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Management of Abstinence

Management of Abstinence. Bradley J. Phillips, MD. Substance Abuse. Alcohol Abuse 76 million people in the US MVC leading cause of death 50% of MVC involve alcohol 2/5 Americans involved 67% of home, fire, and job injuries Illicit Drug Abuse cocaine > 50% of trauma

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Management of Abstinence

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  1. Management of Abstinence Bradley J. Phillips, MD

  2. Substance Abuse • Alcohol Abuse • 76 million people in the US • MVC leading cause of death • 50% of MVC involve alcohol • 2/5 Americans involved • 67% of home, fire, and job injuries • Illicit Drug Abuse • cocaine > 50% of trauma • cocaine > 80% of violent crime

  3. Pitfalls of Intoxication • Increased incidence of diagnostic errors • desire to “treat and street” • assuming just a “repeater” • failure to recognize serious neurologic lesions • decreased pain perception

  4. Acute/Chronic EtOH Effects on Physiology • Respiratory • “snoring” = partial airway obstruction • prone to aspirate • Cardiovascular • decreased compensatory response to hemorrhage • increased arrhythmias • increased cardiomyopathy

  5. Acute/Chronic EtOH Effects on Physiology • Neurologic • Korsakoff’s syndrome • Wernicke’s syndrome • peripherial neuropathy • GI • cirrhosis • GI bleeds • varices • peptic ulcers

  6. Acute/Chronic EtOH Effects on Physiology • Metabolism • alcohol ketoacidosis • hypoglycemia • Hematology • coagulopathies • anemia • poor resistance to infection

  7. Illicit Drugs Effects on Physiology • Cocaine/amphetamines/hallucinogens • respiratory difficulty • tachycardia • hypertension • Narcotics/barbiturates/tranquilizers • hypoventilation • bradycardia • hypotension

  8. Cocaine • Local anesthetic and sympathomimetic • Hyperdynamic cardiovascular response • CVA (hypertensive crisis) • Myocardial infarcts • Aortic dissection • Pulmonary edema/bronchospasm • Rhabdomyolysis • GI ischemia/perforations • Mental status (judgement, paranoia)

  9. Opiates • Decreased mental status • Hypotension • Hypovolemia • Pulmonary congestion • Infectious (heroin)

  10. Day 1 Day 2 Day 3 Day 4 Day 5 Day 6 Day 7 tremulous hallucinatory epileptic delirious Historical Withdrawal • Victor and Adams, 1953 • Ist comprehensive account • 4 “states” • occur separately or in combinations • mortality = 15% (delirium state)

  11. “Modern” EtOH Withdrawal • Acute Withdrawal • hours to days • irritability, tremulous, tachycardia • Delirium tremens (DT’s) • usually > 48 hrs tremors tachycardia confusion hypertension delusions hyperreflexia hallucinations seizures

  12. “Modern” Time Course Foy, Kay, Taylor. QJM, 1997

  13. Symptoms drug craving restlessness irritability dec. pain tolerance nausea cramps anxiety myoclonus delirium Signs tachycardia sweating vomiting diarrhea hypertension fever seizure tachypnea Diagnosis

  14. Evaluation • History • timing of last usage • amount • previous withdrawal/seizures • family member informant • Labs • EtOH/toxicology screen (blood/urine) • CBC/coags • electrolytes/bun/cr/mg/phos/LFT’s

  15. Differential Dx • Hypoxia • Shock/hypovolemia • Head trauma • Sepsis • Hypoglycemia • Electrolyte abnormalities • Withdrawal

  16. DT’s Complications • Significant co-morbidity • Cardiac collapse • CI 36% • O2 consumption 25% • Seizures • Renal failure • Mortality • 1 to 15%

  17. Onset/Duration of Complications Duration (hrs.) Time to Onset (hrs.) Foy, Kay, Taylor. QJM, 1997

  18. Shown beneficial benzodiazepines alpha-adrenergic agonist anti-seizures Propofol barbiturates neuroleptics clomethiazole No efficacy (humans) beta-adrenergic antagonist Ca-channel blockers ethyl alcohol magnesium thiamine Pharmacological Management

  19. Benzodiazepines • Moskowitz et al, Alcohol Clin Exp Res, 1983 - 81 studies • Only proven efficacious drug • Drugs of choice • Safer than other drugs if taken in excess

  20. Benzodiazepines • Pharmacological characteristics • CNS and peripherial interaction with GABA receptors • no particular one better at preventing withdrawal symptoms • ? longer-acting better at preventing seizures • no data on reducing delirium • duration of action dependent on lipophilicity, volume of distribution and half-life • hepatic metabolism only

  21. Long-acting Chlordiazepoxide (Librium) active metabolites t1/2 = 1-8 days po/IV/IM avoid IM Diazepam (Valium) active metabolites t1/2 = 25-100 hrs po/IV/IM avoid IM Short-acting Lorazepam (Ativan) no active metabolites t1/2 = 10-20 hrs. slower onset of action po/IV/IM Midazolam (Versed) active metabolites t1/2 = < 12 hrs IV/IM Benzodiazepines

  22. Benzodiazepines • Method of Dosing • scheduled vs. prn • Sellers et al, Clin Phar Ther, 1983 • valium 20 mg q 1-2 hrs prn • successful = 72% (valium) vs 56% (placebo) • 90% improved in 30 hrs. • Saitz et al, JAMA, 1994 • po Librium scheduled vs prn • scheduled = 68 hrs. vs prn = 9 hrs. • scheduled = 425 mg vs. prn = 100 mg

  23. Benzodiazepines Foy, Kay, Taylor. QJM, 1997

  24. Benzodiazepines • Adverse effects • respiratory depression • cardiovascular depression • iatrogenic withdrawal • metabolic acidosis • propylene glycol • carrier in diazepam IV • converted to lactic acid • also found in silver sulfadiazene, IV nitro, and etomidate

  25. Barbiturates • Used by 10% of detoxification programs • No controlled studies for effectiveness • Advantages • low abuse potential • cheap • well-documented anti-seizure • Disadvantages • greater respiratory depression • cardiovascular depression • lower safety profile than benzodiazepines

  26. Clonidine • Alpha1-adrenergic agonist • Controlling withdrawal symptoms/signs • superior to placebo • equivalent to carbazepine + neuroleptic • superior to clomethiazole • Controlling delirium/seizures • no adequate sized studies • Clonidine vs benzodiazepine • only one randomized study • no significant difference • seizure patients excluded

  27. Neuroleptics • No controlled studies • Early studies less effective than benzos • Advantages • effective for psychosis • safe respiratory/cardiovascular profile • Disadvantages • increased seizures (thorazine,promazine) • extra-pyramidal side-effects

  28. Carbamazepine • Used in Europe • Efficacious vs clomethiazole/placebo • Advantages • lower abuse potential • less CNS depression • Disadvantages • side-effects = N/V, vertigo, rash • 50% stop therapy secondary SE • IV not available in US

  29. Propofol • Activates GABA-A receptor • Effectiveness • no controlled studies • ? benefit in refractory withdrawal • adjunct to primary therapy • Advantage • short-acting • easily titratable • Disadvantage • tolerance • cost

  30. Alternative Agents • Beta-adrenergic antagonists • IV/po differential effectiveness • studies support effective for tremors • Advantages • ? may be effective for mild withdrawal • no addiction potential • Disadvantages • cardiovascular effects • cause hallucinations • no role for mod-severe withdrawal

  31. Alternative Agents • Clomethiazole (Used in Europe) • effective as benzos and barbiturates • severe adverse effects • Ethyl alcohol • no trials on safety/efficacy • numerous adverse effects • Magnesium • no reduction in delirium/seizures • Thiamine • no reduction in delirium/seizures • prevention of Wernicke-Korsakoff

  32. Recommendations • Benzodiazepines • ativan/valium prn • Clonidine • adjunctive agent • excellent control of hyperadrenergic state • po preferred over patch • Neuroleptics • excellent control of psychosis • possible side-effects (less likely with Haldol) • Propofol/barbiturates • 2nd line adjuncts

  33. Recommendations • Dosing • Closely monitored setting • prn dosing • IV for acute withdrawal/inability to tolerate po • Untrained monitoring setting • fixed-scheduled po dosing

  34. Outcomes • Increased mortality • Luna et al, J Trauma, 1984 • double mortality vs sober with similar injuries • Waller et al, JAMA, 1986 • 1.7 to 2.1x mortality vs. matched sober MVC • Tinkoff, Ann Surg, 1990 • 30-40% mortality in cirrhotic trauma • sepsis and MSOF • predictors - ascites, PT, bilirubin, laparotomy

  35. Delay in Treatment Foy, Kay, Taylor. QJM, 1997

  36. Length of Stay Foy, Kay, Taylor. QJM, 1997

  37. Risk Factors Foy, Kay, Taylor. QJM, 1997

  38. ICU Withdrawal Syndrome • Cammarano, Crit Care Med, 1998 • Retrospective study • Trauma/surgical ICU • 28 mechanically ventilated patients • > 7 day ICU stay

  39. ICU Drug Potencies Cammarano et al, Crit Care Med, 1998

  40. Non-withdrawal Withdrawal ICU Withdrawal vs Drug Cammarano et al, Crit Care Med, 1998

  41. Non-withdrawal Withdrawal Duration Cammarano et al, Crit Care Med, 1998

  42. Non-withdrawal Withdrawal Mean Doses Cammarano et al, Crit Care Med, 1998

  43. ICU Withdrawal Syndrome • Results • 32 % acute withdrawal • opiates/benzodiazepines • ICU stay > 7 days • withdrawal group • higher daily doses of fentanyl and ativan • received neuromuscular blockade • received propofol • longer duration of agents

  44. ICU Withdrawal Syndrome • Prevention • adequate monitoring of level of sedation • avoid neuromuscular blockade if possible • realization of predisposition • ARDS • younger patients • wean opiates/benzo in pts at risk • 5-10% / day • ? change to longer acting agent po • use bolus method over continuous

  45. Questions…?

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