Intermediate Syndrome in Organophosphate Poisoning:

IMS is a critical phase of OP poisoning because patients often appear stable after initial treatment, only to deteriorate due to muscle weakness that compromises breathing.

Pathophysiology:

The exact mechanism of IMS is not fully understood, but it is believed to result from prolonged exposure to excessive acetylcholine at nicotinic receptors at the neuromuscular junction. This leads to dysfunction or desensitization of these receptors, causing muscle weakness. Other contributing factors may include:

• Depletion of acetylcholine stores after initial overstimulation.
• Desensitization of nicotinic receptors at the neuromuscular junction.
• Prolonged inhibition of acetylcholinesterase (AChE) by organophosphates, leading to continuous acetylcholine buildup.

Unlike the acute phase of poisoning, which primarily involves overstimulation of muscarinic and nicotinic receptors, IMS predominantly affects nicotinic receptors.

Clinical Features:

IMS typically develops 24-96 hours after the acute phase of OP poisoning has subsided and after the initial administration of atropine and pralidoxime. It presents with the following features:

1. Muscle Weakness:

   • Proximal muscle weakness (neck, limb girdle muscles) is prominent.
   • Weakness in neck flexors, causing an inability to lift the head from the pillow.
   • Weakness of proximal upper and lower limb muscles.

2. Cranial Nerve Palsy:

   • Ophthalmoplegia (weakness of eye muscles).
   • Facial muscle weakness (difficulty smiling, chewing).
   • Dysphagia (difficulty swallowing).

3. Respiratory Muscle Weakness:

   • Intercostal muscle and diaphragm weakness leading to respiratory insufficiency or failure.
   • This can progress to the need for mechanical ventilation in severe cases.

4. Absence of Cholinergic Symptoms:

   • Unlike the acute cholinergic crisis, muscarinic symptoms (e.g., miosis, bronchorrhea, salivation) are typically absent during IMS.

Diagnosis:

The diagnosis of IMS is based on clinical presentation and the timing of onset after initial treatment for acute OP poisoning. Key diagnostic features include:

1. Timing: Onset 24-96 hours after resolution of the acute cholinergic crisis.
2. Progressive proximal muscle weakness: Particularly in the neck and limbs.
3. Absence of cholinergic signs such as salivation or diarrhea, differentiating it from the acute cholinergic crisis.
4. Respiratory involvement: Patients may present with hypoxia and hypercapnia due to respiratory muscle weakness.

Electromyography (EMG): May show a decremental response on repetitive nerve stimulation, indicating neuromuscular junction dysfunction.

Management:

1. Respiratory Support:

   • Close monitoring of respiratory function is essential.
   • Early intervention with mechanical ventilation may be necessary, as respiratory muscle weakness can lead to respiratory failure.
   • Pulse oximetry and arterial blood gases should be monitored to detect hypoxia or hypercapnia.

2. Atropine:

   • Atropine is not effective for IMS as it primarily antagonizes muscarinic receptors, and IMS predominantly affects nicotinic receptors.
   • Continuous atropine administration should be maintained to prevent the recurrence of cholinergic symptoms, but it has no role in treating the muscle weakness of IMS.

3. Pralidoxime (2-PAM):

   • Pralidoxime should be continued in patients with IMS as it helps reactivate acetylcholinesterase and may improve nicotinic receptor function.
   • Prolonged administration (up to several days) may be necessary in IMS cases.

4. Supportive Care:

   • Regular repositioning and care to prevent pressure sores in patients with muscle weakness.
   • Nutritional support, including tube feeding in patients with dysphagia.
   • Physical therapy to aid in the recovery of muscle function during convalescence.

5. Monitoring for Complications:

   • Frequent monitoring of respiratory rate, oxygen saturation, and arterial blood gases is crucial in detecting early respiratory failure.
   • Close observation for aspiration pneumonia in patients with dysphagia or reduced gag reflex.

Prognosis:

The prognosis of IMS depends largely on early recognition and adequate respiratory support. With prompt intervention, patients usually recover from IMS over several days to weeks. However, in the absence of timely mechanical ventilation, respiratory failure can be fatal.

• Recovery: Most patients recover muscle strength over time, but the process may take weeks. Intensive care support is often required during this period.
• Long-term Outcomes: Patients usually recover fully without long-term neuromuscular complications, but there may be residual weakness in some cases.

Prevention:

Preventing IMS is challenging since it occurs after the acute cholinergic phase has resolved. However, prolonged use of pralidoxime and close monitoring of neuromuscular function in the first 48-96 hours after OP poisoning are crucial in preventing severe complications.

About the Author

Dr. Akif Ahamad Baig is a Consultant Cardiologist who completed his DM in Cardiology from Guntur Medical College. He specializes in coronary interventions and complex cardiac procedures. Dr. Baig is passionate about medical education and research, contributing to textbooks and case reports aimed at improving medical training and patient care.