Stability of N-Acetylcysteine 60 mg/mL in Extemporaneously Compounded Injectable Solutions.

BACKGROUND: N-Acetylcysteine (NAC) administered by the IV route is the current treatment of choice for acetaminophen overdose. However, the protocol approved by health authorities in most countries has a complex dosing regimen, which leads to dosage errors in one-third of cases. Therefore, the Canadian Antidote Guide in Acute Care Toxicology and individual poison centres have begun to recommend a simplified regimen using continuous IV infusion. Unfortunately, no study has demonstrated the stability of IV solutions of NAC at concentrations above 30 mg/mL or in solutions other than 5% dextrose. OBJECTIVE: To evaluate the stability of solutions of NAC 60 mg/mL in 0.9% sodium chloride, 0.45% sodium chloride, or 5% dextrose, stored for up to 72 hours in polyvinyl chloride (PVC) bags at 25°C. METHODS: Solutions of the desired concentration were prepared from a commercial solution of NAC 200 mg/mL, with dilution in 0.9% sodium chloride, 0.45% sodium chloride, or 5% dextrose, and were then stored at room temperature in PVC bags for up to 72 hours. At predetermined time points (0, 16, 24, 40, 48 and 72 h), samples were collected and analyzed using a stability-indicating high-performance liquid chromatography method. A solution was considered stable if it maintained at least 90.0% of its initial concentration. Particulate matter count was also evaluated to confirm chemical stability. Finally, organoleptic properties, such as odour and colour, were evaluated to assess the stability of the solutions. RESULTS: All solutions maintained at least 98.7% of their initial concentration. No obvious changes in odour or colour were observed. Moreover, particle counts remained acceptable throughout the study, according to the criteria specified in United States Pharmacopeia (USP) General Chapter <788>. CONCLUSIONS: NAC 60 mg/mL, diluted in 0.9% sodium chloride, 0.45% sodium chloride, or 5% dextrose and stored in PVC bags at 25°C, was chemically and physically stable for a period of at least 72 hours.

CONTEXTE: La N-acétylcystéine (NAC) administrée par IV est actuellement le traitement de choix en cas de surdose d'acétaminophène. Cependant, le protocole approuvé par les autorités sanitaires de la plupart des pays s'accompagne d'un schéma posologique complexe qui entraîne des erreurs de dosage dans un tiers des cas. C'est pourquoi, le Guide canadien des antidotes en toxicologie d'urgence et les centres antipoison ont commencé à recommander un schéma simplifié utilisant des perfusions IV. Malheureusement, aucune étude n'a permis de démontrer la stabilité des solutions IV de NAC à des concentrations supérieures à 30 mg/mL ou dans des solutions autres que 5 % de dextrose. OBJECTIF: Évaluer la stabilité des solutions de 60 mg/mL de NAC dans 0,9 % de chlorure de sodium, 0,45 % de chlorure de sodium ou 5 % de dextrose, stockées jusqu'à 72 heures dans des pochettes de chlorure de polyvinyle (PVC) à 25 °C. MÉTHODES: Les solutions ont été préparées à partir d'une solution commerciale de 200 mg/mL de NAC, avec une dilution dans 0,9 % de chlorure de sodium, dans 0,45 % de chlorure de sodium ou dans 5 % de dextrose. Elles ont ensuite été stockées à température ambiante dans des pochettes en PVC pendant une période allant jusqu'à 72 h. À des instants prédéterminés (0, 16, 24, 40, 48 et 72 h), des échantillons étaient recueillis et analysés à l'aide d'une méthode de chromatographie en phase liquide à haute performance indiquant la stabilité. Si la solution préservait au moins 90 % de sa concentration initiale, elle était jugée stable. Un comptage de particules a aussi permis de confirmer la stabilité chimique. Finalement, les propriétés organoleptiques, comme l'odeur et la couleur, ont été examinées pour évaluer la stabilité des solutions de NAC. RÉSULTATS: Toutes les solutions préservaient au moins 98,7 % de leur concentration initiale. Aucun changement manifeste d'odeur ou de couleur n'a été observé. De plus, le nombre de particules est resté acceptable pendant toute la durée de l'étude selon les critères indiqués dans le chapitre général de la Pharmacopée américaine (USP) <788>. CONCLUSIONS: La solution de 60 mg/mL de NAC, diluée dans 0,9 % de chlorure de sodium, dans 0,45 % de chlorure de sodium ou dans 5 % de dextrose et stockée dans des pochettes en PVC à 25 °C était chimiquement et physiquement stable pendant au moins 72 h.

Loperamide toxicity: recommendations for patient monitoring and management.

Who: This position statement is a collaborative effort by the American Academy of Clinical Toxicology (AACT) and the American Association of Poison Control Centers (AAPCC) and has been endorsed by the American College of Medical Toxicology (ACMT). The position statement describes loperamide misuse, proposed mechanisms of toxicity, adverse clinical effects, and recommendations for the acute monitoring and management of patients with loperamide toxicity.Why: Use of high-dose loperamide for its euphoric effects and to self-treat opioid use disorder (in place of evidence-based therapies, like buprenorphine or methadone), is increasing. Despite reports in the medical literature and lay press, many remain unaware of high-dose loperamide use and how to manage patients with loperamide-associated toxicities.Target audience: Providers in Emergency Medicine; Prehospital; Intensive Care; Internal Medicine; Primary Care; Gastroenterology; Addiction Medicine; Pharmacy.

Over-the-Counter Drugs and Other Substances Used in Attempted Suicide Presented to Emergency Departments in Montreal, Canada.

Background: Over-the-counter (OTC) analgesics are frequently used in suicide attempts. Accessibility, toxicity, and unsupervised acquisition of large amounts may be facilitators. Aims: To identify patient characteristics associated with OTC drug use as a suicide attempt method among adults. Method: A cross-sectional study was conducted using chart review of all individuals who presented to the emergency department (ED) of two adult general hospitals following a suicide attempt during 2009-2010 in Montreal, Canada. Results: Among the 369 suicide attempters identified, 181 used overdosing, 47% of whom used OTC drugs. In logistic regression, women and those with medical comorbidity were more likely to use overdosing, while those with substance use disorders were less likely to do so. Among those who overdosed, women were more likely to use OTC drugs, while those who were Caucasian, had children, comorbidities, diagnoses with substance use disorders, and made attempts in the Fall were less likely to do so. Substances most frequently used were: acetaminophen among OTC drugs (30%); antidepressants (37%), anxiolytics (30%), opioids (10%), and anticonvulsants (9%) among prescription drugs; and cocaine (10%) among recreational drugs. Limitations: Reasons for the suicide method choice were not available. Conclusion: OTC drugs, in particular acetaminophen, are frequently used in suicide attempts. Accessibility to these drugs may be an important contributor.

Opioid prescribing and dispensing: Experiences and perspectives from a survey of community pharmacists practising in the province of Quebec.

BACKGROUND: Canada leads in opioid prescription and consumption rates, and this has resulted in high levels of opioid-related morbidity and mortality. Pharmacists' input could contribute significantly to understanding the disadvantages of opioid prescribing and dispensing and improving the service. This study aimed to examine the experiences of community pharmacists in relation to opioid prescribing and dispensing, with a focus on optimizing collaboration and communication. METHODS: An online survey was performed among pharmacists from the province of Quebec, Canada, in 2016. Pharmacists were eligible if registered and working in community pharmacies. RESULTS: In all, 542 questionnaires were analyzed (participation rate of 8.1%). Pharmacotherapy-related problems were reported in at least 50% of opioid prescriptions: additional drug(s) required (reported by 30% of pharmacists), interaction(s) between opioid(s) and other drug(s) (16%), physician did not meet the general issuing standards for opioid prescriptions (26%) and patient had mild to moderate pain that was easily managed by a nonopioid analgesic (20%). Half of the patients were reported as requesting anticipated refills, possibly indicating abuse or poor pain control. Most pharmacists (89.6%) reported needing to contact physicians in 1 to 3 out of 10 opioid prescriptions, but many pharmacists (71.8%, often or very often) reported difficulties communicating with physicians. CONCLUSIONS: Pharmacists' observations of pharmacotherapy-related problems and patients' unusual behaviours reveal a significant number of issues related to opioid prescribing and dispensing in an outpatient setting. Improved collaboration between physicians and pharmacists appears mandatory to address the issues reported in this study.

Drug Administration to the Wrong Nursing Home Residents Reported to the Québec Poison Center: A Retrospective Study.

OBJECTIVE: This study examined the association between the administration of drugs to the wrong nursing home residents with a need for hospital treatment or as an indicator of mortality. DESIGN: A retrospective observational study of medical records from February 1, 2016, to January 31, 2017. SETTING: Calls made to the Quebec Poison Center. PARTICIPANTS: Nursing home residents aged ≥65 years. INTERVENTION(S): Medication administered to the wrong resident. MAIN OUTCOME MEASURE(S): Death, hospital referral and treatment, number of drugs or type of drug classes. RESULTS: Of the 6282 calls received by the Quebec Poison Center concerning medication errors, 494 cases were included in the retrospective study. Half of the patients (51%) received at least 5 different drugs that were not prescribed for them. Most patients (82%) were asymptomatic at the time of the call to the poison center; however, a third (34%) of the exposures were considered potentially toxic and were treated at the hospital. The most prominent drug classes involved include antihypertensives, antiarrhythmics, and antipsychotics. In particular, almost a quarter (23%) of cases of clozapine maladministration resulted in moderate or severe effects. No deaths were reported. CONCLUSIONS/IMPLICATIONS: Medication errors in nursing homes are prevalent. The medical provider and probably the poison control center should be consulted as soon as possible when people are aware of administration of medication to the wrong patient, which is considered a medical emergency until proven otherwise. Public policies should seek for better surveillance and prompt intervention. Research should be undertaken to limit errors of drug administration to the wrong nursing home residents.

Opioid Prescribing Practices and Training Needs of Québec Family Physicians for Chronic Noncancer Pain.

AIM: To examine medical practices and training needs of Québec family physicians with respect to pain management and opioid prescription for chronic noncancer pain (CNCP). METHODOLOGY: An online survey was carried out in 2016. RESULTS: Of 636 respondents (43.0% men; 54.3% ≥ 50 years old), 15.2% and 70.9% felt very or somewhat confident that they could properly prescribe opioids for CNCP. Concerns related to abuse (72.5% strongly/somewhat agree), dependence (73.2%), and lack of support (75.4%) were the main barriers reported. Only 19.7% always/often screened their patients for risks of abuse and dependence using a screening tool. About two-thirds of participants (65.7%) had recently (last five years) taken part in continuing education programs on opioid use for CNCP and 73.4% on CNCP management. Patient evaluation and differential diagnoses of chronic pain syndromes were rated as a top priority for further training. CONCLUSIONS: This study provides insights into Québec family physicians' concerns, practices, and needs with respect to the management of CNCP. Physicians' difficulties around the application of strategies to mitigate the problem of opioid abuse and addiction are worrying. The need to better train physicians in the field of pain and addiction cannot be emphasized enough.

Intraosseous administration of antidotes - a systematic review.

CONTEXT: Intraosseous (IO) access is an established route of administration in resuscitation situations. Patients with serious poisoning presenting to the emergency department may require urgent antidote therapy. However, intravenous (IV) access is not always readily available. OBJECTIVE: This study reviews the current evidence for IO administration of antidotes that could be used in poisoning. The primary outcome was mortality as a surrogate of efficacy. Secondary outcomes included hemodynamic variables, electrocardiographic variables, neurological status, pharmacokinetics outcomes, and adverse effects as defined by each article. METHODS: A medical librarian created a systematic search strategy for Medline, subsequently translated to Embase, BIOSIS, PubMed, Web of Science, Cochrane, Database of Abstracts of Reviews of Effects (DARE), and the CENTRAL clinical trial register, all of which we searched from inception to 30 June 2016. Interventions included IO administration of selected antidotes. Articles included volunteer studies, poisoning, or other resuscitation contexts such as cardiac arrest, burns, dehydration, seizure, hemorrhagic shock, or undifferentiated shock. We considered all human studies and animal experiments to the exception of in vitro studies. Two reviewers independently selected studies, and a third adjudicated in case of disagreement. Three reviewers extracted all relevant data. Three reviewers evaluated the risk of bias and quality of the articles using specific scales according to each type of study design. RESULTS: A total of 47 publications (46 articles and one abstract) met our inclusion criteria and described IO administration of 13 different antidotes. These included one case series and 21 case reports describing 26 patients, and 25 animal experiments. Of those, seven human case reports and four animal experiments specifically reported the use of antidotes in poisoning. Human case reports suggested favorable outcomes with IO use of atropine, diazepam, hydroxocobalamin, insulin, lipid emulsion, methylene blue, phentolamine, prothrombin complex concentrate, and sodium bicarbonate. Clinical outcomes varied according to the antidote used. The only reported adverse event was ventricular tachycardia following IO naloxone. Regarding the animal experiments, IO administration of lipid emulsion and of hydroxocobalamin showed improved survival in bupivacaine-poisoned rats and in cyanide-intoxicated swine, respectively. Animal data also suggested an equivalent bio-availability between IO and IV administration for atropine, calcium chloride, dextrose 50%, diazepam, methylene blue, pralidoxime, and sodium bicarbonate. Adverse effect reporting of fat emboli after IO administration of sodium bicarbonate, for example, was conflicting due to the significant heterogeneity in the timing of lung examination across studies. CONCLUSION: The evidence supporting the use of IO route for the administration of antidotes in a context of poisoning is scarce. The majority of the evidence consists of case reports and animal experiments. Common antidotes such as acetylcysteine, fomepizole, and digoxin-specific antibody fragments have not been studied or reported with the use of the IO route. Despite the low-quality evidence available, IO access is a potential option for antidotal treatments in toxicological resuscitation when IV access is unavailable.