Conj Assoc Prof Ingrid Berling

Although rare, snake envenoming can occur in patients presenting to GPs or hospitals in rural areas, where specialists and laboratory resources may be limited. Improved treatment guidelines and access to expert telephone advice have enabled an improved approach to the treatment of snakebite, with a focus on early clinical assessment and identifying signs and symptoms of systemic envenoming, rather than the type of snake involved, to guide early decision-making about antivenom treatment.

Objective: Recreational gamma-hydroxybutyrate (GHB) use is rising in Australia. We aimed to describe ED presentation patterns related to GHB over time and the impact this has on ED resource use. Methods: Retrospective review of prospective data collection from two clinical toxicology units based in Queensland and New South Wales. Results: There were 751 GHB-related presentations to the two units (Newcastle, 127; Princess Alexandria, 624), with marked increases in presentations occurring in 2019 and 2023. The major intervention was intubation, with 95 (13%) patients intubated. Conclusion: GHB presentations to ED are rising and the impact on acute bed space and clinical resources is significant.

Ethylene glycol (EG) is metabolized into glycolate and oxalate and may cause metabolic acidemia, neurotoxicity, acute kidney injury (AKI), and death. Historically, treatment of EG toxicity included supportive care, correction of acid¿base disturbances and antidotes (ethanol or fomepizole), and extracorporeal treatments (ECTRs), such as hemodialysis. With the wider availability of fomepizole, the indications for ECTRs in EG poisoning are debated. We conducted systematic reviews of the literature following published EXTRIP methods to determine the utility of ECTRs in the management of EG toxicity. The quality of the evidence and the strength of recommendations, either strong ("we recommend") or weak/conditional ("we suggest"), were graded according to the GRADE approach. A total of 226 articles met inclusion criteria. EG was assessed as dialyzable by intermittent hemodialysis (level of evidence = B) as was glycolate (Level of evidence = C). Clinical data were available for analysis on 446 patients, in whom overall mortality was 18.7%. In the subgroup of patients with a glycolate concentration = 12¿mmol/L (or anion gap = 28¿mmol/L), mortality was 3.6%; in this subgroup, outcomes in patients receiving ECTR were not better than in those who did not receive ECTR. The EXTRIP workgroup made the following recommendations for the use of ECTR in addition to supportive care over supportive care alone in the management of EG poisoning (very low quality of evidence for all recommendations): i) Suggest ECTR if fomepizole is used and EG concentration > 50¿mmol/L OR osmol gap > 50; or ii) Recommend ECTR if ethanol is used and EG concentration > 50¿mmol/L OR osmol gap > 50; or iii) Recommend ECTR if glycolate concentration is > 12¿mmol/L or anion gap > 27¿mmol/L; or iv) Suggest ECTR if glycolate concentration 8¿12¿mmol/L or anion gap 23¿27¿mmol/L; or v) Recommend ECTR if there are severe clinical features (coma, seizures, or AKI). In most settings, the workgroup recommends using intermittent hemodialysis over other ECTRs. If intermittent hemodialysis is not available, CKRT is recommended over other types of ECTR. Cessation of ECTR is recommended once the anion gap is < 18¿mmol/L or suggested if EG concentration is < 4¿mmol/L. The dosage of antidotes (fomepizole or ethanol)¿needs to be adjusted during ECTR.

Objective: To evaluate the Assistant in Medicine (AiM) programme and its impact on physician burden and productivity in the ED. Methods: Calvary Mater Newcastle ED employed eight final year medical students as part-time AiMs for a 10-week period from October to December 2021. Each student worked one 10-h shift per week. During these shifts, AiMs were assigned to a supervising doctor postgraduate year 3 or above to assist them with tasks including documentation, patient reviews, hospital consults, procedures, and discharge preparation. At the conclusion of each shift, the supervising doctor completed an online questionnaire of their experience. Results: Forty-seven responses were received. Thirty-six doctors (77%) felt they were able to see more patients in comparison to an average shift without an AiM and 40 doctors (85%) felt that having an AiM increased their overall productivity. Forty-five doctors (96%) supported the implementation of final year medical students as AiMs as a permanent addition to the medical workforce in the ED. Conclusion: The present study demonstrates the strong potential the AiM programme has to improve productivity, workflow and efficiency in the ED.

Toxicity from gabapentin and pregabalin overdose is commonly encountered. Treatment is supportive, and the use of extracorporeal treatments (ECTRs) is controversial. The EXTRIP workgroup conducted systematic reviews of the literature and summarized findings following published methods. Thirty-three articles (30 patient reports and 3 pharmacokinetic studies) met the inclusion criteria. High gabapentinoid extracorporeal clearance (>150 mL/min) and short elimination half-life (<5 hours) were reported with hemodialysis. The workgroup assessed gabapentin and pregabalin as "dialyzable" for patients with decreased kidney function (quality of the evidence grade as A and B, respectively). Limited clinical data were available (24 patients with gabapentin toxicity and 7 with pregabalin toxicity received ECTR). Severe toxicity, mortality, and sequelae were rare in cases receiving ECTR and in historical controls receiving standard care alone. No clear clinical benefit from ECTR could be identified although major knowledge gaps were acknowledged, as well as costs and harms of ECTR. The EXTRIP workgroup suggests against performing ECTR in addition to standard care rather than standard care alone (weak recommendation, very low quality of evidence) for gabapentinoid poisoning in patients with normal kidney function. If decreased kidney function and coma requiring mechanical ventilation are present, the workgroup suggests performing ECTR in addition to standard care (weak recommendation, very low quality of evidence).

Background: ß-adrenergic antagonists (BAAs) are used to treat cardiovascular disease such as ischemic heart disease, congestive heart failure, dysrhythmias, and hypertension. Poisoning from BAAs can lead to severe morbidity and mortality. We aimed to determine the utility of extracorporeal treatments (ECTRs) in BAAs poisoning. Methods: We conducted systematic reviews of the literature, screened studies, extracted data, and summarized findings following published EXTRIP methods. Results: A total of 76 studies (4 in vitro and 2 animal experiments, 1 pharmacokinetic simulation study, 37 pharmacokinetic studies on patients with end-stage kidney disease, and 32 case reports or case series) met inclusion criteria. Toxicokinetic or pharmacokinetic data were available on 334 patients (including 73 for atenolol, 54 for propranolol, and 17 for sotalol). For intermittent hemodialysis, atenolol, nadolol, practolol, and sotalol were assessed as dialyzable; acebutolol, bisoprolol, and metipranolol were assessed as moderately dialyzable; metoprolol and talinolol were considered slightly dialyzable; and betaxolol, carvedilol, labetalol, mepindolol, propranolol, and timolol were considered not dialyzable. Data were available for clinical analysis on 37 BAA poisoned patients (including 9 patients for atenolol, 9 for propranolol, and 9 for sotalol), and no reliable comparison between the ECTR cohort and historical controls treated with standard care alone could be performed. The EXTRIP workgroup recommends against using ECTR for patients severely poisoned with propranolol (strong recommendation, very low quality evidence). The workgroup offered no recommendation for ECTR in patients severely poisoned with atenolol or sotalol because of apparent balance of risks and benefits, except for impaired kidney function in which ECTR is suggested (weak recommendation, very low quality of evidence). Indications for ECTR in patients with impaired kidney function include refractory bradycardia and hypotension for atenolol or sotalol poisoning, and recurrent torsade de pointes for sotalol. Although other BAAs were considered dialyzable, clinical data were too limited to develop recommendations. Conclusions: BAAs have different properties affecting their removal by ECTR. The EXTRIP workgroup assessed propranolol as non-dialyzable. Atenolol and sotalol were assessed as dialyzable in patients with kidney impairment, and the workgroup suggests ECTR in patients severely poisoned with these drugs when aforementioned indications are present.

Background: The assessment and management of patients with QT interval prolongation in poisoning requires an appropriate method of measuring and adjusting the QT interval for the heart rate (HR) in order to decide if the patient is at risk of life-threatening dysrhythmias, notably torsade de pointes (TdP). As the Clinical Toxicology Collaborative (CTC) workgroup reviewed the published literature on drug-induced QT interval prolongation in poisoning, it became obvious that many publications were missing essential data that were necessary to thoroughly assess and compare the evidence. The aim of this guidance document is to identify essential and ideal criteria required when reporting a case of drug-induced QT interval prolongation and/or TdP in poisoning. Methods: We employed a mixed methods approach as follows. Initially, we reviewed 188 cases of available published case reports and series in the literature regarding drug-induced QT interval prolongation and/or TdP in poisoning as the first step to another project. Common features and deficiencies were identified. Given the large gaps in reporting quality, we conducted an iterative consultative process involving all 23 members of the CTC to identify essential and ideal criteria to analyse publications of QT interval prolongation in poisoning. A priori standards were developed for acceptance or rejection of individual criteria. Results: Survey response was 100%. A minimum set of essential criteria for reporting cases of QT interval prolongation and drug-induced TdP in overdose setting are provided and a 35-item checklist is presented. Conclusions: We report a QT reporting checklist to ensure published case reports and series describing drug-induced QT interval prolongation in poisoning can contribute to the fund of knowledge of QT interval prolongation, TdP and other malignant dysrhythmias.

Context: Inpatient toxicology services undertake remote as well as inpatient management of poisoned patients. The aim of this study is to describe the introduction of a tablet-based electronic data collection tool allowing data to be captured on inpatient and remote consultations. Methods: Retrospective review of all cases entered in the database from 1 March 2014 to 28 February 2016. Data collected included demographics (age, sex), clinical details (exposure category), presentation facility and disposition. Results: The database included 3616 cases: 59 (1.6%) were excluded due to inadequate details, 122 (3.4%) had no electronic medical record available, 1985 (54.9%) presented to the inpatient unit facility and 1450 (40.1%) were external consultations. Of these 1450, 223 (6.2%) were paediatric (aged less than 12¿years), 395 (10.9%) adolescent (12¿17¿years) and 832 (23.0%) adults (18¿years and over). The proportion of paediatric cases (median age 2¿y; 45.7% females) with pharmaceutical ingestions was 122 (54.7%; 95% confidence intervals (CIs): 48.2¿61.1) compared with 345 (87.3%; 95% CI: 83.7¿90.3) in adolescents (median age 15¿y; 79.5% females). Of the adult presentations, 659 (18.2%) were metropolitan/regional facility presentations and 173 (4.8%) rural facilities with 125 (3.4%) adults subsequently transferred to the inpatient facility. Median age was 38¿years (interquartile range (IQR) 35¿52) with 338 (51.4%) females in the metropolitan group and 37¿years (IQR 26¿48) with 51 (30.5%) females in the rural group. There were more bites and stings in the rural group, 41 (23.7%; 95% CI: 18.0¿30.6) versus 54 (8.2%; 95% CI: 6.3¿10.5), more recreational substance exposures 27 (15.6%; 95% CI: 11.0¿21.8) versus 40 (6.1%; 95% CI: 4.5¿8.2) and less pharmaceutical exposures 93 (53.8%; 95% CI: 46.3¿61.0) versus 462 (70.1%; 95% CI: 66.5¿73.5). Conclusions: The tablet based database provided useful information on populations of poisoned patients not accessible previously. It demonstrated important differences in the types of patients presenting to rural versus metropolitan hospitals.

Objectives: There is an increased rate of sudden cardiac death (SCD) in mental health patients. Some antipsychotic medications are known to prolong the QT interval, thus increasing a patient's risk of SCD via the arrhythmia, torsades de pointes (TdP). Our aim was to evaluate assessment for QT prolongation within a public inpatient mental health facility by auditing electrocardiograph (ECG) use. Methods: We reviewed records of all mental health inpatient admissions to a public emergency mental health inpatient unit between 1 January 2016 and 11 February 2016. ECG availability was noted and QT interval was manually measured and assessed for risk of TdP using the QT nomogram when present. Demographic information and medication use was collected. Results: Of 263 mental health inpatient admissions, 50 (19%) presentations had an ECG. A total of four (8%) had a prolonged QT interval. Of the 50 patients with an ECG, 12 (24%) were taking medication known to prolong the QT interval. Conclusions: There was very limited risk assessment for QT prolongation in a public hospital psychiatric inpatient unit, with less than 20% of patients having an ECG performed. Our study supports an association between QT-prolonging drugs and a clinically significant prolonged QT interval; however, a larger study with routine ECG screening is required.

Context: The current 3-phase acetylcysteine infusion for paracetamol poisoning delivers half the dose over 15-60 min and frequently results in adverse reactions. Objective: We aimed to determine adverse reaction frequency with a modified 2-phase infusion protocol with a longer initial infusion. Materials and methods: A prospective observational study of a modified 2-phase acetylcysteine protocol was undertaken at two hospitals. Acetylcysteine was commenced on admission and ceased if paracetamol concentrations were low-risk (below the nomogram line). The first infusion was 200 mg/kg over 4-9 h based on ingestion time or 4 h for staggered/chronic ingestions. The second infusion was 100 mg/kg over 16 h. Pre-defined outcomes were frequency of adverse reactions (systemic hypersensitivity reactions or gastrointestinal); proportion with alanine transaminase (ALT) > 1000 U/L or abnormal ALT. Results: 654 paracetamol poisonings were treated with the new protocol; median age 29 y (15-98 y); 453 females; 576 acute and 78 staggered/chronic ingestions. In 420 (64%) acetylcysteine was stopped for low-risk paracetamol concentrations. An adverse reaction occurred in 229/654 admissions (35%; 95% CI: 31-39%): 173 (26.5%; 95% CI: 23-30%) only gastrointestinal, 50 (8%; 95% CI: 6-10%) skin only systemic hypersensitivity reactions; and three severe anaphylaxis (0.5%; 95% CI: 0.1-1.5%; all hypotension). Adverse reactions occurred in 111/231 (48%) receiving full treatment compared to 116/420 (28%) in whom the infusion was stopped early (absolute difference 20%; 95% CI: 13-28%; p < 0.0001). In 200 overdoses < 10 g, one had toxic paracetamol concentrations, but 53 developed reactions. Sixteen patients had an ALT > 1000 U/L and 24 an abnormal ALT attributable to paracetamol; all but one had treatment commenced >12 h post-ingestion. Conclusion: A 2-phase acetylcysteine infusion protocol results in a fewer reactions in patients with toxic paracetamol concentrations, but is not justified in patients with low-risk paracetamol concentrations.

Aims: Morbidity and mortality from drug overdose has decreased over three decades. This is credited to safer drugs and therefore better outcomes in overdose. We aimed to investigate changing prescriptions of antipsychotic medications and associated changes in antipsychotic overdoses over a 26-year period. Methods: All antipsychotic poisoning presentations to a tertiary referral toxicology unit between 1987 and 2012 were reviewed. Data were collected prospectively on demographics, ingestion information, clinical effects, complications and treatment. Rates of antipsychotic drug use in Australia were obtained from Australian government publications for 1990¿2011 and linked to overdose admissions by postcode. Results: There were 3180 antipsychotic overdoses: 1235 first generation antipsychotics, 1695 'atypical' second generation antipsychotics and 250 lithium overdoses. Over 26 years, antipsychotic overdoses increased 1.8-fold, with first generation antipsychotics decreasing to one-fifth of their peak (¿80/year to 16) and second generation antipsychotics increasing to double this (¿160/year), olanzapine and quetiapine accounting for 78%. All antipsychotic overdoses had a median length of stay of 18.6 h, 15.7% admitted to intensive care unit, 10.4% ventilated and 0.13% died in hospital, which was the same for first generation compared to second generation antipsychotics. There was a 2.3-fold increase in antipsychotic prescriptions over the same period; first generation antipsychotics declined whereas there was a dramatic rise in second generation antipsychotics, mainly olanzapine, quetiapine and risperidone (79%). Conclusion: Over 26 years there was an increase in antipsychotic prescribing associated with an increase in antipsychotic overdoses. Although the type of antipsychotics changed, the morbidity and mortality remained the same, so that antipsychotics are an increasing proportion of overdose admissions.

Background: Marine stings are common but most are minor and do not require medical intervention. Severe and systemic marine envenoming is uncommon, but includes box jellyfish stings, Irukandji syndrome, major stingray trauma and blue-ringed octopus envenoming. Almost all marine injuries are caused by jellyfish stings, and penetrating injuries from spiny fish, stingrays or sea urchins. Objective: This article describes the presentation and management of marine envenomations and injuries that may occur in Australia. Discussion: First aid for jellyfish includes tentacle removal, application of vinegar for box jellyfish, and hot water immersion (45°C for 20 min) for bluebottle jellyfish stings. Basic life support is essential for severe marine envenomings that result in cardiac collapse or paralysis. Irukandji syndrome causes severe generalised pain, autonomic excess and minimal local pain, which may require large amounts of analgesia, and, uncommonly, myocardial depression and pulmonary oedema occur. Penetrating marine injuries can cause significant trauma depending on location of the injury. Large and unclean wounds may have delayed healing and secondary infection if not adequately irrigated, debrided and observed.

Hematologic abnormalities are the most common effects of snake envenoming globally. Venom-induced consumption coagulopathy (VICC) is the commonest and most important. Other hematologic abnormalities are an anticoagulant coagulopathy and thrombotic microangiopathy. Venom-induced consumption coagulopathy is a venom-induced activation of the clotting pathway by procoagulant toxins, resulting in clotting factor consumption and coagulopathy. The type of procoagulant toxin differs between snakes and can activate prothrombin, factor X, and factor V or consume fibrinogen. The most useful investigation in VICC is a prothrombin time/international normalized ratio. The d-dimer may assist in early diagnosis, but fibrinogen levels often add little in the clinical setting. Bedside investigations would be ideal, but point-of-care testing international normalized ratio and whole blood clotting tests have been shown to be unreliable in VICC. The major complication of VICC is hemorrhage, including intracranial hemorrhage which is often fatal. The role of antivenom in VICC is controversial and may only be beneficial for some types of snakes including Echis spp where the duration of abnormal clotting is reduced from more than a week to 24 to 48 hours. In contrast, antivenom does not appear to speed the recovery of VICC in Australian snake envenoming. Other treatments for VICC include factor replacement, observation and prevention of trauma, and heparin. An Australian study showed that fresh-frozen plasma speeds recovery of VICC, but early use may increase consumption. There is no evidence to support heparin.

Case report. We report a fatal case of a 37 year old gentleman who ingested a MCPA/bromoxynil co-formulation herbicide. Although clinically well on initial examination, our patient declined dramatically over his 18 h admission with increasing CO2 production, hyperthermia and metabolic derangement to eventually die from cardiac asystole 20 h post ingestion. Two hours after ingestion the MCPA concentration was 83.9 µg/mL and bromoxynil concentration was 137 µg/mL. Discussion. The patients' mechanism of death appeared to be uncoupling of oxidative phosphorylation, excess CO2 production and hyperthermia. There is limited knowledge on the acute toxicity of these herbicides, in particular bromoxynil, and this case highlights the relentless progression of severe toxicity in humans.

Intracranial haemorrhage (ICH) is a rare life-threatening consequence of venom induced consumption coagulopathy in snake-bite. It is unclear why certain patients haemorrhage. We aimed to investigate ICH in snake envenoming. Cases of venom-induced consumption coagulopathy from July 2005-June 2014 were identified from the Australian Snakebite Project, a prospective multicentre cohort of snake-bites. Cases with venom-induced consumption coagulopathy were extracted with data on the snake-bite, clinical effects, laboratory investigations, treatment and outcomes. 552 cases had venom-induced consumption coagulopathy; median age, 40 y (2-87 y), 417 (76%) males, 253 (46%) from brown snakes and 17 died (3%). There were 6/552 (1%) cases of ICH; median age, 71 y (59-80 y), three males and five from brown snakes. All received antivenom and five died. All six had a history of hypertension. Time to onset of clinical effects consistent with ICH was 8-12 h in four cases, and within 3 h in two. Difficult to manage hypertension and vomiting were common. One patient had a normal cerebral CT on presentation and after the onset of focal neurological effects a repeat CT showed an ICH. ICH is rare in snake-bite with only 1% of patients with coagulopathy developing one. Older age and hypertension were associated with ICH.

Study objective: Antipsychotic drugs are frequently reported to cause QT prolongation and torsade de pointes. We aim to investigate the potential risk of torsade de pointes in antipsychotic overdose by assessing the QT interval with the QT nomogram. Methods: All presentations to a toxicology service between January 1987 and May 2013 were reviewed. Admissions with single ingestions of an antipsychotic greater than maximum daily dose were extracted. Demographics, dose, ECG, and outcomes (arrhythmias and death) were obtained. QT intervals in multiple leads were manually measured and the median taken. QT-heart rate (QT-HR) pairs were plotted on the QT nomogram and defined as prolonged if above the abnormal line. The QTcF (Fridericia's HR correction) was calculated and compared with dose. Results: From 2,356 antipsychotic overdoses, 494 were included. There were no abnormal QT-HR pairs in 4 aripiprazole, 31 pericyazine, 14 trifluoperazine, and 7 haloperidol overdoses. Abnormal QT intervals occurred in 9 of 16 amisulpride overdoses (56%; 95% confidence interval [CI] 31% to 79%), 16 of 57 thioridazine overdoses (28%; 95% CI 17% to 42%), and 5 of 29 chlorpromazine overdoses (17%; 95% CI 7% to 36%). Abnormal QT intervals occurred in 5 of 41 risperidone overdoses (12%; 95% CI 5% to 27%), 10 of 202 quetiapine overdoses (5%; 95% CI 3% to 9%), and 2 of 76 olanzapine overdoses (3%; 95% CI 0.5% to 10%), but there was no correlation between dose and QTcF, and most abnormal QT intervals were at fast HR. An additional 186 single antipsychotic ingestions with noncardiotoxic coingestants had similar proportions of abnormal QT. There was 1 case of torsade de pointes in a thioridazine overdose. Conclusion: There appeared to be significant risk of QT prolongation with amisulpride and thioridazine overdoses. Although there were abnormal QT intervals for quetiapine, olanzapine, and risperidone overdoses, they were associated with tachycardia and not dose dependent, and so were unlikely to be associated with increased torsade de pointes risk.

Context. Toxicity from recreational substances marketed for other purposes is a well-documented clinical entity. We present two cases of phenibut toxicity procured via the internet. Case Details. A 20-year-old female presented to the emergency department (ED) having used phenibut the prior day. The main finding was a decreased level of consciousness, however when roused she became delirious. Supportive care only was required with no specific intervention. The patient made a full recovery over a 24-hour period and admitted to use of phenibut purchased online. Plasma phenibut concentration was 29.7 µg/ml. A 38-year-old male presented to ED with an agitated delirium. The prior evening he had used tetrahydrocannabinol or THC, alcohol and phenibut, the latter purchased via the internet. His behavioural state had a suboptimal response to parenteral sedation. He was subsequently intubated for airway protection in the context of ongoing sedation to optimally manage his behavioural state. Post extubation the next morning he admitted using phenibut. Plasma phenibut concentration was 36.5 µg/ml. Discussion. Altered mental status was the predominant manifestation of phenibut toxicity in these cases. Clinicians to be aware of how phenibut toxicity may present as the internet has widened access to such substances.

Objectives: Measuring the QT interval on an electrocardiogram (ECG) is integral to risk assessment of Torsade de Pointes (TdP). This study aimed to investigate the accuracy of the 1/2 RR rule as a risk assessment tool for drug-induced TdP, comparing it to the QT nomogram, Bazett's corrected QT (QTcB), and Fridericia's corrected QT (QTcF). Methods: The authors calculated sensitivity and specificity of the 1/2 RR rule using a published data set of 129 cases of drug-induced TdP and 316 controls (noncardiotoxic overdoses), compared to the QT nomogram, QTcB > 500 msec and QTcF > 500 msec. To further determine the value of the 1/2 RR rule, its observed positive, and negative agreement were calculated when compared to the QT nomogram for determining an abnormal QT in eight samples of different drugs in overdose. Results: The sensitivity and specificity of the 1/2 RR rule were 88% (95% confidence interval [CI] = 80% to 93%) and 53% (95% CI = 47% to 58%), respectively, compared to the QT nomogram (sensitivity = 97%, 95% CI = 92% to 99%; specificity = 99%, 95% CI = 97% to 100%). It was also less sensitive than QTcB > 500 msec and had a lower specificity than QTcB > 500 msec and QTcF > 500 msec. In drug overdose patients, the 1/2 RR rule had poor observed agreement averaging 41%, which was mainly due to poor positive agreement, except for amisulpride where there was good agreement. Conclusions: The 1/2 RR rule was not as sensitive as the QT nomogram or QTcB > 500 msec for drug-induced TdP. It had poor positive agreement in almost all overdose patients, resulting in over half of patients receiving unnecessary cardiac monitoring and repeat ECGs.