Delirium: causes and pathogenesis

The causes of delirium

The elucidation of the cause of delirium is based on the clinical interpretation of the data that was obtained. The main categories of disorders that need to be excluded include infections, metabolic and endocrine disorders, injuries, nutritional or exogenous effects, neoplasms, drug effects or substance abuse. In DSM-IV, the following categories of states that cause delirium are distinguished: general diseases, intoxication or abstinence, delirium of multiple etiology, resulting from several causes. Most often the development of delirium depends on a combination of many provoking factors. Not all causes of delirium are reversible or become known.

Delirium caused by intoxication or withdrawal of psychoactive substances

Intoxic delirium is diagnosed when it occurs due to the administration of a medicinal or other chemical substance. The purpose of treatment in this case is to remove this substance from the body. The substance that caused delirium can be determined from anamnesis, physical examination or laboratory examination, for example, toxicological screening. It may be important to get acquainted with the most common intoxication syndromes, as this will make it possible to conduct a laboratory study more specifically, in particular, to include in the screening program a study for additional agents. Consultation can be obtained at the local toxicology center, which has a database on reactions to the most frequent medicines, chemicals, plants. After identifying the suspected agent that caused delirium, adequate treatment can be initiated. There are developed methods for treating overdose with substances such as acetaminophen, aspirin, organic solvents, ethylene glycol, opioids, benzodiazepines, barbiturates, anticholinergics. The physician should also be familiar with the most common substances that are abused and capable of causing delirium. These include cocaine, phencyclidine, heroin, alcohol, nitrous oxide, spid, marijuana, ecstasy. Delirium caused by opioids can be stopped by naloxone, an antagonist of opioid receptors. The effect of the drug is often temporary and can trigger an abstinence syndrome. During delirium or intoxication, patients who abuse opioids have an increased risk of contracting HIV through general needles or through sexual contact.

Intoxication with benzodiazepines can also trigger delirium. In addition to supporting measures, treatment in this case may include the administration of a benzodiazepine receptor antagonist to flumenese. When treating an overdose of benzodiazepines, alcohol or opioids, it is important to avoid the development of an abstinence syndrome, as it can itself be the cause of delirium. Treatment should include controlled detoxification in order to prevent the increase in delirium or even death, which may be associated with the development of withdrawal symptoms.

With alcohol and benzodiazepine withdrawal, the agent that caused delirium is replaced with benzodiazepine and the dose of the drug is gradually reduced. The dose of benzodiazepines should be brought to a level that prevents hyperactivity of the autonomic nervous system. In addition, with alcohol withdrawal, the patient should be prescribed thiamine, folic acid, as well as multivitamins. Benzodiazepine detoxification is often carried out more slowly than alcohol detoxification. Opioid withdrawal syndrome manifests itself as flu-like symptoms and may be accompanied by delirium. In the case of resorting to a gradual withdrawal of the opioid or its replacement with a long-acting opioid, for example, methadone. Treatment of dependence on psychoactive substances also includes non-drug measures. An example is the "12 Steps" program, used by the Society of Anonymous Alcoholics and the Society of Anonymous Drug Addicts.

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The pathogenesis of delirium

Hoth delirium was first described in the medical literature at least 2500 years ago, the pathogenesis of this syndrome remains unclear, although there are several theories of its origin.

Neurochemical changes

Since the cholinergic system participates in the processes of attention, wakefulness, memory, sleep with rapid eye movements, a decrease in its activity may be a factor in the pathogenesis of delirium. Moreover, it has been shown that anticholinergic drugs weaken memory and concentration of attention and are capable of causing delirium, and at delirium their serum level is increased, and at its resolution - decreases. The introduction of atropine to laboratory animals causes behavioral changes and EEG, which indicates the important role of the cholinergic system in the development of delirium. Cognitive impairment caused by anticholinergic drugs can be stopped by acetylcholinesterase inhibitors-physostigmine, donepisyl or ENA-713.

Dopaminergic system can also play a role in the pathogenesis of delirium. Neuroleptics block the activity of the dopaminergic system and reduce the symptoms of delirium. Means that enhance dopaminergic activity, such as levodopa, buproprion and amantadine, can cause delirium as a side effect. Hypoxia, which can also cause delirium, increases the extracellular level of dopamine.

In cerebrospinal fluid, the level of somatostatin-like reactivity and beta-endorphin in patients with delirium is lower than in healthy individuals of the same age. This decrease in protein concentration persisted for the following year. However, since these patients were diagnosed with a degree of dementia, it is this factor that can cause a decrease in the level of beta-endorphin and somatostatin in the cerebrospinal fluid.

Damage to neurons

Changes in oxidative metabolism can lead to neuronal damage. In one report, changes in the EEG associated with delirium regressed in patients with hypoxia on the background of oxygen treatment, in patients with hypoglycemia after glucose administration, and in patients with anemia after blood transfusion. In subsequent studies, direct investigation of the processes of oxidative metabolism in delirium was not carried out. Hypoxia and hypoxemia reduce the synthesis and release of acetylcholine, which can explain the relationship between the change in oxidative metabolism and delirium.

Changes in the glu- matergic transmission in the brain can lead to the development of apoptosis and damage to neurons. Thus, excessive activation of NMDA receptors causes cell death, and phencyclidine is capable of causing delirium by blocking these receptors. Ketamine, also blocking NMDA receptors, affects the level of consciousness. In the future, for the treatment of delirium, agonists of glutamate NMDA receptors may be used.

Damage to the blood-brain barrier can also lead to neuronal damage and delirium. Intraventricular administration of interleukin-1 to experimental animals resulted in the development of clinical and EEG delirium manifestations. Delirium often occurs in patients who are being treated with interleukin-2 chemotherapy, lymphokine-activated killer cells or alpha interferon. Presumably, the mechanism of delirium development is associated with damage to the endothelium of the capillaries and the blood-brain barrier.

The study of the mechanisms of delirium development in hepatic encephalopathy can help to elucidate the pathogenesis of this condition. These include the accumulation of unmetabolized ammonia, the production of false neurotransmitters, activation of GABA receptors, changes in cerebral metabolism, and Na + / K + / ATPase activity. A certain role can also play the deposition of manganese in the basal ganglia, zinc deficiency, changes in the activity of urea cycle enzymes. The most effective approach to the treatment of hepatic encephalopathy is to increase the metabolism of ammonia or reduce its production.

[6], [7], [8], [9], [10], [11]