Venous Cannulation Pain as a Marker of Postoperative Pain Vulnerability: A Pre-Specified Secondary Analysis of a Randomized Controlled Trial

<b>Background</b>: Identification of patients at risk and prevention of acute postoperative pain (APOP) are central to individualized anesthesia and analgesia. Venous cannulation pain (VCP) has shown promise as a predictor of APOP. In the PeriOPerative Individualization Trial (POPIT), VCP was evaluated as a pain-sensitivity stratification method to guide anesthesia and reduce postoperative pain. This report presents a predefined secondary analysis with the primary aim to evaluate VCP as a method for postoperative pain prediction. As a secondary aim, we sought to explore factors that influence VCP. <b>Methods</b>: 271 patients were stratified into two cohorts, high-risk (VCP ≥ 2.0) and low-risk (VCP < 2.0), for APOP, based on their VCP. Within each group, patients were randomized to receive either: standard care or opioid-free anesthesia (low-risk cohort), and standard care or multimodal anesthesia with opioids (high-risk cohort). Differences in acute and persistent pain, quality of recovery, postoperative opioid consumption, and proportion of patients experiencing moderate to severe APOP depending on VCP levels were investigated. The predictive capacity of VCP was evaluated and adjusted for in terms of potential confounders. <b>Results</b>: High-risk patients, grading VCP ≥ 2.0 (VAS units) experienced more APOP on the day of surgery (difference 0.9 NRS-units, 95% CI 0.2-1.6, <i>p</i> = 0.009) and after 24 h during movement (difference 0.6 NRS-units, 95% CI 0.0-1.3, <i>p</i> = 0.048). Patients grading VCP < 2.0 had better quality of recovery after 24 hr (difference 7, 95% 1-13, <i>p</i> = 0.002) and lower postoperative opioid consumption (difference 7.5 mg, 95% 5.7-9.3, <i>p</i> < 0.001). The OR for VCP ≥ 2.0 to predict APOP in PACU was 1.76 (95% CI 1.02-3.04, <i>p</i> = 0.043), but in a multivariate model, adjusted for age, VCP ≥ 2, gender, pain catastrophizing, preoperative pain, and pain on the day of surgery, female gender was the only independent predictor of APOP (OR 2.65 (95% CI 1.33-5.29), <i>p</i> = 0.006). <b>Conclusions</b>: Pain during venous cannulation as a predictor of acute pain after surgery was significant in univariate regression, but the results were lost when adjusting for confounders like gender and current pain. However, VCP continues to show potential in associated postoperative recovery outcomes such as opioid consumption. The level of pain associated with venous cannulation is influenced by gender, preoperative pain, and current pain on the day of surgery. Pain sensitivity stratification needs refinement before implementation in clinical practice.