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Background: An optimal opioid-sparing multimodal analgesic regimen to treat severe pain can enhance recovery after total knee arthroplasty. The hypothesis was that adding five recently described intravenous and regional interventions to multimodal analgesic regimen can further reduce opioid consumption.Methods: In a double-blinded fashion, 78 patients undergoing elective total knee arthroplasty were randomized to either (1) a control group (n = 39) that received spinal anesthesia with intrathecal morphine, periarticular local anesthesia infiltration, intravenous dexamethasone, and a single injection adductor canal block or (2) a study group (n = 39) that received the same set of analgesic treatments plus five additional interventions: local anesthetic infiltration between the popliteal artery and capsule of the posterior knee, intraoperative intravenous dexmedetomidine and ketamine, and postoperatively, one additional intravenous dexamethasone bolus and two additional adductor canal block injections. The primary outcome measure was 24-h cumulative opioid consumption after surgery and secondary outcomes were other analgesics, patient recovery, functional outcomes, and adverse events.Results: Opioid consumption was not different between groups at 24 h (oral morphine equivalents, mean ± SD; study: 23.7 ± 18.0 mg vs. control: 29.3 ± 18.7 mg; mean difference [95% CI], -5.6 mg [-2.7 to 13.9]; P = 0.189) and all other time points after surgery. There were no major differences in pain scores, quality of recovery, or time to reach rehabilitation milestones. Hypotensive episodes occurred more frequently in the study group (25 of 39 [64.1%] vs. 13 of 39 [33.3%]; P = 0.010).Conclusions: In the presence of periarticular local anesthesia infiltration, intrathecal morphine, single-shot adductor canal block and dexamethasone, the addition of five analgesic interventions-local anesthetic infiltration between the popliteal artery and capsule of the posterior knee, intravenous dexmedetomidine, intravenous ketamine, an additional intravenous dexamethasone dose, and repeated adductor canal block injections-failed to further reduce opioid consumption or pain scores or to improve functional outcomes after total knee arthroplasty.Editor’s Perspective: [ABSTRACT FROM AUTHOR]

Synthetic cannabinoids are compounds made in the laboratory to structurally and functionally mimic phytocannabinoids from the Cannabis sativa L. plant, including delta-9-tetrahydrocannabinol (THC). Synthetic cannabinoids (SCs) can signal via the classical endogenous cannabinoid system (ECS) and the greater endocannabidiome network, highlighting their signalling complexity and far-reaching effects. Dronabinol and nabilone, which mimic THC signalling, have been approved by the Food and Drug Administration (FDA) for treating nausea associated with cancer chemotherapy and/or acquired immunodeficiency syndrome (AIDS). However, there is ongoing interest in these two drugs as potential analgesics for a variety of other clinical conditions, including neuropathic pain, spasticity-related pain, and nociplastic pain syndromes including fibromyalgia, osteoarthritis, and postoperative pain, among others. In this review, we highlight the signalling mechanisms of FDA-approved synthetic cannabinoids, discuss key clinical trials that investigate their analgesic potential, and illustrate challenges faced when bringing synthetic cannabinoids to the clinic. [ABSTRACT FROM AUTHOR]

Background: Intrathecal morphine is commonly and effectively used for analgesia after joint arthroplasty, but has been associated with delayed respiratory depression. Patients with obstructive sleep apnea may be at higher risk of postoperative pulmonary complications. However, data is limited regarding the safety of intrathecal morphine in this population undergoing arthroplasty.Methods: This retrospective cohort study aimed to determine the safety of intrathecal morphine in 1,326 patients with documented or suspected obstructive sleep apnea undergoing hip or knee arthroplasty. Chart review was performed to determine clinical characteristics, perioperative events, and postoperative outcomes. All patients received neuraxial anesthesia with low-dose (100 μg) intrathecal morphine (exposure) or without opioids (control). The primary outcome was any postoperative pulmonary complication including: (1) respiratory depression requiring naloxone; (2) pneumonia; (3) acute respiratory event requiring consultation with the critical care response team; (4) respiratory failure requiring intubation/mechanical ventilation; (5) unplanned admission to the intensive care unit for respiratory support; and (6) death from a respiratory cause. The authors hypothesized that intrathecal morphine would be associated with increased postoperative complications.Results: In 1,326 patients, 1,042 (78.6%) received intrathecal morphine. The mean age of patients was 65 ± 9 yr and body mass index was 34.7 ± 7.0 kg/m. Of 1,326 patients, 622 (46.9%) had suspected obstructive sleep apnea (Snoring, Tired, Observed, Pressure, Body Mass Index, Age, Neck size, Gender [STOP-Bang] score greater than 3), while 704 of 1,326 (53.1%) had documented polysomnographic diagnosis. Postoperatively, 20 of 1,322 (1.5%) patients experienced pulmonary complications, including 14 of 1,039 (1.3%) in the exposed and 6 of 283 (2.1%) in the control group (P = 0.345). Overall, there were 6 of 1 322 (0.5%) cases of respiratory depression, 18 of 1,322 (1.4%) respiratory events requiring critical care team consultation, and 4 of 1,322 (0.3%) unplanned intensive care unit admissions; these rates were similar between both groups. After adjustment for confounding, intrathecal morphine was not significantly associated with postoperative pulmonary complication (adjusted odds ratio, 0.60 [95% CI, 0.24 to 1.67]; P = 0.308).Conclusions: Low-dose intrathecal morphine, in conjunction with multimodal analgesia, was not reliably associated with postoperative pulmonary complications in patients with obstructive sleep apnea undergoing joint arthroplasty. [ABSTRACT FROM AUTHOR]