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Isbister G.K.,Calvary Materials Newcastle Hospital | Isbister G.K.,University of Newcastle | Balit C.R.,Poison Information Center | MacLeod D.,Victorian Poison Information Center | Duffull S.B.,University of Otago
Journal of Clinical Psychopharmacology | Year: 2010

This study aimed to describe the effects of the antipsychotic amisulpride in overdose, including the frequency of QT prolongation and torsades de pointes. Cases of amisulpride overdose (>1 g) were recruited from 2 state poison centers and a tertiary toxicology unit over 5 years. A 1-page clinical research form was used to collect clinical information. Copies of all electrocardiograms were obtained. Electrocardiogram parameters (QRS and QT intervals) were manually measured as previously described, and plots of QT-heart rate (HR) pairs were compared with the QT nomogram. There were 83 patients with amisulpride overdoses with a median age of 29 years (interquartile range [IQR], 23-40 years), and 42 (51%) were female. The median dose ingested was 6 g (IQR, 3-13 g, range, 1.2-120 g). The median HR was 66 beats/min (IQR, 60-81 beats/min). Bradycardia occurred in 20 cases (24%), and hypotension in 19 (23%). From 440 electrocardiograms (average of 5 per case; range, 1-15), an abnormal QT-HR pair occurred in 61 cases (73%). Torsades de pointes developed in 6 cases (7%), with doses of 4, 4.6, 18, 24, 32, and 80 g. The patient taking 32 g died after a cardiac arrest. Widened QRS did not occur except transient rate-dependent bundle-branch block in 3 cases. There were significant associations of bradycardia, hypokalemia, and hypocalcaemia, with QT prolongation and torsades de pointes. Central nervous system effects were uncommon with coma in 7 cases, seizures in 2, and dystonic reactions in 2. Amisulpride overdose commonly causes QT prolongation, bradycardia, and hypotension. Torsades de pointes occurred commonly enough to suggest that amisulpride is highly cardiotoxic in overdose. © 2010 Lippincott Williams & Wilkins. Source

Coulter C.V.,University of Otago | Isbister G.K.,Calvary Materials Newcastle Hospital | Isbister G.K.,University of Newcastle | Duffull S.B.,University of Otago
Clinical Pharmacokinetics | Year: 2011

Background and Objective: Methanol is a toxic alcohol that can cause significant morbidity and mortality in overdose, while ethanol is a readily available and effective antidote. Little is known about the pharmacokinetics of methanol in the presence of ethanol and vice versa. This paper explores the influence of methanol and ethanol on the pharmacokinetics of each other along with the effect of continuous venovenous haemodiafiltration (CVVHD) on alcohol removal. Methods: Multiple plasma, urine and dialysate samples were collected from a 42-year-old male who ingested 166 g of methanol. Methanol and ethanol concentrations in both plasma and urine were assayed and the concentration-time data were modelled using nonlinear mixed-effects modelling software NONMEM® VI. Simulations were performed using the final model parameters in MATLAB® software where a variety of initial doses and ethanol infusions were assessed. Results: The final model included a competitive metabolic interaction between methanol and ethanol as well as first-order elimination due to renal, CVVHD and an additional non-renal non-CVVHD mechanism. Simulations from the model show a loading dose of 28.4 g/70 kg of ethanol results in a target plasma concentration of 1 g/L. Due to the competitive interaction between methanol and ethanol, higher amounts of methanol require lower maintenance doses of ethanol but for longer. CVVHD was shown to increase the dose rate of ethanol required but to decrease the duration of the maintenance phase. Conclusion: A detailed understanding of the pharmacokinetics of methanol and ethanol in the presence of each other is required to accurately determine the doses of ethanol required to treat different methanol poisonings. © 2011 Adis Data Information BV. All rights reserved. Source

Sharpley C.F.,University of New England of Australia | Bitsika V.,Bond University | Denham J.W.,Calvary Materials Newcastle Hospital | Denham J.W.,University of Newcastle
Psycho-Oncology | Year: 2014

Objectives To identify the factors underlying prostate cancer (PCa) patients' depression-anxiety, sexual problems, urinary dysfunction and androgen deprivation therapy (ADT)-linked breast changes and hot flushes, and test these as predictors of loss of masculinity (LoM) over 36months following diagnosis. Methods One thousand seventy patients from the TROG 03.04 (RADAR) trial the EORTC QLQ C-30 and PR 25 questionnaires, and the International Prostate Cancer Symptom Score of the American Urological Association at baseline, 3, 7, 12, 18, 24 and 36months. Selected items from these scales were factor-analysed to identify a four-component solution for responses at 18 and 36months, and these components were regressed against a single-item measuring LoM. Results Depression-anxiety factor was the most powerful predictor of LoM at both time points, followed by sexual problems of ADT side effects (breast changes and hot flushes). Urinary dysfunction was not a consistent predictor of LoM. Depression-anxiety was also the most significant factor distinguishing between those men who reported LoM and those who did not. Conclusions Although LoM is often reported as arising from ADT, the relative power of depression-anxiety in predicting LoM, both at the selected time points and using a time-lagged analysis, plus the finding that depression-anxiety was the most consistent difference between men who reported LoM and those who did not, argues for the presence of adverse mood states as being the key ingredient in deciding if PCa patients experience loss of their feelings of masculinity. Copyright © 2013 John Wiley & Sons, Ltd. Copyright © 2013 John Wiley & Sons, Ltd. Source

Isbister G.K.,University of Newcastle | O'Leary M.A.,Calvary Materials Newcastle Hospital | Elliott M.,University of Melbourne | Brown S.G.A.,University of Western Australia
Medical Journal of Australia | Year: 2012

Objectives: To describe the clinical syndrome associated with definite tiger snake (Notechis spp) envenoming and to examine the ability of tiger snake antivenom (TSAV) to bind free venom in vivo. Design, setting and participants: We conducted a prospective cohort study within the Australian Snakebite Project, reviewing all definite tiger snake envenoming cases between October 2004 and June 2011. Definite cases were identified by venom-specific enzyme immunoassay or expert snake identification. Main outcome measures: Clinical effects of tiger snake envenoming; peak venom concentrations; number of vials of antivenom administered. Results: Fifty-six definite tiger snake envenomings were identified. Clinical effects included venom-induced consumption coagulopathy (VICC) (n=53), systemic symptoms (n = 45), myotoxicity (n =11) and neurotoxicity (n=17). Thrombotic microangiopathy occurred in three patients, all of whom developed acute renal failure. There were no deaths. A bite-site snake venom detection kit test was done in 44 patients, but was positive for tiger snake in only 33 cases. Fifty-three patients received TSAV and eight of these patients had immediate hypersensitivity reactions, severe enough in one case to satisfy diagnostic criteria for severe anaphylaxis. The median peak venom concentration in 50 patients with pretreatment blood samples available was 3.2 ng/mL (interquartile range [IQR], 1-12 ng/mL; range 0.17-152 ng/mL). In 49 patients with post-treatment blood samples available, no venom was detected in serum after the first antivenom dose. Ten patients were given 1 vial of TSAV; the median dose was 2 vials (range, 1-4 vials). Pretreatment serum venom concentrations did not vary significantly between patients given 1 vial of TSAV and those given 2 or more vials. Conclusion: Tiger snake envenoming causes VICC, systemic symptoms, neurotoxicity and myotoxicity. One vial of TSAV, the dose originally recommended when the antivenom was first made available, appears to be sufficient to bind all circulating venom. Source

McGarvey A.C.,Calvary Materials Newcastle Hospital | McGarvey A.C.,University of Newcastle | Osmotherly P.G.,University of Newcastle | Hoffman G.R.,University of Newcastle | Chiarelli P.E.,University of Newcastle
Archives of Physical Medicine and Rehabilitation | Year: 2013

Objective: To assess the dynamic activity of scapular muscles in patients with accessory nerve dysfunction after neck dissection surgery, compared with both their unaffected side and with age- and sex-matched controls. Design: A case-control investigation. Setting: Physiotherapy department of a hospital. Participants: Two groups of 10 participants were recruited. One group consisted of neck dissection patients with demonstrated clinical signs of accessory nerve injury. The second group was composed of matched healthy individuals. Interventions: Surface electromyographic activity of the upper trapezius, middle trapezius, rhomboid major, and serratus anterior muscles was compared dynamically during scapular strengthening exercises. Main Outcome Measures: Electromyographic activity comparisons were made between the neck dissection affected side, the neck dissection unaffected side, and the matched healthy control side. Raw data and data expressed as a percentage of maximal voluntary isometric contraction were compared. Results: The neck dissection affected side demonstrated significantly less upper trapezius and middle trapezius muscle activity compared with the neck dissection unaffected side and matched control group. The neck dissection unaffected side had significantly less upper trapezius muscle activity than the matched control group. Conclusions: Trapezius muscle activity is significantly reduced in accessory nerve shoulder dysfunction as a result of neck dissection, both in the affected and unaffected sides. This needs to be considered in the rehabilitation of this patient group. © 2013 American Congress of Rehabilitation Medicine. Source

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