Acute cholinergic syndrome is characterized by increased stimulation of the vagus nerve. The cause of this stimulation is an increased concentration of acetylcholine, which is a neurotransmitter in the parasympathetic nervous system. Treatment of acute cholinergic syndrome is by blocking muscarinic acetylcholine receptors with atropine.
What is acute cholinergic syndrome?
Acute cholinergic syndrome is characterized by increased stimulation of the vagus nerve. The cause of this stimulation is an increased concentration of acetylcholine. Acute cholinergic syndrome represents overstimulation of the vagus nerve. The vagus nerve is a part of the parasympathetic nervous system, which is responsible for the function of the internal organs. Stimulation of the parasympathetic nervous system is accomplished by the neurotransmitter acetylcholine. For this purpose, acetylcholine binds to the nicotinic or muscarinic acetylcholine receptors of the nerve cells. In addition to acetylcholine, nicotine can also bind to the nicotinic acetylcholine receptors. Accordingly, the muscarinic toxin muscarin, which is found in fly agaric, for example, can bind to the muscarinic acetylcholine receptors. In acute cholinergic syndrome, there is an oversupply of acetylcholine, which leads to the corresponding symptoms via binding to the muscarinic acetylcholine receptors of the vagus nerve. The vagus nerve represents the tenth cranial nerve. It is responsible for the regulation of almost all internal organs. In Latin there is the word “vagaris”, which means “to wander around”. Therefore, the term vagus nerve in translation means the “roving nerve”. It innervates various organs to control their motor or sensory function. It has a particular influence on the involuntary control of the motor function of the larynx, pharynx and esophagus. Furthermore, it mediates the taste sensations of the tongue or touch sensations in the pharynx, external auditory canal or larynx. In the chest and abdomen, the vagus nerve is responsible for mediating reflexes. This affects the heart, lungs, trachea or esophagus in the chest cavity. In the abdominal cavity, the stomach, pancreas, intestines, gall bladder, liver or even kidneys are stimulated. Therefore, overstimulation of these organs occurs in acute cholinergic syndrome.
Causes
Because the neurotransmitter acetylcholine is responsible for stimulating the internal organs, too much acetylcholine must be present in acute cholinergic syndrome. Acetylcholine is broken down into choline and acetic acid with the help of the enzyme acetylcholinesterase after release in the synaptic cleft. However, if the enzyme is suppressed in its effectiveness, this degradation can no longer take place sufficiently. Thus, acetylcholine accumulates in the synaptic cleft. It binds more strongly to the acetylcholine receptors, which then begin permanent signal transmission between the individual nerve cells of the vagus nerve. The enzyme acetylcholinesterase can be deactivated by certain organophosphate compounds, among others. These organophosphates irreversibly bind to the active site of the enzyme. These substances include the nerve agents tabun and sarin or the pesticides malathion and diazinon. The chemotherapeutic agent irinotecan also inhibits the enzyme acetylcholinesterase. The same applies to the drugs neostigmine and physostigmine, both of which are reversible inhibitors of acetylcholinesterase. This means that although the drugs bind to the enzyme, they can be cleaved again. Overall, it can be said that acute cholinergic syndrome is a poisoning syndrome. The effects of these poisons vary. The nerve agents tabun and sarin were used as combat agents in war. They have a lethal effect within seconds, whereas other acetylcholinesterase inhibitors produce milder symptoms.
Symptoms, complaints, and signs
Acute cholinergic syndrome is characterized by symptoms of diarrhea, sweating, increased salivation, watery eyes, abdominal pain, constricted pupils with visual disturbances, lightheadedness, dizziness, malaise, chills, conjunctivitis, and low blood pressure due to vasodilation. All symptoms are expressions of motor as well as sensory overstimulation of internal organs. In the best case, they are side effects of the use of certain medications.Organophosphorus compounds, however, can already cause massive poisoning, often leading to death in seconds in the case of the nerve agents tabun and sarin.
Diagnosis and course
The diagnosis of acute cholinergic syndrome is based on the history of the patient. Compilation of the typical symptoms may already lead to a tentative diagnosis. It is also analyzed which drugs were administered in which concentration. In addition, it can also be inquired in this context with which substances the affected person has otherwise come into contact.
Complications
The tenth cranial nerve, known as the vagus nerve, is responsible for regulating a large number of the internal organs. Patients suffering from acute cholinergic syndrome exhibit overstimulation of this cranial nerve, causing immediate dysfunction of the affected organs in the chest and abdomen. This overstimulation affects the heart, liver, lungs, esophagus, and trachea in the chest. In the abdominal cavity, the pancreas, stomach, intestines, liver, gallbladder and kidneys are affected. Acute cholinergic syndrome has a particular impact on the control of motor function in the pharynx, esophagus, and larynx. The multiple organic disorders cause diarrhea, eye tearing, increased salivation, and abdominal pain. Low blood pressure, muscle spasms and dilated vessels are also typical. This symptomatology is treated with the neurotoxin atropine. This produces an opposite effect, leading to blockage of the parasympathetic nervous system. This blockage is called anticholinergic syndrome. Therapy with atropine as an antidote eliminates the multiple organic disturbances. Since in most cases this poisoning syndrome is due to drugs that act directly on the autonomic nervous system, patients receive a positive prognosis. A complete cure usually occurs after a short period of treatment. Treatment must be given promptly after diagnosis or severe complications may occur.
When should you see a doctor?
In this syndrome, there are very many different symptoms. As a rule, a doctor should always be consulted. Since the symptoms usually occur after taking certain medications, these must either be discontinued or replaced by other medications. However, this should always be done only after consulting a doctor. The affected person suffers from malaise, drowsiness and confusion. The ability of the affected person to cope with stress is also considerably reduced and visual disturbances or diarrhea may occur. If these symptoms occur for no particular reason, a doctor must be consulted in any case. Medical assistance is also necessary in case of low blood pressure or loss of consciousness. If there is a loss of consciousness, the emergency doctor can also be called. Not infrequently, the internal organs are also affected by this syndrome. Therefore, if there are problems with the kidneys or heart, urgent treatment of the patient is also necessary. In acute emergencies, a hospital should always be visited or the emergency doctor should be called.
Treatment and therapy
Acute cholinergic syndrome is mainly treated with the administration of atropine. Atropine is actually a poison that blocks the action of acetylcholine. It binds to the muscarinic acetylcholine receptor, displacing acetylcholine from this site. When the concentration of atropine is substantial, the opposite anticholinergic syndrome occurs, which is characterized by the blocking of the parasympathetic nervous system. However, when the concentration of acetylcholine is increased due to inhibition of acetylcholinesterase, atropine acts as an antidote, preventing the symptoms of acute cholinergic syndrome. In the case of the very potent organophosphorus neurotoxins such as tabun or sarin, treatment is often unsuccessful because these substances bind irreversibly to the enzyme, thus blocking it. However, it is mainly poisoning due to overdose with cholinergic drugs that respond much better to treatment with atropine. In addition to atropine, the active substance midazolam is also administered for muscle spasms. This substance from the benzodiazepine group enhances the effect of the neurotransmitter gamma-aminobutyric acid (GABA). If acidosis still occurs as a symptom, sodium bicarbonate is administered to neutralize it.
Outlook and prognosis
In this syndrome, patients usually suffer from various symptoms. In most cases, this involves watery eyes and severe diarrhea. Increased sweating and salivation are also common symptoms. Furthermore, the patient may also experience abdominal pain and drowsiness. The affected person feels unwell, tired and sick. There is a chill and not infrequently dizziness. Due to the reduced blood pressure, the affected person may also lose consciousness. This may possibly result in an injury due to a fall. It is not uncommon for this syndrome to also cause conjunctivitis. In very severe cases, the poisoning can cause the death of the patient after only a few minutes. Medication can be used to treat the symptoms of this syndrome. However, in some circumstances the internal organs are irreversibly damaged by the poisoning. Universal prediction about the course of the disease is not possible in this case. However, as a rule, with prompt treatment, there are no further complications and no reduction in life expectancy.
Prevention
To prevent acute cholinergic syndrome, overdose should be avoided when cholinergic drugs are administered.
Follow-up
As a rule, very few or even no measures and options for aftercare are available to the affected person with this syndrome. The affected person is primarily dependent on the rapid and, above all, early diagnosis of the syndrome, so that no further complications or complaints occur. Only early detection of this disease can prevent further complaints. Therefore, early diagnosis is in the foreground in this syndrome. The affected person is dependent on inpatient treatment for this disease, whereby this usually takes place in a closed institution. Furthermore, the affected person is often dependent on the care and support of his own family or friends, so that it comes to a relief in everyday life. Intensive and loving conversations are also very important to prevent depression and other psychological upsets. Furthermore, taking the antidote is also necessary to alleviate the symptoms. Thereby, the affected person should pay attention to a correct dosage and also to a regular intake. Whether there is a reduced life expectancy due to this syndrome cannot be universally predicted in this regard.
What you can do yourself
Acute cholinergic crisis is a medical emergency. The affected person or a first responder must alert the emergency physician and ensure that the physician is promptly informed of possible causes. If the symptoms occur immediately after ingestion of medication or any toxins, the physician should be informed. In addition, the patient should be placed in a quiet supine position and should not move until medical assistance arrives. Artificial vomiting should only be performed under the supervision of a professional. For severe abdominal pain or fever, home remedies such as cooling compresses or green tea will help. Medications should not be taken during an acute cholinergic crisis. The condition requires inpatient treatment. Afterwards, the patient should take it easy and, if necessary, change his or her diet to promote recovery. The triggering drug or toxin must be identified and avoided. The patient should consult the physician for this and, if necessary, also involve a nutritionist. If, despite all measures, signs of acute cholinergic syndrome reappear, the physician in charge must be informed immediately.
