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

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

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

Acetaminophen Metabolism Glucuronidation (non toxic) Sulfation (non toxic) ~ 5% NAPQI N-acetylcysteine (NAC) Glutathione + NAPQI = nontoxic product Liver cell damage

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?

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

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?

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)

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

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

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

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

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

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

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

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?

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

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

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

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

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

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

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

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

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

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

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

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

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!?!?)

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)

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)

Potential indications for WBI Cocaine-filled condoms Iron pills

1-800-8POISON (California) 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)