Tylenol OD
                        ==========
þ Who to send home?
 - if level < 150 4 hours after ingestion (no need to check second level).
 - < 50 micrograms/mL 1-4 hours suggetive of nontoxic
   ingestion; unable to conclude that if delayed gastric emptying, or other
   clinical risk factors (Dr. Katz from Presby, 8/14/03)

þ Late crossing of nomogram line:
 - perhaps delayed absorption with the Benadryl in Tylenol PM
 - not associated with serious problems

þ Therapeutic Levels
 - <30 micrograms/mL an hour later

þ Quick and Dirty
 - ingestions less than 150 mg/kg (7.5g=15 extra-strength) for an average adult) unlikely to be
   toxic
 - severe intoxication with 10-15g range in adults (20-30 extra-strength, or
   30-60 regular strength)
 - 4-hour level less than 200 ug/mL or better 150 ug/mL is OK, above this is
   toxic and needs NAC
 - use nomogram if unable to get 4-hour level

þ If time of ingestion unknown:
 - get stat level and level after 3 hours in ED, baseline PT and AST
 - if AST elevated _regardless_ of APAP level, treat with mucomyst
 - If AST normal and APAP > 10 mcg/mL, treat with mucomust

þ Chronic OD:
 - if signs or symptoms of liver disease (jaundice, RUQ tenderness/pain), treat
 - assess risks for hepatotoxicity (fever, preexisting liver disease,
   malnourished, induced Cytochrome P-450 such as EtOH, Dilantin, INH,
   rifampin, chronic illness)
 - febrile child, > 75 mg/kjg/24hr
 - nonfebrile, > 150 mg/kg/24hr
 - adult with increased risk: > 4g/24hr
 - adult without increased risk: > 7.5g/24hr
 - check level 4 hours after last ingestion, if known (if 10-20 mcg/mL, OK; if
   high, i.e., 150 mcg/mL, treat)
 - obtain immediate level if has symptoms
 - check LFTs, PT

þ APAP levels:
 - some false positive tylenol levels with some lab machines with elevated
   bilirubin (recheck with gas spec via PC lab or similar)
 - don't confuse mg/dL with micrograms/mL!

þ Alcohol and APAP:
 - by competing for Cytochrome P-450, alcohol protective
 - by inducing P-450, chronic alcohol is a risk

þ Pediatric OD
 - children's liver
 - no cases of hepatotoxicity from accidental OD on pediatric preparations
   (doesn't include adult preparations, intentional OD)

þ Charcoal
 - give within one hour of ingestion
 - Highly bound by charcoal.
 - Should increase dose of Mucomyst (N-acetyl cysteine) to 235 mg/kg if giving
   charcoal to compensate for charcoal absorption.  [Chamberlain JM et al.
   Use of activated charcoal in a simulated poisoning with acetaminophen:  a
   new loading dose for N-acetylcysteine?  Ann Emerg Med 1993;22:1398 et seq.]
   but questioned by others.

þ N-acetyl cysteine (Mucomyst)
  <Mucomyst.TXT>

þ Tylenol may cause renal failure
 - even in absence of liver failure: 1-2%? [Curry RW et al.  Acute renal
   failure after acetaminophen ingestion. JAMA 1982;247(7):1012 et seq.]
 - usually a bit later than the liver damage (3-6 days after insult)

þ Tylenol may cause liver failure in alcoholics even in "therapeutic" doses
 - [Kaysem. Arch Int Med 1985;145:2019 et seq.]

þ Criteria for predicting death and need for liver transplantation in patients
  with acetaminophen poisoning [NEJM 1993;329:1862.]
  - pH < 7.3 (regardless of degree of encephalopathy)  OR
  - PT > 100 seconds, or continuing to rise on day 4-5
  AND serum creatinine > 3.4 mg/dl

þ Extended Relief (_not_ Extended Release) Tylenol
 - packaged slightly differently, and provides statistically extended pain
   relief; probably response to release of Advil, Nuprin, etc.
 - mistakenly taken as extended release, even in letter in NEJM.
 - some anecdotal reports of extended toxicity, e.g. [Bizovi et al: J Toxicol
   Clin Toxicol:1995;5:510]
 - treat same as regular Tylenol: [Douglas et al:  Acad Emerg Med 1995;2:397]
   [Stork et al:  J toxicol Clin Toxicol 1995;5:511.]
 - In poisoned patients, half-life similar,  [Cetaruk et al:  J Toxicol Clin
   Toxicol 1995;5:511.]
 - manage same as regular tylenol OD but get additional delayed tylenol level:
   4-hour level; if below dotted line but above 10 micrograms per mL, then
   at 6 hours, or 4 - 6 hours later (8-10 hours post-ingestion) get another
   level; plot at hours taken.
   (If first level < 10 ug/mL, don't need to give NAC; if first level above
   dotted line, start NAC)
   if any plasma level is above the dotted line on the standard Rumack/Matthew
   nomogram, administer or complete administration of NAC (standard dose).
 - releases acetaminophen for up to 8 hours, but by 5 hours at least 95% has
   been released.
 - Tylenol PM: also has Benadryl, treat same as "regular" APAP OD
 - Tylenol 8-hour: treat same as "regular" APAP OD

þ Toxic Pathway:
 - APAP metabolized via Cytochrome P-450 to NAPQI which is toxic