Cholinergic Crisis: Causes, Symptoms & Treatment

Cholinergic crisis is caused by an overdose of cholinesterase inhibitors. It is characterized by acute muscle weakness and nicotine-like side effects.

What is a cholinergic crisis?

A cholinergic crisis occurs when there is an excess of acetylcholine. Acetylcholine is biogenic amine that functions as a neurotransmitter in the body. The neurotransmitter is found in both the central nervous system and the peripheral nervous system. Among other things, it acts at the neuromuscular end plate, where it enables the voluntary movements of skeletal muscles. However, acetylcholine also occurs as a signal substance in the preganglionic neurons of the parasympathetic and sympathetic nervous systems. When an action potential arrives, acetylcholine is released into the synaptic cleft. There it binds to the so-called cholinoceptors. These are receptors on the postsynaptic membrane. Binding to the receptor changes the ion permeability. This change can result in inhibition or excitation. Subsequently, acetylcholine is cleaved into acetic acid and choline in the synaptic cleft by the enzyme acetylcholinesterase. The neurotransmitter is produced in the terminal heads of certain axons. Acetylcholine is produced from choline and acetyl-CoA by the enzyme choline acetyl transferase and stored in small vesicles in neurons.

Causes

Under normal circumstances, endogenous synthesis processes cannot induce a cholinergic crisis. The main cause is overdose of acetylcholinesterase inhibitors. Inhibition of the enzyme acetylcholinesterase causes less acetylcholine to be broken down, resulting in an oversupply. However, this requires dosages of at least 600 milligrams of pyridostigmine per day. Purely cholinergic crises are generally rare. More often, signs of overdose mixed with symptoms indicating acetylcholine deficiency are found in poorly controlled patients. Acetylcholinesterase inhibitors (AChE inhibitors) are used to treat Alzheimer’s disease. Alzheimer’s disease refers to a progressive atrophy of the cerebral cortex. This is accompanied by a decline in cognitive, social and emotional abilities. Affected patients suffer from forgetfulness, memory loss, a lack of speech comprehension, speech disorders and a lack of sympathy. Taking acetylcholinesterase blockers is thought to increase neuronal excitability. Although this does not cure the disease, it does relieve symptoms.

Symptoms, complaints, and signs

In an overdose, too much acetylcholine remains in the synaptic cleft. This causes generalized muscle weakness. Patients experience shortness of breath due to weakness of the respiratory muscles. The shortness of breath is aggravated by a strong bronchial secretion. Due to the increased secretion, pulmonary edema may develop in an emergency. Pulmonary edema is characterized by shortness of breath, severe cough, and frothy sputum. Patients feel nauseous and vomit. Profuse sweating is also a typical symptom of cholinergic crisis. Furthermore, gastrointestinal cramps and diarrhea may occur. The heartbeat is slowed and blood pressure is too low (hypotension). A slowed heartbeat is also called bradycardia in medical terminology. Typical of cholinergic crisis are the so-called fasciculations. These are involuntary contractions of very small muscle groups. These are visible just under the skin, but usually do not result in any movement. In many cases, these small muscle twitches can be provoked by pinching the muscle. However, in addition to these small muscle movements, large and painful muscle spasms can also occur. Patients experience anxiety and may show cerebral symptoms. Other symptoms that may occur during a cholinergic crisis include increased salivation and constricted pupils. Nicotine-related side effects also include bladder voiding dysfunction.

Diagnosis and course

The diagnosis is usually made on the basis of the clinical presentation. A brief medication history can quickly confirm suspicion. Radiographs or CT scans may show pulmonary edema, depending on the severity of the cholinergic crisis. Physical examination will reveal decreased blood pressure and pulse. The cholinergic crisis must be differentiated from the myasthenic crisis.Myasthenic crisis is a complication of the disease myasthenia gravis. Myasthenic crisis is accompanied by almost the same symptoms. However, it lacks the muscarinic and nicotinic side effects. Thus, unlike cholinergic crisis, myasthenic crisis does not cause diarrhea or other gastrointestinal symptoms.

Complications

In most cases, cholinergic crisis results in very severe muscle weakness. In this case, the patient is usually no longer able to perform ordinary activities of daily living and is severely limited as a result. Respiratory distress may also occur. Many patients react to shortness of breath with a panic attack, which further worsens the condition. The shortness of breath itself is often also associated with a cough. It is not uncommon for sufferers to experience diarrhea and stomach discomfort similar to the stomach flu. The patient’s quality of life is extremely reduced by the cholinergic crisis and honest limitations occur. Emptying of the bladder can also often no longer be controlled and there is increased salivation. Treatment is primarily aimed at controlling the breathing difficulties. This also stabilizes the circulation and prevents acute kidney failure. The patient must take antibiotics. In severe cases, an antidote may also be administered. If the symptoms are recognized and treated early, no further complications usually occur.

When should you see a doctor?

If muscle weakness and other signs of a cholinergic crisis occur after taking cholinesterase inhibitors, a doctor should be consulted immediately. If shortness of breath and severe coughing are added, there is a risk of pulmonary edema – so alert emergency services immediately. General symptoms such as gastrointestinal complaints and cardiovascular problems should also be clarified quickly. Since the cholinergic crisis is a medical emergency in any case, do not wait with the medical diagnosis. In particular, people who regularly take cholinesterase inhibitors are at risk. Taking appropriate medication is best done under medical supervision. If this is not possible, the medication should be slowly adjusted to the desired level so that a cholinergic crisis does not occur in the first place. If the medication does become overdosed: Do not wait for the aforementioned symptoms to appear, but immediately go to the nearest hospital. There, neurological and intensive medical monitoring may be initiated immediately. If symptoms then occur, the necessary measures can be taken immediately.

Treatment and therapy

Cholinergic crisis is an emergency requiring immediate neurologic and intensive medical monitoring. The focus is on stabilization of breathing and circulation. Often, maintenance of breathing is possible only by intubation. Artificial respiration may be required. Attention must also be paid to renal function, as renal failure may also occur in the course of cholinergic crisis. If infection is suspected, antibiotic therapy must be initiated early. The muscarinic side effects such as diarrhea, increased salivation, and increased sweating can be well treated with atropine as an antidote. An antidote is also called an antitoxin. Atropine is an alkaloid found in nightshade plants such as angel’s trumpet, belladonna, datura, and henbane. It has a parasympatholytic effect, i.e., it reduces the action of the parasympathetic nervous system. It also displaces excess acetylcholine from muscarinic receptors. If the cholinergic crisis was precipitated by an overdose of acetylcholinesterase inhibitors, patients must be immediately restarted on medication.

Outlook and Prognosis

Without prompt emergency medical treatment, cholinergic crisis results in patient death. In most cases, survivors suffer from lifelong health impairments. In addition to muscle discomfort as well as motor limitations, anxiety results from the experienced respiratory distress. This can lead to psychological problems, which significantly alters the healing process. The patient’s general physical condition often remains severely weakened, resulting in decreased performance. With immediate medical attention, some patients experience a full recovery after a few months of the emergency.The effects of intubation have subsided and ventilation occurs by a natural route. Therefore, the prognosis of a cholinergic crisis is not the same for all patients. However, complete recovery is rather rare. In most cases, the affected person suffers from another underlying disease that cannot be cured. Although the cholinergic crisis is overcome in these patients, the underlying disease leads to permanent damage due to the already weakened state of health. Since the cause of the cholinergic crisis is usually an excess of acetylcholine or other substances, a renewed cholinergic crisis occurs only in rare exceptional cases. Medical treatment stabilizes the patient so that relapse does not occur.

Prevention

The cholinergic crisis can be prevented only by a well-controlled medication. Therefore, the physician should be consulted at the slightest signs of overdose. Warning signs include muscle twitching, headache, and increased salivation. Diarrhea may also indicate an acetylcholinesterase blocker overdose.

Follow-up

During follow-up of cholinergic crisis, it is important that the medication is properly adjusted by the physician. This means that patients need regular follow-up appointments. This allows for accurate adjustment, which can prevent later cholinergic crises or at least reduce the risk. In connection with the therapy, the dose should be strictly adhered to. In the event of an overdose, patients must seek immediate medical attention or go to hospital. Here, depending on the circumstances, intensive medical and neurological monitoring takes place. Since the cholinergic crisis is often accompanied by other diseases, the appropriate therapeutic measures must also be carried out. Otherwise, the underlying disease may cause an exacerbation or even permanent damage to health. For this reason, medical treatment and care are essential. Relapses can also be avoided by stabilizing health. Close monitoring of signs related to the disease is also part of follow-up care. If acute muscle weakness is feared at an inopportune time, it is also wise to take certain measures to prevent accidents. Sufferers should be careful with their own health. Less stress and strain will help contain the dangers in daily life.

Here’s what you can do yourself

A cholinergic crisis is an emergency that usually requires immediate intensive medical monitoring. Without immediate emergency medical intervention, life may even be in danger. After surviving a cholinergic crisis, the further prognosis is not the same for all patients, nor can a complete recovery be assumed in the majority of cases, unfortunately. Therefore, complete education of the patient about the clinical picture and its leading symptoms is of crucial prognostic importance. The aim of intensive medical treatment is initially to stabilize the patient, but also to keep the risk of relapse as low as possible. Here, the cooperation of the patient is absolutely necessary in the sense of prophylaxis of a renewed crisis. First of all, a suitable individual medication must be put together, which is also adjusted to other underlying diseases. The adjustment with the medication can only be successful if a patient also adheres strictly to the prescription plan in the long term. Unauthorized discontinuation or change of medication could quickly lead to a renewed cholinergic crisis. Overdosing must also be avoided at all costs. The acetylcholinesterase blocker, which is frequently used against the clinical picture, causes typical warning signs in the case of overdose, which the patient must recognize at all costs in order to recognize a renewed cholinergic crisis at an early stage. These include, in particular, diarrhea, increased salivation, uncontrolled muscle twitching, and headache. Even the appearance of just one of these symptoms should therefore be reason enough to consult the doctor in the context of self-help.