Intravenous Lipid Emulsion does NOT have a role in severe poisoning: CON.

Intravenous lipid emulsion (ILE) has been suggested as a potential universal antidote for cardiovascular and central nervous system toxicity resulting from a multitude of pharmaceutical and nonpharmaceutical poisonings. While there is some evidence to suggest that ILE may have a positive effect in cardiovascular system toxicity after accidental intravenous lipophilic local anaesthetic overdose, this cannot be extrapolated to cases of severe poisoning resulting from oral drug overdose. Treatment recommendations are based upon variable outcome animal studies and low-level clinical evidence with a significant degree of positive reporting bias. Currently, there is a paucity of controlled clinical data to support ILE use to treat severe drug poisoning after oral overdose. ILE use should be limited to well-designed, ethically approved, controlled clinical trials aimed at determining the true effectiveness of this therapy. This should replace the current scattergun clinical use in a multiplicity of poisoning scenarios and subsequent anecdotal reporting approach.

The NACSTOP Trial: A Multicenter, Cluster-Controlled Trial of Early Cessation of Acetylcysteine in Acetaminophen Overdose.

Historically, intravenous acetylcysteine has been delivered at a fixed dose and duration of 300 mg/kg over 20 to 21 hours to nearly every patient deemed to be at any risk for hepatotoxicity following acetaminophen overdose. We investigated a 12-hour treatment regimen for selected low-risk patients. This was a multicenter, open-label, cluster-controlled trial at six metropolitan emergency departments. We enrolled subjects following single or staggered acetaminophen overdose with normal serum alanine transaminase (ALT) and creatinine on presentation and at 12 hours, and less than 20 mg/L acetaminophen at 12 hours. Patients were allocated to intervention (250 mg/kg over 12-hour) or control (300 mg/kg over 20-hour) regimens by site. The primary outcome was incidence of "hepatic injury" 20 hours following initiation of acetylcysteine treatment, defined as ALT doubling and peak ALT greater than 100 IU/L, indicating the need for further antidotal treatment. Secondary outcomes included incidence of hepatotoxicity (ALT > 1,000 IU/L), peak international normalized ratio (INR), and adverse drug reactions. Of the 449 acetaminophen overdoses receiving acetylcysteine, 100 were recruited to the study. Time to acetylcysteine (median 7 hours [interquartile ratio 6,12] versus 7 hours [6,10]) and initial acetaminophen (124 mg/L [58,171] versus 146 mg/L [66,204]) were similar between intervention and control groups. There was no difference in ALT (18 IU/L [13,22] versus 16 IU/L [13,21]) or INR (1.2 versus 1.2) 20 hours after starting acetylcysteine between groups. No patients developed hepatic injury or hepatotoxicity in either group (odds ratio 1.0 [95% confidence interval 0.02, 50]). No patients represented with liver injury, none died, and 96 of 96 were well at 14-day telephone follow-up. Conclusion: Discontinuing acetylcysteine based on laboratory testing after 12 hours of treatment is feasible and likely safe in selected patients at very low risk of liver injury from acetaminophen overdose.

Interventions for escalation of therapy for acute exacerbations of asthma in children: an overview of Cochrane Reviews.

BACKGROUND: Asthma is an illness that commonly affects adults and children, and it serves as a common reason for children to attend emergency departments. An asthma exacerbation is characterised by acute or subacute worsening of shortness of breath, cough, wheezing, and chest tightness and may be triggered by viral respiratory infection, poor compliance with usual medication, a change in the weather, or exposure to allergens or irritants. Most children with asthma have mild or moderate exacerbations and respond well to first-line therapy (inhaled short-acting beta-agonists and systemic corticosteroids). However, the best treatment for the small proportion of seriously ill children who do not respond to first-line therapy is not well understood. Currently, a large number of treatment options are available and there is wide variation in management. OBJECTIVES: Main objective - To summarise Cochrane Reviews with or without meta-analyses of randomised controlled trials on the efficacy and safety of second-line treatment for children with acute exacerbations of asthma (i.e. after first-line treatments, titrated oxygen delivery, and administration of intermittent inhaled short-acting beta2-agonists and oral corticosteroids have been tried and have failed) Secondary objectives - To identify gaps in the current evidence base that will inform recommendations for future research and subsequent Cochrane Reviews - To categorise information on reported outcome measures used in trials of escalation of treatment for acute exacerbations of asthma in children, and to make recommendations for development and reporting of standard outcomes in future trials and reviews - To identify relevant randomised controlled trials that have been published since the date of publication of each included review METHODS: We included Cochrane Reviews assessing interventions for children with acute exacerbations of asthma. We searched the Cochrane Database of Systematic Reviews. The search is current to 28 December 2019. We also identified trials that were potentially eligible for, but were not currently included in, published reviews. We assessed the quality of included reviews using the ROBIS criteria (tool used to assess risk of bias in systematic reviews). We presented an evidence synthesis of data from reviews alongside an evidence map of clinical trials. Primary outcomes were length of stay, hospital admission, intensive care unit admission, and adverse effects. We summarised all findings in the text and reported data for each outcome in 'Additional tables'. MAIN RESULTS: We identified 17 potentially eligible Cochrane Reviews but extracted data from, and rated the quality of, 13 reviews that reported results for children alone. We excluded four reviews as one did not include any randomised controlled trials (RCTs), one did not provide subgroup data for children, and the last two had been updated and replaced by subsequent reviews. The 13 reviews included 67 trials; the number of trials in each review ranged from a single trial up to 27 trials. The vast majority of comparisons included between one and three trials, involving fewer than 100 participants. The total number of participants included in reviews ranged from 40 to 2630. All studies included children; 16 (24%) included children younger than two years of age. Most of the reviews reported search dates older than four years. We have summarised the published evidence as outlined in Cochrane Reviews. Key findings, in terms of our primary outcomes, are that (1) intravenous magnesium sulfate was the only intervention shown to reduce hospital length of stay (high-certainty evidence); (2) no evidence suggested that any intervention reduced the risk of intensive care admission (low- to very low-certainty evidence); (3) the risk of hospital admission was reduced by the addition of inhaled anticholinergic agents to inhaled beta2-agonists (moderate-certainty evidence), the use of intravenous magnesium sulfate (high-certainty evidence), and the use of inhaled heliox (low-certainty evidence); (4) the addition of inhaled magnesium sulfate to usual bronchodilator therapy appears to reduce serious adverse events during hospital admission (moderate-certainty evidence); (5) aminophylline increased vomiting compared to placebo (moderate-certainty evidence) and increased nausea and nausea/vomiting compared to intravenous beta2-agonists (low-certainty evidence); and (6) the addition of anticholinergic therapy to short-acting beta2-agonists appeared to reduce the risk of nausea (high-certainty evidence) and tremor (moderate-certainty evidence) but not vomiting (low-certainty evidence). We considered 4 of the 13 reviews to be at high risk of bias based on the ROBIS framework. In all cases, this was due to concerns regarding identification and selection of studies. The certainty of evidence varied widely (by review and also by outcome) and ranged from very low to high. AUTHORS' CONCLUSIONS: This overview provides the most up-to-date evidence on interventions for escalation of therapy for acute exacerbations of asthma in children from Cochrane Reviews of randomised controlled trials. A vast majority of comparisons involved between one and three trials and fewer than 100 participants, making it difficult to assess the balance between benefits and potential harms. Due to the lack of comparative studies between various treatment options, we are unable to make firm practice recommendations. Intravenous magnesium sulfate appears to reduce both hospital length of stay and the risk of hospital admission. Hospital admission is also reduced with the addition of inhaled anticholinergic agents to inhaled beta2-agonists. However, further research is required to determine which patients are most likely to benefit from these therapies. Due to the relatively rare incidence of acute severe paediatric asthma, multi-centre research will be required to generate high-quality evidence. A number of existing Cochrane Reviews should be updated, and we recommend that a new review be conducted on the use of high-flow nasal oxygen therapy. Important priorities include development of an internationally agreed core outcome set for future trials in acute severe asthma exacerbations and determination of clinically important differences in these outcomes, which can then inform adequately powered future trials.

Pharmacokinetic modelling of modified acetylcysteine infusion regimens used in the treatment of paracetamol poisoning.

PURPOSE: Paracetamol overdose is common and is treated with acetylcysteine to prevent the development of hepatotoxicity. N-acetyl-p-benzoquinone imine (NAPQI) is the toxic metabolite of paracetamol overdose. We aimed to assess the expected acetylcysteine concentration time profiles following delivery of modified acetylcysteine regimens proposed for those at high and low risk of hepatotoxicity. In addition, we will determine acetylcysteine concentrations post-cessation of abbreviated infusions. METHOD: We performed pharmacokinetic simulations using Berkeley Madonna (version 8.3.23.0) comparing the time course of acetylcysteine concentration during and after the cessation of an abbreviated 12-h regimen (250 mg/kg) using a two-bag infusion and compared this to the standard 21-h three-bag (300 mg/kg) regimen. We also simulated extended duration acetylcysteine regimens and other increased dosing strategies that have been recommended in specific paracetamol poisoning scenarios. RESULTS: A more sustained serum concentration is achieved when the acetylcysteine loading dose is delivered over 4 h using the two-bag compared to the 1-h loading dose of the three-bag regimen. When administering an abbreviated 12-h acetylcysteine regimen, circulating acetylcysteine is detectable for 8 h after cessation of the infusion. This may provide a continued hepatoprotective effect if NAPQI is still being generated after the infusion is ceased. CONCLUSION: This pharmacokinetic simulation study is an important step in determining plasma acetylcysteine concentrations that are likely to be achieved using various modified treatment regimens. Importantly, for patients at low risk of liver injury after acute overdose, acetylcysteine is likely to be detectable many hours post-cessation of a 12-h regimen. This should provide a safety factor against development of hepatotoxicity for any ongoing paracetamol metabolism after cessation of the acetylcysteine infusion.

Calcium channel antagonist and beta-blocker overdose: antidotes and adjunct therapies.

Management of cardiovascular instability resulting from calcium channel antagonist (CCB) or beta-adrenergic receptor antagonist (BB) poisoning follows similar principles. Significant myocardial depression, bradycardia and hypotension result in both cases. CCBs can also produce vasodilatory shock. Additionally, CCBs, such as verapamil and diltiazem, are commonly ingested in sustained-release formulations. This can also be the case for some BBs. Peak toxicity can be delayed by several hours. Provision of early gastrointestinal decontamination with activated charcoal and whole-bowel irrigation might mitigate this. Treatment of shock requires a multimodal approach to inotropic therapy that can be guided by echocardiographic or invasive haemodynamic assessment of myocardial function. High-dose insulin euglycaemia is commonly recommended as a first-line treatment in these poisonings, to improve myocardial contractility, and should be instituted early when myocardial dysfunction is suspected. Catecholamine infusions are complementary to this therapy for both inotropic and chronotropic support. Catecholamine vasopressors and vasopressin are used in the treatment of vasodilatory shock. Optimizing serum calcium concentration can confer some benefit to improving myocardial function and vascular tone after CCB poisoning. High-dose glucagon infusions have provided moderate chronotropic and inotropic benefits in BB poisoning. Phosphodiesterase inhibitors and levosimendan have positive inotropic effects but also produce peripheral vasodilation, which can limit blood pressure improvement. In cases of severe cardiogenic shock and/or cardiac arrest post-poisoning, extracorporeal cardiac assist devices have resulted in successful recovery. Other treatments used in refractory hypotension include intravenous lipid emulsion for lipophilic CCB and BB poisoning and methylene blue for refractory vasodilatory shock.

The PICHFORK (Pain in Children Fentanyl or Ketamine) trial: a randomized controlled trial comparing intranasal ketamine and fentanyl for the relief of moderate to severe pain in children with limb injuries.

STUDY OBJECTIVE: We compare the analgesic effectiveness of intranasal fentanyl and ketamine in children. METHODS: This was a double-blind, randomized, controlled trial comparing fentanyl at 1.5 µg/kg with ketamine at 1 mg/kg in children aged 3 to 13 years and weighing less than 50 kg, with isolated limb injury and pain of more than 6 of 10 at triage. The sample size was 40 in each arm. Subjects were coadministered oral ibuprofen at 10 mg/kg. The primary outcome was median pain rating reduction at 30 minutes. Secondary outcomes were pain rating reduction at 15 and 60 minutes, subjective improvement and satisfaction, University of Michigan Sedation Score, adverse events, and rescue analgesia. RESULTS: Eighty children enrolled, and 73 were available for analysis: 37 fentanyl and 36 ketamine. Median age was 8 years; 63% were male children; median baseline pain rating was 80 mm. At 30 minutes, median reductions for ketamine and fentanyl were 45 and 40 mm, respectively (difference 5 mm; 95% confidence interval [CI] -10 to 20 mm). Reductions exceeded 20 mm for ketamine and fentanyl in 82% and 79% of patients, respectively (difference 3%; 95% CI -22% to 16%). Pain rating reduction was maintained to 60 minutes in both groups. Satisfaction was reported for ketamine and fentanyl by 83% and 72% of patients, respectively (difference 11%; 95% CI -9% to 30%). Adverse events, mainly mild, were reported for ketamine and fentanyl by 78% and 40% of patients, respectively (difference 38%; 95% CI -58% to 16%). Three ketamine patients had a moderate degree of sedation by University of Michigan Sedation Score. CONCLUSION: Intranasal fentanyl and ketamine were associated with similar pain reduction in children with moderate to severe pain from limb injury. Ketamine was associated with more minor adverse events.

A retrospective descriptive study of the characteristics of deliberate self-poisoning patients with single or repeat presentations to an Australian emergency medicine network in a one year period.

BACKGROUND: A proportion of deliberate self-poisoning (DSP) patients present repeatedly to the emergency department (ED). Understanding the characteristics of frequent DSP patients and their presentation is a first step to implementing interventions that are designed to prevent repeated self-poisoning. METHODS: All DSP presentations to three networked Australian ED's were retrospectively identified from the ED electronic medical record and hospital scanned medical records for 2011. Demographics, types of drugs ingested, emergency department length of stay and disposition for the repeat DSP presenters were extracted and compared to those who presented once with DSP in a one year period. Logistic regression was used to analyse repeat versus single DSP data. RESULTS: The study determined 755 single presenters and 93 repeat DSP presenters. The repeat presenters contributed to 321 DSP presentations. They were more likely to be unemployed (61.0% versus 39.9%, p = 0.008) and have a psychiatric illness compared to single presenters (36.6% versus 15.5%, p < 0.001). Repeat presenters were less likely to receive a toxicology consultation (11.5% versus 27.3%, p < 0.001) and were more likely to abscond from the ED (7.5% versus 3.4%, p = 0.004). Repeat presenters were more likely to ingest paracetamol and antipsychotics than single presenters. The defined daily dose for the most common antipsychotic ingested, quetiapine, was less in the repeat presenter group (median 1.9 [IQR: 1.3-3.5]) compared with the single presenter group (4 [1.4-9.5]), (OR 0.85, 95% CI 0.74-0.99). CONCLUSION: Patients who present repeatedly to the ED with DSP have pre-existing disadvantages, with increased likelihood of being unemployed and having a mental illness. These patients are also more likely to have health service inequities given the greater likelihood to abscond from the ED and lower likelihood of receiving toxicology consultation for their DSP. Early recognition of repeat DSP patients in the ED may facilitate the development of individualised care plans with the aim to reduce repeat episodes of self-poisoning and subsequent risk of successful suicide.

Has the rescheduling of modified-release paracetamol in Australia affected the frequency of overdoses?

OBJECTIVES: In June 2020, modified-release paracetamol (paracetamol-MR) preparations were up-scheduled from schedule-2 (available in pharmacy) to schedule-3 (available by request to a pharmacist only). The present study aims to ascertain whether up-scheduling affected the frequency of paracetamol-MR overdoses. METHODS: This is a retrospective cohort study of two data sets from 1 June 2017 to 31 May 2022. Monash Health data were extracted using the diagnosis of paracetamol overdose coding and electronic medical records data. Calls regarding paracetamol-MR overdoses to Victorian Poisons Information Centre (VPIC) were extracted from the Poisons centre call database. We used a quasi-experimental research design with interrupted time series analysis to evaluate the immediate impact and change in trend of poisoning-related calls and ED presentations before and after June 2020. The change in proportion of paracetamol-MR cases in both databases was analysed using the Χ2 test. RESULTS: The proportion of paracetamol-MR cases in both data sets did not change. From Monash Health, there was no level change in monthly paracetamol-MR overdose-related presentations following re-scheduling (rate ratio [RR] = 1.08, 95% confidence interval [CI] = 0.57-2.01). There was no change in monthly paracetamol-MR overdose-related calls to VPIC following re-scheduling (RR = 1.05, 95% CI = 0.96-1.14). CONCLUSION: The proportion of paracetamol-MR overdoses did not decrease after the up-scheduling to S3. Similarly, the frequency of overdoses by month remained similar. Further limitations on access to paracetamol products may need to be considered.

Analysis of guideline recommendations for treatment of asthma exacerbations in children: a Pediatric Emergency Research Networks (PERN) study.

RATIONALE: There is significant practice variation in acute paediatric asthma, particularly severe exacerbations. It is unknown whether this is due to differences in clinical guidelines. OBJECTIVES: To describe and compare the content and quality of clinical guidelines for the management of acute exacerbations of asthma in children between geographic regions. METHODS: Observational study of guidelines for the management of acute paediatric asthma from institutions across a global collaboration of six regional paediatric emergency research networks. MEASUREMENTS AND MAIN RESULTS: 158 guidelines were identified. Half provided recommendations for at least two age groups, and most guidelines provided treatment recommendations according to asthma severity.There were consistent recommendations for the use of inhaled short-acting beta-agonists and systemic corticosteroids. Inhaled anticholinergic therapy was recommended in most guidelines for severe and critical asthma, but there were inconsistent recommendations for its use in mild and moderate exacerbations. Other inhaled therapies such as helium-oxygen mixture (Heliox) and nebulised magnesium were inconsistently recommended for severe and critical illness.Parenteral bronchodilator therapy and epinephrine were mostly reserved for severe and critical asthma, with intravenous magnesium most recommended. There were regional differences in the use of other parenteral bronchodilators, particularly aminophylline.Guideline quality assessment identified high ratings for clarity of presentation, scope and purpose, but low ratings for stakeholder involvement, rigour of development, applicability and editorial independence. CONCLUSIONS: Current guidelines for the management of acute paediatric asthma exacerbations have substantial deficits in important quality domains and provide limited and inconsistent guidance for severe exacerbations.

Acetaminophen protein adduct formation following low-dose acetaminophen exposure: comparison of immediate-release vs extended-release formulations.

PURPOSE: Acetaminophen (APAP) protein adducts are a biomarker of APAP metabolism, reflecting oxidation of APAP and generation of the reactive metabolite N-acetyl-p-benzoquinone imine. High levels of adducts correspond to liver toxicity in patients with APAP-related acute liver failure. Adduct formation following low-dose exposure to APAP has not been well studied. APAP protein adducts were measured in blood samples collected from fasted individuals who participated in a crossover study of APAP (80 mg/kg) comparing extended release (ER) and immediate release (IR) formulations. METHODS: Adducts were quantified in all postdose blood samples using a validated high-performance liquid chromatography electrochemical detection (HPLC-EC) assay. RESULTS: Comparison of pharmacokinetic parameters for adducts did not reveal significant differences between ER and IR formulations, with one exception. Formation rates for adducts were faster for IR than the ER formulation (0.420 ± 0.157 vs. 0.203 ± 0.080 1/h), respectively. Maximum plasma concentrations (Cmax) of adducts for IR and ER were 0.108 (±0.020) and 0.100 (±0.028) nmol/ml serum, respectively, and were two orders of magnitude lower than adduct levels previously reported in adults with acute liver failure secondary to APAP. CONCLUSIONS: APAP protein adducts are rapidly formed following nontoxic ingestion of APAP at levels significantly lower than those associated with acute liver failure.

Characteristics of paediatric frequent presenters to an Australian emergency medicine network.

AIM: The study aims to describe the characteristics of paediatric emergency department (ED) patients defined as frequent presenters (FP) presenting to an Australian ED health service and compare these with a cohort of non-frequent presenters (NFP). METHOD: A retrospective chart review utilising an electronic emergency medicine patient medical record database was performed on paediatric patients (18 years or younger) presenting to Monash Health EDs from March 2009 to March 2010. NFPs were defined as patients presenting five or less times and FPs as presenting eight or more times in the study period. Characteristics of both groups were described and compared. RESULTS: During the 12-month study period, there were 130 paediatric FP patients with 839 admissions and 34,262 paediatric NFP patients with 46,043 admissions. FPs to the ED were more likely to be female, utilise the ambulance service to arrive at the hospital and more likely to be admitted to hospital. In particular, FPs were more likely to require admission for a mental health-related problem. They were also more likely to have a discharge diagnosis related to oncology, neurology, respiratory, endocrinology and psychiatric complaints, compared with NFP who were more likely to present with a diagnosis related to injury or trauma. CONCLUSIONS: Paediatric FPs are a vulnerable population with complex multidisciplinary care needs. A holistic approach towards their needs is essential to understanding the reasons for their higher frequency of attendance. By considering all the elements of the child's well-being, the child and family need support to assist in integration with other non-ED service providers. By focusing on wellness and self-management, there is a potential to reduce the reliance on acute emergency care for ongoing chronic health problems.

Evolution in the choice of therapies used to treat latrodectism: Redback spider antivenom or standard analgesic medications. Nothing to rave about.

OBJECTIVES: Redback spider (RBS) antivenom (RBSAV) use appears to have decreased since the results of the RAVE-2 antivenom efficacy study were released. The aims of this study were to assess change in RBSAV use over time and compare responses to treatment for antivenom and other analgesics. METHODS: Retrospective audit of RBS bite referrals to a toxicology unit, from January 2010 to January 2022. Data included demographics, pain severity, treatment (analgesia or RBSAV), response to treatment, re-presentation rate, adverse events, change in antivenom use over time. RESULTS: Of 270 presentations, 157 with moderate or severe pain were included (RBSAV n = 51, analgesia n = 106). Median age was 39 years, n = 81 (51%) female. Those receiving antivenom were more likely to report severe pain n = 46/51 (84%) versus n = 68/106 (58%) (P = 0.006). Eighty-three percent of antivenom doses were administered between 2010 and 2013. Analgesia-only group received various combinations of paracetamol, NSAIDs, and opioids. In those receiving RBSAV, 17/48 (35%), 26/48 (54%), 5/48 (10%) reported a partial, complete or no reduction in pain, respectively, versus 30/77 (39%), 43/77 (58%) and 4/77 (5%), for analgesia-only group. Post-treatment pain was not recorded in three RBSAV and 28 analgesia-only patients. Pain reduction was no different for intravenous and intramuscular antivenom. Re-presentation for ongoing pain was more common in the analgesia-only group, 16/106 (15%) versus 1/51 (2%) for antivenom (P = 0.013). CONCLUSION: Antivenom use fell over the study period. There was no difference in pain relief between RBSAV and analgesia-only groups. RBSAV, regardless of route of administration, was no better than standard analgesics in pain reduction in the present study.

From signal to alert: A cluster of exposures to counterfeit alprazolam tablets containing five novel benzodiazepines.

OBJECTIVE: To illustrate the toxicosurveillance role of the Emerging Drugs Network of Australia - Victoria (EDNAV) project in informing timely harm minimisation interventions. METHODS: Utilisation of an ethics approved clinical registry storing de-identified clinical and analytical data on Victorian ED illicit drug-related presentations. RESULTS: In April 2022, six adults presented to hospital with varying levels of sedation, following the use of counterfeit benzodiazepines. Comprehensive toxicological analysis identified five separate novel benzodiazepines within blood samples from each patient. A public 'Drug Alert' was subsequently issued, and local emergency physicians were notified. CONCLUSION: Toxicosurveillance projects, such as EDNAV, are critical to the continued monitoring and reporting of illicit substance use in the community.

Acute paediatric asthma treatment in the prehospital setting: a retrospective observational study.

OBJECTIVES: To describe the incidence of and patterns of 'escalated care' (care in addition to standard treatment with systemic corticosteroids and inhaled bronchodilators) for children receiving prehospital treatment for asthma. DESIGN: Retrospective observational study. SETTING: State-wide ambulance service data (Ambulance Victoria in Victoria, Australia, population 6.5 million) PARTICIPANTS: Children aged 1-17 years and given a final diagnosis of asthma by the treating paramedics and/or treated with inhaled bronchodilators from 1 July 2019 to 30 June 2020. PRIMARY AND SECONDARY OUTCOME MEASURES: We classified 'escalation of care' as parenteral administration of epinephrine, or provision of respiratory support. We compared clinical, demographic and treatments administered between those receiving and not receiving escalation of care. RESULTS: Paramedics attended 1572 children with acute exacerbations of asthma during the 1 year study period. Of these, 22 (1.4%) had escalated care, all receiving parenteral epinephrine. Patients with escalated care were more likely to be older, had previously required hospital admission for asthma and had severe respiratory distress at initial assessment.Of 1307 children with respiratory status data available, at arrival to hospital, the respiratory status of children had improved overall (normal/mild respiratory distress at initial assessment 847 (64.8%), normal/mild respiratory distress at hospital arrival 1142 (87.4%), p<0.0001). CONCLUSIONS: Most children with acute exacerbations of asthma did not receive escalated therapy during their pre-hospital treatment from ambulance paramedics. Most patients were treated with inhaled bronchodilators only and clinically improved by the time they arrived in hospital.

Non-fatal intoxications involving the novel benzodiazepine clonazolam: case series from the Emerging Drugs Network of Australia - Victoria project.

INTRODUCTION: Clonazolam is an unregistered novel benzodiazepine which emerged in global illicit drug markets in 2014. We describe the clinical features of four cases of non-fatal clonazolam mono-intoxications from patients presenting to emergency departments in Australia. CASES: Four patients aged between 16 and 19 years presented to hospital with a sedative toxidrome (Glasgow Coma Scale range 8-13) and elevated heart rate (median heart rate 100 beats per minute, range 92-105) following reported benzodiazepine exposure. Three patients reported the use of a large quantity (7-20 tablets) of Xanax®, a brand of alprazolam not commercially available in Australia. Two patients required nasopharyngeal airway insertion following the development of airway obstruction. The median time to return of a normal conscious state (Glasgow Coma Scale 15) was 23 h (range 5-30 h). Clonazolam (range 0.2-2.1 µg/L) and its main metabolite 8-aminoclonazolam (range 5.9-19.1 µg/L) were the only substances detected by liquid chromatography-tandem mass spectrometry in blood samples of all patients. CONCLUSION: Clonazolam intoxication resulted in sedation with mild sinus tachycardia. Three patients who reported multiple tablet exposures experienced prolonged sedation, and two of these patients developed airway obstruction. In this series, clonazolam was unknowingly ingested through possible illicit substitution within an unregulated counterfeit benzodiazepine product.