WHAT IS DELIRIA SYNDROME AND HOW TO TREAT IT

Alan T. Bates, MD, PhD and Yesne Alici, MD December 20, 2014

Delirium is a mental disorder from which no one is immune. Because, if you're unlucky, even the right set of medications prescribed by a doctor can cause attention problems, disorientation and psychosis in any of us.

However, despite the universality of the risk, relatively high prevalence and potential long-term consequences, the topic of delirium is nowhere addressed; there are no public groups dedicated to promoting, preventing, or even informing humanity about the seriousness of the disorder. Even in medicine, delirium cannot find a home. Describing this pathology in 1959, Engel and Romano placed it somewhere between the field of internal medicine and the field of psychiatry: “... by an unfortunate coincidence, the topic of brain disturbances in delirium has been suspended between the interests of internists and psychiatrists...”.

The situation has not changed much since then, but modern developments in psychosomatic medicine, as well as wider recognition of the negative consequences of delirium by the medical and surgical communities, have helped to accelerate progress in this direction. The American Delirium Society and the European Delirium Association are examples of organizations working to bridge the gap between medical fields regarding delirium. Advances in the prevention and treatment of delirium will not happen overnight; and delirium promises to burden the healthcare system with “dementia-related costs” for a long time to come. Meanwhile, more and more evidence is accumulating in support of Engel and Romano's seemingly prescient claim that delirium “...carries a serious risk of permanent and irreversible brain damage.”

Diagnosis: from DSM-IV to DSM-5

The DSM-IV diagnostic criteria for delirium can ultimately be reduced to impairments of consciousness (eg, changes in orientation or attention) associated within this clinical entity with other cognitive impairments (eg, memory, language disorders) if they are not the result of dementia. The next criterion is a relatively acute onset with fluctuations in the severity of symptoms throughout the day; and the last criterion: delirium is usually caused by some disease (for example, pneumonia).

As has been the case with many other diagnoses, delirium has become the subject of much debate: what changes should be made to the DSM-5? After all, the differences between DSM-IV and DSM-5 are very small. As a result, the DSM-5 omits the vague concept of “consciousness”; the emphasis is placed directly on disturbances of attention and orientation. This clearly differentiates, for example, delirium and coma; less successfully - delirium and dementia (a disorder that is most often combined with delirium).

conclusions

Delirium is an acute condition with sudden development, having a different etiology. It causes persistent changes in consciousness, major disruptions in vital activity and is life threatening. Patients are not aware of their actions; such mental disorders can traumatize others. The effectiveness of delirium treatment is based on the emergency adoption of somatic measures, minimizing pharmacological therapy, and creating a trusting atmosphere. Only specialists can provide first aid, carry out separate measures, and guarantee recovery. It is strictly forbidden to fight psychosis on your own or not take any measures.

Delirium as a syndrome

Meagher et al attempted to describe delirium as a syndrome in detail using a sample of 100 patients receiving palliative care for their disorder. Some of the most common signs and symptoms they identified are the same as those mentioned in the DSM-5:

• Attention disturbance (97% of patients)

• Deterioration of long-term memory (89%)

• Deterioration of short-term memory (88%)

• Disorientation (76%)

• Decreased ability for spatial-visual orientation (87%)

• Speech disorders (57%)

• Perceptual disturbances (50%)

Since hallucinations are the symptom that most often brings patients to a psychiatrist, it is worth noting that at least half of the patients denied their presence.

The results of this study highlight other pitfalls in the path of the clinician dealing with delirium disorder. Physicians in medical records usually abbreviate phrases regarding activity and disorientation in self, place and time, replacing them with shorthand: “A&O ? 3” (“alert, oriented to person, place, and time” = “active, oriented to person, place and time”). Even if this record reflects a thorough examination of disorientation, 25% of the patients in the sample show abnormalities on at least one item. Meagher and colleagues also reported sleep-wake cycle disturbance (97%), motor agitation (62%), and retardation (62%) as common symptoms, although these symptoms are not listed among DSM-5 criteria. The fact that each of these three symptoms—in addition to their widespread prevalence—occurs in the early stages of delirium reflects their important clinical significance. Common signs and symptoms of delirium are listed in Table 1.

Causes

The cause of the development of alcoholic delirium is the systematic abuse of alcohol and its substitutes for 5-10 years, accompanied by a long period of heavy drinking and a sharp withdrawal from it. Factors that provoke the development of alcoholic delirium include pathologies of the central nervous system/traumatic brain injury, previous alcoholic psychosis , infectious diseases , concomitant somatic pathology , intoxication with other substances / medicines .

Variants of the course and differential diagnosis of delirium

One of the most common discussions between clinicians after evaluating the same patient is whether the patient is confused or cognitively intact. The wave-like nature of the course of delirium can lead to the fact that the patient during the examination reveals, for example, exceptional clarity of mind, and after a few hours finds himself completely disorganized and disoriented. Instead of serving as a basis for suspecting colleagues of incompetence, these polar assessments should have been accepted as important diagnostic information.

Consequences of delirium tremens and complications

The consequences of alcoholic delirium are largely determined by the severity of its course, the presence of concomitant somatic pathology and the timeliness of treatment. Complications of severe alcoholic delirium may include water-electrolyte imbalance, liver cirrhosis , acute renal failure , alcoholic cardiomyopathy , acute pancreatitis , acid-base imbalance, rhabdomyolysis , pneumonia , cerebral edema .

Persons who have suffered acute alcoholic psychosis in the form of moderate/severe acute or chronic alcoholic encephalopathy with severe hallucinatory/delusional manifestations and suffering from stage 2-3 alcoholism may be limited in their ability to work for various periods.

Rating scales

Rating scales may have a role in differentiating delirium from other disorders and in monitoring response to therapy. Although there is no single generally accepted scale for diagnosing delirium, the Mini-Mental State Examination (MMSE) is most often used for this purpose. This scale provides a rough assessment of a range of cognitive functions such as orientation, language, numeracy and memory. However, the MMSE does not differentiate delirium from other causes of cognitive dysfunction, although deficits in various cognitive domains may certainly be caused by other specific lesions or deficits.

The Montreal Cognitive Assessment (MoCA) has similar shortcomings, although many clinicians have begun to use it instead of the MMSE for brief cognitive screening. MoCA has greater sensitivity in detecting mild cognitive impairment and provides better assessment of frontal cortex functions, including executive functions, abstract reasoning, and word generation. This scale is free and available for clinical use in several languages at www.mocatest.org.

Several rating scales for delirium have been developed, and each has its own advantages and disadvantages. The Confusion Assessment Method (CAM) is used probably because of its simplicity. It contains only 4 points (acute onset and wave-like course; decreased level of attention, and either disorganized thinking or a change in the level of consciousness); that is, this scale can be used to assess a patient's condition by nurses and other health care personnel with less training in psychiatry. While the relative simplicity of CAM allows it to be used for screening large numbers of patients in non-psychiatric areas of medicine, its sensitivity may depend largely on the individual experience of the examiner.

Ely et al adapted the CAM scale for use in mechanically ventilated patients in intensive care units and named the CAM-ICU scale. However, some caution must be exercised when using the CAM-ICU outside the specific IT department environment, because in these cases it is not sensitive enough.

The Delirium Rating Scale-Revised-98 (DRS-R-98), which includes 13 severity criteria and 3 diagnostic criteria, can be used to differentiate delirium from dementia, depression, or schizophrenia; and also to assess the severity and record the phenomenological features of a particular case for clinical or research purposes. This scale is usually used by doctors with psychiatric training.

The Memorial Delirium Assessment Scale (MDAS) is also intended for use by clinicians with more advanced training. The MDAS, which was originally approved for use with patients with advanced cancer or AIDS, was designed to be administered repeatedly over the same day, thereby providing an assessment of the patient's progress in response to therapy or medical procedures.

Despite the fact that the diagnosis often indicates one or another subtype of delirium, even the most comprehensive rating scales, as a rule, contain only 1 or 2 items aimed at differentiating these subtypes (for example, in the DRS-R-98 scale - item 7: “Motor agitation” and item 8: “Motor retardation”; in the MDAS scale – item 9: “Decreased or increased psychomotor activity”). While rating scales are very valuable and can be useful clinical tools, the gold standard for obtaining information about attentional fluctuations remains a thorough clinical assessment, supplemented by information from family and medical personnel.

Stress for patients, their families and medical staff.

Delirium is often a very frightening experience for patients, their families and friends. It can also make nursing care difficult or even dangerous. Breitbart and colleagues found severe delirium-related distress among hospitalized cancer patients, as well as their spouses, caregivers, and nurses. The presence of delusional disorders was the strongest predictor of distress in patients with both hypoactive and hyperactive delirium.

Jones and colleagues demonstrated an association between delusional memories and PTSD in ventilated patients in intensive care units. Overall, they found that 9.2% of previously mechanically ventilated patients in intensive care units developed associated PTSD 3 months after weaning from the ventilator.

Long-term consequences

Although it is difficult to definitively trace cause and effect, there is growing evidence that delirium is associated with long-term cognitive decline. Bickel et al examined cognitive function in 200 patients over 60 years of age 38 months after hospital discharge for hip surgery. In 41% of cases, patients experienced postoperative delirium. During follow-up, the MMSE score was below 24 in 54% of patients who experienced delirium and only 4% of those who did not. Processing the study results using logistic regression - taking into account the age, gender, concomitant disease and preoperative level of cognitive function of patients - revealed a significant association between the experience of delirium and existing cognitive deterioration, subjective memory loss and the need for long-term care.

Meta-analysis results show that in older patients, delirium is associated with an increased risk of death (38% versus 28% in the control group) at a mean follow-up of 23 months, and an increased risk of social maladjustment (33% versus 11%) at a mean follow-up of 15 months. , and an increased risk of dementia (63% versus 8%) over a median follow-up of 4 years. Studies included in the meta-analysis certainly took into account additional factors such as age, gender, comorbidity, severity and premorbid dementia.

More recently, Pandharipande and colleagues assessed cognitive decline in patients with respiratory failure or shock who required intensive care in their study. The researchers found that delirium developed in 74% of the 821 people who took part in the experiment. At 12-month follow-up, 34% of patients in this sample had cognitive function at the same level as patients with moderate traumatic brain injury, and 24% had levels consistent with mild Alzheimer's disease. Longer duration of delirium correlated with more severe cognitive dysfunction in prognosis.

Typology of disorders of consciousness

Disorders of consciousness are extremely heterogeneous, ranging from inhibition to excitation [18], in extreme cases of inhibition at times approaching comatose states, and in extreme cases of excitation resembling schizophreniform psychoses. Cognitive disorders also vary in severity, including both forms of cognitive impairment that are limited to attention disorders and forms with transient “focal” cognitive deficits.

Psychiatrists who have studied the clinical features of somatogenic psychoses have described a variety of manifestations of disorders of consciousness. In a systematic analysis of symptomatic psychoses, K. Bonhoeffer [19] distinguished delirious, amental and twilight disorders of consciousness. Following him, E. Kraepelin [20] mentioned delirium and amentia as manifestations of parainfectious psychoses. In later classifications, amentia could be classified as a type of delirium [4], which was confirmed by early observations that identified forms of delirium with more pronounced cognitive fragmentation [19]. Recent work conducted with the participation of a contingent of elderly patients in a multidisciplinary hospital [21] revealed several types of confusion, including delirium (37.9%), amentia (18.7%) and forms of confusion with confabulation (11.8%), approaching Korsakov's syndrome.

Despite the fact that the boundaries between different types of disorders of consciousness are blurred, the creation of a clinical typology has not only scientific, but also practical value. First, it equips the researcher with a more sensitive diagnostic tool that can capture individual differences while at the same time integrating them into delineated nosological units. Secondly, attention to various clinical manifestations allows us to evaluate their prognostic significance.

Another trend (and so far the prevailing one) is to follow the syndromic and statistical classification, which, without making a nosological distinction, combines a variety of post-stroke clouding of consciousness into the group F05.x “Delirium not caused by alcohol or other psychoactive substances” [22]. But even with a syndromic approach, clinical needs force us to consider syndromes that go beyond the usual somatogenic psychoses: for example, evening confusion in patients with dementia [23, 24].

Although foreign works do not distinguish between delirious, oneiric and amentive disorders of consciousness, such a distinction is of great practical importance, since different syndromes may have different etiologies and prognosis. Thus, delirious and oneiric symptoms are often found in infectious-toxic diseases [25].

The creation of a clinical typology for patients with brain damage primarily pursues a pragmatic goal - to distinguish disorders directly related to damage to certain structures from disorders the appearance of which is caused by secondary factors (biochemical post-ischemic cascade or intoxication of a somatic nature).

In this regard, the approach of the Russian neuropsychiatric school, which is used to classify the consequences of traumatic brain disease, is interesting [26]. The authors separate the syndromes of stupefaction (delirium, oneiroid, twilight changes in consciousness) from various forms of confusion (amnestic, amnestic-confabulatory, speech, etc.). The presence of confusion reflects predominantly the disintegration of cognitive functions (and certain damage to brain structures), while delirium and oneiroid are manifested by disorientation, closely associated with hallucinatory-delusional symptoms (and secondary toxic brain damage).

Mortality

In at least some cases, delirium has been associated with premature death in patients. In a controlled study of baseline cognitive function, physiological function level, and general health status, Curyto et al found that delirium in hospitalized older adults was significantly associated with an increased mortality rate at 3 years after hospitalization (75% vs. 51% in the control group). ). The same negative association was seen between delirium and mortality in elderly patients. The development of delirium in mechanically ventilated patients in the intensive care unit also appears to be a very poor prognostic sign. In elderly intensive care unit patients, the risk factor appears to be not only the occurrence of delirium, but also its duration.

Outpatient

The second part of the therapy can be done at home. Recovery takes place under the supervision of a specialist. Therapy includes:

A calm atmosphere and establishing contact with others. At home, the patient should be given attention, not disturb him unnecessarily and not cause negative emotions. It is important not to raise your intonation or provoke conflict. Initially, the patient may experience frequent mood swings, aggression, and tearfulness. Occasionally, a distortion of reality is recorded.
Elimination of factors that provoke the condition. The drug that causes psychosis should be immediately removed from the patient’s field of vision. If the cause was delirium tremens, you should give up any alcoholic beverages and undergo coding. If a factor cannot be excluded (for example, a systemic disease), then it is worth minimizing its consequences by continuing therapy as indicated.
Psychotherapy. To restore the ability to think and soberly assess the situation, as well as to track dynamics, it is recommended to continue psychotherapy. Group and individual lessons help.
Healthy lifestyle. Lifestyle also plays a certain role. It is especially important to give up smoking, drugs, alcohol and monitor your sleep patterns. To some extent, normalization of nutrition has a beneficial effect.

Many experts talk about the beneficial effects of reflexology, massage, and swimming. With timely treatment, proper treatment and compliance with recommendations, complete remission is usually observed.

Prevalence and incidence

An analysis of survey data from the East Baltimore Mental Health Review found that the prevalence of delirium in the community increases significantly with advancing age: 0.4% in patients over 18 years of age and 1.1% in patients over 55, but the rate is increasing up to 13.6% in patients over 85 years of age. Delirium can also develop in children. In pediatric practice, delirium develops in at least 30% of seriously ill children.

In persons over 75 years of age in nursing homes, the prevalence of delirium may approach 60%. There is also evidence of a high incidence of delirium in persons undergoing emergency medical intervention. The postoperative period is especially dangerous in this regard. Cardiac surgery is more likely to cause delirium than other types of surgery. The results obtained by Rudolph and colleagues call the incidence of delirium after cardiac surgery in patients over 60 years of age: 52%. Up to 70% of patients who require intensive care unit admission experience delirium at some point during their admission; and the incidence of delirium reaches 88% in patients with end-stage diseases.

Risk factors

Knowing the risk factors for delirium is important for 2 reasons. First of all, it can help predict the risk of developing delirium in the future. For example, the presence of multiple risk factors in the preoperative period might mean the need for prior consultation with a psychiatrist for complete postoperative monitoring. Elimination of the disease that may contribute to the development of delirium is the most radical way to treat it; for this reason, knowledge of the risk factors for its development helps to eradicate the main causes of delirium (Table 3).

Many researchers have attempted to identify premorbid risk factors that might predict (and hopefully prevent) delirium. There have been attempts to develop an algorithm that would standardize such a procedure. Despite the fact that certain risk factors in many studies have traditionally been assigned the role of the most threatening in terms of the development of delirium, there are still known discrepancies between the data of various studies. This is partly because the studies are conducted on dissimilar samples (for example, postoperative patients in one case and nursing home residents in another).

One of the most studied samples is patients of cardiac surgery clinics. Giltay et al collected data on 8139 patients who underwent coronary artery bypass grafting and/or artificial heart valve implantation. They found that postoperative psychosis was associated with preoperative factors such as age, renal failure, dyspnea, heart failure, left ventricular hypertrophy; and also with perioperative factors: hypothermia, hypoxemia, low hematocrit, renal failure, high blood sodium levels, infection and stroke. Unfortunately, despite the large sample size, the study did not identify a definitive list of key risk factors.

In a review of risk factors for delirium in heart surgery patients, Sockalingam and colleagues identified a long list of risk factors, ranging from the expected, such as opioid use, to the unexpected, such as marital problems. Here's an example of how risk factors vary across samples. Inouye et al described dementia, visual impairment, functional impairment, high comorbidity, and use of physical restraints as the most important risk factors for the development of delirium in older patients.

Pathogenesis

The pathogenesis of delirium tremens is still not fully understood. It is generally accepted that the development of the disease is based on the following factors:

Deficiency of various biologically active substances that ensure the normal functioning of nervous tissue

Particularly alcoholic patients are predisposed to a deficiency of vitamin B1 (thiamine), which is a cofactor for the main enzymes of the Krebs cycle/pentose phosphate pathway. Thiamine deficiency is caused by malnutrition, a factor of decreased absorption of the gastrointestinal tract, a decrease in the process of transformation of thiamine into the active form and, accordingly, a decrease in its content in liver tissue. Thiamine deficiency is one of the causes of metabolic , initiating tissue damage in areas of the brain with high metabolic demands, which is manifested by encephalopathies manifesting delirious symptoms.

Decreased GABA content in the central nervous system

Drinking alcoholic beverages enhances the release of the neurotransmitter GABA and increases the sensitivity of its receptor, which leads to an increase in inhibitory neurotransmission and changes in excitatory neurotransmission. Elimination of alcohol from the body disrupts the regulation of glutamate neurotransmission and contributes to the suppression of GABA activity, which leads to the development of alcohol withdrawal syndrome/alcohol withdrawal syndrome with delirium.

Excitotoxic effects of amino acids glutamate/aspartate

Alcohol competitively inhibits the binding of N-methyl-D-aspartate receptors in the brain to glycine , thereby stopping the effect of the excitatory neurotransmitter glutamate on NMDA receptors. The structure of the brain gradually functionally adapts against the background of chronic alcohol consumption, which forms the “phenomenon of tolerance.” In order to compensate for the inhibition of the binding process of NMDA receptors and glycine, the expression of NMDA receptors and the suppression of GABAA receptors are gradually increased. This process also results in the need to reach higher levels of alcohol in the blood to achieve the same effect. With the constant presence of alcohol in the body, a balance in stimulating and inhibitory effects is maintained.

Increased dopamine levels in the central nervous system

Against the background of chronic alcohol consumption, when it is withdrawn, there is an increase in the level of dopamine , which causes hallucinations and hyperexcitation.

Impaired metabolism of CNS modulators and changes in the activity of other neurotransmitters (acetylcholine, serotonin, endorphins, etc.)

Liver damage

Causes disruption of its detoxification function and inhibition of the process of synthesis of protein fractions of the blood, which contributes to toxic damage to the diencephalic parts of the central nervous system and disruption of compensatory neurohumoral mechanisms. As a result, the oxidation of alcohol slows down with the formation of the toxic product acetaldehyde .

Electrolyte imbalance

A particularly important role is played by the redistribution of electrolytes between extracellular fluid and cells. Thus, the trigger for the development of delirium is a sharp change in internal homeostasis . In some cases, the development of alcoholic delirium may be preceded by provoking factors - traumatic brain injuries, infectious diseases, concomitant somatic pathology, intoxication with drugs and other substances.

Pathophysiology

Maldonado, in his reviews, brought together everything that is known about the pathophysiology of delirium. He summarized the known theories and created several hypotheses: neuroinflammatory, oxidative stress, neurotransmitter deficiency, neuroendocrine, circadian dysregulation, network uncoupling and neuronal aging.

The neuroinflammatory hypothesis proposes that systemic inflammatory processes caused by infection or surgery trigger an inflammatory response in the brain. Evidence includes a study by de Rooij and colleagues, who found elevated cytokine levels in patients with delirium even after infection, age, and cognitive deficits were taken into account.

The oxidative stress hypothesis views delirium as a consequence of fundamental damage to brain metabolism with a lack of oxygenation, which leads to delirium disorder.

The neurotransmitter deficiency hypothesis is likely the best known and most basic. She describes delirium as a disorder associated with a deficiency of acetylcholine and an excess of dopamine. This theory is likely most closely related to clinical practice, since doctors who deal with delirium first of all try to find anticholinergic drugs among patients' medications and stop them. In addition, dopamine-blocking antipsychotics are standard pharmacological treatments for delirium.

The neuroendocrine hypothesis focuses primarily on the effects of elevated glucocorticoid levels observed during physiological stress. At Memorial Sloan Kettering Cancer Center, we routinely see patients who develop delirium in response to external glucocorticoids as part of chemotherapy regimens or to limit the side effects of drugs used to treat cancer.

The circadian dysregulation theory points to a link between delirium and disrupted sleep, and points to the fact that insufficient sleep usually precedes the onset of delirium.

The “network disconnect” hypothesis uses a systems neuroscience approach to explain the pathophysiology of delirium and incorporates evidence from modern imaging techniques, including functional MRI, of poor coordination between different parts of the brain.

The neuronal aging hypothesis combines aspects of several other hypotheses and provides a pathophysiological rationale for the fact that older patients are more susceptible to delirium. Maldonado emphasizes that there are "areas of overlap" between the main hypotheses and views them primarily as complementary rather than competing.

Stationary

The first aid for delirium is 24-hour hospitalization. In Moscow and other Russian cities, doctors are successfully fighting the condition and its consequences. Recovery is mainly achieved through a combination of medication and psychotherapy. The following stages are expected:

Detecting causes and prescribing appropriate therapy;
Minimizing the amount of medications taken;
Detoxification is carried out if necessary;
Creating a favorable and calm environment;
Relieving disorientation in space, time and society;
Drawing up a recovery plan for the body.

Before starting therapy, it is necessary to diagnose the brain using X-rays. The method of magnetic resonance or computed tomography allows identifying a condition of traumatic, organic etiology, as well as vascular, the treatment of which is important to begin immediately. Additionally, it is necessary to conduct a general blood and urine test. Laboratory tests make it possible to assess the patient’s condition, detect intoxication, inflammation, and symptoms of renal failure. The department of the hospital that treats delirium becomes specialized for the main diagnosis: narcology, gastroenterology, urology, nephrology.

Securing the patient should be strictly avoided. This leads to aggravation of the stage, the patient suffers and becomes nervous. Limb binding is used only in cases of life-threatening situations (suicide attempt) or during periods of aggression.

Non-drug prevention and treatment

In a study of 852 elderly patients admitted to a network of general hospitals, it was possible to reduce the incidence of delirium from 15% to 9% using a number of non-pharmacological measures, for example, frequent reorientation of patients, participation in cognitively stimulating activities, sleep induction with specific stimuli (eg , relaxation tapes, drinking warm milk), as well as using a sleep-promoting environment (eg, reducing noise), encouraging physical activity, using visual and auditory devices (eg, glasses, portable amplifiers), and early management of dehydration.

Although pharmacotherapy for delirium in elderly patients should be considered as a last resort after non-pharmacological approaches, most medical and surgical departments do not provide a therapeutic environment for patients (Inouye et al). Although it is clear that the most effective measures used to reduce the number and severity of delirium may be environmental changes in hospital wards and changes in the behavior of nursing staff.

Drug prevention

To date, the prophylactic use of antipsychotics in surgical patients has been studied little. Of the studies using haloperidol for this purpose, two found a reduction in the incidence of delirium, while the third only showed a reduction in the duration of delirium. There is some evidence that prophylactic use of risperidone and olanzapine reduces the incidence of postoperative delirium, and a meta-analysis shows that prophylactic use of antipsychotics reduces the incidence of delirium by half.

Prevention of delirium in intensive care units has not been as successful. In a sample of mechanically ventilated intensive care unit patients, there was no difference between haloperidol and placebo. Using a completely different pharmacological strategy, Al-Aama and colleagues found that in patients over 65 years of age who were hospitalized in intensive care units, the incidence of delirium was reduced by prophylactic use of melatonin.

Thus, there is evidence of the effectiveness of the use of antipsychotics to prevent the development of delirium in the postoperative period, but not in patients in intensive care units. Further research has confirmed the effectiveness of alternative strategies such as the use of melatonin.

Pharmacotherapy

Pathogenetic therapy for delirium involves eliminating its causes, which often requires the use of medications (for example, antibiotics to treat urinary tract infections). In addition, certain symptoms of delirious disorder are relieved with medication. Some researchers argue that symptom therapy serves only to reduce suffering and ensure the safety of the patient, visitors, and staff. Others point to the long-term consequences of delirium and suggest that treatments that reduce the severity and/or duration of delirium also reduce the risk of subsequent cognitive deficits.

Among the antipsychotics used to treat delirium, haloperidol is the most commonly used. A drug with potent dopamine antagonism and weak anticholinergic effects, haloperidol is a logical choice for treating a disorder thought to be associated with a hyperdopaminergic/hypocholinergic state. Other advantages of this drug include its potential for intravenous administration and lack of serious effects on the autonomic nervous system. However, when comparing the effectiveness of known antipsychotics against delirium, no difference was found between them.

• Chlorpromazine and risperidone were equally effective with haloperidol in a randomized, double-blind trial.

• No significant differences were found between olanzapine and haloperidol or risperidone in a randomized, blinded trial

• Quetiapine reduced the duration of delirium compared with placebo in a randomized, double-blind trial.

• No significant differences were found between aripiprazole and haloperidol in a non-randomized open-label study

When choosing a drug, it is best to be guided by the specific status of a particular patient. For example, quetiapine may be a good choice for the treatment of delirium in patients with Parkinson's disease.

It should be noted that completely different tactics must be used to relieve alcoholic delirium. The history of the search for this tactic is beyond the scope of this review, but, as a rule, the use of benzodiazepines is indicated in such a situation. Unfortunately, delirium delirium can be difficult to distinguish from other types of delirium. Factors that aid in the differential diagnosis of delirium tremens include a significant history of alcohol use, history of abstinence, and laboratory tests that support alcohol abuse (eg, positive blood alcohol test, elevated β-glutamyltransferase (GGT), elevated carbohydrate-deficient transferrin (CDT). , change and increase in the AST/AlAT ratio, increase in mean blood cell volume (MCV)), instability of vital functions, sweating and tremor.

Treatment of alcoholic delirium in a hospital

Alcoholic delirium (ALD) (delirium tremens, or delirium tremens) is one of the most severe urgent conditions associated with alcohol intake. AlD is an acute psychotic state characteristic of the later stages of alcoholism. AlD refers to the so-called withdrawal delirium, which occurs in persons suffering from drug addiction or substance abuse against the background of withdrawal syndrome (abstinence).

AlD usually develops between the ages of 25 and 60, with the most common age being between 40 and 50 years. It is known that AlD accounts for, according to various sources, from 1/2 to 3/4 of all cases of alcoholic psychosis (they, in turn, develop in 10% of people who systematically abuse alcohol). Severe AlD usually occurs in cases where the duration of alcohol abuse exceeds 10–15 years. However, in recent years there has been a tendency towards a significant reduction in this period. According to a number of authors, the mortality rate from AlD in a hospital is about 5%.

The pathogenesis of alcoholic delirium is still not fully understood. The following factors that contribute to the development of AlD are noteworthy [4]:

nutritional deficiency of biologically active substances necessary for the functioning of nervous tissue;
excitotoxic effects of excitatory amino acids (glutamate and aspartate);
reduced GABA content in the central nervous system;
changes in the activity of acetylcholine and monoamines;
direct neurotoxic effect of ethanol and its metabolites;
liver damage and decreased function.

The situation with alcohol consumption that has developed in recent years in Russia could not but affect the incidence of alcoholic psychoses (most of which are AlD). A separate risk group for the development of alcoholic psychosis consists of people who have stopped drinking alcohol due to emergency admission to a medical hospital. It has long been noted that a number of therapeutic departments (gastroenterology, pulmonology, cardiology, etc.) are a kind of “filter” for identifying patients with alcoholism, who often have never sought help from a specialist psychiatrist-narcologist.

In this regard, the risk of developing AlD in such patients in conditions of, for example, an emergency therapeutic hospital is extremely high. Doctors at multidisciplinary somatic hospitals need to know the clinical manifestations of AlD, be able to diagnose and provide the necessary medical care to this category of patients.

Currently, regarding the treatment of AlD that developed in somatic hospitals, experts have two opinions. Some consider it advisable to carry out treatment in a psychiatric (narcological) department, others - to treat developed AlD in the conditions of the department of the pathology, the treatment of which requires hospitalization at the moment, more often - in the conditions of an intensive care unit. In the first case, the “profile” treatment of mental pathology is observed (since AlD is psychosis). In the second, those severe (urgent) therapeutic conditions accompanying AlD, which are the prerogative of therapists or doctors of other specialties, are taken into account.

Clinical picture

Symptoms of delirious syndrome are usually represented by a state of confusion with impaired ability to navigate in place and time, a predominance of visual deceptions (hallucinations, illusions and pareidolia); combined with figurative delirium (an influx of scattered, inconsistent, unstable, fragmentary ideas), motor agitation. The above symptoms of delirium are the same and are observed regardless of the disease in which it occurs: alcoholism or other types of drug addiction, senile dementia, cerebral forms of vascular diseases, etc. In other words, delirious disorders can also be observed in other diseases, which is not always understood General practitioners are sometimes inclined to classify any development of delirious syndrome as AlD.

A rapid diagnosis of mental status can be carried out using the questions given in the table. It must be remembered that this test is nonspecific and its results may indicate not only a delirious state of consciousness, but also manifestations of dementia (acquired dementia).

To make a conclusion, it is necessary to calculate the total number of points (maximum number - 30). If a patient scores ≥29, they are unlikely to have delirium or dementia. If the patient scored ≤23 points, it is very likely that we are talking about delirium or dementia.

In addition to the mental symptoms characteristic of AlD, it is usually accompanied by somatoneurological symptoms inherent in alcohol withdrawal syndrome (AAS).

Thus, with AlD, three main syndromes are distinguished:

organic brain damage,
psychotic,
vegetative.

The syndrome of organic brain damage is manifested by disorientation, changes in the level of consciousness, affective lability (euphoria, depression or fears), psychomotor excitability, sensory hypersensitivity, sleep disturbance, and epileptic seizures. The reason for such changes is considered to be a decrease in the inhibitory effect of the γ-aminobutyrergic system and cholinergic insufficiency.

Psychotic syndrome is caused by hyperreactivity of the dopamine system and is manifested by illusions, visual, auditory and tactile hallucinations, and increased suggestibility.

Autonomic imbalance develops due to hyperreactivity of the sympathoadrenal system and insufficiency of the parasympathetic autonomic nervous system. Characteristic: hyperthermia up to 38–38.5°C (a higher temperature indicates an inflammatory process); arterial hypertension up to 180/110 mm Hg. Art. (more severe hypertension forces one to look for an independent cause); tachycardia, tremor, sweating, increased tendon reflexes.

During AlD there are three stages [3].

Stage I, or threatening delirium. Alcohol withdrawal symptoms in the form of sympathetic hyperreactivity and/or psychotic symptoms with transient hallucinations come first. Mainly in the evening, restlessness, tremors, anxiety and other manifestations of adrenergic syndrome increase, and inexplicable fear appears. Further, the ability to navigate in time and space is impaired (awareness of one’s own personality is preserved). Patients are restless, constantly fiddling with their clothes and bedding, turning their heads, talking to someone, their speech is unintelligible. Episodes of visual hallucinations provoke psychomotor agitation. Subfebrile body temperature, tachyhyperpnea, and severe hyperhidrosis are possible. This stage is in most cases reversible and symptoms can resolve spontaneously: delirium ends as unexpectedly as it began. In 3–10% of cases, epileptic seizures develop, usually within 48 hours after stopping alcohol. Resuming alcohol intake may prevent the progression of AlD. Unfavorable prognostic signs for the progression of AlD include: the presence of concomitant somatic diseases, anamnestic indications of long-term alcohol abuse and previous delirium, convulsive syndrome, and hallucinations.

Stage II, or complete delirium. At this stage, all the syndromes characteristic of AlD are clearly expressed. Hallucinatory (visual, auditory, tactile) and delusional experiences appear and increase, most often of unpleasant content (persecution, destruction, etc.), which frighten patients.

In this regard, psychomotor agitation and affective disorders may increase. The body temperature is low-grade, shortness of breath is observed (RR up to 22-24 per minute). Spontaneous cure of AlD is no longer possible. Intensive therapy is required. Lack of help leads to depression of consciousness, spontaneous decrease in blood pressure and reduction of other signs of adrenergic syndrome. The length of this phase largely depends on the concomitant pathology and the efficiency of treatment measures, since after just a few hours AlD can move into the next final phase.

Stage III, or life-threatening delirium. All symptoms of AlD occur with more severe vegetative manifestations. Lethargy appears, the patient’s excitement subsides, statements become abrupt, incomprehensible, speech is mumbled, the voice is quiet, the reaction to external commands fades. Characterized by mydriasis, hypotension, tachycardia, shortness of breath and tremor of the whole body. Rigidity of the neck muscles and depression of consciousness from stupor to coma increase. Cerebral edema develops, followed by the death of the patient. This is a phase of decompensation, often with irreversible disorders of internal organs and functional systems, which determines the severity of the patient’s condition.

Patients with severe AlD exhibit the following symptoms.

The motor component of excitation is less pronounced. Excitement, as a rule, is limited to the boundaries of one’s own apartment, and in the advanced stage – to the boundaries of the bed.
The behavior of patients is less often determined by existing hallucinatory-delusional disorders.
Body functions aimed at maintaining such components of homeostasis as the feeling of thirst and hunger are disrupted.
From the side of the autonomic nervous system, a change in the activation of the sympathetic (which dominates) and parasympathetic systems is revealed. Lability of blood pressure is noted, tachycardia and tachypnea persist.
Polyuria gives way to oliguria.

It must be emphasized that in case of AlD, restriction of motor excitation outside the bed, reduction of hyperhidrosis and normalization of blood pressure are often perceived by doctors as an improvement in the condition due to the therapy, while these alarming symptoms indicate a deterioration of the condition [1–3]. In addition, complications of AlD may occur at each stage.

Complications of AlD

The severity of the condition of a patient with AlD is largely determined by concomitant somatic pathology [1, 2]. A patient who abuses alcohol for a long time usually has damage to internal organs, described as chronic toxic polyvisceropathy. Delirium is a trigger for decompensation of any of these diseases.

Most often, AlD is accompanied and can cause the death of the patient by the following diseases.

Pneumonia. Accompanies severe AlD in 30% of cases, provokes its development, complicates the course and largely determines the prognosis. In 10% of cases, respiratory support is required due to increasing respiratory distress. In addition to community-acquired pneumonia, such patients may develop hospital-acquired and aspiration pneumonia.

Alcoholic cardiomyopathy. Heart failure as part of alcoholic cardiomyopathy accompanies severe AlD in 25% of cases. In 2–3% of cases it becomes the direct cause of death of patients. Symptoms of cardiomyopathy are characteristic of congestive heart failure: dyspnea, orthopnea, pulmonary congestion, peripheral edema, dilatation of the jugular veins. Arrhythmias are common, and peripheral thromboembolism is less common. The ECG may show changes in the ST segment and T wave, and left bundle branch block.

Acute pancreatitis. One of the most common companions of ALD is often the cause of hospitalization. Diagnostic signs: intense mesoepigastric pain radiating to the back, nausea, vomiting, intoxication, Cullen's symptoms (blue discoloration in the periumbilical region as a result of hemoperitoneum) and Gray Turner (purple or brown-green discoloration of the skin in the flanks of the abdomen due to tissue decomposition of hemoglobin) , signs of “acute abdomen” and intestinal paresis, increased serum amylase activity.

Liver failure. Liver damage occurs in 50% of cases of alcohol abuse. With AlD, indicating advanced alcoholism, the liver is almost always affected, but changes in liver function vary from asymptomatic forms (only biochemical changes are noted) to the development of liver failure.

Liver cirrhosis also affects the course of AlD and significantly worsens the prognosis. The most dangerous manifestation of liver failure is encephalopathy, which is characterized by impaired consciousness (up to the development of coma). The prognosis for the development of hepatic encephalopathy is extremely unfavorable.

Acute renal failure (ARF). Characterized by oliguria (less than 15 ml of urine per hour) or anuria and increased levels of creatinine and potassium in the blood. AKI in severe AlD can be prerenal (as a result of hypovolemia) and/or renal (as a result of myoglobinuria, toxic kidney damage, acute tubular necrosis). In prerenal acute renal failure, high relative density of urine (more than 1020) and low sodium content in urine (less than 10 mmol/l) are noted (if diuretics were not used). In renal acute renal failure, urine has a low relative density (less than 1010). Clinically, signs of acute renal failure include confusion, nausea, and vomiting. There may be signs of both dehydration and hypervolemia with pulmonary edema, peripheral edema and hyponatremia.

Cerebral edema , leading to a significant increase in intracranial pressure, is the most common (75%) cause of death in severe AlD. Clinically, increased intracranial pressure is manifested by intense headache, vomiting, depression of consciousness (up to the development of coma), convulsions, breathing problems, and congestive optic discs may be observed.

With AlD, focal symptoms may appear, even in the absence of changes on a CT scan. The causes are considered to be hyponatremia, hypoglycemia, or Todd's palsy.

Water and electrolyte imbalances. AlD is often accompanied by dehydration (up to the development of hypovolemic shock). Causes of dehydration in delirium tremens may include hyperhidrosis, fever, vomiting, and insufficient fluid intake.

To determine the presence and severity of dehydration, a thorough examination is necessary, since sometimes AlD occurs with sodium and water retention (with liver damage) or hyponatremic hyperhydration with excessive secretion of antidiuretic hormone. In this situation, intravenous administration of large amounts of fluid can lead to swelling of the brain.

It is necessary to control the level of potassium, sodium, calcium, and plasma osmolarity, since with severe AlD, changes in these parameters are possible in both one and the other direction.

The main cause of hyponatremia, as already mentioned, is hyperhidrosis. Hypokalemia, characteristic of severe AlD, is a risk factor for the development of cardiac arrhythmias. Hyperkalemia is possible with rhabdomyolysis and severe renal failure.

Hypomagnesemia almost always occurs in chronic alcoholism due to deficiency of intake, malabsorption, and excessive renal excretion of magnesium.

Violation of the acid-base state (ABC). Changes in acid-base balance are possible both in the direction of acidosis and in the direction of alkalosis. Causes of acidosis: fasting (ketoacidosis), prolonged or repeated convulsions, hypovolemic shock, hypoxia. Causes of alkalosis: hyperventilation, vomiting. Treatment of acid-base balance disorders involves correcting the underlying cause.

Violation of vitamin metabolism. More than 50% of patients with alcoholism have a clinically significant deficiency of vitamin B1. In the presence of clinical manifestations of Wernicke encephalopathy (confusion, oculomotor and pupillary disorders, ataxia), the daily dose of thiamine is 1000 mg on the 1st day of treatment. In 10% of cases, patients with alcoholism are diagnosed with vitamin B6 deficiency and other hypovitaminosis, which must be corrected.

Rhabdomyolysis. The causes of rhabdomyolysis in AlD are muscle damage (positional syndrome) and seizures. Clinically, myoglobinuria and increased levels of creatine phosphokinase in the blood are observed. Myoglobinuria can cause acute renal failure. To prevent it, large volumes of fluids are administered intravenously. Diuresis is stimulated with mannitol (25 g intravenously). After achieving adequate diuresis, sodium bicarbonate is administered intravenously, maintaining urine pH above 6.5 (prevention of myoglobin breakdown in the kidney tubules). Furosemide can cause acidification of urine and precipitation of myoglobin [3].

Pathological anatomy of AlD

Pathomorphological examination of patients who died as a result of AlD, as a rule, reveals atrophic changes in the cerebral hemispheres, most pronounced in the frontal lobes. There is an increase in the third and lateral ventricles of the brain. Macroscopically, swelling or pronounced edema of the brain is noticeable; hemorrhagic syndrome is not constant.

Histological examination reveals dystrophic changes in nerve cells with a decrease in their number and multiple foci of neuronophagia and cellular devastation, which is especially pronounced in the third and fourth layers of the cerebral cortex. Microscopically, hemorrhages in the brain stem are detected, as well as diffuse phenomena of toxic-anoxic encephalopathy, including pronounced granular decay and vacuolar degeneration of neurocytes. There is a predominant lesion of the stem, in particular the hypothalamic, parts of the brain. This corresponds to changes in the endocrine glands characteristic of a state of stress (according to Selye).

AlD treatment

Many drugs have been proposed for the treatment of AlD [6–10], but none of them meets all the necessary criteria: the presence of a sedative effect without suppressing protective reflexes, increasing the seizure threshold, suppressing autonomic hyperactivity, and antipsychotic effect.

In Europe, clomethiazole is considered the drug of choice (not registered in Russia). It has sedative properties, suppresses the activity of the sympathetic autonomic nervous system, and has anxiolytic and anticonvulsant effects, but its antipsychotic effect is limited.

In Russia (as in the USA), benzodiazepines are the drugs of choice. Of these, the most commonly used are diazepam, chlordiazepoxide and midazolam.

Disadvantages of these drugs include cumulative sedation, respiratory depression, and an increased risk of aspiration.

Compared with benzodiazepines, antipsychotics (including phenothiazines and haloperidol) do not have the same effect on the development of delirium. When treating severe AlD, the treatment of choice is combination intravenous therapy with benzodiazepines and haloperidol (or droperidol). It must be recalled that such treatment should only be carried out in an intensive care unit. And neuroleptics (especially aminazine) as monotherapy for AlD can be simply dangerous.

A meta-analysis showed that benzodiazepines are effective in reducing the incidence of delirium and seizures. Despite the anticonvulsant activity of benzodiazepines, some patients require additional anticonvulsant therapy with hydantoin or barbiturates.

Carbamazepine is effective in eliminating agitation and seizures at stage I of AlD. The drug is more successful than benzodiazepines in relieving psychotic symptoms. But in the case of severe AlD, it is not used.

Clonidine and α-blockers are used to treat sympathetic hyperreactivity. The best results for the control of sympathetic hyperreactivity have been obtained with the use of the α2-receptor agonist clonidine.

The principles of treatment of possible concomitant somatic pathology are outlined in the table (see the section “Under glass”).

Thus, AlD is a severe, potentially fatal disease. Patients with delirium tremens need constant observation and careful monitoring of all vital functions, timely prevention and correction of concomitant somatic diseases. Accordingly, if a patient has AlD that developed in a therapeutic bed in a somatic hospital, treatment is possible only in the intensive care unit. The management of patients with AlD in a narcological hospital must necessarily be carried out with the involvement of a general practitioner for the timely detection of possible concomitant fatal somatic pathology. n

Literature

Pelepets A.V. Clinical and epidemiological aspects of somatic and mental pathology in modern forms of metal-alcohol psychoses and withdrawal states // News of Kharkov Psychiatry, 2002. - https://www.psychiatry.org.ua/articles/paper040.htm.
Kuzminov V.N., Yurchenko N.P., Yurchenko A.N. Diagnostic and therapeutic problems in acute psychosis in persons with alcohol dependence // International Medical Journal. - 2003. - T. 9. - No. 3. - P. 31-33.
Kekelidze Z.I., Zemskov A.P., Filimonov B.A. Severe alcoholic delirium // RMJ. - 1998. - T. 6. - No. 2. - https://www.rmj.ru/rmj/t6/n2/4.htm.
Sivolap Yu. P., Savchenkov V. A., Akselrod B. A., Marshev M. Yu., Yanushkevich M. V., Vandysh M. V. Alcohol-induced delirium in general clinical practice // Critical Condition Medicine. - 2004. - No. 2. - P. 30-36.
Handbook-guide for a practicing physician: Emergency conditions from A to Z: Transl. from English / Ed. A. L. Vertkina. - M.: GEOTAR-MED, 2003. - 352 p.
Gofman A.G. Treatment of patients with alcoholic psychoses // RMJ. - 2002. - T. 10. - No. 12 - 13. - https://www.rmj.ru/rmj/t10/n12-13/556.htm.
Mayo-Smith MF, Beecher LH, Fischer TL et al. Management of alcohol withdrawal delirium. An evidence-based practice guideline // Arch. Intern. Med. 2004; 12; 164(13):1405-1412.
Mayo-Smith MF Pharmacological management of alcohol withdrawal. A meta-analysis and evidence-based practice guideline. American Society of Addiction Medicine Working Group on Pharmacological Management of Alcohol Withdrawal // JAMA. 1997; 9; 278 (2): 144-151.
Holbrook AM, Crowther R., Lotter A., Cheng C., King D. Meta-analysis of benzodiazepine use in the treatment of acute alcohol withdrawal // CMAJ. 1999; 9; 160 (5): 649-655.
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V. G. Moskvichev, Candidate of Medical Sciences R. Yu. Volokhova M. A. Zinovieva

MGMSU, NNPOSMP, Moscow Yaroslavl Regional Clinical Narcological Hospital, Yaroslavl

Family education

It is very good if there is no obvious conflict between the patient and his family members. A relative at the patient's bedside can provide invaluable assistance both in diagnosis and in the treatment process. It is family members who provide constant reorientation and support to the patient, and they also help the patient meet immediate needs. Unfortunately, family members usually know little about delirium, which can lead to defensive reactions to the doctor's efforts to diagnose and treat their ill relative (eg, “You don't understand. He's not crazy. He doesn't need a psychiatrist!”).

Gagnon et al found that training family members to understand delirium increased their trust in health care procedures and interventions. Similarly, Otani and colleagues reported that 81% of family members found that they benefited from receiving a leaflet that included information about the nature and treatment of delirium.

Although patients' relatives may not know anything about delirium, they are often the first to notice that "something is wrong" with the patient. Steis et al found that family members may be helpful in more formalized assessments of delirium disorders. Researchers showed that family caregivers using the Family Assessment of Confusion Method (FAM-CAM) demonstrated 88% sensitivity and 98% specificity in identifying delirium using CAM as the diagnostic standard.

There are a number of educational websites dedicated to the topic of delirium, which can certainly be of benefit to both families and those doctors who, due to their line of work, rarely encounter this disorder. www.thisisnotmymom.ca is an example of a site that demonstrates the important role of family members and also provides case examples that can help guide clinicians.

Questions and answers

How to provide first aid for delirium tremens?

A person with signs of psychosis should be put to bed and care should be taken that he does not leave it until the narcologist arrives. A person can be given cold drinking water. Communication with persons in a fever should be conducted taking into account the unconsciousness of their actions. Swearing and screaming will only increase the anxiety of patients.

Are there measures to prevent delirium?

Avoiding psychosis will help avoid the systematic use of alcohol-containing liquids. Patients diagnosed with alcoholism should be referred for treatment to specialized clinics. Getting rid of alcohol addiction will help you avoid bouts of delirium.

Directions of development

Compared with disorders such as schizophrenia or depression, delirium has always attracted relatively less clinical and research interest in psychiatry. Unfortunately, just as little attention is paid to it in emergency medicine, resuscitation, surgery, and other areas where delirium, nevertheless, is a very common phenomenon. This historical neglect represents enormous potential for advances in research and clinical practice that will ultimately lead to significant benefits for patients.

The complex pathophysiology of delirium and the wide range of variability in clinical symptoms suggest that it is possible to study the effects of different drugs on different physiological processes and tailor therapy to each individual patient. Instead of serving as an obstacle to care, delirium should become an area of cooperation between psychiatrists, neurologists, resuscitators, surgeons, geriatricians, and doctors of other specialties. Researchers involve various medical specialists to solve the problems they face; They integrate in their work the methods of genetics, clinical neurophysiology, psychopharmacology, and neuroimaging. We can firmly count on the fact that in the near future they will lead us to a better understanding of the work of attention and the cognitive sphere both in healthy people and during illness.

Based on materials from the site: https://www.psychiatrictimes.com/

All materials on the site are presented for informational purposes only, approved by a certified physician, Mikhail Vasiliev, diploma series 064834, in accordance with license No. LO-77-005297 dated September 17, 2012, a certified specialist in the field of psychiatry , certificate number 0177241425770.