The objective of this systematic review was to evaluate the efficacy and tolerability of perioperative gabapentin administration for the control of acute postoperative pain. We searched Medline (1966-2006), the Cochrane Library (2006), Scopus, CINAHL and bibliographies from clinical trials and review articles. We included randomized controlled trials (RCTs) comparing gabapentin with inactive controls in surgical patients. Sixteen valid RCTs were included. Weighted mean difference (WMD) for postoperative pain intensity (0-100 mm visual analogue scale) was -16.55 mm at 6 h and -10.87 mm at 24 h for treatment with a single preoperative dose of gabapentin 1200 mg. Cumulative opioid consumption at 24 h was also significantly decreased with gabapentin (WMD, -27.90 mg). When gabapentin was administered at doses less than 1200 mg, pain intensity was also lower at 6 h (WMD, -22.43 mm) and 24 h (WMD, -13.18 mm). Cumulative 24 h opioid consumption was also lower (WMD, -7.25 mg). Gabapentin was associated with an increased risk of sedation (Peto OR 3.86; 95% CI 2.50-5.94) but less opioid-related side effects such as vomiting (Peto OR 0.58; 95% CI 0.39-0.86) and pruritus (Peto OR 0.27; 95% CI 0.10-0.74). In conclusion, gabapentin has an analgesic and opioid-sparing effect in acute postoperative pain management when used in conjunction with opioids.

Multimodal analgesia is advocated for perioperative pain management to reduce opioid use and its associated adverse effects. Serotonin and norepinephrine are involved in the modulation of endogenous analgesic mechanisms via descending inhibitory pain pathways in the brain and spinal cord. An increase in serotonin and norepinephrine may increase inhibition of nociceptive input and improve pain relief. Duloxetine, a selective serotonin and norepinephrine reuptake inhibitor, has demonstrated efficacy in chronic pain conditions such as painful diabetic neuropathy and post-herpetic neuralgia. The objective of the study was to evaluate the efficacy of duloxetine in reducing morphine requirements in patients after knee replacement surgery. Fifty patients received either two doses of oral duloxetine 60 mg (2 h before surgery and on first postoperative day) or placebo. All patients received patient-controlled analgesia with morphine for 48 h after operation. Pain and adverse effects were assessed at 0.5, 1, 2, 6, 12, 24, and 48 h after surgery on an 11-point numeric rating scale. Twenty-three patients in the duloxetine group and 24 patients in the placebo group completed the study. Morphine requirements during the 48 h after surgery were significantly lower in the duloxetine group [19.5 mg, standard deviation (sd) 14.5 mg] compared with the placebo group (30.3 mg, sd 18.1 mg) (P=0.017). There were no statistically significant differences between the groups in pain scores (at rest and on movement) or in adverse effects. Perioperative administration of duloxetine reduced postoperative morphine requirements during the first 48 h after knee replacement surgery, without significant adverse effects.

COX2-selective and nonselective (ns) nonsteroidal anti-inflammatory drugs (NSAIDs) are widely used for chronic pain management. There are marked differences in the risk of adverse gastrointestinal (GI) and cardiovascular (CV) events among different NSAIDs. In 2017, publication of two randomized controlled trials and an individual patient-data meta-analysis provided robust data on the relative GI and CV tolerability profiles of currently available NSAIDs. The PRECISION study showed similar CV-event rates with celecoxib vs naproxen and ibuprofen, but GI tolerability was better for celecoxib. In the CONCERN study of high-GI-risk patients, celecoxib was associated with fewer adverse GI-tract events than naproxen. The meta-analysis showed no significant difference between celecoxib and ns-NSAIDs in the rate of acute myocardial infarction, and celecoxib was the only COX2-selective NSAID with a lower risk of adverse CV and GI events vs ns-NSAIDs. These data add to the body of knowledge about the relative tolerability of different NSAIDs and were used to propose an updated treatment algorithm. The decision about whether to use an NSAID and which one should be based on a patient’s risk of developing adverse GI and CV events. Lower- and upper-GI-tract events need to be considered. Celecoxib has a better lower-GI-tract tolerability profile than ns-NSAIDs plus a proton-pump inhibitor. In addition, the latest data suggest that long-term use of celecoxib 200 mg/day may be appropriate for patients at increased CV risk.

The use of selective 5-hydroxytryptamine type 3 receptor antagonists has improved the management of postoperative nausea and vomiting, but has not completely eliminated it. In this article, we discuss the pharmacology of 5-hydroxytryptamine type 3 receptor antagonists and the impact of pharmacogenetics on postoperative nausea and vomiting. Dolasetron, granisetron, ondansetron, palonosetron, and tropisetron have similar mechanisms of action but different pharmacokinetic and pharmacodynamic properties. Genetic polymorphism in the cytochrome P450 mono-oxygenase system, drug efflux transporter adenosine triphosphate-binding cassette subfamily B member 1 and 5-hydroxytryptamine type 3 receptor subunits also contribute to the interindividual variation in response to different 5-hydroxytryptamine type 3 receptor antagonists. These differences account for differences in the duration of action and clinical efficacy of these agents. Pharmacogenetics testing in patients may help differentiate responders to 5-hydroxytryptamine type 3 receptor antagonists from non-responders and allow the anesthesiologist to individualize antiemetic therapy. The cost-effectiveness of such screening in postoperative nausea and vomiting management has, however, not been evaluated. Given the multifactorial nature of postoperative nausea and vomiting, a multimodal approach to reduce or eliminate risk factors will be most successful in its management.

Oral amitriptyline, a tricyclic antidepressant, is effective for treating neuropathic pain. We conducted a double-blind, randomized, placebo-controlled crossover study to evaluate the efficacy of topical 5% amitriptyline and 5% lidocaine in treating patients with neuropathic pain. Thirty-five patients with postsurgical neuropathic pain, postherpetic neuralgia, or diabetic neuropathy with allodynia or hyperalgesia were assigned to receive 3 topical creams (5% amitriptyline, 5% lidocaine, or placebo) in random sequence. The primary outcome measure was change in pain intensity (baseline vs. posttreatment average pain) using a 0 to 100 mm Visual Analog Scale. Secondary outcome measures included the McGill Pain Questionnaire, requirement for rescue medication, and patient satisfaction. Primary statistical comparisons were made with paired t tests or signed-rank tests. A reduction in pain intensity was observed with topical lidocaine (P<0.05). No significant change in pain intensity was found with topical amitriptyline or placebo. In pairwise comparison of treatments, topical lidocaine and placebo each reduced pain more than topical amitriptyline (P<0.05). This randomized, placebo-controlled crossover study examining topical 5% amitriptyline and 5% lidocaine in the treatment of neuropathic pain showed that topical lidocaine reduced pain intensity but the clinical improvement is minimal and that topical 5% amitriptyline was not effective.