The Intermediate Syndrome.IN DETAIL

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intermediate syndrome in OP poisioning


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Intermediate syndrome :

Intermediate syndrome Presenter- Dr Manjunath F V Moderator- Prof. Taruni Ng.


Introduction Pesticide poisonings remain a serious public health problem worldwide. Among the numerous pesticides that can result in death, organophosphate insecticides are the most common culprit agents because of their high toxicity .

cholinesterase inhibitors :

cholinesterase inhibitors

Nicotinic and Muscarinic effects of Cholinesterase inhibitors:

Nicotinic and Muscarinic effects of Cholinesterase inhibitors

Categories of Pathological Effects:

Categories of Pathological Effects

Intermediate Syndrome :

Intermediate Syndrome Why is it so named? Risk factors Incidence Probable mechanisms Clinical features Diagnosis Complications Treatment Prognosis Summary


Description The term IMS was first described by Senanayake and Karalliedde in 1987 . It is a delayed-onset of muscular weakness and paralysis following an episode of acute cholinesterase inhibitor poisoning. It is so named because it arose in the interval between the end of the acute cholinergic crisis and the onset of OPIDN.

Risk Factors:

Risk Factors Prolonged and severe inhibition of acetylcholinesterase , Delayed metabolism of organophosphates, Inadequate or late oxime therapy, Exposure to specific organophosphates, namely fenthion , dimethoate and monocrotophos , all of which are dimethoxy compounds.


Incidence Estimates are that 10-68% of those poisoned with organophosphorus agents will develop intermediate syndrome. (Leon, Pradilla et al. 1996; Karalliedde , Wheeler et al. 2000) Although some authors have maintained that the syndrome only occurs after severe cases of acute toxicity, (De Bleecker , Van Den Neucker et al. 1993; Ray 1998; Kwong 2002) Khan et al. (2001) found that the syndrome occurred in 22% of those with mild poisoning and 17% of those with moderate poisoning . (Khan, Hemalatha et al. 2001)

Mechanisms :

Mechanisms IMS is well recognized as a disorder of the neuromuscular junction; however, its exact underlying mechanisms are not clearly defined . Senanayake and Karalliedde in their first report of IMS suggested that the syndrome might be caused by pathologic changes( myonecrosis ) in the postsynaptic end-plate region of striated muscles.


Cont.. Benson and McIntire, suggested that either different susceptibility of various cholinergic receptors or inadequate oxime therapy played a role in the development of IMS.


Cont.. In 1997, Sedgwick and Senanayake further proposed that downregulation or desensitization of postsynaptic acetylcholine receptors after prolonged acetylcholine stimulation could explain the occurrence of IMS.

Signs and Symptoms :

Signs and Symptoms Karalliedde ( Karalliedde and Senanayake 1989) first described the syndrome in 1987 and observed that, although clinical findings occurred in a delayed fashion , they were described as acute in onset .


Cont.. Typically occur within 24 to 96 hours , Affects conscious patients without fasciculation or other cholinergic signs. Marked weakness of neck flexion and varying degree of proximal limb muscle weakness , manifesting as weakness of shoulder abduction and hip flexion, are the constant clinical features.


Cont.. Respiratory insufficiency is also common and frequently draws medical attention to the onset of the syndrome. Other possible manifestations are involvement of muscles innervated by motor cranial nerves and decreased deep tendon reflexes. Sensory impairment is not a clinical manifestation of IMS.


Cont.. Atypical manifestations of IMS, Frequently reported in the literature. Especially, a relapse of cholinergic signs superimposed on IMS (De Bleecker et al) or A rebounding of acute cholinergic crisis prior to the development of IMS (He et al).


Cont.. According to the report by Senanayake and Karalliedde , the regression of toxic signs among patients who survived IMS followed a distinct pattern. Muscle power first resumed in cranial nerve-innervated muscles, followed by respiratory muscles, proximal muscles, and neck flexors.

Diagnosis :

Diagnosis History- type of poison, route, dose, severity of symptoms, delay in treatment, inadequate therapy Neurophysiological examination Electrophysiological study

Electrophysiologic Findings :

Electrophysiologic Findings Electrophysiologic study has been proposed as a specific diagnostic tool for patients with IMS. Nevertheless, findings of electrophysiologic studies in patients with IMS did not yield consistent results. Authors conclusion : IMS is probably a spectrum disorder and neurophysiologic examinations might be useful in predicting the development of IMS.





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The electrophysiological findings in other common neuromuscular junction disorders The characteristic response to RNS at 2 to 3 Hz stimulation rate in myasthenia gravis is a progressive decrement in amplitude of the CMAP. In Lambert-Eaton syndrome , there is a presynaptic neuronal conduction block. Marked facilitation of CMAP amplitude after brief muscle contraction or following highfrequency (20–50 Hz) RNS.


Cont.. In botulism there is enzymatic cleavage of proteins that are needed for the exocytosis of ACh . The most consistent electrophysiological abnormality is a small evoked muscle action potential in response to a single supramaximal nerve stimulus in a clinically affected muscle.


Complications The neuromuscular effects can progress to frank paralysis with respiratory failure and death . Unfortunately, many cases are not diagnosed until significant respiratory insufficiency has developed. (Erdman 2004) Data from India implicates the syndrome as the main cause of morbidity and mortality from organophosphorus poisoning. (Khan, Hemalatha et al. 2001)

Treatment :

Treatment IMS carries a high risk of death among patients with respiratory failure. Therefore, prompt recognition of the syndrome is the cornerstone of IMS management. Treatment of IMS per se is mainly supportive and there are no specific antidotes available for this devastating syndrome.


Cont.. Nevertheless, because IMS generally concurs with severe organophosphate toxicity and persistent inhibition of acetylcholinesterase , early aggressive gastrointestinal decontamination, followed by appropriate therapy of atropine and oximes , and prompt institution of ventilatory support , should be helpful in ameliorating the magnitude and/or the incidence of IMS.


Cont.. Repeated dose of fresh frozen plasma therapy has been proposed in the treatment of IMS. Guven et al found that frozen plasma therapy could prevent the development of IMS and related mortality through the restoration of plasma acetylcholinesterase .


Prognosis If there has not been hypoxic damage, and if proper supportive care has been provided, survival can be expected in most cases. The condition usually resolves spontaneously within 1-2 weeks . ( Karalliedde and Senanayake 1989; Erdman 2004)

Summary :

Summary IMS is a major cause of morbidity and mortality in patients with acute organophosphate insecticide poisoning. Although IMS is well recognized as a disorder of neuromuscular junctions, its exact etiology, incidence, and risk factors are not clearly defined.


Cont.. Without a clear understanding of the pathophysiology of IMS, specific therapy is not available and supportive measures remain the cornerstone in the management of IMS. The prognosis of IMS, however, is likely to be favorable if respiratory failure can be promptly recognized and treated accordingly.

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