Alcohol Related Disorders

1. Alcohol Related Disorders Simon Pulfrey MSc, MD, CCFP December 5, 2002

3. Denver man. 46 yo. Passenger in MVC 2 hours ago. • Driving with sister. T-boned low speed. Belted. No airbags. Spinal precautions via EMS • No LOC • 36o, 145/90, 92 reg, 97% RA • Contusion R forehead • Fracture R 3rd and 4th proximal phalanges • 3 R-sided rib #

4. Case 1 Continues • Normal hematocrit, lytes, glucose • Lives with sister. Telemarketer • No meds, no allergies, no hospitalizations, no insurance… • Not confused. Shaky • States “just nervous”

5. 4 hours later • 37.50, 150/100, 98, 98%RA • Normal CT head and cervical spines • Anxious and “still recovering from the shock of the accident” • Sister states “he is a nervous guy” • On casual exam – generalized tremor

6. 5 hour post arrival ED • 7 hours post MVC – generalized seizure x 3 mins, then 15 mins then 15 mins…and so on… • Lorazepam, haloperidol • Seizures abate an hour later • Very confused, agitated, and delirious • Admitted and required over 800mg of lorazepam over the next two days

7. Alcohol Withdraw Syndrome • Incomplete understanding of neuropathophysiology • State of CNS excitation • Develops 6 to 36 hours after cessation or reduction of EtOH intake

8. Classic Signs of Minor EtOH Withdraw • 6 to 36hrs • Mild autonomic hyperactivity • Nausea, anorexia, tremor, tachycardia, hypertension, hypereflexia, anxiety, disturbed sleep…

9. Major Withdraw Sx? • Usually 12 – 50 hours post • More pronounced sx as per minor WD • Major anxiety, auditory and visual hallucinations, decreased seizure threshold, delirium

10. Delirium Tremens • Extreme end of EtOH WD spectrum • Gross tremor, fever, incontinence, frightening hallucinations

11. This guy is in EtOH withdraw…What do you have to rule out? • Other ingestion and/or WD syndrome • Intracranial pathology • Infection • Hypoglycemia • Electrolyte abnormalities • Hypoxia • Organ failure

12. Denver Man Case • Stopped drinking 24 hours ago. • 6 rye/day several years • EtOH withdraw…Delirium tremens • Treatment?

13. Management of AWS - DT • Provide relief from anxiety and hallucinations • Help prevent seizures • Allow detection of psychiatric illness • Prepare for long-term treatment!

14. Management of AWS • More than 150 drugs and combinations reported • Benzodiazepines considered cornerstone • No clear superiority of any on BDZ • Consider delivery modality, bioavailability, t1/2

15. BDZ • Lorazepam • Good bioavailability po, im,iv, • T1/2 7-14 hrs • Rel safe in hepatic/renal dysfxn • Diazepam • Chlordiazepoxide • May require massive doses – eg diazepam 2600mg/48hr, midazolam 75 mg 1 hr,

16. Butyrophenones • Haloperidol and droperidol • May have synergistic effect with BDZ • IV, IM, PO

17. Others • Beta-blockers • AWS increased noradrenergic activity • BDZ no direct na affects • Consider obvious contraindications 2. Alpha agonists

18. Adjunctive Therapy • Thiamine 100 mg IV or PO • MgSO4 2-4g IV (po in non-acute setting has improved strength, LTs, electrolytes) • Volume repletion • Electrolyte normalization • Phenothiazines unhelpful • Hypotension, decrease seizure threshold, extrapyramidal effects

19. EtOH Related Seizures • Differentiate between alcohol related seizures and alcohol withdraw seizures • Underlying and non-EtOH related seizure disorder?

20. EtOH and Seizures Causes • AWS • Neurotoxic effects • Metabolic brain disorder • Cerebral trauma • Precipitating seizures with underlying epilepsy • Cerebral compromise – infection, bleed

21. DIMS

22. Management Issues • Glucose, thiamine, MgSO4, • Anticonvulsants?

23. EtOH. 7 min generalized seizure, 1st time. N CT, Lytes, glucose • Do you start phenytoin?

24. EtOH. Multiple past hx seizures. Negative epilepsy w/u in past. N CT, glucose, lytes. Non-adherent with dilantin.Do you restart it? • Controversial. • May increase incidence of seizures if suddenly stopped • Must determine cause and effect- is it EtOH?, nonadherence?, new etiology? • Rehab!!

25. EtOH. Status epileptcus.Management? Would you still use dilantin? • ABC • BDZ • Phenytoin

26. The case 1 clinical clerk • What drug would you use?

27. What is Zero-Order Kinetics? • Elimination at a constant rate regardless of concentration. Linear

28. What is first-order kinetics? • Rate of elimination is proportional to concentration.

29. Who Cares? • Alcohols largely zero-order therefore, t1/2 can be difficult to predict • ASA and phenytoin at high concentrations

30. Case 2 - “Father Tito” • Found slumped at bottom of stairs at home by fellow priests. • Empty bottle of beer at feet, multiple empty beer cans • No obvious trauma • Mumbling incoherently, unable to stand, c/o headache

31. Case 2 • LOC declines rapidly • Intubated en route to FMC for GCS<8 Spinal precautions • GCS 8 • 80/55 90 370 • PER sluggish 4mm B, Withdraw to pain, N fundi, R sided crackles, blue fluid on shirt • Foley - anuric

32. What now? • Na 141, K 4, Cl 95, HCO3 20, glucose 6, creatinine 90, urea 3, AG 26 • ABG – 7.2/27/112/18/-10 • CXR R infiltrate nil else • What are your thoughts on diagnosis?

33. Common sources of methanol? • Sternos, glass cleaners, carburator fluid, antifreeze, window-washer fluid, shallacs, laquers, adhesives, copy fluid, inks

34. Can methanol be absorbed via transdermal and the respiratory routes? • Yes • What toxic alcohol doesn’t work for “huffing”?

35. What metabolites are responsible for methanol’s toxic effects? • What B-Vitamin is necessary for methanol metabolism?

36. Methanol Metabolism

37. Why is it important to know what time pt ingested WW fluid? • Methanol’s toxic effects related to metabolites. • T1/2 variable, prolonged and increased with co-ingestion of EtOH • Sx may not appear until 12 –30 hrs post-injestion • Zero-order kinetics at higher doses

38. Pathophysiology • Optic neuropathy and putaminal necrosis two main complications • Increased lactate production from formate-induced inhibition of mitochondrial respiration exacerbates acidemia • Formaldehyde – retinal edema and optic papillitis

39. Methanol Pathophysiology • Peak absorption 30-90min post GI • Transdermal and pulmonary possible • Toxic metabolites 14h-30h depending upon dose and co-ingestants

40. Clinical Features • Wary of delayed presentation • CNS depression, HA, seizures • Visual disturbances – variable, “snowstorm” • Abdominal pain, N, Vx • Anion-gap metabolic acidosis

41. Ophthalmologic exam • Dilated pupils • Sluggish or absent reaction to light • Poor accomadation • Hyperemia of optic disc • Retinal edema

42. Other Findings in Methanol Toxicity • CT head – basal ganglia infarction –”Parkinsonian-like” • GI - N, Vx, severe epigastric pain • Acute pancreatitis

43. Harbringer of poor outcomes • Hypotension • Bradycardia • Outcome is better correlated to severity of metabolic acidosis rather than methanol level

44. Gaps • Father Tito had an osmol gap of 8. Does this r/o significant methanol toxicity? • Can have N osmol gap • Wary of lab calculations and calculated osmol gaps. Consider 2Na +glucose+urea • Freezing point depression

45. Anion-gap metabolic acidosis • Strong and relatively consistent finding in methanol toxicity

46. “Father Tito” • Methanol level 24 mmol/l • EtOH 19 mmol/l • Aspiration pneumonitis • Hemodialysis recommended > 7.8mmol/L

47. Disposition • ICU • EtOH therapy • Hemodialysis • FIFE • D/C ICU after 3 days • F/U ophthalmology

48. What makes you the most drunk? • Isopropanol, methanol, ethylene glycol, or EtOH • Isopropanol, ethelyen glycol, EtOH, methanol

49. What alcohol causes long QT? • Why?

50. Case 3 - 19 yo man. Suicide attempt with ingestion of 250ml antifreeze 6 hours ago • Rural community – EMS to FMC • GCS 15 • 120/80, 90, 16, SpO2 99%, 36.7 • CVS, Resp, CNS, abdo exam normal • No other ingestions