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The spectrum of intermediate syndrome following acute organophosphorus poisoning: a retrospective cohort study from a teaching Hospital of Chhattisgarh.

INTRODUCTION: Organophosphorus compounds are the commonest pesticides used for agricultural purposes in India. Being economical & readily available, these compounds are a household commodity. Therefore, they are incriminated as suicidal poison in cases of crop failure or sociocultural disharmony. Nowadays, newer varieties of pesticides that have come into the market are often a mixture of conventionally known agents, differing in mode of action & their antagonism, resulting in enhanced morbidity & mortality. WHO estimated 3 million cases of poisoning and 2.5 million deaths worldwide annually. (1) Chemically, pesticides can be organo phosphorus compounds, organo chlorines, carbamates & pyrethenoids, which produce varied clinical manifestations, differing in severity & management protocol.

Organophosphorus poisoning presents in 3 well defined clinical phases:

1. Acute cholinergic crisis.

2. Intermediate syndrome.

3. Organophosphorus induced delayed neuropathy (OPIDN).

Acute Cholinergic Crisis: Occurs immediately after the ingestion of poison. Mainly the muscarinic symptoms predominate, like nausea, vomiting, diarrhea, urinary incontinence, miosis, salivation, lacrimation, bronchorrhea, bradycardia and hypotension etc. Nicotinic symptoms like fasciculations, muscle-weakness even muscle paralysis can occur; CNS symptoms include dizziness, confusion and coma.

Intermediate Syndrome- Occurs within 48-96 hrs. After ingesting organo-phosphorus insecticide. Wadia in 1974 called it "Type II paralysis". (2) Senanayake in 1987 coined the term "Intermediate syndrome" because it occurs after the acute phase & before OPIDN. It is characterized by respiratory difficulty, weakness of proximal limb muscles, developing 2-3 days after ingestion of poison, difficulty in shoulder abduction & hip flexion, inability to flex the neck & ultimately respiratory paralysis. Motor cranial nerves--III, IV & X are usually involved with no sensory nerve involvement. Recovery is in reverse order. (3)

OPIDN- (Organophosphorus Poisoning Induced Delayed Neuropathy): develops 2-3 weeks later. Predominantly, the motor neuropathy, manifesting primarily as numbness and weakness of lower extremities with progressive ascending weakness of limb muscles occurs. OPIDN may persist for months to years. (3)

MATERIAL & METHODS: In this retrospective study of one year duration, a total of 720 cases of acute poisoning, admitted in ICU of a teaching hospital were included. Of these, 682 patients had the history of ingestion of organo-phosphorus poisoning and among total cases, 64 patients went into intermediate syndrome during the course of treatment. Clearance was obtained from the hospital ethical committee. All data regarding incidence, age, sex, type of compound, signs and symptoms, outcome etc. were collected from the medical record department of our hospital.

The data were analyzed following SPSS i.e. statistical package of social sciences 11.5 version. Suspected patients of organophosphorus poisoning with a particular smell of organophosphorus compound on naso-gastric suction, or insecticide containers brought by the relatives with strong suspicion were included in the study.

Exclusion criteria employed were, unconscious patient with history of fever, past history of epilepsy or weakness of muscles without history of poison ingestion. Diagnosis of Intermediate syndrome was made in patients, who developed muscle weakness, inability to flex shoulders, hips, proximal limb and neck after becoming conscious following acute phase of poisoning.

RESULTS: In a study period of one year, a total of 684 cases of acute poisoning were analysed.64 cases were diagnosed to have intermediate syndrome. M: F ratio was found to be 8:10. Maximum number of patients (56.25%) belonged to the age group of 21-30 yrs. The Organo-phosphorus compound mostly predisposing to intermediate syndrome was, Fenthion (35%). In all 64 cases, incidence of respiratory muscle weakness & shoulder muscle paresis was 100%.

These patients required respiratory support, atropine & pralidoxime medication with continuous monitoring apart from other supportive measures. Average recovery time was between 4-30 days, while the case fatality rate was 18%. The important risk factors for intermediate syndrome were dose of poison ingested, or respiratory muscle paralysis developing 24 to 96 hours after taking the insecticide.

The predictors of outcome of intermediate syndrome can be standard neurological tests for function of the extra-ocular, facial, neck, flexor and proximal limb muscles. Significant muscle weakness in at least 3 of these muscle groups observed 24 hours after organo-phosphorus poisoning is diagnostic of classical intermediate syndrome. Electrophysiological measurements are more useful in predicting progression rather than recovery. Further research into this mechanism is further required.

DISCUSSION: Organo phosphorus poisoning is the commonest type of self- poisoning presenting and admitted in ICU in our set-up. WHO estimated it to be 3 million cases of poisoning worldwide, while it kills an estimated 2, 50, 000 people every year. (1) Organophosphorus compounds phosphorylates the esteratic site of the enzyme cholinesterase (ACHE), due which, it is unable to hydrolyse acetylcholine. (4) This leads to accumulation of huge amount of acetylcholine at synapses causing immediate cholinergic symptoms. Overstimulation of nicotinic cholinergic receptors at neuromuscular junction results in depolarization blockade.

The resultant clinical features are muscle fasciculations & followed by generalized muscle weakness. There is another specific pattern of muscle weakness- first of proximal limbs, followed by neck muscles, muscles innervated by cranial nerves, accessory respiratory muscles & diaphragm. Wadia et al in 1974 first reported it as type II paralysis following OP poisoning. (2) It was termed as "intermediate syndrome "(IMS) by Senanayake & Karalliede in 1987. (3)

Organophosphorus compounds causing IMS include chlorpiriphos, diazinon, diamethoate, ethyl parathion, fenthion, malathion, methamidophos and parathion. (5) Not all organophosphorus compounds produce IMS. Identifying the severity of OP poisoning is more significant than the specific compound in determining the development of IMS. (6) Onset of IMS is within 1 to 4 days after ingestion. It lasts for 2-3 weeks. (3) In our case series it took 4-30 days to recover. The exact pathophysiology underlying the development of IMS is still unclear.

Necrotizing myopathy or muscle injury, earlier thought as the probable cause, fails to explain the clinical scenario. (5, 6, 7) Electromyography & repetitive nerve stimulation have shown IMS might be caused due to a combination of pre & post synaptic impairment of neuromuscular transmission at junction. (5, 6) In our study, all 64 patients presented with respiratory & proximal muscle weakness. Infact, it is difficult to wean such patient off the ventilator, even when the cholinergic symptoms are well controlled. (8, 9) 14 patients (87.5%) had difficulty in lifting their neck. Cranial N palsy was not noted in any of our patients.

Earlier, it was thought early & adequate oxime therapy may prevent the development of IMS. (10, 11) But subsequent studies have failed to support it or prove conclusively, the merits of oxime therapy in managing organophosphorus insecticide poisoning (12-15)

Close observation of the patients for ventilatory & supportive care after the cholinergic crisis is over, remains the cornerstone treatment of this syndrome. Extubation of E T tube should be considered with precaution. Incidence of IMS is 7-60% worldwide. (5, 6, 14)

In our study the survival was 82% & mortality 18%. In this retrospective study, we have focused on the incidence, clinical presentation & outcome of patient with IMS syndrome so that early recognition & prompt treatment can save lives of patients of organo-phosphorus insecticide poisoning, in our area. Our limitations being we could not do electrophysiological studies on our patients.

DOI: 10.14260/jemds/2014/2629


(1.) World Health Organization. The Impact of Pesticides on Health: Preventing intentional and Unintentional Deaths from Pesticide Poisoning. Available at: health/ prevention/suicide/en/ PesticidesHealth2.pdf [Date accessed: March 15, 2007].

(2.) Wadia RS, Sadgopalan C, Amin RS, Sardesai HV. Neurological manifestation of Poisoning. Journal of N eurology & Psychiatry.1974:37:841-7.

(3.) Senanayke N, Karalliede L. Neurotoxic effects of OP insecticides: An intermediate syndrome. New England Journal of Medicine.1987:316; 7613.

(4.) Wadia RS. Treatment of Organophosphate Poisoning. Indian J Crit Care Med [cited 2009 Feb 14]; 7:85-7.

(5.) HeF, XuH, Qin F, Xu L, Huang J, He X. Intermediate Syndrome following acute organophosphorus poisoning, an analysis of 21 cases. Hum Exp Toxicol 1998; 17: 40-5.

(6.) Poojara L, Vasudevan D, Arun Kumar, Kamat V. Organophosphate poisoning: diagnosis of intermediate syndrome. Indian Journal of Critical Care Medicine 2003; 7:94-102.

(7.) John M, Oomen A, Zacharich A. Muscle injury in OP Poisoning & its role in the development of Intermediate Syndrome. Neurotoxicology 2003; 24:43-53.

(8.) Sameul J, Thomas K, Jayaseelan L, Peter JV, Cherian AM. Incidence of Intermediate Syndrome in OP Poisoning. JAPI, 1995:43(5):321-3.

(9.) Routier RJ, Lipman J, Brown K. Difficulty in weaning from respiratory support in a patient with the intermediate Syndrome of organophosphate poisoning. Crit Care Med 1989; 17:1075.

(10.) Bessar R, Weilmann LS, Gutmann L. Efficacy of Obidoxime in human organophosphorus poisoning; determination by neuromuscular transmission studies. Muscle Nerve 1995 18: 15-22.

(11.) Zheng G, Song S, Li M. Comparison of effects between concentrated dose & non-concentrated dose of Pralidoxime chloride on respiratory muscle paralysis in acute OP Pesticide Poisoning. Zhonghua Nei K Za Zhi.2000; 39: 655-7.

(12.) Johnson S, Peter JV, Thomas K, Jeyasselan L, Cherian AM. Evaluation of two treatment regimens of Pralidoxime (1 gm bolus vs. 12 gm) infusion in the management of OP Poisoning. J Assoc Physician India 1996; 44:529-31.

(13.) de Silva HJ, Wijewickrema R, Senanayake N. Does Pralidoxime affect outcome of management in acute organophosphorus poisoning? Lancet 1992; 339; 1136-8.

(14.) Sangur M, Guven M. Intensive care management of organophosphorus poisoning, Criticare 2001; 5: 211

(15.) Buckley N, Edddleton M, Szinicz N. Oximes for acute organophosphorus pesticide poisoning. Cochrane Database Syst Rev 2005:CD005085.

(16.) The Spectrum of Intermediate Syndrome Following Acute Organophosphate Poisoning: A Prospective Cohort Study from Sri Lanka Pradeepa Jayawardane, Andrew H. Dawson, Vajira Weerasinghe, Lakshman Karalliedde, Nicholas A. Buckley, Nimal Senanayake.

(17.) Jayawardane P, Dawson AH, Weerasinghe V, Karalliedde L, Buckley NA, et al. (2008) The Spectrum of Intermediate Syndrome Following Acute Organophosphate Poisoning: A Prospective Cohort Study from Sri Lanka. PLoS Med 5(7): e147. doi:10.1371/journal.pmed.0050147

(18.) Kenneth D KatzT. The spectrum of intermediate syndrome following acute organophosphate poisoning: a prospective cohort study from Sri Lanka. Organophosphate Toxicity. PLoS Med.2008; 5: e 147.

M. Murthy [1], D. Kosam [2], R. Nigam [3], S. Chatterjee [4], R. Murthy [5], Sachin Pandey [6]


[1.] M. Murthy

[2.] D. Kosam

[3.] R. Nigam

[4.] S. Chatterjee

[5.] R. Murthy

[6.] Sachin Pandey


[1.] Associate Professor, Department of Anaesthesiology, Chhattisgarh Institute of Medical Sciences, Bilaspur (C. G.) State.

[2.] Assistant Professor, Department of Anaesthesiology, Chhattisgarh Institute of Medical Sciences, Bilaspur (C. G.) State.

[3.] Associate Professor, Department of Anaesthesiology, Chhattisgarh Institute of Medical Sciences, Bilaspur (C. G.) State.

[4.] Professor, Department of Anaesthesiology, Chhattisgarh Institute of Medical Sciences, Bilaspur (C. G.) State.

[5.] Professor, Department of Microbiology, Chhattisgarh Institute of Medical Sciences, Bilaspur (C. G.) State.

[6.] Assistant Professor, Department of Community Medicine, Chhattisgarh Institute of Medical Sciences, Bilaspur (C. G.) State.


Dr. M. Murthy, #31, Guru Vihar Colony, Sarkanda, Bilaspur (C.G.)-495001, Email:

Date of Submission: 06/04/2014.

Date of Peer Review: 07/04/2014.

Date of Acceptance: 05/05/2014.

Date of Publishing: 19/05/2014.
TABLE 1: Comparison of characteristics between patients with IMS
& without IMS

                                          WITH IMS
No.    CHARACETRISTIC                    A            %

1      Age               16-30yrs        43          7.52
                         30-50yrs        17          2.97

2      Gender              Male          24          4.20
                          Female         40          6.99

3      Intent of exposure

         Suicidal           yes          62         10.84
                            No           2           0.35
         accidental         Yes          4           0.70
                            No           60         10.49

4      amount of            yes          64         11.19
                            No           0           0.00

5      co-ingestant         yes          5           0.87
       alcohol              No           59         10.31

6      Initial              yes          51          8.92
       treatment with       No           13          2.27
       atropine 30amp
       in 15 minute

7      Initial              Yes          54          9.44
       treatment with       No           10          1.75
       initial PAM

8      Abnormal Lab         Yes          55          9.62
       data--ARF            No           9           1.57

Mean S.D.                             (31.78,

                                         WITHOUT IMS
No.    CHARACETRISTIC                    B            %

1      Age               16-30yrs       432          7.78
                         30-50yrs       186          3.35

2      Gender              Male         212          3.82
                          Female        406          7.31

3      Intent of exposure

         Suicidal           yes         525          9.46
                            No           93          1.68
         accidental         Yes          93          1.68
                            No          525          9.46

4      amount of            yes          20        [??][??]
       exposure                                    [??][??]
                            No          588         10.59

5      co-ingestant         yes         124          2.23
       alcohol              No          494          8.90

6      Initial              yes         185          3.33
       treatment with       No          433          7.80
       atropine 30amp
       in 15 minute

7      Initial              Yes         216          3.89
       treatment with       No          402          7.24
       initial PAM

8      Abnormal Lab         Yes          62          1.12
       data--ARF            No          556         10.01

Mean S.D.                             (308.44,

TABLE 2: Comparison of characteristics between
Patients with intermediate syndrome who died
& who survived

No.    Characteristic               Died      %

1      Age             18-30 yrs     12      9.23

2      Gender          male          8       6.15
                       female        4       3.08

3      Intent of       suicidal      12      9.23
       exposure        Accidental    0       0.00

4      Amount of                     12      9.23

5      Co-             yes           0       0.00
       ingestant       no            12      9.23

6      Initial         30amp in      12      9.23
       treatment       15 min.
       atropine        30amp in      0       0.00
                       30 min

7      Initial         1gm/8hr.      12      9.23
       with PAM        500mg/8hr.    0       0.00

8      Abnormal Lab                  12      9.23
       data ARF                      0       0.00

9      Convulsions     yes           4       3.08
                       no            8       6.15

10     ARDS            yes           8       6.15
                       no            14     10.77
Mean S.D. (7.22, 5.36)                     (27.78,
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Article Details
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Author:Murthy, M.; Kosam, D.; Nigam, R.; Chatterjee, S.; Murthy, R.; Pandey, Sachin
Publication:Journal of Evolution of Medical and Dental Sciences
Article Type:Report
Date:May 19, 2014
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