Intraoperative and Post-operative Analgesic Effect of IV Acetaminophen for Sinus Surgery (IVAPAP)

A Double Blind, Randomized, Placebo-controlled Study to Investigate the Effectiveness of IV Acetominophen Administered During Functional Endoscopic Sinus Surgery in Reducing the Use of Opiates to Treat Postoperative Pain

The purpose of this study is to assess the use of IV acetaminophen (Ofirmev) as a and safe and efficacious agent in reducing post-operative pain; we hypothesize that its use will reduce post-operative pain when compared to a control group using the visual analogue score (VAS) analog pain scoring system.

Study Overview

• Status: Completed
• Conditions: Chronic Sinusitis
• Intervention / Treatment: Drug: IV Acetaminophen; Drug: Placebo

Detailed Description

Unrelieved postoperative pain may result not only in suffering and discomfort, but may also lead to multiple physiological and psychological consequences which can contribute to adverse perioperative outcomes. Inadequate perioperative analgesia can potentially contribute to a higher incidence of myocardial ischemia. Additionally, the use of opioids has been associated with major side effects that can include impaired wound healing and delayed gastrointestinal (GI) motility that results in prolonged postoperative ileus.

Intravenous acetyl-para-aminophenol (APAP, also known as acetaminophen) is considered as the non-opioid analgesic of choice to treat postoperative mild and moderate pain, and has been demonstrated in several randomized trials to be both safe and effective at reducing acute post-operative pain in both children and adults. Furthermore, in the treatment of severe pain, it can reduce the need for opioid-analgesics while exhibiting a relatively limited side effect profile when compared to opioids and nonsteroidal anti-inflammatory drugs.

Chronic rhinosinusitis (CRS) describes a group of disorders characterized by inflammation of the nasal mucosa and/or paranasal sinuses for at least 12 consecutive weeks. In the United States, CRS affects approximately 30 million people, and represents 2% of the primary diagnoses in physician office visits, resulting in an estimated 200,000 sinus procedures annually. Patients suffering from CRS that is refractory to medical management complain of symptoms that include fatigue, headache, nasal drainage, facial pain and pressure, and decreased sense of smell. Functional endoscopic sinus surgery (FESS) represents a surgical approach to treating CRS that is unresponsive to medical management. Outcomes studies have identified FESS as efficacious at reducing the majority of symptoms related to CRS. Despite this, pain associated with CRS remains a significant co-morbidity that often is resistant to both medical and surgical management. Reducing the incidence and severity of acute post-operative pain is paramount to reducing the development of chronic pain that may exacerbate a patient's existing pain. The use of pre- and intra- operative IV acetaminophen thus serves as a unique pain management modality in this setting, as it has the potential for reducing post-operative complications and pain, with the additional benefit of minimal intraoperative bleeding, an undesirable complication often associated with FESS and with the use of non-steroidal anti-inflammatory drugs (NSAIDs).

The use of IV acetaminophen in ear, nose, and throat (ENT) surgery is not a novel endeavor. Indeed, studies have demonstrated the efficacy and safety of IV acetaminophen for use in tonsillectomy and FESS. We wish to provide a more comprehensive analysis of pain management in the setting of FESS in the following ways :

1. by administering IV acetaminophen perioperatively (before start of surgery, and after surgery completion;
2. by employing a pain score of 4 (whereas other studies use 3) as a cutoff for breakthrough pain; and,
3. by addressing novel outcomes including patient sedation and patient satisfaction, in addition to opioid analgesic use.

In our institution, we have completed a preliminary pilot study exploring the use of intravenous anesthesia which included acetaminophen during bilateral endoscopic sinus surgery. Secondary outcomes measured during the study included:

1. Pain
2. Rescue analgesic use
3. Nausea/Vomiting
4. Time spent in recovery
5. Successful discharge from the PACU and the Hospital

Our pilot data has reaffirmed that the procedure is overall benign, with few associated risks and adverse events. Of note, none of the patients in our preliminary study required admission to the hospital after surgery for further observation as a result of uncontrolled pain or nausea. Based on this experience, we would like to explore the efficacy of intravenous acetaminophen (Ofirmev), a non opioid/non steroidal analgesic, in endoscopic sinus surgery.

• Study Type: Interventional
• Enrollment (Actual): 62
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United States
  • Texas
    • Houston, Texas, United States, 77030
      • The University of Texas Health Sciences Center at Houston

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 68 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion criteria:

1. Patients undergoing surgical management for CRS (with or without polyps)
2. Operating time must be at least 2 hours in duration.
3. Number of sinuses involved must be 3 or greater

Exclusion criteria:

1. History of hypersensitivity to acetaminophen
2. End stage renal disease
3. End stage liver disease
4. History of chronic pain, or use of opioid medication in the previous two weeks
5. Severe depression or anxiety
6. Use of gabapentin or any other pain modulator
7. History of acute sinusitis or mucocele
8. History of seizures
9. Known or suspected history of alcohol or drug abuse
10. Known or suspected history of morphine intolerance

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Supportive Care
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: IV Acetaminophen; The experimental group will receive a preoperative dose of 1000mg IV acetaminophen over 15 minutes. This will occur at least 15 minutes before the start of surgery. Another 1000mg dose of IV acetaminophen will be administered 4 hours after the first dose. A rescue analgesic containing oxycodone will also be provided (with APAP concentrations of 325 mg per Hospital and FDA recommendations).	Drug: IV Acetaminophen; 1000mg IV acetaminophen over 15 minutes every 4 hours for up to 2 doses.; Other Names: OFIRMEV (Cadence Pharamceutical, San Diego, USA)
Placebo Comparator: Control; The control group (Placebo) will receive 100 mL of 0.9% normal saline in place of IV acetaminophen in the same manner as the experimental group; the investigator/physician in question will be blinded to the agent that is being administered. Patients will be discharged with instruction to continue APAP 500 mg PO every 6-8 hours. A rescue analgesic containing oxycodone will also be provided (with APAP concentrations of 325 mg per Hospital and FDA recommendations).	Drug: Placebo; 100 mL of 0.9% normal saline over 15 minutes in place of IV acetaminophen.; Other Names: Normal Saline

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Pain Level Assessed Using a Visual Analogue Scale (VAS) Scale	VAS is a validated, self-reported data sheet assessing average pain intensity. Possible scores range from 0 (no pain) to 10 (highest level of pain).	15 minutes and 120 minutes Post-Operatively

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Total Doses of Postoperative Opiate (Morphine) Use	The total amount of morphine utilized in Postoperative Acute Care Unit (PACU) will be recorded. One dose is a 1mg bolus of morphine.	During Postoperative Acute Care Unit (PACU) stay (up to 4 hours after surgery)
Number of Participants Who Received Intraoperative Supplemental Fentanyl	Number of participants who received intraoperative supplemental fentanyl. The decision to administer fentanyl is based on hemodynamic changes, such as increasing blood pressure and heart rate.	During Postoperative Acute Care Unit (PACU) stay (up to 4 hours after surgery)
Number of Participants Who Experienced Postoperative Morbidity (Nausea)	Post-operative nausea will be monitored and measured through direct observation and nursing clinical record	During Postoperative Acute Care Unit (PACU) stay (up to 4 hours after surgery)
Postoperative Vital Sign (Systolic Blood Pressure)	Postoperative vital signs (systolic and diastolic blood pressure, pulse, temperature, and respiratory rate) were measured at different time points up to 4 hours after surgery.	During Postoperative Acute Care Unit (PACU) stay (up to 4 hours after surgery)
Postoperative Vital Sign (Diastolic Blood Pressure)	Postoperative vital signs (systolic and diastolic blood pressure, pulse, temperature, and respiratory rate) were measured at different time points up to 4 hours after surgery.	During Postoperative Acute Care Unit (PACU) stay (up to 4 hours after surgery)
Postoperative Vital Sign (Pulse)	Postoperative vital signs (systolic and diastolic blood pressure, pulse, temperature, and respiratory rate) were measured at different time points up to 4 hours after surgery.	During Postoperative Acute Care Unit (PACU) stay (up to 4 hours after surgery)
Postoperative Vital Sign (Temperature)	Postoperative vital signs (systolic and diastolic blood pressure, pulse, temperature, and respiratory rate) were measured at different time points up to 4 hours after surgery.	During Postoperative Acute Care Unit (PACU) stay (up to 4 hours after surgery)
Postoperative Vital Sign (Respiratory Rate)	Postoperative vital signs (systolic and diastolic blood pressure, pulse, temperature, and respiratory rate) were measured at different time points up to 4 hours after surgery.	During Postoperative Acute Care Unit (PACU) stay (up to 4 hours after surgery)

Collaborators and Investigators

• Sponsor: The University of Texas Health Science Center, Houston
• Collaborators: Mallinckrodt
• Investigators: Principal Investigator: Davide Cattano, MD, PhD, The University of Texas Health Sciences Center at Houston

Publications and helpful links

General Publications

• Tyler MA, Lam K, Ashoori F, Cai C, Kain JJ, Fakhri S, Citardi MJ, Cattano D, Luong A. Analgesic Effects of Intravenous Acetaminophen vs Placebo for Endoscopic Sinus Surgery and Postoperative Pain: A Randomized Clinical Trial. JAMA Otolaryngol Head Neck Surg. 2017 Aug 1;143(8):788-794. doi: 10.1001/jamaoto.2017.0238.

Study record dates

Study Major Dates

• Study Start: July 1, 2012
• Primary Completion (Actual): September 1, 2014
• Study Completion (Actual): September 1, 2014

Study Registration Dates

• First Submitted: May 25, 2012
• First Submitted That Met QC Criteria: May 29, 2012
• First Posted (Estimate): May 31, 2012

Study Record Updates

• Last Update Posted (Estimate): October 16, 2015
• Last Update Submitted That Met QC Criteria: September 25, 2015
• Last Verified: September 1, 2015

More Information

Terms related to this study

• Keywords: Chronic Sinusitis; Pain Relief; Post-Operative Opioid Requirement; IV Acetaminophen; Functional Endoscopic Sinus Surgery; FESS
• Additional Relevant MeSH Terms: Infections; Respiratory Tract Infections; Respiratory Tract Diseases; Otorhinolaryngologic Diseases; Paranasal Sinus Diseases; Nose Diseases; Sinusitis; Physiological Effects of Drugs; Peripheral Nervous System Agents; Analgesics; Sensory System Agents; Analgesics, Non-Narcotic; Antipyretics; Acetaminophen
• Other Study ID Numbers: HSC-MS-12-0111