Liverpool Health Service Policy Issued: May 2002

Guideline

Intensive Care Unit

ORGANOPHOSPHATE POISONING MANAGEMENT

Expected Outcome
The patient with organophosphate poisoning will have adequate reversal of the poisoning and maintenance of their organ function.

Policy Statement
Protective equipment necessary for the management of Organophosphate Poisoning will be available for staff and visitor protection. Staff involved in patient care will wear the prescribed personal protective equipment at all times: charcoal mask, impermeable gown, rubber gloves. The patient will be cared for in a single room with negative pressure airflow with the doors to remain closed. Neuromuscular blocking agent: succinylcholine, and morphine are contraindicated in the management of the patient. The environment and spills within the environment are to be cleaned using dilute hypochlorite solution (household bleach).

Background
Poisoning:
Organophosphates are toxic chemicals that may be ingested, inhaled or absorbed. Dermal or occupational exposure differs in severity from oral ingestion. Oral ingestion is associated with a 100-1,000 fold greater concentration of poisoning. Metabolism is via hydrolysis in the liver. Some organophosphates are readily stored in body fat and released slowly and intermittently, complicating management. Excretion of organophosphates from the patient is via skin, body fluids and exhaled air. Organophosphates cause irreversible inhibition of the enzyme acetylcholinesterase. Carbamates (including physostigmine, neostigmine and edrophonium (Tensilon) are reversible inhibitors of the enzyme acetylcholinesterase. Inhibition of acetylcholinesterase allows the neurotransmitter acetylcholine (ACh) to remain active in the synapse - resulting in sustained depolarisation of the post-synaptic neuron. Effects are seen in the: Central Nervous System: Sensory and behavioural disturbances, incoordination, depressed motor function, coma and possible seizure activity. Muscarinic sites in the peripheral nervous system: Sustained stimulation of the parasympathetic nervous system where nerve junctions with smooth muscle and gland cells are stimulated causing: Contraction of intestinal and bronchial smooth muscle - diarrhoea, vomiting, bronchospasm, bronchorrhoea. Decreased pupil size - miosis, absent pupillary reflex. Increased secretions from all secretory glands - lacrimation, salivation. Decreased sinus node activity, bradycardia, AV conduction defects, occasional ventricular arrhythmias. Nicotinic sites in the sympathetic and parasympathetic ganglia and nicotinic sites at the neuromuscular junction these sites are stimulated and then depressed: Excess ACh may be excitatory (causing muscle twitching) but at higher levels it may also weaken and paralyse the cell by depolarising the motor endplate. Sympathetic stimulation may result in tachycardia and hypertension, then hypotension. Respiratory depression and pulmonary oedema are the usual causes of death without prompt intervention.

Excretion:

Mode of Action/Response

Reviewed: February 2004 Review date: February 2006

Author: M. Edgtton-Winn

Organophosphate Poisoning Page 1 of 5

Liverpool Health Service Policy Issued: May 2002

Guideline

Intensive Care Unit

Grading of Severity of Poisoning:

Normal serum acetylcholinesterase level is 3,500 - 8,500 U/L Mild Walks and talks. Headache, dizzy. Nausea and vomiting. Abdominal pain. Sweating, salivation. Rhinorrhoea. Serum acetylcholinesterase enzyme (ACHe) is 20-50% of normal. Results: > 700 - 1700 U/L. Moderate Cannot walk. Soft voice. Muscle twitching. (fasciculations) Weakness. Anxiety, restlessness. Small pupils (miosis). Serum acetylcholinesterase enzyme (ACHe) is 10-20% of normal. Results: >350 to 750 U/L. Severe Unconscious, no pupillary reflex. Muscle twitching, flaccid paralysis. Increased bronchial secretions. Dyspnoea, crackles/wheeze. Possible convulsions. Respiratory failure. Serum acetylcholinesterase enzyme (ACHe) is < 10% of normal. Results: <350 U/L.

1. Management of the Patient

Diagnosis/Confirmation of Poisoning
Treatment is to be instituted immediately based upon the clinical picture of organophosphate poisoning. Clinical picture of cholinergic symptoms. Onset within 12 hours of exposure (exception: highly fat-soluble organophosphate esters) Laboratory Tests: Reduction of serum and RBC acetylcholinesterase to < 50% baseline values. Reduced symptoms with atropine, and relief of muscarinic symptoms by atropine. Respiratory Symptoms: pulmonary oedema, large mucous production, decreased respiratory muscle function, bronchial smooth muscle spasm. Neurologic Symptoms: seizure, coma, delirium, respiratory centre depression, fasciculation, ataxia, long-term neuropsychiatric sequelae, depression, and peripheral neuropathy. GIT: diarrhoea, vomiting, pancreatitis (spasm of the sphincter of Oddi, check serum amylase). CVS: increased and unbalanced autonomic outflow (esp. vagal) tachy and brady dysrhythmias, Torsades de Pointes VT, hypo/hypertension. Secretions: tears, saliva, sputum, gastric acid and perspiration. Metabolic Disturbances: hypo/hyperglycaemia, metabolised in the liver (monitor LFTs).

ICU management
Airway: protection, prevention of aspiration, clearance of secretions and adequate ventilation. If unable to protect airway - intubate and ventilate; do not use neuromuscular blocking (NMB) agent succinylcholine, as it may result in prolonged paralysis of hours to days. If using non-depolarising NMBs, there may be delayed onset with higher dosage required to obtain effect. Breathing: Improve tissue oxygenation prior to administration of atropine - minimises risk of ventricular fibrillation. If ventilated - establish a "gas scavenger" set-up: an external reservoir of exhaled gas that is 'suctioned' away; see Protocol in the ICU Clinical Resource Manual. Circulation: Blood pressure support with cautious use of noradrenaline. Blood pressure may be high or low. Deficits: seizures may occur - treat with atropine followed by benzodiazepines, may require further treatment with barbiturates.

Reviewed: February 2004 Review date: February 2006

Author: M. Edgtton-Winn

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Liverpool Health Service Policy Issued: May 2002

Guideline

Intensive Care Unit

Drug Therapy:
Atropine competitively blocks the effects of acetylcholine. 1-2mg IV in moderate poisoning; 2-5mg IV in severe poisoning or as an infusion at 1020mg/hour. Continue stat doses every 10 - 30 minutes until muscarinic signs (sweating, salivation, bronchorrhoea) subside. Infusion: 60mg atropine in a 50mL syringe: 50 x 1.2mg ampoules. Titrate from 100 micrograms/hour (0.1mL/hour) to 10-20mg (8.5 to 17mL/kour) Nebulised atropine may improve respiratory distress and oxygenation by decreasing bronchial secretions, however; where ingestion results in hydrocarbon aspiration, an ARDS picture occurs (refractory pulmonary oedema and poor oxygenation). Tachycardia is not a contraindication to therapy (it may be secondary to hypoxia or sympathetic stimulation). Pupillary dilatation is not a sign of adequate therapy. Atropine is ineffective against nicotinic effects - (thus respiratory depression, muscle weakness remain in the presence of atropine). Pralidoxime; regenerates acetylcholinesterase and acts synergistically with atropine. Before administering, ensure blood specimen (heparinised tube) is taken for acetylcholinesterase analysis. Rapid administration may result in tachycardia, laryngeal spasm, muscle rigidity and transient neuromuscular blockade. Pralidoxime is used in moderate/severe poisoning where respiratory function or seizures/coma occur. Do not use in carbamate poisoning (as in neostigmine, physostigmine, Tensilon) Delayed presentation of a symptomatic patient is not a contraindication to the use of pralidoxime. Initial dose of 2 grams IV over 30 minutes. In mild to moderate poisoning, administer 1 gram IV every 8 hours. In severe poisoning the infusion rate is at 500mg/hour: 1gram in 40mL (total of 50mL) at 25mg/hour (20mL/hour). Infusion is ceased based upon clinical testing and mixed plasma cholinesterase test. Pralidoxime is metabolised by the liver and excreted by the kidneys. Frusemide is considered for persistent pulmonary oedema after full atropinization. Activated charcoal is administered in the emergency department as the first dose; nil further administrations are required in the Intensive Care Unit.

Observations: continuous ECG, arterial BP monitoring, SpO2, CVC access, CXR.

Observe for deterioration post reduction of drug therapies, auscultate lung bases for crackles. If crackles heard or there is a return of miosis, bradycardia or sweating, re-establish atropinization. Continuous monitoring is required for 72 hours or longer as organophosphate may be intermittently released from fat stores.

Contraindications: do not prescribe/administer morphine, succinylcholine, theophylline, phenothiazines, reserpine. Pain relief:
Administer paracetamol and non-opioid analgesia for relief of muscle pain. Ensure discharge planning/rehabilitation process has commenced upon admission. Involve patient in simple activities such as reading, listening to radio/CDs, watching TV during isolation and periods of reduced contact with staff, relatives, carers.

Supportive Measures for Patient Comfort:

Reviewed: February 2004 Review date: February 2006

Author: M. Edgtton-Winn

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Liverpool Health Service Policy Issued: May 2002

Guideline

Intensive Care Unit

2. Practicalities of the environment and safety issues

Environment
Place patient in a single isolation room with negative pressure flow. Doors are to remain closed. There is to be minimal contact beyond that required to care appropriately for the patient.

Decontamination - in the Emergency Department, concurrent with resuscitation and

antidotal measures Initial skin decontamination is usually required for occupational or accidental exposures. Ingestion of organophosphates (associated with suicide or accidental ingestion) may require skin decontamination as the metabolites are excreted dermally and through body fluids and exhaled air. It is recommended that there be an initial process of decontamination during resuscitation, followed by a second, thorough cleansing of the patient - thus further cleansing may be required after admission to the Intensive Care Unit. All staff involved in the care of the acutely ill patient are to wear: charcoal mask, impermeable gown and rubber gloves (vinyl gloves provide no protection). Skin - contamination of skin, clothing, hair, eyes. Flush the chemical from the eyes with copious amounts of normal saline. Remove clothing and wash patient/shampoo hair, using copious amounts of soap and water. Ensure skin folds and underneath of fingernails are cleansed. Contaminated clothing should be removed, bagged and may be laundered by the family. Contaminated leather articles should be discarded as the leather absorbs the chemical and cannot effectively be cleaned - document in notes and explain necessity to the family. Soap containing chlorhexidine and alcohol helps remove lipophilic compounds.

Safety precautions for staff and visitors during the acute stage of management
Charcoal mask and impermeable gown are to be worn in the isolation room. When caring for the patient, rubber gloves are to be worn (as per chemotherapeutic precautions). When the patient is exhibiting signs and symptoms of moderate/severe poisoning the above precautions are to be maintained. In severe poisoning, industrial goggles for eye protection/comfort should be worn. When the patient is admitted to the ICU without adequate decontamination or in cases of severe poisoning: Consider hourly rotation of staff on patient admission. Consider rotation of staff as per discomfort - headache, nausea, distress from noxious odour of the organophosphate metabolism.

Staff rotation

Cleaning bed area during patient therapy

If spills occur - wipe over with dilute hypochlorite solution (household bleach) to inactivate the organophosphorus ester. Ensure minimal contact time within the room. Keep bed area orderly so as to reduce need for prolonged time to tidy environment. Linen skip to be placed within the isolation room. When full, tie up the bag and place outside room for collection as per normal routine. Laundering is as per normal routine.

Bed linen

Reviewed: February 2004 Review date: February 2006

Author: M. Edgtton-Winn

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Liverpool Health Service Policy Issued: May 2002

Guideline

Intensive Care Unit

Cleaning bed area upon patient transfer

Page the Isolation Cleaner on 25327 (0600 - 2300hours) for terminal cleaning of bed area. After Hours if urgent, phone Supervisor on 2778, ensure all equipment is thoroughly cleaned and curtains have been replaced. The bed area is to be cleansed with a bleach solution (dilute hypochlorite solution household bleach). Ensure negative pressure within the isolation room continues to remain active for @ 3 hours post cleaning/transfer of the patient (added precaution, not described in the literature). All staff involved in the cleaning of the bed area are to wear: an impermeable gown and rubber gloves, (vinyl gloves provide no protection). If odour in room causes discomfort, staff are to wear a charcoal mask.

Patient Admission to the Ward

Patients may be considered for transfer to the ward after cessation of drug therapies and the absence of signs and symptoms of organophosphate poisoning. Serum acetylcholinesterase levels are to measure > 1700U/L, approaching the normal levels of 3,500 - 8,500U/L. Patient management on the ward preferably requires a single room. Staff caring for the patient are to wear protective mask, rubber gloves and impermeable gown when cleaning away large collections of bodily fluids such as incontinence of faeces/urine or vomitus. If the patient represents with sweating, salivation and rhinorrhoea, nausea and vomiting then protective wear must be worn within the room. If the patient's condition deteriorates, requiring further treatment with atropine and pralidoxime, then liaison needs to occur with the admitting team and the Intensive Care Senior Registrar on call.

References

Reigart, J.R. and Roberts, J.R. (1999). Recognition and Management of Pesticide Poisonings in National th Pesticide Telecommunications Network. (5 Ed.). http://ace.orst.edu/info/nptn/rmpp.htm Jackson, J.E. and Aaron, C.K. (1996). Cholinergic Agents. In Rippe, J.M., Irwin, R.S., Fink, M.P. and Cerra, F.B. (Third Ed., Volume II). Intensive Care Medicine. Boston: Little, Brown and Company. 1546 - 1553. Morgan, D.P. (1989). Organophosphate Insecticides. In Recognition and Management of Pesticide Poisonings. (4th Ed.). Environmental Protection Agency: Iowa and University of Florida. Cholinesterase - (1998). Pesticide Fact Sheet and Tutorial at http://pmep.cce.cornell.edu/facts-slidesself/facts/gen-posaf-chol.html Lesson of the Week: A foodbourne outbreak of organophosphate poisoning. (2001). British Medical Journal 317:268-269 at http://www.hedleytech.com/980725_britishmedicaljournal.htm Slapper, D. (2001). Toxicity, Organophosphate and Carbamate from Emergency Medicine/Toxicology. 1st February, 2001: www.emedicine.com/emerg/topic346.htmHu, H. and Speizer, F.E. (1994). Environmental and occupational hazards. In Isselbacher, K.J., Braunwald, E., Wilson, J.D., Martin, J.B., Fauci, A.S. and Kasper, D.L. Harrison's Principles of Internal Medicine. (13th Ed.). New York: McGraw-Hill Inc. Paraquat. (1999). Hazardous Substance Fact Sheet. New Jersey Department of Health and Senior Services September 1999. Nosocomial poisoning associated with emergency department treatment of organophosphate toxicity - Georgia, 2000. MMWR - January 5th, 2001. Pp: 1156-1159. Bruzel, A. (1998). New Acetylcholinesterase Inhibitors. From About http://chemistry.about.com/science/c.../aa040698a.htm?iam=dpile&terms=%2Bcarbamat Chemistry:

Policy Author(s): M. Edgtton-Winn, ICU - CNC, L. Williams, ICU - NUM. Reviewed by: Director of ICU, CNC ICU.

Reviewed: February 2004 Review date: February 2006

Author: M. Edgtton-Winn

Organophosphate Poisoning Page 5 of 5