Daily Anesthesiology Research Analysis

BACKGROUND: Gabapentin is an anticonvulsant medication with approval for use in neuropathic pain and epileptic disorders. It is frequently added to multimodal analgesic regimens during and after surgery to reduce opioid use while controlling pain effectively. There is little evidence to show its effectiveness in major surgery. METHODS: In this multicenter, double-blinded randomized controlled trial, adults undergoing major cardiac, thoracic, or abdominal surgery were randomized to receive either gabapentin (600 mg before surgery, 300 mg twice daily for 2 days after surgery) or placebo. The primary outcome was length of hospital stay. Secondary outcomes included acute and chronic pain, total opioid use, adverse health events, and health-related quality of life. Patients were followed up daily in-hospital until discharge and then at 4 weeks and 4 months after surgery. RESULTS: A total of 1,196 participants were randomized (500 underwent cardiac, 346 thoracic, and 350 abdominal surgery); 596 were allocated to placebo, and 600 were allocated to gabapentin. Median length of hospital stay was similar in the two groups (gabapentin, 5.94 [interquartile range (IQR), 4.08 to 8.04] days; placebo, 6.15 [IQR, 4.22 to 8.97] days; hazard ratio, 1.07; 95% CI, 0.95 to 1.20; P = 0.26). Overall, 384 participants experienced one or more serious adverse events (gabapentin, 189 of 596 [31.7%]; placebo, 195 of 599 [32.6%]), with some variation across surgical specialties. CONCLUSIONS: Among patients undergoing major cardiac, thoracic, and abdominal surgery, adding gabapentin to multimodal analgesic regimes did not alter the length of hospital stay or the number of serious adverse events.

BACKGROUND: Multimodal analgesia (MMA) is a perioperative pain management strategy that targets various pain pathways, resulting in reduced postoperative pain and opioid use. Unfortunately, the optimal combinations of pain medications to use with perioperative MMA remain uncertain. Our goal was to estimate the treatment effect of MMA on postoperative pain and opioid use and identify optimal non-opioid medication combinations to enhance MMA benefits. METHODS: The study population includes all patients undergoing elective non-cardiac surgery with general anesthesia between 1 January 2017 and 31 December 2022 at six geographically similar Veterans Health Administration hospitals. An instrumental variable (IV) analysis was conducted using the anesthesiologist as the instrument to emulate randomization to receiving specific pain medication combinations. Outcomes were self-reported pain and opioid use after surgery. RESULTS: Of the 23 238 procedures included in the study, 46.1% received MMA. MMA was more common in younger patients, females and those with a lower probability of mortality. With IV analysis, inpatients with MMA required 6.8 fewer oral morphine equivalents (OMEs, 95% CI -10.2, to -3.4) in the postoperative period, and outpatients with MMA reported postoperative pain scores that were, on average, 1.0 unit lower than patients who did not receive MMA (95% CI -1.6 to -0.4). Combinations of non-steroidal anti-inflammatory drugs (NSAIDs) plus dexamethasone or regional anesthesia resulted in the greatest reductions in postoperative opioid use (mean reduction -29.5 OMEs, 95% CI -36.9 to -19.5 and mean reduction -28.4 OMEs, 95% CI -40.1 to -16.8, respectively). CONCLUSION: Our findings further support existing evidence on the effectiveness of MMA in reducing postoperative pain and opioid use following non-cardiac surgery. Importantly, our study highlights that dexamethasone and NSAIDs, not acetaminophen, which is almost universally used in MMA regimens, resulted in the greatest reduction of postoperative pain and postoperative opioid use. This has significant implications for the continued use of NSAIDs and dexamethasone in MMA protocols and underscores the need for future studies exploring the independent effect of intravenous acetaminophen on postoperative pain.

BACKGROUND: Activation of nociceptive pathways by surgical trauma can induce central sensitization, which is associated with greater pain severity and persistence. The N -methyl- d -aspartate receptor antagonist ketamine blocks central sensitization but has a variable track record for preventing postsurgical pain. Patient-level factors contribute to variability in pain and may serve as markers of differential efficacy of preventive effect. METHODS: This prospective, longitudinal randomized controlled trial investigated the effectiveness of intraoperatively administered ketamine to decrease postoperative pain after breast surgery. Before surgery, patients reported demographic and medical information and completed validated pain and psychosocial questionnaires. A subset of patients also underwent quantitative sensory testing to assess baseline temporal summation of pain (central sensitization tendency). Analyses of covariance, controlling for relevant pre- and perioperative factors, examined treatment group (ketamine vs . saline) differences in 2-week postoperative pain outcomes. Exploratory moderation analysis explored whether the efficacy of ketamine differed based on patients' baseline temporal summation of pain. RESULTS: Of the sample of 225 patients, 113 received ketamine, and 112 received placebo. The majority of patients underwent lumpectomy (53%), with 16% undergoing mastectomy and 30% mastectomy with reconstruction. There were no significant treatment group differences in pain severity or impact reported 2 weeks after surgery. However, moderation analysis revealed that among patients with higher baseline temporal summation of pain, ketamine was associated with lower pain severity and impact scores. CONCLUSIONS: Ketamine was not associated with an analgesic benefit over placebo in the acute postoperative period, as measured using a variety of pain assessments. However, exploratory moderation analysis suggested that patients with evidence of a greater central sensitization at baseline may derive an analgesic effect of ketamine. These findings support future collection of baseline phenotypic patient characteristics related to relevant mechanisms in trials to identify which patients may derive a larger benefit from analgesic interventions.