Managing Alcohol Withdrawal Syndrome

1. Managing Alcohol Withdrawal Syndrome Behnam shariati M.D. Iran University of Medical Sciences

2. INTRODUCTION • Such a common condition that virtually every clinician is confronted with its complications • About 8 million alcohol dependent people in the United States. • Approximately 500,000 episodes of moderate to severe withdrawal

3. PATHOPHYSIOLOGY

4. Overview • Some individuals suffer from more severe AWS • Genetic predisposition may play a role • Longer periods of use is associated with more severe AWS

5. Gamma-aminobutyric acid • The major inhibitory neurotransmitter in the brain. • Chronic ethanol use induces an insensitivity to GABA. • Cessation of alcohol or a reduction from chronically elevated concentrations results in decreased inhibitory tone.

6. Excitatory amino acids • Glutamate binds to the NMDA receptor and leads to neuronal excitation. • Ethanol inhibits glutamate induced excitation. • Adaption occurs by increasing the number of glutamate receptors • Cessation results in excess excitation.

7. Neurobiology of Alcohol • ↑ GABA • ↓ glutamate • ↑ NE • ↓ GABA • ↑ NMDA • ↓ NE ACUTE CHRONIC

8. Neurobiology of Alcohol WITHDRAWAL • ↑excitatation by: ↓ GABA, ↑ glutamate  tremor, seizures • norepinephrine sensitivity  autonomic instability

9. MINOR WITHDRAWAL SYMPTOMS • due to central nervous system hyperactivity: ● Insomnia ● Tremulousness ● Mild anxiety ● Gastrointestinal upset; anorexia ● Headache ● Diaphoresis ● Palpitations • Onset within six hours of the cessation • If withdrawal does not progress, these findings resolve within 24 to 48 hours.

10. Alcohol witAWSDefinitionhdrawalsyndrome (AWS) ≥2 • Hallucinations and illusions • Agitation • Anxiety • Seizures • ↑ HR and BP • Tremor • Insomnia • Nausea/vomiting

11. Severe AWS: Risk Factors • Amount/ time • # of prior episodes • Use of other substances • ↑ BAC • Severe symptoms on presentation • Medical/surgical comorbidity • ↑Age

12. Signs and symptoms: • Tremor • ↑ autonomic activity: • ↑ blood pressure/HR • ↑ reflexes • Fever • Insomnia/Anxiety • Sweating Alcohol withdrawal: Phase I Time abstinent or cut down: 6- 24 hours

13. Alcohol withdrawal: Phase II Signs and symptoms: • Distractibility • Autonomic instability (↑↓heart rate, ↑↓ blood pressure) • Grand mal seizures Time Abstinent: 7-48 hours

14. Alcohol withdrawal: Phase III Delirium Tremens: • Confusion/disorientation • Severe autonomic instability • Intense tremor • Hallucinations? • Agitation Time Abstinent: 72-96 hours

15. ALCOHOLIC HALLUCINOSIS • Usually visual develop within 12 to 24 hours and resolve within 24 to 48 hours (the earliest point at which delirium tremens develops) • In contrast to delirium tremens, is not associated with clouding of the sensoriumand vital signs are normal.

16. DELIRIUM TREMENS (DT)

17. Clinical manifestations of severe AWS and DT • DT is defined by hallucinations, disorientation, tachycardia, hypertension, hyperthermia, agitation, and diaphoresis. • Symptoms of DT persist for up to seven days. • Patients have significantly elevated cardiac indices, oxygen delivery, and oxygen consumption. • pH rises due to hyperventilation • Hyperventilation results in a significant decrease in cerebral blood flow.

18. AWS and Electrolytes • Almost all patients in AWS are hypovolemic. • Hypokalemiais common • Hypomagnesemiais common and may predispose to dysrhythmias and seizures. • Hypophosphatemia due to malnutrition and if severe, may contribute to cardiac failure and rhabdomyolysis.

19. Risk factors • Five percent of patients with AWS suffer from DT • DT typically begins between 48 and 96 hours after the last drink and lasts one to five days. • Risk factors for the development of DT include: • A history of sustained drinking • A history of previous DT • Age greater than 30 • The presence of a concurrent illness • The presence of significant alcohol withdrawal in the presence of an elevated alcohol level ● A longer period of symtomssince the last drink

20. Mortality • Up to 5 percent. • Death usually is due to arrhythmia, complicating illnesses, such as pneumonia, or failure to identify an underlying problem that led to the cessation of alcohol use, such as pancreatitis, hepatitis, or central nervous system injury or infection. • Older age, preexisting pulmonary disease, core body temperature greater than 40ºC (104ºF), and coexisting liver disease are associated with a greater risk of mortality.

21. MANAGEMENT

22. Ruling out alternative diagnoses • It may be necessary to perform extensive testing, including lumbar puncture and cranial CT, to rule out other diagnostic considerations. • Conditions, such as infection (eg, meningitis), trauma (eg, intracranial hemorrhage), metabolic derangements, drug overdose, hepatic failure, and gastrointestinal bleeding, can mimic or coexist with alcohol withdrawal.

23. TREATMENT of AWS

24. Treatment: General Care • Multivitamins (MVI): 1 tablet daily • Thiamine: 100 mg daily • Folic acid: 1 mg daily • Fluid repletion if dehydrated

25. Symptom control and supportive care • Benzodiazepines for psychomotor agitation and prevention of progression to more severe withdrawal. • Supportive care, including IV fluids, nutritional supplementation, and frequent reassessment of vital signs, is important. • Quiet environment. • Mechanical restraint for patients suffering from DT • Once adequate chemical sedation is achieved, physical restraints should be removed

26. Thiamine and glucose should be administered in order to prevent or treat Wernicke'sencephalopathy. • Multivitamins supplemented with folate should be given routinely • deficiencies of glucose, potassium, magnesium, and phosphate should be corrected as needed. • Initially treatment should be intravenous as gastrointestinal absorption is impaired in many patients. • Some clinicians infuse of a combination of thiamine, folate, and a multivitamin in isotonic saline with 5 percent dextrose, this is referred to as a “banana bag”.

27. During the early phases patients are NPO to prevent aspiration. • Initially, parenteral glucose supplementation is sufficient, but additional nutrition may be needed for patients who remain unable to eat for more than a day or two. • Patients considered high risk should be monitored in an ICU.

28. Treatment of psychomotor agitation with benzodiazepines

29. Treatment: Benzodiazepines • First line • Effective to ↓: • Severity of withdrawal • Incidence of delirium • Incidence of seizures • 2 types: • Longer acting ( ½ life ~ 30 hours) e.g. diazepam, chlordiazepoxide • Shorter acting ( ½ life ~15 hours) e.g. lorazepam, oxazepam • Longer acting better for ↓ seizures, but  sedation

30. BZD Dosing Strategies “Fixed schedule” • Set doses at fixed intervals • PRNs for breakthrough symptoms • Tapered over 3-5 days • Problems: over/under- medication Examples: • Lorazepam 2 mg q4h • Diazepam 10-20 mg q6h • Chlordiazepoxide 25-50 mg q6h

31. BZD Dosing Strategies “Symptom- triggered” • Medication given when CIWA >8 • ↓ Dose, side effects, tx time • Problems:  cost/staff time Examples • Lorazepam 2 mg q1h CIWA 8-13 • Lorazepam 3 mg q1h CIWA 14-20 • Lorazepam 4 mg q1h CIWA >20

32. Drug selection • In general, long-acting benzodiazepines with active metabolites are preferred • We recommend a symptom-triggered approach to treatment with benzodiazepines. • lorazepamoroxazepamfor the treatment of patients with advanced cirrhosis or acute alcoholic hepatitis. • Treatment with agents available in parenteral form (eg, lorazepam, diazepam) may be necessary in patients who cannot receive oral medications.

33. Route • Patients with seizures, DT or tremulousnessrequire IV therapy with Bnzds. • IM administration should be avoided. • Oral formulations are preferred in most outpatient settings, for the prevention of withdrawal in asymptomatic patients known to be at risk

34. Dosing • Titration should be based upon a patient's risk factors and ability to tolerate DT. • IVdiazepam, 5 to 10 mg IV every 5 to 10 minutes, until the appropriate level of sedation. • Lorazepam, 2 to 4 mg IV every 15 to 20 minutes, can also be used. • Equivalent doses of oral chlordiazepoxide. • Fixed schedule therapy is administered despite evidence against it. • This is most useful for preventing withdrawal in patients at risk, but asymptomatic or minimally symptomatic. • The only advantage of this strategy is for the provider, as frequent reassessment is not required.

35. Symptom-triggered therapy • Provide medication only when a patient has symptoms. • Aregular assessment should be made of the patient's status using a validated instrument CIWA-Ar, a measure of withdrawal severity , or some equivalent assessment. • Evaluation intervals as frequent as every 10 to 15 minutes for severe symptoms. • Once severe symptoms are controlled, hourly reassessment. • Interval of four to six hours is reasonable for stable patients. • When the score is elevated, additional medication is given. • For acute withdrawal, givediazepam 5 to 10 mg IV for any score of 8 or greater on the CIWA-Ar.

36. CIWA-ArScore 0→7 on: • Nausea, vomiting • Tremor • Sweating • Anxiety • Agitation • Tactile hallucinations • Auditory hallucinations • Visual hallucinations • Headache • Disorientation

37. Alternative and contraindicated agents • Other drugs have been used with benzodiazepines or, rarely, alone. • These agents are less studied and may mask the hemodynamic signs of withdrawal, which can precede seizures. • Shouldnot be used routinely. • Such drugs include: • Ethanol • Antipsychotics • Anticonvulsants • Centrally acting alpha-2 agonists • Beta blockers • Baclofen

38. Ethanol • Shouldnot be used as therapy in the setting of acute alcohol withdrawal. • It is difficult to titrate, associated with many adverse metabolic and end-organ effects, and clearly inferior to benzodiazepines.

39. Antipsychotics • Phenothiazinesand butyrophenones(haloperidol) lower the seizure threshold and should not be used routinely . • Treatment with antipsychotics would only be appropriate when a decompensated thought disorder (such as schizophrenia) coexists. • If a clinician determines that antipsychotic therapy is indicated, we recommend an ECG to screen for QT prolongation

40. Anticonvulsants • The overwhelming majority of seizures from withdrawal are self-limited and do not require treatment with anticonvulsants. • In status epilepticusphenobarbital or propofol may be used for short-term management in conjunction with benzodiazepines. • Carbamazepine may have a role in the outpatient management of mild alcohol withdrawal.

41. alpha-2 agonists • these agents may reduce some symptoms of withdrawal. • There are no controlled trials showing that they prevent the development of seizures or DT. • Shouldnot be used as a primary treatment for acute severe alcohol withdrawal.

42. Beta blockers • May reduce minor symptoms of withdrawal, but they have not been shown to prevent the development of seizures or DT. • Shouldnot be used for the treatment of acute severe alcohol withdrawal. • In sustained tachycardia and hypertension.

43. Baclofen • A selective agonist of GABA-B receptor used to treat reversible spasticity • Its effectiveness in controlling severe symptoms remains unproven. • Baclofen should not be used

44. PROPHYLAXIS • Patients with a history of seizures, delirium tremens, or prolonged, heavy alcohol consumption, who are minimally symptomatic and are admitted to the hospital for other reasons, can be prophylactically treated with  chlordiazepoxide. • For prophylaxis, give 25 to 100 mg every six hours for one day, followed by 25 to 50 mg every six hours for an additional two days. • Asymptomatic or minimally patients at lower risk should be closely monitored and may be treated with  chlordiazepoxide 25 to 50 mg every hour as needed when a score of 8 or greater is achieved on the CIWA-Ar.

45. SUMMARY AND RECOMMENDATIONS • Rule out other diagnoses. • Alcohol withdrawal syndromes encompass symptoms ranging from mild tremulousness to life-threatening delirium tremens. • DT is characterized by agitation, disorientation, hallucinations, and autonomic instability (tachycardia, hypertension, hyperthermia, and diaphoresis) and is associated with a mortality rate of up to 5 percent and higher if the condition goes untreated. • Alcoholic hallucinosis and DT are distinct clinical entities.

46. Risk factors for delirium tremens: • A history of sustained drinking • A history of previous DT • Age greater than 30 • The presence of a concurrent illness • The presence of significant alcohol withdrawal in the presence of an elevated ethanol level • A longer period (more than two days) between the last drink and the onset of withdrawal

47. SUMMARY AND RECOMMENDATIONS • Treat patients with signs and symptoms of moderate or severe alcohol withdrawal with benzodiazepines. • Givediazepam 5 to 10 mg IV, repeated every 5 to 10 minutes until symptoms are controlled. • Give lorazepam2 to 4 mg IV, repeat every 15 to 20 minutes. • The general goal of sedation is a calm but alert state. • IV benzodiazepines should be continued until it is clear that the patient is no longer delirious and at high risk for aspiration, and that absorption from the gut is reliable.

48. SUMMARY AND RECOMMENDATIONS • Use a validated assessment tool(CIWA-Ar) • Evaluate patients with severe symptoms every 10 to 15 minutes; an interval of four to six hour for stable patients with mild symptoms. • Asymptomatic or minimally symptomatic patients at risk for withdrawal, but admitted to the hospital for other reasons, should be closely monitored and may be treated prophylactically with oral benzodiazepines.

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