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Toxic Withdrawals

Toxic Withdrawals. Jennifer Nicol PGY-1 Dr. Yael Moussadji May 27 th , 2010. Outline. Will cover withdrawal from: Alcohol Opioids Benzodiazepines Cocaine. The Facts: addiction and withdrawal. Emergency physicians must recognize and treat many phases of substance abuse

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Toxic Withdrawals

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  1. Toxic Withdrawals Jennifer Nicol PGY-1 Dr. Yael Moussadji May 27th, 2010

  2. Outline • Will cover withdrawal from: • Alcohol • Opioids • Benzodiazepines • Cocaine

  3. The Facts: addiction and withdrawal • Emergency physicians must recognize and treat many phases of substance abuse • 80% Canadians drink alcohol • Majority moderation without harm • 17% high risk drinking • 2002: Cost of illicit drugs, tobacco, and alcohol • Canada $40 billion • Alberta $4.4 billion

  4. Principles of Withdrawal • Every withdrawal syndrome has two characteristics: • pre-existing adaptation to a drug, the continuous presence of which prevents withdrawal • decreasing concentrations of that drug

  5. Principles of Withdrawal • Withdrawal syndromes that fulfil both criteria are treated by re-administration followed by weaning of drug • Opiates, benzodiazepines, alcohol • Withdrawals that fulfil only first criteria are treated by supportive measures only • I.e. cocaine, marijuana

  6. DSM-IV: withdrawal • Withdrawal is manifested by either of the following: • a characteristic withdrawal syndrome for the substance • the same (or a closely related) substance is taken to relieve withdrawal symptoms.

  7. Case: • 56 yo F chronic alcoholic • Stopped drinking 3 days prior. Now feels tremulous, nauseous, disoriented, • Has had numerous falls in the past 3 days, can’t use her right hand • Thoughts?

  8. Case (con’t) • PMHx: • alcohol withdrawal seizures, DT • CAD, HTN, Afib, COPD • ICU admission 2 months ago for DTs • NSTEMI during admission • Meds: • ASA, tinzaparin, metoprolol, trazadone, advair, lipitor • Do you have any concerns?

  9. Alcohol Withdrawal Syndrome (AWS) • 15-20% inpatients and ED patients are alcohol dependant • Many present with unrelated problems • Trauma • Infections / sepsis • Pancreatitis, renal failure • ACS, stroke

  10. Historical Perspective

  11. Pathophysiology • Alcohol has depressant effect on CNS • Effects of alcohol dependency and tolerance mediated primarily through 2 receptor systems: • GABAα • NMDA • Withdrawal characterised by CNS excitation

  12. NMDA • EtOH inhibits excitatory neurotransmitter glutamate function at NMDA • chronic EtOH use – upregulation of NMDA receptors. • When EtOH withdrawn, increased NMDA receptor activity

  13. Clinical Presentation • “The patient is restless and agitated, requiring restraints… conversation being garbled and unintelligible. Autonomic over-activity is manifested by dilated pupils, tachycardia, and an elevated temperature, attributable occasionally to no other cause other than delirium.” • Victor and Adams 1953

  14. I swear, I only had one drink 2 nights ago.

  15. Clinical Presentation • Three sets of symptoms: • Autonomic hyperactivity • Tremor, hypertension, hyperthermia, hyper-reflexia • Sleep disturbances, diaphoresis, nausea, vomiting, • Neuronal excitation • Alcohol withdrawal seizures • DT’s • Extreme end of AWS spectrum • Profound confusion, delirium, hallucinations • Hyperadrenergic state

  16. Clinical Presentation • Symptoms develop 6-12 hrs after reduction of EtOH intake. • Spectrum of withdrawal: • Mild • Moderate • Delirium tremens • Duration of withdrawal up to 7 days

  17. Clinical Presentation - Classification • Minor • Early onset 6hrs, peak 24-48 hrs • Mild autonomic hyperactivity: nausea, anorexia, coarse tremor, hypertension, tachycardia, sleep disturbance • Major • Later onset 24 hrs, peak 50hrs-5days • Tremor, fever, irritation, ++anxiety, insomnia, anorexia, hypertension, tachycardia • Decreased seizure threshold, hallucinations, hyper-reflexia

  18. Clinical Presentation - Classification • Delirium Tremens • Serious complication of, not synonymous with AWD • 5-10% pts admitted for alcohol WD • Appears day 3-5 post abstinence (rarely before) • Lasts 5-10 days, up to 2 weeks • Main concern is recognition and early management • MEDICAL EMERGENCY!!!

  19. Delirium Tremens DeBellis et al. J Intens Care Med.2005;20:164

  20. DT: Risk Factors • Tachycardia at admission • WD signs with BAL >0.16 mmol/l (1g/L) • Infectious process • History of withdrawal seizures • History of delirious episodes associated with withdrawal DeBellis et al. J Intens Care Med.2005;20:164

  21. DT: Mortality • 5-15% mortality rate • Secondary to complications • RF’s for Mortality • Khan et al. Acad emerg Med. 2008;15:787 • Risk factors: • Physical Restraints • Hyperthermia • Protective: • Use of clonidine • Diagnosis in ED

  22. DeBellis et al. J Intens Care Med.2005;20:164

  23. Back to the case • VS: HR130, BP160/90, temp37.6, RR18, SaO2 96 2LNP • On exam: • Confused but oriented, agitated, PERL, tremulous • Large bruise right arm and face • Think she can’t extend right wrist but can’t be sure – she is so tremulous • What other conditions do you want to rule out?

  24. AWD – Differential Considerations Wren et al. Amer J Emerg Med. 1991;9(1):57

  25. Differential Considerations • CNS: encephalitis, meningitis, IC bleed • Infectious: Numerous sources. • GI: hepatic encephalopathy • Tox: • Toxidromes: anticholinergic, stimulant • WD: Sedative hypnotics (opiates, benzos, barbituates) • Contemporary alcoholic often polydrug users • Metabolic: thyrotoxicosis, hypoglycemia • Psychiatric: drug induced psychosis, schizophrenia

  26. Physical Exam • Level of consciousness • Signs hepatic failure • Signs of focal infection • Trauma • Complete neuro exam • Reflexes • Deficits • Pupils, occulomotor function • Gait if possible, coordination

  27. Investigations • CBC, lytes, LFT’s, lipase, coags, BUN, Cr, BG • EtOH +/- toxic EtOH • Blood Cultures • Urinalysis, urine culture • CXR • ECG

  28. Investigations • Consider • LP, CT head, VBG, tox screen • Look at your anion & osmolar gaps

  29. Diagnosis of Alcohol WithdrawalDSM-IV • Cessation or reduction of alcohol use that has been heavy and prolonged • Two or more of the following, developing within several hours to a few days after criterion A: • autonomic hyperactivity (sweating, HR>100/min) • Increased hand tremor • Nausea or vomiting • Insomnia • Transient visual, tactile, or auditory hallucinations or illusions • Psychomotor agitation • Anxiety • grand mal seizures • The symptoms in criterion B cause clinically significant distress or impairment in social, occupational, or other important areas of functioning • The symptoms are not sue to a general medical condition and are not better accounted for by another mental disorder.

  30. Return to Case • Hbg 107, WBC 7.4, plt 174 • Na 113! K 2.6, Mg 0.47, PO4 0.5 • Urinalysis: +nitrates, WBC, RBC • CT head: nil acute

  31. Management Principles • 4 principles of treatment 1) Evaluate for concurrent illness 2) Restore inhibitory tone to CNS 3) Identify and correct electrolyte & fluid deficiencies 4) Allow pt to recover with the least amount of physical restraint to decrease the risk of hyperthermia and rhabdomyolysis EM Reports 26(16) July 25, 2005

  32. Pharmacologic Intervention • Ideal drug profile for EtOH withdrawal: • Rapid onset • Wide margin safety • Minimal hepatic metabolism • Limited abuse potential • (Cost effective) • High doses, infusions

  33. Pharmacologic Intervention • >150 drugs have been used in the last 30 years to treat alcohol withdrawal • Benzodiazepines are the mainstay of current therapy • Potentiate the effects of GABA • Restore the inhibitory tone

  34. Mechanism of BZD in Alcohol WD • GABAα downregulated • Loss of chronic inhibition from EtOH • Benzos restores inhibitory tone provided by EtOH

  35. Pharmacotherapy - BZD • Numerous prospective trials demonstrating benzos more effective than placebo in decreasing signs and sx of WD • Bowman et al. Dis Nerv Syst. 1966;27:342 • Sellers et al. J Stud Alcohol. 1977;3:575 • Adinoff et al. Alcohol Clin Exp Res. 1995;18:873 • Also beneficial over placebo in decreasing incidence of Sz and delirium • Mayo-Smith, JAMA 1997 278(2):144 • meta analysis 5 pRCTs

  36. Choice of Benzo • When considering which benzo to initiate, need to consider: • Route of administration • Hepatic function • Half life • Formulary status • Regime • Symptom triggered vs. Fixed scheduled

  37. Benzo profiles

  38. Choice of Benzo • No significant difference has been shown between benzos in reducing Sx/signs of WD • Generally: • Long acting: • smoother WD course with fewer rebound and breakthrough WD. • Better seizure prevention • Rapid onset: • control agitation more quickly • Diazepam: long acting and rapid acting • Not on ED formulary Mayo-Smith. Arch int Med. 2004 164:1405

  39. Choice of Benzo • No significant difference has been shown between benzos in reducing Sx/signs of WD • However, long acting can result in increased sedation • Elderly, hepatic failure • Lorazepam: no active metabolites, shorter t½

  40. Benzo Dosing • Diazepam 5-10mg IV q5-10 min • Lorazepam 2-4 mg IV q15-20min • May require massive doses - >2000mg/48hrs • Titrate to desired balance between agitation/withdrawal and level of consciousness (don’t want to intubate the patient!) • “light somnolence”

  41. Benzos – Dosing regime • Fixed dose regime • Give set amount of medication at regular intervals • Breakthrough doses for WD symptoms • Taper at end of therapy (ie day7) • Loading Dose • Give initial large dose of long acting medication, which is decreased through metabolism • Not commonly used • Symptom Triggered dosing • Quantify symptoms of WD and dose accordingly

  42. Symptom Triggered • Monitored by a structured assessment scale • Given medication only when crosses threshold of severity • Dappen Arch Int Med. 2002;162:1117 • N=117, comparing Sx triggered to fixed dosing • Six fold decrease in amount benzo required (37.5mg vs. 231.4mg) • Shorter duration of therapy (20 vs. 62.7 hrs) • Jaegger et al. Mayo Clinic Proceedings 2001;76 • No change in duration of stay • Decreased DT

  43. Kosten et al. NEJM 348;18: 1786

  44. Pharmacotherapy • Doctor, your patient has received 250 mg IV benzos, and now has significant abrasions from his 4 point restraints • Failure of benzo to control symptoms and signs of WD? • What are you going to do now?

  45. Resistant Alcohol Withdrawal • Subgroup who require very large doses of benzos to achieve sedation • ICU admission for close monitoring, +/- intubation • Symptom triggered vs. fixed dosingvs. benzo infusion • Spies CD et al. Intensive Care Med. 2003;29:2230 • Second line GABAergic drug • Barbituates • Propofol

  46. Barbituates • Good alternative for WD resistant to BZD • Directly open GABA ion channels • Usually do not fail to manage AW symptoms • PRO: • Low abuse potential • Long acting • IV/PO/IM • CON • Increased respiratory depression • Lower safety profile in larger doses Young et al. Ann Emerg Med.1987;16:847-850 Yeh et al. J Gen Intern Med. 1992;7:123

  47. Barbituates • Phenobarbital • Long acting (t½ 80-100hrs) • Difficult to titrate to sedation vs loss of consciousness • 260mg IV over 5min • Repeat at 30 min 130mg over 3min until desired effect • Pentobarbital • Short acting • 3-5mg/kg IV bolus followed by 100mg/hr infusion

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