Emergency treatment of delirium tremens on the background of acute infectious diseases
KUTKO I.I., FROLOV V.M.
Institute of neurology and psychiatric addictology, AMS of Ukraine, Kharkov Lugansk State Medical University
Summary. Emergency treatment with reamberin, glutargin and enterosorption was
pathogenically substantiated in a study of signs of metabolic intoxication syndrome and LPO in 182 patients with delirium tremens on the background of acute infection.
Key words: delirium tremens, emergency treatment.
Introduction
Delirium tremens (DT) is currently the most common acute psychotic condition occurring in the practice of psychiatrists, addictologists and emergency physicians. Clinical experience shows that in the recent years DT most frequently occurs on the background of acute infectious diseases (moderate and especially severe course) - pneumonia, erysipelas, angina, dysentery, flu, etc., probably due to combination of specific infectious intoxication occurring in violation of metabolic processes and perverted metabolism course (especially of protein) in patients
systematically misusing alcohol. It is known that one of the index laboratory criteria of intensity of "metabolic" intoxication is serum concentration of middleweight molecules (MM) - with molecular weight from 500 to 5000 D, having a high toxicity. [4] In our previous works
pathogenetic role of "metabolic" intoxication was established and, in particular, accumulation of MM in the body of DT patients, including the background of an acute infectious disease [10].
This made it necessary to radically reconsider the approaches to emergency treatment of AD: If previously the focus was on the use of antipsychotic drugs, it is now, we believe the main features of the full detoxification and elimination syndrome "metabolic" intoxication [9].
In this regard, reamberin should be named first - a new substance for infusion therapy in the critical care medicine [5]. Reamberin is a balanced polyionic solution supplemented with 1.5%
of a salt of succinic acid - sodium succinate than is a unique component of the drug in comparison with other detoxifying fluids used for intravenous infusions. Reamberin has
detoxifying, anti-hypoxic, antioxidant, hepato-, nephron- and cardioprotective properties, i.e. is an organoprotector [5]. Thus, basic pharmacological effect of the drug is due to its ability to activate aerobic glycolysis in the Krebs cycle and thus increase the intracellular energy
compounds - ATP and creatine phosphate. Clinical observations have shown that reamberin does not cause pyrogenic allergic reactions and is well tolerated by patients. Moderately pronounced diuretic effect of the drug helps to eliminate toxic substances with the urine. A characteristic feature of the pharmacological effect of reamberin is to improve the functional state of the liver parenchyma, and in particular, anti-toxic normalization of liver function in patients with DT.
There was also a positive effect of reamberin on the state of microvasculature and energy metabolism in patients with alcoholic psychosis. As a result, reamberin in adequate (optimum) doses accelerated the elimination of psychotic manifestations and accelerated conalescence from delirium.
Along with reamberin in the recent years we have extensively used Glutargin, the original Ukrainian product (Kharkov), in the complex of therapeutic agents for the treatment of delirium tremens. Chemical structure of Glutargin represents L-glutamate-L-arginine and has a very high biological activity [2]. Glutargin has distinct detoxifying, antioxidant, antihypoxic,
hepatoprotective effect, increases the functional activity of the liver, including its detoxifying properties. [2] The drug is able to bind ammonia in the blood, turning it into a non-toxic compound - glutamine. This is extremely important for the treatment of patients with delirium tremens, as their body accumulates ammonia and other products of protein degradation due to the predominance of catabolic processes and increased protein breakdown. It is significant that
along with reduction of free ammonia in the blood of patients treated with Glutargin, it also reduces MM concentration in the blood serum, which indicates a decrease in the manifestations of "metabolic" intoxication.
Extremely effective is the use of enterosorbents in the treatment of DT. Currently we use modern silica enterosorbents (enterosgel, polisorb, enterosorb and others). Enterosorption quickly
reduces the concentration of middleweight molecules in the blood, indicating that the liquidation of "metabolic" intoxication increases the functional activity of the liver parenchyma, indices recovered metabolic homeostasis [8].
The aim of this study was to summarize the experience of DT emergency treatment on the background of acute infectious disease with the use of modern means of detoxification and normalization of metabolic homeostasis.
Materials and methods
We have observed 182 patients with DT, which developed on the background of an acute
infectious disease (68 – flu, 32 - pneumonia, 29 - acute dysentery, 25 – erysipelas inflammation, 22 - acute tonsillitis, 6 - diphtheria).there was significantly more males (169 patients.; 92.2%) and 13 women (7.1%) at the age from 26 to 60 years. The clinical picture of DT was typical, and its onset - acute; delirium occurred predominantly in the evening and by night (from 6 p.m. to 3 a.m.), at the peak of infectious endotoxemia, often on day 2-3 of illness (the first, at least the second day of admission to hospital infection), against the background of acute fever. According to history, all patients with DT for a long time (5 to 15 years) abused alcohol, which makes the presence of chronic alcohol intoxication (HAI) as that of the pathological background, which was formed in DT. However, only 8 of them (4.4%) visited the psychiatrist about alcohol addiction.
Apart from clinical examination of all patients over time of every 3 days CM concentration in the serum was studied according to the method [7]. Prior to treatment and after intensive therapy blood levels of LP products - malondialdehyde (MDA) [1] and diene conjugates (DC) was studied [3].
To implement the study objectives, all the patients were divided into two groups - main (102 patients) and comparison group (80 patients), randomized by sex, age, severity of clinical DT manifestations and the nature of the background of an infectious disease. Patients in both groups received antipsychotics by conventional scheme [9], and if necessary, correction of infection (antibiotics, anti-inflammatory or anti-infective drugs, respectively to the nosology and infection severity). In addition, the study group received detoxifying agents in accordance with the method developed. The start drug was reamberin injected i.v. 400 ml twice a day with an interval of 8-10 hours the first 2-3 days of treatment, followed by 400 ml once a day for 3-4 days. After
administration of reamberin patients were administered infusion "combination" as follows:
Trisolum or Quartasolum - 400 ml, prednisolone - 2.0 ml, Corglycon 0.06% - 1.0 ml,
cocarboxylase - 200 mg, Lasix 1% - 4-6 ml then, providing a good urine discharge through the catheter from the bladder, Glutargin 4% solution 25-30 ml was administered in 150-200 ml infusion of isotonic sodium chloride solution twice a day for 3-4 days.
At the same time, modern silica enterosorbents (Polisorb, Sillard P, Enterosgel) were
administered in a 2% aqueous suspension. In the first days the sorbents were administered per rectum, and in some cases also into the stomach through a catheter; with the release of a patient from a psychotic state oral administration of enterosorbents 2% suspension 200-250 ml began between meals 3 times a day. For correction of LPO the patients received i.v. ascorbic acid (20- 30 ml of 10% solution) and tocopherol acetate (vitamin E) in 1 ml of oil solution i.m. With the release from a psychotic state to oral ascorbic acid (500 mg) and vitamin E (0.2 ml of a 50%
solution in capsules 2-3 times a day).
The resulting digital material was processed mathematically using modern methods of variation statistics designed to evaluate the clinical efficacy of drugs, on a PC Intel Pentium III 800 with
the help of multivariate analysis of variance using the packages of licensed software of Microsoft Office 97, Microsoft Excel Stadia 6.1 / prof and Statistica.
Results
Results of clinical observations and laboratory studies have shown that during the intensive therapy of AD in 58 (56.9%) patients of the group of delirium ceased by the end of the first day of treatment. So, at the start of infusion therapy in 8-9 hours in the morning to the same time the next day the patient is largely cleared up consciousness, he began eagerly ingest suspension enterosorbent and a day completely out of the psychotic state. A feature of this group of patients was a young age (26-32 years), the relatively smaller length of alcohol (up to 5 years), and in terms of laboratory - rapid decline of CM in the blood (an average of 0.12 ± 2,52 g / L 0.86 ± 0,03 g / l, i.e. 2.9 times for the first three days of intensive care). It is significant that in this group of patients had intense urination when administered Lasix and urinary registered a high level of CM 10-16 times Preview depleting norm. This indicates the preferential deducing their SM kidneys and a rapid decrease in the intensity of the "metabolic" intoxication.
In 34 (33.3%) patients of the group out of the psychotic condition was more gradual, for 2-3 days, after which they have for several more days, the complaint remained tserebrastenicheskom nature, worse in the evening (weakness, malaise, diffuse headache, sometimes dizziness,
decreased appetite, insomnia, etc.). Patients in this group ranged in age from 40 to 60 years, duration of alcohol abuse - from 7 to 15 years. Finally, 10 patients (9.8%) had an intermediate state of speed out of delirium between the two groups.
In general, the main group in the disappearance of psychotic disorders marked by an average of 2,6 ± 0,2 days earlier than in the comparison group (p <0.01), and the duration of conservation or astenonevroticheskih asthenic symptoms was at 7,8 ± 0, 35 days less (p <0.001). There was also a more rapid decrease in the concentration of CM in the blood, indicating a more intense pace of liquidation of "metabolic" intoxication (Table. 1).
From Table. 1 shows that the main group of patients with pre-treatment level of SM in serum was 4.85 times higher than the norm, in the group of comparison - in 4.79 times higher than normal (p <0.001). No significant differences between the two groups was not found (p> 0.1). At re-examination after 3 days in the basic group the SM concentration in serum decreased on average 2.84 times relative to the initial level and reached 1.71 ± 0,09 g / l; Group comparisons fold decrease in the concentration was 1.35 times relative to the initial level.
Thus, the concentration of the CM in the serum of patients by the end of 3 days ICU BP has an average of 2.1 times lower than in the study group than in the comparison group (P <0.01). On the 6th day of intensive therapy level of SM decreased an average of 3.88 times compared to the original in the main group and only 1.95 times in the comparison group (p <0.01). At the same time the data of CM concentration in serum of patients of the main group had an average of 1.97 times lower than in the comparison group (P <0.01). On the 10th day of intensive therapy of AD (when clinically in all patients achieved complete elimination of psychotic deviation) level of SM in serum of patients of the main group decreased to upper limit of normal (p> 0.1). In the comparison group in the study period the concentration CM in the serum remained at 4.1 times higher than the norm (P <0.001) and exceeded the level of the indicator in the main group at 1.93 times (p <0.01). In the latter study, the concentration of CM in 2 weeks since the start of
intensive therapy level of this index was on average 2.1 times higher than the norm (P <0.001) and in 1.98 times higher than in the study group (p <0.01) .
The study of LP for the start of the treatment, that is, at the time of the first visit to a doctor, helped to establish the activation of lipid peroxidation. Patients of the main group in the serum
concentration of the end product of lipid peroxidation MDA increased in comparison with the norm (3,6 ± 0,2 mmol / l) on average 2.5 times, ie, was 8,95 ± 0,3 mmol / l (p <0.01) in the comparison group, this figure increased to 8,89 ± 0,2 mmol / l, which was above the normal average is also 2.5 times ( p <0.01). The concentration of the intermediate products of lipid peroxidation (DC) to the beginning of treatment in the study group and comparison group and had no significant differences (p> 0.1). Thus, the examined main group DC level increased to 18.7 ± 0.3 mmol / l, and group comparisons - up to 18,4 ± 0.2 mmol / L, which was higher than the average rate of 3-fold (p <0.001 ) (Table. 2).
In analyzing the content of lipid peroxidation products found that AD patients who received intensive therapy complex reamberin, Glutargin and chelators, there was almost complete normalization by the studied parameters, which is not the comparison group of patients who received only conventional drugs.
The concentration of MDA in the examinees from the main group decreased from baseline by an average of 2.6 times, that is up to 3,5 ± 0,2 mmol / l, which is almost in line with the norm (p>
0.1). In the comparison group, this indicator decreased to 5,1 ± 0,2 mmol / l, that is 2.5 times the original value, but remained above normal by 1.6 times (p <0.05) and higher concentration of MDA in main group 1.5 times (p <0.05).
As for the level of lipoperoxidation intermediates (DC), the comparison group this indicator dropped to 10,1 ± 0.4 mmol / L, which was below the starting value (at the beginning of the treatment) of 1.8 times, but still remained above normal and the same period in the study group, on average, 1.6 times (p <0.05). In the main group of patients with AD who receive offers us a set of drugs, showed complete normalization of DC, namely, the figure dropped from baseline by an average of 3 times and posted almost normal (p> 0.1).
Discussion of Results
Thus, these data suggest that the use of complexes of detoxification improves the results of treatment of patients with AD: hastens patients in a psychotic state, reduces the duration of conservation or astenoneurotic asthenic syndrome, encephalasthenia and thus contributes to a more rapid and complete recovery of patients. The laboratory biochemical studies revealed a positive effect combinations reamberin, Glutargin enterosorption and the state of lipid
peroxidation, which is manifested in a decrease in the serum concentration of the intermediate (DC) and the final (MDA) metabolites of lipid peroxidation. It should be emphasized the rapid decline in the concentration of CM in serum of patients with AD, we find this combination of drugs, which indicates a decrease in symptoms, and then the complete elimination of the syndrome of "metabolic" intoxication. In the comparison group (patients who receive intensive care in a complex only conventional drugs) also showed a trend toward improvement of
biochemical parameters studied, but much less clear. The findings suggest pathogenetically justified and clinically appropriate application we developed a method of emergency treatment of patients with AD on the background of an acute infectious disease.
Conclusions
Inclusion in the complex intensive therapy of patients with AD on a background of acute infectious diseases combined detoxifying drugs reamberin, Glutargin enterosorption and accelerates release of patients from a psychotic condition and the shortening encephalasthenia syndrome.
The developed method of intensive care blood pressure causes the elimination of the syndrome of "metabolic" toxicity, as evidenced by the reduction of CM in the serum, as well as
normalization of lipid peroxidation products - MDA and DC - in the blood of patients with this pathology.
Based on these data, we can recommend the method we developed for wide use in intensive care of patients with AD.
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