2005 update on management of poisoning

1. 2005 update onmanagementof poisoning Kent R. Olson, MD Medical Director, SF Division California Poison Control System UC San Francisco

2. Case • A 16 year old boy with nausea and vomiting • Broke up with his girlfriend last night • “Might have taken some aspirin” • HR 100/min BP 120/70 T 98.6 F RR 12 • Exam unremarkable • Na 140 K 3.8 Cl 108 HCO3 22 • Salicylate = not detectable • UTox = negative

3. Acetaminophen ingestion • Often overlooked • Hx incorrect or not available • Hidden ingredient in many drugs • Nonspecific symptoms (N/V) • Initial labs usually normal

4. AcetaminophenMetabolism P450 Sulfation (non toxic) Glucuronidation (non toxic) ~ 5% NAPQI N-acetylcysteine (NAC) Glutathione + NAPQI = nontoxic product Liver cell damage

5. NAC treatment • Best if started within 8 hours of ingestion • However, late treatment still beneficial • Vomiting often complicates PO dosing • Use antiemetics? • Give via NG tube? • Give the NAC intravenously?

6. So what’s new? • IV acetylcysteine • Duration of treatment • Other tidbits: • Acidosis early after ingestion • Early (transient) elevated INR

7. IV acetylcysteine • Conventional product (Mucomyst) not FDA approved for parenteral use • But, can be given IV via micropore filter • New, approved IV product = Acetadote™ • Advantages? • Side effects?

8. IV acetylcysteine • Both products can cause an anaphylactoid reaction (flushing, hypotension) • May be infusion rate related (despite recent report in Ann Emerg Med 2005 Apr;45(4):402-8) • We recommend giving initial loading dose more slowly (45-60 min versus 15 min)

9. Oral or IV? • < 7 hours after OD • Use oral dosing regimen if not vomiting • Switch promptly to IV if begins vomiting • > 7 hours after OD • Start IV dosing immediately • Either product is okay • Can give first dose IV then switch to PO

10. How long to treat? • Conventional US protocol was 72 hours • Shorter regimens have proven effective • We have used 24-36 hours for years • Europeans have always used 20 hrs • Acetadote uses 20-hour IV infusion • Bottom line: • 20 hours IV or PO okay in most cases • Treat longer if evidence of liver toxicity

11. Other acetaminophen tidbits • Acidosis early after ingestion • Usually with levels > 500-600 mg/L • May also see early coma, hypotension with acute massive overdose • Not secondary to liver failure • Transient early rise in PT/INR • First 24 hrs • Not secondary to liver failure

12. Case • 55 yo man found unresponsive in his bedroom • Charcoal stove was being used to heat the room • Wife experiencing severe headache, dizziness, nausea

13. Carbon monoxide poisoning • Suggested by Hx of charcoal stove use, more than one victim with ALOC • Other clues? • “Cherry red” skin color - not reliable • pO2, pulse oximetry usually normal • Sx are often nonspecific, flu-like

14. Treatment of CO poisoning • Initial: highest available flow oxygen • 15L nonrebreather or • ET intubation and 100% oxygen • What about hyperbaric oxygen? (HBO) • Potentially more rapid CO removal • Can it prevent CNS damage? • Persistent neurological damage • Delayed neuropsychiatric sequelae

15. HBO vs normobaric oxygen • Scheinkestel 1999 Med J Aust 170:203 • Randomized, double-blind, placebo-controlled using “sham” HBO • No difference in outcome, in fact HBO group did slightly worse • Weaver 2002 NEJM 347:1057 • Also RCCT, double-blind • Showed slight advantage with HBO

16. So: HBO or NBO? • Issue remains unsettled, but consideration of HBO is now suggested when . . . • Hx of loss of consciousness • Older or pregnant patient • Presence of metabolic acidosis • COHgb level over 25% • Cerebellar findings?

17. Case • 65 yo woman undergoing transesophageal echocardiography for evaluation of cardiac thrombus prior to cardioversion • Hx of ASCVD, s/p CABG, HTN, Type II DM, hyperlipidemia, obesity, and atrial fibrillation • Meds: amiodarone, ASA, enoxaparin, glyburide, T4, metoprolol, niacin, rabeprazole, simvastatin, and warfarin

18. Case continued . . • During procedure O2 saturation was measured at 90% • After the procedure her pulse ox fell further and she appeared cyanotic despite 100% O2 • ABG: pO2 293 J Am Osteopathic Soc 2005; 105:381

19. Methemoglobinemia • Oxidized form of hemoglobin • Unable to carry oxygen efficiently • Blood appears “chocolate brown” • pO2 is normal (dissolved O2) • Pulse oximetry usually 88-90%, even with severe MetHgb (eg, 50%) • Treatment: methylene blue

20. Causes of methemoglobinemia • Many poisons and drugs • Any oxidant is a potential cause • Some drugs: dapsone; sulfonamides; nitrites; phenazopyridine (Pyridium); and some local anesthetics • The patient had been treated with a topical anesthetic spray containing benzocaine

21. Case • A 34 year old man is found unconscious, with resp. depression and pinpoint pupils • He awakens rapidly after injection of IV naloxone 0.2 mg • He signs out AMA 15 min after arrival

22. Opioid overdose • Usually easy to recognize • Coma • Pinpoint pupils • Respiratory depression • Treatment: naloxone • Start with small doses (0.2-0.4 mg) to reduce risk of sudden withdrawal Sx • Observe for at least 3 hrs after naloxone

23. Opioids, continued • Methadone • Long half-life (20-30 hrs!) • Can see relapse 1-2 hrs after naloxone • Not included in all Urine Tox screens

24. New opioid • Buprenorphine (Subutex, Suboxone) • Used in Rx of opioid-dependent patients • Longer duration of action • Partial agonist and antagonist effects • Lower “ceiling” effect makes it less prone to abuse and safer in OD • Can cause acute opioid withdrawal Sx See http://buprenorphine.samhsa.gov

25. (eg, morphine) lower “ceiling” (eg, buprenorphine)

26. Case • 23 yo woman with confusion, agitation • BP 110/70 HR 120/min RR 26/min T 100 • Na 140 K 3.9 Cl 106 HCO3 16 • Glucose 98 mg/dL BUN/Cr 15/0.9

27. Metabolic acidosis “MUDPILES” • Methanol, Metformin • Uremia • DKA • Phenformin, Paracetamol (Tylenol in U.K.) • INH, Iron • Lactic acidosis • Ethylene glycol • Salicylate

28. Salicylate poisoning • Acute OD or chronic overmedication • Anion gap acidosis • Hyperventilation • Typical ABG shows mixed alkalemia and acidosis; eg, pH 7.47 pCO2 18

29. Case, continued • The woman’s roommate brings in an empty bottle of Long’s Drugs brand Aspirin • Bottle originally contained #300 • What is the recommended dose of activated charcoal? • 300 tabs x 325 mg each = 97.5 gm • Optimal ratio AC:Drug = 10:1 • Dose of AC = 975 gm (16 bottles!?!?)

30. Gut decontamination • What’s OUT: • Ipecac – except for rare use on scene if hospital more than 60 min away • ? Gastric Lavage – unless large, recent ingestion • What’s IN: • Activated charcoal – if it can be given early and airway is protected • Whole bowel irrigation (WBI)

31. Whole bowel irrigation • Balanced electrolyte solution containing non-absorbable polyethylene glycol to maintain normal osmolarity • Can be given at 2 L/hr for hrs-days without change in electrolytes, fluid balance • Indications: • Massive ingestions • SR preparations • Agents not adsorbed by AC (eg, Fe, Li)

32. Potential indications for WBI Cocaine-filled condoms Iron pills

33. Poison Control Center • 24/7 access to expert advice • Diagnosis & management • Indications for and use of antidotes, hemodialysis, antivenom • MD-toxicologist back-up 1-800-8POISON (California) 1-800-222-1222 (nationwide)