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The Arum palaestinum plant is one of the 26 species of the Arum genus of the Araceae family. This plant species is found through the Mediterranean region, Western Asia, and Europe. The leaves and seeds of the plant contain needle-shaped oxalate crystals that can irritate the affected tissue (skin, oral cavity, or GI tract) upon exposure. Up to this date, there is no available literature supporting the epidemiology or the clinical manifestations of poisoning by this plant. We retrospectively reviewed all Arum palaestinum exposures to children younger than 18 years of age reported to the Israel National Poison Information Center during 2017 from the IPIC computerized data system. We extracted demographic data and clinical data from those digital files. We reviewed the files of 53 patients' files and found slight male predominance (58% vs. 42%), and the age of exposure ranged from 9 month to 15 years. The main site of exposure was at home in most cases (47%) followed by outdoor exposure in 40% of the cases. In 66% of the cases, minor clinical manifestations were reported, mainly erythema and mouth irritation, agitation, and drooling. Asymptomatic patients composed 34% of the cases. In 17% of the cases, patients were recommended to visit an ambulatory facility, and other 15% of the cases were referred to the emergency department. There were no cases of severe poisoning, upper airways compromise, or death.Conclusion: Poisoning by Arum palaestinum is one of the most common pediatric plant poisoning in Israel. Our study supports with clinical data for the first time that this poisoning is self-limited, confined to the affected mucosa, and most likely does not necessitate any intervention. What is Known • A. palaestinum poisoning is one of the most common pediatric plant poisoning in Israel. • The leaves and seeds of the plant contain needle-shaped oxalates crystals. What is New • Pediatric exposure to A. palaestinum usually causes only mild and self-limited poisoning. • Expectant observation is the preferred management of such exposure.

Most calls to poison information centers are from the public, pertaining to young children, and due to minor or nontoxic exposures. Rational poison center consultations can prevent unnecessary visits to emergency departments (EDs), callers’ adherence to such advice is required. Estimate adherence of callers from the public to the poison center concerning exposures of young children to the advice provided by the clinical toxicologist, estimate the number of unnecessary ED visits of these children prevented by poison center consultations. Prospective, phone-survey cohort study. Calls from the public concerning children under 6 years old were recorded and collected, telephone follow-up was performed within two weeks. Data collected included: demographics, exposure, severity, triage advised, adherence to the advice, reasons for nonadherence, and what the caller would have done had the poison center been unavailable. The study was conducted over 3 months representing different seasons and holidays times during a 1-year period. 1762 callers completed the telephone follow-up; 1443 (81.9%) cases were asymptomatic at the time of call; 1452 (82.3%) were advised to remain at home, 175 (9.9%) and 137 (7.8%) were referred to community clinics and EDs, respectively; 1648 (93.5%) of callers adhered to the advice provided; highest adherence rate was among callers advised to stay home (98.3%, 1427), and 78.9% (108) and 62.1% (109) among callers referred to EDs and community clinics, respectively. Among callers advised to stay home, 491 stated that they would have referred themselves to the ED had the poison center been unavailable, an annual estimate of 4309 cases. The main parameter predicting nonadherence was calls made during night shift. The high adherence of callers to the poison center consultation suggests it plays an important role in preventing unnecessary ED visits of young children due to poison exposures, and may substantially reduce ED load and costs.

Introduction One session of water-pipe tobacco smoking (WPS) can increase carboxyhemoglobin (COHb) to levels comparable to those reported in carbon monoxide poisoning, which may cause memory impairment and confusion. Methods A prospective study evaluating healthy volunteers pre- and post-30 min of WPS session. Primary outcome parameters were executive cognitive measures [digit span test and Paced Auditory Serial Addition Test (PASAT)]. The effect of repeated cognitive testing 30 min apart without WPS was evaluated in age- and sex-matched healthy volunteers. Secondary outcome parameters included cardio-pulmonary, COHb, serum nicotine, and cytokine changes. Results Thirty-five subjects aged 25.6 ± 4.5 years smoked water-pipe for a 30-min session. Control group included 20 subjects aged 25.2 ± 5.1 years. Digit span test median score decreased after WPS (16 and 15, respectively, p = .003), insignificant decrease in controls. Median PASAT score increased after WPS (49 and 52, respectively, p = .009); however, a much larger significant increase was observed in controls (p ≤ .001). One WPS session resulted in significant increases in heart and respiratory rates and significant decrease in FEF25–75%. Post WPS, median COHb levels increased (from 2.2% to 10.7%, p < .0001) as did median serum nicotine levels (from 1.2 to 26.8 ng/mL, p < .0001). Serum cytokines levels: IL-2 and IL-6 increased (p < .0001 for each), and IL-10 and IL-5 decreased (p < .0001 and p = .04, respectively). Conclusions One session of WPS resulted in significant negative effects on cognitive executive measures, significant increases in COHb and serum nicotine levels, and significant changes in serum cytokines. Our findings call for increasing awareness towards the possible consequences of cognitive alterations following a 30-min session of WPS. Implications One 30-min session of water-pipe smoking resulted in negative effects on executive cognitive measures, increased carboxyhemoglobin and serum nicotine, and significant changes in serum cytokine levels. This study adds to the accumulating evidence on the harmful effects of water-pipe smoking, a growing epidemic, and calls for awareness of its possible consequences of acute cognitive alterations.

During pregnancy and breastfeeding, many women require prescription medications. Concerns about drug effects on the fetus or breastfed infant may lead to decreased adherence. Our objective was to evaluate the adherence of pregnant and breastfeeding Israeli women to prescription drugs, the information they received regarding drug safety, and the women's awareness and pattern of the use of Teratogen Information Services (TIS) in Israel.We conducted a prospective observational cohort study among pregnant and breastfeeding women who had contacted the Israel Poison Information Center (IPIC) to consult about prescription medications. In a follow-up telephone call, we assessed adherence (defined as medication initiation by the time of the follow-up call) and the patients' recollection of the safety information given by the prescribing physician. In an additional cohort of post-partum women, we assessed their awareness about TIS in Israel.We included 59 pregnant women (62 prescriptions), 75 breastfeeding women (80 prescriptions), and 49 postpartum women. About two-thirds of all prescriptions were for antimicrobial drugs. By the time of the follow-up call, most participants (89% of pregnant and 89% of breastfeeding women) had initiated medications. Eight (11%) breastfeeding women stopped breastfeeding their babies while using the medication. Patients reported receiving explicit and unequivocal information concerning medication safety by the prescriber for 50% and 55% of prescriptions to pregnant and breastfeeding women, respectively. 70% of postpartum women interviewed in the maternity ward were not aware of TIS in Israel.We observed high adherence rate to prescription medication therapy among pregnant and breastfeeding women in our cohort. Only about half of the women reported receiving comprehensive drug safety information by the prescriber. Raising awareness of the importance of medication safety counseling among both physicians and patients may contribute to the quality of medical care of pregnant and breastfeeding women in Israel.

The Mediterranean region is, by far, a prime travel destination, having hosted more than 330 million tourists in 2016, mostly for seaside holidays. A greatly increased influx of thermophilic Red Sea species, introduced through the Suez Canal in a process referred to as Lessepsian invasion (in honor of Ferdinand de Lesseps who instigated the building of the Suez Canal), have raised awareness among scientists, medical personnel, and the public, of health risks caused by some venomous and poisonous marine species. The main species of concern are the poisonous Lagocephalus sceleratus, and the venomous Plotosus lineatus, Siganus luridus, Siganus rivulatus, Pterois miles, Synancea verrucosa, Rhopilema nomadica, Macrorhynchia philippina and Diadema setosum. Recognizing that the main factors that drive the introduction and dispersal of Red Sea biota in the Mediterranean, i.e., Suez Canal enlargements and warming seawater, are set to increase, and international tourist arrivals are forecasted to increase as well, to 500 million in 2030, an increase in intoxications and envenomations by alien marine species is to be expected and prepared for.

Plotosus lineatus is a venomous fish that has migrated from the Indo-Pacific region to the Mediterranean Sea (Lessepsian migrant). Its presence in the Mediterranean Sea was first recorded in 2002 and was observed in growing schools. Its spines contain toxins with lytic, hemolytic and edematous activities.To characterize the injuries caused by Plotosus lineatus in the Southeastern Mediterranean Sea.A prospective observational case series of consultations provided by a national Poison Center pertaining to Plotosus lineatus from 2007 to 2016. Demographic and clinical data and method of fish identification were retrieved from the medical toxicological records, and described.Eighty four cases were included; the main findings are: median age 35 (range 3-80) years, 91.7% males, 51.2% fishermen, 78.6% palm injuries, 94% and 4.8% were mildly and moderately injured, respectively. Main local manifestations included pain, puncture wound, swelling, and erythema (90.5%, 70.2%, 33.3%, and 16.7%, respectively). Systemic signs were minor and infrequent (≤7.1%), including hypertension, tachycardia, vomiting, chills, and weakness. Management included wound disinfection, immersion in hot water, tetanus prophylaxis, and analgesics. No patient required hospital admission. The fish was identified mostly by the victim with the aid of the Poison Center (mainly by typical description, and a picture), and some by marine biologists.Plotosus lineatus is a new fish in the Southeastern Mediterranean Sea. It affects fishermen handling fishing nets, and beach hikers stepping on or holding it. Injuries caused by its spines usually result in minor effects; pain may be intense. Treatment includes disinfection, analgesics, and antitetanus and antibiotics as needed. No lethal cases were recorded, unlike exposure of animals to the venom of the Indo-Pacific species; reason is unclear. Our series illustrates the consequences of manmade disruption of ecosystem resulting in invasion of toxic species to a new environment, affecting human health.

BACKGROUND Therapeutic drug monitoring (TDM) for busulfan supports dose adjustment during conditioning for stem cell transplantation. The authors aimed to develop and validate limited sampling strategies (LSS) of 4-5 samples for a precise estimation of the area under concentration (AUC)-time curve of busulfan, in plasma as an alternative to an intensive sampling strategy (ISS) requiring 9-10 samples. METHODS ISS TDM data from 297 patients (≤18 years of age) were used. AUCLSS was calculated using the trapezoidal rule and multiple linear regression (MLR). Unlike more complex modeling methods, MLR does not require sophisticated software or advanced training of personnel. MLR coefficients were estimated in the development subset containing randomly selected 50% of the records and were then used to calculate the AUCLSS of the remaining records (the validation subset). The agreement between dose adjustment recommendations (DAR) based on ISS and LSS, in the validation subset, was evaluated by a Bland-Altman analysis. A DAR deviating from an ISS-based reference by

The Israel Poison Information Center (IPIC), Rambam Health Care Campus, provides 24-hour telephone consultations on clinical toxicology and drug and reproductive toxicology. It participates in research, teaching and regulatory activities, and provides laboratory services. In 2014, nurse specialists in poison information joined the IPIC.To report the epidemiology of poison exposures in Israel.We present computerized queries and a descriptive analysis of the medical records database of the IPIC for 2017.A total of 39,928 poison exposure cases were recorded, reflecting increases of 226.3% and 26.7% compared with 1995 and 2012, respectively. Children6 years of age were involved in 47.0% of cases; 80.4% of calls were made by the public and 17.8% by physicians; 74.2% of exposures were unintentional and 7.3% intentional. Pharmaceuticals were involved in 51.4% of cases, chemicals in 36.9%, bites and stings in 2.2%, and plants and mushrooms in 1.5%. Substances most frequently involved were analgesics, cleaning products, and antimicrobials. Clinical severity was moderate/major in 3.3%, mainly due to insecticides, drugs of abuse, and corrosives. Three fatalities were recorded (due to colchicine, organophosphates, and volatile substance inhalant abuse).Poison exposures and poisonings have markedly increased in Israel, contributing substantially to morbidity. The IPIC prevented unnecessary referrals to emergency departments. Its database is a valuable national resource for collecting and monitoring poisoning exposure cases. It can be used as a real-time surveillance system for the benefit of public health. It is recommended that reporting to the IPIC become mandatory, and its activities adequately supported by national resources.

The unmonitored use of herbal medicinal remedies by patients with cancer presents a significant challenge to oncology healthcare professionals. We describe an increasingly popular herbal “wonder drug,” Ephedra foeminea (Alanda in Arabic), whose use has spread from the Palestinian patient population throughout the Middle East. We conducted a multicentered and multidisciplinary collaborative research effort in order to understand the potential benefits and harms of this popular herbal remedy. We conducted an in-depth search of the medical literature, both traditional and modern, for any mention of the clinical use of Alanda for the treatment of cancer. We then tested the remedy, first for toxic ephedra alkaloid components and then for anticancer effects, as well as effects on the cytotoxic activity of chemotherapy agents (cisplatin and carboplatin) on breast cancer cell cultures. We found no mention in the literature, both conventional and traditional, on the use of Alanda for the treatment of cancer. Laboratory testing did not find any toxic components (i.e., ephedra alkaloids) in the preparation. However, in vitro exposure to Alanda led to a reduced cytotoxic effect of chemotherapy on breast cancer cell cultures. The use of an integrative ethnobotanical, laboratory and clinical research-based approach can be extremely helpful when providing nonjudgmental and evidence-based guidance to patients with cancer, especially on the use of traditional herbal medicine. The effectiveness and safety of these products need to be examined by integrative physicians who are dually trained in both complementary medicine and supportive cancer care.

Background Increasing use of cannabis for medical and recreational purposes has augmented concerns about associated poisoning, and specifically pediatric and adolescent poisonings. Synthetic cannabinoids, often marketed as cannabis replacement, have recently emerged and knowledge and awareness of their toxic effects is growing. The objective of this study was to characterize and compare cannabinoid poisonings (medical and recreational cannabis, and synthetic cannabinoids) in Israel during the period 2007–2018. Methods The three types of cannabinoid exposures reported to the Israel Poison Information Center (IPIC) between 2007 and 2018 were identified. Differences in distribution of the three types of agents with respect to demographic and clinical factors were examined using univariate statistics, and time trends were plotted. Results Out of the total 615 poison-exposure cases identified, 55% were recreational cannabis cases, 33% were synthetic cannabinoid cases and 12% were medical cannabis cases. Compared to recreational cannabis exposures, synthetic cannabinoid exposures were more likely to be male, to have both gastrointestinal and cardiovascular manifestations and less likely to be called in by the public as opposed to called in by health care professionals and less likely to be treated on-site. Medical cannabis exposures were less likely to be male, more likely to be called in by the public, less likely to present with co-use of other substances and more likely to have gastrointestinal manifestations. Throughout the study period an increase in exposure cases were observed for medical and recreational cannabis cases, whereas synthetic cannabinoid cases showed an increase until 2014 and then a steep decrease. Conclusions Despite the low toxicity of different types of cannabinoids, training of physicians and other health care professionals related to cannabinoid poisoning is important. This is particularly important in jurisdictions where legal access to cannabis is becoming increasingly available.

A 70-year-old woman suffered severe irritation in her oral cavity after biting Dieffenbachia amoena petiole. She was treated a few hours after the exposure with systemic and local analgesics, as well as with systemic first generation antihistamine, and her symptoms improved rapidly. Dieffenbachia is a common household plant that contains oxalate raphides which cause irritation and microtrauma. Injuries are caused by exposure through the mouth, and also by contact with eyes or skin. Clinical presentation is dependent on the route of exposure. It includes pain and edema in the oral cavity following biting the leaves or the stem of the plant. Direct oral contact with the plant juice can also cause symptoms. There are some case reports of severe injuries that caused oro-pharyngeal inflammation and edema, with impending obstruction of the upper airways. Treatment includes respiratory support. Water or milk can be given to alleviate oral and throat irritation; some clinicians recommend first generation antihistamines. It should be noted that treatment recommendations are based on reports, not on clinical trials.

Liquid chromatography with mass spectrometry (LC-MS/MS) is the method of choice for the determination of everolimus whole blood concentrations but is not always available. Therefore, immunoassays have been developed for clinical monitoring of everolimus. In previous studies, the Quantitative Microsphere System (QMS) immunoassay had a positive bias compared with LC-MS/MS, but was judged acceptable, although clinical agreement (eg, 95% limits of agreement) was not reported. The objective of this study was to assess whether the agreement between the QMS assay and an LC-MS/MS method was clinically acceptable for use interchangeably in therapeutic everolimus monitoring.Whole blood samples from organ-transplanted patients on everolimus therapy were analyzed by both QMS (on Architect ci4100 analyzer) and LC-MS/MS. Paired results were compared using paired Student t test, Bland-Altman plots, and Deming regression analysis. The proportions of falsely supratherapeutic and subtherapeutic results on the QMS assay compared with the LC-MS/MS were calculated.Among 250 samples (169 patients), mean everolimus concentrations determined by LC-MS/MS and QMS assays were 4.8 ± 2.1 ng/mL and 6.3 ± 2.1 ng/mL, respectively (P0.001), with 95% lines of agreement between -2.1 and 5.2 ng/mL, a range corresponding to 152% of the mean concentration. When stratified by the type of transplant, a similar positive bias was found in each subgroup (all P0.014). Sixty-nine percent of the samples yielding supratherapeutic concentrations (8 ng/mL) on the QMS assay were within the therapeutic range on the LC-MS/MS.The everolimus QMS immunoassay, using the Architect ci4100 analyzer, had a significant positive bias compared with LC-MS/MS, with a wide range between the limits of agreement. The lack of agreement may result in inadequate everolimus dose adjustments, suggesting that the QMS assay cannot be used interchangeably with the LC-MS/MS method for therapeutic everolimus monitoring in organ-transplanted patients.

To characterize poison exposures in young Israeli military personnel as reported to the national poison center.Retrospective poison center chart review over a 14-year period. Cases included were Israeli soldiers aged 18-21 years, the compulsory military service age required by the Israeli law.1770 records of poison exposures in young military personnel were identified. Most exposed individuals involved males (n = 1268, 71.6%). Main routes of exposure were ingestion (n = 854, 48.3%), inhalation (n = 328, 18.6%) and ocular (n = 211, 11.9%). Accidents or misuse (n = 712, 40.2%) were the most frequently reported circumstances, followed by suicide attempts (370, 20.9%), and bites and stings (161, 9.1%). More than half of the cases involved chemicals (n = 939, 53.1%); hydrocarbons, gases and corrosives were the main causative agents. Pharmaceuticals (mainly analgesics) were involved in 519 (29.3%) cases, venomous animals (mainly scorpions, centipedes, and snakes) in 79 (4.5%). Clinical manifestations were reported in 666 (37.6%) cases, mostly gastrointestinal, neurologic, and respiratory. The vast majority of cases (1634, 92.3%) were asymptomatic or mildly affected; no fatalities were recorded. In 831 (46.9%) cases the clinical toxicologist recommended referral to an emergency department; ambulatory observation was recommended in 563 (31.8%) cases, and hospitalization in 86 (4.9%).Our data show that poison exposures among young soldiers involve mainly males, accidents, misuse and suicides, oral route and chemicals; most exposures were asymptomatic or with mild severity. Repeated evaluations of poison center data pertaining to military personnel is advised for identifying trends in poison exposure and characteristics in this particular population.

Calcium channel blocker (CCB) overdose is a potentially fatal poisoning. The use of intravenous lipid emulsion (ILE) therapy for CCB poisoning has emerged in the past few years. In 2017, the American College of Medical Toxicology published interim guidance for the use of ILE resuscitation in these cases. We report an uncommon complication of ILE, acute respiratory distress syndrome, treated with veno-venous extracorporeal membrane oxygenation (ECMO). Case report: A 40-year-old hypertensive woman presented with shock (blood pressure 62/34 mmHg, pulse 86/ min) following ingestion of 4,800 mg verapamil slow release and 1,500 mcg clonidine during a suicide attempt. She was treated with calcium gluconate, sodium bicarbonate, IV high dose insulin, IV glucagon, cardiac amines and vasopressors without response (blood pressure 69/37 mmHg, pulse 78/min). ILE was initiated, and two hours later, she developed acute respiratory failure necessitating intubation and mechanical ventilation. Due to poor oxygenation (pO2 44 mmHg; FiO2 100%) emergent veno-venous ECMO was instituted. After one hour her blood pressure increased to 104/50 mmHg (pulse 80, pO2 75 mmHg), and continued so until weaning from ECMO and ventilation. Conclusion: Acute respiratory distress syndrome can be a major life threating complication following ILE; venovenous ECMO is suggested for its treatment.

Aim: Bronchial hyper-reactivity (BHR) provides a tool for asthma diagnosis, assessment of severity and response to treatment. The effect of beclomethasone dipropionate in ultrafine particles (BDP-HFA) on BHR as measured by the adenosine challenge test in young children has not yet been determined. Our aim was to determine the effect of BDP-HFA (100 μg twice daily) on BHR as evaluated by a reduction of 20% from baseline FEV1 (PC20-FEV1) values in young asthmatic children. Methods: Twenty-one young children (13 males), mean age 4.95 ± 1.05 years, with partially controlled or controlled asthma completed a double-blind randomized, placebo-controlled, cross-over study. Each child received 4 weeks of treatment with either 100 μg BDP-HFA twice daily or placebo, and after a 2-week washout period the other way around. Primary outcomes were PC20-FEV1 concentration, and the stage number at which FEV1 values dropped by 20%. Results: Following 4 weeks of treatment, median PC20-FEV1 was 81.28 mg/mL while on BDP-HFA, compared with 9.64 mg/mL on placebo (p

Colchicine is used mainly for the treatment and prevention of gout and for familial Mediterranean fever (FMF). It has a narrow therapeutic index, with no clear-cut distinction between nontoxic, toxic, and lethal doses, causing substantial confusion among clinicians. Although colchicine poisoning is sometimes intentional, unintentional toxicity is common and often associated with a poor outcome.We performed a systematic review by searching OVID MEDLINE between 1966 and January 2010. The search strategy included "colchicine" and "poisoning" or "overdose" or "toxicity" or "intoxication."Colchicine is readily absorbed after oral administration, but undergoes extensive first-pass metabolism. It is widely distributed and binds to intracellular elements. Colchicine is primarily metabolized by the liver, undergoes significant enterohepatic re-circulation, and is also excreted by the kidneys. THERAPEUTIC AND TOXIC DOSES: The usual adult oral doses for FMF is 1.2-2.4 mg/day; in acute gout 1.2 mg/day and for gout prophylaxis 0.5-0.6 mg/day three to four times a week. High fatality rate was reported after acute ingestions exceeding 0.5 mg/kg. The lowest reported lethal doses of oral colchicine are 7-26 mg.CYP 3A4 and P-glycoprotein inhibitors, such as clarithromycin, erythromycin, ketoconazole, ciclosporin, and natural grapefruit juice can increase colchicine concentrations. Co-administration with statins may increase the risk of myopathy.Colchicine's toxicity is an extension of its mechanism of action - binding to tubulin and disrupting the microtubular network. As a result, affected cells experience impaired protein assembly, decreased endocytosis and exocytosis, altered cell morphology, decreased cellular motility, arrest of mitosis, and interrupted cardiac myocyte conduction and contractility. The culmination of these mechanisms leads to multi-organ dysfunction and failure. REPRODUCTIVE TOXICOLOGY AND LACTATION: Colchicine was not shown to adversely affect reproductive potential in males or females. It crosses the placenta but there is no evidence of fetal toxicity. Colchicine is excreted into breast milk and considered compatible with lactation.Colchicine poisoning presents in three sequential and usually overlapping phases: 1) 10-24 h after ingestion - gastrointestinal phase mimicking gastroenteritis may be absent after intravenous administration; 2) 24 h to 7 days after ingestion - multi-organ dysfunction. Death results from rapidly progressive multi-organ failure and sepsis. Delayed presentation, pre-existing renal or liver impairment are associated with poor prognosis. 3) Recovery typically occurs within a few weeks of ingestion, and is generally a complete recovery barring complications of the acute illness.History of ingestion of tablets, parenteral administration, or consumption of colchicine-containing plants suggest the diagnosis. Colchicine poisoning should be suspected in patients with access to the drug and the typical toxidrome (gastroenteritis, hypotension, lactic acidosis, and prerenal azotemia).Timely gastrointestinal decontamination should be considered with activated charcoal, and very large, recent (60 min) ingestions may warrant gastric lavage. Supportive treatments including administration of granulocyte colony-stimulating factor are the mainstay of treatment. Although a specific experimental treatment (Fab fragment antibodies) for colchicine poisoning has been used, it is not commercially available.Although colchicine poisoning is relatively uncommon, it is imperative to recognize its features as it is associated with a high mortality rate when missed.

The maximal recommended local anesthetic dose of lidocaine is 7 mg/kg; higher doses are used in tumescent liposuction. The objective of this study was to characterize the pharmacokinetics of high-dose diluted lidocaine administered together with epinephrine for local anesthesia in facelift procedures. This was a prospective study of six female patients undergoing elective facelift surgery. The local anesthetic solution consisted of 0.33% lidocaine, 0.07% sodium bicarbonate, and 1:600,000 epinephrine in normal saline. Plasma lidocaine levels were determined in the course of 24 hours and were subjected to pharmacokinetic analysis. Patients' age was 58.5 +/- 8 years and weight 68.5 +/- 18.7 kg. Mean lidocaine dose was 21.6 +/- 3.6 mg/kg (range, 17.5-26.3 mg/kg) infiltrated subcutaneously over 20 minutes or less. No lidocaine-related adverse effects were recorded. Major bleeding was not observed. Postoperative analgesia was required only at 11.8 +/- 4.6 hours after surgery. Pharmacokinetic analysis was peak concentration 1.41 +/- 0.4 microg/mL, time to reach peak concentration 9.3 +/- 1.6 hours, terminal half-life 6.2 +/- 1.5 hours, area under the curve from time zero to last data point 1379.8 +/- 470 microg/min/mL, and area under the curve from time zero to infinity 1530.6 +/- 471.6 microg/min/mL. Plasma lidocaine concentrations formed almost a plateau between 2 and 12 hours (ie, at approximately 1.2 microg/mL) after infiltration. It is concluded that local anesthesia with diluted lidocaine at a dose 3.1 times higher than the currently recommended dose (7 mg/kg) administered with epinephrine yielded a peak plasma lidocaine level that was 72% below the level considered safe (5 microg/mL).

Objective: To report the limited efficacy of both multiple doses of activated charcoal (MDAC) and whole bowel irrigation (WBI) in a patient with severe overdose of slow-release carbamazepine. Case Summary: A 25-year-old man was admitted in a comatose state with seizures after a suicide attempt with slow-release carbamazepine. Serum carbamazepine concentration on admission (16 h postingestion) was 52.08 μg/mL. The patient was mechanically ventilated and treated with MDAC and a 4 hour charcoal hemoperfusion. Carbamazepine concentration at the end of hemoperfusion was 27.16 μg/mL. Despite continuous treatment with MDAC, a rebound in carbamazepine concentration to 36 μg/mL was observed 32 hours after hemoperfusion (58 h postingestion). WBI was performed over a 10 hour period. The carbamazepine concentration continued to increase to 38.55 μg/mL and seizures recurred. After WBI was performed, MDAC was reinstituted; 33 hours later (102 h postingestion), the carbamazepine concentration began to decline. The hospitalization course was complicated by pneumonia, which necessitated continuation of mechanical ventilation and administration of antibiotics. The patient recovered completely and was discharged without sequelae 15 days after admission. Discussion: Serum carbamazepine concentration and toxicity were effectively reduced by hemoperfusion. The role of MDAC coadministered during hemoperfusion cannot be ruled out. However, a rebound in carbamazepine concentration with recurrent seizures was observed despite MDAC and WBI. The most likely explanation for this rebound (65 h postingestion, 39 h posthemoperfusion) is prolonged absorption, possibly from a pharmacobezoar. Redistribution cannot be excluded, but this is not supported by the concentration–time course and previous reports. Conclusions: Both MDAC and WBI may be ineffective in reducing absorption and enhancing elimination in overdose of slow-release carbamazepine. Repeated hemoperfusion or other elimination enhancement techniques should be considered when the clinical and toxicokinetic course suggests the presence of a refractory pharmacobezoar.

Exposure to silica gel, a common desiccant, is considered common and non-toxic although data are limited.To evaluate the characteristics of silica gel ingestion, and to attempt to estimate the associated health care costs.We conducted a one year retrospective review of charts of a national poison information center to characterize ingestions of silica gel and estimate its direct cost to health care services. Cost evaluation was based on emergency department and community clinic tariffs (NIS 807/US$ 213 and NIS 253/US$ 67, respectively).A total of 546 cases were recorded, 2.1% of the annual calls to the poison information center. Most ingestions occurred in children younger than 6 years old (91.4%, 65.2%2 years). Median monthly exposure was 42; the peak (74) occurred in April, before the Passover holiday. Sixty calls (11%) came from health care facilities and the rest were reported by the public; 2.7% were symptomatic, mainly mild self-limited mouth and throat discomfort. The direct annual treatment cost of patients who referred themselves to health care facilities without consulting first with the Poison Center (n = 60) was NIS 24,598/US$ 6507 (emergency department and community clinic visit fees).Silica gel ingestion is relatively common, occurring mainly in young children; it is rarely symptomatic but is a source of unnecessary referrals to health care facilities. The potential annual saving by preventing unnecessary referrals due to poison information center advice was estimated at NIS 375,678/US$ 99,383. The availability of poison information center services may prevent unnecessary referrals to health care facilities and thus save costs.

The Israel National Poison Information Center (IPIC), Rambam Health Care Campus, provides 24 hour telephone consultations in clinical toxicology as well as drug and teratogen information. It participates in research, teaching and regulatory activities, and also provides laboratory services.To report data on the epidemiology of poisonings and poison exposures in Israel.We made computerized queries and descriptive analyses of the medical records database of the IPIC during 2012.A total of 31,519 poison exposure cases were recorded, a 157.6% increase compared with 1995. Children6 years of age were involved in 43.1% of cases; 74.0% of calls were made by the public and 23.7% by physicians; 74.8% of exposures were unintentional and 9.1% intentional. Chemicals were involved in 35.8% of all cases (single and multiple substances), pharmaceuticals in 48.8%, bites and stings in 3.8%, and plants and mushrooms in 1.6%. Substances most frequently involved were analgesics, cleaning products and antimicrobials. Clinical severity was moderate/major in 3.4%. Substances most frequently involved in moderate/major exposures were corrosives, insecticides and snake venom. Four fatalities were recorded; all were intentional exposures in adults (corrosive, medications, energy drink).Poison exposures and poisonings have increased significantly and have contributed substantially to morbidity and mortality in Israel. The IPIC database is a valuable national resource for the collection and monitoring of poisoning exposure cases. It can be used as a real-time surveillance system for the benefit of public health. It is recommended that reporting to the IPIC become mandatory and its activities be adequately supported by national resources.

Xylene is a commonly used toxic volatile organic solvent. Diagnosis of acute xylene poisoning is limited by the lack of a readily available analytic assay. Methylhippuric acid, a metabolite of xylene excreted in the urine, is used for biomonitoring occupational exposures to xylene. We report two cases of acute occupational poisoning from xylene inhalation suggested by determination of high urinary methylhippuric acid. Two 21 and 23 years old healthy male adults collapsed after inhaling an unknown paint thinner during painting. On admission to the emergency department, they were confused and agitated, without hemodynamic or respiratory impairment. Admission urinary methylhippuric acid determined by HPLC with UV detector were 2.57 and 2.68 g/g creatinine (Biologic Exposure Index, BEI, 1.5 g/g creatinine). Urinary hippuric acid was below the previously used BEI for toluene. Mild increases in alanine aminotransferase (80 U/L) and aspartate aminotransferase (71 U/L) were found 12 hours after exposure, returning to normal after 24 hours. The patients gradually regained full consciousness within 24 hours and discharged after 48 hours' observation without any sequelae. High urinary methylhippuric acid concentrations suggested the diagnosis of acute xylene poisoning following its inhalation. Diagnosis in previous reports of acute xylene poisonings relied on history and clinical manifestations. Urinary methylhippuric acid assay is specific and available in special laboratories. It is suggested to determine urinary methylhippuric acid together with metabolites of other widely available organic solvents (e.g., hippuric acid, trichloroacetic acid) whenever unintentional exposure or abuse of volatile organic compounds is suspected.

The clinical effects of self injections of atropine-trimedoxime auto-injectors distributed to the civilian population as a field antidote for nerve agent attack were assessed.Data on self injections by adults (or = 18 years) were collected from the Israel Poison Information Center and a hospital Emergency Department's records during a 2-year period. The data included demographics, time interval from injection, type of auto-injector, clinical manifestations and atropinization score.Sixty-five patients, all with unintentional self injections, were reported. Systemic atropine effects were observed in 24 patients, but no severe atropinization. The atropinization score was significantly higher in the 2 mg atropine dose group than in the two lower dose groups, which were in the normal range. No specific adverse effects attributable to trimedoxime were observed. Intravenous fluids and physostigmine were not required.Only mild reactions were observed following self-injection of atropine trimedoxime auto-injectors in adults, attesting to their relative safety under these conditions.

The aim of this study is to report our experience with a child who developed extrapyramidal perturbations complicating acute organophosphate insecticides poisoning and to review the literature reporting on basal ganglia impairment associated with this poisoning. Our patient had developed overt parkinsonism presenting with a resting tremor, expressionless face, and lack of blinking along with marked cogwheel rigidity and a stooped, slow gait. He was alert, coherent, and cooperative, yet agitated. The parkinsonian perturbations developed 5 days after an accidental ingestion of a raw eggplant sprayed with the organophosphate dimethoate (Rogor) when he had already recovered from the acute cholinergic crisis, the first stage of organophosphate poisoning. Such a presentation was initially perceived by his caregivers as severe reactive depression or even psychosis. Once a parkinsonian syndrome was diagnosed, he was begun on amantadine and completely recovered within 1 week with no relapse of symptoms. Basal ganglia impairment should be considered in any patient who develops extrapyramidal symptoms such as marked rigidity and bradykinesia or choreoathetosis while recovering from the acute cholinergic phase of organophosphate insecticide poisoning. Thus, administration of a drug such as amantadine, which probably enhances neurotransmission, may hasten the rate of recovery and prevent long-term neurologic and emotional sequelae.

A sampling protocol for biomonitoring of the volatile solvent methylene chloride (MeCl(2)) by analysis of urine from exposed workers was established. Storage temperature, sample volume in headspace vial (HSV), and time to sealing HSV on determination of MeCl(2) in urine were evaluated. MeCl(2) was analyzed by a solid-phase microextraction technique combined with gas chromatography. Volume of urine in HSV has no effect on MeCl(2) analysis. Delays of 30 and 60 min from collection of urine until sealing the HSV caused 14.47 +/- 6.98% and 26.17 +/- 9.57% decreases from baseline concentration, respectively. MeCl(2) concentration in spiked urine samples stored in sealed HSVs decreased on day 2 and then remained stable for 2 weeks. Refrigeration did not improve recovery although it seems to be associated with less variability. MeCl(2) in urine samples of seven exposed workers was in the range of 0.02-0.06 mg/L. Sampling of MeCl(2)-containing urine should include collection of urine in closed plastic bottles, transfer to HSV within 15 min, sealing and clamping of HSV within 15 s, and storage of HSV in refrigeration until analysis, but no longer than 2 weeks. Standard samples should be prepared on the day of test sample collection and handled under the same conditions.

Objective To describe the effects of combined trimedoxime (TMB4) and atropine poisoning from automatic injectors (AI) in children. Study design Data was collected from two sources: calls to the Israel Poison Information Center (IPIC) during a 1-year period and a cohort of children who presented to pediatric emergency departments (EDs) after unintentional injection of an AI. Demographic data and data regarding the type of AI, site and time of injection, and the clinical manifestations were abstracted. Results Data were available for 142 patients. The median age was 8.5 years (range 1.25-18 years). The dose of atropine and TMB4 was higher than the recommended dose for age in 22 (15.5%) cases. There were few side effects attributable to atropine: dilated pupils (26.7%), dryness of mucous membranes (24.6%), and tachycardia (22.5%). Compared with children injected with an age-appropriate dose, children injected with an AI that contained a dose that exceeds the recommended one were more likely to be symptomatic (P = .029). There were no side effects characteristic to oximes, and no specific medical intervention was required. Conclusions Unintentional pediatric atropine and TMB4 injection, even an adult dose in a small child, does not cause significant side effects.

Background: Deliberate self-poisoning (DSP) is a major health problem with increasing incidence mainly among young people. Objective: To examine the clinical and toxicological characteristics of DSP, it is compared to unintentional (non-DSP) exposures and those characteristics which might be associated with increased toxicological risk are identified. Methods: Two-year retrospective poison centre chart review. Statistics: χ2 analysis. Results: 3802 DSP cases were reported. Most calls (95%) were made by physicians compared to 51%) in non-DSP exposures, P

Dipyrone is a pyrazolone derivative used as an analgesic and antipyretic. Agranulocytosis, dipyrone's most serious and potentially fatal adverse effect, has led to its withdrawal in several countries. However, agranulocytosis is subject to geographical variability, ratio with at risks ranging from 0.8-23.7. In many countries dipyrone is still widely used in adults and children and even as an over-the-counter (OTC) preparation. Information on the effects of dipyrone overdose is scanty.To determine the demographic and clinical characteristics of dipyrone overdose.Retrospective review of prospectively collected poison center data on acute exposure to dipyrone over a three-year period. The data were subjected to descriptive analysis. Mann-Whitney test and Chi-square analysis were performed where relevant.A total of 243 records met the inclusion and exclusion criteria. Median age was 17y (4m-83y), median amount 5 g (250 mg-45 g), and median time to consultation was 2 h (5 min-48 h). Toxic events (49) occurred in 39 (16%) patients; 57% of these were gastrointestinal and all were mild. Time to consultation was longer in the symptomatic patients (4 h vs. 1.5 h, respectively, p=0.001) and in children (8 h vs. 3.5 h in adults). Suicidal patients ingested significantly larger amounts (8 g vs. 3.7 g, respectively, p=0.001), as did patients with gastrointestinal symptomatology (7.5 g vs. 5 g in asymptomatics, p=0.001). No agranulocytosis was reported.Dipyrone overdose is associated with mild, mainly gastrointestinal toxicity; this was noted at a median dose of 7.5 g. Early gastrointestinal decontamination may have prevented toxicity. The suggested treatment includes gastrointestinal decontamination (if1 h since ingestion) and supportive measures.

Volatile alkyl nitrites have been used during the past decades for "recreational purposes," and for intensifying sexual experience. Their use has been associated with methemoglobinemia and hemolysis. We report three patients who presented over the past year with acute hemolysis after inhalation of butyl nitrite, two of them had glucose-6-phosphate dehydrogenase (G6PD) deficiency.

Introduction:The use of inhaled corticosteroids (ICS) via infant aerochamber in young, asthmatic children is increasing. However, concern has been raised about its long-term impact. Hypercalciuria is a known adverse effect of systemic corticosteroids.Objective:To determine whether ICS-induced hypercalciuria occurs in young, asthmatic children.Setting:Two outpatient clinics.Methods:Urinary calcium/creatinine ratio (UCa/Cr) was determined in 32 asthmatic children (age 6–36 mo) who were receiving inhaled budesonide or beclomethasone 200–600 μg/d for two to three months. A control group of asthmatic children within the same age range (n = 23) who did not receive ICS was included. None of the children were receiving oral corticosteroids, diuretics, antibiotics, or theophylline.Statistics:Student's t-test and χ2analysis.Results:The treated and control groups were similar with regard to age and male/female ratio. Mean ± SD UCa/Cr was significantly higher in the asthmatic children receiving ICS (0.23 ± 0.19 vs. 0.09 ± 0.07, respectively; p = 0.002). Fourteen (43.75%) of the treated patients had hypercalciuria (UCa/Cr >0.2) compared with only one (4.35%) in the control group (p = 0.002). Renal ultrasonography failed to demonstrate nephrocalcinosis in eight of the treated hypercalciuric patients.Conclusions:Treatment of young, asthmatic children with ICS may be associated with hypercalciuria. More studies are needed to evaluate the clinical significance of this finding.

Pulmonary manifestations of Crohn's disease are infrequent in adults and even less common in children. Our literature search found only a few cases of Crohn's disease causing pulmonary manifestations in children. We report on the case of a 13-year-old girl in whom severe pulmonary disease was found four years after the onset of Crohn's disease. Open lung biopsy uncovered bronchiolitis obliterans and granulomatous lung disease. Aggressive treatment has yielded gradual improvement. This case emphasizes the importance of recognizing the association, the differential diagnosis, and treatment implications. Pediatr Pulmonol. 2000; 29:151–154. © 2000 Wiley-Liss, Inc.

1 Endogenous digoxin-like immunoreactive substances (DLIS) cross-react in immunoassays of digoxin. The postmortem rise in digoxin levels in patients treated with the drug may be due to its redistribution. It is unclear what is the contribution of DLIS to this increase and whether DLIS are present postmortem in patients not treated with digoxin. 2 The objectives of this study were to determine whether DLIS are present after death in patients not treated with digoxin, whether a postmortem increase in DLIS is detectable and whether sampling site can affect DLIS concentrations. 3 DLIS (measured as digoxin, TDx Abott) were determined in blood samples drawn antemortem from ICU patients; postmortem samples from femoral artery and cardiac chambers were taken at least 12 h after the death of these same patients. 4 DLIS concentrations ≥0.2 ng/ml were measured in 44 and 40% of patients antemortem and postmortem (femoral), respectively. No difference was found in DLIS levels between antemortem and postmortem femoral and cardiac samples. Age, ICU stay and postmortem sampling time did not affect the postmortem increase in DLIS. None of the levels was in the toxic range. 5 DLIS may be present after death and their concentration does not increase postmortem. The interpretation of postmortem digoxin concentrations that fall in the therapeutic range should be done cautiously; such measurable levels do not necessarily indicate misuse or malicious intent even in patients who had not been treated with the drug.

A woman was admitted to hospital in the 39th week of gestation due to syncope, followed by nausea and headache. The patient's history revealed a 10-hour, unintentional exposure to carbon monoxide (CO), secondary to burning charcoal for indoor heating. Because of monitored fetal distress, a cesarean section was performed. The newborn had an Apgar score of 4, 9, and 10 at 1, 5, and 10 minutes post-delivery, respectively. The 1-minute Apgar was low due to lack of spontaneous breathing, reduced tonus, bluish coloration, and reduced response to pain. The neonate's carboxyhemoglobin level seven hours post-CO exposure was 22%, and arterial pH was 7.28. Neurological examination 30 minutes after delivery showed no pathology. The neonate was treated with 100% normobaric oxygen for 12 hours. We discuss the treatment options for fetal CO poisoning and specific considerations that had to be taken into account in the present case.

Phenol is a general protoplastic poison which has been in use in medicine and industry for decades. It is readily absorbed through the skin causing both local and systemic toxicity.A 47-year-old male had 90% phenol spilled over his left foot and shoe (3% of body surface area). After a 4 1/2-hour exposure, manifestations included confusion, vertigo, faintness, hypotension, ventricular premature beats, atrial fibrillation, dark-green urine, and tense swelling, blue-black discoloration, hypalgesia, and hypoesthesia of the affected area. Treatment consisted of irrigation with copious amounts of water, incisions, and supportive measures.Peak serum phenol was 21.6 micrograms/mL, considered in the fatal range. Peak urine phenol plus urine-conjugated phenol was 13,416 mg/g creatinine, indicating a major absorption. Elimination half-life was 13.86 hours, considerably longer than previously reported.Prolonged skin contact with concentrated phenol in an occlusive environment may result in a major absorption and a long elimination half-life even if the area involved is small. Prolonged elimination may be explained by extensive tissue distribution or by "slow-release reservoir" properties of the skin. Such exposure may be associated with severe systemic and local toxicities. Immediate removal from exposure and aggressive decontamination of the skin are essential to reduce these risks.

1 Although calcium gluconate (CG) is recommended in the treatment of hydrofluoric acid (HF) eye burn its efficacy seems to be controversial, and controlled human or animal studies are limited. The study's objective is to compare the efficacy of 1% CG and normal saline irrigation for the treatment of HF eye injury in animals. 2 0.05 ml 2% HF was instilled to anesthetized rabbit's eyes. One minute later, four treatment groups were studies: (1) irrigation with normal saline followed by topical antibiotics, corticosteroids and cycloplegics for 48 h ( n=10); (2) irrigation with 1% CG followed by the same topical treatment ( n=9); (3) as group 1 and 1% CG drops over 48 h ( n=10); (4) as group 3, and injection of 1% CG subconjunctivally after irrigation ( n=9). 3 Corneal erosion area, corneal haziness, conjunctival status, vascularization (pannus) and acidity were assessed before injury, immediately after intitial treatment and 1, 2, 7 and 14 days thereafter by slit lamp aided by fluorescein staining. 4 Conjunctival pH dropped from 6.0 - 6.5 to 2.5 - 3 after injury and increased to 6 - 6.5 after irrigation. Corneal erosion: smaller in groups 2, 3, significantly so at 2 days, but not different at 14 days. Corneal haziness: more severe in group 4, at 14 days, insignificant. Conjunctival damage: significantly worse in group 4 at 2, 7 and 14 days. Pannus appeared in 2 - 4 eyes in each group. 5 It seems that for HF injury 1% CG did not have any significant advantage over saline irrigation and topical treatment only. It might have some initial and temporary effect on healing process especially that involving erosion. Given subconjunctivally, 1% CG may be toxic and worsens clinical outcome.

The use of helium and oxygen recompression treatment of neurologic decompression sickness (DCS) has several theoretical advantages over the traditionally used air and oxygen recompression tables that have been confirmed by findings from recent animal experiments.To evaluate the outcome of patients with neurologic DCS who had been treated with a helium-oxygen protocol and to compare it with that of a retrospective control group that was treated with air-oxygen tables.The study and control groups included 16 and 17 diving casualties, respectively. The severity of neurologic DCS was estimated according to a 9-point scale weighting motor, sensory, and sphincter control functions. The study group was treated with a helium-oxygen decompression protocol, and the control group was treated with the US Navy air-oxygen Table 6 or 6A. Persistent residual dysfunction was treated in both groups with daily hyperbaric oxygen sessions, at 2.5 absolute atmospheres for 90 minutes, until no further clinical improvement was noted.The Israel Naval Medical Institute (Israel's national hyperbaric referral center), Haifa.Significant clinical score increments were found for both the helium-oxygen- and air-oxygen-treated groups: 2.8 +/- 2.4 (mean +/- SD) and 7.4 +/- 1.1 at presentation vs 7.6 +/- 2.1 and 8.1 +/- 1.5 at discharge, respectively (P.001 and P = .005, respectively). Although the score at presentation was significantly lower for the helium-oxygen-treated group (P.001), no difference was found between the groups' average outcome scores. While most of the improvement in the patients in the study group could be attributed to the helium-oxygen treatment and not to the supplemental hyperbaric oxygen, in the control group, no significant difference could be demonstrated between the scores at presentation and at completion of the air-oxygen recompression table. In 5 patients who were treated with the use of the air-oxygen tables, deterioration was observed after recompression. No deterioration or neurologic DCS relapse occurred in the helium-oxygen-treated group.The results suggest an advantage of helium-oxygen recompression therapy over air-oxygen tables in the treatment of neurologic DCS.

Indoor group water-pipe tobacco smoking, commonly referred to as water-pipe smoking (WPS), especially in coffee shops, has gained worldwide popularity. We performed a comprehensive laboratory and clinical evaluation of the acute effects of active and passive indoor group WPS.This comparative study evaluated pre- and post-30-min active and passive indoor group WPS. The outcome parameters were carboxyhemoglobin (COHb), nicotine, and cotinine levels; CBC count; and cardiorespiratory parameters. Exhaled breath condensate (EBC) cytokines and endothelial function (using the EndoPat device [Itamar Medical Ltd]) were measured only in active smokers. Statistical methods used were Student t test, Wilcoxon signed rank test, Fisher exact test, analysis of variance, and Newman-Keuls post hoc test where relevant.Sixty-two volunteers aged 24.9±6.2 years were included; 47 were active smokers, and 15 were passive smokers. COHb level increased postactive WPS (active smokers, 2.0%±2.9% vs 17.6%±8.8%; P.00001); six subjects (12.7%) had a25% increase, and two subjects (4.2%) had a40% increase. Plasma nicotine level increased postactive WPS (active smokers, 1.2±4.3 ng/mL vs 18.8±13.9 ng/mL; P.0001); plasma cotinine and urinary nicotine and cotinine levels also increased significantly. EBC IL-4, IL-5, IL-10, IL-17, and γ-interferon decreased significantly with postactive smoking; endothelial function did not change. WPS was associated with adverse cardiorespiratory changes. In passive smokers, COHb level increased (0.8%±0.25% vs 1.2%±0.8%, respectively, P=.003) as did respiratory rate.One session of active indoor group WPS resulted in significant increases in COHb and serum nicotine levels (eightfold and 18-fold, respectively) and was associated with adverse cardiorespiratory health effects. The minor effects found in passive smokers suggest that they too may be affected adversely by exposure to WPS. The results call for action to limit the continuing global spread of WPS in coffee shops.ClinicalTrials.gov; No.: NCT1237548; URL: www.clinicaltrials.gov.

Corrosive substance ingestion is a toxicological emergency with relatively high mortality requiring rational surgical decisions.Evaluate the role of chest and abdominal computed tomography (CT) in assessing the severity of acute corrosive ingestion.A retrospective study of adults admitted due to corrosive ingestion, who underwent gastrointestinal endoscopy and CT within 48 h of admission. Endoscopy findings were graded as 0, 1, 2a, 2b, 3a, and 3b (Zargar's criteria), CT findings were graded as 0, 1, 2, and 3. For each patient endoscopy and CT grades were compared, and sensitivity and specificity for predicting mortality or emergency laparotomy were calculated.Twenty-three patients were included, aged 18-87 years; seven underwent emergency laparotomy, five died. Endoscopy grading was higher than CT grading in 14 patients (66%). The sensitivities of endoscopy grades 2b and 3 to predict mortality and emergency laparotomy were 1 and 0.8, respectively; the specificities were 0.38 and 0.37, respectively. The sensitivities of CT grade 3 to predict mortality and emergency laparotomy were 0.4 and 0.28, respectively; the specificities were 0.94 and 0.93, respectively. Three patients had pulmonary infiltrates on CT but not on chest X-ray. DISCUSSION. CT tends to underestimate the severity of corrosive ingestion compared with endoscopy. It has lower sensitivity and higher specificity than endoscopy in predicting major outcome. CT can provide important information on lung injury, and when endoscopy cannot be completed.CT should not be the only basis for surgical decisions during the initial phase of acute corrosive ingestions.

Medication errors (ME) are a major concern to healthcare systems. Most studies evaluated ME occurring in healthcare facilities; only few focused on ME outside them. The objective was to characterise ME occurring outside healthcare facilities. A prospective observational follow-up study evaluating all ME occurring outside healthcare facilities reported to a national poison information centre during a 5-month period. For each ME case, a detailed questionnaire was filled and a follow-up call was made within 7 days. The collected data included demographics, circumstances, type of error and outcome. Of 1381 consecutive ME cases were included; 97.8% involved a single incident and 88.3% one drug. The main characteristics of the ME were as follows: children younger than 6 years old (58.9%), parents responsible for 55.6% of cases, wrong dose 34.5% and different medication 30.1%. Analgesics (27.4%) and antimicrobials (12.2%) were the most common pharmaceuticals. The main reasons for the ME were look-alike packaging (31.4%) and misunderstood instructions (28%). Most followed up patients (97.1%) were asymptomatic or mildly affected; there was one severe case and no mortality. Most ME occurring outside healthcare facilities are single incidents, involving young children who were administered a wrong dose or medication due to look-alike packaging or misunderstood instructions with asymptomatic or mild outcome. Improved packaging, labelling and patient education are suggested to reduce ME.

Background Sulfonylureas are used extensively for treating type-2 diabetes mellitus. Sulfonylurea poisoning can produce sustained and profound hypoglycemia refractory to IV dextrose, particularly in children and the elderly. Objective To review the use of octreotide, a long-acting somatostatin analog, in the treatment of sulfonylurea-induced hypoglycemia. Methods A computerized search of U.S. National Academy of Medicine, Embase, PubMed and Toxline databases was undertaken using the keywords "octreotide", "sulfonylurea", "poisoning", "intoxication", "overdose" and "children". Textbooks of Clinical Toxicology and Pharmacology and the articles cited in their bibliographies were also searched. Twenty-four publications (19 articles and five conference abstracts) were identified; no publication was excluded. PHARMACOLOGY OF OCTREOTIDE: Octreotide, a synthetic peptide analog of somatostatin, binds to G protein-coupled somatostatin-2 receptors in pancreatic beta-cells, resulting in decreased calcium influx and inhibition of insulin secretion. Octreotide markedly inhibited insulin secretion and decreased the number of hypoglycemic events and supplemental dextrose requirements in animal studies. In humans octreotide markedly inhibited insulin release, increased serum glucose concentration, reduced dextrose requirement, prevented recurrent hypoglycemia and was superior to IV dextrose and diazoxide after administration of sulfonylureas. EFFICACY OF OCTREOTIDE IN PEDIATRIC SULFONYLUREA POISONING: Fourteen pediatric patients were reported; 13 ingested second-generation sulfonylureas, with time to hypoglycemia of 1.5-16 hours. IV dextrose (10-25%) was administered before and after octreotide therapy. Octreotide was given after failure to correct hypoglycemia with IV dextrose in doses of 0.51-2 μg/kg IV or SC; two also required an IV octreotide infusion. Seven patients (50%) had recurrent hypoglycemia and received IV dextrose and additional octreotide. EFFICACY OF OCTREOTIDE IN ADULT SULFONYLUREA POISONING: Fifty-three patients were reported in prospective controlled (n = 22) and retrospective (n = 9) studies, case series (n = 6) and case reports. Fifty-one ingested second-generation sulfonylureas with time to hypoglycemia of 1-13 hours. All received IV dextrose (10-50%) before and after octreotide treatment. Octreotide 40-100 μg SC or IV was administered followed by additional doses in most patients; three patients also required an IV infusion. Octreotide significantly increased serum glucose concentrations, decreased dextrose requirement and recurrent hypoglycemic events compared with IV dextrose. Recurrent hypoglycemia was recorded in 22-50% of the patients treated with octreotide. THERAPEUTIC RECOMMENDATIONS: Based on the published clinical and pharmacokinetic data of sulfonylureas and octreotide, we suggest the following dose regimens: in children, octreotide 1-1.5 μg/kg IV or SC, followed by 2-3 more doses 6 hours apart. In adults, octreotide 50 μg SC or IV, followed by three 50 μg doses every 6 hours. During this treatment IV dextrose infusion should be gradually tapered off. Adverse events Hypertension and apnea were recorded in one pediatric patient 30 minutes after IV octreotide; the relationship to octreotide is unclear. One adult patient with chronic renal failure treated with atenolol developed severe hyperkalemia. Conclusions Although relatively limited, the available data suggest that octreotide should be considered first-line therapy in both pediatric and adult sulfonylurea poisoning with clinical and laboratory evidence of hypoglycemia. Maintenance doses of octreotide may be required to prevent recurrent hypoglycemia.

The neurotoxicity of methotrexate (MTX) is more severe when administered intrathecally (IT) than by the oral and intravenous (IV) routes, and has been reported even with a single administration of therapeutic doses of 12 or 15 mg. Prompt recognition and treatment are essential to improve the outcome after massive IT-MTX overdose. Treatment options include CSF drainage or CSF exchange, ventriculolumbar perfusion, IT corticosteroids to reduce CSF inflammation and IV leucovorin to reduce systemic toxicity. Toxicity resulting from IT injection of leucovorin is controversial. CSF drainage and exchange are particularly effective if performed soon after the overdose. In this paper we describe a protocol of treatment for severe cases of IT-MTX overdose in excess of 100 mg. The mainstay of treatment is dilution and removal from CSF of excessive methotrexate alongside with specific antidotal therapy.