Transcript Update on poisoning 2005

2005
update on
management
of poisoning
Kent R. Olson, MD
Medical Director, SF Division
California Poison Control System
UC San Francisco
Case
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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
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Often overlooked
 Hx incorrect or not available
 Hidden ingredient in many drugs
 Nonspecific symptoms (N/V)
 Initial labs usually normal
Acetaminophen
Metabolism
P450
Glucuronidation
(non toxic)
Sulfation
(non toxic)
~ 5%
NAPQI
N-acetylcysteine (NAC)
Glutathione + NAPQI
= nontoxic product
Liver cell damage
NAC treatment
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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?
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IV acetylcysteine
Duration of treatment
Other tidbits:
 Acidosis early after ingestion
 Early (transient) elevated INR
IV acetylcysteine
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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
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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)
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We recommend giving initial loading dose
more slowly (45-60 min versus 15 min)
Oral or IV?
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< 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?
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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
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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
Case
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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
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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
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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
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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
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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
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Enhance insulin release
 Some agents have long half-lives,
prolonged effect
 Admit all symptomatic cases
Antidotes:
 Glucose
 Inhibit insulin release:
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Diazoxide (older agent)
Octreotide (somatostatin analog) - PREFERRED
Case
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A 65 year old woman presented with
nausea, diaphoresis, weakness.
BP 78/40 mm
Heart Rate 51/min
ECG: junctional rhythm
Calcium antagonist toxicity
Decreased
Automaticity
& Conduction
Negative
Inotropic
Effects
Dilated Vascular
Smooth Muscle
HR
AV Block
CO
SVR
SHOCK
Reversal of CCB toxicity
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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
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Initial dose 2-3 gm calcium chloride
Repeated doses up to 10-12 gm reportedly
effective in severe poisonings
Serum Ca++ levels as high as 16.3 mg/dL
(ref range 4.5-5.3) reported in one case
involving sustained-release diltiazem.
Hantsch et al: J Clin Toxicol 1997; 35:495
High-dose insulin therapy
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Favorable animal studies and several
human case reports
 Purported mechanism: enhanced
intracellular carbohydrate metabolism
 May also work for beta-blocker OD
Dose: 0.5-1 unit/kg regular insulin bolus
 0.5-1 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
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Many are sustained-release preparations:
 Calan SR
 Diltiazem-CD
Aggressive GI decontamination needed:
 Activated charcoal
 Whole bowel irrigation
Whole bowel irrigation
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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
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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
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What’s OUT:
 Ipecac – except for rare use on scene if
hospital more than 60 min away
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AAP no longer recommends home stocking
of ipecac
? Gastric Lavage
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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
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What’s IN:
 Activated charcoal – if it can be given
early and airway is protected
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Consider risk vs benefit in small ingestion of
moderate toxicity drug (eg, benzodiazepine)
Whole bowel irrigation (WBI)
Calif. Poison Control System
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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)