What is Cholinergic Crisis?

Cholinergic crisis is a medical condition that occurs when there is too much stimulation of certain receptors in the nerve-muscle connections and synapses. This can happen when an enzyme called acetylcholinesterase, which normally breaks down a chemical called acetylcholine, is blocked or not working properly. As a result, there is too much acetylcholine in these nerve-muscle connections and synapses. This can cause a variety of symptoms, including cramps, excess saliva, tears, muscle weakness, paralysis, muscle twitches, diarrhea, and blurred vision.

This condition can often be seen in certain situations such as:

  • Patients with a disease called myasthenia gravis who are being treated with high doses of drugs that block acetylcholinesterase.
  • Patients who have recently been under general anesthesia and were given high doses of drugs that block acetylcholinesterase to counter the effects of drugs given to relax their muscles, like neostigmine.
  • People who were exposed to a chemical that stops acetylcholinesterase from working. These can include nerve gases like sarin, tabun, soman, and other substances like pesticides and insecticides.

What Causes Cholinergic Crisis?

Several health conditions can bring on a cholinergic crisis, a sudden surge in nerve impulses caused by too much acetylcholine (a chemical which functions as a neurotransmitter). Here are some common circumstances:

Taking Too Much Acetylcholine Esterase Inhibitor Medicine in treating Myasthenia Gravis

Myasthenia gravis (MG) is an immune system disorder that interferes with communication between nerves and muscles, causing muscle weakness and fatigue, which can even lead to life-threatening breathing problems. One form of MG is associated with the production of muscle-specific tyrosine kinase (MuSK) antibodies and is often seen in women.

A typical treatment for myasthenia gravis is using drugs that inhibit acetylcholinesterase (AChEI) like pyridostigmine. These drugs prevent acetylcholine from getting broken down, increasing its levels in the body to help nerves communicate with muscles. Overuse of this medication, though, may lead to a cholinergic crisis, causing toxicity.

A severe complication of MG is the myasthenia crisis, which can be triggered by infection, surgery, menstruation, and certain medications including calcium channel blockers and some antibiotics. Myasthenia crisis and cholinergic crisis can have similar symptoms. Therefore, it is crucial to decipher which of the two crisis forms is causing muscle weakness. A drug called Edrophonium can be administered as a test: its use will improve symptoms in a myasthenia crisis but worsen them in a cholinergic crisis.

In Contact with Organophosphates

A cholinergic crisis can also be triggered by exposure to substances that suppress acetylcholine breakdown, such as nerve gas and organophosphate compounds found in pesticides, insecticides, and herbicides. These exposures can happen by breathing in the substances, direct skin contact, or swallowing them.

Organophosphates are often used in chemical warfare. They inhibit the breakdown of acetylcholine, leading to excessive nerve impulses. At their worst, these chemicals can cause anything from mild to severe nerve gas poisoning.

Even exposure to pesticides and insecticides containing organophosphates in our daily life can trigger a cholinergic crisis. Symptoms for this kind of exposure might include neurological issues like headaches, dizziness, and tingling sensations.

Using Neuromuscular Blockage Reversal Agents

Lastly, using specific medications like neostigmine or pyridostigmine to reverse nerve and muscle blockages can also trigger a cholinergic crisis. These medications block a chemical that breaks down acetylcholine, letting more of it build up to help overcome the muscle-paralyzing effects of certain drugs. Too much of these medications, though, can kickstart a cholinergic crisis and cause symptoms like bronchospasms and increased secretions from glands and the digestive system. To help moderate these effects, anticholinergic drugs like glycopyrrolate are often given alongside reversal drugs.

Risk Factors and Frequency for Cholinergic Crisis

Cholinergic crisis is a medical condition that is not extensively studied but is often seen in children and people with a condition called myasthenia gravis. Kids are particularly at risk if they accidentally come in contact with or swallow a group of chemicals called organophosphates. This risk is higher for children living in rural areas. The US has strict regulations on the sale of these chemicals since 2013.

Across the world, around three million people are exposed to organophosphate poisoning every year, leading to roughly 300,000 deaths. This poisoning can result from accidently ingesting agricultural substances like insecticides or pesticides, or through food items such as wheat, flour, cooking oil, fruits, and vegetables that might have been contaminated.

Production of nerve gases, which can also cause a cholinergic crisis, has been significantly reduced since World War II. Manufacturing these gases has been classified as a war crime since the Geneva Convention in 1925, and this has greatly reduced the incidences of nerve gas poisoning in contemporary times. The most recent large-scale use was reported in Syria in 2013.

Signs and Symptoms of Cholinergic Crisis

Diagnosing a cholinergic crisis can be challenging, especially for those who are not familiar with its signs and symptoms. To identify this condition, doctors need to take a detailed history of the patient’s health and conduct a thorough physical examination. It’s particularly important to check the nervous, respiratory, cardiovascular, and gastrointestinal systems, as these areas typically show the most significant symptoms.

There are two mnemonics, “SLUDGEM” and “DUMBELS,” that can help remember the symptoms related to overstimulation of the muscarinic receptors due to an excess of acetylcholine (ACh).

  • SLUDGEM:
  • S – Salivation
  • L – Lacrimation
  • U – Urinary frequency
  • D – Diarrhea
  • G – Gastrointestinal cramping and pain
  • E – Emesis (vomiting)
  • M – Miosis (pupil contraction)
  • DUMBELS:
  • D – Diaphoresis (sweating) and Diarrhea
  • U – Urinary frequency
  • M – Miosis
  • B – Bronchospasm (tightening of the airway muscles) and Bronchorrhea (excessive mucus in the airways)
  • E – Emesis
  • L – Lacrimation
  • S – Salivation

Apart from the muscarinic receptors, there’s additional abnormal stimulation in the nicotinic receptors and the Central Nervous System. The symptoms include:

  • Muscle weakness
  • Muscular fatigue and twitching (fasciculation)
  • Respiratory muscle weakness
  • Rapid heart beat (Tachycardia)
  • High blood pressure (Hypertension)
  • Seizures
  • Coma
  • Loss of coordination (Ataxia)
  • Slurred speech
  • Agitation and restlessness

The cause of the cholinergic crisis should also be identified, which may include medication for myasthenia gravis or glaucoma, exposure to insecticides, pesticides, herbicides, or nerve gas, or the reversal of neuromuscular blockage. It’s vital to determine when, how, and where the exposure or ingestion happened because there is a 48-hour window to administer pralidoxime, the antidote that can save the patient’s life.

Testing for Cholinergic Crisis

If you’re being examined for a cholinergic crisis, doctors will ask questions about your health history and perform a physical exam to look for signs linked with the crisis.

There are some additional tests that might be done to aid in the diagnosis:

* A Complete Blood Count (CBC) could be conducted to see if your white blood cells are elevated. If they are, it could indicate an infection.

* A Comprehensive Metabolic Panel (CMP) might be done to check for any changes in the body’s electrolytes, which could be tied to a specific type of poisoning called organophosphate poisoning.

* A test might be done to measure the activity of a substance called cholinesterase in your red blood cells. This is usually lower in cholinergic crisis and can help confirm the diagnosis. They can also check a substance called pseudocholinesterase in the plasma, but this is generally less accurate.

* An Electrocardiography (ECG) could be performed to check for heart rhythm problems that can be caused by organophosphate poisoning.

* A Chest X-Ray might be ordered to check for fluid in the lungs or signs of inhalation of food, liquid or vomit into the lungs.

If your mental status changes or if there are significant changes in your level of consciousness as measured by the Glasgow Coma Scale, a brain CAT scan may be necessary.

Treatment Options for Cholinergic Crisis

Treating a cholinergic crisis, which is a severe response to medications or substances that affects things like heart rate and digestion, generally involves three stages: (1) initial treatment when medical help is summoned, (2) treatment in the emergency room, and (3) long-term, in-hospital care.

Firstly, the goal of care before the patient reaches the hospital is to stabilize the patient and remove the poison causing the illness, if applicable. If the crisis is due to an organophosphate or nerve gas, it’s important to remove all clothing from the patient to stop ongoing contact with the toxic substance and protect medical responders from harm.

Once in the hospital’s emergency room, the patient’s Airway, Breathing, and Circulation (ABC) are the main focus. The caretakers should ensure that the patient’s airway is open and they are breathing on their own. If there’s a risk of an obstructed or blocked airway, advanced measures to maintain the airway should be taken, which could include intubation (inserting a tube to support breathing). When there are large amounts of facial and mouth secretions, mental confusion, signs of unstable blood circulation, or extreme breathing muscle weakness, this would be necessary.

Access to the patient’s veins should also be set up as quickly as possible to ensure adequate circulation, monitored through continuous pulse and vital sign assessment. If the patient’s circulation is unstable, medication should be delivered directly into the larger central veins of the body.

If the patient remains in the hospital for ongoing care, they will continue to receive heart and lung support and constant monitoring. They will most likely need to stay in the intensive care unit.

To counter the effects of the cholinergic crisis, two types of antidotes can be used: atropine and a group of drugs referred to as “oximes”.

Atropine can effectively block the body’s severe reactions to acetylcholine, a puppet master molecule that controls our muscles and other functions. Children usually receive 0.03-0.05 mg/kg of Atropine, while adults typically receive 2 mg. You’ll know the Atropine is working when the heart speeds up, the skin becomes warm, dry and flushed, and the pupils in the eyes widely open. However, Atropine has no impact on the body’s ‘nicotinic’ receptors.

For the effects on the ‘nicotinic’ receptors in the cholinergic crisis, we use the “oximes” drugs, such as pralidoxime. This works like a “molecular crowbar,” prying away the the toxic substance from where it has bonded in the body. This then allows the body to start breaking down the harmful substance. But, there’s a limited time in which oximes remain effective before the effects of the poison become irreversible, with the time frame varying based on the specific toxin.

The signs indicating the use of pralidoxime include weakening of the breathing muscles or overall muscular weakness. The administration should continue until muscle weakness improves. However, pralidoxime doesn’t counteract the effects of poisoning on the brain, hence Atropine is used for that purpose.

If the patient is having a seizure or seems agitated due to the cholinergic crisis, medications like midazolam or lorazepam can be used to help. Additionally, care should be taken to avoid giving certain medications like loop diuretics (water pills), theophylline (used for lung diseases), caffeine, and succinylcholine (used for causing muscle relaxation), which might worsen the toxicity.

It is recommended to involve a clinical toxicologist and intensive care unit specialist in the treatment of a cholinergic crisis.

If a patient is suspected to be having a myasthenic crisis, it’s important to distinguish this from another condition known as cholinergic crisis. This can be done using a test involving a drug called edrophonium. When this drug is given, the symptoms will worsen if the patient is experiencing a cholinergic crisis. However, if they have a myasthenic crisis, the opposite will occur; symptoms will improve.

It is also crucial to consider other causes that may lead to a cholinergic crisis. These include exposure to nerve gas, the use of certain chemicals known as organophosphates, and the use of drugs used to reverse the effects of muscle relaxants during surgery. All of these possibilities should be kept in mind during the diagnostic process.

What to expect with Cholinergic Crisis

The death rate for cholinergic crisis – a medical condition – varies between 3% and 25%. The most frequent cause of death in this situation is worsening problems with breathing.

Possible Complications When Diagnosed with Cholinergic Crisis

In a cholinergic crisis, where the muscarinic and nicotinic receptors are overstimulated, certain complications can develop. These problems affect different systems in the body including the respiratory, cardiovascular, central nervous and gastrointestinal systems.

Complications for each system are as follows:

Respiratory System

  • Respiratory failure due to severe weakness of the breathing muscles
  • Aspiration pneumonia caused by too much saliva and bronchial secretions
  • Serious narrowing of the airways (severe bronchospasm)

Cardiovascular System

  • Slower heart rate (bradycardia)
  • Low blood pressure (hypotension)
  • High blood pressure (hypertension)
  • Irregular heartbeats (arrhythmia)

Central Nervous System

  • Hallucinations
  • Mental disorders (psychosis)
  • Seizures
  • Change in mental state (altered mental status)

Gastrointestinal System

  • Electrolyte imbalances due to vomiting and diarrhea
Frequently asked questions

Cholinergic crisis is a medical condition that occurs when there is too much stimulation of certain receptors in the nerve-muscle connections and synapses. This happens when the enzyme acetylcholinesterase is blocked or not working properly, leading to an excess of acetylcholine in these connections and synapses. This can cause various symptoms such as cramps, excess saliva, tears, muscle weakness, paralysis, muscle twitches, diarrhea, and blurred vision.

Cholinergic crisis is not extensively studied, but it can occur in various circumstances such as taking certain medications, exposure to organophosphates, and using specific reversal agents.

The signs and symptoms of Cholinergic Crisis include: - Salivation - Lacrimation - Urinary frequency - Diarrhea - Gastrointestinal cramping and pain - Emesis (vomiting) - Miosis (pupil contraction) - Diaphoresis (sweating) - Bronchospasm (tightening of the airway muscles) - Bronchorrhea (excessive mucus in the airways) - Muscle weakness - Muscular fatigue and twitching (fasciculation) - Respiratory muscle weakness - Rapid heart beat (Tachycardia) - High blood pressure (Hypertension) - Seizures - Coma - Loss of coordination (Ataxia) - Slurred speech - Agitation and restlessness These symptoms can be remembered using the mnemonics "SLUDGEM" and "DUMBELS." It's important to note that there may also be additional abnormal stimulation in the nicotinic receptors and the Central Nervous System.

A cholinergic crisis can be caused by several factors, including taking too much acetylcholine esterase inhibitor medicine in treating myasthenia gravis, being in contact with organophosphates, and using neuromuscular blockage reversal agents.

Exposure to nerve gas, the use of certain chemicals known as organophosphates, and the use of drugs used to reverse the effects of muscle relaxants during surgery.

The types of tests that may be ordered to diagnose a cholinergic crisis include: - Complete Blood Count (CBC) to check for elevated white blood cells, which could indicate an infection. - Comprehensive Metabolic Panel (CMP) to assess changes in electrolytes, which could be linked to organophosphate poisoning. - Measurement of cholinesterase activity in red blood cells, which is typically lower in cholinergic crisis and can help confirm the diagnosis. - Electrocardiography (ECG) to check for heart rhythm problems caused by organophosphate poisoning. - Chest X-Ray to look for fluid in the lungs or signs of inhalation of food, liquid, or vomit into the lungs. - Brain CAT scan may be necessary if there are significant changes in mental status or level of consciousness. These tests can aid in the diagnosis of a cholinergic crisis and help guide appropriate treatment.

Treating a cholinergic crisis generally involves three stages: initial treatment when medical help is summoned, treatment in the emergency room, and long-term, in-hospital care. The goal of care before reaching the hospital is to stabilize the patient and remove the poison causing the illness if applicable. In the emergency room, the main focus is on the patient's airway, breathing, and circulation. Access to the patient's veins should be set up quickly, and medication may be delivered directly into the larger central veins of the body if circulation is unstable. If the patient remains in the hospital for ongoing care, they will continue to receive heart and lung support and constant monitoring. Two types of antidotes, atropine and "oximes" drugs, can be used to counter the effects of the cholinergic crisis. Atropine blocks severe reactions to acetylcholine, while "oximes" drugs like pralidoxime pry away the toxic substance from where it has bonded in the body.

The side effects when treating Cholinergic Crisis include: - Respiratory System: - Respiratory failure due to severe weakness of the breathing muscles - Aspiration pneumonia caused by too much saliva and bronchial secretions - Serious narrowing of the airways (severe bronchospasm) - Cardiovascular System: - Slower heart rate (bradycardia) - Low blood pressure (hypotension) - High blood pressure (hypertension) - Irregular heartbeats (arrhythmia) - Central Nervous System: - Hallucinations - Mental disorders (psychosis) - Seizures - Change in mental state (altered mental status) - Gastrointestinal System: - Electrolyte imbalances due to vomiting and diarrhea

The prognosis for Cholinergic Crisis varies between 3% and 25% death rate. The most frequent cause of death in this situation is worsening problems with breathing.

A clinical toxicologist and an intensive care unit specialist.

Join our newsletter

Stay up to date with the latest news and promotions!

"*" indicates required fields

This field is for validation purposes and should be left unchanged.

We care about your data in our privacy policy.