Joint RCEM and NPIS best practice guideline: assessment and management of acute opioid toxicity in adults in the emergency department.

The Royal College of Emergency Medicine Toxicology Special Interest Group in collaboration with the UK National Poisons Information Service and the Clinical Toxicology Department at Guy's and St Thomas' NHS Foundation Trust has produced guidance to support clinicians working in the ED with the assessment and management of adults with acute opioid toxicity.Considerations regarding identification of acute opioid toxicity are discussed and recommendations regarding treatment options and secondary prevention are made. There is a focus on making recommendations on the best available evidence.

Medication errors involving intravenous paracetamol in children: experience from enquiries to the National Poisons Information Service.

INTRODUCTION: Children are at higher risk of medication errors due to the complexity of drug prescribing and administration in this patient group. Intravenous (IV) paracetamol overdose differs from overdose by ingestion as there is no enteral absorptive buffering. We provide the first national UK data focusing on paediatric IV paracetamol poisoning. METHODS: All telephone enquiries to the National Poisons Information Service between 2008 and 2021 regarding children less than 18 years old in the UK concerning IV paracetamol overdose were extracted from the UK Poisons Information Database (UKPID). Data were analysed using descriptive statistics. RESULTS: Enquiries were made concerning 266 children, mostly involving children under the age of 1 year (n=145; 54.5%). Acute and staggered overdoses were the most frequent types of exposure. Common error themes included 10-fold overdose in 45 cases (16.9%) and inadvertent concomitant oral and IV dosing in 64 cases (24.1%). A high proportion of cases were asymptomatic (87.1%), with many calls regarding overdoses below the treatable dose of 60 mg/kg (41.4%). Treatment with the antidote acetylcysteine was advised in 113 cases (42.5%). CONCLUSIONS: Inadvertent IV paracetamol overdose appears to occur more frequently in young children. A significant proportion were calculation errors which were often 10-fold errors. While these errors have the potential for causing serious harm, thankfully most cases were asymptomatic. Errors with IV paracetamol might be reduced by electronic prescribing support systems, better communication regarding administration and consideration of whether other routes are more appropriate.

Diagnosis and practical management of digoxin toxicity: a narrative review and consensus.

There are currently no universally accepted guidelines for the management of digoxin toxicity. In the absence of clinical practice guidelines, a set of consensus recommendations for management of digoxin toxicity in the clinical setting were developed through a modified Delphi approach. The recommendations highlight the importance of early recognition of signs of potentially life-threatening toxicity that requires immediate treatment with digoxin-specific antibodies. The consensus identifies a straightforward approach to dosing immune antibody fragments according to the presence or absence of signs of life-threatening toxicity. Supportive measures and management of specific signs of toxicity are also covered.

Metformin-associated lactic acidosis reported to the United Kingdom National Poisons Information Service (NPIS) between 2010 and 2019: a ten-year retrospective analysis.

INTRODUCTION: Metformin toxicity following therapeutic use or overdose may result in metabolic acidosis with hyperlactatemia. This study aims to assess the relationship between serum lactate concentration, arterial pH, and ingested dose with severity of poisoning, and to identify if serum lactate concentration is a useful marker of severity in metformin toxicity. METHODS: A retrospective study of telephone enquiries relating to metformin exposures to the National Poisons Information Service between 2010 and 2019 from hospitals in the United Kingdom. RESULTS: Six-hundred and thirty-seven cases were identified; 117 involved metformin only and 520 involved metformin with other drugs. The majority of cases involved acute (87%) and intentional (69%) exposures. There was a statistically significant difference in doses between the Poisoning Severity Scores, as well as between intentional and unintentional or therapeutic error doses (P < 0.0001). The distribution of cases for each Poisoning Severity Score differed between the metformin only and metformin with other drugs cases (P < 0.0001). Lactic acidosis was reported in 232 cases. Serum lactate concentration and arterial pH differed across Poisoning Severity Scores. Arterial pH inversely correlated with ingested dose (r=-0.3, P = 0.003), and serum lactate concentration positively correlated with ingested dose (r = 0.37, P < 0.0001). Serum lactate concentration and arterial pH did not correlate with each other. Twenty-five deaths were recorded, all following intentional overdoses. DISCUSSION: The dataset focuses mostly on acute, intentional overdoses. Increasing ingested metformin dose, a higher serum lactate concentration and worsening arterial pH were all associated with an unfavourable Poisoning Severity Score in patients in both metformin only and metformin with other drugs groups. As serum lactate concentration did not correlate with arterial pH, it represents an independent marker of poisoning severity. CONCLUSIONS: Data from the present study suggest that serum lactate concentration can be used to assess severity of poisoning in patients who have reportedly ingested metformin.

Toxicology in the emergency department: what's new?

Intentional and accidental drug overdose, recreational drug use and exposure to toxic substances are common reasons for people presenting to emergency departments. Although the mortality rate associated with these presentations is low in the UK, they can lead to significant morbidity and prolonged hospital admissions. This review discusses new developments in the management of paracetamol overdose. Several new protocols for the infusion of acetylcysteine, the antidote for paracetamol overdose, have been proposed in the past decade and evaluated in clinical studies. The 12-hour Scottish and Newcastle Acetylcysteine Protocol regimen and 20-hour Australian two-infusion bag protocol have been widely adopted into clinical practice and endorsed in national guidelines because of their shorter duration, reduction in adverse effects and efficacy in treating overdose. This article includes a care pathway that can facilitate the implementation of the Scottish and Newcastle Acetylcysteine Protocol. This article also discusses the emergency management of ingested button batteries, describes the emerging threat of novel psychoactive substances, and provides an update on new UK antidote guidelines. Further up-to-date guidance on management of clinical toxicology is available to healthcare professionals on the internet database TOXBASE.

Bites by exotic snakes reported to the UK National Poisons Information Service 2009-2020.

Introduction: Snakebite is recognised as a neglected tropical disease and a cause of substantial morbidity and mortality. Whilst the most medically important snakes are typically native of Asia, Africa, Latin America and Oceania, the possibility of encountering these snakes is no longer limited by geography due to an increasing number of exotic (non-native) snakes being held in captivity.Methods: A retrospective review of snakebite enquiries to the UK National Poisons Information Service (NPIS) between 2009 and 2020. Enquiries about the European adder (Vipera berus) or where the identity of the snake was unknown were excluded.Results: There were 321 exotic snakebites in 300 patients involving 68 different species during this period. Ten patients were bitten on more than one occasion. The majority of patients (64.5%) were male. Most bites were inflicted by snakes of the family Colubridae (184/321, 57.3%); seventeen bites resulted in moderate symptoms (predominantly swelling of the bitten limb). There were 30 (9.3%) bites by Viperidae and 14 (4.3%) bites by Elapidae. All severe cases (n = 15) resulted from bites by either Viperidae (n = 10) or Elapidae (n = 5). Antivenom was given in 17 cases. One fatality was recorded.Conclusions: Despite their low incidence, exotic snakebites present a substantial challenge for UK healthcare professionals. Although rare, these bites typically occur in individuals (usually male) who keep snakes as part of their occupation or hobby and are therefore at risk of multiple bites. Bites can result in venom hypersensitisation and the risk of venom-induced anaphylaxis. Rapid access to expert clinical advice is available in the UK on a 24-hour basis through the National Poisons Information Service and is strongly recommended in all cases of exotic snakebite.

Potential cyanide poisoning reported to the UK national poisons information service: 2008-2019.

INTRODUCTION: Cyanide is a prevalent, lethal chemical. Possible sources of exposure include products of combustion, plant material, industry, chemical warfare and terrorism. METHODS: Retrospective review of UK Poisons Information Database of telephone enquiries to the National Poisons Information Service between 1st January 2008 and 31st December 2019 where cyanide poisoning was considered a possibility. Data extracted included demographics, exposure source, clinical features, Poisoning Severity Score, lactate concentration and antidotes given. RESULTS: A total of 1,252 cases of suspected cyanide poisoning were identified, 239 (19%) involved children under 10 years. The commonest sources of exposure were ingestion of plant material (437 cases; 35%) and smoke inhalation (399; 32%). Smoke inhalation caused the majority of severe and fatal cases (139; 71%). Clinical features associated with fatal outcomes were cardiac arrest (OR 36.4; 95% CI 14.4-92.2), hypotension (15.8; 7.0-35.9), coma (10.8; 5.6-21.0) and lactic acidosis (7.8; 4.1-14.8). 110 patients (9%) were given an antidote and 40 patients (3%) died.Lactate concentrations correlate with Poisoning Severity Score category (r = 0.6, p < 0.0001). Serum lactate <2.0 mmol/L was associated with Poisoning Severity Score None or Minor (sensitivity 76%; specificity 86%) and >11.0 mmol/L was associated with fatal outcome (sensitivity 74%; specificity 80%). 61 cases (5%) had severe carboxyhaemoglobin toxicity (COHb >30%). This was associated with a fatal outcome (OR 7.0; 95% CI 1.5-33.7) and there was positive correlation between carboxyhaemoglobin and Poisoning Severity Score, r = 0.57, p < 0.0001. CONCLUSIONS: Most cases of ingestion of plant material involved children under five years and resulted in no or mild symptoms. In adults smoke inhalation was associated with the most severe poisoning. The lactate cut-off values associated with each severity score calculated in this study are lower than the values used by NPIS on TOXBASE. Analytical conformation of cyanide exposure was unavailable in the majority of case, limiting the strength of these conclusions.

Treating ethylene glycol poisoning with alcohol dehydrogenase inhibition, but without extracorporeal treatments: a systematic review.

CONTEXT: Ethylene glycol is metabolized to toxic metabolites that cause acute kidney injury, metabolic acidemia, and death. The treatment of patients with ethylene glycol poisoning includes competitively inhibiting alcohol dehydrogenase with ethanol or fomepizole to prevent the formation of toxic metabolites, and extracorporeal treatments such as hemodialysis to remove ethylene glycol and its metabolites. In the absence of significant metabolic acidemia or kidney injury, it is hypothesized that extracorporeal treatments may be obviated without adverse outcomes to the patient if alcohol dehydrogenase inhibitors are used. OBJECTIVES: The objectives of this study are to: (1) identify indicators predicting ADH inhibitor failure in patients with ethylene glycol poisoning treated with either ethanol or fomepizole for whom extracorporeal treatment was not performed (aside from rescue therapy, see below) (prognostic study), and (2) validate if the anion gap, shown in a previous study to be the best surrogate for the glycolate concentration, is associated with acute kidney injury and mortality (anion gap study). METHODS: We conducted a systematic review to identify all reported patients with ethylene glycol poisoning treated without extracorporeal treatments but with either fomepizole (fomepizole monotherapy) or ethanol (ethanol monotherapy). Analyses were performed using both one case per patient and all cases (if multiple events were reported for a single patient). Data were compiled regarding poisoning, biochemistry, and outcomes. Treatment failure was defined as mortality, worsening of acid-base status, extracorporeal treatments used as rescue, or a worsening of kidney or neurological function after alcohol dehydrogenase inhibition was initiated. Also, we performed an analysis of previously described anion gap thresholds to determine if they were associated with outcomes such as acute kidney injury and mortality. RESULTS: Of 115 publications identified, 96 contained case-level data. A total of 180 cases were identified with ethanol monotherapy, and 231 with fomepizole monotherapy. Therapy failure was noted mostly when marked acidemia and/or acute kidney injury were present prior to therapy, although there were cases of failed ethanol monotherapy with minimal acidemia (suggesting that ethanol dosing and/or monitoring may not have been optimal). Ethylene glycol dose and ethylene glycol concentration were predictive of monotherapy failure for ethanol, but not for fomepizole. In the anion gap study (207 cases), death and progression of acute kidney injury were almost nonexistent when the anion gap was less than 24 mmol/L and mostly observed when the anion gap was greater than 28 mmol/L. CONCLUSION: This review suggests that in patients with minimal metabolic acidemia (anion gap <28 mmol/L), fomepizole monotherapy without extracorporeal treatments is safe and effective regardless of the ethylene glycol concentration. Treatment failures were observed with ethanol monotherapy which may relate to transient subtherapeutic ethanol concentrations or very high ethylene glycol concentrations. The results are limited by the retrospective nature of the case reports and series reviewed in this study and require prospective validation.

Carbon monoxide exposures reported to the UK National Poisons Information Service: a 4-year study.

BACKGROUND: Unintentional carbon monoxide (CO) poisoning poses a public health challenge. The UK National Poisons Information Service (NPIS) provides advice to healthcare professionals via the online database, TOXBASE®, and a 24-hour telephone line. Our aim was to analyse all CO-related enquiries to the NPIS. METHODS: We analysed enquiries regarding unintentional CO exposure (1st July 2015-30th June 2019). Information on patient demographics, CO source and location, clinical features and poisoning severity was collected from telephone enquiries and TOXBASE accesses. RESULTS: 2970 unintentional non-fire-related CO exposures were reported. Exposures occurred commonly in the home (60%) with faulty boilers frequently implicated (27.4%). Although five fatalities were reported, 68.7% of patients experienced no or minor symptoms only (headache most frequently reported). Despite being the gold standard measurement, blood carboxyhaemoglobin concentration was only recorded in 25.6% patients, with no statistically significant correlation with severity. CONCLUSIONS: Unintentional CO exposures in the UK commonly occur in domestic settings and although are generally of low severity, fatalities continue to occur. Carboxyhaemoglobin measurement is important to confirm exposure but further work is required to assess its validity as a prognostic indicator in CO exposure. Public health policy should continue to focus on raising awareness of the dangers of CO.

Moderate-to-severe Vipera berus envenoming requiring ViperaTAb antivenom therapy in the UK.

BACKGROUND: Bites by the European adder (Vipera berus) in the UK are uncommon but potentially life threatening, and can be associated with marked limb swelling and disability. Following an interruption in Zagreb Imunoloski zavod antivenom supply around 2012, the UK changed its national choice of antivenom for Vipera berus to ViperaTAb, an ovine Fab monospecific antivenom. In the absence of randomised controlled trials, we established an audit to review its use in clinical practice. METHODS: A prospective audit of ViperaTAb use was conducted from March 2016 until November 2020 by the UK National Poison Information Service (NPIS). Users of the NPIS online toxicology database, TOXBASE, considering the use of antivenom for V. berus envenoming were invited to discuss the case with the on-call clinical toxicology consultant. Information was collected prospectively on indications, administration, adverse reactions and outcome of patients administered ViperaTAb antivenom. RESULTS: One hundred and seventy patients were administered ViperaTAb antivenom over five years. One hundred and thirty-two were adults and 38 children (median age and range: 38, 2-87 years). Bites occurred across the UK, but most commonly in coastal regions of Wales and of South-West and East England. Median time to presentation was 2.1 (IQR 1.5-4.0) h and to antivenom administration from presentation was 2.0 (IQR 0.9-3.6) h. A minority of patients presented to hospital more than 12 h after being bitten (n = 19, 11.2%) or received antivenom more than 12 h after presenting to hospital (n = 17, 10.0%). Features of systemic envenoming were present in 64/170 (37.6%) patients, including 23 (13.5%) with anaphylaxis and 26 (15.3%) with hypotension (nine with both). Clinician assessment considered the initial antivenom to have been effective in 122/169 (72.2%) patients. Repeated dosing was common, occurring in 55/169 (32.5%), predominantly due to persisting or worsening local effects (46/51, 90.2%). There were three cases of probable early adverse reaction. No deaths occurred during the study. Complications of envenoming were rare but included four patients that underwent surgery, three patients each with acute kidney injury, mild coagulopathy, or thrombocytopenia (one severe). The median duration of hospital stay was 43.7 (IQR 22.5-66.5) h, longer for children than adults (52.5 vs 41.3 h). CONCLUSION: ViperaTAb antivenom appears to be effective and safe and should be administered as soon as possible for patients meeting clinical criteria. Patients require close observation following antivenom to detect adverse reactions and progression or recurrence of envenoming. Close collaboration with expert NPIS consultant advice can help optimise antivenom timing, ensure repeated dosing is given appropriately, and avoid unnecessary surgical intervention. All hospitals, particularly those located in areas of relatively high incidence, should stock sufficient antivenom available at short notice, 24 h a day.

Safety and Efficacy of the SNAP 12-hour Acetylcysteine Regimen for the Treatment of Paracetamol Overdose.

BACKGROUND: Acetylcysteine (NAC) is effective at preventing liver injury after paracetamol overdose. The Scottish and Newcastle Anti-emetic Pre-treatment for Paracetamol Poisoning (SNAP) Study demonstrated that a 12 h NAC regimen was associated with fewer adverse drug reactions compared with the standard 21 h regimen. Here, we describe the clinical effectiveness of the SNAP NAC regimen. METHODS: The SNAP regimen, consisting of intravenous NAC 100 mg/kg over 2 h then 200 mg/kg over 10 h, was introduced to treat all paracetamol overdose patients at the Royal Infirmary of Edinburgh, the Royal Victoria Infirmary, Newcastle and St Thomas' Hospital, London. Patient data were prospectively and systematically collected before and after the change in treatment (total patients N = 3340, 21 h N = 1488, SNAP N = 1852). Health record linkage was used to determine patient outcome after hospital discharge. FINDINGS: There was no difference in liver injury or liver synthetic dysfunction between regimens. Hepatotoxicity (peak ALT > 1000 U/L) occurred in 64 (4.3%) and 67 (3.6%) patients, respectively, in the 21 h and SNAP groups (absolute difference - 0.7%, 95% CI - 2.1 to 0.6). Multivariable logistic regression did not identify treatment regimen as an outcome-associated factor. No patients were readmitted to hospital with, or died from, liver failure within 30 days of discharge. Anti-histamine treatment (for NAC anaphylactoid drug reactions) was prescribed for 163 (11.0%) patients with the 21 h regimen and 37 (2.0%) patients with the SNAP regimen (absolute difference 9.0% (95% CI 7.3 to 10.7)). INTERPRETATION: In clinical use the SNAP regimen has similar efficacy as standard therapy for preventing liver injury and produces fewer adverse reactions.

Management of poisoning with ethylene glycol and methanol in the UK: a prospective study conducted by the National Poisons Information Service (NPIS).

BACKGROUND: Poisoning with methanol and ethylene glycol can cause serious morbidity and mortality. Specific treatment involves the use of antidotes (fomepizole or ethanol) with or without extracorporeal elimination techniques. METHODS: A prospective audit of patients with methanol or ethylene glycol poisoning reported by telephone to the National Poisons Information Service (NPIS) in the UK was conducted during the 2010 calendar year and repeated during the 2012 calendar year. The study was conducted to determine the frequency of clinically significant systemic toxicity and requirement for antidote use and to compare outcomes and rates of adverse reaction and other problems in use between ethanol and fomepizole. RESULTS: The NPIS received 1315 enquiries involving methanol or ethylene glycol, relating to 1070 individual exposures over the 2-year period. Of the 548 enquiries originating from hospitals, 329 involved systemic exposures (enteral or parenteral as opposed to topical exposure), of which 216 (66%) received an antidote (204 for ethylene glycol and 12 for methanol), and 90 (27%) extracorporeal treatment (86 for ethylene glycol and 4 for methanol). Comparing ethanol with fomepizole, adverse reactions (16/131 vs. 2/125, p < 0.001) and administration errors, lack of monitoring, or inappropriate use (45/131 vs. 6/125, p < 0.0001) were reported more commonly, whereas non-availability and inadequate stocks were reported less commonly (6/125 vs. 33/131, p < 0.0001). Eight fatalities and complications or sequelae occurred in 21 patients. Poor outcome (death, complications, or sequelae) was significantly associated with older age, higher poisoning severity scores, and lower pH on admission (p < 0.001). CONCLUSIONS: Systemic poisoning with ethylene glycol or methanol results in hospitalisation at least 2-3 times per week on average in the UK. No difference in outcome was detected between ethanol and fomepizole-treated patients, but ethanol was associated with more frequent adverse reactions.

Position paper update: whole bowel irrigation for gastrointestinal decontamination of overdose patients.

CONTEXT: A position paper on the use of whole bowel irrigation (WBI) was first published in 1997 by the American Academy of Clinical Toxicology (AACT) and the European Association of Poisons Centres and Clinical Toxicologists (EAPCCT) and updated in 2004. The aims of this paper are to briefly summarize the content of the 2004 Position Paper and to present any new data and recommendations. METHODS: A systematic review of the literature from January 2003 to February 28, 2013 was conducted using multiple online databases for articles concerning WBI for gastrointestinal decontamination. An evidence table was created for applicable articles. The authors produced the initial draft that was reviewed by AACT and EAPCCT. RESULTS: The literature search produced 60 articles with the possibility of applicable human data. Based mainly on volunteer studies, WBI can be considered for potentially toxic ingestions of sustained-release or enteric-coated drugs particularly for those patients presenting later than 2 h after drug ingestion when activated charcoal is less effective. WBI can be considered for patients who have ingested substantial amounts of iron, lithium, or potassium as the morbidity is high and there is a lack of other potentially effective options for gastrointestinal decontamination. WBI can be considered for removal of ingested packets of illicit drugs in "body packers." However, controlled data documenting improvement in clinical outcome after WBI are lacking. WBI is contraindicated in patients with bowel obstruction, perforation, or ileus, and in patients with hemodynamic instability or compromised unprotected airways. WBI should be used cautiously in debilitated patients and in patients with medical conditions that might be further compromised by its use. The concurrent administration of activated charcoal and WBI might decrease the effectiveness of the charcoal. The clinical relevance of this interaction is uncertain. CONCLUSION: WBI can facilitate removal of select toxicants from the gastrointestinal tract in some patients, but there is no convincing evidence from clinical studies that it improves the outcome of poisoned patients. There is no new evidence that would require a major revision of the conclusions of the 2004 position statement.

Patterns of presentation and clinical features of toxicity after reported use of ([2-aminopropyl]-2,3-dihydrobenzofurans), the 'benzofuran' compounds. A report from the United Kingdom National Poisons Information Service.

OBJECTIVE: To characterise the patterns of presentation and clinical features of toxicity following reported recreational use of benzofuran compounds ((2-aminopropyl)-2,3-dihydrobenzofurans) in the UK, as reported to the National Poisons Information Service (NPIS), and to compare clinical features of toxicity with those after reported mephedrone use. METHODS: NPIS patient-specific telephone enquiries and user sessions for TOXBASE(®), the NPIS online information database, related to (2-aminopropyl)-2,3-dihydrobenzofurans and associated synonyms were reviewed from March 2009 to August 2013. These data were compared with those of mephedrone, the recreational substance most frequently reported to NPIS, collected over the same period. RESULTS: There were 63 telephone enquiries concerning 66 patients and 806 TOXBASE(®) user sessions regarding benzofuran compounds during the period of study. The first telephone enquiry was made in July 2010 and the highest numbers of enquiries were received in August 2010 (33 calls, 112 TOXBASE(®) sessions). Patients were predominantly male (82%) with a median age of 29 years; 9 reported co-ingestion of other substances. Comparing the 57 patients who reported ingesting benzofuran compounds alone with 315 patients ingesting mephedrone alone, benzofurans were more often associated with stimulant features, including tachycardia, hypertension, mydriasis, palpitation, fever, increased sweating, and tremor, (72% vs. 38%, odds ratio [OR] 4.2, 95% confidence interval [CI] 2.27-7.85, P < 0.0001) and mental health disturbances (58% vs. 38%, OR 2.3, 95% CI 1.29-4.07, P = 0.006). Other features reported after benzofuran compound ingestion included gastrointestinal symptoms (16%), reduced level of consciousness (9%), chest pain (7%), and creatinine kinase elevation (5%). CONCLUSIONS: Reported ingestion of benzofuran compounds is associated with similar toxic effects to those of amphetamines and cathinones. Mental health disturbances and stimulant features were reported more frequently following reported ingestion of benzofuran compounds than after ingestion of mephedrone.

Mechanistic biomarkers provide early and sensitive detection of acetaminophen-induced acute liver injury at first presentation to hospital.

UNLABELLED: Acetaminophen overdose is a common reason for hospital admission and the most frequent cause of hepatotoxicity in the Western world. Early identification would facilitate patient-individualized treatment strategies. We investigated the potential of a panel of novel biomarkers (with enhanced liver expression or linked to the mechanisms of toxicity) to identify patients with acetaminophen-induced acute liver injury (ALI) at first presentation to the hospital when currently used markers are within the normal range. In the first hospital presentation plasma sample from patients (n = 129), we measured microRNA-122 (miR-122; high liver specificity), high mobility group box-1 (HMGB1; marker of necrosis), full-length and caspase-cleaved keratin-18 (K18; markers of necrosis and apoptosis), and glutamate dehydrogenase (GLDH; marker of mitochondrial dysfunction). Receiver operator characteristic curve analysis and positive/negative predictive values were used to compare sensitivity to report liver injury versus alanine transaminase (ALT) and International Normalized Ratio (INR). In all patients, biomarkers at first presentation significantly correlated with peak ALT or INR. In patients presenting with normal ALT or INR, miR-122, HMGB1, and necrosis K18 identified the development of liver injury (n = 15) or not (n = 84) with a high degree of accuracy and significantly outperformed ALT, INR, and plasma acetaminophen concentration for the prediction of subsequent ALI (n = 11) compared with no ALI (n = 52) in patients presenting within 8 hours of overdose. CONCLUSION: Elevations in plasma miR-122, HMGB1, and necrosis K18 identified subsequent ALI development in patients on admission to the hospital, soon after acetaminophen overdose, and in patients with ALTs in the normal range. The application of such a biomarker panel could improve the speed of clinical decision-making, both in the treatment of ALI and the design/execution of patient-individualized treatment strategies.

National audit of antidote stocking in acute hospitals in the UK.

BACKGROUND: Inadequate stocking of essential antidotes in hospitals for the treatment of poisoned patients has been reported worldwide. Joint National Poisons Information Service (NPIS)/College of Emergency Medicine (CEM) guidelines for antidote stocking in UK emergency departments and acute hospitals were published in 2008. AIM: To determine the impact of these guidelines by surveying the availability of antidotes in acute hospitals in the UK. METHODS: A two-page questionnaire consisting of antidote stocking information was distributed in 2010 to the Chief Pharmacist in all acute hospitals in the UK. The availability of 28 antidotes in the NPIS/CEM antidote guidelines as well as that of Intralipid was surveyed. RESULTS: Surveys were completed for 196 of the 224 (87.5%) hospitals. Over 90% of hospitals had acetylcysteine, activated charcoal, dantrolene, desferrioxamine, naloxone, flumazenil and vitamin K available within the recommended time period. Pralidoxime was reported to be held in only 33% of hospitals, though pralidoxime is supplied by the Department of Health to 95 hospitals in the UK that act as holding centres. Cyproheptadine and viper venom antiserum were held in around 50% of acute hospitals. For the treatment of cyanide and toxic alcohol poisoning, more than one antidote is available. For cyanide poisoning, most hospitals held at least one antidote (usually dicobalt edetate) but 9 (5%) held none of the four antidotes. For toxic alcohol and glycol poisoning, most hospitals held ethanol for intravenous use but not fomepizole and 30 (15%) did not stock any antidote for toxic alcohol poisoning. CONCLUSION: Stocking of less commonly used antidotes is inconsistent. This is likely to result in delayed access to treatment and worse patient outcomes.

Extracorporeal elimination in acute valproic acid poisoning.

INTRODUCTION: Valproic acid (VPA) is an antiepileptic drug that is now used for a variety of neurological and psychiatric indications. Clinical manifestations of severe VPA poisoning include central nervous system depression, hypotension, electrolyte and acid-base disturbances, and hyperammonemia. Although extracorporeal methods have been used to enhance VPA elimination, the indications for and effectiveness of these methods have not been fully characterized. METHODS: A systematic literature search was performed, which identified 31 reports of the use of extracorporeal elimination in VPA poisoning. RESULTS: VPA has a low molecular weight of 144 Da and a low volume of distribution, but at therapeutic concentrations, it is highly protein bound (85-95%). Protein-binding studies during hemodialysis demonstrate that at high VPA concentrations protein binding is saturated, allowing substantial clearance of the free VPA fraction. Case reports consistently show that during hemodialysis the elimination half-life of VPA can be reduced to around 2 h and the enhanced VPA clearance is often associated with improvement clinically. Hemoperfusion also enhances VPA elimination, but its effectiveness may be limited by column saturation. "In-series" hemodialysis and hemoperfusion have been used, but the combination offers little benefit over hemodialysis alone. Continuous renal replacement techniques are increasingly being used although continuous venovenous hemofiltration and continuous venovenous hemodiafiltration do not appear to be as effective as hemodialysis. No controlled trials are available comparing clinical outcomes with or without extracorporeal elimination in VPA poisoning. Novel techniques such as slow low-efficiency dialysis with filtration and supplementation of the dialysate with albumin are being evaluated. INDICATIONS: Extracorporeal methods of elimination should be considered in patients with features of severe VPA poisoning (coma or hemodynamic compromise) and plasma VPA concentration >850 mg/L (coma is more likely to be present at concentrations >850 mg/L), particularly if severe hyperammonemia and electrolyte and acid-base disturbances are present. CONCLUSIONS: Based on limited anecdotal evidence, hemodialysis appears to be the extracorporeal method of choice to enhance VPA elimination in acute poisoning. Controlled, randomized trials are required to better characterize the effect of extracorporeal treatment on clinical outcome.