Modulating Influence of State Anxiety on the Effect of Midazolam on Postsurgical Pain

Abstract

Anxiety contributes to postsurgical pain, and midazolam is frequently prescribed preoperatively. Conflicting results have been described concerning the impact of midazolam on pain. This study aims to evaluate the effect of systemic midazolam on pain after open inguinal hernia repair, clarifying its relationship with preoperative anxiety. A prospective observational cohort study was conducted in three Portuguese ambulatory units between September 2018 and March 2020. Variable doses of midazolam were administered. Postsurgical pain was evaluated up to three months after surgery. We enrolled 306 patients and analyzed 281 patients. The mean preoperative anxiety Numeric Rating Scale score was 4 (3) and the mean Surgical Fear Questionnaire score was 22 (16); the mean midazolam dose was 1.7 (1.1) mg with no correlation to preoperative anxiety scores. Pain ≥4 was present in 67% of patients 24 h after surgery and in 54% at seven days; at three months, 27% were classified as having chronic postsurgical pain. Preoperative anxiety correlated to pain severity at all time points. In multivariable regression, higher midazolam doses were associated with less pain during the first week, with no apparent effect on chronic pain. However, subgroup analyses uncovered an effect modification according to preoperative anxiety: the decrease in acute pain occurred in the low-anxiety patients with no effect on the high-anxiety group. Inversely, there was an increase in chronic postsurgical pain in the very anxious patients, without any effect on the low-anxiety group. Midazolam, generally used as an anxiolytic, might impact distinctively on pain depending on anxiety.