐variable, risk‐prediction nomogram was developed for identifying high‐risk patients and predicting the risk of mortality. Study results showed that SBP of <92.5 mmHg (p = 0.006); HCO₃^‐ < 12.9 mEq/L (p = 0.01), UOP < 1725 mL/day (p = 0.04); and GCS < 14.5 (p = 0.003) were significant predictors of AlP mortality. Scoring systems analysis showed SAPS II score >24.5, APACHE II score >8.5 and SOFA score >7.5 were predictive of non‐survival patients. The results of our study showed that SBP, GCS, UOP and serum HCO₃ levels are the best prognostic factors for predicting mortality in AlP‐poisoned patients. According to the area under the ROC curve of the APACHE II score, when compared with SOFA and SAPS II scores, the APACHE II score can more effectively discriminate between non‐survivors and survived patients.     

Rare Alleles within the CYP2E1 (MEOS System) Could be Associated with Better Short‐Term Health Outcome after Acute Methanol Poisoning

Genetic polymorphisms influence the metabolism of ethanol and methanol, but the potential effects of genetic predisposition on the clinical course, outcome and short‐term health sequelae of acute methanol poisoning are unknown. To evaluate the role of the MEOS system in methanol poisoning, we analysed the effect of three polymorphisms (RsaI – rs2031920; PstI – rs3813867; insertion/deletion I/D) within the CYP2E1 enzyme (MEOS system) in 50 adult survivors of methanol poisoning and compared their genotype frequencies with 460 controls. The minor allele frequencies of all three polymorphisms were below 5% in both groups. We did not detect significant differences in the genotype frequencies between survivors of methanol poisoning and controls (p = 0.34 for the RsaI variant; p = 0.59 for the PstI variant and p = 0.21 for the I/D polymorphism). The carriers of at least one minor allele in the CYP2E1 gene had less severe clinical symptoms and better short‐term outcome after acute poisoning. Variants within the CYP2E1 gene are likely not significant genetic determinants of acute methanol poisoning (if survivors are analysed), but they may influence the severity of methanol poisoning and its visual/central nervous system (CNS) outcome.     

An Effective Machine Learning Approach for Prognosis of Paraquat Poisoning Patients Using Blood Routine Indexes

The early identification of toxic paraquat (PQ) poisoning in patients is critical to ensure timely and accurate prognosis. Although plasma PQ concentration has been reported as a clinical indicator of PQ poisoning, it is not commonly applied in practice due to the inconvenient necessary instruments and operation. In this study, we explored the use of blood routine indexes to identify the degree of PQ toxicity and/or diagnose PQ poisoning in patients via machine learning approach. Specifically, we developed a method based on support vector machine combined with the feature selection technique to accurately predict PQ poisoning risk status, then tested the method on 79 (42 male and 37 female; 41 living and 38 deceased) patients. The detection method was rigorously evaluated against a real‐world data set to determine its accuracy, sensitivity and specificity. Feature selection was also applied to identify the factors correlated with risk status, and the results showed that there are significant differences in blood routine indexes between dead and living PQ‐poisoned individuals (p‐value < 0.01). Feature selection also showed that the most important correlated indexes are white blood cell and neutrophils. In conclusion, the toxicity or prognosis of PQ poisoning can be preliminarily ascertained by blood routine testing without PQ concentration data, representing an additional tool and innovative approach to assess the prognosis of PQ poisoning.     

Usefulness of Transthoracic Echocardiography Parameters and Brain Natriuretic Peptide as Mortality Predictors in Hospitalized Acutely Poisoned Patients: A Prospective Observational Study

Acute poisonings represent a common cause of morbidity and mortality worldwide. The prognostic utility of the transthoracic echocardiography (TTE) parameters combined with brain natriuretic peptide (BNP) in acute poisoning with different xenobiotics, upon admission in the hospital, was not evaluated. This prospective observational cohort study included 229 acutely poisoned non‐diabetic adults, with a median age of 44 years (range 18–90 years), 50.7% women, with an in‐hospital mortality rate of 8.7%. Univariate logistic regression analysis showed that age, the left ventricle kinetic abnormalities, the E‐wave deceleration time (EDT) and BNP correlated significantly with mortality in acutely poisoned patients. Multivariate logistic regression showed that only EDT [odds ratio (OR) 3.44, 95% confidence interval (CI) 1.54–7.69, p 0.003], BNP (OR 1.61, 95% CI: 1.02–2.55, p 0.04) and age (OR 2.66, 95% CI: 1.23–5.76, p 0.013) are predictive for mortality. The receiver‐operating characteristic (ROC) analysis proved EDT [area under the ROC curve (AUC), 0.85; CI: 0.76–0.94; p 0.001], BNP (AUC, 0.83; CI: 0.75–0.91; p 0.001) and age (AUC, 0.82; CI: 0.74–0.90; p 0.001) as indicators for fatalities. In hospitalized patients acutely intoxicated with undifferentiated poisons, EDT as a parameter of left ventricle diastolic function and BNP are useful to early predict mortality.     

Is the Measurement of Serum Formate Concentration Useful in the Diagnostics of Acute Methanol Poisoning? A Prospective Study of 38 Patients

The aim of this article was to study the role of serum formate (S‐formate) in diagnosing methanol poisoning. A prospective study was undertaken of 38 patients from the Czech methanol mass poisoning in 2012 – median age 51 [interquartile range (IQR) 37–62] years with confirmed methanol poisoning. S‐formate was measured enzymatically. The receiver operating characteristics (ROC) curve was used to examine the predictive ability of S‐formate. Asymptomatic patients had median S‐formate of 1.9 (IQR 1.5–2.4) mmol/L. The median S‐formate was 15.2 (IQR 13.9–17.6) mmol/L in symptomatic subjects with visual disturbances, 15.4 (12.1–18.0) mmol/L in subjects with dyspnoea and 15.7 (IQR 12.8–18.5) mmol/L in comatose patients. The differences in serum formate concentrations in symptomatic patients depending on clinical features were not significant (all p > 0.05). Patients with long‐term visual sequelae of poisoning had median S‐formate of 16.1 (IQR 14.3–19.9) mmol/L; with central nervous system (CNS) sequelae, patients had 15.9 (IQR 14.2–19.5) mmol/L. In lethal cases, the median S‐formate was 15.2 (IQR 13.8–15.9) mmol/L. The probability of a poor outcome (death or survival with sequelae) was higher than 90% in patients with S‐formate ≥17.5 mmol/L, S‐lactate ≥7.0 mmol/L and/or pH <6.87. The ROC analysis showed that the corresponding areas under the curve (AUC) were 0.64 (0.44–0.85 CI 95%) for S‐formate, 0.75 (0.56–0.93 CI 95%) for ‘S‐formate+S‐lactate’ and only 0.54 (0.38–0.69 CI 95%) for serum methanol, which is lower than for S‐formate (p < 0.05). The measurement of S‐formate is an important tool in the laboratory diagnostics and clinical management of acute methanol poisoning. S‐formate ≥3.7 mmol/L can lead to the first clinical signs of visual toxicity, indicating haemodialysis. S‐formate ≥11–12 mmol/L is associated with visual/CNS sequelae and a lethal outcome.     

Patterns of toxicity and factors influencing severity in acute adult trimipramine poisoning

AIMS

To analyze the clinical features of trimipramine poisoning, identify a minimal toxic dose, and the dose bearing a 50% risk of developing a moderate, severe or fatal outcome.

METHODS

All acute adult trimipramine monointoxications reported by physicians to the Swiss Toxicological Information Centre between January 1992 and December 2009 were identified.

RESULTS

Two hundred and thirty cases (26 confirmed and 204 probable) were analyzed, the mean age was 35.7 years and 74% were females. One hundred and thirty-seven patients showed mild, 54 moderate and 21 severe symptoms. Three cases were fatal due to refractory cardiovascular collapse. Ninety-three per cent of the events were attempted or completed suicides. The most common symptoms were central nervous system depression (79.2%), tachycardia (19.1%) and QT_c prolongation (13.9%). The severity of poisoning depended significantly on the ingested dose (P < 0.001). The minimal dose for moderate symptoms was 250 mg (median dose 1.2 g) and 850 mg for severe symptoms (median dose 2.7 g). The dose for a 50% risk of developing a moderate, severe or fatal outcome was 5.11 g. In 38 patients early gastrointestinal decontamination was performed. Overall, these patients ingested higher trimipramine doses than the late- or not-decontaminated patients (P= 0.113). The median doses were also higher in the decontaminated group within each severity category except in the fatal cases.

CONCLUSIONS

We demonstrated that moderate trimipramine poisoning can already occur after ingestion of doses in the high therapeutic range. Poisoned patients have to be monitored for central nervous system depression, dysrhythmias and QT_c prolongation. Early decontamination might be beneficial.     

Acute Methanol Poisoning: Prevalence and Predisposing Factors of Haemorrhagic and Non‐Haemorrhagic Brain Lesions

The purpose was to study the prevalence and predisposing factors of brain lesions in survivors of acute methanol poisoning. Clinical data on 106 patients with methanol poisoning were collected during the Czech mass poisoning outbreak. Of 83 survivors, in 46 (55%) patients, follow‐up examinations including magnetic resonance imaging of brain (MR) were performed 3–8 and 24–28 months after discharge from the hospital. Of 46 patients with a median age of 49 (interquartile range, 35–57) years, 24 (52%) patients had a total of 40 abnormal brain findings with haemorrhagic lesions detected in 15 (33%) and non‐haemorrhagic lesions found in 9 (19%) patients. The patients with haemorrhagic brain lesions were more acidemic (lower arterial blood pH, higher base deficit) and had higher glycaemia and lactacidaemia on admission than those without haemorrhages (all p < 0.05). Thirteen of 32 (41%) of patients with systemic anticoagulation and 2 of 14 (14%) of patients without it had haemorrhagic lesions (p = 0.080). Bleeding complications during the treatment occurred in 4 of 15 (27%) patients, and 5 of 15 (33%) patients had conditions predisposing to haemorrhage in the group with haemorrhagic lesions. In three cases with a series of computer tomography (CT)/MR performed during hospitalization, the necrotic lesions in the brain remained non‐haemorrhagic during hospitalization and haemorrhagic lesions were detected on the follow‐up MR examinations only. No association between brain haemorrhages and systemic anticoagulation during dialysis was found: brain haemorrhages might occur in severely poisoned patients treated without systemic anticoagulation, whereas treatment with high doses of heparin might not lead to brain haemorrhages.     

Advanced Electrocardiogram Analysis in the Amitriptyline‐poisoned Pig Treated with Activated Charcoal Haemoperfusion

Coated activated charcoal haemoperfusion (CAC‐HP) does not reduce the plasma concentration in amitriptyline (AT)‐poisoned pigs. The aim of this non‐blinded, randomized, controlled animal trial was to determine if CAC‐HP reduces the pathological ECG changes caused by AT poisoning. Fourteen female Danish Landrace pigs (mean weight 27.7 kg, range 20–35 kg (CAC‐HP) and 24.4 kg, range 18–30 kg (control group, CG), n = 7 in each group) were included. After randomization, the pigs were anaesthetized and intravenously poisoned with AT. The intervention group underwent 4 hr of CAC‐HP plus standard care (oral activated charcoal). Intervention was compared to standard care alone. From each pig, a 12‐lead ECG and haemodynamic variables were obtained at baseline, at full AT loading dose, before and during CAC‐HP. Baseline ECG variables (RR, PR, QRS, QTc, QTp, QTe, TpTe and TpTe/QT) for lead II, v2 and v5 were not significantly different (F = 0.035–0.297, p‐values 0.421–0.919). Differences within groups over time and between groups were tested by anova repeated measures. For all variables, the time‐plus‐group level of significance revealed a p‐value > 0.05. Severe cardiovascular arrhythmias occurred in both groups with 3 in the CAC‐HP group versus 1 incident with premature death in the CG. The attenuating effect of CAC‐HP to orally instilled activated charcoal alone on AT‐induced ECG alterations did not differ significantly. We conclude that the use of modern CAC‐HP as an adjunctive treatment modality in AT‐poisoned pigs is inadequate.     

Tailored dose baclofen in patients with alcoholic liver disease: A case series with 2-year follow-up of hospitalisation

Introduction: Alcohol addiction is a major health burden with its consequences including liver disease and frequent hospitalisations. We used tailored-dose baclofen in patients with alcoholic liver disease and investigated hospital re-admissions before and after baclofen dose was initiated as well as tolerability and patient-reported alcohol consumption. Methods: Fifty-three hospitalised patients with alcoholic liver disease started tailored dose baclofen (median: 5.05 months, median highest dose before tapering down: 60?mg). Patients were followed-up for hospitalisation data from the health board database (mean hospitalisation follow up: 31 months) and patients were sent standardized questionnaires. Results: Baclofen was generally well tolerated with dose reductions in four patients. In the 2 years after initiation of the treatment, patients spent on an average of 19.1?d in the hospital per year compared to 25.48?d before the treatment initiation (p?=?0.59). Respondents (19 patients) reported a reduction in alcohol consumption by an average of 58.7% (240.1?g to 144.09?g). Conclusions: After initiation of the baclofen treatment, there was a trend towards decrease in hospitalisations and in patients who answered the questionnaire, alcohol consumption decreased.     

Is there a relationship between the WHO hazard classification of organophosphate pesticide and outcomes in suicidal human poisoning with commercial organophosphate formulations?

The WHO classification of pesticides by hazard is based primarily on the acute oral and dermal toxicity to rats. In several Asian countries there is no legislation against the sale of Class I insecticides. We evaluated if there was an association between the WHO hazard Class I, II or III organophosphate compound and outcomes in human poisoning. Two-hundred and fifty-one patients with mean (SD) age of 30.4 (11.8) years, admitted with symptomatic poisoning and treated with atropine and supportive care, were followed up until death or hospital discharge. The admission pseudocholinesterase level of 818.8 (1368) IU/L indicated significant suppression of cholinesterase activity. Class I compounds were ingested by 126, Class II by 113 and Class III by 12 patients. The hospital mortality rate was 16.7%, 5.3% and 0% with Class I, II and III organophosphate compounds, respectively (P = 0.01). Ventilatory requirements were higher with Class I compared with Class II poisoning (77.0% vs. 54.9%, P < 0.001). Patients with Class I poisoning needed mechanical ventilation for a longer period (10.55 (7.4) vs. 7.0 (5.2) days, P = 0.002). The linear relationship between the WHO hazard class and mortality in acute organophosphate poisoning mandates the restriction of the sale of organophosphate compounds associated with higher lethality amongst humans.