IMPORTANCE Harms and benefits of opioids for chronic noncancer pain remain unclear. OBJECTIVE To systematically review randomized clinical trials (RCTs) of opioids for chronic noncancer pain. DATA SOURCES AND STUDY SELECTION The databases of CENTRAL, CINAHL, EMBASE, MEDLINE, AMED, and PsycINFO were searched from inception to April 2018 for RCTs of opioids for chronic noncancer pain vs any nonopioid control. DATA EXTRACTION AND SYNTHESIS Paired reviewers independently extracted data. The analyses used random-effects models and the Grading of Recommendations Assessment, Development and Evaluation to rate the quality of the evidence. MAIN OUTCOMES AND MEASURES The primary outcomes were pain intensity (score range, 0-10 cm on a visual analog scale for pain; lower is better and the minimally important difference [MID] is 1 cm), physical functioning (score range, 0-100 points on the 36-item Short Form physical component score [SF-36 PCS]; higher is better and the MID is 5 points), and incidence of vomiting. RESULTS Ninety-six RCTs including 26 169 participants (61% female; median age, 58 years [interquartile range, 51-61 years]) were included. Of the included studies, there were 25 trials of neuropathic pain, 32 trials of nociceptive pain, 33 trials of central sensitization (pain present in the absence of tissue damage), and 6 trials of mixed types of pain. Compared with placebo, opioid use was associated with reduced pain (weighted mean difference [WMD], −0.69 cm [95% CI, −0.82 to −0.56 cm] on a 10-cm visual analog scale for pain; modeled risk difference for achieving the MID, 11.9% [95% CI, 9.7% to 14.1%]), improved physical functioning (WMD, 2.04 points [95% CI, 1.41 to 2.68 points] on the 100-point SF-36 PCS; modeled risk difference for achieving the MID, 8.5% [95% CI, 5.9% to 11.2%]), and increased vomiting (5.9% with opioids vs 2.3% with placebo for trials that excluded patients with adverse events during a run-in period). Low-to moderate-quality evidence suggested similar associations of opioids with improvements in pain and physical functioning compared with nonsteroidal anti-inflammatory drugs (pain: WMD, −0.60 cm [95% CI, −1.54 to 0.34 cm]; physical functioning: WMD, −0.90 points [95% CI, −2.69 to 0.89 points]), tricyclic antidepressants (pain: WMD, −0.13 cm [95% CI, −0.99 to 0.74 cm]; physical functioning: WMD, −5.31 points [95% CI, −13.77 to 3.14 points]), and anticonvulsants (pain: WMD, −0.90 cm [95% CI, −1.65 to −0.14 cm]; physical functioning: WMD, 0.45 points [95% CI, −5.77 to 6.66 points]). CONCLUSIONS AND RELEVANCE In this meta-analysis of RCTs of patients with chronic noncancer pain, evidence from high-quality studies showed that opioid use was associated with statistically significant but small improvements in pain and physical functioning, and increased risk of vomiting compared with placebo. Comparisons of opioids with nonopioid alternatives suggested that the benefit for pain and functioning may be similar, although the evidence was from studies of only low to moderate quality.

BACKGROUND: Drugs such as propofol and ketamine are used alone or in combination to provide sedation for medical procedures in children. The purpose of this systematic review was to compare the safety and effectiveness of propofol and ketamine to other drug regimens. METHODS: We searched Medline, Embase, Cochrane Central Register of Controlled Trials (CENTRAL), Cochrane Database of Systematic Reviews (CDSR), Web of Science, and the grey literature (meta-Register of Controlled Trials, ClinicalTrials.gov, and Google Scholar) for randomized controlled studies comparing intravenous propofol and ketamine to any other single or combination drug regimen administered to children undergoing diagnostic or therapeutic procedures. Meta-analyses were performed for primary (hemodynamic and respiratory adverse events) and secondary outcomes using RevMan 5.3. We assessed the risk of bias and the certainty (quality) evidence for all outcomes using Grading of Recommendations Assessment, Development and Evaluation (GRADE) methodology. RESULTS: Twenty-nine studies were included for analysis. Based on low-to-moderate quality evidence, we concluded that the use of propofol and ketamine may result in a slight-to-small reduction in the risk of hypotension, bradycardia, and apnea, and a slight increase in the risk of tachycardia, hypertension, and other respiratory adverse events, such as cough or laryngospasm. The ratio of propofol to ketamine and comparator drug regimen subgroups effects were important for desaturation and some secondary outcomes. CONCLUSIONS: The use of propofol and ketamine had a minimal effect on the incidence of adverse events and other secondary outcomes. Large-scale studies are required to more accurately estimate adverse event rates and the effects of propofol and ketamine on patient-important outcomes.

Background In the perioperative period, intravenous lidocaine has been used as an opioid-sparing systemic analgesic with additional anti-inflammatory and anti-hyperalgesic properties. Objective The aim of this retrospective study was to review the utilization, efficacy, and safety of intravenous lidocaine on our Acute Pain Service (APS) and identify surgical and patient populations where this intervention was found to be useful. Patients and Methods This retrospective study was designed to assess acute pain management in patients who received an intravenous lidocaine infusion between February 2013 and December 2017. Data collected included demographics, surgery type, infusion duration, pain scores, analgesic consumption, and adverse effects. Pain scores included rest and active pain scores and were analyzed by surgical model and subgroups. Clinically important differences (CIDs) in pain were determined by changes in pain score difference of ≥ 2 (11-point scale) or ≥ 30% reduction in pain intensity. A patient was considered to have a true CID if a CID was observed with rest and/or active pain scores at both first to second (4-24 h) and first to final time point (4 h to infusion end) comparisons. Results In total, 544 patients received intravenous lidocaine during this period, and 394 were included in the final analysis. The average (± standard deviation) duration of infusion was 68.60 ± 49.52 h. Surgical specialties included gastrointestinal surgery (41%), orthopedics (28%), neurosurgery (15%), vascular surgery (10%), and others (6%). Overall, 56.1% of the study population experienced a CID, with reduced pain scores at rest and/or with activity. CIDs were also observed in patients with chronic pain (53.5%) and when intravenous lidocaine was used as a rescue technique (69.6%). Within the rescue cohort, opioid-dependent and opioid-naïve patients experienced 23.0% and 45.6% reductions, respectively, in their 8-h intravenous opioid consumption. In total, 37 patients in the study experienced transient signs of mild local anesthetic toxicity, which resolved with infusion titration (conservative) management. One serious adverse event required intervention, and the patient was successfully resuscitated. Conclusions This retrospective study at a single institution with an APS policy for intravenous lidocaine in the postoperative period identifies benefits of intravenous lidocaine in certain surgical and patient populations. The findings need to be confirmed with further research.