kevin maskell, md division of toxicology vcu medical center virginia poison center with slides...
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Kevin Maskell, MDDivision of ToxicologyVCU Medical CenterVirginia Poison Center
APAP / ASA
With slides adapted from B-Wills
SHAMELESSLY PILFERED!
By the end you will know:
Mechanism of toxicity Types of ingestion Diagnostic keys Management/Antidotes How not to kill your patient
Why do we care?CommonDeadlyWe can fix it
APAP
Glucuronidation/Sulfation
SafeMercaptateNAPQI2E1 GSH
Lipid peroxidation
Death
APAP is just APAP right?
Acute Repeat supratherapeutic Late presenter
Stages (acute)
1) Nonspecific NV, malaise (0-24) 2) Hepatic injury (8-36) 3) Fulminant failure (3-4 d) 4) Recovery (weeks?)
Rumack-Mathew nomogram
Nomogram
When can we use?Extended release?Coingestants?
..
Repeat Supratherapeutic APAP ingestion
Stratify by Risk
High Risk: 1. APAP >10 and AST > normal2. APAP <10 with AST > 2x or symptomatic3. APAP level > expected for appropriate dose
Minimal Risk: APAP <10 + normal AST
Low Risk:APAP <10 + AST nml to 2x nml and asymptomatic
Antidote N-Acetylcysteine
NAC is universallyeffective if given within___ hours?
Delay (hrs) in NAC admin vs hepatotoxicity
0 4 8 12 16 20 24(hrs)
%
0% 0-8hrs6% 8-10hrs26% 10-24hrs41% 16-24hrs
Smilkstein M: NEJM 1988
N-Acetylcysteine
Indications• Acute ingestion plotted ______ treatment nomogram
• Time unknown and APAP level is __________
• Non-reassuring repeated supratherapeutic ingestion (↑ APAP level and/ or ↑ LFT’s)
• ED presentation > ___ hours post ingestion
above
8
detectable
IV vs PO NAC?
Dosing regimen PO intolerant? Anaphylactoid reactions? Other reasons?
What if we fail?
pH < 7.3 after 12 hrs resuscitation Lactate >3.5 after 4 hrs Cr > 3.4 INR >6.5 Grade 3 or 4 encephalopathy Phosphorus >3.75 at 48 hrs
Survival Points: APAP
1. Doses > 150-200 mg/kg could be concerning (> 200 mg/kg in peds)
2. Can only plot single acute OD’s on the nomogram
3. Repeated supratherapeutic OD: ND APAP + Nl AST = YOU’re DONE
4. NAC within 8 hrs is ~100% effective (in preventing hepatic failure)
5. Sick patients: refer to King’s College criteria of who might lose their liver
6. IV NAC is 150 mg/kg over 60 minutes
7. Get 2nd level for co-ingestants with opioids/ diphenhydramine
8. Allergy is likely anaphylactoid rather than anaphylaxis (this means you can can Rx with benadryl and usually restart the infusion with no problems)
ASPIRIN AND YOUIn 8 minutes…ish…
Why does ASA kill you?
ASA
ASA
ASA-
pH lowpH high
Why is pH the key for treatment?
Answers:1. Protects the CNS2. Enhances ASA elimination
Acidic Environment
ASA
Alkaline Environment
ASA
ASA-
“Ion Trapping”
Clinical Features
Early1.Tinnitus/
Vertigo2.Fever3.N/V/D4.Hyperpnea
Late5.AMS /
Coma6.Seizures7.ARDS8.Death
Labs
ASA level (Q2 hrs)Urine pH (also Q2 if able)Blood gasChemistry
Treatment
Airway/Breathing: Intubation?Circulation : Fluids,
electrolytes
Decontamination?Enhanced elimination?
Disposition?
Why is pH the key for treatment?
Answers:1. Protects the CNS2. Enhances ASA elimination
Acidic Environment
ASA
Alkaline Environment
ASA
ASA-
“Ion Trapping”
Alkalinization of Urine
1. Urine pH of 7.5-8.0, avoid serum pH >7.60
2. 1-2 mEq/kg NaHCO start ggt
3. Correct K+ depletion
Dialysis? My God! What is this, the Dark Ages?
Chronic Salicylism?
Old and dwindling with…
• Gastroenteritis• Urosepsis• Metabolic acidosis of unknown etiology• AMS/ encephalopathy• Influenza (ARDS)
Survival Points: ASA1. ASA overdose generates M&M’s because its underappreciated
2. Units screw people up; use mg/dl for salicylates
3. Salicylate levels should be obtained Q2h until they peak and start to fall
4. Consider urinary alkalinization for levels > 30 mg/dl(Reasonable infusion is 3 amps in 1L D5W at 2x maintenance)
5. Consider dialysis when levels > 80 mg/dl for acute cases
6. Keep sick patients breathing: allow them to hyperventilate; if you over-sedate or intubate them, you could kill them if you don’t maintain a high minute ventilation
7. Protect the CNS with bicarb
8. Chronic salicylism is more likely to be diagnosed as: old person with gastroenteritis, urosepsis, influenza, or metabolic acidosis of unknown etiology…
QUESTIONS?
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