ABSTRACT
INTRODUCTION: Adding adjuvants to local wound infiltration (LWI) provides long analgesic duration with fewer adverse effects. We aimed to compare the clinical effects of nalbuphine and ketorolac as an adjuvant to LWI in patients undergoing open colorectal cancer surgery. METHOD: A total of 126 ASA I-III patients aged ≥ 18 years who were scheduled for open colorectal cancer surgery were included. Patients were randomly assigned to receive LWI using 10 mL 0.75% ropivacaine, with 20 mL normal saline (group R), 10 mg nalbuphine in 1 mL (group RN), or 25 mg ketorolac in 0.8 mL (group RK). Analgesia duration was the primary outcome. The total 48-h postoperative morphine-equivalent consumption and additional rescue analgesia rates were recorded as key secondary outcomes. RESULTS: Among 126 patients randomized, 124 completed the trial. The duration until the first press of the analgesia pump was significantly shorter in group R (median: 320.0 min) compared with group RN (median: 829.5 min) and group RK (median: 820.0 min) (P < 0.001). The median difference in morphine consumption was 113.0 mg for group R vs. group RN (P < 0.001), and 115.5 mg for group R vs. group RK (P < 0.001). The proportion of patients using additional morphine within the first day after surgery in group R showed a higher relative risk (RR) compared with group RN (RR, 3.89; P = 0.001) and group RK (RR, 3.17; P = 0.001). There were no apparent differences between the RN and RK groups in any outcomes, whether in adjusted or unadjusted analysis. CONCLUSIONS: Among patients undergoing open colorectal cancer surgery, both nalbuphine and ketorolac infiltration achieved equally prolonged duration of analgesia and reduced morphine consumption compared with ropivacaine alone after surgery, suggesting that the equivalent analgesic dose of nalbuphine and ketorolac as local anesthetic adjuvants in LWI could have a similar analgesic effect. TRIAL REGISTRATION: ChiCTR1800019209.
ABSTRACT
INTRODUCTION: Evidence on the use of inhaled methoxyflurane in the management of trauma pain is conflicting and obfuscated. This study aimed to determine the efficacy and safety of inhaled methoxyflurane for trauma pain on the basis of published randomized controlled trials (RCTs). METHODS: RCTs assessing the efficacy of methoxyflurane in adults or adolescents with acute trauma pain published in PubMed, Web of Science, Embase, Cochrane Library, and Google Scholar were searched. The control groups were those that received placebo or standard analgesic treatment (SAT). The primary outcome was the change from baseline in pain scores during the first 30 min of treatment. Secondary outcomes included time to first pain relief, the proportion of patients experiencing pain relief, rescue analgesia rate, the treatment satisfaction of patients and investigators, and the methoxyflurane-related treatment-emergent adverse events (TEAEs). RESULTS: A total of nine RCTs (1806 patients) were identified. Results revealed that methoxyflurane provided a clinically unimportant benefit by improving the mean difference of change from baseline in pain intensity (from - 0.44 to - 1.23 cm, p < 0.001) at various time points within the first 20 min compared to control treatment. Besides, methoxyflurane decreased the time of onset of pain relief (mean difference - 5.29 min; 95% CI - 6.97 to - 3.62) and the proportion of patients who needed rescue analgesic medication (risk ratio 1.41; 95% CI 1.17-1.70) despite it increasing the risk of non-severe TEAEs (risk ratio 3.09; 95% CI 1.72-5.57). Notably, the benefit of almost all secondary pain-related outcomes was rendered clinically nonsignificant between methoxyflurane and SAT strata besides the time of onset of pain relief. The quality of evidence was low or very low in all outcomes. CONCLUSIONS: In emergency situations without effective therapy, this systematic review and meta-analysis provides low-quality evidence that methoxyflurane can be used as a rapid-acting and effective treatment for acute trauma pain, although its utilization is associated a risk of non-severe TEAEs. However, the current evidence does not support the notion that inhaled methoxyflurane offered superior analgesic efficacy to SAT. CLINICAL TRIAL NUMBER: PROSPERO registration number CRD42020223000.