Analgesia Regimens Following Trans-sphenoidal Surgery for Pituitary Tumors

Study Overview
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Brief Summary
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A randomized, double-blind, placebo-controlled intervention trial involving 100 treated subjects undergoing endonasal trans-sphenoidal (ENTS) resection of pituitary lesion. Subjects will be randomized into two groups: 50 treated in the opioid-sparing arm and 50 treated in the standard post-operative medication arm.

Detailed Description
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Post-operative pain control is a common concern patients have when they consider undergoing a surgical procedure. Although effective for treating acute pain, opioid analgesics are also associated with dose-dependent adverse effects, including constipation, nausea and vomiting, altered mental status, and respiratory depression, all of which have been shown to increase patient length of stay. The use of non-opioid analgesics with different mechanisms of actions for acute pain control via a multi-modal approach is efficacious in reducing opioid consumption, decreasing the incidence of adverse effects, improving patient satisfaction and recovery time, and decreasing hospital costs.Certain minimally invasive procedures may afford many patients the opportunity to achieve adequate post-operative pain control with minimal to no requirement of opioid analgesics, thereby sparing the patient known adverse effects that can increase length of stay and costs. The ENTS approach for resection of pituitary tumors is the standard surgical procedure for these lesions, and is associated with pain that is more easily managed post-operatively, making it an ideal procedure for an opioid-sparing post-operative pain regimen. Anecdotally, the investigators note that in the investigator's post-operative pituitary patient population that post-operative pain can frequently be adequately managed with scheduled non-opioid analgesics, often without requiring breakthrough opioid doses. Another safe and effective non-opioid analgesic that is widely used in multi-modal pain management for moderate pain is IV Caldolor (ibuprofen). After literature review, the investigators were unable to find a study that had attempted to use an opioid-sparing analgesic regimen for post-operative pain control following ENTS approach for resection of pituitary tumors.

Official Title
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Randomized, Double-Blind, Placebo-Controlled Trial Comparing Opioid-Sparing and Opioid-Containing Analgesia Regimens Following Trans-sphenoidal Surgery for Pituitary Tumors

Conditions
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Pituitary Tumor, Pain

Intervention / Treatment
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* Drug: IV Caldolor
* Drug: IV Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Adult patient undergoing ENTS surgery for resection of pituitary tumor. Adults >18 years and <80 years of age. English speaking and literate or able to understand the use of a pain scale. Body Mass Index >19 and <40 kg/m2 Exclusion Criteria: Renal failure (acute or chronic) or creatinine >2.0 Allergy or intolerance to acetaminophen, ibuprofen, or opioids Pre-operative opioid tolerance, dependence, or abuse Anaphylaxis to opioids History of peptic ulcer disease or recent gastrointestinal bleed requiring surgery Cirrhosis, hepatitis, liver transplant, or liver function studies out of normal range, defined as aspartate aminotransferase (AST)/alanine aminotransferase (ALT)/bilirubin> 3x upper limit of normal range Subject unwilling or unable to sign informed consent for the study Pregnancy Incarcerated patients

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 79 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Supportive Care
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: IV Caldolor (ibuprofen)<br>Intravenous (IV) Caldolor (ibuprofen) (800mg every 8 hours) initiated during surgery and oral acetaminophen 1000mg every 6 hours initiated post-operatively and continued for the duration of the hospital stay (an expected average stay of 2 days) or 48 hours, whichever comes first. Breakthrough pain will be treated with rescue narcotics (IV morphine 2-4mg every 2 hours and oral oxycodone 5-15mg every 4 hours immediately post-operatively through discharge, an expected average stay of 2 days). Hydromorphone (IV 0.5-2mg every 2 hours and oral 2-4mg every 4 hours) will be used in patients with morphine or oxycodone allergy or intolerance. | Drug: IV Caldolor<br>* IV Caldolor (IV ibuprofen) intraoperatively and postoperatively<br>* Other names: Opioid Sparing group;|
| Placebo Comparator: standard treatment group<br>IV placebo will be initiated during surgery and oral acetaminophen 1000mg every 6 hours will be initiated post-operatively and continued for the duration of the hospital stay (an expected average stay of 2 days) or 48 hours, whichever comes first. Breakthrough pain will be treated with rescue narcotics (IV morphine 2-4mg every 2 hours and oral oxycodone 5-15mg every 4 hours immediately post-operatively through discharge, an expected average stay of 2 days). Hydromorphone (IV 0.5-2mg every 2 hours and oral 2-4mg every 4 hours) will be used in patients with morphine or oxycodone allergy or intolerance. | Drug: IV Placebo<br>* IV Placebo intraoperatively and postoperatively<br>* Other names: Standard treatment group;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Comparison of Mean Pain Scores Between Two Arms (Measured Every 4 Hours Over 48 Hour) | Comparison of pain scores between two arms using Visual Analog Scale (VAS) for Pain. Units of measure are 0=No Pain, 1=Annoying, 2=Mild Pain, 3=Troublesome, 4=Nagging Pain, Uncomfortable, 5=Distressing, 6=Miserable, 7=Horrible, 8=Intense, Dreadful, 9=Unbearable, 10=Worst Possible Pain. Higher values represent a worse outcome. There are no subscales. | mean pain score over 48 hours | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Breakthrough Narcotic Requirement | Rescue narcotic in both groups will be recorded and compared using a standard equianalgesic oral morphine equivalent (OME) calculation | until discharge from hospital, an expected stay of 2 days | 
| Other Adverse Events | Epistaxis, potentially related to IV ibuprofen, will be compared between two groups | until discharge from hospital, an expected stay of 2 days |