N-Acetylcysteine treatment of neonatal acetaminophen toxicity caused by transplacental transfer - a case report.

We describe a case of maternal acetaminophen toxicity leading to Caesarean section delivery of a pre-term neonate with acetaminophen-induced hepatic injury and encephalopathy at 33 weeks gestational age. Delayed treatment with N-acetylcysteine (NAC) was initiated in the baby 11 h after delivery, with eventual discharge of a healthy baby at 12 days of age. The baby was treated with a standard but extended duration NAC protocol. Post-operatively, liver biopsy of the mother demonstrated acetaminophen-induced hepatic injury overlying mild hepatic steatosis. This was also managed with NAC therapy leading to complete clinical resolution of acetaminophen induced hepatic injury and discharge on post-operative day 10. This case of delayed NAC therapy for the treatment of pre-term neonatal acetaminophen toxicity is one of very few reported in the literature and can be used as a guide in the management of subsequent cases.

Organ and tissue donation from poisoned patients in the emergency department: A Canadian emergency physician survey.

OBJECTIVES: Screening for organ and tissue donation is an essential skill for emergency physicians. In 2015, 4,631 Canadians were on a waiting list for a transplant, and 262 died while waiting. Canada's donation rates are less than half of comparable countries, so it is essential to explore strategies to improve the referral of donors. Poisoned patients may be one such underutilized source for donation. This study explores physician practices and perceptions regarding the referral of poisoned patients as donors. METHODS: In this cross-sectional unidirectional survey, 1,471 physician members of the Canadian Association of Emergency Physicians were invited to participate. Physicians were presented with 20 scenarios and asked whether they would refer the patient as a potential organ or tissue donor. Results were reported descriptively, and associations between demographics and referral patterns were assessed. RESULTS: Physicians totalling 208 participated in the organ or tissue donation scenarios (14.1%); 75% of scenarios involving poisoning were referred for organ or tissue donation, compared with 92% in a non-poisoning scenario. Poisons associated with lower referrals included sedatives, acetaminophen, chemical exposure, and organophosphates. A total of 175 physicians completed the demographic survey (11.9%). Characteristics associated with increased referrals included previous referral experience, donation training, donation support, >10 years of service, urban practice, emergency medicine certification, and male gender. CONCLUSIONS: Scenarios involving poisoning were referred less often when compared with an ideal scenario. Because poisoning is not a contraindication for referral, this represents a potential source of donors. Targeted training and referral support may help improve donation rates in this demographic.

A system-wide solution to antidote stocking in emergency departments: the Nova Scotia antidote program.

OBJECTIVE: Inadequate stocking of essential antidotes in hospitals is an internationally documented problem. A concrete and sustainable system-wide solution for easy access to antidotes in emergency departments (EDs) was developed and implemented in Nova Scotia, Canada. METHODS: Antidote stocking guidelines and a systemwide antidote management strategy were established. A standardized collection of antidotes housed in highly visible containers in provincial EDs was implemented for timely access. Antidote-specific online administration guidelines were developed. Using the poison centre for surveillance, the antidote program maintained a database of antidote utilization patterns; 11 years of data were available for analysis. RESULTS: 2/2 (100%) tertiary care, 9/9 (100%) regional EDs, and 21/25 (84%) community EDs in Nova Scotia stock antidote kits, for an overall compliance rate of 32/36 (89%). A total of 678 antidotes (excluding N-acetylcysteine) were used for 520 patients. The distribution of antidote use by hospital type was 99/678 (14.6%) at community hospitals, 379/678 (55.9%) at regional hospitals, and 200/678 (29.5%) at tertiary care hospitals. The five most commonly used antidotes were: naloxone 143/678 (21.1%), fomepizole 111/678 (16.4%), glucagon 94/678 (13.9%), calcium 70/678 (10.3%), and sodium bicarbonate 67/678 (9.9%). Of the 520 patients in whom antidotes were used, death occurred in 3% (15/520), major outcomes in 35% (183/520), and moderate outcomes in 39% (205/520). CONCLUSION: The Nova Scotia Antidote Program demonstrates that a solution to inadequate antidote stocking is achievable and requires a system-wide approach with ongoing maintenance and surveillance. The frequency and distribution of antidote usage documented in this program supports the need for enhancement of emergency preparedness. The poison centre and hospital pharmacies are crucial to surveillance and maintenance of this program.

Effect of γ-hydroxybutyrate (GHB) on driving as measured by a driving simulator.

RATIONALE: Gamma-hydroxybutyrate acid (GHB), a GABAB receptor agonist approved for treatment of narcolepsy, impairs driving ability, but little is known about doses and plasma concentrations associated with impairment and time course of recovery. OBJECTIVE: To assess effects of oral GHB (Xyrem®) upon driving as measured by a driving simulator, and to determine plasma concentrations associated with impairment and the time course of recovery. METHODS: Randomized, double-blind, two-arm crossover study, during which 16 participants received GHB 50 mg/kg orally or placebo. GHB blood samples were collected prior to and at 1, 3, and 6 h post dosing. Driving simulator sessions occurred immediately after blood sampling. RESULTS: Plasma GHB was not detectable at baseline or 6 h post dosing. Median GHB concentrations at 1 and 3 h were 83.1 mg/L (range 54-110) and 24.4 mg/L (range 7.2-49.7), respectively. Compared to placebo, at 1 h post GHB dosing, significant differences were seen for the life-threatening outcome collisions (p < 0.001) and off-road accidents (p = 0.018). Although driving was not faster, there was significantly more weaving and erratic driving with GHB as measured by speed deviation (p = 0.002) and lane position deviation (p = 0.004). No significant impairment regarding driving outcomes was found in the GHB group at 3 and 6 h post dose. CONCLUSION: GHB in doses used to treat narcolepsy resulted in severe driving impairment at 1 h post dosing. After 3 to 6 h, there was full recovery indicating that safe driving is expected the next morning after bedtime therapeutic GHB use in the absence of other substances.

Medication-related emergency department visits in pediatrics: a prospective observational study.

BACKGROUND AND OBJECTIVE: There are few data on the rate and characterization of medication-related visits (MRVs) to the emergency department (ED) in pediatric patients. We sought to evaluate the frequency, severity, preventability, and classification of MRVs to the ED in pediatric patients. METHODS: We performed a prospective observational study of pediatric patients presenting to the ED over a 12-month period. A medication-related ED visit was identified by using pharmacist assessment, emergency physician assessment, and an independent adjudication committee. RESULTS: In this study, 2028 patients were enrolled (mean age, 6.1 ± 5.0 years; girls, 47.4%). An MRV was found in 163 patients (8.0%; 95% confidence interval [CI]: 7.0%-9.3%) of which 106 (65.0%; 95% CI: 57.2%-72.3%) were deemed preventable. Severity was classified as mild in 14 cases (8.6%; 95% CI: 4.8%-14.0%), moderate in 140 cases (85.9%; 95% CI: 79.6%-90.8%), and severe in 9 cases (5.5%; 95% CI: 2.6%-10.2%). The most common events were related to adverse drug reactions 26.4% (95% CI: 19.8%-33.8%), subtherapeutic dosage 19.0% (95% CI: 13.3%-25.9%), and nonadherence 17.2% (95% CI: 11.7%-23.9%). The probability of hospital admission was significantly higher among patients with an MRV compared with those without an MRV (odds ratio, 6.5; 95% CI: 4.3-9.6) and, if admitted, the median (interquartile range) length of stay was longer (3.0 [5.0] days vs 1.5 [2.5] days, P = .02). CONCLUSIONS: A medication-related cause was found in ∼1 of every 12 ED visits by pediatric patients, of which two-thirds were deemed preventable. Pediatric patients who present to the ED with an MRV are more likely to be admitted to hospital and when admitted have a longer length of stay.

Nerve blocks for initial pain management of femoral fractures in children.

BACKGROUND: Children and adolescents with femoral fractures are almost always admitted to hospital. They invariably start their hospital experience in the Emergency Department, often requiring transfer to a specialist children's hospital. They require analgesia or anaesthesia so that radiographs can be obtained and for management of their fractures. The initial care process involves from two to six transfers from stretcher to stretcher/imaging/operating-suite table or hospital bed within the first few hours, so prompt pain relief is essential. Systemic analgesia can be provided orally or parenterally. Alternatively, a nerve block may be used where local anaesthetic is injected around a nerve to block sensation or freeze the involved area. OBJECTIVES: To assess the effects (benefits and harms) of femoral nerve block (FNB) or fascia iliaca compartment block (FICB) for initial pain management of children with fractures of the femur (thigh bone) in the pre-hospital or in-hospital emergency setting, with or without systemic analgesia. SEARCH METHODS: We searched the Cochrane Bone, Joint and Muscle Trauma Group Specialised Register (11 January 2013), the Cochrane Central Register of Controlled Trials (2012 Issue 12), MEDLINE (1946 to January Week 1 2013), EMBASE (1980 to 2013 Week 01), Google Scholar (31 January 2013) and trial registries (31 January 2013). We handsearched recent issues of specialist journals and references of relevant articles. SELECTION CRITERIA: Randomised and quasi-randomised controlled trials assessing the effects of FNB or FICB for initial pain management compared with systemic opiates in children (aged under 18 years) with fractures of the femur receiving pre-hospital or in hospital emergency care. Primary outcomes included failure of analgesia at 30 minutes, pain levels during procedures and transfers (e.g. to a stretcher or hospital ward) for up to eight hours, and adverse effects. DATA COLLECTION AND ANALYSIS: Two review authors independently extracted data using a pre-piloted form. Two authors independently assessed the risk of bias for the included study and assessed quality of the evidence for each outcome using the GRADE approach; i.e. as very low, low, moderate or high. Meta-analysis of results was not possible as we found only one trial that could be included in the review. MAIN RESULTS: We included one randomised trial of 55 children aged between 16 months to 15 years. It compared anatomically-guided FICB versus systemic analgesia with intravenous morphine sulphate. The small sample size and the high risk of bias relating to lack of blinding resulted in a low quality rating for all outcomes.Overall, the trial provided low quality evidence for better pain management in the FICB group. Fewer children in the FICB group had analgesia failure at 30 minutes than in the morphine group (2/26 (8%) versus 8/28 (29%); risk ratio (RR) 0.33, 95% confidence interval (CI) 0.09 to 1.20; P value 0.09). The trial did not report on pain during procedures or transfers, or application of analgesia. The trial provided low quality evidence that FICB has a better safety profile than morphine, with only four (15%) reports of redness and pain at the injection site, and no reports of the type of adverse effects of systematic analgesia that occurred in the morphine group, such as respiratory depression (six cases (21%)) and vomiting (four cases (14%)). No long-term adverse events were reported for either intervention. Clinically significant pain relief was achieved in both groups at five minutes; with limited evidence of greater initial pain relief in the FICB group. Based on an inspection of graphically-presented data, at least 46% (12/26) of children in the FICB group had no supplementary medication (mainly analgesia) for the six hours of the study, while only 5% (1 or 2/28) of children in the intravenous morphine group went without additional analgesia. There was insufficient evidence to determine whether child or parental satisfaction with the method of analgesia favoured either method. Resource use was not measured. AUTHORS' CONCLUSIONS: Low quality evidence from one small trial suggests that FICB provides better and longer lasting pain relief with fewer adverse events than intravenous opioids for femur fractures in children. Well conducted and reported randomised trials that compare nerve blocks (both FNB and FICB) with systemic analgesia and that use validated pain scores are needed.

Medication-related emergency department visits and hospital admissions in pediatric patients: a qualitative systematic review.

OBJECTIVE: To review and describe the current literature pertaining to the incidence, classification, severity, preventability, and impact of medication-related emergency department (ED) and hospital admissions in pediatric patients. STUDY DESIGN: A systematic search of PubMED, Embase, and Web of Science was performed using the following terms: drug toxicity, adverse drug event, medication error, emergency department, ambulatory care, and outpatient clinic. Additional articles were identified by a manual search of cited references. English language, full-reports of pediatric (≤18 years) patients that required an ED visit or hospital admission secondary to an adverse drug event (ADE) were included. RESULTS: We included 11 studies that reported medication-related ED visit or hospital admission in pediatric patients. Incidence of medication-related ED visits and hospital admissions ranged from 0.5%-3.3% and 0.16%-4.3%, respectively, of which 20.3%-66.7% were deemed preventable. Among ED visits, 5.1%-22.1% of patients were admitted to hospital, with a length of stay of 24-72 hours. The majority of ADEs were deemed moderate in severity. Types of ADEs included adverse drug reactions, allergic reactions, overdose, medication use with no indication, wrong drug prescribed, and patient not receiving a drug for an indication. Common causative agents included respiratory drugs, antimicrobials, central nervous system drugs, analgesics, hormones, cardiovascular drugs, and vaccines. CONCLUSION: Medication-related ED visits and hospital admissions are common in pediatric patients, many of which are preventable. These ADEs result in significant healthcare utilization.

Intensity of anticoagulation with warfarin and risk of adverse events in patients presenting to the emergency department.

BACKGROUND: The ability of patients receiving warfarin to maintain an international normalized ratio (INR) within the desired therapeutic range is important for both efficacy and risk of adverse events. It is unclear whether the desired INR is maintained in patients receiving warfarin who present to the emergency department (ED) and whether they have a higher rate of adverse events. OBJECTIVE: To evaluate the intensity of anticoagulation with warfarin and the risk of bleeding and thromboembolic complications in patients in the ED. METHODS: A prospective observational study was performed using a convenience sample of patients receiving warfarin and presenting to the ED over an 18-week period. Data were collected using a standardized form that included chief complaint, history of present illness, past medical history, medication history, and allergy status. Information from the physical examination, laboratory results, and other diagnostic tests obtained as part of routine assessment in the ED, was used as necessary. The primary outcome was the proportion of patients whose INR was within, above, or below the desired therapeutic range. Bleeding complications and thromboembolic events were recorded in an attempt to determine the relationship between the intensity of anticoagulation and adverse outcomes. RESULTS: Two hundred one patients were included, with a mean (SD) age of 74.0 (13.2) years; 53.7% were female. Primary indications for warfarin were atrial fibrillation (75.6%) and venous thromboembolic disease (14.9%). A therapeutic INR was observed in 88 patients (43.8%; 95% CI 37.1 to 50.7), while 45 patients (22.4%; 95% CI 17.2 to 28.7) and 68 patients (33.8%; 95% CI 27.6 to 40.6) had subtherapeutic and supratherapeutic INRs, respectively. Overall, there were 28 (18 major and 10 minor) bleeding complications (13.9%; 95% CI 9.8 to 19.4) and 4 thromboembolic events (2.0%; 95% CI 0.6 to 5.2). Among patients with a bleeding complication, 14 (50.0%) had a supratherapeutic INR, while 2 patients who experienced a thromboembolic event (50.0%) had a subtherapeutic INR. CONCLUSIONS: The majority of patients receiving warfarin on presentation to the ED had INRs outside the desired therapeutic range. By establishing the impact of warfarin-related adverse events in this population, focused interventions can be established in this setting to address factors that can be targeted to reduce these events.

L-carnitine for acute valproic acid overdose: a systematic review of published cases.

OBJECTIVE: To review the evidence supporting the efficacy and safety of l-carnitine in the management of acute valproic acid overdose. DATA SOURCES: MEDLINE (1950-May 2010), EMBASE (1980-May 2010), and Google Scholar (to May 2010) were searched, using the terms carnitine, valproic acid, and carnitine for valproic acid overdose. Reference citations from identified publications were reviewed. STUDY SELECTION AND DATA EXTRACTION: Full-text publications evaluating the use of l-carnitine for management of valproic acid overdose in humans were sought. All studies, regardless of design, case series, and case reports reporting efficacy or safety endpoints were included. All languages were included. Two authors extracted primary data elements including patient demographics, presenting features, clinical management, and outcomes. DATA SYNTHESIS: Seven articles discussing 8 patients and 1 reporting safety data from records of 674 patients were reviewed. Reports covered both pediatric and adult patients with acute exposures to valproic acid mono- and polydrug overdose who were treated with various regimens of l-carnitine. All patients recovered clinically and no adverse effects were noted. CONCLUSIONS: Published evidence of the efficacy and safety of l-carnitine as an antidote for acute valproic acid overdose is limited. Based on the available evidence, it is reasonable to consider l-carnitine for patients with acute overdose of valproic acid who demonstrate decreased level of consciousness. We recommend intravenous administration of 100 mg/kg once, followed by infusions of 50 mg/kg (to a maximum of 3 g per dose) every 8 hours thereafter, continuing until ammonia levels are decreasing (if they were elevated initially) and the patient demonstrates signs of clinical improvement or until adverse events associated with l-carnitine occur.