Organophosphate poisoning

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Organophosphate poisoning
ICD-10 T60.0
ICD-9 989.3

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Many organophosphates are potent neurotoxins, functioning by inhibiting the action of acetylcholinesterase (AChE) in nerve cells. They are one of the most common causes of poisoning worldwide, and are frequently intentionally used in suicides in agricultural areas.


The effects of organophosphate poisoning are recalled using the mnemonic SLUDGE (Salivation, Lacrimation, Urination, Diaphoresis (or Defecation), Gastrointestinal motility, Emesis)[1]


Atropine can be used as an antidote in conjunction with pralidoxime, though the use of "-oximes" has been found to be of no benefit, or possibly harmful, in at least two meta-analyses.[2][3]

Potential effects of environmental organophosphates

The use of the organophosphates in aviation lubricating oils and hydraulic fluids and its impact on health and flight safety is a matter of some debate. Airline employees set up a non profit group in 2001 to highlight their concerns called the Aviation Organophosphate Information Site (AOPIS).[4]

Purdey (1998) suggested that organophosphates, in particular Phosmet, induced the transmissible spongiform encephalopathy epidemic of BSE.[5] An European Union food safety Scientific Steering Committee examined the evidence and did not find a link.[6]

As opposed to the two examples given above, the toxicological literature on persistent chronic toxicity from acute poisonings or long-term low level exposure is quite extensive. The phenomenon of OPIDP (organophosphate induced delayed polyneuropathy, also OPIDN), which causes degeneration of the peripheral nerves, has been noted to occur several weeks after exposure to some organophosphates. [7]

Ginger Jake

A striking example of OPIDN occurred during the 1930s Prohibition Era when thousands of men in the American South and Midwest developed arm and leg weakness and pain after drinking a "medicinal" alcohol substitute. The drink, called "Ginger Jake," contained an adulterated Jamaican ginger extract containing tri-ortho-cresyl phosphate (TOCP) which resulted in partially reversible neurologic damage. The damage resulted in the limping "Jake Leg" or "Jake Walk" which were terms frequently used in the blues music of the period. Europe and Morocco both experienced outbreaks of TOCP poisoning from contaminated abortifacients and cooking oil, respectively.[8]


Other studies suggest a link between chronic low level organophosphate exposure and neuropsychiatric and behavioral effects. Jamal has suggested the term COPIND, or "Chronic Organophosphate-Induced Neurologic Dysfunction,"[9] and Abou Donia the term, OPICN, or Organophosphate-Induced Chronic Neuropathy for describing these effects.[10]

Low-level effects on the developing brains of fetuses, infants, and children have been documented as well.

Differential Diagnosis

Diseases History and Physical Diagnostic tests Other Findings
Motor Deficit Sensory deficit Cranial nerve Involvement Autonomic dysfunction Proximal/Distal/Generalized Ascending/Descending/Systemic Unilateral (UL)

or Bilateral (BL)


No Lateralization (NL)

Onset Lab or Imaging Findings Specific test
Adult Botulism + - + + Generalized Descending BL Sudden Toxin test Blood, Wound, or Stool culture Diplopia, Hyporeflexia, Hypotonia, possible respiratory paralysis
Infant Botulism + - + + Generalized Descending BL Sudden Toxin test Blood, Wound, or Stool culture Flaccid paralysis (Floppy baby syndrome), possible respiratory paralysis
Guillian-Barre syndrome[11] + - - - Generalized Ascending BL Insidious CSF: ↑Protein


Clinical & Lumbar Puncture Progressive ascending paralysis following infection, possible respiratory paralysis
Eaton Lambert syndrome[12] + - + + Generalized Systemic BL Intermittent EMG, repetitive nerve stimulation test (RNS) Voltage gated calcium channel (VGCC) antibody Diplopia, ptosis, improves with movement (as the day progresses)
Myasthenia gravis[13] + - + + Generalized Systemic BL Intermittent EMG, Edrophonium test Ach receptor antibody Diplopia, ptosis, worsening with movement (as the day progresses)
Electrolyte disturbance[14] + + - - Generalized Systemic BL Insidious Electrolyte panel ↓Ca++, ↓Mg++, ↓K+ Possible arrhythmia
Organophosphate toxicity[15] + + - + Generalized Ascending BL Sudden Clinical diagnosis: physical exam & history Clinical suspicion confirmed with RBC AchE activity History of exposure to insecticide or living in farming environment. with : Diarrhea, Urination, Miosis, Bradycardia, Lacrimation, Emesis, Salivation, Sweating
Tick paralysis (Dermacentor tick)[16] + - - - Generalized Ascending BL Insidious Clinical diagnosis: physical exam & history - History of outdoor activity in Northeastern United States. The tick is often still latched to the patient at presentation (often in head and neck area)
Tetrodotoxin poisoning[17] + - + + Generalized Systemic BL Sudden Clinical diagnosis: physical exam & dietary history - History of consumption of puffer fish species.
Stroke[18] +/- +/- +/- +/- Generalized Systemic UL Sudden MRI +ve for ischemia or hemorrhage MRI Sudden unilateral motor and sensory deficit in a patient with a history of atherosclerotic risk factors (diabetes, hypertension, smoking) or atrial fibrillation.
Poliomyelitis[19] + + + +/- Proximal > Distal Systemic BL or UL Sudden PCR of CSF Asymmetric paralysis following a flu-like syndrome.
Transverse myelitis[20] + + + + Proximal > Distal Systemic BL or UL Sudden MRI & Lumbar puncture MRI History of chronic viral or autoimmune disease (e.g. HIV)
Neurosyphilis[21][22] + + - +/- Generalized Systemic BL Insidious MRI & Lumbar puncture CSF VDRL-specifc

CSF FTA-Ab -sensitive[23]

History of unprotected sex or multiple sexual partners.

History of genital ulcer (chancre), diffuse maculopapular rash.

Muscular dystrophy[24] + - - - Proximal > Distal Systemic BL Insidious Genetic testing Muscle biopsy Progressive proximal lower limb weakness with calf pseudohypertrophy in early childhood. Gower sign positive.
Multiple sclerosis exacerbation[25] + + + + Generalized Systemic NL Sudden CSF IgG levels


Clinical assessment and MRI [26] Blurry vision, urinary incontinence, fatigue
Amyotrophic lateral sclerosis[27] + - - - Generalized Systemic BL Insidious Normal LP (to rule out DDx) MRI & LP Patient initially presents with upper motor neuron deficit (spasticity) followed by lower motor neuron deficit (flaccidity).
Inflammatory myopathy[28] + - - - Proximal > Distal Systemic UL or BL Insidious Elevated CK & Aldolase Muscle biopsy Progressive proximal muscle weakness in 3rd to 5th decade of life. With or without skin manifestations.


The U.S. Food Quality Protection Act (FQPA), passed in 1996, designated the United States Environmental Protection Agency (EPA) to conduct a 10 year review process of the health and environmental effects of all pesticides, beginning with the Organophosphates. The process has taken longer than expected, but was recently concluded and eliminated or modified thousands of uses. NYTimes Aug 4, 2006

Many non-governmental and research groups, as well as the EPA's Office of Inspector General, have published concerns that the review did not take into account possible neurotoxic effects on developing fetuses and children, an area of developing research. OIG report. A group of leading EPA scientists sent a letter to the chief administrator, Stephen Johnson, decrying the lack of developmental neurotoxicity data in the review process. EPA Letter EHP article New studies have shown toxicity to developing organisms during certain "critical periods" at doses much lower than those previously suspected to cause harm.[29]

See also


  1. "eMedicine - Toxicity, Organophosphate and Carbamate : Article by Daniel K Nishijima, MD". Retrieved 2007-08-22. 
  2. Rahimi R, Nikfar S, Abdollahi M. Increased morbidity and mortality in acute human organophosphate-poisoned patients treated by oximes: a meta-analysis of clinical trials. Hum Exp Toxicol. 2006 Mar;25(3):157-62. PMID 16634335
  3. Peter JV, Moran JL, Graham P. Oxime therapy and outcomes in human organophosphate poisoning: an evaluation using meta-analytic techniques. Crit Care Med. 2006 Feb;34(2):502-10. Review. PMID 16424734
  4. "Aviation Organophoshate Information Site: Informing crews to the potential of organophosphate exposure due to the contamination of the aircraft air conditioning system.". Retrieved 2007-07-30. 
  5. Purdey M. High-dose exposure to systemic phosmet insecticide modifies the phosphatidylinositol anchor on the prion protein: the origins of new variant transmissible spongiform encephalopathies? Med Hypotheses 1998;50:91-111. PMID 9572563.
  6. "Health and Consumer Protection - Scientific Steering Committee - Outcome of discussions 18". Retrieved 2007-07-30. 
  7. Costa LG (2006). "Current issues in organophosphate toxicology". Clin. Chim. Acta. 366 (1-2): 1–13. PMID 16337171. doi:10.1016/j.cca.2005.10.008. 
  8. Morgan JP, Tulloss TC. The Jake Walk Blues. A toxicologic tragedy mirrored in American popular music. Annals of Internal Medicine. 1976 Dec;85(6):804-8. PMID: 793467.
  9. Jamal GA. "Neurological syndromes of organophosphorus compounds." Adverse Drug React Toxicol Rev. 1997 Aug;16(3):133-70. PMID: 9512762
  10. Abou-Donia MB. "Organophosphorus ester-induced chronic neurotoxicity." Arch Environ Health. 2003 Aug;58(8):484-97. PMID: 15259428
  11. Talukder RK, Sutradhar SR, Rahman KM, Uddin MJ, Akhter H (2011). "Guillian-Barre syndrome.". Mymensingh Med J. 20 (4): 748–56. PMID 22081202. 
  12. Merino-Ramírez MÁ, Bolton CF (2016). "Review of the Diagnostic Challenges of Lambert-Eaton Syndrome Revealed Through Three Case Reports.". Can J Neurol Sci. 43 (5): 635–47. PMID 27412406. doi:10.1017/cjn.2016.268. 
  13. Gilhus NE (2016). "Myasthenia Gravis.". N Engl J Med. 375 (26): 2570–2581. PMID 28029925. doi:10.1056/NEJMra1602678. 
  14. Ozono K (2016). "[Diagnostic criteria for vitamin D-deficient rickets and hypocalcemia-].". Clin Calcium. 26 (2): 215–22. PMID 26813501. doi:CliCa1602215222 . 
  15. Kamanyire R, Karalliedde L (2004). "Organophosphate toxicity and occupational exposure.". Occup Med (Lond). 54 (2): 69–75. PMID 15020723. 
  16. Pecina CA (2012). "Tick paralysis.". Semin Neurol. 32 (5): 531–2. PMID 23677663. doi:10.1055/s-0033-1334474. 
  17. Bane V, Lehane M, Dikshit M, O'Riordan A, Furey A (2014). "Tetrodotoxin: chemistry, toxicity, source, distribution and detection.". Toxins (Basel). 6 (2): 693–755. PMC 3942760Freely accessible. PMID 24566728. doi:10.3390/toxins6020693. 
  18. Kuntzer T, Hirt L, Bogousslavsky J (1996). "[Neuromuscular involvement and cerebrovascular accidents].". Rev Med Suisse Romande. 116 (8): 605–9. PMID 8848683. 
  19. Laffont I, Julia M, Tiffreau V, Yelnik A, Herisson C, Pelissier J (2010). "Aging and sequelae of poliomyelitis.". Ann Phys Rehabil Med. 53 (1): 24–33. PMID 19944665. doi:10.1016/ 
  20. West TW (2013). "Transverse myelitis--a review of the presentation, diagnosis, and initial management.". Discov Med. 16 (88): 167–77. PMID 24099672. 
  21. Liu LL, Zheng WH, Tong ML, Liu GL, Zhang HL, Fu ZG; et al. (2012). "Ischemic stroke as a primary symptom of neurosyphilis among HIV-negative emergency patients.". J Neurol Sci. 317 (1-2): 35–9. PMID 22482824. doi:10.1016/j.jns.2012.03.003. 
  22. Berger JR, Dean D (2014). "Neurosyphilis". Handb Clin Neurol. 121: 1461–72. PMID 24365430. doi:10.1016/B978-0-7020-4088-7.00098-5. 
  23. Ho EL, Marra CM (2012). "Treponemal tests for neurosyphilis--less accurate than what we thought?". Sex Transm Dis. 39 (4): 298–9. PMC 3746559Freely accessible. PMID 22421697. doi:10.1097/OLQ.0b013e31824ee574. 
  24. Falzarano MS, Scotton C, Passarelli C, Ferlini A (2015). "Duchenne Muscular Dystrophy: From Diagnosis to Therapy.". Molecules. 20 (10): 18168–84. PMID 26457695. doi:10.3390/molecules201018168. 
  25. Filippi M, Preziosa P, Rocca MA (2016). "Multiple sclerosis.". Handb Clin Neurol. 135: 399–423. PMID 27432676. doi:10.1016/B978-0-444-53485-9.00020-9. 
  26. Giang DW, Grow VM, Mooney C, Mushlin AI, Goodman AD, Mattson DH; et al. (1994). "Clinical diagnosis of multiple sclerosis. The impact of magnetic resonance imaging and ancillary testing. Rochester-Toronto Magnetic Resonance Study Group.". Arch Neurol. 51 (1): 61–6. PMID 8274111. 
  27. Riva N, Agosta F, Lunetta C, Filippi M, Quattrini A (2016). "Recent advances in amyotrophic lateral sclerosis.". J Neurol. 263 (6): 1241–54. PMC 4893385Freely accessible. PMID 27025851. doi:10.1007/s00415-016-8091-6. 
  28. Michelle EH, Mammen AL (2015). "Myositis Mimics.". Curr Rheumatol Rep. 17 (10): 63. PMID 26290112. doi:10.1007/s11926-015-0541-0. 
  29. Slotkin TA, Levin ED, Seidler FJ. Comparative developmental neurotoxicity of organophosphate insecticides: effects on brain development are separable from systemic toxicity. Environ Health Perspect. 2006 May;114(5):746-51. PMID: 16675431