Acute acohol intoxicaion

alcohol perturbs the balance between excitatory and inhibitory influences in the brain, resulting in Anxiolysis. An increased reaction time, diminished fine motor control, impulsivity, and impaired judgement be come evident when the concentionof alcohol in the blood is 20-30mg/dl.
More than 50% of persons are grossly intoxicated by a conc. Of 150mg/dl.
The defintion of intoxication varies by country.
Alcohol can be measured in saliva, urine,sweat,and blood, level in exheled air remains the primary method of assessing the level of intoxication.
Ethanol (CH 3 CH 2 OH) is a water-soluble alcohol that rapidly crosses cell membranes.
Absorption of ethanol occurs via the gastrointestinal system, primarily in the stomach (70 percent) and duodenum (25 percent), with a small amount absorbed by the remaining intestine .
When the stomach is empty, peak blood ethanol levels are reached between 30 and 90 minutes after ingestion.

1. BY ALIYU USMAN MUHAMMAD MBchB KAMPALA INTERNATIONAL UNIVERSITY, UGANDA FACILLITATOR: Dr. Isaac April,2018 ACUTE ACOHOL INTOXICATION,WERNICKE’S ENCEPHALOPATHY AND WKS

2. INTRODUCTION Alcohol perturbs the balance between excitatory and inhibitory influences in the brain, resulting in Anxiolysis , Ataxia and sedation. An increased reaction time, diminished fine motor control, impulsivity, and impaired judgement be come evident when the concentionof alcohol in the blood is 20-30mg/dl. More than 50% of persons are grossly intoxicated by a conc. Of 150mg/dl. The defintion of intoxication varies by country. Alcohol can be measured in saliva, urine,sweat,and blood, level in exheled air remains the primary method of assessing the level of intoxication.

3. FACTORS AFFECTING INTOXICATION RISK Body weight and composition Rate of absorption from GIT Om average, the ingestion of 3 standard drink (42g alcohol) on an empty stomach results in amaximum blood conc. Of 67-92mg/dl in men. Concentrations of alcohol in blood will be higher in women because on average women are smaller than men, have less body water per unit of weight into which alcohol can distribute, and less gastric ADH activity than men.

4. ALCOHOL METABOLISM   — Ethanol is metabolized via several pathways, each of which can contribute to toxicity. The primary hepatic pathway generates acetaldehyde and reduced nicotinamide adenine dinucleotide (NAD) Ethanol is metabolized first in the liver to acetaldehyde; this process occurs in the hepatocyte cytosol via a reaction catalyzed by the enzyme alcohol dehydrogenase (ADH) The acetaldehyde that is generated is subsequently metabolized to acetate, a process that occurs in the mitochondria and is catalyzed by a different enzyme, acetaldehyde dehydrogenase (ALDH).

5. PATHOPHYSIOLOGY Ethanol (CH  3  CH  2  OH) is a water-soluble alcohol that rapidly crosses cell membranes. Absorption of ethanol occurs via the gastrointestinal system, primarily in the stomach (70 percent) and duodenum (25 percent), with a small amount absorbed by the remaining intestine . When the stomach is empty, peak blood ethanol levels are reached between 30 and 90 minutes after ingestion.

6. CLINICAL FEATURES Signs and symptoms of acute ethanol intoxication vary with severity and can include; slurred speech nystagmus , disinhibited behavior Incoordination unsteady gait memory impairment stupor, or coma. Hypotension and tachycardia may occur as a result of ethanol-induced peripheral vasodilation , or secondary to volume loss.

7. CLINICAL FEATURES CONT….. Acute alcohol intoxication can also induce multiple metabolic derangements including Hypoglycemia lactic acidosis Hypokalemia Hypomagnesemia hypocalcemia , and hypophosphatemia

8. CLINICAL FEATURES CONT….. Among patients who do not abuse alcohol, clinical signs often associated with particular ranges of the blood alcohol concentration (BAC) are as follow : With a BAC between 0.01 and 0.10 percent (<100 mg/ dL  or 22  mmol /L), euphoria and mild deficits in coordination, attention, and cognition may be observed. With a BAC between 0.10 and 0.20 percent, an individual experiences greater deficits in coordination and psychomotor skills, decreased attention, ataxia, impaired judgment, slurred speech, and mood variability. With a BAC between 0.20 to 0.30 percent, severe alcohol intoxication results in a lack of coordination, incoherent thoughts, confusion, and nausea and vomiting. When the BAC exceeds 0.30 percent, stupor and loss of consciousness can occur. Some patients experience coma and respiratory depression, and death is possible.

9. DIAGNOSIS   —  Alcohol intoxication as a cause of altered mental status is a diagnosis of exclusion and should be considered only after ruling out more serious conditions such as head trauma, hypoxia , hypoglycemia , hypothermia , hepatic encephalopathy, and other metabolic and physiologic derangements.

10. LABORATORY EVALUATION Serum alcohol concentration and associated signs   — Measurements from serum provide the most accurate determination of a patient’s alcohol level. Alternative methods, such as breath analysis, provide more rapid results, but often give slightly lower ethanol concentrations than those obtained from venous blood . Additional studies   — (serum glucose, basic electrolytes).

11. TREATMENT    The treatment for acute ethanol intoxication is primarily supportive. As a general rule, all intoxicated patients should receive a rapid bedside glucose determination, followed by dextrose infusion if hypoglycemia is present. In addition, all patients presenting with acute ethanol intoxication should be carefully assessed for occult traumatic injuries. Patients presenting with coma secondary to ethanol intoxication should receive at least 100 mg of parenteral thiamine to prevent or treat Wernicke's encephalopathy, along with dextrose.

12. TREATMENT CONT… Some patients with acute ethanol intoxication and altered sensorium can be agitated, violent, and uncooperative. In such cases, the use of chemical sedation may be needed to prevent the patient from harming themselves or others. Benzodiazepines and typical antipsychotics are frequently used in these patients, but caution must be taken as these drugs can worsen the respiratory depression caused by alcohol

13. WERNICKE'S ENCEPHALOPATHY

14. WERNICKE'S ENCEPHALOPATHY Or now often Wernicke's disease refers to the presence of neurological symptoms caused by biochemical lesions of the central nervous system after exhaustion of B-vitamin reserves, in particular thiamine. Classically, Wernicke's encephalopathy is characterised by the triad ophthalmoplegia , ataxia, and confusion. However, only 10% of patients exhibit all three features, and other symptoms may also be present.

15. EPIDEMIOLOGY    — Typical brain lesions of Wernicke's encephalopathy (WE) are observed at autopsy in 0.8 to 2.8 percent of the general population in the Western world, and the vast majority of affected patients are alcoholic

16. Associated conditions    WE occurs also in the setting of poor nutrition caused by malabsorption , poor dietary intake, increased metabolic requirement ( eg , during systemic illnesses), or increased loss of the water-soluble vitamin thiamine ( eg , in renal dialysis). Conditions associated with WE include: Chronic alcoholism Anorexia nervosa or dieting Hyperemesis of pregnancy Prolonged intravenous feeding without proper supplementation Prolonged fasting or starvation, or unbalanced nutrition, especially with refeeding Gastrointestinal surgery (including bariatric surgery) Systemic malignancy Transplantation Hemodialysis or peritoneal dialysis Acquired immunodeficiency syndrome

17. PATHOPHYSIOLOGY Thiamine deficiency and errors of thiamine metabolism, are believed to be the primary cause of Wernicke encephalopathy. Thiamine, also called B1, helps to breakdown glucose. Specifically, it acts as an essential coenzyme to the TCA cycle and the pentose phosphate shunt. Thiamine is first metabolised to its more active form, thiamine diphosphate (TDP), before it is used. The body only has 2–3 weeks of thiamine reserves, which are readily exhausted without intake, or if depletion occurs rapidly, such as in chronic inflammatory states or in diabetes.

18. Thiamine is involved in: Metabolism of carbohydrates, creating energy. Production of neurotransmitters including glutamic acid and GABA. Lipidmetabolism , necessary for myelin production. Amino acid modification. Probably linked to the production of taurine , of great importance cardiac. Neuromodulation .

19. Neuropathy   The primary neurological-related injury caused by thiamine deficiency in WE is three-fold: oxidative damage, mitochondrial injury leading to apoptosis, and directly stimulating a pro-apoptotic pathway. Thiamine deficiency affects both neurons and astrocytes , glial cells of the brain. Thiamine deficiency alters the glutamate uptake of astrocytes , through changes in the expression of astrocytic glutamate transporters EAAT1 and EAAT2, leading to excitotoxicity . Other changes include those to the GABA transporter subtype GAT-3, GFAP, glutamine synthetase , and the Aquaporin 4 channel. Focal lactic acidosis also causes secondary oedema , oxidative stress, inflammation and white matter damage.

20. Thiamine deficiency in alcohol abusers results from a combination of inadequate dietary intake Reduced gastrointestinal absorption Decreased hepatic storage, and Impaired utilization

21. PATHOLOGICAL ANATOMY   Despite its name, WE is not related to Wernicke's area, a region of the brain associated with speech and language interpretation.  In most, early lesions completely reversed with immediate and adequate supplementation.  Lesions are usually symmetrical in the periventricular region, diencephalon, the midbrain, hypothalamus, and cerebellar vermis . Brainstem lesions may include cranical nerve III, IV, VI and VIII nuclei, the medial thalamic nuclei, and the dorsal nucleus of the vagus nerve. Oedema may be found in the regions surrounding the third ventricle, and fourth ventricle, also appearing petechiae and small hemorrhages. Chronic cases can present the atrophy of the mammillary bodies. 

22. CLINICAL MANIFESTATIONS Classic signs   — The classic triad of Wernicke's encephalopathy (WE) includes: Encephalopathy Oculomotor dysfunction Gait ataxia Clinical recognition of WE is straightforward when an alcoholic presents with this classic triad. However, this may be the exception, not the rule.

23. CLINICAL MANIFESTATIONS CONT… Encephalopathy — The encephalopathy is characterized by profound disorientation, indifference, and inattentiveness . Oculomotor dysfunction — Nystagmus , lateral rectus palsy, and conjugate gaze palsies reflect lesions of the oculomotor , abducens , and vestibular nuclei. Ocular abnormalities usually occur in combination rather than alone.  Gait ataxia — Ataxia primarily involves stance and gait and is likely due to a combination of polyneuropathy , cerebellar involvement, and vestibular dysfunction . Cerebellar pathology is generally restricted to the anterior and superior vermis . Vestibular dysfunction may be the major cause of acute gait ataxia in WE.

24. Other signs  Patients with WE may also present with the following findings: Evidence of protein-calorie malnutrition is observed frequently in patients with WE Vestibular dysfunction without hearing loss is a common finding Peripheral neuropathy is common and typically involves just the lower extremities . Patients complain of the gradual onset of weakness, paresthesias , and pain affecting the distal lower extremities. Cardiovascular signs and symptoms are common and include tachycardia, exertional dyspnea , elevated cardiac output, and EKG abnormalities. These reverse with thiamine administration.

25. DIAGNOSIS   —  Wernicke's encephalopathy (WE) is primarily a clinical diagnosis. Laboratory studies and neuroimaging studies can be helpful, but the biggest barrier to diagnosis is a low index of suspicion when all clinical symptoms are not present and in the nonalcoholic patient. Institution of treatment takes priority over diagnosis, and response to treatment may be diagnostic

26. LABORATORY TESTING    — There are no laboratory studies that are diagnostic of WE. Thiamine deficiency can be most reliably detected by measurement of erythrocyte thiamine transketolase (ETKA) before and after the addition of thiamine pyrophosphate (TPP). A low ETKA, along with a more than 25 percent stimulation, establishes the diagnosis of thiamine deficiency. A serum thiamine or thiamine pyrophosphate level in serum or whole blood can also be measured by chromatography.

27. TREATMENT    — The diagnosis of WE is difficult to confirm and, untreated, most patients progress to coma and death. Fortunately, intravenous administration of thiamine is safe, simple, inexpensive, and effective. Adverse reactions, including anaphylaxis and bronchospasm are reported but are extremely rare

28. TREATMENT   CONT…. Patients with suspected Wernicke's encephalopathy (WE) require immediate parenteral administration of thiamine. A recommended regimen is 500 mg of thiamine intravenously, infused over 30 minutes, three times daily for two consecutive days and 500 mg intravenously or intramuscularly once daily for an additional five days, in combination with other B vitamins. Administration of glucose without thiamine can precipitate or worsen WE; thus, thiamine should be administered before glucose . Because gastrointestinal absorption of thiamine is erratic in alcoholic and malnourished patients, oral administration of thiamine is an unreliable initial treatment for WE.

29. TREATMENT   CONT…. dietary requirements for thiamine are only 1 to 2 mg daily, absorption and utilization of thiamine are incomplete, and some patients have genetically determined requirements for much larger doses. Daily oral administration of 100 mg of thiamine should be continued after the completion of parenteral treatment and after discharge from the hospital until patients are no longer considered at risk. Magnesium and other vitamins are replaced as well, along with other nutritional deficits if present.

30. PREVENTION The prevention of WE and Korsakoff's amnestic syndrome (KS) might be possible through the widespread oral administration of thiamine to outpatients at risk. Enrichment of flour with thiamine. Fortification of alcoholic beverages has also been proposed.

31. WERNICKE–KORSAKOFF SYNDROME (WKS)

32. INTRODUCTION Wernicke–Korsakoff syndrome (WKS)—also called wet brain, Korsakoff's psychosis, and alcoholic encephalopathy)— The syndrome is a combined manifestation of two namesake disorders, Wernicke's encephalopathy and Korsakoff's psychosis, named after Carl Wernicke and Sergei Korsakoff respectively. It is a manifestation of thiamine (vitamin B1) deficiency, a spectrum of disorders which also encompasses beriberi, Wernicke's encephalopathy, and Korsakoff's psychosis. These disorders may manifest concurrently or separately. WKS is usually secondary to alcohol abuse. It mainly causes vision changes, ataxia and impaired memory.

33. Diagnosis Diagnosis of Wernicke–Korsakoff syndrome is by clinical impression and can sometimes be confirmed with formal neuropsychological assessment. Wernicke's encephalopathy typically presents with ataxia and nystagmus , and Korsakoff's psychosis with anterograde and retrograde amnesia and confabulation upon relevant lines of questioning

34. PATHOPHYSIOLOGY    Brain atrophy associated with WKS occurs in the following regions of the brain; the mamillary bodies, the thalamus, the periaqueductal grey, the walls of the 3rd ventricle, the floor of the 4th ventrical , the cerebellum, and the frontal lobe. In addition to the damage seen in these areas there have been reports of damage to cortex, although it was noted that this may be due to the direct toxic effects of alcohol as opposed to thiamine deficiency that has been attributed as the underlying cause of Wernicke-Korsakoff Syndrome

35. The amnesia that is associated with this syndrome is a result of the atrophy in the structures of the diencephalon (the thalamus, hypothalamus and mamillary bodies), and is similar to amnesia that is presented as a result of other cases of damage to the medial temporal lobe. It has been argued that the memory impairments can occur as a results of damage along any part of the mamillo -thalamic tract, which explains how WKS can develop in patients with damage exclusively to either the thalamus or the mamillary bodies.

36. CLINICAL MANIFESTATIONS It involves an acute Wernicke -encephalopathy phase, followed by the development of a chronic Korsakoff's syndrome phase.

37. KORSAKOFF'S SYNDROME   KS is described as an acute onset of severe memory impairment without any dysfunction in intellectual abilities. The DSM IV lists the following criteria for the diagnosis of Korsakoff's Syndrome:   Anterograde amnesia Variable presentation of retrograde amnesia   One of:   Aphasia Apraxia Agnosia A deficit in executive functions   In addition, the DSM IV indicates that normal activities and function will be impaired by the memory deficits and that the experience of amnesia must occur outside of times where the individual is in a state of delirium, intoxification , or withdrawal.   Cognitive effects  

38. Memory deficits As mentioned previously, the amnesic symptoms of WKS include both retrograde and anterograde amnesia. The retrograde deficit has been demonstrated through an inability of WKS patients to recall or recognize information for recent public events. The anterograde memory loss is demonstrated through deficits in tasks that involve encoding and then recalling lists of words and faces, as well as semantic learning tasks.

39. Confabulation   Patient's suffering from WKS often show confabulation, spontaneous confabulation being seen more frequently than provoked confabulation. Spontaneous confabulations refer to incorrect memories that the patient holds to be true, and may act on, arising spontaneously without any provocation. Provoked confabulations can occur when a patient is cued to give a response, this may occur in test settings.

40. MANAGEMENT PREVENTION AS FOR WERNICKE’S ENCEPHALOPATHY