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?