Deliberate Self-poisoning with a Lethal Dose of Pentobarbital with Confirmatory Serum Drug Concentrations: Survival After Cardiac Arrest with Supportive Care.

INTRODUCTION: Pentobarbital (PB) is a euthanasia drug in doses of 2 to 10 grams, causing death within 15-30 minutes. We report a case of recovery from lethal pentobarbital deliberate self-poisoning with confirmatory serum drug concentrations. CASE REPORT: A 45-year-old male purchased 20 grams of PB powder over the Internet. He ingested this powder and then alerted his mother 10 minutes later. She found him unresponsive and commenced cardiopulmonary resuscitation (CPR). Within 20 minutes of ingestion, emergency medical services arrived and initiated advanced life support. On arrival to the emergency department, heart rate was 116 bpm, BP 117/62 mmHg, on an epinephrine infusion. He was hypotonic and hypothermic, with absent brainstem reflexes. ECG and CT brain were normal. Activated charcoal was administered and he was admitted to ICU. He remained comatose with absent brainstem reflexes until day 5. Cerebral angiogram on day 3 was normal. Qualitative urine testing detected pentobarbital suggesting ongoing drug effects as the cause of coma. He was extubated on day 10, eventually making a full recovery. At 2.5 hours post-ingestion, PB concentration was 112 mg/L; PB peaked at 116 mg/L at 29 hours; PB was 2 mg/L at 190 hours and undetectable over 200 hours post-ingestion. DISCUSSION: Average PB concentration in fatalities is reported around 30 mg/L. This patient survived higher serum concentrations with early CPR and prolonged cardiorespiratory support in the ICU. Assessment of brainstem death should be deferred until PB has been adequately eliminated.

Paracetamol metabolite concentrations following low risk overdose treated with an abbreviated 12-h versus 20-h acetylcysteine infusion.

CONTEXT: To compare degree of liver injury and paracetamol metabolite concentrations after treatment with standard of care (20-h) vs. abbreviated (12-h) acetylcysteine regimens used in paracetamol overdose (NACSTOP trial). METHODS: Timed blood samples from a cohort of subjects enrolled in the cluster-controlled NACSTOP trial evaluating a 12-h acetylcysteine regimen (200 mg/kg over 4 h, 50 mg/kg over 8 h) were assayed for paracetamol metabolites as a pilot study, using liquid chromatography/mass spectrometry. Control group subjects received a 20-h course of acetylcysteine (200 mg/kg over 4 h, 100 mg/kg over 16 h). The intervention group received a 12-h acetylcysteine regimen (stopped after at least 12 h of treatment). Positive control groups not in the trial with acute liver injury (ALI) or hepatotoxicity were also studied. RESULTS: One hundred and forty-one blood samples were collected from 40 patients receiving acetylcysteine after paracetamol overdose. Median ALT after 20 h of acetylcysteine was 12 U/L (IQR 8.14) in the abbreviated regimen group, compared to the control group 16 U/L (IQR 11.21) (p = .46). There was no significant difference in median metabolite concentrations on presentation and after 20 h of acetylcysteine between these two groups (p > .05). Presentation median sum CYP-metabolite/total metabolite percentages were 2.5 and 3.0 in the abbreviated and control NACSTOP groups, respectively. CONCLUSIONS: An abbreviated 12-h acetylcysteine regimen for paracetamol overdose used in the NACSTOP trial had similar circulating metabolite concentrations compared to a 20-h regimen in selected subjects with low risk of hepatotoxicity. This suggests that further acetylcysteine may not be needed in the abbreviated group at time of cessation.

The use of sustained low efficiency dialysis (SLED) in massive paracetamol overdose.

CONTEXT: Massive paracetamol ingestion causing mitochondrial dysfunction is uncommon. Use of sustained low-efficiency dialysis (SLED) to improve acidaemia and enhance paracetamol elimination has not been previously described. CASE DETAILS: A 44-year-old male presented to the emergency department 2.5 hours post overdose of 200 g (2.5 g/kg) of paracetamol. Examination revealed a BP 85/60 mmHg, pulse 112 bpm, temperature 33.9 °C and blood glucose of 13.9 mmol/l. Venous blood gas 5.5-hours post-ingestion showed a pH 6.9, pCO2 58 mmHg, HCO3 13 mmol/l and lactate 14 mmol/l. Fifty-grams of nasogastric activated charcoal and double-strength intravenous acetylcysteine were administered. Paracetamol concentration peaked at 4207 µmol/l six hours post-ingestion. SLED was commenced nine-hours post ingestion and acetylcysteine dose was doubled again during dialysis. Paracetamol extraction ratio was 47-52%. Plasma paracetamol clearance was steady throughout SLED (53-58 ml/min). Hepatotoxicity did not develop and the patient recovered. DISCUSSIONS: Intermittent hemodialysis (IHD) is more efficient than SLED or continuous renal replacement therapy for enhancing paracetamol elimination and clearance. IHD plasma clearance is reported to range from 36 to 215 ml/min compared with endogenous clearance of 224 ml/70 kg/min. CONCLUSIONS: SLED improved acidaemia with only moderate overall increase in paracetamol plasma clearance. Lack of development of hepatotoxicity was likely the result of early administration of acetylcysteine rather than any effect of SLED on paracetamol elimination.

Do antiemetic drugs benefit adult emergency department patients with nausea? The literature says no, but is it right?

Nausea is a common problem in ED patients. Antiemetic drugs have been used in the ED for decades, but a recent Cochrane review found no convincing evidence for the benefit of antiemetic drugs over placebo. This was largely based on three placebo-controlled trials, which found mean Visual Analog Scale (VAS) changes for various drugs and placebo, to be similar. However, reliance on mean VAS change as the primary outcome measure has probably been a mistake. It does not give information on the number of improved patients, so these cannot be compared between groups. Alternative primary outcome measures warrant further exploration. Use of a VAS cut-off level indicative of clinically significant symptom improvement would allow comparison of numbers of patients with improved nausea ratings. This is proposed as the best option currently available. Preliminary testing of this outcome measure suggests that the conclusions of past studies may be misleading, and that the question of antiemetic efficacy for ED patients is not yet answered.

Treatments for Latrodectism-A Systematic Review on Their Clinical Effectiveness.

Latrodectism or envenomation by widow-spiders is common and clinically significant worldwide. Alpha-latrotoxin is the mammalian-specific toxin in the venom that results in toxic effects observed in humans. Symptoms may be incapacitating and include severe pain that can persist for days. The management of mild to moderate latrodectism is primarily supportive while severe cases have variously been treated with intravenous calcium, muscle relaxants, widow-spider antivenom and analgesic opioids. The object of this systematic review is to examine the literature on the clinical effectiveness of past and current treatments for latrodectism. MEDLINE, EMBASE and Google Scholar were searched from 1946 to December 2016 to identify clinical studies on the treatment of latrodectism. Studies older than 40 years and not in English were not reviewed. There were only two full-publications and one abstract of placebo-controlled randomised trials on antivenom use for latrodectism. Another two randomised comparative trials compared the route of administration of antivenom for latrodectism. There were fourteen case series (including two abstracts), fourteen case reports and one letter investigating drug treatments for latrodectism with the majority of these also including antivenom for severe latrodectism. Antivenom with opioid analgesia is often the major treatment reported for latrodectism however; recent high quality evidence has cast doubt on the clinical effectiveness of this combination and suggests that other treatments need to be investigated.

Methodology for AACT evidence-based recommendations on the use of intravenous lipid emulsion therapy in poisoning.

Intravenous lipid emulsion (ILE) therapy is a novel treatment that was discovered in the last decade. Despite unclear understanding of its mechanisms of action, numerous and diverse publications attested to its clinical use. However, current evidence supporting its use is unclear and recommendations are inconsistent. To assist clinicians in decision-making, the American Academy of Clinical Toxicology created a workgroup composed of international experts from various clinical specialties, which includes representatives of major clinical toxicology associations. Rigorous methodology using the Appraisal of Guidelines for Research and Evaluation or AGREE II instrument was developed to provide a framework for the systematic reviews for this project and to formulate evidence-based recommendations on the use of ILE in poisoning. Systematic reviews on the efficacy of ILE in local anesthetic toxicity and non-local anesthetic poisonings as well as adverse effects of ILE are planned. A comprehensive review of lipid analytical interferences and a survey of ILE costs will be developed. The evidence will be appraised using the GRADE system. A thorough and transparent process for consensus statements will be performed to provide recommendations, using a modified Delphi method with two rounds of voting. This process will allow for the production of useful practice recommendations for this therapy.

Neuroleptic malignant syndrome developing after acute overdose with olanzapine and chlorpromazine.

UNLABELLED: Neuroleptic malignant syndrome (NMS) is a relatively uncommon side effect that may develop after a recent increase in the therapeutic dose of an antipsychotic medication or the addition of a new agent in therapeutic doses. CASE REPORT: We report a case of NMS developing in a 36-year-old female patient 2 days following deliberate self-poisoning with 30 x 10-mg olanzapine tablets, 7 x 100-mg chlorpromazine tablets and an unknown amount of escitalopram. These were the patient's own medications. She had not been taking these for several weeks. The patient initially presented with sedation from her overdose which resolved over the next 24 hours. Following this, over the subsequent 24 hours, she became progressively confused, ataxic, hypertonic, ferbrile and tachycardic, with marked lead pipe rigidity of the limbs. Head CT, lumbar puncture and septic screen were all negative. She was treated with intravenous midazolam infusion, nasogastrically administered bromocriptine, external cooling and was mechanically ventilated. She gradually improved over a period of 10 days, with residual confusion lasting another week, and was discharged well with no deterioration from her premorbid neurologic state. CONCLUSION: To our knowledge, although there are numerous cases reported with therapeutic use, NMS has not been reported to develop following acute olanzapine overdose. Clinicians should be aware that this may be an uncommon side effect of antipsychotic medication.

Pethidine in emergency departments: promoting evidence-based prescribing.

OBJECTIVE: To reduce pethidine prescribing in hospital emergency departments (EDs). DESIGN: Multi-centre drug use evaluation (DUE) process. SETTING AND PARTICIPANTS: Emergency departments in 23 public hospitals (22 in New South Wales, 1 in Victoria) from 1 September 2002 to 31 August 2003. Participating hospitals included seven principal referral hospitals, six major non-teaching hospitals and 10 district or community hospitals. Data for comparison were collected from 12 non-participating hospitals. INTERVENTIONS: Hospital coordinators at each participating hospital were provided with support to implement a range of prescribing interventions in their ED in each of three DUE cycles. Interventions included educational materials (guidelines, posters, prescribing reminders), audit and feedback, and small-group discussions. Three audits of pethidine prescribing were undertaken. Prescribing was compared with evidence-based guidelines and non-concordance identified. MAIN OUTCOME MEASURES: Number of dosage units of parenteral analgesics issued to the ED from each hospital's pharmacy department was recorded monthly and aggregated in 3-month periods. RESULTS: In the 12 months between the preintervention period and the equivalent post-intervention period, pethidine use decreased by 62% in project hospitals (4669 to 1793 units) and 56% in control hospitals (1476 to 648 units). Six months after project completion there was a significantly greater reduction from baseline in participating hospitals (71%; 4669 to 1348 units) compared with non-participating hospitals (64%; 1476 to 532 units; P < 0.001). There was a concurrent increase in use of both morphine and tramadol. CONCLUSION: There was a sustained reduction in pethidine use during the study period, which may indicate successful promotion of safer analgesic prescribing. It is not clear whether changes were a result of collaborative DUE methods or other factors.