Intravenous Acetaminophen in Craniotomy
Condition: Postoperative Pain
MeSH terms: Pain, Postoperative
Study type: Interventional
Phase: Phase 4

Summary: 
      The purpose of this study is to assess the use of intravenous Acetaminophen (OFIRMEV) as an
      effective adjunct therapeutic agent in patients undergoing craniotomy.
    

Detailed description: 
      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.
    

Intervention name(s): Acetaminophen; Placebo
Intervention type(s): Drug; Drug
Intervention description(s): Intravenous Acetaminophen, 1000 mg/100mL, Every 6 hours, Infused over 15 minutes.; 100 mL 0.9% Sodium Chloride
Other intervention name(s): OFIRMEV; 0.9% Sodium Chloride
Intervention MeSH terms: Acetaminophen
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary purpose: Supportive Care
Keywords: Acetaminophen; Intravenous Acetaminophen; Opioid Requirement; Pain; Post-Operative Pain; Craniotomy; Post-Craniotomy Pain