1. Kevin Maskell, MD Division of Toxicology VCU Medical Center Virginia Poison Center With slides adapted from B-Wills SHAMELESSLY PILFERED!

2. By the end you will know:  Mechanism of toxicity  Types of ingestion  Diagnostic keys  Management/Antidotes  How not to kill your patient

3. Why do we care?  Common  Deadly  We can fix it

4. APAP Glucuronidation/ Sulfation Safe MercaptateNAPQI 2E1 GSH Lipid peroxidation Death

5. APAP is just APAP right?  Acute  Repeat supratherapeutic  Late presenter

6. Stages (acute)  1) Nonspecific NV, malaise (0-24)  2) Hepatic injury (8-36)  3) Fulminant failure (3-4 d)  4) Recovery (weeks?)

7. Rumack-Mathew nomogram

8. Nomogram  When can we use?  Extended release?  Coingestants?

9. ..

10. Repeat Supratherapeutic APAP ingestion Stratify by Risk High Risk: 1. APAP >10 and AST > normal 2. APAP 2x or symptomatic 3. APAP level > expected for appropriate dose Minimal Risk: APAP <10 + normal AST Low Risk: APAP <10 + AST nml to 2x nml and asymptomatic

11. Antidote N-Acetylcysteine NAC is universally effective if given within ___ hours?

12. Delay (hrs) in NAC admin vs hepatotoxicity 0 4 8 12 16 20 24(hrs) % 0% 0-8hrs 6% 8-10hrs 26% 10-24hrs 41% 16-24hrs Smilkstein M: NEJM 1988

13. 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

14. IV vs PO NAC?  Dosing regimen  PO intolerant?  Anaphylactoid reactions?  Other reasons?

15. 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

16. 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 2 nd 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)

17. In 8 minutes…ish…

18. Why does ASA kill you? ASA ASA - pH low pH high

19. Why is pH the key for treatment? Answers: 1. Protects the CNS 2. Enhances ASA elimination Acidic Environment ASA Alkaline Environment ASA ASA - “Ion Trapping”

20. Clinical Features Early 1.Tinnitus/ Vertigo 2.Fever 3.N/V/D 4.Hyperpnea Late 1.AMS / Coma 2.Seizures 3.ARDS 4.Death

22. Labs ASA level (Q2 hrs) Urine pH (also Q2 if able) Blood gas Chemistry

23. Treatment Airway/Breathing: Intubation? Circulation : Fluids, electrolytes Decontamination? Enhanced elimination? Disposition?

24. Why is pH the key for treatment? Answers: 1. Protects the CNS 2. Enhances ASA elimination Acidic Environment ASA Alkaline Environment ASA ASA - “Ion Trapping”

25. 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

27. Chronic Salicylism? Old and dwindling with… Gastroenteritis Urosepsis Metabolic acidosis of unknown etiology AMS/ encephalopathy Influenza (ARDS)

28. Survival Points: ASA 1.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…