THIODON 35 WP INTOXICATION
Pestisid olarak tanımlanan madde gurubundan biri de insektisidlerdir. Organik klorlu insektisidler yavaş elimine olup çevrede uzun süre kalırlar. İnsan vücuduna deri, inhalasyon veya ağız yoluyla geçebilirler. Kaza ile maruz kalınmadıkları zamanda ise ucuz ve kolay ulaşılabilir oldukları için kolaylıkla intihar amaçlı kullanılabilirler. Burada sunulan 39 yaşındaki kadın vaka intihar amaçlı Endosulfan aldıktan sonra kafa travması geçiren, nörolojik olarak ağır bir tabloda gelen hastadır. Hastanın stabilizasyonu sırasında karşılaşılan metabolik ve nörolojik sorunları paylaşarak bu konuda literatür önerilerini sunduk.
A group of chemicals containing substances such as insecticide, fungicide, herbicide and rodenticide is generally called pesticides. Insecticides are compounds used to kill insects. Organic chlorinated insecticides are slowly metabolised and stable substances in the environment so their action is durable. Most of the substances will act as CNS stimulants. Here we present a case of Endosulfan intoxication with resistant seizure activity, and had to be intubated to control seizue activity and to protect airway from secretions.
Poisoning can occur with many different toxins. Acute pesticide poisoning, which constitutes a significant portion of cases in Turkey, is also a major cause of mortality all over the world. Although most cases of poisoning are unintentional, their use for suicide and murder is not negligible because they are easily obtainable. Organic chlorinated pesticides are also one of the most important groups of pesticides because they remain in the environment for a long time by bioaccumulation, and slow biodegradation. They can enter the human body by dermal route, by inhalation or by oral route according to the techniques and formulations employed. They are easily absorbed from all membranes due to their lipophilic nature. For this reason; they are absorbed rapidly from the skin, conjunctiva, lung and especially oral route. The main toxic effect for organic chlorinated pesticides is based on neurotoxic properties. Organo-chlorinated pesticides are aromatic or aliphatic chlorinated hydrocarbon compounds with chlorine in their structure. Here we present a case of endosulfan poisoning. Our aims for presenting this case are to keep in mind intoxications due to organic chlorinated insecticides in unconcious patients with generalized tonic-clonic seizures and, furthermore, to discuss this topic with the help of the novel literature.
A 39-year-old unconcious female patient was admitted to emergency service resuscitation room with generalized seizures by an ambulance and was accompanied by a close relative. She was reported to have had a drug-induced suicide attempt with accompanying head trauma. Her vitals in emergency service were; TA: 105/69 mm/Hg, Pulse: 100/min, Temperature: 36.7°C, SO2: 99% (oxygenated). There was a 3 cm superficial lesion in the left anterolateral region of the nasal region. Patient had no response to the verbal stimulus, could pull his limbs with painful stimuli, but could not open his eyes. GCS was 6. The light reflexes were slow and pupils were isochoric. In motor neurological examination; the motor strength was 2/5 in all of her extremities. The heart beat was rhythmic, tachycardic, with no additional cardiac sound or murmur. The chest oscultation was normal except for a few rough rales and coarse ronchus. Her blood and urine tests, ECG, and radiology scanning were completed. Arterial blood gas results were; pH: 7.12, PCO2: 26mmHg, PO2:117 mmHg (with oxygen mask), SO2: 96.9%, COHb: 1.2 , Lactate: 9.4 mmol/L, Base gap: -19.89 mmol/L, HCO3: 8.1 mmol/L, and Anion Gap: 13.8. The laboratory results were WBC: 33.100, HGB: 12.0 g/dL, PLT: 374.000, glucose: 524 mg/dL, urea: 19 mg/dL, creatinine:1.19, normal liver tests, Na: 136, K: 3.62, Cl: 100,PT: 11.2, INR:0.97, APTT: 71.9, Troponin-I: 0.78, Total-Hcg: 0.05. She also had glucosuria. In the first ECG; there was normal sinus rhythm. Chest x- ray was normal. In brain CT; there was an increase in subcutaneous soft tissue thickness in the frontal region, millimetric calcification in the bilateral lentiform nucleus.
The patient was monitored in the resuscitation room and connected to the defibrillator. Deep nasotracheal and orotracheal aspiration was performed because the patient had increased secretions. After securing the airway, oxygen was started. However, the patient started to have generalised tonic clonic seizures (GTCS) , and she was given diazepam 10 mg IV. Her gastric decontamination was done and saline infusion was started. The patient started to have (GTCS) after 10 minutes and again she was given diazepam 10 mg IV. There was no decrease in the patient's secretions and atropine 1 mg iv. was given repeatedly every ten minutes. Then the patient had 3rd GTCS and she was given midazolam and intubated for the protection of the airway and cessation of the recurring seizures under midazolam infusion. The patient's was 461 at that time and insulin infusion was also started.
Her relative said that they had found rat poison next to the patient. Relative was requested to bring the empty medicine box found near the patient. Since the patient's metabolic acidosis persisted after intubation, sodium bicarbonate infusion was started. Cardiac arrest occurred 2 hours and 40 minutes after admission. CPR was made for 10 minutes, and then ROSC was received. Toxin box, namely Thiodon 35 WP, was finally brought by a patient's relative. Thiodon 35 WP; is an organic chlorinated insecticide with the active substance as 32.9% endosulfan. The poison call center (tel. 114) was called. We learned that the drug can cause metabolic acidosis, hypotension, coma, renal insufficiency, epileptic seizures, cardiac arrhythmia; had no antidote; hemodialysis treatment would not have any benefit; and there was no proven knowledge of hemoperfusion therapy. Cholestyramine may be used to bind these highly lipophilic agents. Cholestyramine reduces reabsorption and retains bound agent in the GI tract for fecal elimination. However, our major concern for the patient was to support ABC and to control seizures which is the mainstay of the therapy. The patient was admitted to the Anesthesia Reanimation Intensive Care at the hospital. She was treated and sent home after full recovery.
THIODON 35 WP INTOXICATION
Endosulfan from organic chlorinated insecticides; metabolizes in microsomal enzyme system in liver. Endosulfan is absorbed from the gastrointestinal tract, respiratory system and skin. It acts as a GABA antagonist and inactivates GABA-A dependent chlorine channels.Endosulfan shows its effects mainly on Central Nervous System (CNS). Excitability in the CNS increases and recurrent neuronal discharge can be seen. In our case, recurrent tonic-clonic seizures were seen at the first visit of the patient and at the following hours in accordance with the literature. In endosulfan poisoning; an increase in blood pressure and transient hyperthermia can be seen. Vital signs of our present case were normal. In endosulfan poisonings, visual impairment due to accomodation disorder, myosis or mydriasis, transient deafness, increase in nasal secretions, nasal obstruction can be seen. In our case, light reflexes were bilaterally weak in the eye examination, and the patient had increased oral and nasal secretions. Organic chlorinated insecticides and endosulfan, make myocardium susceptible to endogenous catecholamines and have been shown to lead to various arrhythmias in animal experiments. There was no abnormal rhythm until the cardiac arrest.
Clinical manifestations in endosulfan poisoning occur in three phases. The first stage is cardiac and convulsive symptoms, the second stage is subacute pulmonary and convulsive symptoms, the third stage is slow recovery. The most frequent complaints are CNS stimulation and seizures. Nausea, vomiting, paresthesia, convulsions, coma, respiratory insufficiency and cardiac insufficiency are seen with acute poisoning. These three phases were not observed in a sequence in this patient. Cardiac markers before arrest were as follows; CK:159, CK-MB:28, Troponin-I:0. The ECGs before the arrest were in the sinus rhythm, and sinus tachycardias were seen afterwards. In the following hours, the patient had cardiopulmonary arrest and was admitted to the mechanical ventilator.
Our case had a trauma story, her brain CT was taken and no significant pathological condition was detected. No evidence of cerebral edema was found. Common metabolic acidosis is seen in endosulfan poisonings due to recurrent seizures. As reported, extensive metabolic acidosis had developed, and the patient was intubated due to worsened clinical findings. Barbiturates (preferably phenobarbital IV 0.1-0.2 g or pentobarbital) or diazepam are used to control symptoms such as hyperactivity, tremor and convulsions in endosulfan poisonings. Propofol is also preferred for resistant seizures. In our case, IV benzodiazepines (diazepam and midazolam) were used in the patients' seizures in accordance with the literature and after the intubation, propofol infusion was started.
Cholestyramine may be used to bind these highly lipophilic agents. Cholestyramine reduces reabsorption and retains bound agent in the GI tract for fecal elimination.
Organic chlorinated insecticides and endosulfan are the most neurotoxic agents. The most common form of presentation is impaired consciousness, coma and recurrent seizures.For this reason, poisoning with organic chlorinated insecticides should be kept in mind in emergency department patients who have an intoxication history and have confusion in their clinic, followed by coma and recurrent tonic-clonic seizures and treatment should be started after making the diagnosis at the earliest stage.
- Acilde Klinik Toksikoloji, Editör: Dr. Salim Satar. Nobel Tıp Kitabevi. Sayfa:505-513.
- Vural N. Toksikoloji. Ankara: Ankara Üniversitesi Eczacılık Fakültesi Yayınları. 1996;73:342-373.
- World Health Organization. Organophosphorus Pesticides.Erişim: http.www.who.org.Erişim tarihi:13.07.2007
- Klassen CD, Amdur MO, Doull J. Casarett and Doull’s Toxicology: Basic Science of Poisons. 6th Edition.McGraw-Hill İnternational Editions.New York. 2001: 763-784.
- Dökmeci İ. Toksikoloji. Zehirlenmelerde Tanı ve Tedavi.Nobel Tıp Kitabevleri. İstanbul. 2001.
- Baban N. Adli toksikoloji. Adli Tıp Kurumu Yayınları-8, İstanbul, 2003.
- Endosülfan.Erişim:http://www.inchem.org/documents/pds/pds/pest 15_e.htm, Erişim Tarihi:17.07.2007.
- Marrs CT, Ballantyne B. Pesticide Toxicology and International Regulation, John Wiley & Sons Ltd, England, 2004.
- Dağlıoğlu N. Akut Organofosfatlı Pestisit Entoksikasyonlarının Sıçanlarda Deneysel olarak Gösterilmesi. Yüksek lisans Tezi. Çukurova Üniversitesi , Adana, 2004.