Self-adjusted nitrous oxide eases pain during transrectal prostate biopsy

Patient use of self-adjusted nitrous oxide (N₂O) at levels of 20 percent to 45 percent during transrectal prostate biopsy is safe and well tolerated, according to a study. Delivery of low-dose N₂O is associated with reduced pain, but its effect on anxiety does not seem significant.

“These results suggest that the option of adjuvant N₂O may improve patients’ experience of care as they undergo diagnostic evaluation for prostate cancer,” the researchers said.

A total of 133 patients undergoing transrectal prostate biopsies were enrolled in this single-institution, prospective, double-blind, randomized controlled trial. Participants were randomly assigned to receive either self-adjusted N₂O (n=66) or oxygen (n=67), in addition to routine periprostatic bupivacaine block. N₂O at levels between 20 percent and 45 percent were adjusted to the patients’ desired effect.

A visual analogue scale (VAS) for anxiety (State Trait Anxiety Inventory) and a VAS for pain immediately before and after biopsy were completed by the participants. A blinded operating urologist assessed the ease of procedure. The researchers also evaluated the periprocedural vitals and complications. After the procedure, patients were allowed to drive home on their own.

No significant difference was observed in the State Trait Anxiety Inventory or the VAS for anxiety scores between the N₂O and oxygen groups. However, those who use self-adjusted N₂O reported lower pain scores than did those receiving oxygen (p=0.026). [J Urol 2024;211:214-222]

Side effects

In terms of tolerability, the operating urologists’ rating of the procedure showed better scores for patients in the N₂O group (p=0.03). Biopsy performance time did not significantly differ between the N₂O and oxygen groups. Additionally, complications were low between the two groups.

“When assessing the safety of N₂O, it is important to consider both potential side effects for patients and risks to practitioners,” the researchers said. “Although this study found no significant complications in the 61 men who received self-adjusted N₂O, common side effects of receiving ≤50 percent N₂O can include headache, dizziness, and nausea (<2 percent).” [Sci Transl Med 2021;13:eabe1376]

Previous studies also revealed risks of occupational exposure to N₂O, resulting in reduced utilization of N₂O in medical procedures in the US. For instance, a 1992 study of female dental assistants reported reduced fertility following exposure to high levels of unscavenged N₂O. [N Engl J Med 1992;327:993-997]

“This same study did not find reduced fecundability when using N₂O with a scavenging system,” the researchers said. “The Nitrouseal system used at this study’s institution is self-scavenging, and personal N₂O badge monitors for operators demonstrate levels that are well within acceptable limits.”

Limitations

Earlier studies also pointed to rectal probe insertion as the greatest sources of pain during prostate biopsy. [N Z Med J 2008;121:39-43]

In the current study, the operating urologist reported no significant difference in ease of rectal probe insertion between the two groups. However, one limitation was the N₂O was initiated at 20 percent. Although a mean maximum of 39 percent was achieved, “this was generally at a time after probe insertion.”

“Thus, this current study may not have reached sufficient analgesia before rectal probe insertion,” the researchers said.

“In follow-up protocols, self-adjusted N₂O was initiated at 30 percent prior to the intervention, which appears to provide improved analgesia. Future studies should investigate the optimal mechanism and timing for titration of optimal N₂O concentrations,” they added.