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Biomedical subjects

G K Isbister

Publications and source records attributed to G K Isbister.

At least 19 recordsLinked to original sources

An in vivo examination of the stability of venom from the Australian box jellyfish Chironex fleckeri.

We have previously characterised the pharmacological activity of a number of jellyfish venoms with a particular emphasis on the profound cardiovascular effects. It has been suggested that jellyfish venoms are difficult to work with and are sensitive to pH, temperature and chemical changes. The current study aimed to examine the working parameters of the venom of the Australian box jellyfish Chironex fleckeri to enable fractionation and isolation of the toxins with cardiovascular activity. C. fleckeri venom was made up fresh each day and subjected to a number of different environments (i.e. a pH range of 5-9 and a temperature range of 4-30 degrees C). In addition, the effect of freeze drying and reconstituting the venom was investigated. Venom (50 microg/kg, i.v.) produced a transient hypertensive response followed by cardiovascular collapse in anaesthetised rats. This biphasic response was not significantly effected by preparation of the venom at a pH of 5, 7 or 9. Similarly, venom (50 microg/kg, i.v.) did not display a loss of activity when exposed to temperatures of 4, 20 or 30 degrees C for 1.5h. However, the cardiovascular activity was abolished by boiling the venom. Freeze drying, and then reconstituting, the venom did not significantly affect its cardiovascular activity. However, repeated freeze drying and reconstituting of extracted venom resulted in a significantly loss of activity. This study provides a more detailed knowledge of the parameters in which C. fleckeri venom can be used and, while supporting some previous studies, contradicts some of the perceived problems of working with the venom.

Animals↗

Collett's snake (Pseudechis colletti) envenoming in snake handlers.

BACKGROUND: Collett's snake (Pseudechis colletti) is a member of the black snake genus and occurs in a warm temperate to sub-tropical region of central Queensland, Australia. There are no reports of bites occurring in the wild, and bites were previously thought to cause only minor effects. They are a popular snake among zoos and exotic snake keepers. AIM: To investigate the clinical effects of severe envenoming by Collett's snake, and possible treatment options. DESIGN: Case series. METHODS: Clinical and laboratory features are described for six bites, all in snake handlers. RESULTS: All six bites were from captive snakes, resulting in severe envenoming in four. Two patients were treated early with black snake antivenom, and only developed an anticoagulant coagulopathy and mild myolysis. Two developed anticoagulant coagulopathy and severe rhabdomyolysis associated with acute renal failure, requiring haemodialysis; both received antivenom >10 h after the bite, and initially received minimal fluid replacement. Other effects included thrombocytopenia, non-immune haemolytic anaemia and a marked leukocytosis. DISCUSSION: Collett's snake envenoming is characterized by early generalized systemic effects (nausea, vomiting, abdominal pain, diarrhoea and headache) and an anticoagulant coagulopathy, followed in some cases by rhabdomyolysis and acute renal failure in untreated patients within 24 h. Early initiation of fluid therapy and treatment with black snake antivenom should be undertaken in all envenomed patients.

Acute Kidney Injury↗

Hyperbaric oxygen for carbon monoxide poisoning.

BACKGROUND: Poisoning with carbon monoxide (CO) remains an important cause of accidental and intentional injury worldwide. Several unblinded non-randomized trials have suggested that the use of hyperbaric oxygen (HBO) prevents the development of neurological sequelae. This has led to the widespread use of HBO in the management of patients with carbon monoxide poisoning. OBJECTIVES: To examine randomized trials of the effectiveness of hyperbaric oxygen (HBO) compared to normobaric oxygen (NBO) for the prevention of neurologic sequelae in patients with acute carbon monoxide poisoning. SEARCH STRATEGY: We searched MEDLINE (1966-present), EMBASE (1980-present), and the Controlled Trials Register of the Cochrane Collaboration, supplemented by a manual review of bibliographies of identified articles and discussion with recognized content experts. SELECTION CRITERIA: All randomized controlled trials involving non-pregnant adults acutely poisoned with carbon monoxide (regardless of severity), with adequate or unclear allocation concealment. DATA COLLECTION AND ANALYSIS: Two reviewers independently extracted from each trial information on: the number of randomized patients, types of participants, the dose and duration of the intervention, and the prevalence of neurologic symptoms at follow-up. MAIN RESULTS: Seven randomized controlled trials of varying quality were identified; one was excluded because it did not evaluate clinical outcomes. Of the six remaining trials, two represent incomplete publications (one interim analysis, one abstract). Of these six trials, four found no benefit of HBO for the reduction of neurologic sequelae, while two others did. Although pooled analysis does not suggest a benefit from HBOT (OR for neurological deficits 0.78, 95%CI 0.54 to 1.12, p=0.18), significant methodologic and statistical heterogeneity was apparent among the trials, and this result should be interpreted cautiously. Moreover, design or analysis flaws were evident in all trials. Importantly, the conclusions of one positive trial may have been influenced by failure to adjust for multiple hypothesis testing, while interpretation of the other positive trial is hampered by apparent changes in the primary outcome during the course of the trial. AUTHORS' CONCLUSIONS: Existing randomized trials do not establish whether the administration of HBO to patients with carbon monoxide poisoning reduces the incidence of adverse neurologic outcomes. Additional research is needed to better define the role, if any, of HBO in the treatment of patients with carbon monoxide poisoning. This research question is ideally suited to a multi-center randomized controlled trial.

Carbon Monoxide Poisoning↗

QTc abnormalities in deliberate self-poisoning with moclobemide.

BACKGROUND: Several medications have been found to prolong the QT interval in overdose. This can predispose to torsade de pointes-type ventricular tachycardia. AIMS: To analyse the effects of moclobemide deliberate self-poisoning on the length of both QT and corrected QT (QTc) intervals. METHODS: Electrocardiograms (ECG) of all patients presenting to a regional toxicology service with moclobemide ingestion were reviewed. Cases where a cardiotoxic agent was coingested were excluded. QT and QTc parameters were compared with a comparison group of patients ingesting paracetamol or benzodiazepines. RESULTS: Of 75 patients where ECG were available, the median ingested dose was 4.5 g (interquartile range (IQR): 2.4-7.5; range: 0.6-18 g) and the median age was 34 years (IQR: 26-44). The mean QT interval was 415 ms (standard deviation (SD): 51 ms) with a mean QTc of 459 ms (SD: 44 ms), and were prolonged compared with the comparison group. Twelve female patients had a QTc > 500 ms and in seven of these causality was established based on a pre- or post-ECG with a QTc < 500 ms. Only 10% of the moclobemide cases had a heart rate (HR) > 100 beats per minute, making overcorrection of HR by Bazett's formula an unlikely cause of the findings. No cardiac arrythmias were observed other than one case of first-degree heart block. CONCLUSIONS: Moclobemide prolongs the QT and QTc intervals in overdose and a 12-lead ECG should be done on all moclobemide deliberate self-poisonings. Continuous cardiac monitoring for what is otherwise a relatively benign overdose would appear to be an inappropriate use of resources but can be considered in patients with a QTc > 500 ms or with known risks for QT prolongation.

Adult↗

Prospective cohort study of definite spider bites in Australian children.

OBJECTIVES: To describe the clinical effects of spider bites in a paediatric population and compare to bites in an adult population. METHODS: Prospective follow up study of children with definite spider bites where the spiders were immediately collected and expertly identified. Cases were recruited from Australian emergency departments and poison information centres and followed up. Data were collected on circumstances of bites and clinical effects, and compared with similar data from adult spider bites. RESULTS: There were 163 cases (62% male, 38% female; age <16, median age 7 years, interquartile range (IQR): 3-11 years). The median duration of effects was 2 h (IQR 0.25-12 h). The commonest spiders were Huntsman spiders (Sparassidae) and Orb weavers (Araneidae), and comparatively few bites by theridiid spiders, including Red-back spiders. Pain or discomfort occurred in all bites and was severe in 20%. Local effects included puncture marks/bleeding (36%) and red mark/redness (73%). Systemic effects occurred in only 6% of cases. There were no necrotic lesions or ulcers as a consequence of any spider bites (0%; 97.5% CI 0.0-2.2%) and no early allergic reactions or secondary infections. The median duration of clinical effects was shorter than adults, the frequency of severe pain was less than adults and systemic effects were less common in children. CONCLUSIONS: Paediatric spider bite causes minor effects in the majority of cases, and is unlikely to cause necrotic ulcers, allergic reactions or infection. The severity and duration of effects differ from adults.

Adolescent↗

Black house spiders are unlikely culprits in necrotic arachnidism: a prospective study.

Twenty-five patients with definite bites by Badumna spp. spiders were recruited prospectively. Bites occurred across Australia, 92% from October to March, and most during daylight. Pain occurred in all cases, was severe in seven cases, with a median duration of 5 min. Other effects included: puncture marks (24%), swelling (12%) and erythema (68%). Minor systemic effects occurred in 4 bites. No patient had a necrotic ulcer (0%; 97.5% confidence interval 0-14%). Black house spiders (Badumna spp.) are unlikely to cause necrosis, contrary to reports of suspected bites. Patients can be reassured and do not require any further investigation or treatment.

Adolescent↗

Scorpion stings in Australia: five definite stings and a review.

Despite scorpions being locally abundant in many parts of Australia, scorpion sting is a poorly defined clinical condition in Australia. Many health-care workers are unaware of the effects of their stings and scorpions are often feared based on their international reputation. Five scorpion stings that occurred in different parts of Australia where the scorpion was caught at the time of the sting and identified by a professional arachnologist are reported in the present paper. The spectrum of clinical effects of scorpion stings in Australia and the potential for significant effects are discussed. These cases and recent prospective case series demonstrate that in Australia scorpion stings cause only minor effects. The main effect is localized pain lasting for several hours, associated less commonly with systemic effects, local numbness and paraesthesia. Most stings are from smaller scorpions from the family Buthidae and often occur indoors at night. The stings from Australian buthid scorpions cause more severe effects than from the larger species in the families Urodacidae (genus Urodacus) and Liochelidae (genus Liocheles).

Adult↗

The Hunter Serotonin Toxicity Criteria: simple and accurate diagnostic decision rules for serotonin toxicity.

BACKGROUND: There are difficulties with the diagnosis of serotonin toxicity, particularly with the use of Sternbach's criteria. AIM: To improve the criteria for diagnosing clinically significant serotonin toxicity. DESIGN: Retrospective analysis of prospectively collected data METHODS: We studied all patients admitted to the Hunter Area Toxicology Service (HATS) following an overdose of a serotonergic drug from January 1987 to November 2002 (n = 2222). Main outcomes were: diagnosis of serotonin toxicity by a clinical toxicologist, fulfillment of Sternbach's criteria and treatment with a serotonin receptor (5-HT(2A)) antagonist. A learning dataset of 473 selective serotonin reuptake inhibitor (SSRI)-alone overdoses was used to determine individual clinical features predictive of serotonin toxicity by univariate analysis. Decision rules using CART analysis were developed, and tested on the dataset of all serotonergic overdose admissions. RESULTS: Numerous clinical features were associated with serotonin toxicity, but only clonus (inducible, spontaneous or ocular), agitation, diaphoresis, tremor and hyperreflexia were needed for accurate prediction of serotonin toxicity as diagnosed by a clinical toxicologist. Although the learning dataset did not include patients with life-threatening serotonin toxicity, hypertonicity and maximum temperature > 38 degrees C were universal in such patients; these features were therefore added. Using these seven clinical features, decision rules (the Hunter Serotonin Toxicity Criteria) were developed. These new criteria were simpler, more sensitive (84% vs. 75%) and more specific (97% vs. 96%) than Sternbach's criteria. DISCUSSION: These redefined criteria for serotonin toxicity should be more sensitive to serotonin toxicity and less likely to yield false positives.

Analysis of Variance↗

Feasibility of prehospital treatment with activated charcoal: Who could we treat, who should we treat?

OBJECTIVES: To investigate the feasibility and potential risk benefit of prehospital administration of activated charcoal. METHODS: Review of deliberate self poisoning presentations to the emergency department (ED) of a toxicology unit by ambulance over six years. Data were extracted from a standardised prospective database of poisonings. Outcomes included: number of patients attended by ambulance and number arriving in emergency within one hour. Cases were stratified by ingestion type, based on toxicity and sedative activity. RESULTS: 2041 poisoning admissions were included. The median time to ambulance attendance was 1 h 23 min (IQR 37 min-3 h) and to hospital attendance was 2 h 15 min (IQR 1 h 25 min-4 h). In 774 cases (38%) ambulance attendance occurred within one hour, but in only 161 (8%) did ED attendance occur within one hour. Non-sedating, highly toxic substances were ingested in 55 cases, 24 (23 with GCS>14) with ambulance attendance, and five with ED attendance, within one hour. Conversely 439 patients ingested a less toxic, sedative agent, 160 with ambulance attendance, and 32 with ED attendance, within one hour. Limiting decontamination to patients ingesting highly toxic, non-sedating compounds (GCS<14) reduces the proportion requiring treatment to 23 of the 774 (3.0%), an additional 18 patients. CONCLUSION: More patients could potentially be decontaminated if all patients attended by ambulance within one hour received charcoal. However, this would expose 128 patients with sedative, low risk poisonings to the risk of aspiration, and only treat 18 extra high risk poisonings. This small potential benefit of prehospital charcoal is unlikely to justify the expense in training and protocols required to implement it

Adult↗

Acute myocardial injury caused by Sydney funnel-web spider (Atrax robustus) envenoming.

A 67-year-old female suffered envenoming by a Sydney funnel-web spider (Atrax robustus), complicated by ST elevation and elevated troponin levels consistent with an acute myocardial injury. She was treated primarily with funnel-web spider antivenom, admission to intensive care and initial respiratory support for acute pulmonary oedema. The mechanism by which funnel-web spider envenomation caused myocardial injury is unclear but follow-up nuclear studies in the patient demonstrated that she had minimal atherosclerotic disease.

Aged↗

A prospective study of 750 definite spider bites, with expert spider identification.

BACKGROUND: Spider bite is a subject of much medical mythology with prevalent fears that spiders cause severe envenoming, with neurotoxic effects or necrotic ulcers. Clinical experience and small studies suggest otherwise, but this has not been confirmed by prospective studies of bites by identified spiders. AIM: To describe the clinical effects of bites by accurately identified spiders, and determine whether early clinical features and circumstances can predict spider type. DESIGN: Prospective follow-up study. METHODS: Patients were recruited from admissions to two emergency departments (n=48) and referrals from three state poison information centres (n=1426), over 27 months. Overall, there were 750 people with definite spider bites where the spiders were immediately collected and expertly identified. RESULTS: Significant effects occurred in 44 bites (6%), including 37 (of 56) redback spider bites (Latrodectus hasselti) with significant pain lasting >24 h. Of these, only 6 (11%) received antivenom. One severe neurotoxic envenoming by an Australian funnelweb spider required antivenom. No definite spider bites resulted in necrotic ulcers (0%, 99%CI 0-0.7%). There were no early allergic reactions and secondary infection occurred in seven cases (0.9%, 95%CI 0.4-1.9%). Circumstances and early clinical effects were strongly associated with taxonomic spider identification, with positive predictive values >0.95 for common groups of spiders. CONCLUSIONS: Australian spider bite caused minor effects in most cases and is unlikely to cause necrotic ulcers, allergic reactions or infection. Redback spider bite (widow spider) caused prolonged pain, and antivenom could have been used more frequently. The circumstances and early clinical features of spider bites may allow early appropriate advice and treatment of spider bite without taxonomic identification.

Adolescent↗

Delayed asystolic cardiac arrest after diltiazem overdose; resuscitation with high dose intravenous calcium.

A 51 year old man took a mixed overdose including 1.8-3.6 g of diltiazem, paracetamol, aspirin, isosorbide nitrate, and alcohol. He initially presented to hospital after six hours with mild hypotension and was treated with activated charcoal and intravenous fluids. Eighteen hours after the overdose he had two generalised tonic-clonic seizures. The patient remained unresponsive with junctional bradycardia, unrecordable blood pressure, and then became asystolic. He was resuscitated with high dose (13.5 g) intravenous calcium and adrenaline (epinephrine). He required inotropic support and temporary pacing over the next 48 hours. This case suggests there is a role for aggressive high dose intravenous calcium therapy in severe diltiazem overdose, particularly with the onset of asystole. It should be considered early in cases of cardiac arrest after diltiazem overdose. The case also highlights the problems with delayed toxicity when whole bowel irrigation is not administered.

Calcium Channel Blockers↗

Clinical effects of bites from formally identified spiders in tropical Northern Territory.

OBJECTIVE: To determine the types of spiders causing bites and the clinical effects of their bites in tropical Northern Territory (north of the town of Katherine). DESIGN: A prospective study of confirmed and suspected spider-bites and a retrospective analysis of data from a standardised, local database of spider- and snake-bites. Confirmed spider-bites were those in which there was a clear history of the bite, and the captured spider was identified by an arachnologist. SETTING: Emergency department of a teaching hospital. SUBJECTS AND DATA SOURCE: All subjects with confirmed or suspected spider-bite presenting to the Emergency Department or referred from August 1999 to August 2000, or identified from the database. RESULTS: Thirty-four subjects had a confirmed spider-bite from an identified spider: 25 in the prospective group and nine in the retrospective group. The spiders were Sparassidae (huntsman spider) (12 bites), Missulena pruinosa (northern mouse spider) (7), Latrodectus (widow spider) (4), Araneidae (orb-weaver) (4), Salticidae (jumping spider) (4), Nemesidae (trapdoor spider) (1), Conothele (1) and Selenocosmia (whistling spider) (1). Clinical effects were local pain in 97% (severe in 29%), redness in 47% and swelling in 24% of cases. Systemic effects occurred in three victims, two of whom were bitten by M. pruinosa. There were no cases of confirmed necrotic arachnidism. CONCLUSIONS: None of the spider-bites resulted in severe effects. Compared with data from other parts of Australia, different species were involved and latrodectism was uncommon. Our study highlighted the importance of correctly identifying the spider species.

Adolescent↗