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[Criteria of the efficacy of therapeutic measures in alcoholic delirium. Study on the effectiveness of aprotinin in alcoholic delirium].

30 patients with delirium tremens were given in a double-blind trial--beside the basic treatment with chlormethiazol (Distraneurin)--aprotinin (Trasylol) or placebo. Duration of the delirium and the amount of chlormethiazol used were the criteria for successful treatment. It was shown that the additional application of aprotinin did neither shorten significantly the duration of the delirium not save the amount of chlormethiazol used. Methodologically, special attention was given to the question of duration of the delirium and of registering symptoms. A delirium-rating scale was devised and its analysis showed a good randomization of the items. One main question was as to what extent the individual items were good indicators of a delirium. An item intercorrelation showed that there were two clusters of symptoms: psychological and sympathetic nervous system symptoms. It could be shown that the items 'consciousness, orientation, hallucinations and short-term memory' were good indicators of the delirium, while items of the autonomous nervous system, as tremor of hands and body, facial muscular twitching and exteroceptive reflexes, were less indicative of delirium. The duration of the delirium seems to be the best criterion for the question as to whether a drug is effective or not in delirium tremens. There is a highly significant correlation between the degree of the severity of the delirium and its duration. Other significant predictors for the severity of the delirium were the maximal pulse rate and change in blood pressure. Age, duration of alcoholism and psychological or physical depravation showed no influence on the duration of the delirium.

Adult

Linking cortical structure and delirium in the elderly: insights from cohort study and shared genetic risk analysis.

BACKGROUND: This study aimed to assess the association between regional cortical changes measured via baseline magnetic resonance imaging (MRI) and the incidence of delirium. METHODS: Observational associations were assessed using a prospective cohort from the UK Biobank and an independent clinical cohort. The population-based study included participants aged 60 years or older who had undergone structural brain MRI since 2014. Regional cortical volume, mean thickness, and surface area were extracted based on the Desikan-Killiany cortical atlas. Delirium was defined using ICD-10 diagnostic codes. Additionally, preoperative brain MRI images from participants in another cohort were collected and automatically segmented using deep learning algorithms to obtain cortical measurements. Logistic analysis was performed to investigate the associations between cerebral cortical structure and delirium risk. Lastly, genome-wide association study data derived from the ENIGMA Consortium and FinnGen Biobank were utilized to conduct conditional/conjunctional false discovery rate (cond/conjFDR) analyses to identify shared genetic loci associated with cortical structures and delirium. RESULTS: This observational analysis included 31,890 participants from the UK Biobank and 152 participants from an independent cohort. In the UK Biobank cohort, decreased cortical thickness in the 17 regions was associated with a significantly increased risk of delirium. Similarly, a preoperative reduction in cortical volume in 7 regions was associated with an increased risk of delirium in the independent cohort. Besides, 100 single-nucleotide polymorphisms (SNPs) were identified as significantly associated with cortical structures when conditioned on delirium. Finally, colocalization analysis demonstrated that these pleiotropic risk loci modulated the expression of NT5C2, RGP1, CCDC25, TPM2, EEF1AKMT2, IQANK1 and LHPP in blood and brain tissues. CONCLUSION: Regional cortical atrophy is associated with an increased risk of delirium in the elderly. Brain MRI examinations may be beneficial for preoperative delirium risk assessment in elderly individuals undergoing elective surgery.

Humans

Delirium tremens. Some clinical features. Part I.

Twenty patients with delirium tremens and related states were investigated from the time of admission until the acute state was over. Using strict diagnostic criteria the material was divided into two groups according to the severity of the clinical condition; nine patients had fully developed delirium tremens (grade 3), 11 patients had a less severe clinical state, known as "Predelirium" (grade 2). The material was found to be representative for the condition under discussion. Patients with grade 2 were admitted during the day and the evening, but not during the night; patients with fully developed delirium tremens (grade 3) were admitted during both the day and the night, and this difference is discussed. The two groups had the same pattern of alcohol abuse, but patients with proper delirium tremens had had a drinking bout preceding the acute state; this was not seen among patients with a less severe clinical state. Patients with grade 2 had had symptoms like sleep disturbances and gastro-intestinal disturbances for 12-24 hours before the admission, whereas grade 3 patients had had such symptoms for about 48 hours. Patients with grade 2 stopped drinking when the first symptoms of the acute state appeared, whereas patients with fully developed delirium tremens continued to drink in spite of their condition. These anamnestic were supported by the finding that significantly more patients with proper delirium tremens had alcohol in the blood--several even concentrations about 2 g/l--at the time of admission compared to patients with a less severe clinical state. This lack of "latency period", which previously has been described as a typical feature in the development of delirium tremens, is discussed. It is concluded that due to the methodology used, it has been possible to point out some of the differences between the milder, often harmless, conditions and the potentially serious, fully developed delirium tremens.

Adult

Delirium tremens. Some clinical features. Part II.

Twenty patients with delirium tremens (grade 3) and a less severe clinical state (grade 2) were investigated thoroughly from the time of admission until recovery from the acute state. A lumbar puncture was performed in the majority of the patients immediately after admission and then repeated after recovery from the acute state. The cerebrospinal fluid was found to be both macroscopically and microscopically normal, as was the spinal fluid pressure. The clinical course was without complication, none of the patients were severely dehydrated. All the patients were treated with barbital, a long acting barbiturate. The duration of the acute state and the total amount of drug necessary in the treatment were equal in the two groups of severity. However, patients with proper delirium tremens needed significantly fewer barbital doses during the first hours after treatment was initiated than did patients with a less severe clinical state. The opposite was seen about 12 hours later. These findings are discussed in relation to the high blood alcohol concentration seen at the time of admission in the majority of the patients with proper delirium tremens, but not in patients with grade 2. It is concluded that barbital exerts its effect due to cross-dependence properties with alcohol. The majority of the patients had moderately elevated blood pressure, pulse rate and rectal temperature at the time of admission; these variables were to a great extent normalized within 48 hours after admission. No differences in those physical signs were seen between patients with fully developed delirium tremens and patients with less severe clinical states. The patients' condition during the acute state was followed by means of a delirium tremens rating scale. Physical symptoms were similar in various degrees of severity of the clinical condition. 18-24 hours after admission the differences in mental symptoms between patients with grade 3 and patients with grade 2 had disappeared, 48 hours after admission the patients' condition was to a large extent normalized. Methodological problems in using a rating scale in conditions as delirium tremens are discussed. The results are discussed in relation to aetiology and pathogenesis of delirium tremens. It is concluded that it may be that a qualitative, and not only a quantitative, difference exists between a severe withdrawal reaction and fully developed delirium tremens, and a hypothesis about a "point of no return" is suggested.

Adult

Biochemical investigations into the alcoholic delirium: alterations of biogenic amines.

In eight male patients with alcoholic delirium concentrations of 3-methoxy-4-hydroxyphenylglycol (MHPG) and homovannilic acid (HVA) in CSF, activity of dopamine-beta-hydroxylase (DBH) and urinary excretion of noradrenaline (NA), adrenaline (A), and dopamine (DA) were measured during the delirium and a drug-free control period. MHPG concentration in CSF, excretion of NA and A as well as activity of serum DBH were significantly elevated during the delirium phase as compared to the control period. Urinary DA excretion and HVA in CSF did not show any constant changes. There was a positive correlation (r = 0.64) between DBH activity and the intensity of the delirium (as measured on the delirium rating scale). It is hypothesized that there is a relationship between alcoholic delirium and increased central noradrenergic activity.

Alcohol Withdrawal Delirium

Delirium after coronary artery bypass surgery.

The incidence of postoperative delirium following coronary artery bypass surgery was 28%. This rate is comparable to that after open-heart surgery. However, of those variables which were previously found to correlate with delirium in the open-heart group, only severity of postoperative illness in the recovery room significantly correlated with delirium in patients having bypass. The relationship between personality type and delirium, previously found to be signficant, was suggestively associated in these patients. A history of myocardial infarction prior to surgery was significantly associated with delirium.

Adult

Postcardiotomy delirium: a critical review.

The literature concerning postcardiotomy delirium contains confusing definitions and contradictory results. In a critical review of the subject, we conclude that cardiac status, the severity of physical illness, the complexity of the surgical procedure, and preoperative organic brain disease are the determining factors in postcardiotomy delirium. Preoperative anxiety, denial, and depression also have some correlation. Age, sex, time on bypass, and preoperative psychological profile seem to have no influence on outcome. No psychological etiology for delirium has been proven consistently. The therapeutic influence of preoperative interviews in preventing postoperative psychiatric complications remains equivocal as do theories implicating sensory deprivation in the intensive care unit. Long-term follow-up studies suggest that psychological problems impair functional recovery from heart surgery. The suggested treatment of patients with delirium includes chemotherapy, psychotherapy, and environmental support. Finally we suggest that investigation of biochemical abnormalities in delirium may prove to be a model for clarifying the role of neurotransmitters in functional psychiatric illnesses.

Adult

[Immunologic diagnostic of blood CSF barrier in the course of delirium tremens (author's transl)].

Fifty chronic alcoholics with acute withdrawal (in the state of delirium tremens) were examined initially and in the following weeks by quantitatively testing immunoglobulins in the serum and in the cerebrospinal fluid to study the dynamics of the blood-CSF barrier. Compared -to other persons of the same age, acutely delirious patients show a pathologic IgG-IgA constellation in the CSF which does not depend on the serum. That points to an infrastructural barrier function disorder. After 2--4 weeks, delirium tremens, normally in the process of recovering, shows distinct sanitation of the immunologic spectrum of the CSF. With regard to their dynamic proceedings, the results confirm other findings on brain metabolism, biochemistry, neurophysiology, and pathologic anatomy during delirium tremens. The totally and progressively disturbed blood-CSF barrier system of complicated cases of delirium tremens (e.g., Korsakov's and Wernicke's syndromes) seems to provide the possibility of deterioration of the clinical syndrome. The method, simple to implement in the laboratory, permits not only an overall evaluation of the dynamic blood-CSF barrier function in acute and postdelirious state, but also provides both the possibility to diagnose a persistent infrastructural residual syndrome and to indicate a pathophysiologic complication of the clinical course.

Adult

[Prognosis of alcoholic delirium (author's transl)].

296 cases of delirium tremens treated in 1958-69 were analysed retrospectively. Forty-one patients died in delirium or shortly thereafter. In 72 by now dead patients cirrhosis of the liver was the most common cause of death. Of 68 patients re-examinated, 12 were now teetotallers and six had markedly reduced there intake. Fifty patients had continued drinking and most of them had signs of liver failure, one had hypertension and one also had a polyneuropathy. Those who were abstaining, as well as the patients with a favourable course,and most of them were married. Although the acute death-rate of delirium has been markedly reduced since the introduction of clomethiazole treatment, it remains high after discharge. In almost half of those who were still drinking there had been a slide downwards in their social status. Delirium tremens is almost always precipitated by alcohol withdrawal.

Adult

Barbital and diazepam plasma levels during treatment of delirium tremens.

Plasma concentrations of barbital and diazepam were measured daily during a double-blind study of the efficacy of the two drugs in the treatment of delirium tremens and less severe clinical states. Treatment was estimated as satisfactory in the majority of cases; the present study deals with the satisfactory groups only. Both in the barbital group and in the diazepam group the same plasma level was seen in different clinical states. This result is discussed in relation to the theories about the aetiology of delirium tremens, and it is concluded that the data fits best with the assumption that delirium tremens is released from a withdrawal state, but once established, the delirious state is not interrupted by the drugs. The barbital concentrations were rather high, many at a level where non-alcoholics would show pronounced intoxication symptoms not seen in the present material. The diazepam concentrations on the other hand were low, often below a level where a cerebral effect is measurable in normal subjects. On this basis it is concluded, that the two drugs have different modes of action. Barbital may act by its cross-dependence properties with alcohol and thus diminish the withdrawal reaction, whereas diazepam may act by its anti-anxiety effect, but not in the doses here applied, by cross-dependence properties with alcohol. Finally, this hypothesis is discussed in relation to clinical experience in the treatment of delirium tremens.

Alcohol Withdrawal Delirium

Postcardiotomy delirium: an overview.

Any one of a number of psychologic patterns may appear cardiotomy: (1) Some patients may be elated and confident after awakening from anesthesis and have no severe changes of affect or neurologic deficit. Denial seems to be for them an adequate defense against anxiety. (2) Others are disoriented and manifest neurologic disturbance immediately after awakening, without a lucid interval. The sensorium begins to clear five days after surgery. (3) Some patients go into delirium after being lucid for as long as a week and have hallucinations, illusions, and motor excitation for a few days-or over several weeks. Pathologic brain changes that are apparently anatomical correlates of neurologic deficits in delirium include anoxic lesions of the hippocampus, and infarcted foci. Physiologic factors that contribute to this reaction include: long periods of extracorporeal circulation, arterial hypotension during surgery, emboli, and low postoperative cardiac output. Age, and the type and severity of heart impairment are also factors. Psychologic factors to be taken into account include preexisting psychopathology and the failure of denial under the stress of physical symptoms or hospitalization. Delirium is fostered by sensory overload (or deprivation) in the recovery room and intensive care unit, and by staff tension. Modification of the intensive care unit environment, the administration of antipsychotic drugs, and metabolic correctives are recommended. Preoperative psychologic evaluation, with therapy as needed, preliminary familiarization with perioperative procedures, as well as collaboration between psychiatrist and surgeon, can do much to prevent post-cardiotomy delirium.

Age Factors

Treatment of delirium--a reappraisal.

Delirium is a frequently encountered clinical syndrome which can pose serious problems for the physician and patient. Numerous etiological possibilities exist, and each case is usually associated with multiple causal factors. Although the pathophysiology is poorly understood, the clinical presentation is marked either by stupor and hypoarousal or agitation and hyperarousal. Both types of delirium must be treated by searching for and correcting reversible causative factors. In addition, medication may be quite efficacious in managing the clinical aspects of agitated delirium. Most cases of agitated delirium are either of the "sensory overload" or "sensory deprivation" type. The drug treatment of each is discussed with reference to their respective central nervous system physiological correlates.

Antipsychotic Agents

Diazepam and paraldehyde for treatment of severe delirium tremens. A controlled trial.

Thirty-four patients with severe delirium tremens were allocated randomly to treatment with paraldehyde (10 ml rectally very 30 minutes) or diazepam (10 mg then 5 mg intravenously every 5 minutes) until they were calm but awake. Diazepam-treated patients became calm in one half the time needed to calm patients with paraldehyde. Half of the patients had delirium tremens in association with pneumonia, pancreatitis, or alcoholic hepatitis; these patients required twice as much paraldehyde or diazepam for initial calming as patients with delirium tremens alone. Maintenance of a calm state was accomplished easily with either diazepam, intramuscularly, or paraldehyde, rectally. Adverse reactions occurred in nine patients, all of whom had been treated with paraldehyde; these patients had greater degrees of fever, tachypnea, and tachycardia and required three times longer for initial calming than patients without adverse reactions. Diazepam given under this regimen is a safe and effective sedative for management of combative patients with severe delirium tremens.

Adult

[Plasma ACTH, STH and other hormone levels in various groups under chlormethiazole, haloperidol or reserpine load in alchohol delirium, alcoholic hallucinations, and chronic alcoholism].

Studies of 135 men with safely diagnosed alcohol delirium mostly revealed increased ACTH blood values when sober and increased T4 values in about 1/3 of these patients. There is a correlation between the psychiatric clinical picture of the alcohol delirium and the ACTH content of the plasma. Under load with chloromethiazole, halperidole or with reserpine, there is a significant drop in the increased ACTH and T4 values. In an acute alcoholic hallucinosis (n=16) similar endocrinological changes as in most cases of safely diagnosed alcohol delirium were observed. In a chronic alcoholic hallucinosis (n=11) and in chronic alcoholics (n=31) the endocrinological values were similar to those of patients after alcohol delirium.

17-Hydroxycorticosteroids

Delirium after cataract surgery: review and two cases.

The authors define the delirium seen after cataract surgery on the basis of Dupuytren's original description and review studies using the criteria they set up on this basis. They then present prospective data on 2 patients with postcataractectomy delirium and 25 patients who did not experience this delirium. The data suggest that delirium after cataract surgery represents anticholinergic toxicity.

Aged

[Therapy and course of alcoholic delirium].

During the past ten years, treatment of delirium alcoholicum was almost exclusively by means of chlormethiazol (distraneurin), an agent which has sedative, hypnotic, and antiepileptic effects. A total of 111 deliriants with single and multiple deliria were subjected to 151 treatments. In the majority of cases the state of delirium was overcome after three days of specific treatment. The case histories of three patients, where the course of disease was extremely severe and additionally complicated by secondary diseases and who died during treatment (the percentage being 0.7% relative to 151 cases of treatment), are discussed in detail. In the case of severe states of delirium accompanied by repsiratory diseases it is necessary that the patient receiving specific treatment be supplied with additional amounts of oxygen because distraneurin, like other sedatives, trends to reduce the utilization of oxygen under certain conditions. The majority of deliriants were in their third to fourth decades of life. Accordingly, our patients were younger than those included in the reports presented by other authors. Also discussed by the present authors are attacks accompanying the state of delirium as well as concomitant diseases complicating the clinical picture and adverse effects of alcohol on the nervous system.

Adult