Intravenous Acetaminophen in Craniotomy

General anesthesia will be induced by bolus administration of propofol (1.5-2.5 mg/kg IV),
and fentanyl (2-3 µg/kg IV). Neuromuscular blockade will be achieved with bolus
administration of rocuronium, vecuronium, or succinylcholine. Once the endotracheal tube is
secured in place, the patient will be mechanically ventilated to an end-tidal CO2 of 35 mmHg.
Additional procedures will include radial arterial line placement for invasive arterial blood
pressure monitoring, as well as additional large-bore peripheral IV placements, or central
line placement, if indicated. Anesthesia will be maintained with desflurane, propofol, and
remifentanil.

Once general anesthesia has been induced, but prior to the first surgical incision, the first
dose of the interventional agent will be administered. Repeat doses will be administered
every 6 hours until 24 hours from the time that the patient enters the PACU, for a total of
up to 6 doses. Once the patient has been positioned and prepped for surgery, the surgeon will
infiltrate the scalp with bupivacaine 0.5% with epinephrine 1:200,000 (15-20 ml) before skin
incision.

No other opioids or agents with analgesic properties (e.g., ketorolac, dexmedetomidine,
ketamine) will be administered at any time during the operation. Additional medications that
will be routinely administered for this procedure include dexamethasone 8-12mg IV prior to
incision, and ondansetron 4mg IV at skin closure. Anticonvulsant drugs will be administered
at the surgeon's request.

Emergence and extubation will occur at the completion of the case per standard guidelines.
The time of remifentanil infusion discontinuation and time of extubation will be noted. If
necessary, extubation may occur in the post anesthesia recovery unit (PACU); otherwise,
extubation will occur in the operating room.

The patient will then be taken directly to the PACU. Inability to extubate a patient within
two hours of completion of surgery will result in their withdrawal from the study. Once in
the PACU, immediate postoperative vital signs will be recorded, including blood pressure,
heart rate, respiratory rate, oxygen saturation, and RASS score.

Pain scores will be assessed using the visual analog scale (VAS) upon entering the PACU or
upon extubation in PACU (0 hours), and then again at 1, 2, 4, 8, 12, 16, 20, and 24 hours
post-operatively. The VAS will be a 10 cm scale on a numerical scale of 0 (no pain) to 10
(severe pain) that the patient will point to in order to indicate their current level of
pain. Pain scores will be measured while the patient is at rest. Post-operative nausea will
also be recorded on a 10 cm numeric rating scale (NRS) at the same time intervals, with 0
indicating no nausea and 10 indicating severe nausea. All day-time VAS and NRS measurements
will be made by a research assistant. Night-time measurements will be made by the nurse on
the unit.

While in the PACU, the time until the patient receives their first dose of analgesic medicine
will be recorded. Patients will be given a 2mg nurse-administered dose of morphine upon
request or if they report a pain score of ≥4/10, and will continue to be given morphine doses
based on clinical assessment by the PACU/intensive care nurse, who will be blind to patient
group allocation. The nurse will objectively assess the patient's pain score at least once an
hour using the VAS pain scale, and an assessment of pain ≥4/10 will warrant an additional 2mg
dose of morphine. Morphine dosage requirements will be recorded for 24 hours
post-operatively. If morphine requirement is greater than 10mg in a 30 minute period or the
patient develops an allergic reaction, pruritus, renal insufficiency, drowsiness,
nausea/vomiting, or clinically relevant reason to change medication, the PACU supervising
physician or ICU physician may use their clinical discretion to change the opioid rescue
medication to hydromorphone (0.3mg doses). The reason for changing medication will be
reported by the physician and recorded. The morphine equivalent of hydromorphone will be
estimated to be 7 times the hydromorphone dose. The PACU/ICU nurses will also record any
episodes of emesis, use of rescue anti-emetic medicine, and the occurrence of any other side
effects.

A post-operative neurologic examination will take place in the PACU. Criteria for a
neurological exam to be complete is the patient's ability to successfully lift each leg off
of the bed for more than two seconds on command, and to be able to hold up two fingers on
each hand on command. If these criteria are not met prior to transferring the patient from
the PACU to the ICU, a post-operative neurologic complication will be considered and the
patient will be withdrawn from the study.

The time until the patient is ready to be discharged from the PACU will also be noted.
Patients with a modified Aldrete score of ≥ 8 (see Appendix 1) will be considered ready for
discharge. These criteria will be assessed by either the research assistant or PACU staff.

At the end of the 24 hour post-operative time period, a patient interview will be conducted.
At this interview the patient will asked about their subjective satisfaction with their
analgesic protocol, as well as any adverse effects they may have noticed. The 24 hour
morphine consumption will also be recorded at this time.

After the study is completed, patients may receive IV or oral acetaminophen therapy at the
discretion of the primary physician.

Inclusion Criteria:

- Adults

- Undergoing Craniotomy for Supratentorial Tumor Resection

- Weight between 50 and 120 kilograms

- ASA Physical Status I-III

- Be able to communicate verbally

- Be able to use Visual Analog Score

Exclusion Criteria:

- Allergies to acetaminophen, morphine or any of the anesthetic agents required by the
protocol.

- Use of opioids, tramadol, benzodiazepines, or gabapentin on a daily basis for > 7 days
prior to the day of surgery.

- Use of acetaminophen, NSAIDs, or any other analgesic medication in the 12 hours
immediately prior to study enrollment.

- Hepatic insufficiency (elevated transaminases > 1.5 times the upper limit of normal)
or renal insufficiency (plasma creatinine > 2mg/dl).

- Known or suspected history of alcohol or illicit drug abuse.

- Pregnant or breast-feeding.

- Surgical plan for infratentorial (suboccipital) craniotomy.

- Plan for neurophysiologic monitoring that precludes the use of neuromuscular blockade.

- Inability to communicate due to a language barrier, impaired consciousness, cognitive
defect or intellectual disability.

- Uncontrolled Hypertension