History

Fact Explanation
Excessive salivation, lacrymation, sweating, nausea, Vomiting, diarrhea, fecal incontinence, abdominal cramps, increased urinary frequency, urinary incontinence These symptoms arise due to the action of acetylcholine on muscarinic receptors at the postganglionic parasympathetic nerve endings. These are seen in the acute cholinergic crisis phase. Organophosphate compounds bind to acetylcholinesterase (AChE) enzyme and inhibits its normal action. As a result there is accumulation of excess acetylcholine (ACh) at the cholinergic nerve endings within the peripheral and central nervous systems, giving rise to the characteristic clinical manifestations that are described in this reference. Restoration of AChE is either by spontaneous rephosphorylation of the enzyme or by new enzyme synthesis.[1][2][4][5][6][7][8][10]
"Runny-nose" (rhinorrhea), difficulty breathing, wheeze, productive cough, tightness in the chest These symptoms occur due to Ach acting on muscrinic receptors at the postganglionic parasympathetic nerve endings. Wheezing and dyspnoea results from bronchorrhoea, bronchospasms and airway narrowing in the acute cholinergic crisis phase. During the intermediate syndrome phase, dyspnoea may result from respiratory muscle weakness/paralysis.[1][2][4][5][7][10]
Incoordination, muscle twitching, muscle weakness, paralysis These symptoms occur due to Ach acting on nicotinic receptors at the neuromuscular junctions in the acute cholinergic crisis phase or in the intermediate syndrome phase. Muscle weakness and paralysis can also present in the organophosphate induced delayed polyneuropathy (OPIDN) phase. In OPIDN phase, weakness initially appears in the distal leg muscles causing foot drop, followed by small muscles of the hands. Later it may extend proximally to even involve the truncal muscles[1][2][4][5][6][10]
Palpitation Arrhythmias can occur in patients with organophosphates poisoning which may be sometimes perceived by the patient as palpitations[1][2][10]
Muscle pain Particularly involves quadriceps and calf muscles. Cause cramping pain. Seen in the OPIDN phase[1][2][3][9]
Paresthesia Paresthesia or the sensation of "pins and needles"/ tingling/prickling is seen in the OPIDN phase[1][2][3][9]
Headache, giddiness, confusion, convulsions These symptoms occur as a result of central nervous system (CNS) toxicity. Confusion, convulsions and even coma and death occur in severe intoxication[1][2][5][6][7][10]
References
  1. MULEY A, SHAH C, LAKHANI J, BAPNA M, MEHTA J. To identify morbidity and mortality predictors in acute organophosphate poisoning. Indian J Crit Care Med [online] 2014 May, 18(5):297-300 [viewed 16 June 2014] Available from: doi:10.4103/0972-5229.132488
  2. SINGH S, SHARMA N. Neurological syndromes following organophosphate poisoning. Neurology India[online] 2000:48(4): 308-13[viewed on 12 June 2014] Available from; http://www.ncbi.nlm.nih.gov/pubmed/11146591
  3. SHETYE JV, SURKAR SM, KARNIK ND, MEHTA AA. Delayed onset neuropathy along with recurrent laryngeal nerve palsy due to organophosphate poisoning and the role of physiotherapy rehabilitation Indian J Crit Care Med [online] 2014 Feb, 18(2):102-104 [viewed 14 June 2014] Available from: doi:10.4103/0972-5229.126082
  4. CHOWDHURY FR, BARI MS, ALAM MJ, RAHMAN MM, BHATTACHARJEE B, QAYYUM JA, MRIDHA MS. Organophosphate poisoning presenting with muscular weakness and abdominal pain- a case report BMC Res Notes [online] :140 [viewed 14 June 2014] Available from: doi:10.1186/1756-0500-7-140
  5. DESFORGES JANE F., KULIG KENNETH. Initial Management of Ingestions of Toxic Substances. N Engl J Med [online] 1992 June, 326(25):1677-1681 [viewed 16 June 2014] Available from: doi:10.1056/NEJM199206183262507
  6. ČOLOVIć MB, KRSTIć DZ, LAZAREVIć-PAšTI TD, BONDžIć AM, VASIć VM. Acetylcholinesterase Inhibitors: Pharmacology and Toxicology Curr Neuropharmacol [online] 2013 May, 11(3):315-335 [viewed 16 June 2014] Available from: doi:10.2174/1570159X11311030006
  7. KUMAR MR, KUMAR GP, BABU PR, KUMAR SS, SUBRAHMANYAM BV, VEERAPRASAD M, RAMMOHAN P, SRINIVAS M, AGRAWAL A. A retrospective analysis of acute organophosphorus poisoning cases admitted to the tertiary care teaching hospital in South India. Ann Afr Med [online] 2014 Apr-Jun, 13(2):71-5 [viewed 16 June 2014] Available from: doi:10.4103/1596-3519.129876
  8. JAYASINGHE SS, PATHIRANA KD. Autonomic Function following Acute Organophosphorus Poisoning: A Cohort Study PLoS One [online] , 7(5):e37987 [viewed 16 June 2014] Available from: doi:10.1371/journal.pone.0037987
  9. VASCONCELLOS LF, LEITE AC, NASCIMENTO OJ. Organophosphate-induced delayed neuropathy: case report. Arq Neuropsiquiatr [online] 2002 Dec, 60(4):1003-7 [viewed 16 June 2014] Available from: http://www.ncbi.nlm.nih.gov/pubmed/12563396
  10. AARDEMA H, MEERTENS JH, LIGTENBERG JJ, PETERS-POLMAN OM, TULLEKEN JE, ZIJLSTRA JG. Organophosphorus pesticide poisoning: cases and developments. Neth J Med [online] 2008 Apr, 66(4):149-53 [viewed 16 June 2014] Available from: http://www.ncbi.nlm.nih.gov/pubmed/18424861

Examination

Fact Explanation
Miosis Miosis or pin point pupils results from muscarinic effects due Ach action at the postganglionic parasympathetic nerve endings[1][3][4][5][6][8]
Dyspnoea Occurs due to respiratory difficulty associated with OP poisoning[1][2][6]
Ronchi Are auscultated when the patient develops bronchospasms and air way narrowing due to muscarinic effects in the acute cholinergic crisis phase[1][3][4]
Crackles Auscultated when there is pulmonary edema in the acute cholinergic crisis phase as a result of increased secretions due muscarinic effects of Ach action at the postganglionic parasympathetic nerve endings[1][3][7]
Bradycardia/ tachycardia Depending on the balance between the nicotinic and muscrinic effects, patient may develop tachycardia due to nicotinic actions or bradycardia due to muscarinic actions[1][3][6][8]
Hypotension/ hypertension Depending on the balance between the nicotinic and muscrinic effects, patient may develop hypertension due to nicotinic actions or hypotension due to muscarinic actions[1][3][6][8]
Muscle fasciculation Is a reliable sign of poisoning.Occurs in the acute cholinergic crisis phase from nicotinic effects due to Ach action at the neuromuscular junctions[1][2][3][4][5][8]
Reduced muscle power Seen in the acute cholinergic crisis phaseor in the intermediate syndrome phase or in OPIDN[1][2][3]
Cranial nerve palsy Occurs due to nicotinic effects of Ach acting at the neromuscular junction[1]
Ataxia Results from CNS toxicity[1][3]
Disorientation Results from CNS toxicity[1][3][8]
Absent deep tendon reflexes Seen in the OPIDN phase[1][2][3]
References
  1. DESFORGES JANE F., KULIG KENNETH. Initial Management of Ingestions of Toxic Substances. N Engl J Med [online] 1992 June, 326(25):1677-1681 [viewed 16 June 2014] Available from: doi:10.1056/NEJM199206183262507
  2. SHETYE JV, SURKAR SM, KARNIK ND, MEHTA AA. Delayed onset neuropathy along with recurrent laryngeal nerve palsy due to organophosphate poisoning and the role of physiotherapy rehabilitation Indian J Crit Care Med [online] 2014 Feb, 18(2):102-104 [viewed 14 June 2014] Available from: doi:10.4103/0972-5229.126082
  3. SINGH S, SHARMA N. Neurological syndromes following organophosphate poisoning. Neurology India[online] 2000:48(4): 308-13[viewed on 12 June 2014] Available from; http://www.ncbi.nlm.nih.gov/pubmed/11146591
  4. DESFORGES JANE F., KULIG KENNETH. Initial Management of Ingestions of Toxic Substances. N Engl J Med [online] 1992 June, 326(25):1677-1681 [viewed 16 June 2014] Available from: doi:10.1056/NEJM199206183262507
  5. ČOLOVIć MB, KRSTIć DZ, LAZAREVIć-PAšTI TD, BONDžIć AM, VASIć VM. Acetylcholinesterase Inhibitors: Pharmacology and Toxicology Curr Neuropharmacol [online] 2013 May, 11(3):315-335 [viewed 16 June 2014] Available from: doi:10.2174/1570159X11311030006
  6. DAVIES JO, EDDLESTON M, BUCKLEY NA. Predicting Outcome in Acute Organophosphorus Poisoning with a Poison Severity Score or the Glasgow Coma Scale QJM [online] 2008 May, 101(5):371-379 [viewed 16 June 2014] Available from: doi:10.1093/qjmed/hcn014
  7. VASCONCELLOS LF, LEITE AC, NASCIMENTO OJ. Organophosphate-induced delayed neuropathy: case report. Arq Neuropsiquiatr [online] 2002 Dec, 60(4):1003-7 [viewed 16 June 2014] Available from: http://www.ncbi.nlm.nih.gov/pubmed/12563396
  8. AARDEMA H, MEERTENS JH, LIGTENBERG JJ, PETERS-POLMAN OM, TULLEKEN JE, ZIJLSTRA JG. Organophosphorus pesticide poisoning: cases and developments. Neth J Med [online] 2008 Apr, 66(4):149-53 [viewed 16 June 2014] Available from: http://www.ncbi.nlm.nih.gov/pubmed/18424861

Differential Diagnoses

Fact Explanation
Anticholinesterase drug poisoning Drug such as neostigmine, pyridostigmine, edrophonium block action of acetylcholinesterase and produce muscarinic and nicotinic side effects[1][3]
Carbamate poisoning Produce clinical findings similar to those seen in OP poisoning[1][3]
Mushroom poisoning Poisoning with some mushroom species (e.g. species of genus Clitocybe) can produce features such as gastrointestinal, disturbance, miosis, hypersecretion etc. similar to seen in OP poisoning.[1][2]
Acute gastroenteritis Acute gastroenteritis may present with symptoms such as nausea, vomiting, diarrhea, cramping abdominal pain.[4] These symptoms are also seen in patients with OP poisoning.
References
  1. DESFORGES JANE F., KULIG KENNETH. Initial Management of Ingestions of Toxic Substances. N Engl J Med [online] 1992 June, 326(25):1677-1681 [viewed 16 June 2014] Available from: doi:10.1056/NEJM199206183262507
  2. LIMA AD, COSTA FORTES R, CARVALHO GARBI NOVAES MR, PERCáRIO S. Poisonous mushrooms: a review of the most common intoxications. Nutr Hosp [online] 2012 Mar-Apr, 27(2):402-8 [viewed 16 June 2014] Available from: doi:10.1590/S0212-16112012000200009
  3. ČOLOVIć MB, KRSTIć DZ, LAZAREVIć-PAšTI TD, BONDžIć AM, VASIć VM. Acetylcholinesterase Inhibitors: Pharmacology and Toxicology Curr Neuropharmacol [online] 2013 May, 11(3):315-335 [viewed 16 June 2014] Available from: doi:10.2174/1570159X11311030006
  4. EZEONWU B, IBENEME C, ANEKE F, OGUONU T. Clinical features of acute gastroenteritis in children at university of Nigeria teaching hospital, ituku-ozalla, enugu. Ann Med Health Sci Res [online] 2013 Jul, 3(3):361-4 [viewed 16 June 2014] Available from: doi:10.4103/2141-9248.117948

Investigations - for Diagnosis

Fact Explanation
Plasma (pseudo) cholinesterase activity (PChE) The diagnosis of OP poisoning is based on the characteristic clinical findings mentioned above. Treatment should not be delayed until investigations are done. PChE is an acute phase protein synthesized by the liver and released in to the blood circulation. This is also found in brain white matter. This is a pseudo or non-specific cholinesterase because it hydrolyze not only choline but also aliphatic esters. It hydrolyzes acetylcholine slowly but hydrolyzes butyrylcholine more quickly. Reduced activity(<80% of the lower limit for normal range) suggests OP poisoning[1][2][3][4][5]
Red blood cell acetylcholinesterase activity Reduced activity confirms diagnosis of OP poisoning. Extent of depression of activity crudely correlates with severity of poisoning. Can be used to monitor the effectiveness of pralidoxime treatment. This enzyme is also found in brain grey matter and nerve endings. It is specific for acetylcholine and hydrolyzes acetylcholine readily compared to pseudo cholinesterase[1][2][3][4]
References
  1. SINGH S, SHARMA N. Neurological syndromes following organophosphate poisoning. Neurology India[online] 2000:48(4): 308-13[viewed on 12 June 2014] Available from; http://www.ncbi.nlm.nih.gov/pubmed/11146591
  2. CHAUDHARY SC, SINGH K, SAWLANI KK, JAIN N, VAISH AK, ATAM V, PATEL ML, AGARWAL A. Prognostic Significance of Estimation of Pseudocholinesterase Activity and Role of Pralidoxime Therapy in Organophosphorous Poisoning Toxicol Int [online] 2013, 20(3):214-217 [viewed 16 June 2014] Available from: doi:10.4103/0971-6580.121669
  3. HUNTER JM, NAIR VP. Anticholinesterases and anticholinergic drugs. Oxford Journals. Contin Educ Anaesth Crit Care Pain [online] (2004) 4 (5): 164-168 [viewed on 16 June 2014] Available from; http://ceaccp.oxfordjournals.org/content/4/5/164.full
  4. ČOLOVIć MB, KRSTIć DZ, LAZAREVIć-PAšTI TD, BONDžIć AM, VASIć VM. Acetylcholinesterase Inhibitors: Pharmacology and Toxicology Curr Neuropharmacol [online] 2013 May, 11(3):315-335 [viewed 16 June 2014] Available from: doi:10.2174/1570159X11311030006
  5. MANU MS, PRASHANT V, AKILA P, SUMA MN, BASAVANAGOWDAPPA H. A Retrospective Analysis of Serial Measurement of Serum Cholinesterase in Acute Poisoning with Organophosphate Compounds Toxicol Int [online] 2012, 19(3):255-259 [viewed 16 June 2014] Available from: doi:10.4103/0971-6580.103662

Investigations - Fitness for Management

Fact Explanation
Serum electrolytes Done to assess baseline renal function as OP poisoning is associated with acute renal failure[1][2][3]
Serum creatinine Done to assess baseline renal function as OP poisoning is associated with acute renal failure[1][2][3]
Electrocardiogram (ECG) Patients with OP poisoning can develop arrhythmia. ECG changes such as QT prolongation, ST elevation, ventricular tachycardia, low amplitude T wave etc are seen in these patients[2][3]
References
  1. AREFI M, TAGHADDOSINEJAD F, SALAMATY P, SOROOSH D, ASHRAF H, EBRAHIMI M. Renal Failure Prevalence in Poisoned Patients Nephrourol Mon [online] , 6(2):e11910 [viewed 12 June 2014] Available from: doi:10.5812/numonthly.11910
  2. SINGH S, SHARMA N. Neurological syndromes following organophosphate poisoning. Neurology India[online] 2000:48(4): 308-13[viewed on 12 June 2014] Available from; http://www.ncbi.nlm.nih.gov/pubmed/11146591
  3. DESFORGES JANE F., KULIG KENNETH. Initial Management of Ingestions of Toxic Substances. N Engl J Med [online] 1992 June, 326(25):1677-1681 [viewed 16 June 2014] Available from: doi:10.1056/NEJM199206183262507

Investigations - Followup

Fact Explanation
Nerve-conduction studies Can be done in patients suspected to have organophosphate-induced delayed neuropathy. These studies will show sensory-motor polyneuropathy in case of severe OP poisoning[1][3]
Electromyography Also done for patients with organophosphate-induced delayed neuropathy, which will show denervation changes in muscles with distal axonal degeneration in the lower extremities [1][2]
References
  1. VASCONCELLOS LF, LEITE AC, NASCIMENTO OJ. Organophosphate-induced delayed neuropathy: case report. Arq Neuropsiquiatr [online] 2002 Dec, 60(4):1003-7 [viewed 16 June 2014] Available from: http://www.ncbi.nlm.nih.gov/pubmed/12563396
  2. GENEL F, ARSLANOğLU S, URAN N, DOğAN M, ATLIHAN F. Late-onset distal polyneuropathy due to acute organophosphate intoxication case report. Turk J Pediatr [online] 2003 Jan-Mar, 45(1):67-70 [viewed 16 June 2014] Available from: http://www.ncbi.nlm.nih.gov/pubmed/12718377
  3. MORETTO A, LOTTI M. Poisoning by organophosphorus insecticides and sensory neuropathy. J Neurol Neurosurg Psychiatry [online] 1998 Apr, 64(4):463-8 [viewed 16 June 2014] Available from: http://www.ncbi.nlm.nih.gov/pubmed/9576536

Management - General Measures

Fact Explanation
Emergency management Assess and secure the airway, breathing and circulation. Once there is no acute threat to life take a relevant brief history and do relevant examination to recognize the potential cause for the patient's presentation[5][7]
Oxygen therapy and assissted ventilation Is given to patients with respiratory failure[1][2][4][5][7]
Management of seizures Benzodiazepines such as diazepam is given via intravenous route if patient develops seizures in order to control seizures. Benzodiazepines also reduce agitation[4][5][7]
Gastric aspiration or lavage Useful if done within 1-2 hours from ingestion. Done in the presence of a doctor and in a patient with a protected airway. Should not be done if the patient develops seizures, uncooperative or clinically unstable[4][5][7]
Activated charcoal Once the patient is stabilized, activate charcoal 50-100 g in 200 mL of water is given orally or via nasogastric tube at the end of gastric lavage. This reduces absorption of the ingested OP in to the circulation through the gut[4][5][7]
Temporary cardiac pacing Should be considered to terminate ventricular tachycardia with QT prolongation[4]
Psychiatric referral Should be done if the patient committed deliberate self harm/had suicide intent or if he/she is a known patient with a psychiatric disorder. This will help to reduce recurrence of similar incidents[5][6]
Physiotherapy These patients require physiotherapy to prevent further neuromuscular morbidity and deformity. Chest physiotherapy will be required to prevent accumulation of pulmonary secretions and to prevent development of orthostatic pneumonia[3][4][8]
References
  1. KUMAR MR, KUMAR GP, BABU PR, KUMAR SS, SUBRAHMANYAM BV, VEERAPRASAD M, RAMMOHAN P, SRINIVAS M, AGRAWAL A. A retrospective analysis of acute organophosphorus poisoning cases admitted to the tertiary care teaching hospital in South India. Ann Afr Med [online] 2014 Apr-Jun, 13(2):71-5 [viewed 12 June 2014] Available from: doi:10.4103/1596-3519.129876
  2. AHMED SM, DAS B, NADEEM A, SAMAL RK. Survival pattern in patients with acute organophosphate poisoning on mechanical ventilation: A retrospective intensive care unit-based study in a tertiary care teaching hospital Indian J Anaesth [online] 2014, 58(1):11-17 [viewed 14 June 2014] Available from: doi:10.4103/0019-5049.126780
  3. SHETYE JV, SURKAR SM, KARNIK ND, MEHTA AA. Delayed onset neuropathy along with recurrent laryngeal nerve palsy due to organophosphate poisoning and the role of physiotherapy rehabilitation Indian J Crit Care Med [online] 2014 Feb, 18(2):102-104 [viewed 14 June 2014] Available from: doi:10.4103/0972-5229.126082
  4. SINGH S, SHARMA N. Neurological syndromes following organophosphate poisoning. Neurology India[online] 2000:48(4): 308-13[viewed on 12 June 2014] Available from; http://www.ncbi.nlm.nih.gov/pubmed/11146591
  5. ILLINGWORTH RN, GRAHAM CA, HOGG K. Oxford Handbook of Emergency Medicine. Oxford University Press, 2012;180-185, 206
  6. EDDLESTON M, PHILLIPS MR. Self poisoning with pesticides BMJ [online] 2004 Jan 3, 328(7430):42-44 [viewed 16 June 2014] Available from: doi:10.1136/bmj.328.7430.42
  7. DESFORGES JANE F., KULIG KENNETH. Initial Management of Ingestions of Toxic Substances. N Engl J Med [online] 1992 June, 326(25):1677-1681 [viewed 16 June 2014] Available from: doi:10.1056/NEJM199206183262507
  8. GENEL F, ARSLANOğLU S, URAN N, DOğAN M, ATLIHAN F. Late-onset distal polyneuropathy due to acute organophosphate intoxication case report. Turk J Pediatr [online] 2003 Jan-Mar, 45(1):67-70 [viewed 16 June 2014] Available from: http://www.ncbi.nlm.nih.gov/pubmed/12718377

Management - Specific Treatments

Fact Explanation
Atropine Is an antidote given to counter act the muscarinic effects of Ach. Atropine is given as an intravenous loading dose followed by an infusion guided by the clinical improvement of the patient. The clinical parameters that indicate improvement are the presence of clear lungs on auscultation, heart rate between 80-100 beats/min and systolic blood pressure >80 mmHg. Patient should be monitored at regular intervals for signs of atropine toxicity. If toxicity develops atropine should be stopped, allow the signs of toxicity to pass, then restart atropine at a lower dose[1][2][3][4][5]
Pralidoxime An initial loading dose followed by continuous infusion of is given until clinical recover or for 7 days. Less severely poisoned patients are given intermittent doses of pralidoxime by slow intravenous bolus[1][2][3][4][5][6]
References
  1. KUMAR MR, KUMAR GP, BABU PR, KUMAR SS, SUBRAHMANYAM BV, VEERAPRASAD M, RAMMOHAN P, SRINIVAS M, AGRAWAL A. A retrospective analysis of acute organophosphorus poisoning cases admitted to the tertiary care teaching hospital in South India. Ann Afr Med [online] 2014 Apr-Jun, 13(2):71-5 [viewed 12 June 2014] Available from: doi:10.4103/1596-3519.129876
  2. AHMED SM, DAS B, NADEEM A, SAMAL RK. Survival pattern in patients with acute organophosphate poisoning on mechanical ventilation: A retrospective intensive care unit-based study in a tertiary care teaching hospital Indian J Anaesth [online] 2014, 58(1):11-17 [viewed 14 June 2014] Available from: doi:10.4103/0019-5049.126780
  3. Fernando R. Management of poisoning. Fourth edition. Medical Defence Organization Sri Lanka;2011;38- 45
  4. ILLINGWORTH RN, GRAHAM CA, HOGG K. Oxford Handbook of Emergency Medicine. Oxford University Press, 2012;180-185, 206
  5. DESFORGES JANE F., KULIG KENNETH. Initial Management of Ingestions of Toxic Substances. N Engl J Med [online] 1992 June, 326(25):1677-1681 [viewed 16 June 2014] Available from: doi:10.1056/NEJM199206183262507
  6. EDDLESTON M, SZINICZ L, EYER P, BUCKLEY N. Oximes in Acute Organophosphate Pesticide Poisoning: a Systematic Review of Clinical Trials QJM [online] 2002 May, 95(5):275-283 [viewed 16 June 2014] Available from: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1475922