Definition

The cholinergic crisis is a medical emergency resulting from excessive stimulation of muscarinic and nicotinic receptors. It often occurs due to overuse of anticholinesterase medications like Pyridostigmine, Neostigmine, and organophosphate compounds found in pesticides. Early symptoms of a cholinergic crisis include abdominal cramps, diarrhea, excessive sweating, excessive salivation, and a weakening pulse.

Patients take anticholinesterase drugs with myasthenia gravis (MG) to reduce their symptoms. Patients with MG who experience a cholinergic crisis usually take high doses of medication (about 120 mg every 3 hours). A condition similar to a cholinergic crisis is a myasthenic crisis, though cholinergic crises are less common.

Causes

Acetylcholine (ACh) is an important compound that acts on the parasympathetic, sympathetic, and skeletal muscle nerves. It functions to transmit stimuli or information from the brain to target organs such as the brain, eyes, digestive organs, and skeletal muscles. ACh acts on two different receptors: muscarinic and nicotinic.

In skeletal muscles, ACh works at the neuromuscular junction, where nerves and muscles meet. Whenever a signal is transmitted through a nerve, the nerve releases ACh, which binds to specific receptors on the muscle, known as nicotinic receptors. This binding causes skeletal muscle contraction. After a while, the bond between ACh and its receptor breaks, and ACh is broken down by an enzyme called acetylcholinesterase (ACh-i), preventing excessive muscle stimulation. If there is another stimulus, this process repeats.

Besides acting on skeletal muscles, ACh is also crucial for the autonomic function of other organs in the body, especially in activating the parasympathetic nervous system. Activation of the parasympathetic system causes decreased cardiac output, skeletal muscle relaxation, bronchoconstriction, saliva production, and decreased intestinal motility.

In MG, the amount of ACh is preserved so muscles continue to contract. Therefore, doctors prescribe acetylcholinesterase inhibitors to prevent the breakdown of ACh, allowing muscles to move.

In a cholinergic crisis, the amount of ACh at the neuromuscular junction and throughout the nervous system is excessive, causing continuous activation of nerves and muscles. This leads to symptoms of toxicity involving both nicotinic and muscarinic effects. Several conditions can trigger a cholinergic crisis, including:

• Overuse of anticholinesterase in treating MG
• Exposure to organophosphates (through ingestion, skin contact, mucous membrane contact, or inhalation)

Risk factor

Several conditions can increase the risk of experiencing a cholinergic crisis, such as:

• Receiving high-dose general anesthesia to reduce the effects of nerve-blocking agents
• Children or adults inhaling toxic gases
• Individuals exposed to pesticides or insecticides
• Myasthenia Gravis patients taking high doses of acetylcholinesterase inhibitors

Symptoms

There are two groups of symptoms in a cholinergic crisis.

Muscarinic symptoms

• Difficulty breathing
• Blurred vision and watery eyes
• Nausea, vomiting, and diarrhea
• Slow pulse
• Excessive salivation
• Frequent urination

Nicotinic symptoms

• Seizures or excessive muscle twitching followed by paralysis. Initially, excess ACh causes muscle contraction, but due to overstimulation, muscles can no longer contract and become paralyzed.
• Rapid pulse, which then slows down

Other symptoms include restlessness, inability to be calmed, staggering, fainting, and even coma.

Differentiating myasthenic crisis and cholinergic crisis

Both myasthenic and cholinergic crises share early symptoms of weakness and difficulty breathing. However, a myasthenic crisis is caused by low levels of ACh in the body, resulting in different symptoms such as dilated pupils, rapid pulse, inability to swallow, voice changes, and tongue weakness.

Diagnosis

A cholinergic crisis is a medical emergency. Your doctor will diagnose it based on symptoms, signs, and a comprehensive physical examination. They will ask about your complaints, medications you are taking, and any exposure to certain substances like pesticides. It's crucial to inform your doctor about when you were exposed to a substance or took a certain medication. Your doctor will also distinguish between a cholinergic crisis and a myasthenic crisis as they require different treatments.

Physical examination includes assessing the nervous, respiratory, cardiac, and digestive systems. The doctor will look for signs like excessive salivation, constricted pupils, blood pressure changes, and difficulty breathing.

Supporting tests include:

• Complete blood count to check for infections
• Metabolic panel to rule out other possible causes, such as metabolic issues or abnormalities caused by organophosphate poisoning
• Electrocardiography to detect arrhythmias
• Chest X-ray to check for pulmonary edema and aspiration
• CT scan to rule out other conditions

Management

Treatment for a cholinergic crisis involves several steps:

• Before reaching the hospital, reduce exposure to the substance causing the crisis. Decontamination is crucial if the condition is due to organophosphate exposure, whether gas or liquid. Remove contaminated clothing from the patient to prevent further contamination. Call for medical help if you are near someone suspected of having a cholinergic crisis.
• In the emergency department, treatment includes stabilizing the airway, breathing, and circulation. If the airway is blocked by saliva, the doctor may perform intubation. Breathing assistance is provided if the patient has difficulty breathing, and intravenous fluids are administered.
• Antidotes: The antidotes for organophosphate poisoning are atropine and oxime. Atropine is given if there are signs of a rapid pulse, dry and warm skin, and dilated pupils. Oxime is administered if there are signs of respiratory failure or widespread muscle weakness.
• Other treatments: Seizures and restlessness, which are signs of a cholinergic crisis, can be managed with sedatives.

These treatments should only be administered by medical professionals.

Complications

Complications from a cholinergic crisis include:

• Respiratory failure, is the leading cause of death in cholinergic crises
• Aspiration leading to pneumonia
• Low blood pressure
• Unstable heart rhythms (arrhythmias)
• Hallucinations
• Seizures
• Electrolyte imbalances due to vomiting and diarrhea
• Death, with a mortality rate ranging from 3-25%

Prevention

A cholinergic crisis can be prevented by using personal protective equipment when in close contact with pesticides, insecticides, and herbicides. Taking anticholinergic medications as prescribed by your doctor is crucial to prevent a cholinergic crisis.

When to see a doctor?

If you experience any symptoms of a cholinergic crisis, seek immediate medical attention at the nearest healthcare facility. This condition is an emergency requiring prompt treatment.