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Objectives: To report the frequency and clinical outcomes of Amanita phalloides poisoning in the Australian Capital Territory and New South Wales, and the treatments used (including silibinin)., Design, Setting and Patients: Retrospective case series of patients admitted to public hospitals in Canberra and Sydney for suspected A. phalloides poisoning between 1999 and 2012 (identified from hospital records and calls to the New South Wales Poisons Information Centre)., Main Outcome Measures: Frequency of poisoning and the clinical outcomes., Results: Twelve patients presented with a history suggesting A. phalloides poisoning, 10 with probable poisoning and two with possible poisoning. Eight of those with probable poisoning developed significant hepatotoxicity and four died. Silibinin was administered to nine of those with probable poisoning (the other presented before 2005). Maintaining silibinin supply became a challenge during two clusters of poisoning. Eight of the patients with probable poisoning were not long-term residents of the ACT, and six were immigrants from Asia., Conclusions: The mortality rate due to A. phalloides poisoning in this case series was high despite treatment according to current standards, including use of silibinin, and the frequency of hepatotoxicity was more than double that for the previous decade. Ongoing public health campaigns are required.

Background: Acute organophosphorus pesticide poisoning causes tens of thousands of deaths each year across the developing world. Standard treatment involves administration of intravenous atropine and oxime to reactivate inhibited acetylcholinesterase. The clinical usefulness of oximes, such as pralidoxime and obidoxime, has been challenged over the past 20 years by physicians in many parts of the world., Objectives: To quantify the effectiveness and safety of the administration of oximes in acute organophosphorus pesticide-poisoned patients., Search Strategy: We searched both English and Chinese databases: Cochrane Injuries Group Specialised Register, Cochrane Central Register of Controlled Trials (The Cochrane Library), MEDLINE (Ovid SP), EMBASE (Ovid SP), ISI Web of Science: Science Citation Index Expanded (SCI-EXPANDED), ISI Web of Science: Conference Proceedings Citation Index-Science (CPCI-S) and the Chinese language databases CNKI and WANGFANG. All searches were run in September 2009., Selection Criteria: Articles that could possibly be RCTs were retrieved to determine if they were randomised., Data Collection and Analysis: The published methodology of three RCTs was not clear. We contacted the principal authors of these, but did not obtain further information., Main Results: Seven pralidoxime RCTs were found. Three RCTs including 366 patients studied pralidoxime vs placebo and four RCTs including 479 patients compared two or more different doses. These trials found quite disparate results with treatment effects ranging from benefit to harm. However, many studies did not take into account several issues important for outcomes. In particular, baseline characteristics were not balanced, oxime doses varied widely, there were substantial delays to treatment, and the type of organophosphate was not taken into account. Only one RCT compared the World Health Organization (WHO) recommended doses with placebo. This trial showed no clinical benefits and a trend towards harm in all sub-groups, despite clear evidence that these doses reactivated acetylcholinesterase in the blood., Authors' Conclusions: Current evidence is insufficient to indicate whether oximes are harmful or beneficial. The WHO recommended regimen (30 mg/kg pralidoxime chloride bolus followed by 8 mg/kg/hr infusion) is not supported. Further RCTs are required to examine other strategies and regimens. There are many theoretical and practical reasons why oximes may not be useful, particularly for late presentations of dimethyl OP and those with a large excess of OP that simply re-inhibits reactivated enzymes. Future studies should screen for patient sub-groups that may benefit and may need flexible dosing strategies as clinical effectiveness and doses may depend on the type of OP.

Background: An estimated 2-3 million people are acutely poisoned by organophosphorus pesticides each year, mostly in the developing world. There is a pressing need for new affordable antidotes and clonidine has been shown to be effective in animal studies. Our aim was to determine the safety of clonidine given as an antidote in adult patients presenting with signs or symptoms of acute organophosphate ingestion., Methods: This study was a dose finding, open-label, multicentre, phase II trial. Forty eight patients with acute organophosphate poisoning were randomized to receive either clonidine or placebo: Four to receive placebo and twelve to receive clonidine at each dose level. The first dose level was an initial loading dose of 0.15 mg followed by an infusion of 0.5 mg of clonidine over 24 hours. The initial loading dose was increased to 0.3 mg, 0.45 and 0.6 mg. at all dosing levels however the subsequent infusion remained at 0.5 mg of clonidine over 24 hours., Results: The baseline characteristics of both groups were similar. The trial was stopped after completion of the 3rd dosing level. At the 1st and 2nd dosing level there were no reported adverse drug reactions. At the 3rd dosing level 5 patients (42%) developed significant hypotension during clonidine treatment that responded to intravenous fluids. There were no statistical differences in ventilation rate, pre and post GCS, and mortality rates over all levels., Conclusion: Our findings suggest use of moderate doses of clonidine in acute organophosphate poisoning can be used without causing frequent clinical problems but that higher doses are associated with a high incidence of hypotension requiring intervention. Further studies are needed to study the efficacy of clonidine as an antidote in organophosphate poisoning.

Background: Poisoning with organophosphorus (OP) insecticides is a major global public health problem, causing an estimated 200,000 deaths each year. Although the World Health Organization recommends use of pralidoxime, this antidote's effectiveness remains unclear. We aimed to determine whether the addition of pralidoxime chloride to atropine and supportive care offers benefit., Methods and Findings: We performed a double-blind randomised placebo-controlled trial of pralidoxime chloride (2 g loading dose over 20 min, followed by a constant infusion of 0.5 g/h for up to 7 d) versus saline in patients with organophosphorus insecticide self-poisoning. Mortality was the primary outcome; secondary outcomes included intubation, duration of intubation, and time to death. We measured baseline markers of exposure and pharmacodynamic markers of response to aid interpretation of clinical outcomes. Two hundred thirty-five patients were randomised to receive pralidoxime (121) or saline placebo (114). Pralidoxime produced substantial and moderate red cell acetylcholinesterase reactivation in patients poisoned by diethyl and dimethyl compounds, respectively. Mortality was nonsignificantly higher in patients receiving pralidoxime: 30/121 (24.8%) receiving pralidoxime died, compared with 18/114 (15.8%) receiving placebo (adjusted hazard ratio [HR] 1.69, 95% confidence interval [CI] 0.88-3.26, p = 0.12). Incorporating the baseline amount of acetylcholinesterase already aged and plasma OP concentration into the analysis increased the HR for patients receiving pralidoxime compared to placebo, further decreasing the likelihood that pralidoxime is beneficial. The need for intubation was similar in both groups (pralidoxime 26/121 [21.5%], placebo 24/114 [21.1%], adjusted HR 1.27 [95% CI 0.71-2.29]). To reduce confounding due to ingestion of different insecticides, we further analysed patients with confirmed chlorpyrifos or dimethoate poisoning alone, finding no evidence of benefit., Conclusions: Despite clear reactivation of red cell acetylcholinesterase in diethyl organophosphorus pesticide poisoned patients, we found no evidence that this regimen improves survival or reduces need for intubation in patients with organophosphorus insecticide poisoning. The reason for this failure to benefit patients was not apparent. Further studies of different dose regimens or different oximes are required.

Background: The case-fatality for intentional self-poisoning in the rural developing world is 10-50-fold higher than that in industrialised countries, mostly because of the use of highly toxic pesticides and plants. We therefore aimed to assess whether routine treatment with multiple-dose activated charcoal, to interrupt enterovascular or enterohepatic circulations, offers benefit compared with no charcoal in such an environment., Methods: We did an open-label, parallel group, randomised, controlled trial of six 50 g doses of activated charcoal at 4-h intervals versus no charcoal versus one 50 g dose of activated charcoal in three Sri Lankan hospitals. 4632 patients were randomised to receive no charcoal (n=1554), one dose of charcoal (n=1545), or six doses of charcoal (n=1533); outcomes were available for 4629 patients. 2338 (51%) individuals had ingested pesticides, whereas 1647 (36%) had ingested yellow oleander (Thevetia peruviana) seeds. Mortality was the primary outcome measure. Analysis was by intention to treat. The trial is registered with controlled-trials.com as ISRCTN02920054., Findings: Mortality did not differ between the groups. 97 (6.3%) of 1531 participants in the multiple-dose group died, compared with 105 (6.8%) of 1554 in the no charcoal group (adjusted odds ratio 0.96, 95% CI 0.70-1.33). No differences were noted for patients who took particular poisons, were severely ill on admission, or who presented early., Interpretation: We cannot recommend the routine use of multiple-dose activated charcoal in rural Asia Pacific; although further studies of early charcoal administration might be useful, effective affordable treatments are urgently needed.

1. Pesticide poisoning kills hundreds of thousands of people in the Asia-Pacific region each year. The majority of deaths are from deliberate self-poisoning with organophosphorus pesticides (OP), aluminium phosphide and paraquat. The current response from a public health, medical and research perspective is inadequate. 2. There are few proven or effective treatments; in addition, very little clinical research has been performed to transfer antidotes shown to work in animal studies into clinical practice. 3. The human toxicity of pesticides is poorly studied and better information may inform a more sustained and appropriate regulatory response. Further understanding may also lead to improvements in diagnosis and treatment. 4. The few effective treatments are not being recommended or delivered in an optimal and timely fashion to poisoned patients. A regional approach to facilitate appropriate pricing, packaging and delivery of antidotes is required.

Objective: Warangal district in Andhra Pradesh, southern India, records >1000 pesticide poisoning cases each year and hundreds of deaths. We aimed to describe their frequency and distribution, and to assess quality of management and subsequent outcomes from pesticide poisoning in one large hospital in the district., Methods: We reviewed data on all patients admitted with pesticide poisoning to a district government hospital for the years 1997 to 2002. For 2002, details of the particular pesticide ingested and management were abstracted from the medical files., Findings: During these 6 years, 8040 patients were admitted to the hospital with pesticide poisoning. The overall case fatality ratio was 22.6%. More detailed data from 2002 revealed that two-thirds of the patients were <30 years old, 57% were male and 96% had intentionally poisoned themselves. Two compounds, monocrotophos and endosulfan, accounted for the majority of deaths with known pesticides in 2002. Low fixed-dose regimens were used in the majority of cases for the most commonly used antidotes (atropine and pralidoxime). Inappropriate antidotes were also used in some patients., Conclusions: It is likely that these findings reflect the situation in many rural hospitals of the Asia Pacific region. Even without an increase in resources, there appear to be significant opportunities for reducing mortality by better medical management and further restrictions on the most toxic pesticides.

Objectives: Acute paracetamol poisoning is an emerging problem in Sri Lanka. Management guidelines recommend ingested dose and serum paracetamol concentrations to assess the risk. Our aim was to determine the usefulness of the patient's history of an ingested dose of >150 mg/kg and paracetamol concentration obtained by a simple colorimetric method to assess risk in patients with acute paracetamol poisoning. Materials and Methods: Serum paracetamol concentrations were determined in 100 patients with a history of paracetamol overdose using High Performance Liquid Chromatography (HPLC); (reference method). The results were compared to those obtained with a colorimetric method. The utility of risk assessment by reported dose ingested and colorimetric analysis were compared. Results: The area under the receiver operating characteristic curve for the history of ingested dose was 0.578 and there was no dose cut-off providing useful risk categorization. Both analytical methods had less than 5% intra- and inter-batch variation and were accurate on spiked samples. The time from blood collection to result was six times faster and ten times cheaper for colorimetry (30 minutes, US$2) than for HPLC (180 minutes, US$20). The correlation coefficient between the paracetamol levels by the two methods was 0.85. The agreement on clinical risk categorization on the standard nomogram was also good (Kappa = 0.62, sensitivity 81%, specificity 89%). Conclusions: History of dose ingested alone greatly over-estimated the number of patients who need antidotes and it was a poor predictor of risk. Paracetamol concentrations by colorimetry are rapid and inexpensive. The use of these would greatly improve the assessment of risk and greatly reduce unnecessary expenditure on antidotes. [ABSTRACT FROM AUTHOR]

Background: Cardiac toxicity due to ingestion of oleander plant seeds in Sri Lanka and some other South Asian countries is very common. At present symptomatic oleander seed poisoning carries a mortality of 10% in Sri Lanka and treatment of yellow oleander poisoning is limited to gastric decontamination and atropine administration. The only proven effective antidote is digoxin antibodies but these are not available for routine use because of the high cost. The main objective of this study is to investigate the effectiveness of a new and inexpensive antidote for patients with life threatening arrhythmias due oleander poisoning. Method/design: We set up a randomised double blind clinical trial to assess the effectiveness of Fructose 1, 6 diphosphate (FDP) in acute yellow oleander poisoning patients admitted to the adult medical wards of a tertiary hospital in Sri Lanka. Patients will be initially resuscitated following the national guidelines and eligible patients will be randomised to receive either FDP or an equal amount of normal saline. The primary outcome measure for this study is the sustained reversion to sinus rhythm with a heart rate greater than 50/min within 2 hours of completion of FDP/ placebo bolus. Secondary outcomes include death, reversal of hyperkalaemia on the 6, 12, 18 and 24 hour samples and maintenance of sinus rhythm on the holter monitor. Analysis will be on intention-to-treat. Discussion: This trial will provide information on the effectiveness of FDP in yellow oleander poisoning. If FDP is effective in cardiac glycoside toxicity, it would provide substantial benefit to the patients in rural Asia. The drug is inexpensive and thus could be made available at primary care hospitals if proven to be effective. Trial Registration: Current Controlled trial ISRCTN71018309 [ABSTRACT FROM AUTHOR]