265 Asthma after exposure to glutaraldehyde

Poster Session P11. Clinical toxicology tients. We divided patients in to three groups depending upon RBC cholinesterase on the presentation. (RBC cholinesterase of <500, 500–1000 and >1000). Out of 176 patients 82 (48.24%) were male and 94 (53.41%) were female. Most of the cases were suicidal attempt. Forty six (26.41%) patients developed intermediate syndrome. Twenty eight (54.90%) out of 51patients (RBC cholinesterase <500), 15 (57.69%) out of 26 patients (RBC cholinesterase 500–1000) and 3 (3.03%) out of 99 patients (RBC cholinesterase >1000) developed Intermediate syndrome. Duration of Intermediate syndrome was 5 days (RBC cholinesterase >1000), 9 days (RBC cholinesterase 500–1000) and 12 days (RBC cholinesterase <500). Most common findings were proximal muscle weakness, followed by neck flexors weakness, respiratory muscle weakness and motor cranial nerve paralysis. Time of onset was ranging from 8 to 72 hours. Conclusion: Intermediate syndrome is not rare and its’ onset and prevalence correlates with RBC cholinesterase. 262

muscles, which rapidly subsided as PAM administration was halted. There were no relapses of muscarinic symptoms, nor reduction in pChE or AChE levels in association with these neuromuscular changes. Serum pralidoxime levels ranged from 9 to 18 mcg/ml. Data suggesting a causal role of PAM in the observed neuromuscular changes include the delayed occurrence of these symptoms and their prompt resolution after drug discontinuation in all three patients. PAM neurotoxicity may be of special importance in massive OP poisoning. Pharmacokinetic studies have indicated that the distribution volume of PAM given as an antidote in patients with severe OP poisoning is about 10-times higher than in normal healthy volunteers, a condition reflecting increased drug accumulation in tissues. On this basis, PAM therapy could induce neuromuscular alterations even at moderate dosages in the presence of relatively low serum drug concentrations. This also suggests that measurement of serum PAM levels may not be sufficiently valuable in clinical setting to predict development of PAM-induced neurotoxicity. PAM neurotoxicity can be considered in differential diagnosis of neuromuscular disorders associated with OP poisoning.

OTC - PROGNOSTIC PARAMETER IN ACUTE ORGANOPHOSPHATE POISONINGS

Z. Pereska, L. Petkovska, Dz. Naumovski, C. Bozinovska, Gj. Pilovski, D. Petrovski, A. Babulovska. Clinic of toxicology and Urgent Internal Medicine, Clinical Center, Skopje, Maceodnia Organophosphate-based insecticides (OPI) are irreversibile inhibitors of acetylcholinesterase enzyme activity (ACHE). Clinical presentation of acute poisonings with OPI beside cholinergic syndrome includes also cardiotoxicity that indicates poor prognosis. The aim of this study is to estimate the correlation between ECG signs of myocardial repolarisation disturbances measured as QT interval prolongation corrected for HR (QTc) and a) the level of decrease of plasma (p) CHEA and b) the quantity of used antidotes (atropine) in the first 24 hours. The study include 36 patients acutely exposed to OPI, hospitaly treated at the Clinic of toxicology. The including criteria were 35–50% reduction of pCHEA levels at admission (range 1900– 3800U/l). p (CHEA) was determined by spectrofotometry method (Knedel and Butger). ECG performed at entrance was analyzed. The QTc was calculated by Bazzet’s formula. 450 msec was taken as critical value for QT prolongation for men and 470 msec for women. Patients were devided in 2 groups considering the QTc interval duration. First group (61.1% of pts) is consist of pts with prolonged QTc and second (38.4% of pts) with QTc duration under the critical values. Statistically, the correlation between the QTc interval duration and pCHEA for the first group of pts was positive and statistically significant (p< 0.05) and positive but statistically insignificant (p>0.05) in the second group. The correlation between QTc interval and the quantity of used antidotes (atropine) was statistically significant (p<0.05). Our results show that the OPI-induced cardiotoxicity is dose dependent and is not close correlated with pCHEA. The estimation of QTc interval prolongation can be prognostic parameter for the quantity of used antidotes and clinical course of these poisonings. 263

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SIDE EFFECTS OF ANTIDOTAL THERAPY WITH PRALIDOXIME IN HUMAN ORGANOPHOSPHATE POISONING

C. Locatelli, R. Butera, V. Petrolini, A. Bove, J. Georgatos, A. Agazzi, L. Manzo. Poison Control Center, IRCCS Maugeri Foundation and University of Pavia, Pavia, Italy Although oximes are generally regarded as the antidote of choice in organophosphate (OP) poisoning, the safety profile of these agents has not been sufficiently defined. Experimental studies have indicated that large doses of pralidoxime (PAM) can induce reversible neuromuscular blockade. Similar effects in skeletal muscles are also produced by OPs as a consequence of their nicotinic action. In a study of 3 patients with severe OP poisoning, treatment with PAM given at doses up to 500 mg/hour was associated with occurrence of delayed neuromuscular changes suggestive for PAM-induced neurotoxicity. Six to 7 days after starting PAM therapy, the patients developed fasciculations and tremors involving pectoral, deltoid and respiratory

264

ELECTROCARDIOGRAPHIC CHANGES OBSERVED IN ACUTE INHALATORY IRRITATIVE POISONINGS

J. Naumovski, Z. Pereska, L. Petkovska, C. Bozinovska, I. Naumov, E. Kovkarova. Clinic of Toxicology and Urgent Internal Medicine, Clinical Centre, Skopje, Macedonia Background: Irritant gases exert major effects on upper and lower respiratory tract mucosa. Typical clinical features include cough, labored breathing, and burning of eyes, nose and throat. These poisonings may cause cardiac manifestations, which are monitored less frequently. Material and methods: The study population included 67 poisoned patients, intoxicated with irritative fumes from household bleaches, detergents, and other cleaning/sanitizing agents. 57 patients (85%) were treated as outpatients. Subjective complaints and objective clinical features, as well as electrocardiography, roentgenology and laboratory findings, were recorded and analyzed. Results: At the time of presentation, electrocardiographic changes were detected in 42 patients (63%). The most frequent change observed was sinus tachycardia, which was seen in 37 (55%) of all patients. Unspecific changes of depolarization, such as ST segment and T wave changes were seen in 12 (18%) patients, while less frequent were premature beats, seen in 4 (6%) patients as supraventricular beats, and in 3 (4%) patients as ventricular ectopic beats. Some patients had single electrocardiographic changes, while some patients had a combination of 2 or more simultaneous changes. At the end of the treatment the electrocardiographic changes disappeared in all patients. Conclusion: Cleaning with sanitizing agents is a potential hazard for inhaling chlorine or ammonia gases, which, in poorly ventilated spaces, may cause intoxications. Cardiac complains are not frequent. However, it is important to monitor electrocardiographic changes in order to provide necessary treatment and prevent more serious disturbances of rhythm and conduction in older and patients with previous heart diseases. 265

ASTHMA AFTER EXPOSURE TO GLUTARALDEHYDE

G.F. Desogus. Study Reports of Toxicology, Azienda USL 7 di Carbonia, Italy Epidemiological studies show a direct connection between asthma and concentration of chemical pollutants, that act as adjuvant of the immunological reactions, mediated by a first non specific infiammatory reaction. Some environmental pollutants promote the IgE-mediated allergic sensitization, for adjuvant effect and all this is a base condition because of the increased susceptibility to “react” to occupational allergens. The use of specific chemical disinfectants in hospital (particularly glutaraldehyde and formaldehyde) is linked to the appearance of allergic symtoms and also small doses can induce IgE-dependent reactions both at pulmonary and epithelial level. This work studies if occupational exposure to glutaraldehyde and formaldehyde is associated with an increase of asthma and respiratory

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Poster Session P11. Clinical toxicology

allergic pathologies. Twenty-eight exposed workers (group 1: age 42 ± 7 years, 8 males and 20 females) and thirteen non exposed (group 2: age 43 ± 7 years, 4 males and 9 females) are investigated to verify the presence of respiratory allergic pathologies correlated to the exposure of chemical disinfectants. In the first group, one worker (3,6%) is suffering from bronchial asthma and 14 workers (50%) from clinical symptoms correlated to occupational exposure of chemical disinfectants (allergy, hay fever, bronchitis), probably of poly-allergic nature, while in the second group, we haven’t noticed any specific pathologies. In particular, the pathologies reported in the exposed population are often coincident with the use of disinfectant substances in hospital and under working conditions characterized by indexes of environmental pollution. The exposed poly-allergic workers don’t show with the use of adequate procedures of job and of individual protective measures, even if there is a tendence to the normalization in coincidence with an improvement of some rino-sinu-bronchial symptoms. The difficulty of an efficacious stratification with the habits of life and the state of individual susceptibility and the short period of observation limit the statistic meaning, but these preliminary data require a widest experimentation, also with the contribution of new scientific reports about the occupational allergic pathologies. 266

COMPREHENSIVE SCREENING OF ABUSED DRUGS IN TRAFFIC ACCIDENTS AND TRAUMA VICTIMS 1

2

1 1

T. Söylemezoˇglu , B. Yücesan , S. ¸ S. ¸ Çeçen . Ankara University, Institute of Forensic Medicine, Dikimevi, Ankara, Turkey, 2 Ministry of Health, Ankara Education and Research Hospital, Dr. Nilgün Sönmez Acar Blood Bank, Cebeci, Ankara, Turkey Alcohol consumption and drug addiction, growing problem of world’s mostly industrialized and newly developing countries, are considered to be a major contributor to all types of trauma. In view of the importance of the problem and in the lack of local data the prevalence of drug abuse and alcohol consumption in trauma patients and relationship between drug use and severity of injury and demographics of each trauma patient were evaluated. Sera from 102 patients with trauma injuries, who were admitted to the emergency service were screened for blood alcohol by gas chromatography with flame ionization detector and for drugs of abuse with an enzymatic immunoassay method, CEDIA ® DAU. Patient ages ranged from 16 to 80 and above with a mean of 35. Of this population, the age-sex distribution was predominantly male (80%), and in the third decade of life (30–39 years). Motor-vehicle related injuries accounted for %52 of submitted patients. Of the 102 patients who received toxicological screening, 39.21% tested positive for alcohol+drug, whereas 35.2% of patients tested positive for alcohol only with BAC’s ranging from 25–300 mg/dl. The mean BAC for the alcohol positive patients was 143.87 mg/dl. Only 3.9% of patients were found to have drugs with abuse potential in their urine. The most common detected drugs were barbiturates and benzodiazepines, followed by opiates. Patients who were tested positive for alcohol and drug had low Glasgow coma scales and low trauma scores (7–11) with low probabibility of survival (12–71%). Our results demonstrate that while alcohol continues to be a major problem among trauma patients, drug use, especially barbiturates and benzodiazepines, in combination with alcohol may become a larger problem if spesific precautions are not taken immediately. 267

FATAL METHANOL POISONING

A. Dip 1 , A. Demircan 2 , A. Kele¸s 2 , B. Demirel 3 , A.F. I¸sık 3 , T. Söylemezoˇglu 1 . 1 Inst. of Forensic Medicine, Ankara University, 2 Dept. of Emergency, Fac. of Medicine, Gazi University, Turkey Methyl alcohol is the simplest alcohol in structure, so it is used in antifreeze, solvents and dissolvents, and also as a chemical reagent in the production of many organic chemical compounds. Methanol is the poisonous type of alcohol, intoxication is fatal at high doses and this dose is variable in most cases. We present a case of methanol poisoning in a sibling who take cleansing solution with methanol ingredient as a beverage to get drunk. The woman was 60-year old, the man was 48-year-old and they are arrived

to the hospital after about 18 h with various symptoms including blurred vision and unconsciousness. Metabolic acidosis had started at the arrival time with the serum pH levels of 6,83 and 6,85 respectively. When the patients had come, the blood methanol levels of the woman was 1,325 promil and the man’s was 3,965 promil. Although serum pH was turned to normal level after application of ethanol treatment and hemodialysis, two patients eventually died with extensive neuropathy. Deaths are reported at 45th and 66th hours after methanol intake. The vitrous humor sample of woman were measured as 0,530 and of man as 0,920 promil. Blood samples used in analysis were taken before and after ethanol treatment and vitrous humors were taken after death. Headspace gas chromatography was used to determine the methanol levels, propanol was used as internal standard and the results were given as promil. 268

LONG QT SYNDROME INDUCED BY OXATOMIDE OVERDOSE IN CHILDREN

C. Locatelli 1 , V. Petrolini 1 , R. Butera 1 , D. Lonati 1 , S. Mannarino 2 , E. Stacul 3 , E. Fufi 3 , A. Valli 4 , P. Papa 4 , L. Manzo 1,5 . 1 Pavia Poison Center, IRCCS Fondazione Maugeri, Pavia; 2 Pediatric Cardiology Division, 3 Department of Pediatrics and 4 Laboratory of Clinical Toxicology, IRCCS Policlinico San Matteo, Pavia; 5 University of Pavia, Pavia, Italy Overdose of 2nd generation antihistamines, such as terfenadine and astemizole, has often been associated with ECG abnormalities such as prolongation of the QT interval. In this respect, no data are available on Oxatomide (Ox), an agent which is largely used in Italy (pediatric drops 2.5%) at the recommended dosage of 0.5 mg/kg bis in die. Accidental ingestion of Ox is not rare in children. From July 1998 to November 2002, we examined 12 patients (mean age: 42.4 months, range: 21 days-14 years) admitted to hospital for Ox overdose. Ten subjects had taken the drug in a single dose ranging from 1.6 to 30 mg/kg; two other patients had been repeatedly treated with Ox at doses higher than those recommended in children. Serum Ox levels measured in 8/12 patients by HPLC were 105–1300 ng/ml (normal values: 20–40 ng/ml). The plasma levels were retested till normalization in 6/8 patients. ECG was recorded on admission and before discharge with repeated recordings in the patients showing altered ECG. A total of 5/12 (41.6%) children developed QTc prolongation (447–639 msec). In this group, 2 patients had ingested a single high dose of Ox and 1 patient had repeated overdosage. In one patient showing very high serum concentrations (400 ng Ox/ml) despite moderate drug overdosage (3 mg/kg), Ox had been coadministered with erythromycin. The maximum QT prolongation was found in a 3-week old patient following ingestion of 6.9 mg/kg Ox. Four patients in the group with drug-induced ECG abnormalities showed normal QTc at discharge. These observations indicate that oxatomide poisoning can prolong QT interval in children. 269

APPLICATION OF COTININE DETERMINATION FOR EVALUATION OF EFFECTIVENESS OF BUPROPIONE THERAPY

D. Zuba 1 , E. Florek 2 , W. Piekoszewski 1,3 , E. Gomółka 3 , A. Kamenczak 4 , B. Jenner 3 . 1 Institute of Forensic Research, Krakow, Poland, 2 Laboratoryof Environmental Research, Department of Toxicology, University of Medical Sciences, Poznan, Poland, 3 Department of Clinical and Industrial Toxicology, Jagiellonian University, Krakow, Poland, 4 Toxicology Clinic, Jagiellonian University, Krakow, Poland In pharmacological therapy of tobacco smoke dependence the two approaches are used, the first is nicotine replace therapy and the second is administration of new antidepressive drug bupropione (Zyban). The aim of this study was evaluation of the effectiveness of bupropione (Zyban) therapy just after cessation of bupropione administration and one year after therapy. In the clinical experiment 82 volunteers (41 female and 48 male) took part. The drug was administrated during seven weeks according producer schedule of administration. The effectiveness of therapy was checked by determination of cotinine level in urine. For cotinine determination high performance liquid chromatography was applied.