Efficacy of Acetaminophen in Posterior Fossa Surgery

The primary goal of this study is to compare the efficacy of IV acetaminophen to placebo in
pediatric patients undergoing posterior fossa surgery, with the primary outcome measure being
postoperative opioid requirements (morphine equivalent mg/kg). This will be a prospective,
randomized, double blind control trial. The patient, research team, surgeon, and
anesthesiologist will all be blinded to the patient's treatment group. Patients will receive
either IV acetaminophen or equal volume normal saline (placebo) in the perioperative period.

The interventional component of this study involves the intraoperative and postoperative
administration of IV acetaminophen. Intraoperative and postoperative data pertaining to
adverse events would be collected for safety monitoring purposes.

Enrolled subjects will be randomized to receive either IV acetaminophen or equal volume
saline placebo during surgery and for 24 hours postoperatively. According to a
computer-generated table of random number assignments, each patient will be randomly assigned
to receive one of the following two treatment groups:

Treatment group 1:

IV acetaminophen 15 mg/kg (1.5 mL/kg) IV loading dose prior to incision, followed by a 15
mg/kg (1.5 mL/kg) dose given every 6 hours for the first 24 hours after surgery (total of 4
doses postoperatively). This dosing regimen was chosen based on pharmacokinetic data and
recommended dosing guidelines for IV acetaminophen in children 2 to 12 years of age.

Treatment group 2:

Equal volume of normal saline (placebo control) at the same dose and frequency as treatment
group 1.

Loading dose volumes and subsequent doses every 6 hours will be determined based on weight of
the patient such that they will receive equal volumes of either IV acetaminophen or saline.

Maintenance of anesthesia, including opioid administration, and perioperative management will
proceed as per routine care.

POSTOPERATIVE ANALGESIA

At the completion of surgery, the anesthetic agents will be discontinued as per routine care.
Per routine care, after tracheal extubation, morphine (0.05 mg/kg/dose) will be administered
as needed by the blinded assessor until the patient appears comfortable, defined as the
absence of any verbal or behavioral expression of pain. Patients will then be transferred to
the intensive care unit (ICU).

Time of entry into the intensive care unit will be recorded. The following assessments will
be recorded at time of admission to the ICU:

- vital signs (heart rate, respiratory rate, blood pressure)

- oxygen saturation

- pain score

- sedation score

As part of routine care for postoperative analgesia, patients will receive morphine sulfate
at standard doses (0.05 - 0.1 mg/kg/dose every 3 hours as needed for pain). The frequency and
dose of morphine will be adjusted according to the patient's pain score, with a goal to
maintain a pain score of < 6. In addition, patients will transition to oral opioids as soon
as their diet allows.

The following parameters will be used to measure short-term postoperative analgesia and side
effects:

- Daily opioid consumption (mg/kg/24h in morphine equivalent using the conversion)

- Pain scores at rest

- Sedation score

- The incidence of post-operative nausea and vomiting (PONV) will be assessed by the need
for rescue antiemetics: i.e. ondansetron or promethazine given as needed.

- The incidence and severity of pruritus will be assessed by the need for rescue
anti-pruritic: i.e. diphenhydramine or hydroxyzine given as needed for pruritus

- The incidence of pyrexia (defined as core temperature ≥ 38º Celsius). Ketorolac will be
administered 0.5 mg/kg q6h prn as needed for pyrexia as per routine care.

Data collection will continue for up to 72 hours postoperatively.

DATA ANALYSIS

Data will be analyzed to determine the decrease in postoperative opioid requirements with or
without IV acetaminophen after posterior fossa surgery as the primary outcome. The
investigators hypothesize that IV acetaminophen will decrease postoperative opioid
requirements, pain and sedation scores, and opioid-induced side effects in children
undergoing posterior fossa surgery.

Inclusion Criteria:

1. Any child undergoing posterior fossa surgery, including surgery for Chiari
Malformation

2. The subject's American Society of Anesthesiologists physical status is 1, 2 or 3

3. Males and females 2 to 12 years old (minorities will be included) - recommended dosing
of IV acetaminophen in children is approved for children 2 to 12 years of age

4. Written informed consent from parent/guardian

Exclusion Criteria:

1. Subjects with known or suspected hypersensitivity reaction to acetaminophen

2. Presence or prior history of a known liver disease or coagulation disorder:

3. History of abnormal liver function

4. History of prior liver transplantation

5. Subjects who are on anticoagulant therapy (Coumadin, heparin, aspirin, etc.)

6. History of prior acetaminophen overdose

7. Subjects with the need for mechanical ventilation prior to surgery or postoperatively
- unable to assess accurate pain scores in this context

8. The subject has a history or a family (parent or sibling) history of malignant
hyperthermia

9. The subject had a recent opioid exposure (within 1 month of surgery)

10. The subject is obese (body mass index >30 kg/m2)

11. The subject is an American Society of Anesthesiologist physical status classification
of 4 or greater

12. The subject is scheduled for a surgical sub-procedure

13. Subjects who have been previously enrolled in this protocol may not be enrolled again