Acetaminophen Toxicity Management (JAMA 2023)

Algorithm Steps

1. ▶

   Start

   START: Suspected Acetaminophen Toxicity

   History of APAP ingestion or elevated level

   1. ●

      Action

      Obtain History

      Key information

      • Amount ingested (mg/kg)
      • Time of ingestion (critical for nomogram)
      • Single vs multiple doses
      • Immediate-release vs extended-release
      • Co-ingestants
      • Suicidal intent
      1. ●

         Action

         Initial Labs

         Draw at presentation

         • Serum acetaminophen level
         • LFTs (AST, ALT)
         • PT/INR
         • BMP (Cr, glucose)
         • Lactate if severe
         • Repeat APAP level at 4 hours post-ingestion
         1. ◆

            Decision

            Type of Ingestion?

            Determines treatment approach

            1. ●

               Action

               Acute Single Ingestion

               Known time, single dose

               • Use Rumack-Matthew nomogram
               • APAP level at 4 hours post-ingestion (or ASAP if >4h)
               • Plot level on nomogram
               • Above treatment line → NAC indicated
               1. ●

                  Action

                  GI Decontamination

                  If early presentation

                  • Activated charcoal 1g/kg (max 50g)
                  • Most effective within 1-2 hours of ingestion
                  • Consider up to 4 hours for large ingestions
                  • Contraindicated if altered mental status, aspiration risk
                  1. ◆

                     Decision

                     NAC Treatment Indicated?

                     Based on level/nomogram or clinical

                     • TREAT IF: Level above treatment line, Elevated transaminases with APAP detected, Unknown time but high risk, Massive ingestion (>150 mg/kg)
                     1. ●

                        Action

                        IV NAC Protocol (21-hour)

                        Standard 3-bag regimen

                        • Loading: 150 mg/kg IV over 1 hour
                        • Bag 2: 50 mg/kg IV over 4 hours
                        • Bag 3: 100 mg/kg IV over 16 hours
                        • Total: 300 mg/kg over 21 hours
                        • Anaphylactoid reactions: slow infusion, antihistamines
                        1. ●

                           Action

                           Monitoring During Treatment

                           Assess for hepatotoxicity

                           • LFTs q6-12 hours
                           • PT/INR
                           • Serum creatinine
                           • APAP level until undetectable
                           • Glucose (hypoglycemia in liver failure)
                           1. ◆

                              Decision

                              Continue NAC?

                              Criteria for stopping

                              • STOP NAC IF: APAP undetectable, INR <2, AST/ALT declining or normal
                              • CONTINUE NAC IF: INR >2, AST >1000, clinical hepatotoxicity
                              1. ⚠

                                 Warning

                                 Acute Liver Failure

                                 Transfer to liver transplant center

                                 • King's College Criteria for transplant:
                                 • - pH <7.3 after resuscitation, OR
                                 • - PT >100 sec (INR >6.5) + Cr >3.4 + Grade III/IV encephalopathy
                                 • Continue NAC (reduces mortality even in ALF)
                                 • Early hepatology/transplant consult
                              2. ✓

                                 Outcome

                                 Recovery/Discharge

                                 Hepatotoxicity resolved

                                 • LFTs normalizing
                                 • APAP undetectable
                                 • INR normal
                                 • Psychiatric evaluation if intentional
                                 • Safe medication storage counseling
                     2. ●

                        Action

                        Oral NAC (72-hour)

                        Alternative if IV unavailable

                        • Loading: 140 mg/kg PO
                        • Maintenance: 70 mg/kg PO q4h x 17 doses
                        • Mix with juice/soda for palatability
                        • Repeat dose if vomiting within 1 hour
            2. ●

               Action

               Repeated Supratherapeutic

               RSTI - nomogram not applicable

               • Total dose >4g/day (or >75 mg/kg/day)
               • Treat if: APAP detectable AND AST/ALT elevated
               • Or: Total dose >10g in 24h regardless of labs