Serial repetitive nerve stimulation studies in organophosphorus poisoning indicate two distinct pathophysiological processes occur at the neuromuscular junction in the intermediate syndrome.

INTRODUCTION: Intermediate syndrome is an important cause of respiratory failure following acute organophosphorus pesticide poisoning. The objective of this study was to examine the pathophysiology of this syndrome by analysis of sequential repetitive nerve stimulation studies in patients with acute organophosphorus pesticide poisoning. METHODS: Thirty-four consenting symptomatic patients with acute organophosphorus pesticide poisoning with intermediate syndrome (n = 10) or a milder forme fruste intermediate syndrome (n = 24) were assessed prospectively with daily physical examination and repetitive nerve stimulation done on the right and left median and ulnar nerves. The compound muscle action potential at 1, 3, 10, 15, 20 and 30 Hertz was measured with a train of ten stimuli. The amplitudes of the resulting stimuli were normalized to the first stimulus (100 per cent) and plotted against time. The decrease in the area under the curve of all the second stimulus compound muscle action potentials in the first 0.3 seconds was measured as a means of quantifying the refractory block. The decrease in the area under the curve under the 10, 15, 20 and 30 Hertz compound muscle action potentials relative to this pooled second stimulus compound muscle action potentials-area under the curve indicated the extent of additional rate-dependent block (decreasing compound muscle action potential-area under the curve over the first 0.3 seconds after the first stimulus with increasing Hertz). RESULTS: These new measurements strongly correlated with the severity of weakness. Refractory block was seen in most patients but was more severe in those with intermediate syndrome than those with forme fruste (partial) intermediate syndrome (median 55 per cent versus 16 per cent, P = 0.0001). Similar large differences were found for rate-dependent block (30 per cent versus 7 per cent, P = 0.001), which was uncommon in forme fruste intermediate syndrome but found in nine out of 10 patients with intermediate syndrome. Rate dependent block was generally only observed after 24 hours. The simplest strong predictor was total block at 30 Hertz repetitive nerve stimulation (89 per cent [interquartile range 73 to 94 per cent] versus 21 per cent [4 to 55 per cent]; P < 0.0001), which was very similar to total block calculated by summing other calculations. DISCUSSION: These findings likely represent depolarization and desensitization block from prolonged excessive cholinergic stimulation but it is not clear if these are from pre- or post-synaptic pathology. An animal model of intermediate syndrome with repetitive nerve stimulation studies might enable a better pathophysiological understanding of the two types of block. LIMITATIONS: The limited number of repetitive nerve stimulation studies performed were sufficient to demonstrate proof-of-concept, but further studies with more patients are needed to better define the correlates, clinical relevance and possible diagnostic/prognostic roles for the use of this technique. CONCLUSION: There are two easily distinguishable pathophysiological abnormalities in the neuromuscular block in intermediate syndrome. While they often coincide, both may be observed in isolation. The total and rate-dependent block at 30 Hertz are strongly associated with more severe weakness.

Substance use during hospitalisation requiring an urgent clinical response: an opportunity for intervention.

BACKGROUND: There are few reports on drug use in patients while hospitalised and none regarding management or clinical outcomes. AIMS: To describe cases of drug use by inpatients requiring an urgent clinical response. METHODS: We retrospectively reviewed cases at a teaching hospital in Sydney, Australia, from February 2019 to March 2021. RESULTS: Thirty cases were identified, with no deaths. Two patient groups were identified: (i) substance use disorders, using illicit drugs and (ii) self-harm history, using prescribed or over-the-counter drugs. Management involved cardiac monitoring (40%), intensive care (30%), charcoal (20%), antidotes (20%) and intubation (13%). Discharge was planned in 22 of 30 patients, against medical advice in four and directed by medical staff in four. CONCLUSIONS: Inpatient drug use requiring an urgent clinical response was infrequently recognised but presents a risk of harm to patients and staff and increases service utilisation and costs. Both harm reduction and systematic approaches guided by institutional policy are recommended. Using these events as reachable moments to address driving factors may modify patients' risk from future events.

Compliance with national snakebite treatment guidelines in rural Sri Lankan hospitals: a cluster randomized controlled trial of a brief educational intervention.

BACKGROUND: Snakebite is a global health problem that predominantly occurs in rural areas. In Sri Lanka, the majority of snakebite patients first present to smaller rural primary hospitals. Improving care delivered at rural hospitals has the potential to reduce morbidity and mortality from snakebites. OBJECTIVE: In this study, we evaluated whether an educational intervention would increase compliance with national snakebite treatment guidelines in primary hospitals. METHODS: The hospitals were randomized into educational intervention (n = 24) and control groups (n = 20). The intervention hospitals received a brief educational intervention based on Sri Lankan Medical Association (SLMA) guidelines on the management of snakebites. Control hospitals had free access to the guidelines but no additional promotion. Four outcomes were assessed: pre- and post-test knowledge at the completion of a one-day workshop of educational intervention (intervention group only); improvement in the quality of the patient's medical records; appropriateness of transfers to higher hospitals; and quality of overall management graded by a blinded expert. The data was collected over a period of 12 months. RESULTS: All case notes of snakebite hospital admissions were reviewed. There were 1021 cases in the intervention group hospitals and 1165 cases in the control hospitals. Four hospitals in the intervention group and three hospitals in the control group did not have snakebite admissions and were excluded from the cluster analysis. The absolute quality of care was high in both groups. Post-test knowledge was improved (p < 0.0001) following the intervention group's educational workshop. There was no statistical difference between the two groups in terms of clinical data documentation in hospital notes (scores, p = 0.58) or transfer appropriateness (p = 0.68)-both of which were significantly different from the guidelines. CONCLUSION: Education of primary hospital staff improved the immediate knowledge gained but did not improve record-keeping or the appropriateness of inter-hospital patient transfer. TRIAL REGISTRATION: The study was registered with Sri Lanka Medical Associations' clinical trial registry. Reg. No SLCTR -2013-023. Registered: 30/07/2013.

Role of age-sex as underlying risk factors for death in acute pesticide self-poisoning: a prospective cohort study.

BACKGROUND: There is growing evidence in the literature that patients' age is associated with increased risk of death in acute pesticide poisoning. However, few studies have investigated whether the age effect differs between males and females. We aimed to examine the association between age-sex and risk of death in acute pesticide self-poisoning. METHODS: A prospective cohort of deliberate pesticide-poisoned patients admitted to ten rural Sri Lankan hospitals between March 2002 and December 2019. The pesticide ingested was identified based on identification of container or history. A mixed effects logistic regression was fitted to investigate the effect of age-sex on death in acute pesticide self-poisoning adjusting for clinical symptoms on admission, measured by Glasgow Coma Scale and Poison Severity Score, and controlling for clustering among hospital sites. RESULTS: In total, 201 different pesticides were ingested by patients. 6,643 patients ingested an unknown pesticide. A single pesticide was co-ingested with alcohol by 4,603 patients. Of the 28,303 patients enrolled, 2,028 patients died, resulting in case fatality of 7.2% (95% CI 6.9-7.5). The effect of age on case fatality was stronger for males after 21 years of age. The odds of dying for each 5 years increase in age was 1.26 (95% CI 1.23-1.28) times higher for males versus 1.14 (95% CI 1.10-1.19) times higher for females. Missing data were handled by multiple imputation. CONCLUSION: Patient's age-sex are important risk factors for death in acute pesticide self-poisoning even after controlling for clinical effects. The age effect on the odds of dying was significantly different for males and females, with this effect being stronger for males. Given that patient's age and sex are very easy to collect on admission, our study highlights the need for incorporating these risk factors in policy and clinical decisions.

Circulating intestinal fatty acid binding protein and intestinal toxicity in Russell's viper envenomation.

OBJECTIVE: Abdominal pain is known to be an early clinical predictor of severe systemic Russell's viper (RV) envenomation and is often associated with the later development of coagulopathy and neurotoxicity. The mechanism of abdominal pain is unknown, but we postulated it might be due to intestinal microvascular endothelial gut damage. Gut-toxicity can be detected using the novel biomarker Intestinal Fatty Acid Binding Protein (IFABP). We also wanted to explore the mechanisms and consequences of this toxicity by measuring procalcitonin as a specific marker of sepsis triggered by bacterial endotoxin, and serum cystatin-C (CysC) as a measure of acute kidney injury. We hypothesised that severe gut-injury might lead to gut-barrier failure, translocation of gastrointestinal microorganisms, associated sepsis and systemic inflammatory response syndrome (SIRS), with a possible exacerbation of snake-bite severity, including acute kidney injury that was previously attributed to direct venom effects. METHODS: Serial plasma samples previously collected from 16 RV envenomations with abdominal pain, 15 RV envenomations without abdominal pain and 25 healthy controls were assayed for IFABP. A subgroup of these RV envenomations were assayed for procalcitonin (n = 24) and serum CysC (n = 11). RESULTS: The median peak IFABP for RV envenomations was much higher than healthy controls [3703.0 pg/mL (IQR 2250.1-13702.0 pg/mL) vs. 270.1 pg/mL (IQR 153.5-558.0 pg/mL) (p < 0.001)]. There was no difference in those with and without abdominal pain [3801.4 pg/mL (IQR 2080.5-22446.3 pg/mL) vs. 3696.6 pg/mL (IQR 2280.3-4664.7 pg/mL) (p = 1.0)]. Peak procalcitonin levels were elevated in envenomed patients 30.1 ng/ml (IQR: 13.1-59.7 ng/ml) with a level >2ng/mL indicative of severe sepsis] and also correlated with peak IFABP (r = 0.55, p = 0.006, n = 24). Peak serum CysC was also elevated and also correlated with IFABP (r = 0.71, p = 0.037, n = 9). CONCLUSION: IFABP is significantly elevated indicating enterocyte damage occurs in RV envenomation. IFABP correlated with markers of sepsis (procalcitonin) and acute kidney injury (serum CysC) suggesting that enterocyte damage resulting in translocation of microbial associated molecular patterns (MAMPs) contributes to RV envenomation associated SIRS and sepsis.

Case fatality of agricultural pesticides after self-poisoning in Sri Lanka: a prospective cohort study.

BACKGROUND: Pesticide poisoning is among the most common means of suicide globally, but can be prevented with regulation of the most hazardous agents. We aimed to compare the lethality of pesticides ingested by our cohort, seek evidence on variation between human and regulatory animal toxicity, and establish change over time in the case fatality of individual pesticides in Sri Lanka. METHODS: We examined the case fatality of agricultural pesticides in a prospective cohort in nine hospitals serving rural populations in Sri Lanka. We included all patients (>11 years) who had presented to a South Asian Clinical Toxicology Research Collaboration study hospital during the study period. Patients were enrolled by clinical research assistants and were regularly reviewed. Identification of the ingested pesticide was generally on the basis of history or positive identification of the container, supported by nested blood analysis. FINDINGS: From March 31, 2002, to Dec 31, 2019, 34 902 patients (median age 29 years [IQR 21-40]; 23 060 [66·1%] male) presented with a possible or known pesticide self-poisoning. We identified 23 139 specific pesticides that were ingested. Poisoning was fatal in 2299 (6·6%) patients. Case fatality varied greatly from 0·0% (several substances) to 41·8% (paraquat). The three most toxic agents (ie, paraquat, dimethoate, and fenthion) were banned between 2008 and 2011. Since 2013, the five agents causing the most deaths (ie, profenofos, propanil, fenobucarb, carbosulfan, and quinalphos) had a case fatality of 7·2-8·6%. A steady decline was seen in overall case fatality of pesticide poisoning (10·5% for 2002-06 to 3·7% for 2013-19), largely attributable to pesticide bans. A modest fall in case fatality for non-banned pesticides was also seen. INTERPRETATION: Declines seen in case fatalities of poisonings with non-banned pesticides suggest that medical management improved over time. The human data for acute toxicity of pesticides should drive hazard classifications and regulation. We believe that a global benchmark for registration of pesticides should include a less than 5% case fatality after self-poisoning, which could prevent many deaths and have a substantial effect on global suicide rates. FUNDING: The Wellcome Trust and the National Health and Medical Research Council of Australia. TRANSLATIONS: For the Sinhala and Tamil translations of the abstract see Supplementary Materials section.

Health care cost savings from Australian Poisons Information Centre advice for low risk exposure calls: SNAPSHOT 2.

Introduction: To estimate cost savings from the Australian Poisons Information Centres (PIC) through reductions in unnecessary health resources following unintentional low toxicity poisonings.Methods: Two telephone surveys were conducted. The first to PIC callers over a one-week period about unintentional exposures where the callers' alternate course of action in the hypothetical situation in which the PIC did not exist was questioned. The second survey to determine the proportion of callers followed PIC advice. We estimated cost savings associated with instances where individuals acted on advice not to present to hospital, when they indicated they would have otherwise as well as savings from preventing unnecessarily utilisation of medical resources. Database records of unintentional poisonings from all Australian PICs for 2017 were used.Results: A total of 958 consecutive callers were surveyed. PIC advised 91% of callers to stay at home, remaining callers were referred to hospital (5%), to their GP (3%) or given other recommended management advice (1%). PIC advice was followed by 97.6% of callers. In PIC absence, 22% of callers who were advised to stay home would have presented to hospital (3% via ambulance), 8% would visit their General Practitioner (GP) and only 9% would stay at home. In 2017, PICs were called about 94,913 unintentional poisonings; and PICs generated at least $10.1 million in annual savings.Conclusion: In 2017, PICs provided at least a three-fold return on investment for every dollar invested, demonstrating that PICs are a highly cost effective service.

Paracetamol poisoning-related hospital admissions and deaths in Australia, 2004-2017.

OBJECTIVES: To assess the numbers of paracetamol overdose-related hospital admissions and deaths in Australia since 2007-08, and the overdose size of intentional paracetamol overdoses since 2004. DESIGN, SETTING: Retrospective analysis of data on paracetamol-related exposures, hospital admissions, and deaths from the Australian Institute of Health and Welfare National Hospital Morbidity Database (NHMD; 2007-08 to 2016-17), the New South Wales Poisons Information Centre (NSWPIC; 2004-2017), and the National Coronial Information System (NCIS; 2007-08 to 2016-17). PARTICIPANTS: People who took overdoses of paracetamol in single ingredient preparations. MAIN OUTCOME MEASURES: Annual numbers of reported paracetamol-related poisonings, hospital admissions, and deaths; number of tablets taken in overdoses. RESULTS: The NHMD included 95 668 admissions with paracetamol poisoning diagnoses (2007-08 to 2016-17); the annual number of cases increased by 44.3% during the study period (3.8% per year; 95% CI, 3.2-4.6%). Toxic liver disease was documented for 1816 of these patients; the annual number increased by 108% during the study period (7.7% per year; 95% CI, 6.0-9.5%). The NSWPIC database included 22 997 reports of intentional overdose with paracetamol (2004-2017); the annual number increased by 77.0% during the study period (3.3% per year; 95% CI, 2.5-4.2%). The median number of tablets taken increased from 15 (IQR, 10-24) in 2004 to 20 (IQR, 10-35) in 2017. Modified release paracetamol ingestion report numbers increased 38% between 2004 and 2017 (95% CI, 30-47%). 126 in-hospital deaths were recorded in the NHMD, and 205 deaths (in-hospital and out of hospital) in the NCIS, with no temporal trends. CONCLUSIONS: The frequency of paracetamol overdose-related hospital admissions has increased in Australia since 2004, and the rise is associated with greater numbers of liver injury diagnoses. Overdose size and the proportion of overdoses involving modified release paracetamol have each also increased.

Trends in self-poisoning and psychotropic drug use in people aged 5-19 years: a population-based retrospective cohort study in Australia.

OBJECTIVES: To characterise trends in self-poisoning and psychotropic medicine use in young Australians. DESIGN: Population-based retrospective cohort study. SETTING: Calls taken by the New South Wales and Victorian Poisons Information Centres (2006-2016, accounting for 70% of Australian poisoning calls); medicine dispensings in the 10% sample of Australian Pharmaceutical Benefits Scheme data (July 2012 to June 2016). PARTICIPANTS: People aged 5-19 years. MAIN OUTCOME MEASURES: Yearly trends in intentional poisoning exposure calls, substances taken in intentional poisonings, a prevalence of psychotropic use (dispensing of antidepressants, antipsychotics, benzodiazepines and medicines for attention deficit hyperactivity disorder (ADHD)). RESULTS: There were 33 501 intentional poisonings in people aged 5-19 years, with an increase of 8.39% per year (95% CI 6.08% to 10.74%, p<0.0001), with a 98% increase overall, 2006-2016. This effect was driven by increased poisonings in those born after 1997, suggesting a birth cohort effect. Females outnumbered males 3:1. Substances most commonly taken in self-poisonings were paracetamol, ibuprofen, fluoxetine, ethanol, quetiapine, paracetamol/opioid combinations, sertraline and escitalopram. Psychotropic dispensing also increased, with selective serotonin reuptake inhibitors (SSRIs) increasing 40% and 35% July 2012 to June 2016 in those aged 5-14 and 15-19, respectively. Fluoxetine was the most dispensed SSRI. Antipsychotics increased by 13% and 10%, while ADHD medication dispensing increased by 16% and 10%, in those aged 5-14 and 15-19, respectively. Conversely, dispensing of benzodiazepines to these age groups decreased by 4% and 5%, respectively. CONCLUSIONS: Our results signal a generation that is increasingly engaging in self-harm and is increasingly prescribed psychotropic medications. These findings indicate growing mental distress in this cohort. Since people who self-harm are at increased risk of suicide later in life, these results may foretell future increases in suicide rates in Australia.

Button battery exposures in Australian children: a prospective observational study highlighting the role of poisons information centres.

CONTEXT: Button battery ingestion is a worldwide problem, with evidence of increasing harms and deaths in recent decades. Australian Poisons Information Centre (PIC) experience includes cases of treatment delay due to lack of healthcare professional recognition of risks, and/or lack of local resources. This study aims to characterise Australian button battery exposures, focusing on exposure circumstances, and preventable health system shortcomings. METHODS: A prospective observational study of button battery exposure calls to New South Wales PIC, November 2015-May 2017, using a follow-up survey to obtain outcome data and additional details. Survey data was combined with nationwide PIC data over the same period. RESULTS: Australian PICs were consulted on 578 exposures over the 19-month study period, including 506 paediatric cases. The median (IQR) age for the paediatric cases was 23 months (14-36 months). Where the source was identified, batteries came from toys in 26% of cases, with hearing aids, watches, and remote controls being other common sources. Children in outer regional, remote and very remote areas were overrepresented, and 15 cases were referred to a different hospital due to X-ray facilities being unavailable at their nearest hospital. We identified inconsistent triage from a range of first responders, and knowledge gaps regarding button battery dangers amongst some healthcare professionals. DISCUSSION: Button battery exposures are a common call to Australian PICs. This study highlights a potential role of education campaigns, professional guidelines, and child-resistant battery compartments in toys and household devices. PICs calling ahead to ensure X-ray availability/diversion to a different hospital likely reduced delays for this time-critical exposure. CONCLUSIONS: Button battery exposures continue to be a problem in Australia. Data collected by PICs can provide useful information for public health and product safety initiatives. A PIC-led protocol to direct initial medical management of button battery exposures could reduce delays and improve outcomes.

Carols by glow sticks: a retrospective analysis of Poisons Information Centre data.

OBJECTIVE: To win a Christmas hamper. We also devised a study of our most festive seasonal poisoning, to demonstrate how hard we are working while everyone else is partying. DESIGN: Retrospective analysis of the New South Wales Poisons Information Centre database, which we searched for exposures to the substance code "Cyalume light sticks/glow toys" from 1 July 2013 to 30 June 2017. SETTING: A dimly lit basement with a constantly ringing phone. At the other end of the phone was a highly anxious parent and a luminescent child. MAIN OUTCOME MEASURES: Number of glow stick exposures, route of exposures, patient demographics and seasonal trends in exposures. RESULTS: There were 2918 glow stick exposures over the 4-year study period. The vast majority of exposures (94%) were in children aged 14 years and younger. Medical complications were very rare. Glow stick exposures were 4.38 times more likely in December (95% CI, 3.02-6.35; P < 0.001). Statistically significant increases were also observed in October, November, January, February and March. Glow stick exposures were 4.20 times more likely during the holiday period of 1 December to 7 January (95% CI, 3.42-5.15; P < 0.001), 2.52 times more likely over summer (95% CI, 2.12-3.00; P < 0.001), and 1.77 times more likely during school holidays (95% CI, 1.47-2.13; P < 0.001). CONCLUSIONS: This epidemic of poisoning is perhaps due to mass seasonal synaesthesia. The lack of any significant adverse consequences highlights the contribution that 50 years of injury prevention has made to everyone having a Merry Christmas and a Happy New Year.

Study protocol: a pilot randomized controlled trial to evaluate the acceptability and feasibility of a counseling intervention, delivered by nurses, for those who have attempted self-poisoning in Sri Lanka.

BACKGROUND: Deliberate self-harm in the form of non-fatal self-poisoning is a major public health problem in Sri Lanka. Previous work suggests that many nurses in Sri Lanka-particularly those who work in primary care in the medical treatment of persons who attempt self-poisoning-already approach their role in a holistic fashion and consider "advising" or "counseling" patients after self-poisoning to be a part of their nursing role. But there is no formal training given to such nurses at present nor has the efficacy or feasibility of such an intervention been assessed in Sri Lanka. The aims of this pilot study are to explore the potential efficacy, acceptability, and feasibility of carrying out a counseling intervention that could be delivered by nurses for persons who present to hospital for medical management of non-fatal self-poisoning. METHODS/DESIGN: The study will be carried out at the Toxicology Unit of Teaching Hospital Peradeniya, Sri Lanka. A pilot randomized controlled trial will be carried out among participants admitted to Teaching Hospital Peradeniya for medical management of non-fatal self-poisoning. The primary objective of this study is to explore the acceptability and feasibility of a counseling intervention being delivered by nurses. The secondary objectives are to explore the efficacy of the intervention for the improvement of skills to cope with situations of acute emotional distress, and to reduce rates of anxiety, depression, and future repetition and suicidal ideation. A nurse's experiences and attitudes regarding the acceptability and feasibility of implementing this intervention and participant experiences of the intervention and its effects will be explored via qualitative interviews and focus group discussions. DISCUSSION: It is anticipated that the findings of this pilot study will help determine and assess the acceptability and feasibility of this counseling intervention, as well as indicate the more useful aspects of this intervention in order to develop it for further exploration in a larger trial. TRIAL REGISTRATION: SLCTR/2017/008 Registered on 21st March 2017.

Patterns of poisoning exposure at different ages: the 2015 annual report of the Australian Poisons Information Centres.

OBJECTIVES: To characterise the types of calls received by Australian Poisons Information Centres (PICs) in Australia, and to analyse poisoning exposures by age group, circumstances of exposure, and the types of substances involved. Design, setting: Retrospective analysis of call records from all four Australian PICs (national coverage). MAIN OUTCOME MEASURES: Basic demographic information; exposure circumstances, substance types involved in each age group; recommendations for management (eg, stay at home, go to hospital). RESULTS: There were 204 906 calls to Australian PICs in 2015, 69.0% from the general public, 27.9% from health professionals; 16.2% of calls originated from hospitals. 170 469 calls (including re-calls about an exposure) related to 164 363 poison exposure events; 64.4% were unintentional, 18.1% were the consequences of medication error, and 10.7% involved deliberate self-poisoning. Most exposures were of 20-74-year-old adults (40.1%) or 1-4-year-old toddlers (36.0%). The PICs advised callers to stay at home for 67.4% of exposures, and to present to hospital for 10.9%. The most common substances involved in exposures overall were household cleaners (10.2%) and paracetamol-containing analgesics (7.3%). Exposures of infants and toddlers were most frequently to household cleaning substances (17.8%, 15.3% respectively) and personal care items (6.6%, 7.3%); callers were usually advised to stay at home (88.5%, 86.4%). Deliberate self-poisoning (49.1%) and hospital referral (23.9%) were most frequent for adolescents. Exposures of adults (20-74 years) frequently involved psychotropic pharmaceuticals (17.8%) or painkillers (15.1%). Exposures in adults over 74 were typically medication errors involving cardiovascular (23.6%), anticoagulant (4.6%), or antidiabetic (4.1%) medications. CONCLUSIONS: Poisoning is a significant public health problem throughout life, but the nature of the hazards differs markedly between age groups. PIC data could inform strategic public health interventions that target age-specific poisoning hazards.

Clinico-epidemiology of arthropod stings and bites in primary hospitals of North Western province of Sri Lanka.

OBJECTIVE: Arthropod stinging and bites are common environmental hazards in Sri Lanka. However, their medical importance has not been fully evaluated yet. This study aims to study the burden, epidemiology, and outcome of stings and bites in primary hospitals in the Kurunegala district in North Western Province (NWP) of Sri Lanka. METHODOLOGY: The study was conducted one year from 25th May 2013 to 25th May 2014. Details of all stings and bites admissions and their outcomes were retrospectively extracted from hospital records in all 44 primary hospitals in the district. RESULTS: There were 623 stings and bites with population incidence of 38/100,000 (95% CI 27-52). There were no deaths. Median age was 38 years (IQR: 19-53 years), and 351 (56%) were males. Most of stings and bites (75%) occurred in the daytime. Median time to hospital arrival was 55 minutes (IQR: 30 min to 2 h). The offending arthropods had been identified in 557 (89%) cases, of them, 357 (57%) were Hymenoptera (hornet and bees), 99 centipedes, 61 spiders and 40 scorpions. Local pain occurred in 346 (56%) cases - centipede 69 (70%), Scorpion 24 (60%), spider 36 (59%), Hymenoptera 187 (52%) and unidentified 30 (45%). Hymenoptera stings and spider bites occurred between 06 am to 12 noon, and scorpion stings and centipede bites mostly occurred between 06 pm to 12 midnight. Mild, moderate to severe anaphylaxis reactions occurred in 173 (28%) patients including 110 Hymenoptera stings - mild 39, moderate 62 and severe 9. From primary hospitals, 53(9%) cases had been transferred to tertiary care units for further management. Of them, 41 cases were Hymenoptera stings and 24 (58%) of them had mild, moderate to severe anaphylaxis. In the entire group, 27% severe cases received adrenaline. CONCLUSIONS: The primary hospitals in NW province of Sri Lanka manage large numbers of arthropod stings and bites. These include Hymenoptera (hornet and bee), centipedes, spiders, and scorpions. Pain, swellings and anaphylactic reactions were the most common adverse effects.

Magnesium sulfate and calcium channel blocking drugs as antidotes for acute organophosphorus insecticide poisoning - a systematic review and meta-analysis.

INTRODUCTION: Treatment of acute organophosphorus or carbamate insecticide self-poisoning is often ineffective, with tens of thousands of deaths occurring every year. Researchers have recommended the addition of magnesium sulfate or calcium channel blocking drugs to standard care to reduce acetylcholine release at cholinergic synapses. OBJECTIVE: We aimed to review systematically the evidence from preclinical studies in animals exposed to organophosphorus or carbamate insecticides concerning the efficacy of magnesium sulfate and calcium channel blocking drugs as therapy compared with placebo in reducing mortality or clinical features of poisoning. We also systematically reviewed the evidence from clinical studies in patients self-poisoned with organophosphorus or carbamate insecticides concerning the efficacy of magnesium sulfate and calcium channel blocking drugs as therapy compared with placebo, in addition to standard therapy, in reducing mortality, atropine requirement, need for intubation and ventilation, and intensive care unit and hospital stay. METHODS: We performed a systematic review for articles on magnesium sulfate and calcium channel blocking drugs in organophosphorus or carbamate insecticide poisoning using PubMed and China Academic Journals Full-text (Medicine/Hygiene Series) databases and keywords: "organophosphorus or organophosphate poisoning", "cholinesterase inhibitor poisoning" OR "carbamate poisoning" AND "magnesium", "calcium channel blocker", or generic names of different calcium channel blocking drugs. Review of titles and abstracts revealed 2262 papers of potential relevance. After review of the full papers, a total of 19 papers relevant to the question were identified: five preclinical studies, nine case reports or small case series, and five clinical studies and trials. We also obtained primary data from three unpublished clinical trials of magnesium sulfate, providing data from a total of eight clinical studies and trials for analysis. All studies were of organophosphorus insecticides; no studies of carbamates were found. No pre-clinical or clinical studies of calcium channel blocking drugs and magnesium sulfate in combination were found. We extracted data on study type, treatment regimens, outcome, and side effects. Pre-clinical studies: Two rodent studies indicated a benefit of calcium channel blocking drugs treatment on mortality if given before or soon after organophosphorus exposure, in addition to atropine and/or oxime. In poisoned minipigs, treatment with magnesium sulfate after organophosphorus insecticide poisoning reduced cholinergic stimulation and hypertension. Of note, magnesium sulfate further suppressed serum butyrylcholinesterase activity in one rat study. Observational clinical studies: Calcium channel blocking drugs and magnesium sulfate have been used to treat cardiac dysrhythmias and hypertonic uterine contractions in organophosphorus poisoned patients. A small neurophysiological study of magnesium sulfate reported reversion of neuromuscular junction effects of organophosphorus insecticide exposure. Comparative clinical studies: Only four of eight studies were randomized controlled trials; all studies were of magnesium sulfate, of small to modest size, and at substantial risk of bias. They included 441 patients, with 239 patients receiving magnesium sulfate and 202 control patients. The pooled odds ratios for magnesium sulfate for mortality and need for intubation and ventilation for all eight studies were 0.55 (95% confidence interval [CI] 0.32-0.94) and 0.52 (95% CI 0.34-0.79), respectively. However, there was heterogeneity in the results of higher quality phase III randomized controlled trials providing more conservative estimates. Although a small dose-escalation study suggested benefit from higher doses of magnesium sulfate, there was no evidence of a dose effect across the studies. Adverse effects were reported rarely, with 11.1% of patients in the randomized controlled trials receiving the highest dose of magnesium sulfate requiring their infusion to be stopped due to hypotension. CONCLUSIONS: Both preclinical and clinical data suggest that magnesium sulfate and calcium channel blocking drugs might be promising adjunct treatments for acute organophosphorus insecticide poisoning. However, evidence is currently insufficient to recommend their use. Mechanistic and large multi-center randomized controlled trials testing calcium channel blocking drugs and magnesium sulfate are required to provide the necessary evidence, with careful identification of the insecticides ingested and measurement of surrogate markers of toxicity, including butyrylcholinesterase activity.