Self-Administered Nitrous Oxide (SANO) During Transrectal Prostate Biopsy to Reduce Patient Anxiety and Pain

Transrectal prostate biopsy is a commonly performed ambulatory procedure for diagnosing prostate cancer. Prostate biopsy are associated with pain or anxiety. Nitrous oxide (or laughing gas) is a well-known inhaled anesthetic which is frequently used in dental offices and for pediatric procedures to alleviate a patient's anxiety and pain. This study seeks to determine whether administration of nitrous oxide at the time of prostate biopsy will improve a patient's experience of care.

Study Overview

• Status: Completed
• Conditions: Pain; Benign Prostatic Hyperplasia; Prostate Cancer; Prostate Adenocarcinoma; Anxiety and Fear; Malignancy; Prostate Disease
• Intervention / Treatment: Drug: Self-Administered Nitrous Oxide; Other: Oxygen

Detailed Description

Nitrous oxide is a well-tolerated inhaled anesthetic that has been used for decades in pediatric and adult populations and is largely viewed as effective and safe. In addition to analgesic effect, nitrous oxide also produces a dissociative euphoria and amnesia that could potentially improve patients' anxiety and experience of cancer care. When used as a single agent at concentrations ≤50%, the American Society of Anesthesiologists (ASA) classifies nitrous oxide as Minimal Sedation, producing a state in which a patient responds normally to verbal commands, maintains airway reflexes, and spontaneous ventilation. Over the past several decades nitrous oxide has become less common due to concerns of nitrous oxide environmental exposure to the care team. There are now Federal Drug Administration (FDA)-approved systems that allow patient self-administered nitrous oxide (SANO), and importantly, include a scavenger system to eliminate exhaled environmental nitrous oxide. These systems are rapidly being adopted throughout the United States in Urology practices, but to date, there have been no studies evaluating patient outcomes and possible risks with the adjunct use of SANO. This study is a prospective, randomized, controlled trial to assess patient perceived pain and anxiety related to prostate needle biopsy with or without SANO, and the frequency of complications associated with SANO. A secondary aim will be to demonstrate that the SANO at the time of prostate biopsy does not significantly increase burden on Urologist productivity, nor increase the difficulty of operator ease in performing the prostate needle biopsy.

• Study Type: Interventional
• Enrollment (Actual): 143
• Phase: Phase 4

Contacts and Locations

Study Locations

• United States
  • Massachusetts
    • Boston, Massachusetts, United States, 02215
      • Beth Israel Deaconess Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 85 years (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

• Biological male
• Aged 18 to 85 years
• Scheduled for clinically-indicated prostate needle biopsy
• Suitable for nitrous oxide/oxygen with willingness to be randomized to inhaled SANO or inhaled oxygen during the procedure
• Access to an email and computer

Exclusion Criteria:

• Perioral facial hair impeding good mask seal
• Learning disabilities and/or inability to cognitively complete survey questions
• Taken a pre-procedure benzodiazepine or narcotic.

• Has any of the following medical conditions:

  1. Inner ear, bariatric or eye surgery within the last 2 weeks,
  2. Current emphysematous blebs,
  3. Severe B-12 deficiency.
  4. Bleomycin chemotherapy within the past year.
  5. Class III or higher heart failure.
  6. Undergoing novel therapy for prostate cancer

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Self-Administered Nitrous Oxide; Patients will receive SANO in addition to periprostatic bupivacaine nerve block for the duration of prostate biopsy. After the Urologist describes the procedure, the SANO group will have nitrous oxide turned on to 30%, ensuring that the patient is relaxed but still conversant through the procedure. The nitrous will be adjust up or down based on the patient's response to the question "are you feeling the nitrous" and "are you happy at this level". The range will be between 25 - 45%. At the end of the procedure, the SANO group will be turned down to 0% nitrous oxide, and 100% oxygen will be administered through the mask for an additional 2-3 minutes as the patient is cleaned up and repositioned to the supine position.	Drug: Self-Administered Nitrous Oxide; Nitrous oxide administered at concentrations of mild sedation (20-45%) for the duration of prostate biopsy.; Other Names: nitrous oxide
Placebo Comparator: Oxygen; Patients will receive 100% oxygen at 10 Liters/minute for the duration of prostate biopsy.	Other: Oxygen; Oxygen will be administered at 10 Liters/min for the duration of prostate biopsy.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Post-biopsy Pain (VAS-P)	Pain experienced immediately following prostate biopsy as measured by a Visual Analog Scale for Pain (VAS-P) (range: 0 [no pain] - 10 [worst pain])	5-minutes after prostate biopsy
Post-biopsy Anxiety (VAS-A)	Anxiety experienced immediately following prostate biopsy as measured by a Visual Analog Scale for Anxiety (VAS-A) (range: 0 [no anxiety] - 10 [worst anxiety])	5-minutes after prostate biopsy
Post-biopsy Anxiety Traits (STAI)	Anxious traits exhibited after prostate biopsy as measured by the State Trait Anxiety Inventory (STAI) (range: 6-36; 36 being 'worst' anxiety).	5-minutes after prostate biopsy

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Time of Prostate Biopsy	Length of procedure will be compared between arms to assess whether SANO significantly lengthens prostate biopsy	Length of prostate biopsy; up to 30 minutes
Operator Assessment of "Tolerating Insertion of Rectal Probe"	Operating urologist filled out a survey to assess their perception of patient: Tolerating Insertion of rectal probe. Responses were scored on a 3-point Likert scale as 1 (worse than expected), 2 (as expected), or 3 (better than expected).	Immediately after prostate biopsy; within 5 minutes after completion of biopsy.
Operator Assessment of "Patient Maintenance of Positioning"	Operating urologist filled out a survey to assess their perception of patient: Patient maintenance of positioning. Responses were scored on a 3-point Likert scale as 1 (worse than expected), 2 (as expected), or 3 (better than expected).	Immediately after prostate biopsy; within 5 minutes after completion of biopsy.
Operator Assessment of "Patient Tolerance of Procedure"	Operating urologist filled out a survey to assess their perception of patient: Patient Tolerance of Procedure. Responses were scored on a 3-point Likert scale as 1 (worse than expected), 2 (as expected), or 3 (better than expected).	Immediately after prostate biopsy; within 5 minutes after completion of biopsy.

Collaborators and Investigators

• Sponsor: Beth Israel Deaconess Medical Center
• Collaborators: Brigham and Women's Hospital
• Investigators: Principal Investigator: Heidi Rayala, MD, PhD, Beth Israel Deaconess Medical Center

Publications and helpful links

General Publications

• Loeb S, Carter HB, Berndt SI, Ricker W, Schaeffer EM. Complications after prostate biopsy: data from SEER-Medicare. J Urol. 2011 Nov;186(5):1830-4. doi: 10.1016/j.juro.2011.06.057. Epub 2011 Sep 23.
• Rosario DJ, Lane JA, Metcalfe C, Donovan JL, Doble A, Goodwin L, Davis M, Catto JW, Avery K, Neal DE, Hamdy FC. Short term outcomes of prostate biopsy in men tested for cancer by prostate specific antigen: prospective evaluation within ProtecT study. BMJ. 2012 Jan 9;344:d7894. doi: 10.1136/bmj.d7894.
• Jastak JT, Donaldson D. Nitrous oxide. Anesth Prog. 1991 Jul-Oct;38(4-5):142-53. No abstract available.
• Practice Guidelines for Moderate Procedural Sedation and Analgesia 2018: A Report by the American Society of Anesthesiologists Task Force on Moderate Procedural Sedation and Analgesia, the American Association of Oral and Maxillofacial Surgeons, American College of Radiology, American Dental Association, American Society of Dentist Anesthesiologists, and Society of Interventional Radiology. Anesthesiology. 2018 Mar;128(3):437-479. doi: 10.1097/ALN.0000000000002043. No abstract available.

Study record dates

Study Major Dates

• Study Start (Actual): December 12, 2021
• Primary Completion (Actual): September 2, 2022
• Study Completion (Actual): September 9, 2022

Study Registration Dates

• First Submitted: February 28, 2023
• First Submitted That Met QC Criteria: March 25, 2023
• First Posted (Actual): April 7, 2023

Study Record Updates

• Last Update Posted (Actual): January 30, 2024
• Last Update Submitted That Met QC Criteria: January 3, 2024
• Last Verified: January 1, 2024

More Information

Terms related to this study

• Keywords: prostate cancer; prostate biopsy; ambulatory; nitrous oxide; patient experience of care
• Additional Relevant MeSH Terms: Mental Disorders; Pathologic Processes; Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Genital Neoplasms, Male; Urogenital Diseases; Male Urogenital Diseases; Genital Diseases, Male; Genital Diseases; Prostatic Neoplasms; Anxiety Disorders; Prostatic Hyperplasia; Hyperplasia; Prostatic Diseases; Physiological Effects of Drugs; Central Nervous System Depressants; Peripheral Nervous System Agents; Analgesics; Sensory System Agents; Anesthetics, General; Anesthetics; Analgesics, Non-Narcotic; Anesthetics, Inhalation; Nitrous Oxide
• Other Study ID Numbers: 2021P-000715

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: IPD is not intended to be shared to personnel outside of pre-defined research staff.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No