Organophosphates/Carbamates

Epidemiology

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Agents

Organophosphate Pesticides

General Comments
- Many of These Agents Have a Petroleum or Garlic-Like Odor
Chlorpyrifos
- Sold Under the Brane Name Baygon
- Used in Cockroach/Insect Baits
Diazinon
- Developed in 1952 to Replace Use of the Pesticide DDT
- Heavily Used in the 1970’s-1980’s
Diclorvos (DDVP)
- Sold Under the Brand Name Vapona
- Commercially Available Since 1961
Ethion
- Fifteen Victims were Accidentally Poisoned with this Agent in 2005 After Ingesting Ethion-Contaminated Food in a Ceremony in Magrawa, India
Malathion (Carbophos, Maldison, Mercaptothion) (see Malathion, Malathion)
- Listed as a Probable Carcinogen Associated with Prostate Cancer by the American Cancer Society
- Used in Head Lice Shampoos
Parathion
- Sold Under the Brand Name Folidol

Organophosphate Nerve Gases (Militarized Organophosphates)

Sarin (see Sarin, Sarin)
- Used in Iran-Iraq War (During the 1980’s)
- Used in Tokyo Subway Attack by the Religious Sect, Aum Shinrikyo (in 1995)
Soman
Tabun
- Used in Iran-Iraq War
VX Nerve Agent (see VX Nerve Agent, VX Nerve Agent)

Carbamate Pesticides

Aldicarb
- Sold Under the Brand Name Temik
Ambenonium
- Sold Under the Brand Name Mytelase
Carbaryl
- Sold Under the Brand Name Sevin
Bendiocarb
- Sold Under the Brand Names Ficam and Turcam
Propoxur
- Sold Under the Brand Name Baygon

Medical Carbamates

Donepezil (Aricept) (see Donepezil, Donepezil)
- Used to Treat Alzheimer’s Disease
Ecthiopate
- Used to Treat Glaucoma
Edrophonium (Tensilon, Enlon) (see Edrophonium, Edrophonium)
- Used to Treat Myasthenia Gravis
Galantamine
- Used to Treat Alzheimer’s Disease
Neostigmine (Prostigmin, Vagostigmin) (see Neostigmine, Neostigmine)
- Used to Treat Colonic Pseudo-Obstruction, Elapid Envenomation, and Prolonged Neuromuscular Blockade
Physostigmine (Antilirium) (see Physostigmine, Physostigmine)
- Used to Treat Antimuscarinic (Anticholinergic) Intoxication and Glaucoma
Pyridostigmine (Mestinon) (see Pyridostigmine, Pyridostigmine)
- Used to Treat Myasthenia Gravis and Prolonged Neuromuscular Blockade
Rivastigmine (Exelon) (see Rivastigmine, Rivastigmine)
- Used to Treat Alzheimer’s Disease
Tacrine (Cognex) (see Tacrine, Tacrine)
- Used to Treat Alzheimer’s Disease

Exposure

Routes of Exposure

Skin: organophosphates/carbamates are both well-absorbed
Lungs: organophosphates/carbamates are both well-absorbed
Gastrointestinal (GI) Tract: organophosphates/carbamates are both well-absorbed
Injection

Chemistry/Pharmacology

Chemistry

Organophsophates Contain Carbon and Derivatives of Phosphoric Acid
- Organophosphates are Irreversible Acteylcholinesterase Inhibitors
- “Aging”: the acetylcholinesterase-organophosphate compound undergoes a conformational change over time, resulting in irreversible binding and resistance to reactivation by antidotes (such as oximes)
- Dimethyl Compounds: these compounds undergo rapid aging, mandating early initiation of oxime therapy
- Diethyl Compounds: these compounds may have delayed toxicity and therefore, may require prolonged therapy
Carbamates are Derived from Carbamic Acid
- Carbamates are Reversible Acteylcholinesterase Inhibitors: they spontaneously hydrolyze from the cholinesterase enzymatic site within 48 hrs

Organophosphates and Carbamates are Red Blood Cell Acteylcholinesterase Inhibitors

Acteylcholinesterase Inhibition Results in Accumulation of Acetylcholine at Nicotinic/Muscarinic Synapses and Neuromuscular Junction
Organophosphates Also Inhibit Plasma Cholinesterase (aka Pseudocholinesterase) and Neuropathy Target Esterase (NTE)
- The Clinical Consequences of these Interaction are Unclear
Organophosphates and Carbamates are Structurally Distinct, But Have Similar Clinical/Toxicologic Manifestations
- Carbamate Intoxication Tends to Be Shorter in Duration than that of Organophosphates (Assuming Equivalent Doses), But the Mortality Rates with Both Exposures are Similar

Clinical Effects

Muscarinic Effects
- SLUDGE/BBB Mnemonic
  - Salivation
  - Lacrimation
  - Urination
  - Defecation
  - Gastric Emesis
  - Bronchorrhea
  - Bronchospasm
  - Bradycardia
- DUMBELS Mnemonic
  - Defecation
  - Urination
  - Miosis
  - Bronchorrhea/Bronchospasm/Bradycardia
  - Emesis
  - Lacrimation
  - Salivation
Nicotinic Effects
- Cardiovascular
  - Hypertension
  - Sinus Tachycardia
- Neurologic
  - Areflexia
  - Ataxia
  - Twitching/Fasciculations
  - Weakness/Paralysis
- Pulmonary
  - Acute Respiratory Failure
  - Bronchospasm
  - Laryngospasm
Central Nervous System Effects (Mediated by Muscarinic and Nicotinic Receptors in Brain)
- Altered Mental Status
  - Obtundation-Coma
- Anxiety
- Agitation
- Seizures
- Tremor

Metabolism

Organophosphates Undergo Mostly Hepatic Metabolism (Slowly)
- Oxidative Metabolites (Paroxon/Maloxone) are Active, These are Subsequently Hydrolyzed to Inactive Metabolites
Carbamates Undergo Rapid Elimination by Serum Cholinesterases and Hepatic Metabolism
- Duration of Carbamate Toxicity is Therefore, Generally Shorter and Less Severe than with Organophosphates

Diagnosis

Arterial Blood Gas (ABG) (see Arterial Blood Gas, Arterial Blood Gas)

Useful to Diagnose Metabolic Acidosis and Respiratory Acidosis: their presence correlates with severity of symptoms and mortality

Urine Toxicology Screen

May Detect These Agents

Chest X-Ray/Chest CT (see Chest X-Ray, Chest X-Ray and Chest Computed Tomography, Chest Computed Tomography)

Useful to Rule Out Aspiration Pneumonia, ARDS, etc

Bronchoscopy (see Bronchoscopy, Bronchoscopy)

May Be Required to Rule Out Airway Injury

Red Blood Cell Acetylcholinesterase Activity (see Red Blood Cell Acetylcholinesterase Activity, Red Blood Cell Acetylcholinesterase Activity)

Rationale
- Acute Intoxication
  - Red Blood Cell Acetylcholinesterase Activity Provides a Direct Assessment of the Degree of Toxicity
  - Sequential Assessment May Be Used to Monitor the Effectiveness of Oxime Therapy
- Chronic/Occupational Exposure:
  - Red Blood Cell Acetylcholinesterase Activity May Be Used Diagnostically
Availability: less readily available in most hospital laboratories
Interpretation
- Usually Decreased to <50% Normal in Acute Organophosphate Intoxication
- May Be Normal in Carbamate Intoxication: due to reversible binding of these agents
- Etiology of Falsely-Decreased RBC Cholinesterase Activity
  - Antimalarial Drugs
  - Hemoglobinopathies
  - Drawing Blood in Oxalate Blood Tubes
  - Pernicious Anemia

Plasma Pseudocholinesterase (see Plasma Pseudocholinesterase, Plasma Pseudocholinesterase)

More Readily Available from Hospital Laboratories, But Does Not Correlate Well with the Severity of Toxicity: not clinically useful to guide therapy

Clinical Manifestaions

Acute Toxicity

General Comments

Onset of Symptoms: effects generally occur within 30 min-2 hrs after exposure
- Latency of Symptoms is Related to Route of Exposure
  - Respiratory/Oral Exposure: symptoms usually develop within 3 hrs
  - Dermal Exposure: symptoms may be delayed up to 12 hrs later
- Latency of Symptoms is Related to Lipophilicity of the Agent
  - Lipohilic Agents (Dichlofenthion, Fenthion, Malathion) are Associated with Delayed Onset of Symptoms (Up to 5 Days in Some Cases): may be related to delayed distribution from fat stores

Cardiovascular Manifestations

Arrhythmias
Conduction Defects
- Pharmacology: muscarinic
- Clinical
  - Heart Blocks
    - First Degree Atrioventricular Block (see First Degree Atrioventricular Block, First Degree Atrioventricular Block)
    - Second Degree Atrioventricular Block-Mobitz Type I (Wenckebach) (see Second Degree Atrioventricular Block-Mobitz Type I, Second Degree Atrioventricular Block-Mobitz Type I)
    - Second Degree Atrioventricular Block-Mobitz Type II (see Second Degree Atrioventricular Block-Mobitz Type II, Second Degree Atrioventricular Block-Mobitz Type II)
    - Third Degree Atrioventricular Block (see Third Degree Atrioventricular Block, Third Degree Atrioventricular Block)
  - QT Prolongation (see Torsade, Torsade)
Electrocardiographic (EKG) Changes (see Electrocardiogram, Electrocardiogram)
- Epidemiology: may occur
Elevated Serum Troponin (see Elevated Serum Troponin, Elevated Serum Troponin)
- Epidemiology: may occur
- Clinical: peak troponin usually is present at presentation
Hypertension (see Hypertension, Hypertension)
- Epidemiology: may occur transiently (due to sympathetic stimulation)
- Pharmacology: nicotinic
Hypotension/Shock (see Hypotension, Hypotension)
- Epidemiology: usually present in moderate-severe intoxication
- Pharmacology: muscarinic
- Physiology: may be related to inappropriate vasodilation
- Clinical: may be severe fatal in some cases (Vet Hum Toxicol, 2004) [MEDLINE]
Sinus Bradycardia (see Sinus Bradycardia, Sinus Bradycardia)
- Epidemiology: usually present in moderate-severe intoxication
- Pharmacology: muscarinic
Sinus Tachycardia (see Sinus Tachycardia, Sinus Tachycardia)
- Epidemiology: may occur transiently (due to sympathetic stimulation)
- Pharmacology: nicotinic

Gastrointestinal/Genitourinary Manifestations

Crampy Abdominal Pain (see Abdominal Pain, Abdominal Pain)
- Pharmacology: muscarinic
Nausea/Vomiting (see Nausea and Vomiting, Nausea and Vomiting)
- Pharmacology: muscarinic
Sialorrhea (Hypersalivation) (see Sialorrhea, Sialorrhea)
- Pharmacology: muscarinic
Urinary/Fecal Incontinence (see Urinary Incontinence, Urinary Incontinence and Fecal Incontinence, Fecal Incontinence)
- Pharmacology: muscarinic
Urinary Frequency (see Urinary Frequency, Urinary Frequency)
- Pharmacology: muscarinic

Neurologic Manifestations

Altered Mental Status (see Altered Mental Status, Altered Mental Status)
- Pharmacology: due to involvement of muscarinic/nicotinic receptors in the central nervous system
- Clinical
  - Obtundation-Coma (see Obtundation-Coma, Obtundation-Coma)
Agitation (see Agitation, Agitation)
- Pharmacology: due to involvement of muscarinic/nicotinic receptors in the central nervous system
Anxiety (see Anxiety, Anxiety)
- Pharmacology: due to involvement of muscarinic/nicotinic receptors in the central nervous system
Areflexia (see Hyporeflexia, Hyporeflexia)
- Pharmacology: nicotinic
Ataxia (see Ataxia, Ataxia)
- Pharmacology: nicotinic
Seizures (see Seizures, Seizures)
- Pharmacology: due to involvement of muscarinic/nicotinic receptors in the central nervous system
Tremor (see Tremor, Tremor)
- Pharmacology: due to involvement of muscarinic/nicotinic receptors in the central nervous system
Twitching/Fasciculations (see Fasciculations, Fasciculations)
- Pharmacology: nicotinic
- Clinical: fasciculations are strongly suggestive of cholinergic intoxication
Weakness/Paralysis (see xxxx, xxxx)
- Pharmacology: nicotinic

Pulmonary Manifestations

Acute Respiratory Distress Syndrome (ARDS) (see Acute Respiratory Distress Syndrome, Acute Respiratory Distress Syndrome)
- Pharmacology: muscarinic
Acute Respiratory Failure (see Respiratory Failure, Respiratory Failure)
- Pharmacology: nicotinic
- Physiologic Mechanisms
  - Bronchospasm
  - Decreased Central Respiratory Drive with Acute Hypoventilation (see Acute Hypoventilation, Acute Hypoventilation)
  - Increased Secretions
  - Respiratory Muscle Weakness
- Prognosis: may be fatal in some cases
Bronchorrhea (see Bronchorrhea, Bronchorrhea)
- Pharmacology: muscarinic
Bronchospasm (see Obstructive Lung Disease, Obstructive Lung Disease)
- Pharmacology: muscarinic
Cough (see Cough, Cough)
- Pharmacology: muscarinic
Dyspnea (see Dyspnea, Dyspnea)
- Pharmacology: muscarinic
Laryngospasm (see Laryngospasm, Laryngospasm)
- Pharmacology: nicotinic

Other Manifestations

Acute Kidney Injury (AKI) (see Acute Kidney Injury, Acute Kidney Injury)
- Epidemiology: AKI has been reported (Hum Exp Toxicol, 2003) [MEDLINE] and (Pediatr Emerg Care, 2013) [MEDLINE]
- Physiology: unclear
Acute Pancreatitis (see Acute Pancreatitis, Acute Pancreatitis)
- Epidemiology: has been reported with both organophosphates and carbamates (Hum Exp Toxicol, 2002) [MEDLINE]
Hyperhidrosis (see Diaphoresis, Diaphoresis)
- Pharmacology: muscarinic
Lacrimation (see Lacrimation, Lacrimation)
- Pharmacology: muscarinic

Intermediate (Neurologic) Toxicity

General Comments

Epidemiology
- Occurs in 10-40% of Cases
  - Risk Appears to Be Related to Exposure to a Highly Fat Soluble Organophosphate Agent or Inadequate Therapy with Pralidoxime (Przegl Lek, 1995) [MEDLINE]
  - Rarely Occurs with Carbamate Exposure
- Occurs 24-96 hrs After Exposure
Diagnosis
- Red Blood Cell Acetylcholinesterase Levels: correlates to with clinical deterioration (and improvement)
- Electromyogram (EMG)/Nerve Conduction Velocity (NCV) (see Electromyogram-Nerve Conduction Velocity, Electromyogram-Nerve Conduction Velocity): unique post-synaptic abnormalities are observed
Prognosis
- Usually Resolves Completely within 2-3 Weeks

Neurologic Manifestations

Cranial Nerve Abnormalities
Hyporeflexia (see Hyporeflexia, Hyporeflexia)
Neck Flexion Weakness
Proximal Muscle Weakness (see xxxx, xxxx)
Respiratory Failure (see Respiratory Failure, Respiratory Failure)

Delayed/Long-Term Neurologic Toxicity

Neurologic Manifestations

Difficulties with Abstraction
Memory Loss (see Memory Loss, Memory Loss)
Organophosphate-Induced Delayed Polyneuropathy (OPIDN) (see Peripheral Neuropathy, Peripheral Neuropathy)
- Epidemiology
  - Associated with Chlorpyrifos, Leptophos, Malathion, Merphos, Mipafox,Trichlorfon, and Triorthocresyl Phosphate (TOCP),
  - Rarely Seen with Carbamate Exposure
  - Risk of OPIDN is Independent of the Severity of the Initial Acute Toxicity
- Physiology
  - Inhibition of Neuropathy Target Esterase (NTE) Found in Brain, Peripheral Nerves, and Lymphocytes: enzyme normally functions to degrade esters within the cell
- Diagnosis
  - Electromyogram (EMG)/Nerve Conduction Velocity (NCV) (see Electromyogram-Nerve Conduction Velocity, Electromyogram-Nerve Conduction Velocity): decreased firing of motor conduction units (Electromyogr Clin Neurophysiol, 2003) [MEDLINE]
- Clinical
  - Initial Transient, Painful Stocking-Glove Distribution Parasthesias
  - Subsequent Symmetrical Motor Polyneuropathy with Flaccid Lower (Ascending to Upper) Extremity Weakness
    - Mild Sensory Deficits
    - Distal Muscle Groups are Predominantly Affected with Relative Sparing of Proximal Muscle Groups/Neck Muscles/Cranial Nerves
- Prognosis
  - Recovery May Take Up to 1 Year
  - Severe Cases May Manifest Permanent Upper Motor Neuron Syndrome with Lower Extremity Spasticity
Parkinson’s Disease (see Parkinson’s Disease, Parkinsons Disease)

Chronic Organophosphate Exposure

Pulmonary Manifestations

Occupational Asthma (see Asthma-Occupational, Asthma-Occupational)
- Epidemiology: associated with chronic exposure to organophosphates

Treatment of Acute Toxicity

Decontamination

Evacuate from Site of Exposure: to prevent further contact
Remove and Discard Contaminated Clothing
Wash Skin with Soap and Water
Ocular Irrigation

Forced Emesis

Contraindicated

Gastric Lavage (see Gastric Lavage, Gastric Lavage)

Indications
- Organophosphate/Carbamate Ingestion within the Prior 1 hr: although has no clear impact on morbidity/mortality
Technique
- Perform Only in Intubated Patient After Atropine and Oxime Therapy is Initiated

Activated Charcoal (see Activated Charcoal, Activated Charcoal)

Indications
- Organophosphate/Carbamate Ingestion within the Prior 1 hr: administration is unlikely to be effective after 1 hr (Lancet, 2008) [MEDLINE]
Contraindications
- Avoid Use of Activated Charcoal in Patients Who are Not Intubated
Administration
- Dose: 1 g/kg (maximum dose: 50 g) PO

Treatment of Seizures (see Seizures, Seizures)

Benzodiazepines (see Benzodiazepines, Benzodiazepines)
- Diazepam (Valium): 10 mg IV (repeat, as required)
Avoid Phenytoin (Dilantin) (see Phenytoin, Phenytoin): due to unclear efficacy in this setting

Atropine (see Atropine, Atropine)

Pharmacology: muscarinic receptor antagonist
- Less Effective for Central Nervous System Effects
- Ineffective for Nicotinic Effects (in Particular Neuromuscular Dysfunction): as atropine does not bind to nicotinic receptors
Administration
- Diagnostic Test Dose: 1 mg IV
- Treatment Dose: 2-5 mg IV
  - Escalate Dose q3-5 min Until Clinical Effect (Mucosal Drying, Decreased Secretions, Decreased Wheezing) is Observed
  - Some Cases Require Multiple Doses or Prolonged Infusion Over a Period of Days (Severe Intoxications May Require Up to Hundreds of Milligrams Over Several Days)
  - Heart Rate and Pupillary Size Should Not Be Used as Treatment Endpoints: tachycardia and mydriasis are not contraindications to atropine
- Atropine Autoinjector (Atropen): available for lay person administration in cases of nerve agent/pesticide exposure
Clinical Efficacy
- Open Label Trial of Atropine in Organophosphate Intoxication (J Med Toxicol, 2012) [MEDLINE]
  - Incremental Atropine Bolus Dosing with Infusion Decreased Mortality Rate (and Decreased Atropine Toxicity) in Organophosphate Intoxication, as Compared to Standard Atropine Bolus Dosing with Infusion

Ipratropium Bromide (Atrovent) (see Ipratropium Bromide, Ipratropium Bromide)

Pharmacology
- Short-Acting Muscarinic Antagonist (SAMA)
Indications
- Bronchospasm

Pralidoxime (2-PAM) (see Pralidoxime, Pralidoxime)

Pharmacology: reactivates cholinesterases
- Effective for Treating Both Muscarinic and Nicotinic Effects
- Less Effective for Central Nervous System Effects
Indications
- Any Patient with Evidence of Cholinergic Toxicity in the Setting of Organophosphate/Carbamate Intoxication
- Patient with Neuromuscular Dysfunction in the Setting of Organophosphate/Carbamate Intoxication
- Patients with Exposure to Organophosphates/Carbamates Known to Cause Delayed Neurotoxicity
  - Early Oxime Therapy May Be Beneficial to Prevent the Intermediate (Neurologic) Toxicity Syndrome or OPIDN
Administration
- Bolus Dosage: give at least 30 mg/kg (usually 2 g) IV slowly over 30 min (may repeat in 30 min, as required
  - Always Given with Concomitant Atropine to Prevent Worsening of Symptoms Due to Transient Oxime-Induced Acetylcholinesterase Inhibition
  - If Administered Intramuscular: 600 mg IM (may repeat, as required, to max dose: 1800 mg)
- Continuous Infusion (as Required for Severe Intoxication): 8 mg/kg/hr
Adverse Effects
- Cardiac Arrest (see Cardiac Arrest, Cardiac Arrest): usually associated with rapid infusion
- Muscle Weakness: due to transient acetylcholinesterase inhibition as pralidoxime binds to the enzyme
Monitor
- Red Blood Cell Acetylcholinesterase Activity Can Be Serially Assayed to Monitor the Effectiveness of Oxime Therapy

Respiratory Support

Endotracheal Intubation/Mechanical Ventilation (see Mechanical Ventilation-General, Mechanical Ventilation-General)
- Early Intubation is Often Required
- Avoid Succinylcholine for Rapid Sequence Intubation (RSI) (see Succinylcholine, Succinylcholine): due to the fact that succinylcholine is metabolized by acetylcholinesterase (which is inhibited by organophosphates) and there is a risk of prolonged paralysis
- Nondepolarizing Neuromuscular Blockers (Rocuronium, etc) May Be Less Effective at Standard Doses (Due to Competitive Inhibition at the Neuromuscular Junction: increased doses may be required

Corticosteroids (see Corticosteroids, Corticosteroids)

May be beneficial in Acute Respiratory Distress Syndrome (ARDS), But are Unproven

Prognosis

Predictors of Outcome (QJM, 2008) [MEDLINE]
- Glasgow Coma Score
  - Patients with GCS ≤13 Need Intensive Monitoring
  - However, the Identity of the Agent Should Be Considered, Since Half of the Patients Who Died From Fenthion Poisoning Only Had Mild Symptoms at Presentation
- International Program on Chemical Safety Poison Severity Score (IPCS PSS)
APACHE II and SAPS-II Scoring Have Been Demonstrated to Outperform the Poison Severity Score (PSS) in Terms of Predicting Outcome (Clin Toxicol-Phila, 2013) [MEDLINE]

References

Intermediate syndrome in acute fenitrothion poisoning. Przegl Lek. 1995;52(5):271 [MEDLINE]
QTc prolongation indicates a poor prognosis in patients with organophosphate poisoning. Am J Emerg Med. Sep 1996;14(5):451-3
The Tokyo subway sarin attack: disaster management, Part 3: national and international responses. Acad Emerg Med. 1998 Jun;5(6):625-8 [MEDLINE]
Weapons of mass destruction events with contaminated casualties: effective planning for health care facilities. JAMA. 2000;283(2):242-249 [MEDLINE]
Organic insecticides. Anaesth Intensive Care. Feb 2000;28(1):11-21
The prevalence of pancreatitis in organophosphate poisonings. Hum Exp Toxicol. 2002;21(4):175 [MEDLINE]
Acute renal failure from organophospate poisoning: a case of success with haemofiltration. Hum Exp Toxicol. 2003;22(3):165 [MEDLINE]
The clinical and electrophysiological features of a delayed polyneuropathy developing subsequently after acute organophosphate poisoning and it’s correlation with the serum acetylcholinesterase. Electromyogr Clin Neurophysiol. 2003;43(7):421 [MEDLINE]
Changes in the hemodynamic state of patients with acute lethal organophosphate poisoning. Vet Hum Toxicol. 2004;46(1):5 [MEDLINE]
Clinical review: Tokyo – protecting the health care worker during a chemical mass casualty event: an important issue of continuing relevance. Crit Care. 2005 Aug;9(4):397-400. Epub 2005 Feb 17 [MEDLINE]
Continuous pralidoxime infusion versus repeated bolus injection to treat organophosphorus pesticide poisoning: a randomised controlled trial. Lancet. Dec 16 2006;368(9553):2136-41
Acid-base interpretation can be the predictor of outcome among patients with acute organophosphate poisoning before hospitalization. Am J Emerg Med. Jan 2008;26(1):24-30
The spectrum of intermediate syndrome following acute organophosphate poisoning: a prospective cohort study from Sri Lanka. PLoS Med. 2008 Jul 15;5(7):e147. doi: 10.1371/journal.pmed.0050147 [MEDLINE]
Predicting outcome in acute organophosphorus poisoning with a poison severity score or the Glasgow coma scale. QJM. 2008 May;101(5):371-9. Epub 2008 Mar 4 [MEDLINE]
Multiple-dose activated charcoal in acute self-poisoning: a randomised controlled trial. Lancet. 2008;371(9612):579 [MEDLINE]
Evaluation of the Test-mate ChE (cholinesterase) field kit in acute organophosphorus poisoning. Ann Emerg Med. Dec 2011;58(6):559-564.e6
Open-label randomized clinical trial of atropine bolus injection versus incremental boluses plus infusion for organophosphate poisoning in Bangladesh. J Med Toxicol. 2012;8(2):108 [MEDLINE]
Organophosphate poisoning-induced acute renal failure. Pediatr Emerg Care. 2013 May;29(5):646-7 [MEDLINE]
Performance of clinical scoring systems in acute organophosphate poisoning. Clin Toxicol (Phila). 2013 Nov;51(9):850-4. Epub 2013 Sep 26 [MEDLINE]
Organophosphate and carbamate poisoning. Emerg Med Clin North Am. 2015;33(1):133-151 [MEDLINE]