Helena Ostović, Brankica Šimac, Marko Pražetina, Nikola Bradić, Jasminka Peršec
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引用次数: 0
Abstract
Background: Colorectal resections are associated with a pronounced inflammatory response, severe postoperative pain, and postoperative ileus. The aim of this study was to evaluate the main effects of lidocaine and ketamine, and their interaction in colorectal cancer (CRC) patients after open surgery. The interaction could be additive if the effect of 2 drugs given in combination equals the sum of their individual effects, or multiplicative if their combined effect exceeds the sum of their individual effects. We hypothesized that the combination of lidocaine and ketamine might reduce the inflammatory response additively or synergistically.
Methods: Eighty-two patients undergoing elective open colorectal resection were randomized to receive either lidocaine or placebo and either ketamine or placebo in a 2 × 2 factorial design. After induction of general anesthesia, all subjects received an intravenous bolus (lidocaine 1.5 mg/kg and/or ketamine 0.5 mg/kg and/or a matched saline volume) followed by a continuous infusion (lidocaine 2 mg·kg -1 ·h -1 and/or ketamine 0.2 mg·kg -1 ·h -1 and/or a matched saline volume) until the end of surgery. Primary outcomes were serum levels of white blood cell (WBC) count, interleukins (IL-6, IL-8), and C-reactive protein (CRP) measured at 2 time points: 12 and 36 hours after surgery. Secondary outcomes included intraoperative opioid consumption; visual analog scale (VAS) pain scores at 2, 4, 12, 24, 36, and 48 hours postoperatively; cumulative analgesic consumption within 48 hours after surgery; and time to first bowel movement. We assessed the main effects of each of lidocaine and ketamine and their interaction on the primary outcomes using linear regression analyses. A Bonferroni-adjusted significance level was set at .05/8 = .00625 for primary analyses.
Results: No statistically significant differences were observed with either lidocaine or ketamine intervention in any of the measured inflammatory markers. No multiplicative interaction between the 2 treatments was confirmed at 12 or 36 hours after surgery: WBC count, P = .870 and P = .393, respectively; IL-6, P = .892 and P = .343, respectively; IL-8, P = .999 and P = .996, respectively; and CRP, P = .014 and P = .445, respectively. With regard to inflammatory parameters, no evidence of additive interactions was found. Lidocaine and ketamine, either together or alone, significantly reduced intraoperative opioid consumption versus placebo, and, except for lidocaine alone, improved pain scores. Neither intervention significantly influenced gut motility.
Conclusions: Our study results do not support the use of an intraoperative combination of lidocaine and ketamine in patients undergoing open surgery for CRC.
期刊介绍:
Anesthesia & Analgesia exists for the benefit of patients under the care of health care professionals engaged in the disciplines broadly related to anesthesiology, perioperative medicine, critical care medicine, and pain medicine. The Journal furthers the care of these patients by reporting the fundamental advances in the science of these clinical disciplines and by documenting the clinical, laboratory, and administrative advances that guide therapy. Anesthesia & Analgesia seeks a balance between definitive clinical and management investigations and outstanding basic scientific reports. The Journal welcomes original manuscripts containing rigorous design and analysis, even if unusual in their approach.