National audit of antidote stocking in UK emergency departments.

BACKGROUND: Previous audits of antidote stocking in UK hospitals have demonstrated variable but improving compliance with joint Royal College of Emergency Medicine and National Poisons Information Service guidance on antidote availability in emergency departments. The guidance was updated in 2017. AIM: To provide a current picture of compliance with the 2017 antidote guidance and compare this to previous audits. METHODS: Questionnaires were distributed to all hospitals in the UK with an emergency department via medicines information and regional pharmacy procurement networks. Data were collected on availability and stock levels of category A (immediately available) and category B (available within 1 hour) antidotes. Additionally, data were collected on holdings of category C (held supra-regionally) antidotes and arrangements for sourcing these if not stocked locally. RESULTS: 233 hospitals were surveyed and 178 replies (76.4%) were received. There were 73 hospitals (41.7%) fully compliant with guidance for category A, 34 hospitals (19.1%) for category B and 18 hospitals (10.1%) for both categories A and B antidotes. Few hospitals stocked category C antidotes (1.1%-34.8%). Evidence of formalised regional holding arrangements for category C antidotes, as advised in the guidance, was noted in some areas but many regions remain without such agreements. CONCLUSIONS: Most hospitals remain not fully compliant with stocking recommendations for categories A and B antidotes, with limited recent improvement. Category C antidotes are stocked by few hospitals although awareness of where these can be sourced appears to be increasing. Emergency departments should review their antidote stocking arrangements to ensure compliance with guidance. Formal arrangements for stocking of the more rarely used category C antidotes at a regional level are also required, where not already in existence, in order to assure their availability in an equitable way across the country.

Modest and variable efficacy of pre-exposure hydroxocobalamin and dicobalt edetate in a porcine model of acute cyanide salt poisoning.

Background: Dicobalt edetate and hydroxocobalamin are widely used to treat hydrogen cyanide poisoning. However, comparative and quantitative efficacy data are lacking. Although post-exposure treatment is typical, it may be possible to administer these antidotes before exposure to first attenders entering a known site of cyanide release, as supplementary protection to their personal protective equipment.Methods: We established an anaesthetised Gottingen minipig model of lethal bolus potassium cyanide (KCN) injection to simulate high dose hydrogen cyanide inhalation. Doses were similar to human lethal doses of KCN. Dicobalt edetate and hydroxocobalamin were administered shortly before KCN and their effect on metabolic and cardiovascular variables and survival time were measured.Results: Increases in arterial lactate were similar after 0.08 and 0.12 mmol/kg KCN. KCN 0.08 mmol/kg was survived by 4/4 animals with moderate cardiovascular effects, while the 0.12 mmol/kg dose was lethal in 4/4 animals, with a mean time to euthanasia of 28.3 (SEM: 13.9) min. Administration of dicobalt edetate (0.021 mmol/kg, 8.6 mg/kg) or hydroxocobalamin (0.054 mmol/kg, 75 mg/kg) at clinically licenced doses had modest effect on lactate concentrations but increased survival after administration of KCN 0.12 mmol/kg (survival: dicobalt edetate 4/4, hydroxocobalamin 2/4) but not 0.15 mmol/kg (0/4 and 0/4, respectively). In a subsequent larger study, doubling the dose of hydroxocobalamin (0.108 mmol/kg, 150 mg/kg) was associated with a modest but inconsistent increased survival after 0.15 mmol/kg KCN (survival: control 0/8, 75 mg/kg 1/10, 150 mg/kg 3/10) likely due to variable pharmacokinetics.Conclusions: In this porcine study of cyanide exposure, with pre-exposure antidote administration, licenced doses of dicobalt edetate and hydroxocobalamin were effective at just lethal doses but ineffective at less than twice the estimated LD50. The efficacy of a rapidly-administered double-dose of hydroxocobalamin was limited by variable pharmacokinetics. In clinical poisoning scenarios, with delayed administration, the antidotes are likely to be even less effective. New antidotes are required for treatment of cyanide exposures appreciably above the minimum lethal dose.

Scottish and Newcastle antiemetic pre-treatment for paracetamol poisoning study (SNAP).

BACKGROUND: Paracetamol (acetaminophen) poisoning remains the commonest cause of acute liver injury in Europe and North America. The intravenous (IV) N-acetylcysteine (NAC) regimen introduced in the 1970s has continued effectively unchanged. This involves 3 different infusion regimens (dose and time) lasting over 20 hours. The same weight-related dose of NAC is used irrespective of paracetamol dose. Complications include frequent nausea and vomiting, anaphylactoid reactions and dosing errors. We designed a randomised controlled study investigating the efficacy of antiemetic pre-treatment (ondansetron) using standard NAC and a modified, shorter, regimen. METHODS/DESIGN: We designed a double-blind trial using a 2 × 2 factorial design involving four parallel groups. Pre-treatment with ondansetron 4 mg IV was compared against placebo on nausea and vomiting following the standard (20.25 h) regimen, or a novel 12 h NAC regimen in paracetamol poisoning. Each delivered 300 mg/kg bodyweight NAC. Randomisation was stratified on: paracetamol dose, perceived risk factors, and time to presentation. The primary outcome was the incidence of nausea and vomiting following NAC. In addition the frequency of anaphylactoid reactions and end of treatment liver function documented. Where clinically necessary further doses of NAC were administered as per standard UK protocols at the end of the first antidote course. DISCUSSION: This study is primarily designed to test the efficacy of prophylactic anti-emetic therapy with ondansetron, but is the first attempt to formally examine new methods of administering IV NAC in paracetamol overdose. We anticipate, from volunteer studies, that nausea and vomiting will be less frequent with the new NAC regimen. In addition as anaphylactoid response appears related to plasma concentrations of both NAC and paracetamol anaphylactoid reactions should be less likely. This study is not powered to assess the relative efficacy of the two NAC regimens, however it will give useful information to power future studies. As the first formal randomised clinical trial in this patient group in over 30 years this study will also provide information to support further studies in patients in paracetamol overdose, particularly, when linked with modern novel biomarkers of liver damage, patients at different toxicity risk. TRIAL REGISTRATION: EudraCT number 2009-017800-10, ClinicalTrials.gov IdentifierNCT01050270.