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Self-Adjusted Nitrous Oxide (SANO) during Transrectal Prostate Biopsy: A Survey of Recalled Pain
Michelle R. Shabo, MD1*, Abigail J. Escobar, BS1*, K. Mikayla Flowers, MA2, Suprita Krishna, MD1, Alejandro Abello, MD, MPH1, Boris Gershman, MD1, Andrew A. Wagner, MD1, Aria F. Olumi, MD1, Kristin L. Schreiber, MD, PhD2, Heidi J. Rayala, MD, PhD1.
*These two authors have contributed equally.
1Beth Israel Deaconess Medical Center, Boston, MA, USA, 2Brigham and Women's Hospital, Boston, MA, USA.

Introduction: Studies suggest that a patient's memory of pain may differ significantly from pain reported at the time of a painful procedure. Currently, it is unclear whether a patient's recollection of pain after prostate biopsy changes over time, and whether this impacts willingness to undergo a future prostate biopsy. We previously reported that Self-Adjusted Nitrous Oxide (SANO) is associated with lower pain during transrectal prostate biopsy when compared to oxygen placebo. However, sedation with nitrous oxide has an amnestic effect, which may impact recalled pain and willingness to undergo future biopsy. In the current analysis, we compared patients' recalled pain from prostate biopsy to the pain score they reported the day of the biopsy. We also assessed willingness to undergo this procedure again with or without SANO.
Materials & Methods: A single-center PRCT comparing SANO vs. Oxygen in addition to routine peri-prostatic block was conducted with 128 patients undergoing transrectal prostate biopsy between 12/2021-9/2022. A follow-up survey was sent 4-14 months post-procedure to assess participants' recalled experience of the prostate biopsy. Recalled intra-procedural pain was compared with day-of score (0-10). Patient expectations vs. experience of biopsy was assessed using a 10-point Likert scale (range: -5 [much worse than expected] to 5 [much better than expected]). Willingness to undergo a repeat biopsy, with and without the option to receive SANO, was assessed using a 4-point Likert scale (range: 1 [very unwilling] to 4 [very willing]).
Results: 68.8% of study participants completed the follow-up survey (n=88). Median time elapsed between survey completion and prostate biopsy was 8 months (IQR 6-10 months). Average recalled pain was higher than the day-of biopsy reported pain for all participants (recalled: 4.22 vs. day-of: 1.31; p <0.001). The difference between recalled pain and day-of pain was significantly lower in the SANO vs. Oxygen group, such that patients in the SANO group reported a smaller change in recalled pain compared to their day of-scores (SANO 0.9 → 3.8 vs. Oxygen 1.4 → 4.6; p <0.001). Patients who received SANO reported a significantly "better than expected" experience during prostate biopsy (0.8 vs. -0.45; p=0.037). As time from biopsy increased, patients were more likely to report "better than expected" experience (β=-0.256; p=0.016). Of all participants, 58.6% were willing to undergo a future biopsy regardless of SANO being offered, though 26.4% were willing only if SANO was available. In both groups, patients with higher recalled pain were less willing to undergo a repeat biopsy (p <0.001). Regardless of group assignment, 65.9% of participants preferred to receive SANO for future biopsy.
Conclusions: Patients recollect greater pain from prostate biopsy than they report on the day of the procedure, which has implications for design of future studies of prostate biopsy tolerance. Our findings that patients would prefer to undergo future prostate biopsy with SANO suggest the need for an additional analgesia to supplement the routine peri-prostatic block.

Table 1. Primary and Secondary Outcomes
Primary Measures1Total SANO n = 40Oxygen n = 48Test StatisticP
Patient-reported Pain
Prior non-study biopsy26.3 (2.5)5.9 (2.8)6.7 (2.3)179.50.421
Day of study biopsy1.2 (1.4)0.9 (1.2)1.4 (1.5)777.50.107
Study biopsy recall4.2 (2.7)3.8 (2.9)4.6 (2.4)793.50.16
Paired difference (Δ)33.1 (2.6)2.9 (2.8)3.2 (2.5)-7.249<0.001
Biopsy expectations vs. experience0.1 (2.4)0.8 (2.6)-0.4 (2.1)720.00.037
Secondary Measures4
Willing to undergo repeat prostate biopsy3.2080.361
With or without SANO51 (58.6%)23 (59%)28 (58.3%)
Only with SANO23 (26.4%)12 (30.8%)11 (22.9%)
Only without SANO7 (8%)1 (2.6%)6 (12.5%)
Unwilling6 (6.9%)3 (7.7%)3 (6.3%)
Perceived group assignment3.6670.16
Correct37 (42%)13 (32.5%)24 (50%)
Incorrect27 (30.7%)16 (40%)11 (22.9%)
Unsure24 (27.3)11 (27.5%)13 (27.1%)
Preference for SANO during repeat biopsy58 (65.9%)27 (67.5%)31 (64.6%)0.1210.941
SANO, self-adjusted nitrous oxide. 1Mean (standard deviation); Mann-Whitney U test 2Total, n = 41; SANO, n = 20; Oxygen, n = 21 3Wilcox Rank Sum Test 4Frequency (percent %); Pearson's Chi-Square test


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