The Efficacy of Intravenous Acetaminophen During Perioperative Neurosurgery Period

The Efficacy of Intravenous Acetaminophen During The Perioperative Period Of Neurosurgical Patients Undergoing Craniotomies

This is a prospective randomized double blinded trial study involving 128 patients undergoing any craniotomy procedure at Evanston Hospital. The patients will be randomized by the sealed envelope technique. The anesthesiologist and nurses who will be administering the placebo or intravenous acetaminophen will be blinded to the group in which patients are assigned.

The following general perioperative data will be recorded: patient information/preoperative data, procedural information, postoperative information, and overall satisfaction of pain management at 24 hours after surgery.

Based on a pilot study (N-20) we expect that 25% of the placebo treated patients will require no opioids in the first 24 hour postoperative period. With the use of intravenous acetaminophen, it is hypothesized that the number of patients that do not require opioids in the first 24 hours after surgery will double.

Study Overview

• Status: Completed
• Conditions: Craniotomy; Brain Surgery
• Intervention / Treatment: Drug: Placebo; Drug: Acetaminophen

Detailed Description

This is a prospective randomized double blinded trial study involving 128 patients undergoing any craniotomy procedure at Evanston Hospital. The patients will be randomized by the sealed envelope technique. The anesthesiologist and nurses who will be administering the placebo or intravenous acetaminophen will be blinded to the group in which patients are assigned.

The following information will be recorded for each patient enrolled in this study:

• Patient information/Preoperative Data

  • Age, sex, height, weight,
  • Disease specific information
  • Primary diagnosis
  • Pertinent medical history
  • Medications
  • Pertinent changes in patient status

• Procedural information

  • Operation type
  • Preoperative anesthetic medications
  • Induction meds, intra-operative anesthetic meds, and post-operative anesthetic meds
  • Duration of Surgery and Intubation
  • Amount of dilaudid equivalent narcotics

• Postoperative Information

  • Amount of narcotics administered in the PACU
  • Amount of narcotics administered in the first 24 hour postoperative period
  • Amount of non-narcotic analgesics administered in the first 24 hour postoperative period
  • Time to first rescue analgesic in the PACU
  • Amount of first rescue medication recorded
  • Assessment of Pain Intensity at T0.5 (30min into PACU stay) and T24 (24 hours after end of surgery) (A 10-cm VAS scale will be used and labeled no pain at its left terminus and worst pain imaginable at its right terminus)
  • Temperature in degrees centigrade every 8 hours for 24hours.
  • CAM-ICU is performed by ICU nurses to detect delirium in patients every 8 hours and will be documented on a data collection sheet for the first 24 hours
  • RASS is a sedation scoring system that is used in our ICU and is documented every 8 hours by ICU nursing. We will record the RASS score for the first 24 hours on a data collection sheet as documented by the ICU nurse.
  • Overall satisfaction score at 24 hrs. "Overall satisfaction with pain management" (verbal rating score: scale 1 - 100)

Based on a pilot study (N-20) we expect that 25% of the placebo treated patients will require no opioids in the first 24 hour postoperative period. With the use of intravenous acetaminophen, it is hypothesized that the number of patients that do not require opioids in the first 24 hours after surgery will double.

• Study Type: Interventional
• Enrollment (Actual): 140
• Phase: Phase 4

Contacts and Locations

Study Locations

• United States
  • Illinois
    • Evanston, Illinois, United States, 60201
      • Northshore University Healthsystem

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 90 years (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Subject are able to provide informed consent prior to participation in the study
• Subjects must be scheduled to undergo elective open craniotomy procedure of > 2 hour duration
• Subjects must be >18 years old but less than 90 years old
• Subjects must have an American Society of Anesthesiologists (ASA) class I-IV
• Subjects must have the ability to communicate meaningfully with the investigator staff and read/understand the study procedures and the use of pain scales

Exclusion Criteria:

• Subjects used opioids or tramadol daily for >7 days before study medication administration
• Subjects had been treated with any of the following within 14 days of surgery: chaparral, comfrey, germander, jin bu huan, kava, pennyroyal, skullcap, St. John's wort, or valerian
• Subjects who have a chronic pain condition, significant medical disease or laboratory abnormality that in the investigator's judgment could compromise the subject's welfare
• Subjects with known hypersensitivity to opioids, acetaminophen or the inactive ingredients
• Subjects with known or suspected history of alcohol or drug abuse or dependence in the previous 2 years prior to the proposed surgery

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: QUADRUPLE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: Acetaminophen; Subjects will receive 1000mg of intravenous acetaminophen every 6 hours for 24 hours beginning with dural closure.	Drug: Acetaminophen; Other Names: Tylenol
OTHER: Placebo; Subjects will receive 100cc of normal saline every 6 hours for 24 hours beginning at dural closure.	Drug: Placebo; Other Names: normal saline

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Opioid Requirement After Surgery	The purpose of the study was to determine whether more patients undergoing craniotomies would not require any opioids (i.e., opioid consumption reduced to zero) during the first 24 postoperative hours when receiving intravenous (IV) acetaminophen during that time compared to those receiving placebo (normal saline).	during first 24 hours after surgery

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Time to Rescue Medication in Both Groups	Time (minutes) from end of procedure to first rescue dose in either PACU or ICU	0 to 24 hours after surgery
Amount of Rescue Medication in PACU in Both Groups		0 to 24 hours after surgery
Median Difference in ICU Length of Stay/Hospital Length of Stay Between Both Groups		from 0 to estimated 24 hours after surgery
Number of Participants Who Had a Successful Neurologic Exams Between Intervention and Placebo Group as Determined by a Neurosurgical Provider by Answering Either Yes or No	Successful neurologic exams are performed by neurosurgical team during the first 24 hour period. Successful neurologic exams will be provided by a neurosurgical professional and they will answer Yes or No if the exam is appropriate.	from 0 to estimated maximum of 24 hours after surgery
Median Difference in Temperature Between Intervention and Placebo Groups	Temperature measure in degrees celcius during the first 24hours postoperatively in increments of 8 hours.	from 0 to estimated maximum 24 hours after surgery
Sedation Scores Measured by Richmand-Agitation-Sedation Scale (RASS) Every 8 Hours for 24 Hours in Both Groups	Sedation scores will be evaluated by providers through the Richmand-Agitation-Sedation Scale (RASS) system every 8 hours for the first 24hour postoperatively. The RASS is a 10 point scale with four levels for anxiety or agitation (+1 to +4 (indicates more agitation and alertness the higher number you have)), one level to indicate a calm and alert state (0), and 5 levels of deeper sedation (-1 to -5 ( the more negative number indicating a deeper level of sedation)) patients. It helps guide sedation therapy at the bedside. There are no worse outcomes with different levels of sedation scores. However, typically, we try to keep the scores in the range of 0-+1 to be able to appropriately assess patients and allow them to be mobile in a safe fashion.	during first 24 hours after surgery
Pain VAS Scores (1-100) Every 8 Hours for 24 Hours in Both Groups	Pain was measured using the Visual Analog Scale (VAS) for each patient at the time of arrival and every eight hours after arrival for the first 24 hours of ICU stay. A VAS score of 1 indicates little or no pain and a VAS score of 100 indicates severe pain.	during first 24 hours after surgery
# of Participants With Delirium Measured by a Positive CAM-ICU Every 8 Hours for 24 Hours in Both Groups-	Delirium was assessed in each of the participants upon arrival to the ICU using the Confusion Assessment Method for the ICU (CAM-ICU). The CAM-ICU was performed for each participant every 8 hours following admission for the first 24 hours The CAM ICU scoring is based on a scale of 0-7, 0-2=no delirium, 3-5=miild delirium, 6-7=severe delirium. The positive CAM ICU consists of features 1 and 2 and either 3 or 4: Features 1: Acute onset or fluctuating course Features 2: Inattention Features 3: Disorganized thinking Features 4: Altered level of consciousness	during first 24 hours after surgery
Median Satisfaction Scores on a Verbal Score From 1(Not Satisfied at All) to 100 (Very Satisfied)	on a verbal score 1-100, 1 would mean that the patient is not satisfied at all and 100 would mean that the patient was very satisfied.	During first 24 hours after surgery

Collaborators and Investigators

• Sponsor: NorthShore University HealthSystem
• Collaborators: Cadence Pharmaceuticals
• Investigators: Principal Investigator: Steven Greenberg, MD, NorthShore University Health Sytem - Evanston Hospital Department of Anesthesia

Study record dates

Study Major Dates

• Study Start: January 1, 2012
• Primary Completion (ACTUAL): August 1, 2016
• Study Completion (ACTUAL): January 20, 2017

Study Registration Dates

• First Submitted: November 28, 2012
• First Submitted That Met QC Criteria: November 29, 2012
• First Posted (ESTIMATE): December 3, 2012

Study Record Updates

• Last Update Posted (ACTUAL): November 4, 2021
• Last Update Submitted That Met QC Criteria: October 7, 2021
• Last Verified: October 1, 2021

More Information

Terms related to this study

• Keywords: acetaminophen; craniotomy; Tylenol; brain surgery
• Additional Relevant MeSH Terms: Physiological Effects of Drugs; Peripheral Nervous System Agents; Analgesics; Sensory System Agents; Analgesics, Non-Narcotic; Antipyretics; Acetaminophen
• Other Study ID Numbers: EH11-380

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Data is stored in file at our system
• IPD Sharing Time Frame: anytime
• IPD Sharing Access Criteria: anytime
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; ICF; ANALYTIC_CODE; CSR