Trends in reported GHB-related presentations to Sydney emergency departments between 2012 and 2021.

OBJECTIVES: In overdose, gamma-hydroxybutyrate (GHB) and its precursors can cause decreased levels of consciousness, coma and death. Here, we aim to describe reported exposure to GHB at four EDs in Sydney, New South Wales (NSW), Australia. METHODS: We searched the ED databases of four Sydney metropolitan hospitals for presentations relating to GHB exposure between 2012 and 2021. We calculated annual number of presentations stratified by hospital, age, sex, mode of arrival and triage category. RESULTS: A total of 3510 GHB-related presentations to ED were recorded across the four hospitals. Data for all hospitals were only available from 2015 onwards and between 2015 and 2021; there was a 114% increase in annual presentations (from 228 to 487). Males represented 68.7% of all presentations and the median age was 31 years (range 16-74 years). There was an increase in the proportion of female presentations between 2012 and 2021 (from 27.9% to 37.9%) along with the severity of presentation over the same period, with the proportion of presentations with a triage category 1 increasing from 19.7% to 34.5%. CONCLUSIONS: Increases in recorded absolute number and severity of GHB-related presentations to Sydney EDs are a major public health concern. There may also be shifts in the demographics of those with GHB-related presentations. Renewed efforts are required to understand the drivers of these increases to optimally target harm reduction approaches.

Cognitive impairment following sedative overdose.

INTRODUCTION: Patients with sedative overdose may have residual cognitive impairment at the time they are deemed medically cleared for discharge. Impairment could affect the performance of high-risk activities, including driving. The Trail Making Test is an alpha-numeric assessment that can be performed at the bedside to assess cognitive function. We examined whether there were differences in cognitive function when medically cleared between patients that overdosed on sedative and non-sedative drugs. METHODS: A prospective, observational study assessed cognitive function using the Trail Making Test between 2018 and 2021. Patients (16 years and greater) completed testing upon medical clearance if they spoke English and had no previous neurological injury. Continuous covariates were compared using t-tests or Mann-Whitney U tests and multiple linear regression; binary variables were modelled using logistic regression. RESULTS: Of 171 patients enrolled, 111 (65 per cent) had sedative overdose; they were older (median 32.1 versus 22.2 years) and more likely to be male (58.6 per cent versus 36.7 per cent). Benzodiazepines and paracetamol were the commonest drug overdoses. Patients with sedative overdose performed worse on Trail Making Test part A (37.0 versus 33.1 seconds, P = 0.017) and Trail Making Test part B (112.4 versus 81.5 seconds, P = 0.004). Multiple linear regression analysis indicated that patient age (P < 0.001, 1.7 seconds slower per year, 95 per cent confidence interval: 0.9-2.6 seconds) and perception of recovery (P = 0.006, 36.4 seconds slower if perceived not recovered, 95 per cent confidence interval: 10.8-62.0 seconds) were also associated with Trail Making Test part B times. Patients with sedative overdose were more likely to be admitted to the intensive care unit (Odds Ratio: 4.9, 95 percent confidence interval: 1.1-22.0; P = 0.04). DISCUSSION: Our results are broadly in keeping with previously published work, but include a wider range of drug overdose scenarios (polypharmacy and recreational drugs). While patients demonstrated some perception of their cognitive impairment, our model could not reliably be used to provide individual discharge advice. The study design did not allow us to prove causation of cognitive impairment, or to make comparison between the strength of an overdose to the trail making test time. CONCLUSIONS: Trail Making Test results suggested that patients who had sedative drug overdoses may have significant cognitive deficits even when medically cleared. Risk of harm may be minimised with advice to avoid high-risk activities such as driving. More profound impacts seen on the Trail Making Test part B than A may mean higher-order thinking is more affected than simple cognitive function.

Evaluating Clinical Prediction Rules for Bacteremia Detection in the Emergency Department: A Retrospective Review.

BACKGROUND: Bacteremia is a major cause of morbidity. Blood cultures are the gold standard for diagnosing bacteremia. OBJECTIVE: To compare previously published clinical decision rules for predicting a true positive blood culture (bacteremia) in the emergency department. METHODS: Retrospective analysis of medical records of patients who had a blood culture performed in a tertiary hospital emergency department in 2020 (12 months). Positive blood cultures were compared with randomly selected negative blood cultures (1:4 ratio). Blood cultures were analyzed per patient presentation. Clinical data from patient presentations were extracted and appraised against the modified-Shapiro (mShapiro) rule and systemic inflammatory response syndrome (SIRS) criteria to calculate diagnostic accuracy to detect bacteremia. RESULTS: During the study period, 3870 blood cultures were taken from 2921 patients: 476 (12.3%) cultures were positive for bacterial growth, from 421 individual patient presentations (10 excluded as incomplete data). Of included patients, 338 were true positives and 73 contaminates, these were compared with 1446 patients with negative blood culture presentations. Evaluating mShapiro's rule and SIRS criteria to detect bacteremia vs. no bacteremia (negative + contaminated cultures) had a sensitivity of 94.4% (95% confidence interval [CI] 91.4-96.4%) and 84.9% (95% CI 80.7-88.3%), respectively, and a specificity of 37.9% (95% CI 35.5-40.1%) and 33.8% (95% CI 31.5-36.3%), respectively. Both had a high negative predictive value for bacteremia of 96.8% (95% CI 95.1-98.0) and 91.0% (95% CI 88.3-93.1) for mShapiro's rule and SIRS criteria, respectively. CONCLUSIONS: In this cohort, mShapiro's rule performed better than the SIRS criteria at predicting bacteremia.

Clinical significance of an elevated on-admission beta-hydroxybutyrate in acutely ill adult patients without diabetes.

OBJECTIVE: To determine the relationship between point-of-care ß-hydroxybutyrate (BHB) concentration and outcomes in adult patients without diabetes admitted through ED. METHODS: This was a prospective study from 10 March to 2 July 2021. Admitted patients without diabetes had capillary BHB sampled in ED. Outcomes of length-of-stay (LOS), composite mortality/ICU admission rates and clinical severity scores (Quick Sepsis Organ Failure Assessment score/National Early Warning Score [qSOFA/NEWS]) were measured. BHB was assessed as a continuous variable and between those with BHB above and equal to 1.0 mmol/L and those below 1.0 mmol/L. RESULTS: A total of 311 patients were included from 2377 admissions. Median length-of-stay was 4.1 days (IQR 2.1-9.8), 18 (5.8%) died and 37 (11.8%) were admitted to ICU. Median BHB was 0.2 mmol/L (IQR 0.1-0.4). Twenty-five patients had BHB ≥1.0 mmol/L and five were >3.0 mmol/L. There was no significant difference in median LOS for patients with BHB ≥1.0 mmol/L compared to non-ketotic patients, 5.3 days (IQR 2.2-7.5) versus 4.1 days, respectively (IQR 2.0-9.8) (P = 0.69). BHB did not correlate with LOS (Spearman ρ = 0.116, 95% confidence interval: 0.006-0.223). qSOFA and NEWS also did not differ between these cohorts. For those 25 patients with BHB ≥1.0 mmol/L, an infective/inflammatory diagnosis was present in 11 (44%), at least 2 days of fasting in 10 (40%) and ethanol intake >40 g within 48 h in 4 (16%). CONCLUSIONS: Routine BHB measurement in patients without diabetes does not add to clinical bedside assessment and use should be limited to when required to confirm a clinical impression.

Rivastigmine for the management of anticholinergic delirium.

INTRODUCTION: Anticholinergic agents are commonly taken in overdose, often causing delirium. The spectrum of anticholinergic delirium ranges from mild agitation to severe behavioural disturbance. Physostigmine is an effective treatment for anticholinergic delirium, but its availability is limited. As rivastigmine is readily available, it has been used to manage anticholinergic delirium; however, there is limited research investigating its use. METHOD: This was a retrospective review of patients with anticholinergic delirium treated in two toxicology units with rivastigmine (oral capsule or transdermal patch) from January 2019 to June 2023. The primary outcome was the use of further parenteral treatment (sedation or physostigmine) for delirium post rivastigmine administration. RESULTS: Fifty patients were administered rivastigmine for the management of anticholinergic delirium. The median age was 36 years (interquartile range: 25-49 years) and 27 (54 per cent) were females. Features consistent with anticholinergic toxicity included tachycardia in 44 (88 per cent) and urinary retention requiring catheterisation in 40 (80 per cent). Forty-three patients (86 per cent) were treated with physostigmine before rivastigmine administration. Twenty-two were managed with transdermal rivastigmine (most commonly 9.5 mg/24 hour patch), and 28 with oral rivastigmine 6 mg. Further parenteral sedation and/or physostigmine treatment were required more often in patients given transdermal than oral rivastigmine [16/22 (73 per cent) versus 9/28 (32 per cent), P = 0.010)]. No patients had bradycardia or gastrointestinal symptoms following rivastigmine administration. One patient with a history of epilepsy had a seizure, 1.5 hours post physostigmine administration and 7 hours post transdermal rivastigmine. DISCUSSION: Rivastigmine has been increasingly used for the management of patients with anticholinergic delirium, due to the lack of availability of physostigmine. In this case series, rivastigmine transdermal patch appeared to be less effective than oral rivastigmine capsules, likely due to its slow onset of action and/or insufficient dose. CONCLUSION: Rivastigmine can be used to treat anticholinergic delirium. In our case series oral rivastigmine appeared more effective than transdermal rivastigmine.

Home Therapies to Neutralize Button Battery Injury in a Porcine Esophageal Model.

STUDY OBJECTIVE: Button battery ingestion can cause alkaline esophageal injury. There is interest in first-aid household products to neutralize the injury. The objective was to investigate which household products are effective at reducing button battery injury. METHODS: Two cadaveric porcine experiments were performed. Experiment 1 utilized esophageal mucosal segments. A button battery (3VCR2032) was placed onto the mucosa, and substances (saline control, honey, jam, orange juice, yogurt, milk, and cola) were applied every 10 minutes for 6 applications. Tissue pH was measured every 10 minutes, and macroscopic ulceration size was assessed at 120 minutes. Experiment 2 used an intact esophageal model with a battery inserted into the lumen and jam, honey, and saline irrigation as per experiment 1. Tissue pH, macroscopic and histopathology changes were evaluated at 60, 90 and 120 minutes. RESULTS: In experiment 1, only honey and jam had a lower mean tissue pH at 120 minutes (8.0 [standard deviation [SD] 0.9, n=12] and 7.1 [SD 1.7, n=12], respectively) compared to saline solution 11.9 (SD 0.6, n=6, P<.0001). Both honey (0.24 cm2, SD 0.17) and jam (0.37 cm2, SD 0.40) had smaller mean areas of ulceration compared to saline solution (3.90 cm2, SD 1.03, P<.0001). In experiment 2, honey and jam had significantly lower mean tissue pH at all timepoints compared to saline solution. Histologic changes were evident at 60 minutes in the saline group, whereas honey and jam exhibited no or minimal changes until 120 minutes. CONCLUSIONS: Honey and jam were able to neutralize injury caused by a button battery resulting in a smaller area of ulceration. Jam should be further explored as a possible first-aid option as an alternative to honey in suspected button battery ingestion prior to definitive management.

Intestinal injury in paracetamol overdose (ATOM-8).

BACKGROUND AND AIM: Paracetamol, a widely used medication, is known for its delayed hepatotoxicity in cases of overdose. However, the potential for intestinal toxicity resulting from very high paracetamol concentrations during absorption is not well explored. This study aims to investigate the presence of intestinal toxicity and its correlation with observations in early and late paracetamol toxicity. METHODS: Serial samples of 30 patients with acute paracetamol overdose (> 10 g or 200 mg/kg) were prospectively tested. Markers of enterocyte damage, including plasma intestinal fatty acid binding protein (IFABP) and selected gut-related microRNAs (miR-21, miR-122, miR-194, and miR-215), were analyzed. Sub-analysis was performed on patients presenting with hyperlactatemia defined as a lactate greater than 2 mmol/L within 12 h post ingestion. RESULTS: In paracetamol overdose patients, median plasma IFABP was significantly elevated compared with healthy controls (720 µg/L [interquartile range, IQR, 533-1644] vs 270 µg/L [IQR 153-558], P < 0.001). Four patients had early hyperlactatemia and had significantly higher median plasma IFABP compared with those without early hyperlactatemia (3028 µg/L [IQR 1399-3556] vs 574 µg/L [IQR 526-943], P = 0.007). Furthermore, two microRNAs (miR-122 and miR-215) were downregulated in early hyperlactatemia (P = 0.019 and P = 0.006, respectively). Plasma IFABP concentrations correlated with paracetamol concentration (Spearman's r = 0.55) and lactate (r = 0.60). CONCLUSIONS: Paracetamol overdose causes concentration-related intestinal toxicity, and this is a possible explanation for the early hyperlactatemia syndrome. Intestinal toxicity has potential impacts on pharmacokinetics of other agents ingested and on the evolution of hepatotoxicity. Further studies are required to explore the mechanisms and prognostic implications of intestinal toxicity.

Advances in the understanding of acetaminophen toxicity mechanisms: a clinical toxicology perspective.

INTRODUCTION: Acetaminophen (paracetamol) is a commonly used analgesic and antipyretic agent, which is safe in therapeutic doses. Acetaminophen poisoning due to self-harm or repeated supratherapeutic ingestion is a common cause of acute liver injury. Acetylcysteine has been a mainstay of treatment for acetaminophen poisoning for decades and is efficacious if administered early. However, treatment failures occur if administered late, in 'massive' overdoses or in high-risk patients. AREAS COVERED: This review provides an overview of the mechanisms of toxicity of acetaminophen poisoning (metabolic and oxidative phase) and how this relates to the assessment and treatment of the acetaminophen poisoned patient. The review focuses on how these advances offer further insight into the utility of novel biomarkers and the role of proposed adjunct treatments. EXPERT OPINION: Advances in our understanding of acetaminophen toxicity have allowed the development of novel biomarkers and a better understanding of how adjunct treatments may prevent acetaminophen toxicity. Newly proposed adjunct treatments like fomepizole are being increasingly used without robust clinical trials. Novel biomarkers (not yet clinically available) may provide better assessment of these newly proposed adjunct treatments, particularly in clinical trials. These advances in our understanding of acetaminophen toxicity and liver injury hold promise for improved diagnosis and treatment.

What is the utility of blood beta-hydroxybutyrate measurements in emergency department in patients without diabetes: a systematic review.

BACKGROUND: Ketones are synthesised as an alternative fuel source during times of energy restriction. In the absence of a hyperglycemic emergency, ketosis in patients presenting to the emergency department (ED) may indicate reduced carbohydrate intake. In the perioperative setting, excess fasting with ketosis is associated with worse outcomes; however, whether ketosis in patients without diabetes presenting to ED is also associated with worse outcomes is unclear. This systematic review aims to examine the evidence for ketosis in predicting the need for hospital admission in patients without diabetes, presenting to the ED. METHODS: A systematic review was performed using PRISMA guidelines. We searched electronic bases (OVID-Medline, OVID-EMBASE, Scopus and PubMed) up to December 2022. Eligible studies included children or adults without diabetes presenting to the ED where a point-of-care capillary beta-hydroxybutyrate (BHB) was measured and compared to outcomes including the need for admission. Outcome measures included need for admission and length of stay. Content analysis was performed systematically; bias and certainty assessed using standard tools. RESULTS: The literature search found 17,133 citations, 14,965 papers were subjected to title and abstract screening. The full text of 62 eligible studies were reviewed. Seven articles met the inclusion criteria. Six studies were conducted solely in the paediatric population, and of these, four were limited to children presenting with gastroenteritis symptoms. Median BHB was higher in children requiring hospital admission with an AUC of 0.64-0.65 across two studies. There was a weak correlation between BHB and dehydration score or duration of symptoms. The single study in adults, limited to stroke presentations, observed no relationship between BHB and neurological deficit at presentation. All studies were at risk of bias using the Newcastle-Ottawa Scale and was assessed of "very low" to "low" quality due to their study design in the Grading of Recommendations, Assessment, Development and Evaluation (GRADE) approach. Heterogeneity amongst selected studies precluded meta-analysis. CONCLUSION: The evidence for any utility of BHB measurement in the ED in absence of diabetes is limited to the paediatric population, specifically children presenting with symptoms of gastroenteritis. Any role in adults remains unexplored.

Acetaminophen Metabolites on Presentation Following an Acute Acetaminophen Overdose (ATOM-7).

Acetaminophen (APAP) is commonly taken in overdose and can cause acute liver injury via the toxic metabolite NAPQI formed by cytochrome (CYP) P450 pathway. We aimed to evaluate the concentrations of APAP metabolites on presentation following an acute APAP poisoning and whether these predicted the subsequent onset of hepatotoxicity (peak alanine aminotransferase > 1,000 U/L). The Australian Toxicology Monitoring (ATOM) study is a prospective observational study, recruiting via two poison information centers and four toxicology units. Patients following an acute APAP ingestion presenting < 24 hours post-ingestion were recruited. Initial samples were analyzed for APAP metabolites, those measured were the nontoxic glucuronide (APAP-Glu) and sulfate (APAP-Sul) conjugates and NAPQI (toxic metabolite) conjugates APAP-cysteine (APAP-Cys) and APAP-mercapturate (APAP-Mer). The primary outcome was hepatotoxicity. In this study, 200 patients were included, with a median ingested dose of 20 g, 191 received acetylcysteine at median time of 5.8 hours post-ingestion. Twenty-six patients developed hepatotoxicity, one had hepatotoxicity on arrival (excluded from analysis). Those who developed hepatotoxicity had significantly higher total CYP metabolite concentrations: (36.8 µmol/L interquartile range (IQR): 27.8-51.7 vs. 10.8 µmol/L IQR: 6.9-19.5) and these were a greater proportion of total metabolites (5.4%, IQR: 3.8-7.7) vs. 1.7%, IQR: 1.3-2.6, P < 0.001)]. Furthermore, those who developed hepatotoxicity had lower APAP-Sul concentrations (49.1 µmol/L, IQR: 24.7-72.2 vs. 78.7 µmol/L, IQR: 53.6-116.4) and lower percentage of APAP-Sul (6.3%, IQR: 4.6-10.9 vs. 13.1%, IQR, 9.1-20.8, P < 0.001)]. This study found that those who developed hepatotoxicity had higher APAP metabolites derived from CYP pathway and lower sulfation metabolite on presentation. APAP metabolites may be utilized in the future to identify patients who could benefit from increased acetylcysteine or newer adjunct or research therapies.

Poisonings from hydrocarbon inhalant misuse in Australia.

BACKGROUND AND AIMS: Inhalational misuse of volatile substances has been a significant public health concern because of the risk of sudden death and associated chronic complications such as encephalopathy. The Australian Government released a Consensus-based clinical practice guideline in 2011 on the management of volatile substance use in Australia, which noted a lack of available data particularly on harms. This study aimed to measure (1) the number of calls received by the New South Wales Poisons Information Centre (NSWPIC) regarding inhalational hydrocarbon exposures or poisonings and (2) the number of unintentional deaths reported to the National Coronial Information System (NCIS) in Australia. DESIGN, SETTING, CASES, MEASUREMENTS: We performed a retrospective review of all recreational inhalational hydrocarbon exposure calls to the NSWPIC between 1 January 2010 and 31 December 2020. A search was made of the NCIS database in all states and territories over the same period to determine the number of non-intentional inhalational hydrocarbon-related deaths in Australia. FINDINGS: Between January 2010 and December 2020, there were 752 primary calls made to the NSWPIC regarding hydrocarbon use or exposure. Age or age bracket was recorded in 748 cases, with 508 (67%) calls involving children or adolescents. Over the same time, there were 58 unintentional deaths involving the recreational use of inhalational hydrocarbons. The median age at death was 23 years (interquartile range = 15-30 years), and 72% (42 cases) were male. Cause of death was predominately acute suffocation/asphyxia, encephalopathy related to chronic use, cardiac arrest likely from sudden sniffing syndrome or thermal injuries secondary to unintentional fires sparked by the volatile agents. CONCLUSION: Although death and cardiac arrest are uncommon among people in Australia who misuse hydrocarbons for recreational use, the deaths and cardiac arrests tend to occur in adolescents.

Triage to electrocardiogram sign-off time in patients with acute coronary syndrome at a metropolitan Sydney hospital.

OBJECTIVE: To compare the time from triage to ECG sign-off in patients with acute coronary syndrome, before and after the introduction of an electronic medical record-integrated ECG workflow system (Epiphany). Additionally, to assess for any correlation between patient characteristics and ECG sign-off times. METHODS: A retrospective, single-centre cohort study was performed at Prince of Wales Hospital, Sydney. Patients were included if they were over 18 years, presented to Prince of Wales Hospital ED during 2021, had an ED diagnosis code of 'ACS', 'UA', 'NSTEMI' or 'STEMI' and were subsequently admitted under the cardiology team. ECG sign-off times and demographic data were compared between patients presenting prior to 29 June (pre-Epiphany group) and those presenting after (post-Epiphany group). Those without ECGs signed-off were excluded. RESULTS: There were 200 patients (100 each group) included in the statistical analysis. There was a significant decrease in the median triage to ECG sign-off time, from 35 min (IQR 18-69) pre-Epiphany, to 21 min (IQR 13-37) post-Epiphany. There were only 10 (5%) patients in the pre-Epiphany group and 16 (8%) in the post-Epiphany group, who had ECG sign-off times less than the 10-min. There was no correlation between gender, triage category, age or time of shift with triage to ECG sign-off time. CONCLUSIONS: The introduction of the Epiphany system has significantly reduced the triage to ECG sign-off time in the ED. Despite this, there remains a large proportion of patients with acute coronary syndrome who do not have an ECG signed-off within the guideline-recommended 10 min.

Clean the skin: Reducing blood culture contamination in the emergency department.

OBJECTIVE: To determine whether blood culture contamination (BCC) rates could be decreased in the ED by an educational programme. METHODS: Educational intervention focusing on a 1-min venepuncture cleaning time and providing a larger chlorhexidine alcohol swab. BCC rates were examined retrospectively 12-month pre-, and 9-month post-intervention. RESULTS: Six thousand nine hundred and fifty-three blood cultures were collected over the study period. The BCC rate was 2.4% pre-intervention versus 1.8% post-intervention, with no significant difference in BCC rates (Z-score = 1.862, P = 0.063). CONCLUSION: This educational intervention focusing on skin clean time did not significantly decrease BCC rates in a setting of an already low (<3%) BCC rate.

Tapentadol exposures and poisonings in Australia.

INTRODUCTION: Tapentadol is an atypical opioid with mu-receptor affinity and noradrenaline reuptake inhibition approved for use in Australia in 2011. However, data on tapentadol poisoning are scarce. OBJECTIVES: To investigate tapentadol poisonings and related deaths in Australia. METHODS: We performed a retrospective review of tapentadol poisonings from New South Wales Poisons Information Centre (NSWPIC) and three toxicology units in Australia. The National Coronial Information System (NCIS) database was searched to determine the number of tapentadol-related deaths. RESULTS: Between 2016 and 2020, 220 tapentadol calls were made to NSWPIC, with a 4.5-fold increase in tapentadol exposure calls. The median dose ingested was 575 mg (IQR: 300-1163 mg). Most overdoses included co-ingestions (75%), especially benzodiazepines (26%) and opioids (25%). From Jan 2016 to Dec 2021, 107 patients presented to the three toxicology units with tapentadol poisoning. The median dose ingested was 500 mg (IQR: 200-1400 mg). Most patients took co-ingestants (84%), including benzodiazepines (40%) and opioids (32%). Naloxone was administered in 39 patients (36%), 10 (9%) were intubated and the median length of stay was 18 h (IQR: 9-30). Thirty-five tapentadol-related deaths were recorded within NCIS between Jan 2015 and Oct 2021 with a median age of 51 years (IQR: 42-61 years). CONCLUSION: There are increasing tapentadol poisonings and deaths reported to the NSWPIC, three toxicology units, and NCIS in Australia. Most tapentadol poisonings were taken with benzodiazepines and/or other opioids.

Prescribing trend of tapentadol in a Sydney local health district.

AIMS: Tapentadol, an opioid with mu-opioid receptor agonism and noradrenaline reuptake inhibition, has been increasingly used in Australia since 2011. However, data on hospital prescribing trends and indications are scarce. This study aimed to investigate hospital prescribing trends of tapentadol, oxycodone and tramadol in a Sydney local health district (LHD) and the indications for tapentadol hospital prescriptions in an Australian tertiary hospital. METHODS: We analysed 5-year patient dispensing for tapentadol, oxycodone and tramadol from four hospitals in a Sydney LHD with data expressed as oral morphine equivalents (OME). We also conducted a retrospective review of 140 and 54 patients prescribed tapentadol at a tertiary hospital's surgical and spinal units in 2020. RESULTS: Over 5 years in the Sydney LHD, there was a 19.5% reduction in total dispensing of these opioids from 1 225 210 to 986 477.5 OME milligrams. Decreases were specifically for oxycodone (-37.8% immediate-release, -65.2% sustained-release) and tramadol (-74.6% immediate-release, -70.1% sustained-release). Contrastingly, hospital prescriptions of tapentadol immediate-release increased by 223.2% between 2018-19 and 2020-21 while sustained-release increased by 17.9% from 2016-17 to 2020-21. By 2020-21, tapentadol overtook oxycodone to become the most prescribed opioid in the Sydney LHD (51.4%). At the hospital's surgical units, 137 (97.9%) patients were prescribed tapentadol for acute post-operative pain with the majority (54.0%) prescribed both immediate-release and sustained-release tapentadol, while 71.1% were prescribed for neuropathic pain in the spinal units. CONCLUSION: In a Sydney LHD, tapentadol prescriptions increased significantly to become the preferred opioid analgesic. At the hospital's surgical units, off-label prescriptions of tapentadol sustained-release for acute post-operative pain were observed.

Delayed Acetaminophen Absorption Resulting in Acute Liver Failure.

Introduction. Acetaminophen is a common medication involved in deliberate and accidental self-poisoning. The acetaminophen treatment nomogram is used to guide acetylcysteine treatment. It is rare to develop hepatotoxicity with an initial acetaminophen concentration below the nomogram line. We present a case of acetaminophen ingestion with an initial concentration below the nomogram line that developed hepatic failure, due to a delayed peak acetaminophen concentration secondary to coingesting medications that slow gastric emptying. Case Report. A 43-year-old (55 kg) female presented after ingesting an unknown quantity of acetaminophen, clonidine, and alcohol. Her acetaminophen level was 41 mg/L (256 µmol/L) at 4.5 h post-ingestion, well below the nomogram line, and ALT was 25 U/L. Hence, acetylcysteine was not commenced. She was intubated for decreased level of conscious. A repeat acetaminophen level 4 h later was 39 mg/L (242 µmol/L), still below the nomogram line. She was extubated 24 h later.At 38 h post-ingestion she developed abdominal pain, the repeat acetaminophen level was 85 mg/L (560 µmol/L), ALT was 489 U/L, and acetylcysteine was commenced. The patient developed hepatic failure with a peak ALT of 7009 U/L and INR of 7.5 but made a full recovery. It was discovered that she had ingested a combination acetaminophen product containing dextromethorphan and chlorphenamine. Acetaminophen metabolites were measured, including nontoxic glucuronide and sulfate conjugates and toxic cytochrome P450 (CYP) metabolites. The metabolite data demonstrated increasing CYP metabolites in occurrence with the delayed acetaminophen peak concentration. Discussion. Opioids and antimuscarinic agents are known to delay gastric emptying and clonidine may also have contributed. These coingested medications resulted in delayed acetaminophen absorption. This case highlights the issue of altered pharmacokinetics when patients coingest gut slowing agents.

Too much of a good thing: Bicarbonate toxicity following treatment of sodium channel blocker overdose.

Although sodium bicarbonate can be a life-saving antidote for patients with overdoses resulting in sodium channel blockade, there has been a concerning rise in cases referred to the Poisons Information Centre where inappropriately large doses of bicarbonate have been used resulting in iatrogenic harm. We present a series of three clinical cases where excessive bicarbonate was used to treat poisonings and discuss our approach to managing cardiotoxicity secondary to sodium channel blockade. Serial blood gas analysis should be performed when using bicarbonate to ensure pH targets are met and severe alkalaemia, hypernatraemia and hypokalaemia are avoided. We encourage clinicians to contact the Poisons Information Centre (13 11 26) or their local clinical toxicologist when managing patients with life-threatening sodium channel blockade.