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) NAPQI P450 ~ 5% Glutathione + NAPQI = nontoxic product Liver cell damage N-acetylcysteine (NAC)

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 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 > 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

Case A 15 year old was found in status epilepticus at home. Seizures stopped briefly after diazepam, but recurred in the ED. Patient arrived in U.S. one year ago from Mexico. Fingerstick glucose: 120 Serum bicarbonate: 6 mEq/L

Case, continued Further information: a empty bottle of isoniazid (INH) was found in the bathroom. Up to 30 gm (100 tablets 300 mg) missing. Pyridoxine was ordered from the pharmacy, but they had only 3 g on hand. Other hospitals were immediately contacted to try and find more.

Isoniazid overdose Clues to diagnosis: Recent immigrant or known TB patient Marked metabolic acidosis Note: INH not on most tox screens Treatment: Pyridoxine (Vitamin B-6) Dose: #g for #g ingested, at least 5 g IV Hospital should stock at least 20 g

Antidote Supplies Commonly understocked meds: Atropine Deferoxamine Fab digoxin antibodies Glucagon Pralidoxime (2-PAM) Pyridoxine (B-6) Skolfield et al: J Clin Toxicol 1997; 35:490

Case A 52 year old man was unconscious after overdose of Glucotrol (glipizide) Initial glucose = 12 mg/dL Glucose remained less than 60 after 100 gm of D50 (4 amps) and a D10 drip. Single dose of OCTREOTIDE 50 mcg reversed hypoglycemia within 60 min.

Sulfonylurea overdose Enhance insulin release Some agents have long half-lives, prolonged effect Admit all symptomatic cases Antidotes: Glucose Inhibit insulin release: Diazoxide (older agent) Octreotide (somatostatin analog) - PREFERRED

Case A 65 year old woman presented with nausea, diaphoresis, weakness. BP 78/40 mm Heart Rate 51/min ECG: junctional rhythm

Negative Inotropic Effects Negative Inotropic Effects Decreased Automaticity & Conduction Decreased Automaticity & Conduction Dilated Vascular Smooth Muscle Dilated Vascular Smooth Muscle SVR SVR COHR AV Block SHOCKSHOCK Calcium antagonist toxicity

Reversal of CCB toxicity Most sensitive to calcium administration: Reversal of negative inotropic effect Less sensitive: Partial reversal of AV nodal conduction block Not usually reversible by calcium: Sinus node depression Reduced peripheral vascular resistance

Calcium doses for CCB toxicity Initial dose 2-3 gm calcium chloride Repeated doses up to gm reportedly effective in severe poisonings Serum Ca ++ levels as high as 16.3 mg/dL (ref range ) reported in one case involving sustained-release diltiazem. Hantsch et al: J Clin Toxicol 1997; 35:495

High-dose insulin therapy Favorable animal studies and several human case reports Purported mechanism: enhanced intracellular carbohydrate metabolism May also work for beta-blocker OD Dose: unit/kg regular insulin bolus units/hr insulin infusion plus IV glucose to maintain euglycemia recent lit review in Ann Pharmacotherapy 2005 May;39(5):923-30

GI decontamination for CCBs Many are sustained-release preparations: Calan SR Diltiazem-CD Aggressive GI decontamination needed: Activated charcoal Whole bowel irrigation

Balanced electrolyte-PEG solution GoLytely, CoLyte No net fluid loss or gain No electrolyte abnormalities Dose 2 L/hr via NG tube (kids 500 mL/hr) May use for several hours or even days

Whole bowel irrigation Indications Iron Lithium Sustained-release preparations Drug packets, foreign bodies Possible interaction with charcoal? In-vitro data only We use AC in repeated doses

Gut decontamination 2005 What’s OUT: Ipecac – except for rare use on scene if hospital more than 60 min away AAP no longer recommends home stocking of ipecac ? Gastric Lavage Most effective when used within 60 min Consider later use if massive ingestion, or delayed gastric emptying likely (eg, ASA, anticholinergics, opioids, etc)

Gut decontamination 2005 What’s IN: Activated charcoal – if it can be given early and airway is protected Consider risk vs benefit in small ingestion of moderate toxicity drug (eg, benzodiazepine) Whole bowel irrigation (WBI)

Calif. Poison Control System 24/7 access to expert advice Diagnosis & management Indications for and use of antidotes, hemodialysis, antivenom MD-toxicologist back-up POISON (California) (nationwide)