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Table of Contents
GUEST EDITORIAL
Year : 2019  |  Volume : 7  |  Issue : 4  |  Page : 100-102

Organophosphorus compound poisoning: Hoping against hope to reduce morbidity and mortality


Emeritus Professor of Medicine, Department of Medicine, P. E. S. Institute of Medical Sciences and Research, Chittoor, Andhra Pradesh, India

Date of Web Publication18-Oct-2019

Correspondence Address:
Dr. Y J Vishewshwara Reddy
PES Institute of Medical Sciences and Research, Kuppam, Chittoor - 517 425, Andhra Pradesh
India
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/AJIM.AJIM_58_19

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How to cite this article:
Reddy Y J. Organophosphorus compound poisoning: Hoping against hope to reduce morbidity and mortality. APIK J Int Med 2019;7:100-2

How to cite this URL:
Reddy Y J. Organophosphorus compound poisoning: Hoping against hope to reduce morbidity and mortality. APIK J Int Med [serial online] 2019 [cited 2019 Dec 6];7:100-2. Available from: http://www.ajim.in/text.asp?2019/7/4/100/269569



Poisoning with organophosphorus (OP) pesticides is a significant global health problem and is the principle cause of death through self-poisoning in India.[1] According to the National Crime Records Bureau, India, every 5 min, a person commits suicide and 7 attempt to kill themselves, forming about 100,000 death per year. Majority of the victims belonged to the age group of 14–34 years and organophosphorus compound (OPC) is the most common agent used for suicide purpose.


  Cholinesterase Level in Organophosphorus Compound Top


Signs and symptoms appear, when the cholinesterase level drops to 30% of its normal activity. The fatal period is usually within 24 h in untreated cases and within 10 days if treatment is not successful.[2] Studies suggest that red blood cell acetylcholinesterase (AChE) is a good marker of synaptic function and atropine needs, in patients poisoned with OP, and is therefore probably a good marker of severity.[3] The association between serum cholinesterase level and clinical outcome in patients with OPC poisoning, 1-year hospital-based longitudinal study published in this issue, confirms the current understanding of the outcome of the management.


  Aging of Organophosphorus Compound Top


Aging seems to take place much more quickly after poisoning with atypical OP, such as profenofos, that have neither two methyl groups nor two ethyl groups. The half-life of aging seems to be much less than 1 h; thus, oximes are completely ineffective if the patient presents more than an hour or two after ingestion. OPs are different with regard to toxicity, kinetics, clinical syndromes, and response to antidotes.

Practical difficulties exist in carrying out randomized controlled trials (RCTs) with regard to ethical issues, estimation of poison/cholinesterase, identical cases for comparison, facilities, and medicolegal aspects.


  Management of Acute Organophosphorus Pesticide Poisoning Top


Medical management is difficult, with case fatality generally more than 15%. Half a century, after first use, we still do not know how the core treatments, atropine, oximes, and diazepam, should best be given.[3]


  Stomach Wash Top


Gastric decontamination should be considered only after the patient has been fully resuscitated and stabilized. Lavage should probably only be considered for patients who present soon after ingestion of a substantial amount of toxic pesticide who are intubated or conscious and willing to cooperate.[3]


  Mode of Administration of Atropine Top


A study from South India recorded benefit from an infusion of atropine compared with repeated bolus doses. The infusions could reduce fluctuations in blood atropine concentration, reducing the need for frequent patient observation.[4] There are 38 texts with 31 different recommendations! Go by Indian experience and guidelines for better results. Titrate atropine infusion to a level of slight excess maintain for 3–5 days and taper slowly. In my personal experience at PESIMSR, Kuppam, of more than a decade where good intensive care unit (ICU) facilities are available, nobody died of atropine excess, and a few patients died because of not receiving enough atropine.


  Ventilator Support is Required to Save the Patients in Severe Poisoning Top


Monitor and review respiratory function. Intubate and ventilate patients if tidal volume is below 5 mL/kg or vital capacity is below 15 mL/kg, or if they have apneic spells, or PaO2 is <8 kPa (60 mmHg) or F1O2 is <8 kPa (60 mm Hg) on F1O2 of more than 60%. Peradeniya score of >7 is an indication for ventilation.[5],[6]


  Benzodiazepines Top


Acutely agitated patients will benefit from treatment with diazepam. Diazepam is first-line therapy for seizures.[3]


  Diazepam Top


Diazepam is routinely used in OP poisoning for the treatment of agitated delirium and seizures. It reduces respiratory failure (rats) and cognitive deficit (primates). It is postulated that “uncoordinated stimulation of the respiratory center decreases phrenic nerve output.”

Is there a role for peripheral benzodiazepine receptor? Further research is required.


  Role of Oximes Top


There is no evidence that oximes are useful in the treatment for organophosphate pesticide poisoning.[7] Two published randomized control studies (RCTs) and one abstract RCT have revealed insufficient evidence whether oximes are harmful or beneficial.[8] Two published RCTs and five controlled trials have shown that oximes are either ineffective or harmful.[9]

Six clinical trials have shown that oximes are not effective and can be dangerous.[10]


  New Antidotes, New Therapies in the Pipeline Top


Protect AChE with cholinesterase inhibitors. Sacrifice supply AChE with synthetic and natural fresh frozen plasma (FFP). Reduce acetylcholine (Ach) release using magnesium and clonidine. Protect receptor with neuromuscular blockers. Reduce OP load by increasing hydrolase capacity and by multiple mechanisms maybe it is possible to alter pH.


  Organophosphates and pH Top


Organophosphate hydrolase is pH sensitive. Binding of pralidoxime is pH sensitive.

The level of acetyl cholinesterase, aging of OP-AChe complex, and reactivation determine the outcome of poisoning.


  Other Therapies Top


Magnesium sulfate (MgSO4) blocks ligand-gated calcium channels, resulting in reduced Ach release from presynaptic terminals, thus improving function at neuromuscular junctions and reduced central nervous system over stimulation mediated via N-methyl-D-aspartate receptor activation.

Magnesium reduces Ach release by blocking presynaptic calcium channels in central and peripheral nervous system. Magnesium decreases toxicity in animal models. Continuous MgSO4 infusion, 16 g over 24 h could be tried.[11]


  Usefulness of Clonidine Top


The alpha 2-adrenergic receptor agonist clonidine also reduces Ach synthesis and release from presynaptic terminals. Animal studies show benefit of clonidine treatment, especially in combination with atropine, but effects in human beings are unknown.[12]


  Hemodialysis and Hemofiltration Top


The roles of hemodialysis and hemofiltration are not yet clear; however, a recent nonrandomized controlled study in China suggested a benefit of hemofiltration after poisoning with dichlorvos. RCT to establish good evidence-based treatment guidelines are required.[13]


  Use of Butyrylcholinesterase Top


Turkish doctors have reported the use of butyrylcholinesterase in FFP to treat poisoned patients and recorded benefit.[14]

Daily reducing dose of FFP therapy for 3 consecutive days (4 units 1st day, 3 units 2nd day, and 2 units 3rd day) has beneficial effect in acute OP poisoning by increasing serum cholinesterase enzymes in blood with reduction in total dose of atropine consumption per day. It also reduces the ICU stay with zero mortality in OP poisoning.”

FFP acts by neutralizing toxins released into circulation by redistribution from adipose tissue.[15]

The causes of death among poisoned patients despite ICU management include too much of OPC consumption, too late arrival to casualty, patients on arrival in coma/convulsions/pulmonary edema, aging of OP compound and the type of compound ingested, not doing gastric decontamination by the first contact doctor and often not giving enough Atropine.

Morbidity and mortality due to OP compound poisoning is directly proportional to the age, severity of poisoning, and duration of mechanical ventilation and inversely proportional to serum cholinesterase levels.


  Prevention Top


“Government authorities should be encouraged to control OP product licensing, manufacture, storage, import, methods of use and delivery, food contamination, and disposal.”



 
  References Top

1.
Yatendra S, Joshi SC, Singh M, Joshi A, Kumar J. Organosphosphorus poisoning: An overview. Int J Health Sci Res 2014;4:245-57.  Back to cited text no. 1
    
2.
Ahmad M, Rahman F, Ashrafuzzaman M, Chowdhury D, Ali M. Overview of organophosphorus compound poisoning in Bangladesh and medico-legal aspects related to fatal cases. J Armed Forces Med Coll Bangladesh 2009;5:41-5.  Back to cited text no. 2
    
3.
Eddleston M, Buckley NA, Eyer P, Dawson AH. Management of acute organophosphorus pesticide poisoning. Lancet 2008;371:597-607.  Back to cited text no. 3
    
4.
Sundaray NK, Ratheesh Kumar J. Organophosphorus poisoning: Current management guidelines. Med Update 2010;20:420-5.  Back to cited text no. 4
    
5.
Vernekar PV, Shivaraj K. Peradeniya organophosphorus poisoning scale (POP) as a predictor of respiratory failure and mortality in organophosphorus poisoning. Sch J Appl Med Sci 2017;5:1841-4.  Back to cited text no. 5
    
6.
Shabari Girish T, Kalyan B, Visweswara Reddy YJ. To assess the severity of organophosphorus compound poisoning clinically by using peradeniya score. Indian J Appl Res 2016;6:617-9.  Back to cited text no. 6
    
7.
Buckley NA, Eddleston M, Li Y, Bevan M, Robertson J. Oximes for acute organophosphate pesticide poisoning. Cochrane Database Syst Rev 2011;(2):CD005085. doi: 10.1002/14651858.CD005085.pub2.  Back to cited text no. 7
    
8.
Buckley NA, Eddleston M, Szinicz L. Oximes for acute organophosphate pesticide poisoning. Cochrane Database Syst Rev 2005;(1):CD005085.  Back to cited text no. 8
    
9.
Peter JV, Moran JL, Graham P. Oxime therapy and outcomes in human organophosphate poisoning: An evaluation using meta-analytic techniques. Crit Care Med 2006;34:502-10.  Back to cited text no. 9
    
10.
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;25:157-62.  Back to cited text no. 10
    
11.
Pajoumand A, Shadnia S, Rezaie A, Abdi M, Abdollahi M. Benefits of magnesium sulfate in the management of acute human poisoning by organophosphorus insecticides. Hum Exp Toxicol 2004;23:565-9.  Back to cited text no. 11
    
12.
Liu WF. A symptomatological assessment of organophosphate-induced lethality in mice: Comparison of atropine and clonidine protection. Toxicol Lett 1991;56:19-32.  Back to cited text no. 12
    
13.
Peng A, Meng FQ, Sun LF, Ji ZS, Li YH. Therapeutic efficacy of charcoal hemoperfusion in patients with acute severe dichlorvos poisoning. Acta Pharmacol Sin 2004;25:15-21.  Back to cited text no. 13
    
14.
Güven M, Sungur M, Eser B, Sari I, Altuntaş F. The effects of fresh frozen plasma on cholinesterase levels and outcomes in patients with organophosphate poisoning. J Toxicol Clin Toxicol 2004;42:617-23.  Back to cited text no. 14
    
15.
Dayananda VP, Bhaskara B, Pateel GN. A study of effectiveness of fresh frozen plasma in organophosphorous compound poisoning in reducing length of intensive care unit stay and in reducing need for tracheostomy. Anesth Essays Res 2016;10:268-72.  Back to cited text no. 15
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  In this article
Cholinesterase L...
Aging of Organop...
Management of Ac...
Stomach Wash
Mode of Administ...
Ventilator Suppo...
Benzodiazepines
Diazepam
Role of Oximes
New Antidotes, N...
Organophosphates...
Other Therapies
Usefulness of Cl...
Hemodialysis and...
Use of Butyrylch...
Prevention
References

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