http://nova.newcastle.edu.au/vital/access/services/Feed ${session.getAttribute("locale")} 5 http://nova.newcastle.edu.au/vital/access/manager/Repository/uon:12441 Introduction: Acanthophis genus (i.e. death adders) and the Naja genus (i.e. cobras) belong to the family elapidae. The current study compared the in vitro cytotoxicity of venoms from four Acanthophis spp. and three Naja spp. on rat aortic smooth muscle cells, A7r5, and rat skeletal muscle cells, L6. The ability of CSL death adder antivenom and SAIMR antivenom, for Acanthophis spp. and Naja spp. venom respectively, to negate the cytotoxicity was also examined. Methods: A cell proliferation assay was used to determine cell viability following treatment with venom in the presence or absence of antivenom. Sigmoidal growth curves were obtained, and IC₅₀ values were determined. Results: Acanthophis spp. and Naja spp. venoms produced concentration-dependent inhibition of cell proliferation in both cell lines. Naja spp. venoms were significantly more cytotoxic than the most potent Acanthophis venom (i.e. A. antarcticus) in both cell lines. Naja spp. venoms also displayed higher sensitivity in L6 cells. SAIMR antivenom significantly inhibited the cytotoxic actions of all Naja spp. venoms in both A7r5 and L6 cells. However, death adder antivenom (CSL Ltd) was unable to negate the cytotoxic effects of Acanthophis spp. venoms. Discussion: Concentrations of the predominantly cytotoxic Naja spp. venoms used were approximately three times less than the predominantly neurotoxic Acanthophis spp. venoms. SAIMR antivenom was partially effective in neutralising the effects of Naja spp. venoms. Death adder antivenom(CSL Ltd) was not effective in negating the cytotoxic effects of venom from Acanthophis spp. These results indicate that the cell-based assay is suited to the examination of cytotoxic snake venoms and may be used in conjunction with organ bath experiments to pharmacologically characterise snake venoms. Furthermore, the results suggest that the use of a skeletalmuscle cell line is likely to bemore clinically relevant for the examination of cytotoxic snake venoms. 2013-01-17T02:20:06.777Z ]]> http://nova.newcastle.edu.au/vital/access/manager/Repository/uon:12298 Objective: The objective of the study was to evaluate the effectiveness of the sedation assessment tool (SAT) in assessing patient response to treatment for acute behavioural disturbance (ABD). Methods: The SAT is a simplified version of the altered mental status score (AMSS) and is a 7-point scale assessing levels of agitation and sedation using only two descriptors. To assess the SAT we firstly compared plots of the SAT and the AMSS versus time in patients with ABD recruited to a clinical trial. AMSS were converted to the SAT for this comparison. Second, the sensitivity and specificity were calculated for an increase in the SAT to +2 or +3 as a predictor of whether additional sedation was required in a prospective cohort of 138 patients. Third, interrater reliability was assessed using two individuals to score the same patient at two different time points and finally the time to record the score was measured. Results: Plots of AMSS and SAT for 91 patients in the clinical trial illustrated similar trends in agitation/sedation. Seventeen of 138 patients in the second cohort had an increase in the SAT. Fifteen of 17 (88%) received additional sedation. The sensitivity and specificity of the SAT for additional sedation was 100% (95% CI 75–100%) and 98% (95% CI 94–100%), respectively. The median time for staff to assign the SAT was 10 s (range 3–15 s). Interrater reliability was high with a kappa of 0.87. Conclusion: The SAT is a simple, rapid and useful measure of the level of agitation/sedation in patients with ABD. Increases in the score reliably indicated the need for further sedation. 2012-12-18T05:12:41.826Z ]]> http://nova.newcastle.edu.au/vital/access/manager/Repository/uon:11519 Study objective: We determine whether droperidol, midazolam, or the combination is more effective for intramuscular sedation in violent and acute behavioral disturbance in the emergency department (ED). Methods: We conducted a blinded randomized controlled trial of intramuscular sedation for violent and acute behavioral disturbance, comparing droperidol (10 mg), midazolam (10 mg), and droperidol (5 mg)/midazolam (5 mg). Inclusion criteria were patients requiring physical restraint and parenteral sedation. The primary outcome was the duration of the violent and acute behavioral disturbance, defined as the time security staff were required. Secondary outcomes included time until additional sedation was administered, staff and patient injuries, further episodes of violent and acute behavioral disturbance, and drug-related adverse effects. Results: From 223 ED patients with violent and acute behavioral disturbance, 91 patients were included; 33 received droperidol, 29 received midazolam, and 29 received the combination. There was no difference in the median duration of the violent and acute behavioral disturbance: 20 minutes (interquartile range [IQR] 11 to 37 min) for droperidol, 24 minutes (IQR 13 to 35 minutes) for midazolam, and 25 minutes (IQR 15 to 38 minutes) for the combination. Additional sedation was required in 11 (33%; 95% confidence interval [CI] 19% to 52%) droperidol patients, 18 (62%; 95% CI 42% to 79%) midazolam patients, and 12 (41%; 95% CI 24% to 61%) in the combination group. The hazard ratio for additional sedation in the midazolam versus droperidol group was 2.31 (95% credible interval 1.01 to 4.71); for the combination versus droperidol, 1.18 (95% credible interval 0.46 to 2.50). Patient and staff injuries and number of further episodes of violent and acute behavioral disturbance did not differ between groups. There were two adverse effects for droperidol (6%; 95% CI 1% to 22%), 8 for midazolam (28%; 95% CI 13% to 47%), and 2 for the combination (7%; 95% CI 1% to 24%). An abnormal QT occurred in 2 of 31 (6%; 95% CI 1% to 23%) droperidol patients, which was not different from the other groups. Conclusion: Intramuscular droperidol and midazolam resulted in a similar duration of violent and acute behavioral disturbance, but more additional sedation was required with midazolam. Midazolam caused more adverse effects because of oversedation, and there was no evidence of QT prolongation associated with droperidol compared with midazolam. 2012-09-13T05:10:23.041Z ]]> http://nova.newcastle.edu.au/vital/access/manager/Repository/uon:11215 The most common coagulopathy associated with snake envenoming worldwide is venom-induced consumption coagulopathy (VICC), which results from activation of the coagulation pathway by snake toxins including thrombin-like enzymes, prothrombin activators, and factor X activators. VICC has often been likened to disseminated intravascular coagulation (DIC) because of the elevated D-dimer, prolonged prothrombin time, and low fibrinogen. However, VICC is not characterized by other important features of DIC, such as evidence of systemic microthrombi and end-organ failure. In addition, the time course of VICC differs with rapid onset and resolution, and the mechanism of initiation of coagulation activation differs because thrombin generation in DIC is mediated by the tissue factor/factor VIIa pathway. In a proportion of patients with VICC, a clinical syndrome consistent with thrombotic microangiopathy has been reported and is characterized by acute renal failure, thrombocytopenia, and microangiopathic hemolytic anemia. This thrombotic microangiopathy appears to only occur in conjunction with VICC but in several different snakes worldwide including vipers and elapids. Consistent with thrombotic microangiopathy, it progresses despite the resolution of the coagulopathy, suggesting a distinct but related process. The existence of the overlapping clinical syndromes of VICC and thrombotic microangiopathy in snake envenoming is the likely reason for the mistaken idea that snakebite causes DIC. 2012-08-10T00:00:01.779Z ]]> http://nova.newcastle.edu.au/vital/access/manager/Repository/uon:10953 Objectives: To determine which laboratory tests are first associated with severe envenoming after a snakebite, when (ie, how long after the bite) the test results become abnormal, and whether this can determine a safe observation period after suspected snakebite. Design, patients and setting: Prospective cohort study of 478 patients with suspected or confirmed snakebite recruited to the Australian Snakebite Project from January 2002 to April 2009, who had at least three sets of laboratory test results and at least 12 hours of observation in hospital after the bite. Severe envenoming was defined as venom-induced consumption coagulopathy (VICC), myotoxicity, neurotoxicity or thrombotic microangiopathy. Main outcome measures: International normalised ratio (INR), activated partial thromboplastin time (aPTT), creatine kinase (CK) level, and neurological examination. Results: There were 240 patients with severe envenoming, 75 with minor envenoming and 163 non-envenomed patients. Of 206 patients with VICC, 178 had an INR > 1.2 (abnormal) on admission, and the remaining 28 had an INR > 1.2 within 12 hours of the bite. Of 33 patients with myotoxicity, a combination of CK > 250 U/L and an abnormal aPTT identified all but two cases by 12 hours; one of these two was identified within 12 hours by leukocytosis. Nine cases of isolated neurotoxicity had a median time of onset after the bite of 4 hours (range, 35 min - 12 h). The combination of serial INR, aPTT and CK tests and repeated neurological examination identified 213 of 222 severe envenoming cases (96%) by 6 hours and 238 of 240 (99%) by 12 hours. Conclusion: Laboratory parameters (INR, aPTT and CK) and neurological reassessments identified nearly all severe envenoming cases within 12 hours of the bite, even in this conservative analysis that assumed normal test results if the test was not done. 2012-06-22T06:01:40.313Z ]]> http://nova.newcastle.edu.au/vital/access/manager/Repository/uon:10950 Objective: To describe the clinical features and laboratory findings in patients with definite red-bellied black snake (RBBS; Pseudechis porphyriacus) bites, including correlation with results of venom assays. Design, patients and setting: Prospective cohort study of patients with definite RBBS bites, recruited to the Australian Snakebite Project from January 2002 to June 2010. Main outcome measures: Clinical and laboratory features of envenoming; peak venom concentrations and antivenom treatment. Results: There were 81 definite RBBS bites; systemic envenoming occurred in 57 patients (70%) and local envenoming alone occurred in one patient. Systemic envenoming was characterised by local envenoming in 55 patients (96%), systemic symptoms in 54 patients (95%), anticoagulant coagulopathy with a raised activated partial thromboplastin time (aPTT) in 35 patients (61%) and myotoxicity in seven patients (12%). One patient required non-invasive ventilation for severe myotoxicity that resulted in muscle weakness. Three patients developed local ulceration. There were no deaths. Twenty-two envenomed patients (39%) received tiger snake or black snake antivenom, and administration within 6 hours of the bite was associated with normalisation of the aPTT. Eight patients (36%) had immediate hypersensitivity reactions to antivenom, including one case of anaphylaxis. The median peak venom concentration in 37 systemically envenomed patients with serum available was 19ng/mL (interquartile range, 12-50 ng/mL; range, 3-360ng/mL), which did not correlate with clinical severity. In 17 patients who received antivenom and had venom concentration measured, no venom was detected in serum after the first antivenom dose, including nine who were given one vial of tiger snake antivenom. Conclusion: RBBS envenoming caused local effects, systemic symptoms, anticoagulant coagulopathy and, uncommonly, myotoxicity. One vial of tiger snake or black snake antivenom appears to be sufficient to remove venom and neutralise reversible effects, but hypersensitivity reactions occurred in over a third of patients. 2012-06-22T05:59:53.203Z ]]> http://nova.newcastle.edu.au/vital/access/manager/Repository/uon:10828 Objective: The aim of this study was to describe the clinical and electrocardiographic features of risperidone overdose, including the frequency of dystonic reactions. Methods: A consecutive series of admissions for risperidone overdose (>6 mg) were identified from a prospective database of poisoning admissions to a regional toxicology service. Data extracted included patient demographics, details of ingestion, clinical features including neurological findings and evidence of dystonias, electrocardiographic parameters (heart rate [HR], QRS, and QT intervals), complications, and medical outcomes including intensive care unit admission. In addition to descriptive statistics, visual inspection of plots of QT-HR pairs compared with the QT nomogram was performed. Results: There were 107 patients with 157 presentations, including 38 patients with 45 risperidone-alone overdoses. Of the 38 patients who ingested risperidone alone, the median age was 25 years (interquartile range [IQR],16-31 years), and 19 (50%) were female. The median dose ingested was 33 mg (IQR, 15-75 mg; range, 8-248 mg). Median length of stay was 16 hours (IQR, 8-18 hours), and none was ventilated or admitted to the intensive care unit. There were 5 cases (11%) with dystonic reactions, 26 (58%) with tachycardia (HR ≥100 beats/min), and no cases with hypotension (blood pressure <90 mm Hg). Only 1 patient (2%) recorded a decreased Glasgow Coma Scale score of 14, and there were no seizures or deaths. On review of electrocardiograms in 41 of the 45 cases where risperidone was ingested alone, there were no acute dysrhythmias. In 4 electrocardiograms (10%), there was an abnormal QT-HR pair, but all bar one were associated with an HR of greater than 110 beats/min. The median maximum QRS width was 80 milliseconds (IQR, 80-80 milliseconds; range, 40-120 milliseconds). Conclusions: Risperidone taken alone in overdose causes minimal effects. Tachycardia and dystonic reactions were the main features of toxicity. Significant cardiac and other neurological features seem to be uncommon. 2012-05-21T23:31:23.898Z ]]> http://nova.newcastle.edu.au/vital/access/manager/Repository/uon:10754 The role of drug assays for screening, diagnosis, and guiding treatment decisions in overdose patients remains unclear. The use of drug concentration data in clinical toxicology research is more problematic, with studies using drug concentrations to simply confirm ingestion in observational studies or others report drug concentration time profiles with simplified pharmacokinetics. The reasons for the lack of more substantial pharmacokinetic and/or pharmacodynamic analysis in overdose patients include problems with uncertainty in dose, uncertainty in the time of ingestion, and limited sampling in the absorption phase. Many of these can be overcome by using population pharmacokinetic and pharmacokinetic-pharmacodynamic analysis in prospective studies of overdose patients to understand dose-concentration-effect relationships. Uncertainty in dose and dose time can be included using population analysis techniques, which may involve a clinical assessment of the veracity of the patient history. The pharmacokinetic-pharmacodynamic model can then be used as the basis for predicting toxicity and clinical outcomes from historical information such as dose and early clinical effects. Using such an approach means that the use of drug concentration data in research will improve the risk assessment in overdose patients, without requiring these assays to be rapidly available in the acute health setting. 2012-05-07T03:02:26.835Z ]]> http://nova.newcastle.edu.au/vital/access/manager/Repository/uon:10751 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. 2012-05-07T03:01:25.903Z ]]> http://nova.newcastle.edu.au/vital/access/manager/Repository/uon:10701 Assessment of the procoagulant effect of snake venoms is important for understanding their effects. The aim of this study was to develop a simple automated method to measure clotting times to assess procoagulant venoms. A turbidimetric assay was developed which monitors changes in optical density when plasma and venom are mixed. Plasma was added simultaneously to venom solutions in a 96 well microtitre plate. After mixing, the optical density at 340 nm was monitored in a microplate reader every 30 s over 30 min. The clotting time was defined as the lag time until the absorbance sharply increased. The turbidimetric method was compared to manual measurement of the clotting time defined as the time when a strand of fibrin can be drawn out of the mixture. The two methods were done simultaneously, with the same venom and plasma, and compared by plotting the manual versus turbidimetric clotting times. Within-day and between-day runs were done and the coefficient of variation (CV) was calculated. Plots comparing manual clotting times to the lag time in the turbidimetric assay showed good correlation between the two methods for brown snake (Pseudonaja textilis) venom, including 24 determinations in triplicate over six days for seven different venom concentrations. Good correlation was also found for four other venoms: tiger snake (Notechis scutatus), Carpet viper (Echis carinatus), Russell's viper (Daboia russelii) and Malaysian pit piper (Calloselasma rhodostoma). Between-day CV was in the range 10–20% for both methods, while within-day CV < 10%. The turbidimetric assay appears to be a simple and convenient automated method for the measurement of clotting times to assess the effects of procoagulant venoms. 2012-04-24T05:57:30.362Z ]]> http://nova.newcastle.edu.au/vital/access/manager/Repository/uon:10648 Chironex fleckeri (box jellyfish) are found in the northern tropical waters of Australia. Although C. fleckeri have a wide geographical distribution and are able to swim large distances, adults tend to stay in small restricted areas. Clinical data shows that deaths from envenoming have not been recorded in Western Australia, yet numerous fatalities have occurred in Northern Territory and Queensland waters. One explanation for this discrepancy is a geographical variation in venom composition. This study examined the pharmacological and biochemical profiles of C. fleckeri venom from different geographical locations and seasons. Venoms were screened for cytotoxicity using a rat aortic smooth muscle cell line (A7r5). While all venoms caused concentration-dependent cytotoxicity, differences were seen in the potency of venoms from Mission Beach and Weipa, when collected in different seasons, as indicated by IC50 values. Similarly venoms collected within the same season, from different locations around Australia, displayed marked differences in venom composition as shown by size exclusion HPLC and SDS-PAGE profiles which indicated the absence or reduced quantity of ‘peaks’ in some venoms. Based on IC50 data obtained from the cell assay, the effects of the most potent (i.e. from Weipa in 2006) and the least potent (i.e. from Broome in 2007) venoms were examined in anesthetised rats. Both venoms at 10 μg/kg (i.v.) caused a transient hypertensive phase followed by cardiovascular collapse. However, at 4 μg/kg (i.v.) venom from Weipa 2006 caused a transient hypertensive phase followed by a transient decrease in MAP while venom from Broome 2007 only caused a small transient increase in MAP. This study demonstrates that there is considerable geographical variation in the composition of C. fleckeri venoms which is most distinct between specimens from western and eastern Australia and may explain the geographical variation in reported deaths. 2012-04-16T01:37:59.332Z ]]> http://nova.newcastle.edu.au/vital/access/manager/Repository/uon:358 This study documents the effects of puffer-fish poisoning on peripheral nerve. Excitability measurements investigated membrane properties of sensory and motor axons in four patients. The median nerve was stimulated at the wrist, with compound muscle potentials recorded from abductor pollicis brevis and compound sensory potentials from digit 2. Stimulus-responses, strength-duration time constant (tau(SD)), threshold electrotonus, and current-threshold relations were recorded. The urine of each patient tested positive for tetrodotoxin. Compared with controls, axons were of higher threshold, compound muscle action potentials and compound sensory nerve action potentials were reduced in amplitude, latency was prolonged, and T-SD was reduced. In recovery cycles, refractoriness, superexcitability, and late subexcitability were decreased. Threshold electrotonus of motor axons exhibited distinctive abnormalities with less threshold decline than normal on depolarization and greater threshold increase on hyperpolarization (p < 0.0005 for each patient). The changes in excitability were reproduced in a mathematical model by reducing sodium (Na+) permeabilities by a factor of two. This study confirms that the neurotoxic effects of puffer-fish poisoning can be explained by tetrodotoxin blockade of Na+ channels. It demonstrates the ability of noninvasive nerve excitability studies to detect Na+ channel blockade in vivo and also the utility of mathematical modeling to aid interpretation of altered excitability properties in disease. 2012-03-01T00:34:40.352Z ]]> http://nova.newcastle.edu.au/vital/access/manager/Repository/uon:10032 An understanding of the cross-neutralisation of snake venoms by antibodies is important for snake antivenom development. We investigated the cross-neutralisation of brown snake (Pseudonaja textilis) venom, taipan (Oxyuranus scutellatus) venom and death adder (Acanthophis antarcticus) with commercial antivenoms and monovalent anti-snake IgG, using enzyme immunoassays, in vitro clotting and neurotoxicity assays. Each commercial antivenom bound all three venoms, and neutralised clotting activity of brown snake and taipan venoms and neurotoxicity of death adder venom. The ‘in-house’ monovalent anti-snake venom IgG raised against procoagulant brown snake and taipan venoms, did not neutralise the neurotoxic effects of death adder venom. However, they did cross-neutralise the procoagulant effects of both procoagulant venoms. This supports the idea of developing antivenoms against groups of snake toxins rather than individual snake venoms. 2012-02-10T04:00:03.644Z ]]> http://nova.newcastle.edu.au/vital/access/manager/Repository/uon:10030 We report a 60 year old male bitten by snakes from the Acanthophis genus (Death adder) on two occasions who developed high titres of human IgG antibodies to Acanthophis venom detected at the time of the second bite. The patient was bitten by Acanthophis antarcticus (common death adder) on the first occasion, developed non-specific systemic effects and did not receive antivenom. Three months later he was bitten by Acanthophis praelongus (northern death adder) and he developed significant local myotoxicity associated with a moderate rise in the creatine kinase (maximum 4770 U/L). He was given antivenom 55 h after the bite and recovered over several days. Death adder venom was detected in serum at the time of the first bite, but not the second bite. Human IgG antibodies to death adder were detected on the second admission but not the first. However, despite the presence of antibodies to death adder venom and free venom not being detected, the patient still developed significant local myotoxicity. 2012-02-10T03:50:03.757Z ]]> http://nova.newcastle.edu.au/vital/access/manager/Repository/uon:10025 Despite widespread use of antivenoms, many questions remain about their effectiveness in the clinical setting. The almost universal acceptance of their value is based mainly on in vitro studies, animal studies and human observational studies. Numerous examples exist where they demonstrate clear benefit, such as consumption coagulopathy in viper envenoming, prevention of neurotoxicity in Australasian elapid bites, systemic effects in scorpion and funnel-web spider envenoming. There are also concerns about the quality and efficacy of some antivenoms. However, it is important not to confuse the efficacy of antivenom, defined as its ability to bind and neutralise venom-mediated effects under ideal conditions, and the effectiveness of antivenom, defined as its ability to reverse or prevent envenoming in human cases. There are numerous potential reasons for antivenom failure in human envenoming, of which antivenom inefficacy is only one. Other important reasons include venom-mediated effects being irreversible, antivenom being unable to reach the site of toxin-mediated injury, or the rapidity of onset of venom-mediated effects. A number of recent studies in Australia bring into question the effectiveness of some antivenoms, including snake antivenom for coagulopathy, redback spider and box jellyfish antivenoms. Despite brown snake antivenom being able to neutralise venom induced clotting in vitro, use of the antivenom in human envenoming does not appear to change the time course of coagulopathy. However, it is important that apparent antivenom ineffectiveness in specific cases is correctly interpreted and does not lead to a universal belief that antivenom is ineffective. It should rather encourage further studies to investigate the underlying pathophysiology of envenoming, the pharmacokinetics of venoms and antivenoms, and ultimately the effectiveness of antivenom based on snake type, clinical effects and timing of administration. 2012-02-10T03:20:04.156Z ]]> http://nova.newcastle.edu.au/vital/access/manager/Repository/uon:10024 Venom-induced consumption coagulopathy occurs in snake envenoming worldwide but the interaction between procoagulant snake venoms and human coagulation remains poorly understood. We aimed to evaluate an assay using endogenous thrombin potential (ETP) to investigate the procoagulant properties of a range of Australian whole venoms in human plasma and compared this to traditional clotting and prothrombinase activity studies. We developed a novel modification of ETP using procoagulant snake venoms to trigger thrombin production. This was used to characterise the relative potency, calcium and clotting factor requirements of five important Australian snake venoms and efficacy of commercial antivenom, and compared this to prothrombinase activity and clotting assays. All five venoms initiated thrombin generation in the absence and presence of calcium. Pseudonaja textilis (Brown snake; p < 0.0001), Hoplocephalus stephensii (Stephen’s-banded snake; p < 0.0001) and Notechis scutatus (tiger snake; p = 0.0073) all had statistically significant increases in ETP with calcium. Venom potency varied between assays, with ETP ranging from least potent with Oxyuranus scutellatus (Taipan) venom to intermediate with N. scutatus and H. stephensii venoms to most potent with P. textilis and Tropidechis carinatus (Rough-scale snake) venoms. ETPs for N. scutatus, T. carinatus and H. stephensii venoms were severely reduced with factor V deficient plasma. Antivenom neutralized the thrombin generating capacity but not prothrombin substrate cleaving ability of the venoms. Contrary to previous studies using clotting tests and factor Xa substrates, these venoms differ in calcium requirement. ETP is a useful assay to investigate mechanisms of other procoagulant venoms and is a robust method of assessing antivenom efficacy. 2012-02-10T02:50:06.649Z ]]> http://nova.newcastle.edu.au/vital/access/manager/Repository/uon:9726 Background: Acute behavioural disturbance (ABD) is an increasing problem in emergency departments. This study aimed to determine the impact of a structured intramuscular (IM) sedation protocol on the duration of ABD in the emergency department. Methods: A historical control study was undertaken comparing 58 patients who required physical restraint and parenteral sedation with the structured IM sedation protocol, to 73 historical controls treated predominantly by intravenous sedation, according to individual clinician preference. The primary outcome was the duration of the ABD defined as the time security staff were required. Secondary outcomes were the requirement for additional sedation, drug related-adverse effects and patient and staff injuries. Results: The median duration of the ABD in patients with the new sedation protocol was 21 minutes (IQR: 15 to 35 minutes; Range: 5 to 78 minutes) compared to a median duration of 30 minutes (IQR: 15 to 50 minutes; Range: 5 to 135 minutes) in the historical controls which was significantly different (p = 0.03). With IM sedation only 27 of 58 patients (47%; 95% CI: 34% to 60%) required further sedation compared to 64 of 73 historical controls (88%; 95%CI: 77% to 94%). There were six (10%) drug-related adverse events with the new IM protocol [oxygen desaturation (5), oxygen desaturation/airway obstruction (1)] compared to 10 (14%) in the historical controls [oxygen desaturation (5), hypoventilation (4) and aspiration (1)]. Injuries to staff occurred with three patients using the new sedation protocol and in seven of the historical controls. Two patients were injured during the new protocol and two of the historical controls. Conclusion: The use of a standardised IM sedation protocol was simple, more effective and as safe for management of ABD compared to predominantly intravenous sedation. 2012-01-30T05:21:39.641Z ]]> http://nova.newcastle.edu.au/vital/access/manager/Repository/uon:7015 To investigate factors that predict the probability and duration of mechanical ventilation in quetiapine overdose, and if cardiac toxicity occurs, this cohort study involved 176 patients presenting to a toxicology unit on 286 occasions with quetiapine overdose. Patient demographics, dose, coingestants, single dose activated charcoal (SDAC) administration, requirement for and duration of mechanical ventilation and electrocardiogram parameters (heart rate, QT, QRS) were obtained. A fully Bayesian approach using logistic regression and time-to-event analysis was undertaken to investigate the relationship between predictor variables and the requirement for and duration of intubation. QT versus heart rate was plotted on a QT nomogram to investigate QT prolongation. The commonest clinical effects were central nervous system depression on 136 occasions (48%) and tachycardia (67%). There were no malignant arrhythmias and an abnormal QT occurred in only 24 admissions (8.4%), all with tachycardia. Hypotension (systolic blood pressure <90 mmHg) occurred on 35 occasions (12%). The logistic regression model supported dose and SDAC (<2 h) influencing the probability of intubation, but not age, sex, therapeutic use of quetiapine or coingestants. The probability of intubation was 10% after 2 g, 22% after 5 g, 37% after 10 g and 55% after 20 g and SDAC resulted in a reduced probability of intubation of 7% for 2 g ingestion. The median duration of ventilation was 22 h (interquartile: 19-28 h), which was not affected by SDAC. Ingested dose can inform early decision making about requirements for intensive care unit admission and intubation. SDAC seems to have only modest effects on outcomes but may be considered within 2 h for large ingestions. Electrocardiogram monitoring is unlikely to be necessary. 2012-01-30T05:05:58.940Z ]]> http://nova.newcastle.edu.au/vital/access/manager/Repository/uon:8129 Study objective: We investigate the clinical effects of escitalopram overdose and determine the risk of QT prolongation and serotonin toxicity. Methods: A review of escitalopram overdoses to a clinical toxicology unit was undertaken. Patient demographics, details of the ingestion, clinical effects, including evidence of serotonin toxicity, complications (arrhythmias and seizures), ICU admission, and length of stay were obtained. QT and QRS intervals were manually measured on ECGs by using a standardized approach. In a subgroup of 34 prospectively recruited patients, escitalopram was detected in blood from 33 patients. Medians and interquartile ranges (IQR) were reported, and QT versus pulse rate was plotted on a QT nomogram to investigate QT prolongation. Results: Median ingested dose in the 79 presentations was 140 mg (IQR 75 to 260 mg; range 20 to 560 mg), and escitalopram was the only drug ingested or all coingested drugs were nontoxic in 46 cases. Median length of stay for patients receiving clinically important coingestants was 19 hours (IQR 9 to 33 hours) compared with that of patients receiving escitalopram alone (median 12 hours; IQR 7 to 19 hours). Serotonin toxicity occurred in 7 of the 46 escitalopram-alone ingestions (15%) but in only 1 of the 33 patients coingesting other medications. Common features were inducible clonus and hyperreflexia. Central nervous system depression and ICU admission were rare in escitalopram-alone overdoses compared with those in cases with sedative coingestants. Bradycardia (pulse rate <60 beats/min) occurred in 11 cases (14%) and an abnormal QT–HR pair in 11 (14%), which was associated with normal or slow pulse rates. There were no deaths, seizures, or arrhythmias. Conclusion: Major manifestations of escitalopram overdose were serotonin toxicity, QT prolongation, and bradycardia. The study suggests a potential for cardiac arrhythmias in escitalopram overdose. 2011-07-06T05:10:09.362Z ]]> http://nova.newcastle.edu.au/vital/access/manager/Repository/uon:7887 Aims: To investigate serial electrocardiogram (ECG) parameters, haemodynamic changes and arrhythmias following venlafaxine overdose. Methods: The study included 369 venlafaxine overdoses in 273 patients presenting to a toxicology unit where an ECG was available. Demographic information, details of ingestion, haemodynamic effects [heart rate and blood pressure (BP)] and complications (arrhythmias and conduction defects) were obtained. ECG parameters (QT, QRS) were measured manually and analysed by visual inspection, including plotting QT–HR pairs on a QT nomogram. Results: The median ingested dose was 1500 mg [interquartile range (IQR) 600–3000 mg; range 75–13 500 mg). Tachycardia occurred in 54% and mild hypertension (systolic BP >140 mmHg) in 40%. Severe hypertension (systolic BP >180 mmHg) and hypotension (systolic BP <90 mmHg) occurred in 3% and 5%, respectively. No arrhythmias occurred based on continuous telemetry, and conduction defects were found in only seven of 369 admissions; five of these conduction defects were pre-existing abnormalities. In 22 admissions [6%, 95% confidence interval (CI) 4–10] there was an abnormal QT–HR pair, with larger doses being more likely to be associated with an abnormal QT. The median maximum QRS width was 85ms (IQR 80–90 ms; range 70–145 ms) and the QRS was greater than 120 ms in only 24 admissions (7%, 95% CI 4–10). Conclusions: Venlafaxine overdose causes only minor abnormalities in the QT and QRS intervals, unlikely to be associated with major arrhythmias, except possibly with large doses. 2011-06-20T00:00:17.538Z ]]> http://nova.newcastle.edu.au/vital/access/manager/Repository/uon:7637 Objective: The belief that the full moon and disturbed behaviour are closely linked is alive and well, despite studies to the contrary. We investigated the possibility that there is an association between only extreme behavioural disturbance and the full moon. Design, setting and participants: We undertook an observational study of patients with violent and acute behavioural disturbance who presented to the emergency department of Calvary Mater Newcastle and patients with less severe behaviour for whom hospital security calls were made. Main outcome measure: Proportion of patients for whom presentation or security call occurred in each lunar phase, modelled as a Poisson process. Results: Of 91 patients with violent and acute behavioural disturbance, 21 (23%) presented during the full moon - double the number for other lunar phases (P = 0.002). Sixty (66%) had either alcohol intoxication or psychostimulant toxicity, and five attacked staff (biting [2], spitting [1], kicking [1] and scratching [1]). In contrast, 512 hospital security calls for patients with less severe behaviour were evenly distributed throughout the lunar cycle. Conclusion: Violent and acute behavioural disturbance manifested more commonly during the full moon. 2011-05-03T00:00:02.164Z ]]> http://nova.newcastle.edu.au/vital/access/manager/Repository/uon:7559 Objective: To determine the proportion of adverse events in patients discharged after ED assessment for possible acute coronary syndrome. Methods: Prospective observational cohort study enrolling consecutive patients presenting with symptoms suggestive of coronary syndrome. Main outcome was the proportion of adverse coronary events (defined a priori) within 30 days. Results: Of 2627 patients, 1819 (69%) were discharged without a diagnosis of coronary syndrome and 808 (31%) were admitted for further investigation and treatment. Of these, 385 (14.7%) were given a final diagnosis of acute coronary syndrome. On 30 day follow up, 18 of the discharged patients were diagnosed with acute coronary syndrome (0.7%; 95% confidence intervals [CI] 0.4–1.1%), 10 with unstable angina (0.4%; 95% CI 0.2–0.7%) and 8 with non-ST elevation myocardial infarction (0.3%; 95% CI 0.2–0.6%). There were no cases of ST elevation infarction or death. The sensitivity for diagnosis of acute coronary syndromes was 95.5% (95% CI 92.9–97.3%). Average length of stay was 7 h for discharged patients. Forty-six per cent of patients with diabetes and 47% with a past history of coronary disease were discharged. Subsequent outpatient stress testing was performed in 13.6%. Conclusions: In a large Australian ED, less than 1% of patients presenting with symptoms suggestive of coronary syndrome were discharged and subsequently had a 30 day adverse event. Reducing this proportion by admitting patients with traditional risk factors would markedly increase hospital workload. Opportunities exist to improve both the safety and efficiency of chest pain assessment in the ED. 2011-04-12T03:40:11.148Z ]]> http://nova.newcastle.edu.au/vital/access/manager/Repository/uon:7557 Background: Despite the development of evidence-based practice guidelines in many countries for asthma treatment in children, there is limited evidence that using such guidelines improves patient care. Aims: Our aim was to evaluate whether the implementation of an evidence-based asthma clinical practice guideline (CPG) worksheet changes clinical practice. Methods: The study was a before and after study of the implementation of a paediatric asthma CPG in a tertiary paediatric emergency department (ED). All children aged 2–16 years who had a diagnosis of asthma were included. Clinical data were obtained by retrospective chart review for time periods before (May to September 2003) and after (May to September 2005) the introduction of the CPG worksheet. Primary outcomes were: use of spacers for salbutamol instead of nebulisers, use of ipratropium and use of corticosteroids. Secondary outcomes were use of an ED action plan, ordering chest X-rays (CXR) and admission rate. Results: Before implementation, 240 children presented with asthma and after implementation, 286 children presented. The two groups had similar ages, asthma severity, admission respiratory rate (RR) and oxygen saturation. Following implementation there was an increase in spacer use from 17 to 26% [+9%; 95% confidence interval (CI): 2–16%; p = 0.015] and a reduction in ipratropium use from 58 to 44% (−13%; 95% CI: −22 to −5%; p = 0.0029). The proportion of patients treated with corticosteroids did not change. The number of patients with an ED action plan increased. The number of CXR ordered decreased and the hospital admission rate decreased. Conclusions: The study demonstrates that implementation of an asthma CPG worksheet in a tertiary paediatric ED resulted in modest changes in clinical practice, mainly by increasing clinician adherence to the guidelines. 2011-04-12T03:40:04.161Z ]]> http://nova.newcastle.edu.au/vital/access/manager/Repository/uon:7545 Objective: Behavioural disturbance and aggression in the ED is an increasing problem. The present study describes the characteristics of patients with acute behavioural disturbance and their emergent treatment in an ED with a structured team approach. Methods: This was a retrospective review of acute behavioural emergencies that required response from the Code Black (CB) Team (duress response team) in the ED during 2006. The hospital security log and hospital incident-reporting system identified all documented CB, and the patients' medical records were reviewed. Information extracted included patient demographics and presenting complaint, details of the CB, the use of pharmacological sedation, physical restraint and patient disposition. Injuries to hospital staff were also extracted. Results: There were 122 patients, median age 32 years (interquartile range: 24–43 years, range: 14–81 with 71 male patients (58%) who accounted for 143 CB activations. The primary problems were deliberate self-poisoning or self-harm (38%), alcohol and illicit drug intoxication (33%) and psychiatric, organic illness and drug withdrawal (29%). One hundred and eight (89%) patients had a past history of alcohol/illicit drug abuse or psychiatric illness. Indications for CB activation were threatening harm to others or behaving violently in 67% of cases. Combined pharmacological sedation and physical restraint were required on 66 (46%) occasions, pharmacological sedation alone on 20 (14%), physical restraint alone on 14 (10%) and neither on 43 (30%) occasions. Benzodiazepines were most commonly used for initial sedation, including i.m. (29%), i.v. midazolam (20%), diazepam (42%) and antipsychotics (9%), most commonly droperidol. More diazepam and droperidol were used for subsequent pharmacological sedation. A staff member was injured on only one occasion (0.7%). Conclusions: Acute behavioural disturbance was common in the present study, and underlying causes were predominantly organic in nature. A team approach appears to be valuable in managing these incidents. 2011-04-08T06:10:13.336Z ]]> http://nova.newcastle.edu.au/vital/access/manager/Repository/uon:7354 Introduction: Chironex fleckeri is a large box jellyfish that has been labelled the ‘most venomous animal’ in the world. We have recently shown that the primary effect of C. fleckeri venom in vivo is cardiovascular collapse. This study utilised a cell-based assay to examine the effects of C. fleckeri venom on the proliferation of a rat aortic smooth muscle cell line. In addition, the ability of CSL box jellyfish antivenom and/or various potential treatment strategies to neutralise the effects of the venom was examined. Methods: A7r5 cells were cultured in media containing venom. The effect of CSL box jellyfish antivenom (5 U/mL), CSL polyvalent snake antivenom (5 U/mL), lanthanum (5 μM), MgSO4 (50 mM), verapamil (5 μM) or felodipine (5 μM) was examined. Cell viability was determined using a Cell titer 96 AQueous One Solution cell proliferation assay. Results: Incubation of A7r5 cells with serially diluted venom (2–0.004 µg/mL) caused a concentration-dependent inhibition of cell proliferation with an IC50 value of 0.056 μg/mL. This response was not affected by the absence of calcium or the presence of lanthanum in the media. Box jellyfish antivenom (5 U/mL) prevented the inhibition of cell proliferation caused by the venom. Verapamil (5 μM) had no significant effect on the inhibition. In contrast, felodipine (5 µM) or MgSO4 (50 mM) potentiated the effects of the venom and partially negated the protective effect of the antivenom. Discussion: This study displayed the ability to utilise a cell-based assay to determine the effects of C. fleckeri venom on vascular cell viability. It showed that CSL box jellyfish can neutralise the effects of the venom but only if added prior to the venom. In addition, potential adjunct therapies verapamil, felodipine and MgSO4 were found to be ineffective, with felodipine and MgSO4 potentiating the detrimental effects of the venom. 2011-03-10T21:40:23.142Z ]]> http://nova.newcastle.edu.au/vital/access/manager/Repository/uon:7333 To assess interobserver agreement when trained healthcare staff measure the QT interval using a standardized approach across a range of QT lengths, a sample of 110 electrocardiograms (ECGs) was taken from general and psychotropic overdose admissions to the emergency department including drugs known to cause QT prolongation and Torsades de Pointes. Four of the authors measured the QT interval in all ECGs using a previously developed approach. Each rater was blinded to the ECG admission details and the measurements of the other raters. The primary outcome was the inter-rater agreement for the median QT and interobserver classification as to whether the QT interval was abnormal or not, based on the QT nomogram. There was good agreement between raters (intraclass correlation coefficient, 0.61; 95% CI = 0.53 to 0.69). When classifying the QT as abnormal there was good agreement between the raters with a Fleiss' kappa of 0.61. There was perfect agreement between all four raters on 86 of 110 ECGs (78.2%), agreement between three raters on 18 of 110 (16.3%), and a split between the four on 6 of 110 (5.5%). Disagreement between the automated QT measurement and the majority of the raters was slightly more than within raters. The study demonstrates that there is good agreement between trained observers when manually measuring the QT interval using a standardized approach. This provides an inexpensive method for the measurement of QT in clinical studies of drug overdose and a potentially useful approach in the clinical assessment of patients with possible QT prolongation. 2011-03-02T04:00:09.214Z ]]> http://nova.newcastle.edu.au/vital/access/manager/Repository/uon:7335 Despite the work by Bos et al. reported in Blood and by other researchers on the structure and function of the procoagulant molecules, the pathophysiology of venom-induced consumption coagulopathy (VICC) associated with human envenoming by these snakes remains unclear. Although it would appear that the presence of a factor Va–like toxin in brown snake (Pseudonaja spp) venom that is impervious to regulation by the hemostatic system provides a potent biologic weapon against prey and in human envenoming, clinical research does not fully support this. 2011-03-02T04:00:03.228Z ]]> http://nova.newcastle.edu.au/vital/access/manager/Repository/uon:7323 Monovalent antivenoms have a lower volume of specific antibodies that may reduce reactions but require accurate snake identification to be used. Polyvalent antivenoms are larger volume and may have a higher reaction rate. However, they avoid the problem of snake identification and may be more cost-effective to manufacture. We have previously shown cross-neutralisation of two Australian elapid venoms, tiger snake (Notechis scutatus) and brown snake (Pseudonaja textilis) venoms, by their respective monovalent antivenoms. In this study enzyme immunoassays were used to quantify the amount of monovalent antivenom (quantity of monovalent antibodies to a specific snake venom) in vials of commercially produced antivenom in Australia. All antivenoms tested appeared to be polyvalent and contain varying amounts of all five terrestrial snake monovalent antibodies based on their binding to the five representative venoms. Redback spider antivenom did not have any measurable binding affinity for any of the five snake venoms, showing that the observed binding is not due to non-specific interactions with equine protein. The antivenoms had expiry dates over a 15 year period, suggesting that the antivenoms have been mixtures for at least this time. This study cannot be used to rationalise hospital stocks of antivenom in Australia because there is no guarantee that the antivenoms will remain as mixtures. However, it would be possible for the manufacturer toreduce the number of types of snake antivenoms available in Australia to two polyvalent antivenoms which would simplify treatment of snakebite. 2011-03-01T01:10:09.142Z ]]> http://nova.newcastle.edu.au/vital/access/manager/Repository/uon:206 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. 2011-02-08T23:10:05.076Z ]]> http://nova.newcastle.edu.au/vital/access/manager/Repository/uon:7164 Background: Anaphylaxis is generally unanticipated and requires emergency management. Therefore, the biological mediators in human beings have been difficult to define. Objective: Our aim was to identify cytokines and chemokines whose concentrations increase during anaphylaxis in human beings and to determine how each correlates with severity. Methods: We measured the concentrations of potential mediators, including cytokines, chemokines, mast cell tryptase (MCT), and histamine, over 3 time points in 76 patients presenting to emergency departments with anaphylaxis and correlated these with a global severity scale, hypotension, and hypoxia. Results: IL-2, IL-6, IL-10, TNF receptor 1, MCT, and histamine were significantly elevated in patients with severe reactions (n = 36) compared with moderate reactions (n = 40) and healthy controls. Histamine levels peaked at emergency department arrival, whereas other mediators peaked later. IL-4, IL-5, IL-13, IFN-γ, and TNF-α were marginally elevated in severe reactions compared with healthy controls but did not correlate with reaction severity. Severe reactions tended to be either hypotensive (n = 19) or hypoxemic (n = 12). Levels of IL-6, IL-10, TNF receptor 1, MCT, and histamine correlated with hypotension. No mediator correlated with hypoxemia or other respiratory features. Conclusion: This study confirms that the concentrations of a number of cytokines are elevated in blood during anaphylaxis in human beings and that some correlate with the presence of hypotension. Others were only marginally elevated within a concentration range that available assays do not reliably detect. During respiratory reactions, mediators may be largely confined to the airways so that blood concentrations do not reflect activity. 2011-02-03T00:10:01.909Z ]]> http://nova.newcastle.edu.au/vital/access/manager/Repository/uon:7165 Objectives: To investigate an ED death audit process that included deaths occurring within 48 h of admission in addition to deaths in the ED. Methods: The study was a review of a prospective audit process undertaken in routine clinical practice that included auditing deaths in the ED and deaths of admitted patients within 48 h of ED presentation. Data were extracted from the audit database and included demography, clinical information and medical recommendations. The hospital incident investigation and monitoring system (IIMS) was searched for major incident reports involving death. The main outcome was the number of medical record audits from each group reported to the clinical governance unit for review, and whether the 48 h audit identified relevant cases to the ED in addition to those identified in the ED audit alone. Secondary outcomes were the number of audits resulting in other actions: ED policy review, education, case discussion or review with the inpatient team. Results: Over a 2 year period, 303 deaths were reviewed, including 75 deaths in the ED and 228 deaths within 48 h. The ED auditor recommended no further action in 66/75 (88%) ED deaths and 195/228 (86%) 48 h deaths. A major hospital review was recommended in 4/75 (5%) ED deaths and 11/228 (5%) 48 h deaths, with only 3 and 7 of these, respectively, having been detected by the hospital's IIMS. The audit identified 10 of 13 deaths notified to the IIMS and the remaining 3 did not involve error relevant to the ED. Internal review was recommended in one ED death and eight 48 h deaths. Conclusions: The present study demonstrates that auditing both ED deaths and 48 h deaths identifies additional issues relevant to the ED compared with auditing ED deaths alone or relying on standard hospital incident reporting. 2011-02-02T23:30:03.563Z ]]> http://nova.newcastle.edu.au/vital/access/manager/Repository/uon:1898 Background: Selective serotonin reuptake inhibitors (SSRIs) have increasingly replaced tricyclic antidepressants (TCAs) in the treatment of depression. They appear to be safer in overdose, but there is little information on their spectrum of toxicity in overdose, or relative toxicity of each agent. Objective: To determine the effect of SSRIs in overdose, as a group, and the relative toxicity of five different SSRIs. METHODS: A review of consecutive SSRI poisoning admissions to a single toxicology unit. Outcomes examined were length of stay [LOS], intensive care [ICU] admission rate, coma, seizures, electrocardiographic [ECG] abnormalities, and presence of serotonin syndrome [SS]. Logistic regression was used to model the outcome QTc > 440 msec. Results: There were 469 SSRI poisoning admissions analyzed after exclusions. The median LOS for all SSRI overdose admissions was 15.3 h (IQR: 10.5–21.3) and 30 of 469 (6.4%; 95% CI 4.3–9.0%) cases were admitted to ICU. The incidence of seizures was 1.9% and coma was 2.4%. Serotonin syndrome occurred in 14% of overdoses. Comparison of median QTc intervals of the five SSRIs was significantly different (p = 0.0002); citalopram (450 IQR: 436–484) was individually different to fluoxetine (p = 0.045), fluvoxamine (p = 0.022), paroxetine (p = 0.0002), and sertraline (p = 0.001). The proportion of citalopram overdoses with a QTc > 440 msec was 68%, differing significantly from sertraline (adjusted OR: 5.11 95% CI 2.32–11.27). Comparison of median QT intervals of the five SSRIs was statistically different (p = 0.026); citalopram (400 IQR: 380–440) was individually different from sertraline (p = 0.023). Conclusions: This study shows SSRIs are relatively safe in overdose despite serotonin syndrome being common. The exception was citalopram, which was significantly associated with QTc prolongation. We believe that cardiac monitoring should be considered in citalopram overdose, particularly with large ingestions and patients with associated cardiac disease. 2010-04-27T06:58:09.995Z ]]> http://nova.newcastle.edu.au/vital/access/manager/Repository/uon:1489 Objective: To characterize the frequency of aspiration pneumonitis in an unselected population of overdose patients and, further, to identify factors that predispose to aspiration pneumonitis and the outcomes of patients with aspiration pneumonitis compared with those without. Design: Retrospective cohort study. Setting: Toxicology unit of a tertiary referral hospital. Patients: All poisoning admissions. Measurements and Main Results: A total of 71 of 4,562 poisoning admissions to the Hunter Area Toxicology Service between January 1997 and October 2002 had definite aspiration pneumonitis (1.6%; 95% confidence interval, 1.2-2.0). Older age, Glasgow Coma Score of <15, spontaneous emesis, seizures, delayed presentation to hospital, and ingestion of tricyclic antidepressants were associated with an increased risk of aspiration pneumonitis. Paracetamol poisoning and female sex were associated with a decreased risk of aspiration pneumonitis with univariate analysis. Ingestion of alcohol, benzodiazepines, antipsychotics, and administration of activated charcoal were not associated with aspiration pneumonitis. A logistic regression model for predicting aspiration pneumonitis contained seven predictors: age, sex, Glasgow Coma Score of <15 (odds ratio, 3.14; 95% confidence interval, 1.87-5.27), emesis (odds ratio, 4.17; 95% confidence interval, 2.44-7.13), seizure, tricyclic antidepressant ingestion, and time from ingestion to presentation (delay of >24 hrs [odds ratio, 4.42; 95% confidence interval, 2.42-8.10]). The mortality for patients with aspiration pneumonitis was 8.5% compared with 0.4% for those without (odds ratio, 23; 95% confidence interval, 9-60; p < .0001), and they had a significantly higher intensive care unit admission rate. The median length of stay of patients with aspiration pneumonitis was 126 hrs (interquartile range, 62-210 hrs) compared with 14.7 hrs (interquartile range, 7-23 hrs) in patients without (p < .0001). Conclusions: Our study has shown a number of risk factors in overdose patients that are associated with aspiration pneumonitis that may allow the early identification of these patients for appropriate observation and management. Patients with aspiration pneumonitis have a significantly increased mortality and length of stay in the hospital. 2010-04-27T06:52:37.091Z ]]> http://nova.newcastle.edu.au/vital/access/manager/Repository/uon:1660 This study documents the effects of puffer-fish poisoning on peripheral nerve. Excitability measurements investigated membrane properties of sensory and motor axons in four patients. The median nerve was stimulated at the wrist, with compound muscle potentials recorded from abductor pollicis brevis and compound sensory potentials from digit 2. Stimulus-responses, strength-duration time constant (τSD), threshold electrotonus, and current-threshold relations were recorded. The urine of each patient tested positive for tetrodotoxin. Compared with controls, axons were of higher threshold, compound muscle action potentials and compound sensory nerve action potentials were reduced in amplitude, latency was prolonged, and τSD was reduced. In recovery cycles, refractoriness, superexcitability, and late subexcitability were decreased. Threshold electrotonus of motor axons exhibited distinctive abnormalities with less threshold decline than normal on depolarization and greater threshold increase on hyperpolarization (p < 0.0005 for each patient). The changes in excitability were reproduced in a mathematical model by reducing sodium (Na⁺) permeabilities by a factor of two. This study confirms that the neurotoxic effects of puffer-fish poisoning can be explained by tetrodotoxin blockade of Na⁺ channels. It demonstrates the ability of noninvasive nerve excitability studies to detect Na⁺ channel blockade in vivo and also the utility of mathematical modeling to aid interpretation of altered excitability properties in disease. 2010-04-27T06:28:08.604Z ]]> http://nova.newcastle.edu.au/vital/access/manager/Repository/uon:2911 Objective: The study aimed to provide a recommended list of performance indicators from routinely collected data that measure most aspects of the patient journey through the emergency department (ED). Methods: Data from a large tertiary ED were used to investigate the proposed performance indicators, which fell into 7 categories: background information, time from arrival to triage, time from triage to treatment, length of stay, readmission rate, left without being seen, and deaths in the ED. Main Results: Category 1 patients were triaged, treated, and discharged rapidly. For category 2 patients, the times from arrival to triage increased but times from triage to treatment were relatively stable. Patients in categories 3 and 4 were not triaged rapidly and both the arrival to triage and triage to treatment processes were unstable and deteriorating. The average time to treatment for patients treated outside recommended times was unstable and increasing for categories 2, 3, and 4. The number of patients who left without being seen was stable except for 2 periods, and the readmission rate was stable except for 1 period of increase. Conclusion: The performance indicators use only routinely collected data and clearly identify the areas in which this ED performed poorly. 2010-04-27T06:09:03.839Z ]]> http://nova.newcastle.edu.au/vital/access/manager/Repository/uon:298 2010-04-27T06:02:46.268Z ]]> http://nova.newcastle.edu.au/vital/access/manager/Repository/uon:242 Serotonin toxicity (or serotonin syndrome) has become an increasingly common and important clinical problem in medicine over the last 15 years with the introduction of many new antidepressants that can cause increased levels of serotonin (5-HT) in the central nervous system (CNS). Severe and lille-threatening cases are almost exclusively a result of combinations of antidepressants (usually monoamine oxidase inhibitors and selective serotonin reuptake inhibitors). Unfortunately, the term serotonin syndrome has a number of quite different meanings, and many people writing on this subject have failed to differentiate them. This has led to false conclusions regarding the 5-HT receptor subtypes responsible for the life-threatening effects in animal and human toxicity, and suggestions of ineffective treatment strategies. This review primarily addresses the serotonin receptor subtypes that underlie the clinical manifestations of excess CNS serotonin in humans and animals, and their implications for diagnosis and treatment. More specific diagnostic criteria for serotonin toxicity are required to identify situations when specific antidotes are likely to be useful. However, the mainstay of treatment of severe cases is good supportive care and early intubation and paralysis in life-threatening serotonin toxicity. 2010-04-27T06:01:09.730Z ]]> http://nova.newcastle.edu.au/vital/access/manager/Repository/uon:222 2010-04-27T06:00:49.320Z ]]> http://nova.newcastle.edu.au/vital/access/manager/Repository/uon:186 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. 2010-04-27T05:59:46.721Z ]]> http://nova.newcastle.edu.au/vital/access/manager/Repository/uon:5173 We thank Greene et al for their comments on our study of citalopram overdoses. They raise a number of issues about the study that we can clarify. We agree that it is difficult to determine how useful QT prolongation is as a predictor of citalopram-induced cardiotoxicity. However, Torsades de Pointes (TdP) has been reported in citalopram overdose and there is a well-known association between QT prolongation and malignant arrhythmias. We have recently shown that the QT nomogram used in our study is a valid approach to assessing an abnormal QT interval and risk of Torsades de Pointes. 2010-04-27T04:46:40.670Z ]]> http://nova.newcastle.edu.au/vital/access/manager/Repository/uon:5699 This book comprises a subset of the topics prepared by the Emergency Medicine expert writing group for the electronic product eTG complete. As resuscitation is essential to all aspects of emergency medicine, that section is reproduced in full as an introduction. Otherwise the main focus of the book is toxicology, toxinology, anaphylaxis and wilderness (environmental) medicine, including assessment and management of burns. There is also a limited amount of clinical pharmacological information about drugs used in the management of poisoning. 2010-04-27T04:43:58.543Z ]]> http://nova.newcastle.edu.au/vital/access/manager/Repository/uon:5485 AIMS: There are no studies measuring antivenom concentrations following intramuscular administration. This study aimed to compare antivenom concentrations following intravenous and intramuscular administration of redback spider antivenom (RBSAV). METHODS: Twenty patients recruited to a controlled trial comparing intramuscular and intravenous administration of antivenom had serial blood samples collected at 30 min intervals for 2 h after the administration of one or two doses of antivenom. Antivenom concentration was measured using an enzyme immunoassay. RESULTS: Ten patients received intramuscular antivenom but antivenom could not be detected in serum after either one or two vials, at any time point. The median time of the final sample after commencement of antivenom treatment in these patients was 3.2 h (1.8-5 h). Ten patients received intravenous antivenom (three one vial and seven two or more vials) and antivenom was detected in all patients. CONCLUSIONS: RBS AV given by the intramuscular route is unlikely to be effective in the treatment of redback (widow) spider bite. 2010-04-27T04:34:34.540Z ]]> http://nova.newcastle.edu.au/vital/access/manager/Repository/uon:5331 Irukandji syndrome is usually characterized by delayed severe abdominal, back and chest pain associated with autonomic effects including diaphoresis, hypertension and, in severe cases, myocardial injury and pulmonary oedema. It is most often associated with envenoming by the jellyfish Carukia barnesi, but a number of other jellyfish, including Alatina mordens, are now known to produce Irukandji syndrome. In the present study, nematocyst-derived venom from A. nr mordens (150-250 μg/kg, i.v.) produced a long-lasting pressor effect in anaesthetised rats. This pressor response (250μg/kg, i.v.) was significantly inhibited by prior administration of the α-adrenoceptor antagonist prazosin (200 μg/kg, i.v.) but not by CSL box jellyfish antivenom (300 U/kg, i.v.). A. nr mordens venom 250 μg/kg (i.v.) caused marked increases in plasma adrenaline and noradrenaline concentrations following administration in anaesthetised rats. The venom did not contain appreciable amounts of either adrenaline or noradrenaline. A. nr mordens venom (25 μg/ml) produced a contractile response in rat electrically stimulated vas deferens which was markedly reduced in tissues pre-treated with reserpine (0.1 mM) or guanethidine (0.1 mM). Sodium dodecyl sulphate (SDS)-PAGE analysis showed that A. nr mordens venom is comprised of multiple protein bands ranging from 10 to 200 kDa. Western blot analysis using CSL box jellyfish antivenom indicated several antigenic proteins in A. nr mordens venom, however, it did not detect all proteins present in the venom. This study characterizes the in vitro and in vivo effects of A. nr mordens venom and indicates that the cardiovascular effects are at least partially mediated by endogenous catecholamine release. 2010-04-27T04:30:54.132Z ]]>