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Biomedical subjects

Geoffrey K Isbister

Publications and source records attributed to Geoffrey K Isbister.

At least 19 recordsLinked to original sources
PubMed2007

Spotted black snake (Pseudechis guttatus) envenoming.

We report two cases of spotted black snake (Pseudechis guttatus) envenoming. One patient experienced localised burning pain around the bite and developed nausea, vomiting, diarrhoea, upper abdominal cramping and diaphoresis. He was treated with intravenous fluids and antiemetics, but no antivenom, and was discharged 23 hours after the bite. The second patient developed a severe headache, blurred vision and mild nausea, associated with severe pain and swelling of the bitten limb that took 4 days to resolve. No antivenom was given and the patient had no sequelae. Neither patient developed significant coagulopathy, myolysis or neuromuscular paralysis. Bites by this species appear to cause effects similar to those of the more common red-bellied black snake (P. porphyriacus).

Adult↗
PubMed2006

The in vitro vascular effects of two chirodropid (Chironex fleckeri and Chiropsella bronzie) venoms.

Clinical observations suggest a primary cardiotoxic role in fatal Chironex fleckeri stings. The limited research available indicates that Chiropsella bronzie venom acts in a similar manner although appears to be less potent. The aim of the present study was to elucidate the vascular effects of C. fleckeri and C. bronzie venoms using rat isolated aorta. Both venoms produced a sustained contraction of endothelium-denuded aorta which was not significantly affected by prazosin or box jellyfish antivenom. Felodipine significantly reduced the contractile response to C. fleckeri venom but not C. bronzie venom. Both venoms produced an initial relaxation (Phase 1), followed by a sustained contraction (Phase 2), in pre-contracted endothelium-intact aorta. Removal of the endothelium significantly inhibited both phases of the response. NOLA significantly inhibited Phase 1, but not Phase 2, of the response to both venoms. Atropine, HOE 140 or BQ 123 did not have any significant inhibitory effect on either phase. In conclusion, neither C. fleckeri nor C. bronzie venoms appear to contain components with activity at alpha(1)-adrenoceptors. Antivenom was ineffective in reversing the effects of the venom suggesting it is incapable of completely neutralising nematocyst-derived venom. Determining the mechanism of action of these venoms will allow for the development of better treatment strategies.

Adrenergic alpha-Antagonists↗
PubMed2006

Efficacy of antivenom against the procoagulant effect of Australian brown snake (Pseudonaja sp.) venom: in vivo and in vitro studies.

Snake venom induced consumption coagulopathy (VICC) is a common complication of snake bite due to prothrombin activators or thrombin-like enzymes in the venom. This study aimed to determine the efficacy and dose of antivenom for treating VICC in patients envenomed by brown snakes (Pseudonaja spp.), including in vitro coagulation studies. In serial blood samples from patients with brown snake envenoming, venom and antivenom concentrations were measured using enzyme immunoassays. In vitro mixtures of brown snake venom and antivenom were used to investigate antivenom binding, neutralisation of prothrombin activity, prevention of venom-mediated clotting and effect on thrombin generation parameters using a thrombinoscope. In 27 envenomed patients the median venom concentration was 20 ng/mL (Interquartile range[IQR]:12-44 ng/mL) prior to antivenom and was not detected after antivenom administration, including 9 patients given one vial. In vitro, 200 microg/mL of antivenom bound all free venom at venom concentrations seen in patients. In vitro prothrombinase activity of the venom (using a chromogenic substrate) was not neutralised by antivenom. However, for venom concentrations seen in humans, 100 microg/mL of antivenom prevented venom clotting activity in human plasma and 479 microg/mL neutralised procoagulant venom activity measured by triggering thrombin generation. One vial of antivenom appears to be sufficient to bind and neutralise all venom in patients with severe brown snake envenoming.

Animals↗
PubMed2006

Application of pharmacokinetic-pharmacodynamic modelling in management of QT abnormalities after citalopram overdose.

OBJECTIVE: To develop guidelines for the management of QT prolongation after citalopram overdose, including decontamination with single-dose activated charcoal (SDAC) and cardiac monitoring. DESIGN: Simulation study using a previously developed pharmacokinetic-pharmacodynamic (PKPD) model which predicted the time-course of QT prolongation and the effect of citalopram dose and use of SDAC on QT prolongation. MAIN MEASURES AND RESULTS: The previously developed PKPD model was used to address the following in patients following citalopram overdose: (1) Above what dose should patients be decontaminated? (2) Above what dose should patients have cardiac monitoring? (3) For what period of time should patients be monitored? The primary outcome was QT,RR combinations above an abnormal threshold as a surrogate predictor of torsades de pointes. Simulations were performed using MATLAB for an overdose patient with typical demographics: 30-year-old female with a heart rate of 79 bpm taking citalopram therapeutically. The simulations showed: (1) There was significant benefit associated with the administration of SDAC to patients following citalopram overdose ingesting >600 mg; (2) With citalopram overdoses >1,000mg it was advisable to give SDAC and cardiac monitor the patient; (3) The risk of developing future abnormal QT,RR combinations was less than 1% in patients with normal QT,RR combinations up to 13 h post-dose, so the minimum monitoring time for citalopram overdoses >1,000mg should be 13h. Recommended dose levels for intervention should be lowered in older patients and patients with tachycardia, while men are less sensitive to QT prolongation. CONCLUSIONS: Guidelines for the management of QT prolongation after citalopram overdose were developed. We believe the model will help clinicians to decide which patients to decontaminate and monitor.

Adolescent↗
PubMed2006

Enzyme immunoassays in brown snake (Pseudonaja spp.) envenoming: detecting venom, antivenom and venom-antivenom complexes.

Although a commercial snake venom detection kit (SVDK) is available to distinguish between the five major snake groups in Australia, there is no assay for quantifying venom or antivenom concentrations in envenomed patients. Serum samples were obtained from patients with brown snake (Pseudonaja spp.) envenoming before and after the administration of antivenom and patients with suspected brown snake bites but no evidence of envenoming. Enzyme immunoassays (EIAs) were developed for free venom, free antivenom and the venom-antivenom complex. Standard samples measured in duplicate had a coefficient of variation of less than 10%. The EIA for venom was able to detect brown snake venom down to concentrations of 3 ng/mL. A high baseline absorbance was measured in some patients that did not change with the addition of excess antivenom to the samples. In these patients, the baseline absorbance was subtracted from all measurements to calculate the true venom concentration. The EIA for brown snake antivenom had a limit of detection of 20 microg/mL, but 50 microg/mL was used as a cut-off based on assays in patients who had not received antivenom. The EIA for venom-antivenom complexes was unable to detect these at the low venom concentrations that occurred in patients. Quantification of venom and antivenom will help to determine the dose of antivenom required to bind venom and to establish appropriate end points for antivenom treatment.

Adolescent↗
PubMed2006

A randomised controlled trial of hot water (45 degrees C) immersion versus ice packs for pain relief in bluebottle stings.

OBJECTIVE: To investigate the effectiveness of hot water immersion for the treatment of Physalia sp. (bluebottle or Portuguese Man-of-War) stings. DESIGN: Open-label, randomised comparison trial. Primary analysis was by intention to treat, with secondary analysis of nematocyst-confirmed stings. One halfway interim analysis was planned. SETTING: Surf lifesaving first aid facilities at two beaches in eastern Australia from 30 December 2003 to 5 March 2005. PARTICIPANTS: 96 subjects presenting after swimming in the ocean for treatment of an apparent sting by a bluebottle. INTERVENTIONS: Hot water immersion (45 degrees C) of the affected part versus ice pack application. MAIN OUTCOME MEASURES: The primary outcome was a clinically important reduction in pain as measured by the visual analogue scale (VAS). Secondary outcomes were the development of regional or radiating pain, frequency of systemic symptoms, and proportion with pruritus or rash on follow-up. RESULTS: 49 patients received hot water immersion and 47 received ice packs. The two groups had similar baseline features, except patients treated with hot water had more severe initial pain (VAS [mean +/- SD]: 54 +/- 22 mm versus 42 +/- 22 mm). After 10 minutes, 53% of the hot water group reported less pain versus 32% treated with ice (21%; 95% CI, 1%-39%; P = 0.039). After 20 minutes, 87% of the hot water group reported less pain versus 33% treated with ice (54%; 95% CI, 35%-69%; P = 0.002). The trial was stopped after the halfway interim analysis because hot water immersion was shown to be effective (P = 0.002). Hot water was more effective at 20 minutes in nematocyst-confirmed stings (95% versus 29%; P = 0.002). Radiating pain occurred less with hot water (10% versus 30%; P = 0.039). Systemic effects were uncommon in both groups. CONCLUSIONS: Immersion in water at 45 degrees C for 20 minutes is an effective and practical treatment for pain from bluebottle stings.

Adolescent↗
PubMed2006

Amisulpride deliberate self-poisoning causing severe cardiac toxicity including QT prolongation and torsades de pointes.

Although clinical trials of the antipsychotic amisulpride revealed no cardiac adverse effects, four patients with severe cardiac toxicity after overdose were reported to Australian poisons information centres in 2004-2005. All four had QT prolongation over 500 ms, two had rate-dependent bundle branch block, two developed torsades de pointes, and one died after cardiac arrest. Pending further studies, we recommend electrocardiogram assessment until at least 16 h after amisulpride overdose and, if QT interval is prolonged, cardiac monitoring until the patient is clinically well and conduction intervals are normal.

Adult↗
PubMed2006

Verified bites by the woodlouse spider, Dysdera crocata.

Bites by the woodlouse spider, Dysdera crocata, are virtually innocuous. The main symptom is minor pain, typically lasting less than 1h, probably due mostly to mechanical puncture of the skin. However, because the spider has a strong proclivity to bite, has large fangs which it bares when threatened and is commonly mistaken for the medically important brown recluse spider in the United States, documentation of the mild effects of its bites may prevent excessive, unwarranted and possibly harmful treatment. We present information on eight verified bites reported to us as well as eight additional bites recorded in the literature.

Adolescent↗
PubMed2006

Pharmacokinetic-pharmacodynamic modelling of QT interval prolongation following citalopram overdoses.

AIMS: To develop a pharmacokinetic-pharmacodynamic model describing the time-course of QT interval prolongation after citalopram overdose and to evaluate the effect of charcoal on the relative risk of developing abnormal QT and heart-rate combinations. METHODS: Plasma concentrations and electrocardiograph (ECG) data from 52 patients after 62 citalopram overdose events were analysed in WinBUGS using a Bayesian approach. The reported doses ranged from 20 to 1700 mg and on 17 of the events a single dose of activated charcoal was administered. The developed pharmacokinetic-pharmacodynamic model was used for predicting the probability of having abnormal combinations of QT-RR, which was assumed to be related to an increased risk for torsade de pointes (TdP). RESULTS: The absolute QT interval was related to the observed heart rate with an estimated individual heart-rate correction factor [alpha = 0.36, between-subject coefficient of variation (CV) = 29%]. The heart-rate corrected QT interval was linearly dependent on the predicted citalopram concentration (slope = 40 ms l mg(-1), between-subject CV = 70%) in a hypothetical effect-compartment (half-life of effect-delay = 1.4 h). The heart-rate corrected QT was predicted to be higher in women than in men and to increase with age. Administration of activated charcoal resulted in a pronounced reduction of the QT prolongation and was shown to reduce the risk of having abnormal combinations of QT-RR by approximately 60% for citalopram doses above 600 mg. CONCLUSION: Citalopram caused a delayed lengthening of the QT interval. Administration of activated charcoal was shown to reduce the risk that the QT interval exceeds a previously defined threshold and therefore is expected to reduce the risk of TdP.

Adolescent↗
PubMed2006

Lignocaine and chlorhexidine toxicity in children resulting from mouth paint ingestion: a bottling problem.

BACKGROUND: A pharmaceutical product was marketed in Australia for 'teething' in an almost identical container to a popular paediatric paracetamol preparation. The product contained lignocaine and chlorhexidine. The similarity of the packaging resulted in large number of therapeutic errors in which the 'teething' preparation was given in error for paracetamol. As the exact dose of the erroneously administered mouth paint was known this provided an opportunity for outcome assessment of lignocaine ingestion. METHODS: Calls to two state poison information centres regarding this product were prospectively followed up. Information collected included: demographics, type of exposure, details of the exposure and adverse effects. A systematic review of the literature was used to identify all previous reported cases of lignocaine and chlorhexidine ingestion. RESULTS: There were 28 cases with complete follow up where the product was given in therapeutic errors (10 girls and 18 boys; median age 11 months; range 2 months-4 years). The mean ingested dose of lignocaine was 2.7 mg/kg (standard deviation 1.3 mg) and chlorhexidine was 0.06 mg/kg (standard deviation 0.03 mg). The largest ingested lignocaine dose was 5.9 mg/kg. Two children developed minor symptoms: one vomited twice and the other was reported to have increased salivation and difficulty with solid food for 20 min. No other adverse effects were reported. The literature review suggested that severe effects occurred with doses more than 15 mg/kg. CONCLUSION: No major adverse effects occurred with lignocaine ingestions of less than 6 mg/kg and it would be appropriate to observe these patients at home. Chlorhexidine did not appear to cause clinical effects in this low concentration.

Administration, Oral↗
PubMed2006

Baclofen overdose: defining the spectrum of toxicity.

OBJECTIVES: To describe the spectrum of toxicity of baclofen in overdose, and investigate dose-related clinical effects. METHODS: Consecutive baclofen overdoses were identified from a prospective database of all poisoning admissions presenting to a regional toxicology service. Ingestion was corroborated on more than one occasion and from multiple sources. Demographic, clinical and outcome variables were extracted for each presentation for a retrospective review, and the data sets were divided into high dose (> or = 200 mg) and low dose (< 200 mg) groups for comparison of clinical effects. RESULTS: There were 23 presentations, of which eight patients ingested baclofen alone. Seizures were reported in four cases, a decreased level of consciousness (GCS < 9) occurred in eight patients and delirium was recorded in eight patients. Five patients had miosis and seven patients had dilated pupils, 13 patients had absent or depressed reflexes. The only arrhythmias were sinus bradycardia in six patients and sinus tachycardia in five. Hypertension occurred in 13 patients and hypotension in one. The reported total ingested dose of baclofen was known in 19 patients (Mean 630 mg, SD 730 mg; 80-2500 mg). A higher ICU admission rate, rate of mechanical ventilation and prolonged length of stay occurred in those ingesting 200 mg or more. Coma, delirium and seizures occurred only with doses of 200 mg or more, and hypertension was more common with higher doses. CONCLUSIONS: Baclofen overdose causes mainly neurological effects and excepting hypertension cardiovascular effects were uncommon. Doses greater than 200 mg were predictive of patients developing delirium, coma and seizures, requiring long hospital admissions and ICU admission.

Adolescent↗
PubMed2006

Verified bites by yellow sac spiders (genus Cheiracanthium) in the United States and Australia: where is the necrosis?

Spiders of the genus Cheiracanthium are frequently reported in review articles and medical references to be a definitive cause of dermonecrosis or necrotic arachnidism in humans. We provide 20 cases of verified bites by Cheiracanthium spiders from the United States and Australia, none with necrosis. A review of the international literature on 39 verified Cheiracanthium bites found only one case of mild necrosis in the European species C. punctorium. The basis for the suggestion that this spider genus causes dermonecrosis seems to be mostly inference from venom experiments in rabbits and guinea pigs, circumstantial spider involvement in human skin lesions, and repetitive citation of non-definitive reports in the medical literature. We discuss factors that lead to the erroneous elevation of virtually innocuous spiders to that of significant medical concern, which is a recurring problem in the medical community.

Adolescent↗
PubMed2005

Clinical effects of stings by sponges of the genus Tedania and a review of sponge stings worldwide.

Contact with sponges (Phylum Porifera) usually results in minimal effects or abrasions, except for species that produce crinitoxins and can cause irritation and dermatitis. There are few reports of sponge stings, mainly in divers or collectors. We report a group of sponge stings from handling flame red/orange sponges on the beach, confirmed to be Tedania anhelans in five cases. All seven patients suffered immediate effects ranging from mild to severe pain, and local inflammation. A 38-year-old female and three children had delayed skin involvement including itchiness, pain, swelling and redness. Blistering and desquamation occurred in the female adult and limited desquamation in one child. Similar delayed effects have been reported in Tedania spp. stings previously.

Adult↗
PubMed2005

Funnel-web spider bite: a systematic review of recorded clinical cases.

OBJECTIVE: To investigate species-specific envenoming rates and spectrum of severity of funnel-web spider bites, and the efficacy and adverse effects of funnel-web spider antivenom. DATA SOURCES: Cases were identified from a prospective study of spider bite presenting to four major hospitals and three state poisons information centres (1999-2003); museum records of spider specimens since 1926; NSW Poisons Information Centre database; MEDLINE and EMBASE search; clinical toxinology textbooks; the media; and the manufacturer's reports of antivenom use. DATA EXTRACTION: Patient age and sex, geographical location, month, expert identification of the spider, clinical effects and management; envenoming was classified as severe, mild-moderate or minor/local effects. DATA SYNTHESIS: 198 potential funnel-web spider bites were identified: 138 were definite (spider expertly identified to species or genus), and 77 produced severe envenoming. All species-identified severe cases were attributed to one of six species restricted to NSW and southern Queensland. Rates of severe envenoming were: Hadronyche cerberea (75%), H. formidabilis (63%), Atrax robustus (17%), Hadronyche sp. 14 (17%), H. infensa (14%) and H. versuta (11%). Antivenom was used in 75 patients, including 22 children (median dose, 3 ampoules; range, 1-17), with a complete response in 97% of expertly identified cases. Three adverse reactions were reported, all in adults: two early allergic reactions (one mild and one with severe systemic effects requiring adrenaline), and one case of serum sickness. CONCLUSIONS: Severe funnel-web spider envenoming is confined to NSW and southern Queensland; tree-dwelling funnel webs (H. cerberea and H. formidabilis) have the highest envenoming rates. Funnel-web spider antivenom appears effective and safe; severe allergic reactions are uncommon.

Adult↗