Anxiety and Fear, Benign Prostatic Hyperplasia, Malignancy, Pain, Prostate Adenocarcinoma, Prostate Cancer, Prostate Disease
Conditions
Keywords
prostate biopsy, nitrous oxide, prostate cancer, ambulatory, patient experience of care
Brief summary
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.
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.
Interventions
Nitrous oxide administered at concentrations of mild sedation (20-45%) for the duration of prostate biopsy.
OTHEROxygen
Oxygen will be administered at 10 Liters/min for the duration of prostate biopsy.
Sponsors
Brigham and Women's Hospital
Beth Israel Deaconess Medical Center
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
SUPPORTIVE_CARE
Masking
DOUBLE (Subject, Caregiver)
Masking description
The operating urologist and study participant will be blinded to group assignment for the duration of the study.
Intervention model description
Subjects will be randomized 1:1 to either SANO (treatment) or oxygen (placebo control) after completion of baseline assessment. The results of the randomization will not be disclosed to patients as part of the study (patient-blinded).
Eligibility
Sex/Gender
MALE
Age
18 Years to 85 Years
Healthy volunteers
Yes
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Post-biopsy Pain (VAS-P) | 5-minutes after prostate biopsy | Pain experienced immediately following prostate biopsy as measured by a Visual Analog Scale for Pain (VAS-P) (range: 0 \[no pain\] - 10 \[worst pain\]) |
| Post-biopsy Anxiety (VAS-A) | 5-minutes after prostate biopsy | Anxiety experienced immediately following prostate biopsy as measured by a Visual Analog Scale for Anxiety (VAS-A) (range: 0 \[no anxiety\] - 10 \[worst anxiety\]) |
| Post-biopsy Anxiety Traits (STAI) | 5-minutes after prostate biopsy | Anxious traits exhibited after prostate biopsy as measured by the State Trait Anxiety Inventory (STAI) (range: 6-36; 36 being 'worst' anxiety). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Time of Prostate Biopsy | Length of prostate biopsy; up to 30 minutes | Length of procedure will be compared between arms to assess whether SANO significantly lengthens prostate biopsy |
| Operator Assessment of Patient Tolerance of Procedure | Immediately after prostate biopsy; within 5 minutes after completion of biopsy. | 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). |
| Operator Assessment of Tolerating Insertion of Rectal Probe | Immediately after prostate biopsy; within 5 minutes after completion of biopsy. | 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). |
| Operator Assessment of Patient Maintenance of Positioning | Immediately after prostate biopsy; within 5 minutes after completion of biopsy. | 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). |
Countries
United States
Participant flow
Pre-assignment details
Of note, 143 patients were consented for procedure, but only 133 were randomized. This discrepancy was due to study staff availability or patient cancellation of procedure.
Participants by arm
| Arm | Count |
|---|---|
| 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.
Self-Administered Nitrous Oxide: Nitrous oxide administered at concentrations of mild sedation (20-45%) for the duration of prostate biopsy. | 61 |
| Oxygen Patients will receive 100% oxygen at 10 Liters/minute for the duration of prostate biopsy.
Oxygen: Oxygen will be administered at 10 Liters/min for the duration of prostate biopsy. | 67 |
| Total | 128 |
Baseline characteristics
| Characteristic | Self-Administered Nitrous Oxide | Oxygen | Total |
|---|---|---|---|
| Age, Continuous | 64.5 years STANDARD_DEVIATION 11.5 | 65.8 years STANDARD_DEVIATION 7.8 | 65.2 years STANDARD_DEVIATION 9.7 |
| History of Prostate Cancer Prior to Enrollment | 26 Participants | 17 Participants | 43 Participants |
| Past Medical History of Anxiety | 10 Participants | 10 Participants | 20 Participants |
| Past Medical History of Depression | 7 Participants | 10 Participants | 17 Participants |
| Pre-Biopsy STAI | 12 units on a scale | 12 units on a scale | 12 units on a scale |
| Pre-Biopsy VAS-Anxiety | 3 units on a scale | 2 units on a scale | 2 units on a scale |
| Pre-Biopsy VAS-Pain | 0 units on a scale | 0 units on a scale | 0 units on a scale |
| Race/Ethnicity, Customized Black/African American | 8 participants | 9 participants | 17 participants |
| Race/Ethnicity, Customized Other | 3 participants | 2 participants | 5 participants |
| Race/Ethnicity, Customized White | 50 participants | 56 participants | 106 participants |
| Region of Enrollment United States | 61 Participants | 67 Participants | 128 Participants |
| Sex: Female, Male Female | 0 Participants | 0 Participants | 0 Participants |
| Sex: Female, Male Male | 61 Participants | 67 Participants | 128 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 61 | 0 / 67 |
| other Total, other adverse events | 1 / 61 | 2 / 67 |
| serious Total, serious adverse events | 0 / 61 | 0 / 67 |
Outcome results
Primary
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).
Time frame: 5-minutes after prostate biopsy
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Self-Administered Nitrous Oxide | Post-biopsy Anxiety Traits (STAI) | 11 score on a scale |
| Oxygen | Post-biopsy Anxiety Traits (STAI) | 12 score on a scale |
Primary
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 \[worst anxiety\])
Time frame: 5-minutes after prostate biopsy
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Self-Administered Nitrous Oxide | Post-biopsy Anxiety (VAS-A) | 0 score on a scale |
| Oxygen | Post-biopsy Anxiety (VAS-A) | 1 score on a scale |
Primary
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 \[worst pain\])
Time frame: 5-minutes after prostate biopsy
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Self-Administered Nitrous Oxide | Post-biopsy Pain (VAS-P) | 1 score on a scale |
| Oxygen | Post-biopsy Pain (VAS-P) | 1 score on a scale |
Secondary
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).
Time frame: Immediately after prostate biopsy; within 5 minutes after completion of biopsy.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Self-Administered Nitrous Oxide | Operator Assessment of Patient Maintenance of Positioning | 2 score on a scale |
| Oxygen | Operator Assessment of Patient Maintenance of Positioning | 2 score on a scale |
Secondary
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).
Time frame: Immediately after prostate biopsy; within 5 minutes after completion of biopsy.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Self-Administered Nitrous Oxide | Operator Assessment of Patient Tolerance of Procedure | 2 score on a scale |
| Oxygen | Operator Assessment of Patient Tolerance of Procedure | 2 score on a scale |
Secondary
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).
Time frame: Immediately after prostate biopsy; within 5 minutes after completion of biopsy.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Self-Administered Nitrous Oxide | Operator Assessment of Tolerating Insertion of Rectal Probe | 2 score on a scale |
| Oxygen | Operator Assessment of Tolerating Insertion of Rectal Probe | 2 score on a scale |
Secondary
Time of Prostate Biopsy
Length of procedure will be compared between arms to assess whether SANO significantly lengthens prostate biopsy
Time frame: Length of prostate biopsy; up to 30 minutes
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Self-Administered Nitrous Oxide | Time of Prostate Biopsy | 10.6 minutes |
| Oxygen | Time of Prostate Biopsy | 10.3 minutes |