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Objective: The aim of this study was to determine the association between gabapentinoids on the day of surgery and adverse postoperative outcomes in patients undergoing colorectal surgery in the United States., Background: Gabapentinoids, gabapentin and pregabalin, are recommended in multimodal analgesia protocols for acute postoperative pain management after colorectal surgery. However, current literature focuses on the efficacy in reducing opioid consumption, but provides limited information about adverse risks., Methods: This was a retrospective study including 175,787 patients undergoing elective colorectal surgery using the Premier database between 2009 and 2014. Multilevel regression models measured associations of receipt of gabapentinoids with naloxone use after surgery, non-invasive ventilation (NIV), invasive ventilation (IMV), hospital length of stay (LOS), and parental morphine equivalents (PMEs) on the day of surgery and on the day before discharge., Results: Overall, 4677 (2.7%) patients received gabapentinoids on the day of surgery, with use doubling (1.7% in 2009 to 4.3% in 2014). Compared with patients who were unexposed to ganapentinoids, gabapentinoid exposure was associated with lower PMEs on the day of surgery [-2.7 mg; 95% confidence interval (CI), -5.2 to -0.0 mg], and with higher odds of NIV [odds ratio (OR) 1.22, 95% CI, 1.00-1.49] and receipt of naloxone (OR 1.58, 95% CI, 1.11-2.26). There was no difference between the groups with respect to IMV or PMEs on the day before discharge., Conclusions: Although use of gabapentinoids on the day of surgery was associated with slightly lower PMEs on the day of surgery, it was associated with higher odds of NIV and naloxone use after surgery.

Background: The Opioid Safety Initiative decreased high-dose prescriptions across the Veterans Health Administration. This study sought to examine the impact of this intervention (i.e., the Opioid Safety Initiative) on pain scores and opioid prescriptions in patients undergoing total knee arthroplasty., Methods: This was an ecological study of group-level data among 700 to 850 patients per month over 72 consecutive months (January 2010 to December 2015). The authors examined characteristics of cohorts treated before versus after rollout of the Opioid Safety Initiative (October 2013). Each month, the authors aggregated at the group-level the differences between mean postoperative and preoperative pain scores for each patient (averaged over 6-month periods), and measured proportions of patients (per 1,000) with opioid (and nonopioid) prescriptions for more than 3 months in 6-month periods, preoperatively and postoperatively. The authors compared postintervention trends versus trends forecasted based on preintervention measures., Results: After the Opioid Safety Initiative, patients were slightly older and sicker, but had lower mortality rates (postintervention n = 28,509 vs. preintervention n = 31,547). Postoperative pain scores were slightly higher and the decrease in opioid use was statistically significant, i.e., 871 (95% CI, 474 to 1,268) fewer patients with chronic postoperative prescriptions. In time series analyses, mean postoperative minus preoperative pain scores had increased from 0.65 to 0.81, by 0.16 points (95% CI, 0.05 to 0.27). Proportions of patients with chronic postoperative and chronic preoperative opioid prescriptions had declined by 20% (n = 3,355 vs. expected n = 4,226) and by 13% (n = 5,861 vs. expected n = 6,724), respectively. Nonopioid analgesia had increased. Sensitivity analyses confirmed all findings., Conclusions: A system-wide initiative combining guideline dissemination with audit and feedback was effective in significantly decreasing opioid prescriptions in populations undergoing total knee arthroplasty, while minimally impacting pain scores.

Chronic postsurgical pain impacts most amputees, with more than half experiencing neuralgic residual limb pain. The transition from normal acute postamputation pain to chronic residual limb pain likely involves both peripheral and central inflammatory mechanisms. As part of the Veterans Integrated Pain Evaluation Research study, we investigated links between systemic inflammatory mediator levels and chronic residual limb pain. Subjects included 36 recent active duty military traumatic amputees with chronic residual limb pain and 40 without clinically significant pain. Blood samples were obtained and plasma concentrations of an array of inflammatory mediators were analyzed. Residual limb pain intensity and pain catastrophizing were assessed to examine associations with inflammatory mediators. Pro-inflammatory mediators including tumor necrosis factor (TNF)-α, TNF-β, interleukin (IL)-8, ICAM-1, Tie2, CRP, and SAA were elevated in patients with chronic residual limb pain. Across all patients, residual limb pain intensity was associated positively with levels of several proinflammatory mediators (IL-8, TNF-α, IL-12, TNF-β, PIGF, Tie2, SAA, and ICAM-1), and inversely with concentrations of the anti-inflammatory mediator IL-13, as well as IL-2 and Eotaxin-3. Pain catastrophizing correlated positively with IL-8, IL-12, TNF-β, PIGF, and ICAM-1, and inversely with IL-13. Significant associations between catastrophizing and residual limb pain intensity were partially mediated by TNF-α, TNF- β, SAA, and ICAM-1 levels. Results suggest that chronic postamputation residual limb pain is associated with excessive inflammatory response to injury or to inadequate resolution of the postinjury inflammatory state. Impact of pain catastrophizing on residual limb pain may be because of part to common underlying inflammatory mechanisms., Competing Interests: Authors have no financial conflicts of interest to report.

Purpose of Review: Surgical incision invariably causes some measure of nerve damage and inflammatory response that, in most cases, heals quickly without long-term negative consequence. However, a subset of these patients go on to develop lasting neuropathic pain that is difficult to treat and, in many cases, prevents the return to normal activities of life. It remains unknown why two patients with identical surgical interventions may go on to develop completely divergent pain phenotypes or no pain at all. Aggressive, early analgesic therapy has been shown to reduce the incidence of chronic postsurgical pain (CPSP), but no specific regional anesthetic technique or systemic pharmacologic therapy has been shown to prevent CPSP., Recent Findings: Inflammation and glial cell activation have recently been shown to be just as important in the transition from normal acute pain to pathologic chronic pain as nerve injury itself and that central sensitization may not be solely due to repetitive nociceptive firing at the time of nerve injury. This has opened a number of new therapeutic possibilities for prevention of CPSP., Summary: Here, we discuss the causes of CPSP and current useful preventive strategies in the perioperative period. We also discuss future potential disease-modifying treatments of CPSP.