Organophosphates are irreversible inhibitors of acetylcholinesterases and they lead to acetylcholine accumulation in cholinergic receptors. When there is excessive accumulation of acetylcholine, patients develope symptoms such as central respiratory depression, weakness in respiratory muscles, broncospasm, increase in bronchial secretion, and dyspnea. Respiratory insufficiency is a common cause of death in these patients. A twenty-year old female patient was brought to the emergency department of our hospital since she had attempted suicide by drinking pesticide. As she had a poor general condition and was suffering from respiratory distress, she was hospitalized at intensive care unit, intubated and mechanical ventilation was initiated. Activated charcoal, atropine and pralidoxim were administered intravenously. At day 2, sedation was terminated and weaning protocol from mechanical ventilator was started. At day 3, patient had an improvement in her general condition and therefore was extubated. However, she was uncooperative and agitated so psychiatry department was consulted. She was diagnosed to have delirium and haloperidol(Norodol®, 2 mg/mL) oral drops were started. But her clinical condition did not improve and haloperidol drops were augmented with quetiapine tablets. On the following day, her clinical picture completely recovered and the patient was discharged on the 6th day of admission.
Organophosphates frequently exist in herbicides and insecticides in the form of organophosphorus or carbamate. Their structure mostly involves a paraoxon or parathion ring. They are widely used chemical agents throughout the world for agricultural purposes in order to eradicate harmful microorganisms and other plant-threatening creatures   . Organophosphates are among irreversible inhibitors of acetylcholinesterases and lead to acetylcholine accumulation in cholinergic receptors.
Due to the ease of access, organophosphates are commonly used to commit suicide. Their oral ingestion may result in severe intoxication; also intoxications of various degrees may result from their absorption through skin, mucosal membranes, conjunctiva or their uptake by inhalation     .
Intoxication results from overexistence of acetylcholine and it affects muscarinic, and nicotinic receptors and also central nervous system (CNS). Such intoxications are generally diagnosed based on the clinic manifestations and patient’s medical history. Increased acetylcholine concentration in the CNS may lead to various symptoms ranging from headache, dizziness, anxiety, confusion to coma. It may also cause seizures and depression in respiration center. A combination of increased lacrimation, salivation, urination, myosis, nausea-vomiting, increased pulmonary secretion and weakness in muscles lead to a diagnosis of organophosphate intoxication   . Respiratory insufficiency arising from central respiratory depression, weakness of respiratory muscles, bronchospasm and increased bronchial secretions is a common cause of death. Intoxication may have a very severe manifestation and has a high mortality if the response is delayed. Death due to organophosphate intoxication occurs most prominently between five minutes and 24 hours. Majority of the cases can survive if appropriate first aids or intensive care treatments are initiated on time    .
The aim of this study is to discuss a patient who developed atropine-induced delirium during treatment for organophosphate intoxication at intensive care unit (ICU).
A twenty-year old female who ingested pesticide (Diazinon 60 EC®) during a suicide attempt was not conscious at time of her first examination at the emergency care unit. She was not cooperating. Her orientation to time, place and person was impaired. Her pupils were myotic in “pin point” shape. She was reacting to painful stimuli, light reflexes were +/+, and her respiratory rate was 32/minute. She also had increased bronchial secretions and lacrimation. Auscultation revealed equal contribution of both lungs to respiration and decreased breath sounds. Heart rate was 135/minute, arterial blood pressure was 175/85 mmHg, and body temperature was 37°C.
The patient, with a poor general condition, was hospitalized in ICU and treatment was initiated. Under the flow of 6 L/minute oxygen via a facial mask, arterial blood gas analysis demonstrated pH: 7.14, PaO2: 53 mmHg, PaCO2: 59 mmHg, HCO3: 18.5 mmol/L,SpO2:68%. Therefore the patient was intubated following intravenous administration of 2 mg/kg propofol, 0.5 mg/kg atracurium and mechanical ventilation was started. Mechanical ventilator was set in SIMV mode with FiO2: 50%, Vt: 6 mL/kg, frequency: 14/minute, PEEP: 7 cmH2O. IV infusion of propofol continued. No pathology was detectable in her chest X-ray. Complete blood analysis, biochemistry test results, and total urinalysis were within normal limits. She received 2 mg/kg activated charcoal through a nasogastric tube. The patient had excessive oral and tracheal secretions along with increased sweating.
1 g pralidoxime (Contrathion® %2 Flacon, 10mL, 200 mg) within 100 mL 0.9% sterile saline solution was delivered to the patient within one hour and then we continued infusion at 200 mg/hour. The dose of pralidoxime was gradually decreased and stopped at the end of second day after administration of a total of 9.6 g pralidoxime. Atropine was first given as a 2 mg IV push followed by 1 mg/hour infusion. A few additional IV doses were applied. On the second day of treatment, due to dilatation of pupils to more than 2 mm and decrease in bodily secretions, atropine treatment was ended. A total dose of 48 mg atropine was administered. Adequate hydration and electrolyte replacement was provided. During the course of her stay in the intensive care, ampicillin-sulbactam (4x1.5g, IV) and low molecular weight heparin (enoxaparin sodium) 1 x 4000 IU were administered subcutaneously.
Upon achieving spontaneous respiration movements, patient’s sedation was terminated at the end of the second day and weaning protocol was initiated. On day 3, patient had sufficient spontaneous respiration and muscle strength; arterial blood pressure was 140/80 mmHg and heath rate was 90 beats/minute. Following arterial blood values were measured under 40% FiO2 administration: pH: 7.40, PaO2: 110 mmHg, PaCO2:33.5 mmHg, HCO3: 23 mmol/L, SpO2:98%. On auscultation breath sounds were regular and so the patient was extubated and shifted to 3 L/minute oxygen therapy through facial mask. Following extubation, patient’s spontaneous respiration was sufficient and vital findings were stabile. Patient had fully recovered muscle strength and therefore we tried to get her mobilized. But she was very agitated, she was wandering continuously in ICU and we had to tie her to the bed. Psychiatry consultation was requested.
In her mental status examination she wasn’t cooperating with the examiner (MC), and orientations to time, person and location were impaired. Her short term memory was also impaired and she described tactile hallucinations. Anamnesis from her family members didn’t reveal any previous psychotic disorder. Her family described depressive symptoms beginning a few months before her admission with this suicide attempt. Diagnosis of delirium due to central anticholinergic overdose was made and haloperidol (Norodol®, 2 mg/mL) was initiated at a dose of 3x15 drops. Lack of improvement in her clinical condition after 12 hours led to augmentation of haloperidol with quetiapine. Her condition significantly improved at the following day. On day 5 the patient was easily nourished and mobilized. As the intensive care conditions were no longer needed, the patient was discharged.
Organophosphate intoxications refer to a common and significant cause of morbidity and mortality across the world . Acute organophosphate intoxication is a frequently reported type of intoxication in Turkey. Although suicidal usage accounts for most of the intoxication cases, incidental ingestion, inhalation while applying the pesticide or contact with skin or mucosa may as well occur   . If a person is exposed to high doses of pesticide and treatment is delayed, a severe course takes place and treatment will be more difficult. In this case report we aim to discuss an organophosphate intoxication due to suicide attempt.
First step of treatment in organophosphate intoxication cases is keeping the airway open and providing cardiopulmonary assistance. In cases with skin contact to prevent further absorption of the substance skin should be washed and clothes should be removed. With this method particularly if performed in first six hours subsequent to the contact with the toxic substance 91-94% of toxic substances are reported to be removed . If toxic substance is ingested through the oral route, gastric lavage and activate charcoal must be applied.
Atropine which has an antimuscarinic effect and pralidoxime which is an enzyme reactivator are the agents used for specific treatment. Atropine competitively antagonizes acetylcholine only at muscarinic receptors. It can’t prevent clinical pictures involving muscle weakness, fasciculation, respiratory depression, convulsion and coma due to the fact that it is not effective on nicotinic receptors or CNS. Prior to atropine administration, full oxygenation of the patient should be guaranteed; by this approach cardiac arrhythmias which may arise secondary to the atropine-induced hypoxia can be prevented. Atropine sulphate (0.02-0.05 mg/kg) IV administration is recommended. The dose shall be repeated until findings of atropine administration such as tachycardia, flashing, and mydriasis appear. In general, atropine treatment shall be continued during the initial 12-24 hours as long as the clinical picture is appropriate. This period might be prolonged, if necessary   . Pralidoxime is effective on all muscarinic and nicotinic receptors which act under the cholinergic influence and on CNS by activating the enzyme cholinesterase. Mechanism of this activation is through breaking the organophosphate ester bond which has formed between the cholinesterase and the insecticide. Keeping an aggressive pralidoxime treatment is important until this bond becomes irreversible. Not only pralidoxime breaks the bond between the cholinesterase and insecticide but it also avoids a second binding and enriches the therapeutic effect of atropine. Pralidoxime must be administered within the first 24-36 hours after ingestion of the toxic agent. After 36 hours, the binding between the phosphorus atom of the toxic agent and esteratic point of the enzyme gets stronger and the effectiveness of the reactivator is reduced.
We gave atropine sulphate (1 mg/hour IV) and pralidoxime treatments for two days to our patient with organophosphate intoxication. Although anticholinergics such as atropine and scopolamine are known to lead to delirium and psychosis, this condition is frequently underrecognized in patients being treated at intensive care units  . In this patient agitation, disorientation, and memory impairment after 3 days in intensive care unit are thought to be due to delirium induced by central anticholinergic effects of atropine. When atropine is given as an antidote for organophosphate intoxication, central anticholinergic syndrome is rare but cases have been reported in literature. Erol et al  and Orhan et al  reported cases of central anticholinergic syndrome due to atropine treatment of organophosphate intoxication. They also noted agitation, delirium, and hallucinations in their cases. Rapid improvement in our case after cessation of atropine and introduction of antipsychotics (haloperidol and quetiapine) supports our diagnosis of delirium due to central anticholinergic effects.
In conclusion, in patients suffering from organophosphate intoxication early diagnosis and treatment may be life-saving. However during this treatment, central anticholinergic effects of drugs like atropine and scopolamine should be kept in mind in order not to overlook delirium and to avoid complications due to central anticholinergic syndrome.
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