 1.4.1 NORMAL DOSE
                    A. ORAL
                          1. ACETAMINOPHEN POISONING
                                a. The acute ingestion of acetaminophen in quantities of 150
                                  milligrams/kilogram or greater may result in hepatic toxicity.
                                  Acetylcysteine is most effective in preventing
                                  acetaminophen-induced liver injury following overdose if
                                  administered within 16 hours postingestion. Loading dose is
                                  140 milligrams/kilogram orally followed by 70
                                  milligrams/kilogram orally every 4 hours for 17 additional
                                  doses (Peterson & Rumack, 1977; Peterson & Rumack,
                                b. The manufacturer recommends that regardless of the
                                  quantity of acetaminophen reported to have been ingested,
                                  acetylcysteine should be administered if 24 hours or less
                                  have elapsed from the time of the reported ingestion of an
                                  overdose. Do not wait for the result of laboratory assays for
                                  acetaminophen levels. The following procedures are
                                  recommended (Prod Info Mucomyst(R), 1996):
                                        (1) The stomach should be emptied by lavage or
                                           emesis with syrup of ipecac. Syrup of ipecac should
                                           be given in a dose of 15 to 30 milliliters for children
                                           and 30 to 40 milliliters for adults accompanied by 4
                                           to 6 ounces of water. The dose should be repeated
                                           if emesis does not occur in 20 minutes.
                                        (2) In the cases of a mixed drug overdose, activated
                                           charcoal may be indicated. If activated charcoal is
                                           administered, it is recommended that the patient be
                                           lavaged before administration of acetylcysteine
                                           since activated charcoal adsorbs acetylcysteine in
                                           vitro and may also do so in vivo.
                        (3) Blood should be drawn for acetaminophen
                           plasma assay and for baseline SGOT, SGPT,
                           bilirubin, prothrombin time, creatinine, BUN, blood
                           sugar, and electrolytes. Plasma or serum
                           acetaminophen concentrations should be
                           determined as early as possible but no sooner than
                           4 hours following acute overdose. These levels are
                           essential in assessing the potential risk of
                           hepatotoxicity. If an assay for acetaminophen
                           cannot be obtained, it is necessary to assume the
                           overdose is potentially toxic.
                        (4) Administer the loading dose of acetylcysteine
                           (140 milligrams/kilogram of body weight).
                        (5) Four hours after the loading dose, administer the
                           first maintenance dose of 70 milligrams/kilogram.
                           Maintenance doses should be repeated at 4-hour
                           intervals for a total of 17 doses unless the initial
                           acetaminophen assay reveals a nontoxic level.
                        (6) If the patient vomits the loading dose or any
                           maintenance dose within 1 hour of administration,
                           repeat that dose. If the patient is persistently unable
                           to retain the acetylcysteine, it may be administered
                           by duodenal intubation.
                        (7) Repeat SGOT, SGPT, bilirubin, prothrombin time,
                           creatinine, BUN, blood sugar, and electrolytes daily
                           if the acetaminophen plasma level is in the
                           potentially toxic range.
       2. MUCOLYTIC
              a. Children 6 to 14 years, 300 to 400 mg daily in 3 to 4
                  divided doses; and children 2 to 5 years of age, 200 to 300
                  mg daily in 2 to 3 divided doses (Fachinfo Fluimucil(R) akut,
       1. The 20% acetylcysteine solution should be diluted with cola drinks,
         Fresca, or other soft drinks to a final concentration of 5%. If
         administered via gastric tube or Miller-Abbott tube, water may be
         used as the diluent. The dilution should be freshly prepared and
         utilized within one hour.
       1. Doses of oral acetylcysteine in relation to body weight are (Prod
         Info Mucomyst(R), 1996):
                                     LOADING DOSE**
                         Weight   Acet-     Muco- Dilu-    Total
                         (kg)     ylcys- myst      ent     5% sol-
                                  teine     20%    (mL)    ution
                                    (g)     (mL)           (mL)
                         100-109 15         75     225     300
                          90-99   14        70     210     280
                          80-89   13        65     195     260
                          70-79   11        55     165     220
                          60-69   10        50     150     200
                          50-59   8         40     120     160
                          40-49   7         35     105     140
                          30-39   6         30     90      120
                          20-29   4         20     60      80
                                        MAINTENANCE DOSE**
                         Weight   Acet-     Muco- Dilu-    Total
                         (kg)     ylcys- myst      ent     5% sol-
                                  teine     20%    (mL)    ution
                                    (g)     (mL)            (mL)
                         100-109 7.5        37     113     150
                          90-99   7         35     105     140
                          80-89   6.5       33     97      130
                          70-79   5.5       28     82      110
                          60-69   5         25     75      100
                          50-59   4         20     60      80
                          40-49   3.5       18     52      70
                          30-39   3         15     45      60
                          20-29   2         10     30      40
                         **If patient weighs less than 20 kg
                         (usually patients younger than 6
                         calculate the dose of Mucomyst(R).
                         Each milliliter of 20% Mycomyst(R)
                         200 milligrams of acetylcysteine.                 The
                     dose is 140 milligrams/kilogram. The
                     dose is 70 milligrams/kilogram. Three
            (3) milliliters
                     of diluent are added to each milliliter
                     of 20% Mucomyst(R). Do not decrease
                     proportion of diluent.
       1. When results of the plasma acetaminophen assay are available, the
         Rumack/Matthew nomogram (available in Mucomyst(R) package
         inserts) should be utilized to determine if plasma concentrations are in
         the potentially toxic range. Values above the solid line connecting 200
         micrograms/milliliter at 4 hours with 50 micrograms/milliliter at 12
         hours are associated with a possibility of hepatic toxicity if
         acetylcysteine is not administered. If the plasma level is above the
         broken line on the nomogram, continue with maintenance doses of
         acetylcysteine. If the initial plasma level is below the broken line on
         the nomogram, there is minimal risk of hepatic toxicity and
         acetylcysteine treatment can be discontinued (Prod Info
         Mucomyst(R), 1996).
               a. SUMMARY
                        (1) There is NO FDA-approved commercially
                            available sterile, pyrogen-free, intravenous (IV)
                            formulation of acetylcysteine in the United States.
                            The oral/inhalation preparation is NOT officially
                            approved for IV use. Pyrogen-free intravenous
                            acetylcysteine is available investigationally ONLY
                            through participating poison centers. There are 2
                            intravenous protocols currently under investigation.
                        (2) FORTY-EIGHT HOUR PROTOCOL: Dilute 20%
                            solution 1:5 in dextrose 5% in water (D5W) and give
                            slowly over one hour. If an adverse reaction occurs,
                            diphenhydramine is given and subsequent doses
                            are given over 2 hours. The initial dose is 140
                            milligrams/kilogram, followed by 70
                            milligrams/kilogram every 4 hours for a total of 13
                            doses (Smilkstein et al, 1991).
                        (3) TWENTY HOUR PROTOCOL: Administer 150
                            milligrams/kilogram in 200 milliliters D5W over 15
                            minutes, followed by 50 milligrams/kilogram in 500
                            milliliters D5W over 4 hours, followed by 100
                            milligrams/kilogram in 1 liter D5W over the next 16
                            hours (Prescott et al, 1979; Westman, 1989).
                        (4) There does appear to be a slight increased risk
                            of adverse reactions following intravenous
                             administration (primarily urticaria and/or
                             bronchospasm which are rate-related, but
                             anaphylactoid reactions have occurred).
                b. Intravenous acetylcysteine is safe and effective for
                   preventing the hepatic and renal toxicities following overdose
                   of acetaminophen (Prescott, 1981). Similar findings were
                   reported elsewhere (Shenfeld & Oh, 1980).
                c. Dosing information is as follows (Westman, 1989): Patients
                   who present with toxic levels of acetaminophen less than 10
                   hours after ingestion should receive acetylcysteine
                   intravenously for 20 hours (150 milligrams/kilogram of body
                   weight as a bolus dose, followed by 50 milligrams/kilogram
                   for 4 hours and then 100 milligrams/kilogram for 16 hours).
                   Patients who present with toxic levels of acetaminophen
                   more than 10 hours after ingestion should receive
                   acetylcysteine IV for 48 hours (150 milligrams/kilogram as a
                   bolus dose, followed by 50 milligrams/kilogram for 4 hours
                   and then 286 milligrams/kilogram for 44 hours).
                   Hemoperfusion may be of value and should be considered
                   for patients presenting early with toxic levels of
                   acetaminophen and severe acidosis, presenting early with
                   extremely high levels of acetaminophen (4000 nmol/liter or
                   more) and patients presenting more than 15 hours after the
                   ingestion with serum levels exceeding 1000 nmol/liter.
        1. Adverse reactions to intravenous acetylcysteine appear to be rate-
          dependent. Intravenous acetylcysteine should be administered slowly
          over 1 hour; however if an adverse reaction occurs, diphenhydramine
          is given and subsequent doses are given over 2 hours to minimize
          complications (Smilkstein et al, 1991; Tenenbein, 1984).
                a. There are no reports of acetylcysteine being administered
                   rectally for treatment of acetaminophen poisoning. The extent
                   of its absorption via the rectum is not known (Pers Comm,
                   1983; Pers Comm, 1983a). Rectal administration of
               acetylcysteine solution is not recommended for treatment of
               acetaminophen overdose. For patients not able to retain oral
               doses of acetylcysteine, administration of diluted doses via
               nasogastric tube or by slow intravenous infusion may be
               tried. An intravenous formulation of acetylcysteine is
               available in the United States under an investigational
               protocol through participating poison centers.
             a. Acetylcysteine enemas together with acetylcysteine orally
               have been used with apparent success in neonates,
               children, and adults with bowel obstruction due to meconium
               ileus or meconium ileus equivalent. A 4% to 6%
               acetylcysteine enema (diluted in 100 to 300 milliliters of water
               or normal saline) administered every 6 to 12 hours appears
               to be effective and safe, but higher concentrations have
               been used (Spiro, 1977; Hodson et al, 1976; Derman et al,
               1975; Shaw, 1969; Simpson et al, 1968).
             a. Acetylcysteine has been administered via tracheostomy,
               intratracheal catheter, nebulizer, intermittent positive
               pressure breathing (IPPB), endotracheal tube and cannula
               (Webb, 1962). It is generally felt that direct instillation or
               intermittent positive pressure breathing (IPPB) are much
               superior to nebulization (Poppe, 1964; Miller, 1973). When
               administered by direct instillation, 1 to 2 milliliters of a 10% to
               20% solution may be given as often as every hour. When
               used for the routine care of patients with tracheostomy, 1 to 2
               milliliters of a 10% to 20% solution may be administered
               every 1 to 4 hours by instillation into the tracheostomy (Prod
               Info Mucomyst(R), 1996). A dosage of 2 to 5 milliliters of the
               10% solution is as effective and produces less
               bronchoconstriction than higher (20%) concentrations
               (Hirsch & Kory, 1967).
             b. When nebulized into a face mask, mouth piece, or
               tracheostomy, 1 to 10 milliliters of the 20% solution or 2 to 20
  milliliters of the 10% solution may be given every 2 to 6
  hours. The recommended dose for most patients is 3 to 5
  milliliters of the 20% solution or 6 to 10 milliliters of the 10%
  solution 3 to 4 times daily (Prod Info Mucomyst(R), 1996).
 c. The 20% solution may be diluted to a lesser concentration
  with either sodium chloride for injection, sodium chloride for
  inhalation, sterile water for injection, or sterile water for
  inhalation. The 10% solution may be used undiluted. Any
  unused portion of the solution should be stored in the
  refrigerator and used within 96 hours (Prod Info
  Mucomyst(R), 1996).
 d. For treatment of pulmonary complications of surgery or
  posttraumatic chest conditions, 1 to 2 milliliters of 20%
  acetylcysteine solution or 2 to 4 milliliters of 10% solution
  may be given every 1 to 4 hours via a syringe attached to the
  intratracheal catheter; 2 to 5 milliliters of the 20% solution
  may be introduced with a syringe through a tracheal catheter
  when contact with a particular segment of the
  bronchopulmonary tree is desired (Prod Info Mucomyst(R),
  1996; AHFS, 1989).

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