Severe Ethanol Intoxication Research Articles

Изучение эффективности применения пептидных препаратов при острых тяжёлых отравлениях этанолом

Severe poisoning plays a significant role in ethanol poisoning and is an important cause of increased mortality in the population. Existing treatment regimens for extremely severe ethanol poisoning have shown low effectiveness, necessitating the search for drugs among pharmacological groups that have not previously been used in severe cases of ethanol poisoning. Peptides, which have demonstrated high efficacy in treating critical conditions of the body accompanied by impaired central nervous system and liver function, can be the drugs of choice. The aim of this study was to investigate the effectiveness of peptide drugs with neuroprotective and hepatoprotective activities in rats with acute severe ethanol poisoning. The studies were conducted on male albino rats, in which 40% ethanol was administered intragastrically using a probe at a dose of 1.5 LD50. The investigated pharmacological correction agents included the peptide drug Semax and a hepatoprotective agent with a peptide component, Molixan. The survival rate, average lifespan, neurological status, and vital functions (respiratory rate, heart rate, and body temperature) of the animals were evaluated. The results showed that administration of Semax and Molixan peptides increased the survival rate of rats and had a favorable effect on neurological status and vital body functions in cases of acute severe ethanol intoxication at a dose of 1.5 LD50. This study demonstrated the potential of using peptide drugs in cases of acute severe ethanol intoxication.

Individual Tolerance to Acute Ethanol Intoxication

Relevance: In order to figure out the cause of death and present the evidences to the court, law enforcement authorities instructed forensic medicine experts to carried out differential diagnosis, by using the posthumous exogenous alcoholemia to differentiated between the severity of acute ethanol intoxication, and death caused by alcohol poisoning. However, the experts are difficult to carried out the assessment to determine the severity of alcohol intoxication, even using the following criteria: exogenous alcoholemia level, signs of conditionally fatal ethanol poisoning with trauma. There are differences in the ethanoloxidizing dehydrogenase enzymatic activity, make it easier to determine individual ethanol tolerance, which can be used for forensic medical substantiation to determine severity of acute alcohol intoxication and fatal ethanol poisoning. Purpose of the Study: We carried out the research by evaluating the severity of the acute alcohol intoxication, by taking into account the blood ethanol concentration level and the death caused by the fatal ethanol poisoning; we use the 2 indicators of the ethanol- oxidizing enzymatic activity, which are the alcohol dehydrogenase in liver, and acetaldehyde dehydrogenase in the brain. Material and Methods: Forensic medical experts using 72 corpses to carried out the research, we had identified ethanoloxidizing enzymatic activities in the brain stem and liver and divided into 3 observation groups : Group I – death from fatal ethanol poisoning (FEP) with blood ethanol concentration between the range from 3.0 to 5.3 g/L (22 cases); Group II – death caused by car accidents as the drivers who are having severe ethanol intoxication with vehicle’s mechanical damage, the blood ethanol concentration between the range from 3.0 to 4.8 g/L (25 cases); Group III (controlled group) – death caused by car accidents with vehicle’s mechanical damage without exogenous alcoholemia (25 cases). Results: In the fatal ethanol poisoning group, we compared with the controlled group, there are decrease in enzymatic activities, and there were significant statistically decreases (P<0.05). When comparing these enzymatic activities between IInd and IIIrd group , there were no significant statistically differences (P>0.05).

Accelerated ethanol elimination via the lungs

Ethanol poisoning is endemic the world over. Morbidity and mortality depend on blood ethanol levels which in turn depend on the balance between its rates of absorption and clearance. Clearance of ethanol is mostly at a constant rate via enzymatic metabolism. We hypothesized that isocapnic hyperpnea (IH), previously shown to be effective in acceleration of clearance of vapour anesthetics and carbon monoxide, would also accelerate the clearance of ethanol. In this proof-of-concept pilot study, five healthy male subjects were brought to a mildly elevated blood ethanol concentration (~ 0.1%) and ethanol clearance monitored during normal ventilation and IH on different days. IH increased elimination rate of ethanol in proportion to blood levels, increasing the elimination rate more than three-fold. Increased veno-arterial ethanol concentration differences during IH verified the efficacy of ethanol clearance via the lung. These data indicate that IH is a nonpharmacologic means to accelerate the elimination of ethanol by superimposing first order elimination kinetics on underlying zero order liver metabolism. Such kinetics may prove useful in treating acute severe ethanol intoxication.

DOSE DEPENDENT VASOPLEGIC SHOCK ASSOCIATED WITH ETHANOL INTOXICATION: A CASE REPORT AND LITERATURE REVIEW

SESSION TITLE: Tuesday Fellows Case Report Posters SESSION TYPE: Fellow Case Report Posters PRESENTED ON: 10/22/2019 01:00 PM - 02:00 PM INTRODUCTION: One in six US adults binge drinks four times a month as per the Centers for Disease Control and Prevention. Habits such as these place individuals at personal risk, as well as endanger others. Alcohol intoxication can cause physical effects including respiratory depression, hypotension, shock, coma and death. Here we present a patient who presented with respiratory depression, coma, and shock as a consequence of severe ethanol intoxication with remediation of symptoms directly correlating to metabolism and serum ethanol clearance. CASE PRESENTATION: A 43 year old male with no significant past medical history was admitted to our institute for unresponsiveness and undifferentiated shock requiring norepinephrine infusion. His history revealed that he drank 1 gallon of moonshine over the course of 20 minutes. His laboratory data were significant for a non-anion gap metabolic acidosis, osmolar gap of 40, and ethanol level of more than 700 mg/dl. No other toxic alcohols were detected including methanol and ethylene glycol. Other etiologies of shock were ruled out clinically and with lab and imaging data. Serial monitoring of his blood alcohol level was done over the course of two days, with a resolution of obtundation and shock as a direct correlate to decreasing ethanol levels. He was discharged without permanent end-organ damage. DISCUSSION: Five or more alcoholic drinks is considered binge drinking and may result in acute intoxication. Symptoms largely depend on serum ethanol level, with typical ethanol ranges of 50-400mg/dL in intoxicated patients. Exceedingly high levels may result in respiratory depression, coma, and shock, all of which may result in patient death. Focusing on the hemodynamic effects of ethanol intoxication, it has been reported in rat models by Phelan et al that ethanol may blunt hemodynamic regulatory responses to blood loss and dull response to volume resuscitation. Furthermore, it has been shown that ethanol may produce a vasodilatory effect mediated through alteration of central vasomotor control and via inhibition of vasoconstriction caused by catecholamines, angiotensins and vasopressin. Finally, it is thought that ethanol may have direct effects on vascular physiology, as described by Kudo et al. While the pathophysiology remains unclear, we posit that severe alcohol intoxication may produce hypotension and shock that appears to be concentration dependent and reversible when treated with supportive care. CONCLUSIONS: acute alcohol intoxication is a potentially lethal condition that often requires ventilatory and hemodynamic support. The presentation of shock and degree of vasoplegia appear to be dose-dependent, with high levels correlating to more profound shock. Shock is therefore an important cause of mortality in patients with ethanol intoxication, and early and aggressive supportive care is required to mediate its effect and prevent mortality. Reference #1: Severe hypotension and hypothermia caused by acute ethanol toxicity E Wilson and W S Waring Emerg Med J. 2007 Feb; 24(2): e7. https://doi.org/10.1136/emj.2006.041590 Reference #2: Impact of alcohol intoxication on hemodynamic, metabolic, and cytokine responses to hemorrhagic shock.Phelan H, Stahls P, Hunt J, Bagby GJ, Molina PE. J Trauma. 2002 Apr;52(4):675-82. PMID: 11956381 Reference #3: [Effect of alcohol on vascular function].Kudo R, Yuui K, Kasuda S, Hatake K. Nihon Arukoru Yakubutsu Igakkai Zasshi. 2015 Jun;50(3):123-34. PMID: 26502571 DISCLOSURES: No relevant relationships by Michael Bergman, source=Web Response No relevant relationships by CHINTAN RAMANI, source=Web Response

MOLIXAN AND CYTOFLAVIN ADMINISTRATION TO COMATOSE PATIENTS CAUSED BY ALCOHOL CONSUNPTION IN THE EMERGENCY UNIT

62 patients were admitted to Alexandrovsky City Hospital with acute severe ethanol intoxication (coma 2). The first gr. (21 pts) received by IV bolus the combination of Molixan (3,0 мg/kg) and Cytoflavin (0,14 mg/ kg); 2nd gr (21 pts) received Molixan only (3,0 мг/кг IV bolus). The interventions were identical in all groups including controls (20 pts) via standard therapy (dextrose, saline, vitamins). The awakening effect was achieved in 3,0± 0,1h (molixan+cytoflavin), and 11,5±1,2 h (controls). Molixan and Cytoflavin administration also reduced lactate acidosis, increased quality assurance, and length of stay in the Hospital, as such.

Differences between the measured blood ethanol concentration and the estimated concentration by Widmark's equation in elderly persons

BackgroundThe Widmark's equation (C [BAC]=A/p×r) is the most commonly used formula in legal medicine to estimate the blood alcohol concentration (BAC) from the amount of ingested ethanol and vice versa. Within a drinking experiment with a target BAC of 1.2g/kg, a 75-year-old participant reached a maximum BAC of 1.83g/kg and showed signs of severe ethanol intoxication, while the other nine subjects (age: 19–31 years) had BACs close to the target BAC. This incident brought up the question, if the Widmark's equation is an appropriate tool for aged persons. MethodsA drinking experiment with 50 elderly voluntary test persons (22 males, 28 females, mean age and range [males]: 69.7 years, 60–84 years, mean age and range [females]: 68.5 years, 61–78 years) was performed. The amount of ethanol leading to a BAC of 0.6g/kg was estimated individually using the Widmark's equation (used Widmark factors: 0.7 for males, 0.6 for females). After drinking, the blood ethanol concentrations were measured using headspace gas chromatography/flame ionization detection. ResultsThe measured maximum BACs of the elderly participants were significantly higher (α=0.01) than the target BAC (mean maximum BAC and range: 0.627g/kg, 0.3–0.81g/kg, for males: 0.616g/kg, 0.32–0.78g/kg, for females: 0.635g/kg, 0.3–0.81). The calculated Widmark factors showed a high coefficient of variation (for males: 0.7±0.138 [0.55–1.2, CV: 19.7%], for females 0.59±0.119 [0.46–1.08, CV: 20.2%]). ConclusionThe results demonstrate that BAC calculations by Widmark's equation in elderly individuals may be complicated by a high variation of Widmark factors. There is a tendency to an elevation of the actual BAC with increasing age.

Acute Effects of Ethanol on Glutamate Receptors

Several studies have revealed that acute ethanol inhibits the function of glutamate receptors. Glutamate receptor-mediated synaptic plasticity, such as N-methyl-D-aspartate-dependent long-term potentiation, is also inhibited by ethanol. However, the inhibition seems to be restricted to certain brain areas such as the hippocampus, amygdala and striatum. Ethanol inhibition of glutamate receptors generally requires relatively high concentrations and may therefore explain consequences of severe ethanol intoxication such as impairment of motor performance and memory. Effects of ethanol on glutamate system of developing nervous system may have a role in causing foetal alcohol syndrome. Newly found regulatory proteins of α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid AMPA receptors seem to affect ethanol inhibition thus opening new lines of research.

Treatment of accidental ethanol intoxication with hemodialysis in a dog

To describe the successful treatment of accidental ethanol intoxication with hemodialysis in a dog. A 1.5-year-old female intact mixed breed dog was presented in a comatose state believed to be due to ethanol intoxication. The initial 9 hours of supportive care treatment were complicated by multiple seizures and hypothermia, and resulted in only minimal improvement in the dog's level of consciousness. Hemodialysis was implemented and resulted in rapid clinical recovery, corresponding to a rapid decline in serum ethanol concentration. To the authors' knowledge, this is the first reported case of using hemodialysis to treat accidental ethanol intoxication in a dog. The patient's initial serum ethanol concentration was higher than those previously reported for cases of accidental ethanol intoxication in dogs, and the serum ethanol concentration was shown to rapidly decline during hemodialysis. Treatment with hemodialysis for severe ethanol intoxication was effective in this case and may be able to decrease morbidity and mortality in some cases.

Is the osmole gap a valuable indicator for the need of hemodialysis in severe ethanol intoxication?

Up-to-date no indicator for hemodialysis in severe ethanol intoxication is available. In these cases, the benefits have to outweigh the risks and costs of hemodialysis. In this case report, a suicidal patient had ingested 250 ml of 95% ethanol and was found in deep coma. In literature, some cases, especially of adolescents, are described with severe ethanol poisoning and blood ethanol levels above 740 mg/dL. Hemodialysis, if initiated, decreased ethanol levels significantly as compared to peritoneal dialysis, charcoal or gastric lavage and reduced also clinical costs. While recommendations exist for starting dialysis in ethylene glycol or methanol intoxications, no algorithm is available to determine the situations when hemodialysis is required in ethanol intoxication. The osmole gap may serve as an indicator to differentiate, which patients need haemodialysis - right now, the decision depends upon the physicians experience or preference.

Hemodialysis as a Treatment of Severe Ethanol Poisoning

A 64-year-old woman presented with coma and shock due to severe ethanol intoxication. Her initial, markedly elevated blood alcohol level of 136.5 mM fell only by 16% after a 4-hour period of conservative treatment consisting of mechanical respiration and the administration of intravenous fluids, vasopressors and inotropics. Subsequent hemodialysis rapidly reduced her blood ethanol concentrations to less threatening levels, with prompt restoration of her consciousness. Hemodialysis may be life-saving and should be considered in patients with severe ethanol intoxication.

Hormonal derangements in patients with severe alcohol intoxication.

Controversial results of fluid and electrolyte derangements in patients with moderate alcohol intoxication have been described. However, no information is available about severe alcohol intoxication. We investigated differences of hormonal disorders between alcohol-habituated and alcohol-naive subjects with severe ethanol intoxication. The hormonal derangements and recommendations on therapy of these patients are discussed. Thirty-three patients [10 alcohol-naive (group A) and 23 alcohol-habituated (group B) subjects] with severe alcohol intoxication (blood ethanol > 200 mg/dl) were selected for the study. Electrolytes and osmolarity of serum and urine, blood ethanol, vasopressin, renin, and aldosterone were determined on admission 2, 4, and 6 hr later. Fluid balance was calculated for each hour. All patients received isotonic saline solution according to urine production. Group A: On admission, serum osmolarity was increased (308 mOsmol/kg). Concomitantly, vasopressin level was elevated on admission (9.12 pg/ml). Increased serum osmolarity was correlated with elevated vasopressin levels (r = 0.8211; p < 0.005). Serum electrolytes, renin, and aldosterone values were within normal ranges. Group B: On admission, vasopressin level was significantly decreased (0.9 pg/ml), despite an elevated serum osmolarity (309 mOsmol/kg). Serum osmolarity remained high despite a sufficient fluid substitution. In addition, vasopressin level remained suppressed over the observation period. Aldosterone level was significantly increased on admission (319 ng/ml). Accordingly, serum sodium was increased from 142 to 148 mM/liter, and serum potassium was decreased from 3.9 to 3.4 mM/liter. Response to hyperosmolarity due to severe alcohol intoxication is different in alcohol-naive and alcohol-habituated subjects.(ABSTRACT TRUNCATED AT 250 WORDS)

ALTERATIONS IN SEROTONIN RECEPTOR SUBTYPES IN ETHANOL-DEPENDENT RATS

Serotonin (5-HT) receptor subtypes were investigated during severe ethanol intoxication and withdrawal. Ethanol was administered intragastrically five times a day for 4 days (12 g/kg per day). 5-HT receptor subtypes were studied: (1) in severely intoxicated animals (mean blood ethanol concentration (BEC) = 4.7 g/l); (2) during the withdrawal reaction; and (3) in a control group. The maximal density of [3H] 8-hydroxy-2-(di-n- propylamino)tetralin [( 3H] 8-OH-DPAT) binding (Bmax) to 5-HT1a receptors was decreased by 25 and 17% in the hippocampus during chronic ethanol intoxication and withdrawal, respectively. [3H]Ketanserin binding to 5-HT2 receptors in the cortex, (-)[125I]-iodo-cyanopindolol [( 125I]CYP) binding to 5-HT1b receptors in the striatum and hypothalamus, and [3H] 8-OH-DPAT binding in the cortex were not affected by chronic ethanol administration. Previous in vitro experiments have shown that 5-HT1a receptors in the hippocampus are inhibitory. The down-regulation of these receptors may play a role in physical ethanol dependence, by inducing hyperexcitability of the hippocampus.

Brain marker protein changes after short-and longterm ethanol intoxication and withdrawal in the rat

The brain marker proteins, D1, D2, and D3, localised to neuronal membranes, and mitochondrial and cytoplasmic marker proteins (MM and CM), were studied during 1–6 days (short term) intragastrically-induced severe ethanol intoxication and during 1 month (long-term) ethanol intoxication established by a liquid diet regimen. The concentrations of the same brain protiens were also measured during withdrawal from the ethanol intoxication periods. Three categories of effect were encountered: (1) decreased concentration of brain marker proteins during severe short-term intoxication, the effect being most marked for D3, possibly indicating degradation of mature synapses; (2) increased concentration of proteins D2 and MM during withdrawal, the D2 changes possibly indicating formation of new synapses; (3) increased concentration of D1 protein and MM during long-term intoxication. We suggest that the changes in brain marker proteins reflect dynamic changes of subcellular neuronal structures which may form a part of the basis of functional tolerance to and physical dependence upon ethanol or the reversion of these states after withdrawal of ethanol.

Adrenal and urinary catecholamines during and after severe ethanol intoxication in rats: A profile of changes

Adrenal and urinary levels of adrenaline and noradrenaline were determined in rats subjected to severe ethanol intoxication for periods of up to 96 hours, in rata undergoing withdrawal and in a post-withdrawal period, and in controls. Adrenaline and noradrenaline content of adrenal glands fell markedly to less than eight and twenty percent, respectively, after four days of intoxication. Noradrenaline content, but not adrenaline content, had recovered after a subsequent four day period of recovery. The depletion in adrenal catecholamine levels was coincident with increases in urinary adrenaline and noradrenaline levels over the first 48 hours of intoxication. Urinary catecholamine levels remained higher than control values for next 48 hours of intoxication. Adrenal glands were larger after 12 hours of intoxication, although there was no increase in dry weight. At later times adrenal enlargement was associated with increased dry weight and protein content. This increase in mass was found to be of cortical origin. These results demonstrate that severe ethanol intoxication promotes an intense stimulation of the rat adrenal gland with enhanced synthesis and release of catecholamines, and cortical hypertrophy.

Myocardial hypertrophy, cardiac and urinary catecholamines during severe ethanol intoxication and withdrawal

Cardiomegaly was observed in rats severely intoxicated with ethanol for a 4 day period. It was apparent at 48 hours of treatment, a time at which cardiac protein was elevated and continued into withdrawal. During a 4 day abstinence period the degree of hypertrophy declined towards normal. Cardiac noradrenaline was reduced at the 48 hour time of intoxication, then increased gradually in the further experimental period. As the cardiac hypertrophy occurs at a time that urinary catecholamines are elevated and the adrenal medulla is intensely stimulated, it is proposed that increased levels of circulating catecholamines are largely responsible for the enlargement of the heart.

Adrenal catecholamines in rats after severe ethanol intoxication and acute withdrawal

Adrenal levels of adrenaline and noradrenaline were determined in rats subjected to a 96 hour ethanol intoxication and in animals experiencing moderate to severe withdrawal behaviour. Adrenaline content of adrenal glands of animals sacrificed during intoxication and during withdrawal was less than 30% of treatment controls. The concentration of noradrenaline in withdrawing animals was 52% of control. Compensated adrenal weights of intoxicated animals were 80% larger than control values. These findings suggest that “binge-type” ethanol administration has profound effects on adrenal catecholamine levels and on adrenal gland weight.

The benzodiazepine/GABA receptor complex during severe ethanol intoxication and withdrawal in the rat.

The benzodiazepine/GABA (gammaaminobutyric acid) receptor complex was investigated during severe ethanol intoxication and withdrawal in the rat. The intragastric intubation technique was used to establish physical ethanol dependence in the animals. Cerebral cortex from male Wistar rats was studied 1) after 3 1/2 days of severe ethanol intoxication, 2) during the ethanol withdrawal reaction and 3) in a control group. The effect of GABA-ergic activation by muscimol and THIP (4,5,6,7-tetrahydroisoxazole(5,4-c)pyridin-3-01) on 3H-diazepam binding was unchanged during ethanol intoxication and withdrawal, as was the affinity constant (KD) and the maximal number of binding sites (Bmax) for 3H-flunitrazepam. In conclusion, the benzodiazepine/GABA receptor complex is unlikely to play any causal part in physical ethanol dependence.

Specific brain proteins during severe ethanol intoxication and withdrawal in the rat

In a study of the effects of severe chronic ethanol intoxication and withdrawal, immunoelectrophoretic measurements were made of the specific nervous system proteins D1, D2, D3, synaptin, 14-3-2, and glutamine synthetase in the brain. During chronic ethanol intoxication, none of these proteins deviated significantly from normal values, so the structural background for neuronal function was not measurably disturbed by any toxic effect of ethanol. However, during the ethanol withdrawal reaction, the specific concentrations of neuronal proteins D1, D2, 14-3-2, and synaptin were increased, and they subsequently normalized. D3 in brain and D2 in cerebrospinal fluid were decreased and subsequently normalized. When the neuronal localization and the possible function of these proteins are considered, the results may be interpreted as indicating an increased synthesis of neuronal synapses during the ethanol withdrawal reaction accompanied by a transient halt in synaptic decomposition. No changes occurred in the glial marker glutamine synthetase, and thus the measured changes in specific brain protein concentrations apparently reflect the structural dynamics of establishing the substrate for the functional neuronal hyperactivity constituting the ethanol withdrawal reaction.

Mouthwash: A Source of Acute Ethanol Intoxication

Treatment of a 33-month-old girl who sustained severe ethanol intoxication resulting from mouthwash ingestion prompted us to review the ingestions, compositions, and sales of these common household products. Mouthwashes contain up to 26.9% ethanol (53.8 proof), and each of the leading brands markets single containers that can supply a lethal ethanol dose to a toddler. Mouthwashes are particularly hazardous because they are thought to be innocuous, and they are widely available, attractive, and kept within easy reach of children. Parent education, and restrictions on packaging and ethanol concentration are recommended.

Integrity of blood-brain barrier during ethanol intoxication and withdrawal in the rat: normal glucose transfer and permeability to Na+ and Cl-.

The unidirectional brain uptake of 14-C-D-glucose, 24Na+ and 36Cl- was measured by the Oldendorf tissue uptake method in order to test whether severe ethanol intoxication or withdrawal affected the glucose transfer across the blood-brain barrier (BBB) or the integrity of the BBB to small ions. The Oldendorf technique rests upon the assumption that water is freely diffusible across the BBB, but in the present study a correction was applied, which takes into account the fact that the water extraction actually depends upon the different cerebral blood flow (CBF) in the groups. The 24Na+ and 36Cl- extraction values were about 1% as reported in other studies and this suggests that there was no major effect on the BBB reaction to small ions during severe ethanol intoxication or during withdrawal. The permeability surface area product did not deviate significantly from control values in any group and thus there was no indication that glucose transfer across the BBB differed during ethanol intoxication or withdrawal.