L-Arginine in the treatment of valproate overdose - five clinical cases.

BACKGROUND: Valproic acid and its metabolites - particularly valproyl-CoA - are inhibitors of the enzyme N-acetylglutamate synthetase. The amino acid l-arginine can stimulate N-acetylglutamate synthetase activity and could be potentially used therapeutically to correct hyperammonemia caused by valproate therapy or overdose. Severely valproic-acid-poisoned patients are usually treated with l-carnitine or hemodialysis in order to decrease hyperammonemia. We herein report of five cases, in which l-arginine was administered. METHODS: Observational study on five cases. Patients with hyperammonemia (i.e., ammonia 80 > µg/dL) and symptoms consistent with valproate overdose (i.e., drowsiness, coma) were selected for treatment with l-arginine. Data was collected retrospectively. RESULTS: l-Arginine decreased ammonia levels in a close temporal relation (case I ammonia in EDTA-plasma [µg/dL] decreased from 381 to 39; case II from 281 to 50; case III from 669 to 74; case IV from 447 to 56; case V from 202 to 60). In cases I and II, hemodialysis was performed and l-carnitine was given before the administration of l-arginine. In case III, hemodialysis was performed after the administration of l-arginine was already started. In cases IV and V, treatment with l-arginine was the sole measure to decrease ammonia levels in plasma. CONCLUSION: The results suggest that l-arginine may be beneficial in selected cases of valproate overdose complicated by hyperammonemia. l-Arginine could extend our conventional treatment options for valproic acid overdose.

Dementia, epilepsy and polyneuropathy in a mercury-exposed patient: investigation, identification of an obscure source and treatment.

We present a patient aged 54 years with early onset of dementia, epilepsy and peripheral polyneuropathy. A mercury intoxication was diagnosed in 2010, chelation therapy with 2,3-dimercaptopropane-1-sulfonate had failed. A source of exposure could not be identified. MRI showed unspecific hyperintense brain lesions in 2015. She was referred for diagnosis and treatment. Neuropsychological testing indicated severe memory loss and nerve conduction speed measurements showed chronic neurogenically changed potentials. Mercury levels in blood and urine and neuron-specific enolase (NSE) were elevated. A detailed patient history revealed a daily application of mercury-containing skin lightening creams for 6 years. Treatment with 2,3-dimercaptosuccinic acid (DMSA) was started, blood mercury levels were falling during treatment. She was discharged with DMSA prescriptions. A renewed MRI revealed unchanged brain lesions. Blood and urine mercury levels and NSE were falling. Memory function had improved qualitatively and quantitatively.

Overdose of dolutegravir in combination with tenofovir disaproxil fumarate/emtricitabine in suicide attempt in a 21-year old patient.

A 21 year old MSM patient with newly diagnosed HIV infection was hospitalized in our department after ingestion of an overdose of his antiretroviral therapy (ART) comprising dolutegravir (DTG - Tivicay®) and tenofovir disaproxil fumarate/emtricitabine (Truvada®) in suicidal intention. On admission, the patient did not show any clinical signs of intoxication and laboratory findings were unremarkable. After 6 hours of intensive care monitoring, the patient was referred to a psychiatric clinic. 5 days after the day of intoxication, serum creatinine levels increased to high normal values (1.2 mg/dl). However, levels never exceeded the upper threshold. 8 and 12 weeks later, serum creatinine normalized to levels measured prior to the intoxication. No other adverse events occurred, and the patient does not suffer from permanent impairments.

Organophosphate poisoning in the developed world - a single centre experience from here to the millennium.

Organophosphate (OP) poisoning is still associated with high morbidity and mortality rates, both in resource-poor settings and in well-developed countries. Despite numerous publications dealing with this particular poison, detailed clinical data on more severe overdoses with these agents are relatively sparsely reported. A retrospective study was consequently conducted on 33 patients with OP poisoning admitted to our intensive care unit (ICU) to provide additional data on clinical features. We included moderate to severe poisonings between 2000 and 2012 who required admission to ICU. Patients ingested dimethyl-OPs in 19 cases, diethyl-OPs in 8 cases and otherwise classified OPs in 6 cases. Death (5/33) occurred rather late and only one of these fatalities died during on-going cholinergic crisis. Of the survivors (28/33), 71% recovered fully while 29% showed predominantly neurological disabilities before being transferred to neurologic rehabilitation. Aspiration pneumonia predominated in 27/33 patients and one patient died in refractory acute respiratory distress syndrome (ARDS). The intermediate syndrome occurred twice and cardiopulmonary resuscitation had to be performed in 6/33 patients. Fatalities showed a higher Poison-severity-score, APACHE-II-score and SOFA-score on admission compared with survivors and they showed significantly longer QTc-time in the ECG, lower systolic blood pressure and heart rate, a lower pH and a lower base excess on admission. Patients with diethyl-OPs required intubation significantly earlier and showed lower and more sustained inhibited activity of the plasma-cholinesterase on admission compared with patients ingesting dimethyl-OPs. Treatment with atropine and obidoxime was comparable between these groups and severity of poisoning, outcome, hemodynamics on admission, duration of mechanical ventilation and length of stay in the ICU did not significantly differ between the involved group of dimethyl- and diethyl-OPs. We conclude that the fatality rate in our patient cohort treated in a well-staffed and equipped ICU of a developed country is quite similarly high compared with the rate observed in developing countries. Patients died rather late when severe cholinergic crisis had mostly been overcome and death was therefore related to non-poison specific complications.

Eight cases of fatal and non-fatal poisoning with Taxus baccata.

This paper describes two fatalities, three non-fatal intentional and three accidental oral ingestions of yew (Taxus baccata) leaves. In all cases the post-mortem external examinations showed no signs of violence. Internal examinations revealed small green, needle-like particles on the tongue, in the esophagus and in the stomach. Yew leaves were also identified in the stomach contents, whereas Taxus leaves were cut into small pieces and then ingested in one case. The analytical method used was based on a liquid-liquid-extraction under alkaline conditions followed by LC-MS/MS analysis (QTRAP 5500). Chromatographic separation was achieved by HPLC on a Kinetex C18 2.6u (100×3) mm. The analytical method allows the simultaneous identification and quantification of the commercially available yew alkaloids taxoids (m/z): paclitaxel (854.2→105.0/286.1), 10-deacetyltaxol (10-DAT: 812.2→105.0/286.1), baccatin III (BAC III: 604.0→105.0/327.0), 10-deacetylbaccatin III (10-DAB III: 562.1→105.0/327.0), cephalomannine [taxol B] (562.1→105.0/327.0) and of 3,5-dimethoxyphenol (3,5-DMP: 155.0→111.9/122.9) also encompassing the qualitative analysis of the alkaloidal diterpenoids (Q1→194.0/107.0); reference mass spectra obtained from a yew leaves extract: monoacetyltaxine (MAT: 568.4), taxine B (584.2), monohydroxydiacetyltaxine (MHDAT: 626.4), triacetyltaxine (TAT: 652.4), monohydroxytriacetyltaxine (MHTAT: 668.4). In both fatalities, paclitaxel, 10-DAT and cephalomannine were not identified in urine, cardiac and femoral blood but all taxoids and 3,5-DMP were present in stomach content and excreted into the bile. In urine, highest 3,5-DMP concentration was 7500 µg/L and 23,000 µg/L after enzymatic hydrolysis, respectively. In intentional and accidental poisonings, when electrocardiogram (ECG) examinations revealed ventricular tachycardia and/or prolonged QRS intervals, taxines were identified in plasma/serum, even after the ingestion of a few number of yew leaves, when 3,5-dimethoxyphenol was not even found. According to the data from one near-fatal intentional poisoning, elimination half-life of MAT, TAXIN B, MHDAT and MHTAT in serum was calculated with 11-13 h and taxines were detected up to t=+122 h post-ingestion of approximately two handfuls of yew leaves.

Clinical and analytical features of severe suicidal quetiapine overdoses--a retrospective cohort study.

CONTEXT: Detailed data on severe overdoses with quetiapine are relatively sparsely reported in the literature. OBJECTIVE: To describe a cohort of 20 acute quetiapine overdoses and provide additional data on the pharmacokinetics and clinical features of intoxication with this drug. MATERIAL AND METHODS: A retrospective study was conducted on patients with quetiapine poisoning admitted to our institution. We included moderate to severe overdoses between 2005-2011 who required admission to ICU. RESULTS: Predominantly female patients (n = 17) ingested a median dose of 9.8 g quetiapine. Poison Severity Score was moderate in 9 patients, severe in 10 patients and in one case fatal. Quetiapine was analytically confirmed in all cases. Clinical manifestations included drowsiness or coma (all patients), tachycardia (12 patients) and hypotension (10 patients). Seizures and arrhythmia occurred in 4 patients, each. Intubation and mechanical ventilation was required in 14 patients due to seizures, respiratory depression or loss of airway protection and 15 patients developed pneumonia. Hypokalaemia and hyperglycaemia were present at admission in 10 and 5 patients, respectively. Despite frequent prolongation of the QT(c) in 13 patients, QT interval was normal in most cases and QRS-interval was prolonged in only one patient. Presumably anticholinergic delirium was recognised in 8 patients and 6 patients received physostigmine with good clinical response. In 13 cases quetiapine was analysed quantitatively in serum with a relevantly prolonged half-life (16 ± 12 h) and a median peak serum concentration of 3074 ng/mL. In 4 of these 13 patients we observed an increase of quetiapine serum concentration in the further course. CONCLUSION: In this study, quetiapine overdoses were associated with significant toxicity and a fairly high number of complications. A careful and often prolonged clinical observation in the more severe cases of overdose seems mandatory.

Atropine maintenance dosage in patients with severe organophosphate pesticide poisoning.

Although the importance of atropine in therapy of organophosphate (OP) poisoning is generally recognized, its dosing is a matter of debate. A retrospective analysis of atropine dosing was undertaken in 34 patients who had been enrolled in a clinical study assessing obidoxime effectiveness in OP-poisoning. All patients were severely intoxicated (suicidal attempts) and required artificial ventilation. Atropine was administered routinely by intensive care physicians for life-threatening muscarinic symptoms, with the recommendation to favor low dosage. The pharmacological active enantiomere S-hyoscyamine was determined by a radioreceptor assay. When RBC-AChE activity ranged between 10% and 30%, S-hyoscyamine plasma concentrations of approx. 5 nmol L⁻¹ were sufficient. This concentration could be maintained with about 0.005 mg h⁻¹ kg⁻¹ atropine. Only when RBC-AChE was completely inhibited, therapy of cholinergic crisis required atropine doses up to 0.06 mg h⁻¹ kg⁻¹. Elimination half-life of S-hyoscyamine was 1.5 h, showing occasionally a second slow elimination phase with t(½)=12 h. Malignant arrhythmias were observed in some 10% of our cases, which occurred late and often in the absence of relevant glandular cholinergic signs, when the S-hyoscyamine concentration was below 2.5 nmol L⁻¹. Arrhythmias mostly resolved on reinstitution of atropine.

Risk assessment of moderate to severe alcohol withdrawal--predictors for seizures and delirium tremens in the course of withdrawal.

AIMS: To develop a prediction model for withdrawal seizures (WS) and delirium tremens (DT) during moderate to severe alcohol withdrawal syndrome (AWS) in a large cohort of inpatients treated for AWS (n = 827). METHODS: Re-analysis of a cohort study population treated between 2000 and 2009. All patients received a score-guided and symptom-triggered therapy for AWS. Multivariable binary logistic regression models with stepwise variable selection procedures were conducted providing odds ratio (OR) estimates. RESULTS: In the multivariable regression, significant predictors of WS during AWS therapy were a delayed climax of withdrawal severity since admission [OR/10 h: 1.23; 95% confidence interval (CI): 1.1-1.4; P < 0.001)], prevalence of structural brain lesions in the patient's history (OR 6.5; 95% CI: 3.0-14.1; P < 0.001) and WS as the cause of admittance (OR 2.6; 95% CI: 1.4-4.8; P = 0.002). Significant predictors at admission for the occurrence of DT were lower serum potassium (OR/1 mmol/l 0.33; 95% CI: 0.17-0.65; P = 0.001), a lower platelet count (OR/100.000 0.42; 95% CI: 0.26-0.69; P = 0.001) and prevalence of structural brain lesions (OR 5.8; 95% CI: 2.6-12.9; P < 0.001). CONCLUSION: In this large retrospective cohort, some easily determinable parameters at admission may be useful to predict a complicated course of alcohol withdrawal regarding the occurrence of WS or DT. Using the provided nomograms, clinicians can estimate the percentage likelihood of patients to develop either WS or DT during their course of withdrawal. Prevalence of structural brain lesions in the patient's history does strongly warrant a careful observation of patients.

Carbamazepine and valproate as adjuncts in the treatment of alcohol withdrawal syndrome: a retrospective cohort study.

AIMS: To compare the clinical course, incidence of withdrawal seizures (WS) or delirium tremens (DT) and side effects during treatment of alcohol withdrawal in patients treated with either carbamazepine (CBZ) or valproate (VPA) as an adjunct to clomethiazole and clonidine therapy. METHODS: Retrospective analysis of charts of two cohorts of inpatients treated during 2000-2009: CBZ 374 patients, VPA 453 patients. RESULTS: At baseline, those treated with VPA and those treated with CBZ were similar except for a trend to younger age and a higher incidence of previous WS in the CBZ group. The median duration of pharmacological treatment (91 vs. 76 h; P < 0.001) and the length of stay (8 vs. 6 days; P < 0.001) as well as the need for intensive care treatment (7 vs. 2%; P = 0.001) were significantly higher in the CBZ than the VPA group. Additionally, withdrawal-related complications such as WS occurred more often in the CBZ group (9.6 vs. 5.5%; not significant after adjusting for potential confounders); the incidence of DT in the CBZ group was insignificantly higher (6.6 vs. 4.4%; P = 0.52). Admittance with seizures and older age were predictors of WS and DT, respectively. Adverse drug reactions, mainly affecting the central nervous system, were significantly more frequent with CBZ than VPA (7.6 vs. 2%; P < 0.001). CONCLUSION: During alcohol withdrawal, VPA may offer some benefits compared with CBZ due to favorable tolerability, possibly less incidence of WS and a shorter duration of pharmacological treatment.

Obidoxime in acute organophosphate poisoning: 1 - clinical effectiveness.

OBJECTIVE: The effects of obidoxime in the treatment of organophosphate poisoning were assessed by comparing the clinical course with its effects on laboratory parameters relevant to poisoning. In this article we report clinical findings and activity of cholinesterase in plasma and acetylcholinesterase (AChE) in red blood cells. In a linked paper we describe changes in neuromuscular transmission and atropine concentrations in the same patient cohort. METHODS: We studied 34 atropinized patients with severe parathion, oxydemeton methyl, and dimethoate self-poisoning who were treated with obidoxime in a standard protocol. We measured the AChE activity in blood and related it to clinical features of organophosphate poisoning. RESULTS: Patients poisoned with parathion responded promptly to obidoxime (250 mg bolus followed by continuous infusion at 750 mg/day up to 1 week) with improvement of neuromuscular transmission and increased AChE activity. The effects were only transient in cases with the other poisons. Death (7/34) occurred late and was mostly due to complications rather than due to ongoing cholinergic crisis. CONCLUSIONS: Obidoxime appeared safe and reactivated AChE in parathion poisoning.

Obidoxime in acute organophosphate poisoning: 2 - PK/PD relationships.

OBJECTIVE: The effects of obidoxime in the treatment of organophosphate poisoning were assessed by biochemical and biological effect monitoring. In this article we report effects on neuromuscular function, oxime and atropine concentration, and relate them to acetylcholinesterase (AChE) activity. METHODS: We measured the activity of cholinesterase in plasma and AChE in red blood cells (RBC) and related these data with neuromuscular transmission analysis (ulnar nerve stimulation). Concomitantly, poison and oxon along with plasma obidoxime and atropine levels were measured at regular intervals. RESULTS: We found a close correlation between RBC-AChE activity and neuromuscular transmission and a reciprocal correlation between both the atropine maintenance dose and/or its plasma concentration. The steady state of RBC-AChE activity of reactivation and re-inhibition followed the course predicted by laboratory-determined reaction constants. CONCLUSIONS: Intense monitoring of organophosphate-poisoned patients allowed assessment of why a given obidoxime concentration was, or was not, able to counteract the re-inhibition of the RBC-AChE. RBC-AChE activity mirrors the function of n-receptor- and m-receptor-mediated cholinergic signaling as measured by neuromuscular transmission and atropine requirements.

Risk assessment of severe tricyclic antidepressant overdose.

Prognostic factors for severe complications in tricyclic antidepressant (TCA) overdose remain unclear. We therefore evaluated the value of clinical characteristics and electrocardiograph (ECG) parameters to predict serious events (seizures, arrhythmia, death) in severe TCA overdose of 100 patients using logistic regression models for risk assessment. The overall fatality rate was 6%, arrhythmia occurred in 21% and 31% of the patients developed seizures. Using an univariable logistic regression model, the maximal QRS interval (OR 1.22; 95% CI 1.06-1.41; p = .005), the time lag between ingestion and occurrence of first symptoms of overdose (OR 1.13; 95% CI 0.99-1.29; p = .072) and the age (OR 0.73; 95% CI 0.55-0.98; p = .038) were determined as the solely predictive parameters. In the multivariable logistic regression model, the QRS interval could not be established as independent predictor, however, the terminal 40-ms frontal plane QRS vector (T40) reached statistical significance regarding prediction of serious events (odds ration [OR] 1.70; 95% confidence interval [CI] 1.02-2.84; p = .041), along with age and time lag between ingestion and onset of symptoms of overdose with a sensitivity and specificity of 71% and 70%, respectively. Evaluation of both clinical characteristics and ECG-parameters in the early stage of TCA overdose may help to identify those patients who urgently need further aggressive medical observation and management.

Fetal risk through maternal Amanita phalloides poisoning at the end of pregnancy.

There is a paucity of knowledge about prenatal and perinatal risks through maternal amatoxin poisoning. No symptoms of amatoxin intoxication, except for a slight temporary increase in liver enzymes activity, occurred in a term newborn after delivery despite an Amanita phalloides intoxication of the mother 2 days before. Considering previous reports, severe fetal intoxication may not occur during the entire pregnancy.

Treatment of severe intravenous phenytoin overdose with hemodialysis and hemoperfusion.

BACKGROUND: Phenytoin is a widely used anticonvulsant agent responsible for a number of intentional and unintentional overdoses. However, besides supportive care, specific treatment recommendations to enhance elimination of the parent compound have been discussed controversially and effectiveness of hemoperfusion is under debate. CASE REPORT: A women with a prehistory of cerebral seizures was presented following a severe iatrogenic phenytoin overdose with a peak plasma concentration of 117 mg/L. A Phenytoin overdose could be contributed to both inadequate dosing and missed repeated drug monitoring. Native phenytoin body clearance failed to relevantly lower phenytoin concentration. Thus, three sessions of a four-hour long combination of activated charcoal hemoperfusion and high-flux hemodialysis were performed resulting in considerably reduced half-life during these measures of about 7-13 hours compared to the native half-life wavering between 40-100 hours. This resulted in a substantial clinical improvement in terms of central nervous system toxicity. CONCLUSIONS: Hemodiaperfusion with activated charcoal seems to be a reasonable measure for forced lowering of highly toxic phenytoin plasma concentration and should be considered especially in circumstances following intravenous overdose (e.g. inadequate iatrogenic dosing). Its narrow therapeutic range enforces strictly adequate dosing and subsequent repeated drug monitoring of phenytoin.

Neither DMPS nor DMSA is effective in quantitative elimination of elemental mercury after intentional IV injection.

BACKGROUND: Intravenous injection of elemental mercury (Hg) is rare and considered relatively harmless. Treatment recommendations vary and the effectiveness of chelation therapy is controversial. CASE REPORT: A 27-year-old man intravenously injected 1.5 mL of elemental Hg. Within 12 hours he became febrile, tachycardic and dyspneic. Physical examination was unremarkable. X-rays showed scattered radiodense deposits in the lung, heart, intestinal wall, liver and kidney. The serum Hg level on admission was 172 microg/L and peaked on day 6 at 274 microg/L. Cumulative renal elimination during a five day oral treatment period with 2,3-dimercaptopropane-1-sulfonate (DMPS) and meso-2,3-dimercaptosuccinic acid (DMSA) was 8 mg and 3 mg, respectively. CONCLUSION: Although urinary excretion could be enhanced during chelation therapy, Hg deposits in organs resulted in negligible elimination of mercury compared to the exposed dose.

Lithium poisoning: pharmacokinetics and clearance during different therapeutic measures.

The clinical features and pharmacokinetics of 22 lithium overdoses are described. Effectiveness of different treatment regimens regarding elimination of lithium is discussed. Origin of overdose was due to deliberate poisoning or precipitated by concomitant diseases, coadministration of drugs, or combination of both. Treatment included supportive care, diuretics (15/22), hemodialysis (HD; 9/22), and mechanical ventilation (3/22). Severity of lithium intoxication was classified in 50% as I degrees, in 41% as II degrees, and in 9% as III degrees according to Hansen and Amdisen. Renal impairment on admission was diagnosed in 82% of the patients. Half-life of lithium in serum was 3.5 +/- 0.8 hours during the first HD, and 29 +/- 14 and 29 +/- 6 hours during therapy with diuretics or supportive treatment, respectively. Lithium clearance during HD was 160 +/- 15 mL/min, and renal clearance during HD or treatment with diuretics was approximately 20 and 15 +/- 9 mL/min, respectively. Renal lithium clearance was not influenced by HD therapy. There was no difference regarding half-life and clearance between the group that had an unspecific treatment or the group treated with diuretics. Hemodialysis is the therapy of choice for emergent extracorporeal lithium elimination. Renal impairment and interaction with other drugs were the main reasons for intoxication; thus, more cautious prescription or more frequent supervision of this patient group is warranted. It seems that treatment with diuretics does not have a beneficial effect in the overdose setting.

Acute valproate poisoning: pharmacokinetics, alteration in fatty acid metabolism, and changes during therapy.

The clinical features, complications, and pharmacokinetics of intentional acute valproic acid (VPA) overdoses are described. Alteration in fatty acid metabolism is evaluated and therapy-induced changes are discussed. Central nervous system features were the predominant clinical manifestations (6/6), followed by respiratory failure (5/6) and multiorgan failure (2/6). Mechanical ventilation was required in 5 of 6 patients because of respiratory depression or deep coma. Hemodialysis was applied in 4/6 of the cases due to hyperammonemia, worsening neurologic condition, or organ dysfunction. Cerebral edema and hemorrhagic pancreatitis ensued in 2/6 of the patients and ICU mortality was 2/6. VPA peak levels ranged from 520 to 1700 mg/L with a mean of 1127 mg/L. Ammonia was elevated in all cases with a mean of 550 microg/dL. All patients showed signs of impaired mitochondrial beta-oxidation with increase of medium- and long-chain acylcarnitines in serum. Severe VPA overdose is associated with a high mortality rate requiring early medical interventions. Beside supportive intensive care, hemodialysis can be considered as an adjunctive measure.

Indication of liver transplantation following amatoxin intoxication.

BACKGROUND/AIMS: Indication of liver transplantation in acute liver failure following amatoxin intoxication is still uncertain. METHODS: One hundred and ninety-eight patients were studied retrospectively. The laboratory parameters alanine-aminotransferase, serum bilirubin, serum creatinine and prothrombin index were analyzed over time. Predictors of fatal outcome and survival were determined by receiver-operating-characteristic and sensitivity-specificity analysis. RESULTS: Twenty-three patients died in the median 6.1 days (range, 2.7-13.9 days) after ingestion. Using a single parameter as predictor of fatal outcome the area under the receiver-operating-characteristic curve of prothrombin index (0.96) and serum creatinine (0.93) were both significantly greater (P<0.05) compared with serum bilirubin (0.82) and alanine-aminotransferase (0.69). Prediction of fatal outcome had an optimum, if a prothrombin index less than 25% was combined with a serum creatinine greater than 106 micromol/l from day 3 after ingestion onwards (sensitivity 100%, 95% confidence interval 87-100; specificity 98%, 95% confidence interval 94-100). The median time period between the first occurrence of this predictor in non-survivors and death was 63h (range, 3-230h). CONCLUSIONS: A decision model of liver transplantation following amatoxin intoxication using prothrombin index in combination with serum creatinine from day 3 to 10 after ingestion enables an early and reliable assessment of outcome.

Acute endosulfan poisoning with cerebral edema and cardiac failure.

BACKGROUND: Organochlorine insecticides are highly toxic compounds that are responsible for a number of severe intoxications worldwide with several deaths. Despite their widespread use in agriculture during the 1940s to 1960s and the well-known signs and symptoms of intoxication, the clinical picture in case of poisoning varies. We report two cases of acute intentional endosulfan intoxication with cerebral edema and cardiac failure. CASE REPORTS: Both cases developed life-threatening signs like epileptic state, respiratory insufficiency and hemodynamic instability soon after ingestion. The survivor developed severe myocardial insufficiency and pulmonary edema documented by echocardiography and x-ray of the chest. The deceased patient developed severe cerebral edema and multiorgan failure ten days after ingestion of Thiodan 35. The peak serum concentration of endosulfan in the survivor was 0.12 mg/L approximately 23 hours after ingestion, whereas the peak blood concentration in the fatal case was 0.86 mg/L approximately 25 hours post-ingestion. Post-mortem endosulfan levels in different organs were determined. CONCLUSION: Endosulfan is a highly toxic organochlorine insecticide that produces well-known neurological symptoms of tonic-clonic convulsions, headache, dizziness and ataxia but also can cause gastrointestinal symptoms and metabolic disturbances. Life-threatening cerebral edema and hemodynamic instability may occur. Treatment is symptomatic and supportive.