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      Preincisional administration of intravenous or subcutaneous infiltration of low-dose ketamine suppresses postoperative pain after appendectomy

      , ,

      Journal of Pain Research

      Dove Medical Press

      pain, postoperative, analgesia, ketamine, appendectomy

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          Abstract

          Background

          Ketamine, an N-methyl-D-aspartate receptor antagonist, can suppress hyperalgesia and allodynia. The purpose of the present study was to evaluate the clinical efficacy of preincisional intravenous or subcutaneous infiltration of ketamine for postoperative pain relief after appendectomy.

          Methods

          Ninety patients, aged 18–60 years, scheduled for appendectomy was enrolled in this study. Patients were divided into three groups of 30 each and received subcutaneous infiltration of ketamine 0.5 mg/kg (KS), intravenous ketamine 0.5 mg/kg (KI), or subcutaneous infiltration of normal saline 3 mL (C) before surgery. Visual analog scale (VAS) values and analgesic consumption were evaluated for 24 hours after surgery.

          Results

          VAS scores were significantly lower at the time of arrival in the recovery room, and at 10, 20, and 30 minutes thereafter in group KI and group KS compared with group C ( P < 0.05). VAS scores were not significantly different between group KI and group KS at these intervals. Postoperative VAS scores were significantly lower at 6, 12, 18, and 24 hours in group KI compared with group C ( P < 0.05). In group KS, the postoperative VAS score was significantly lower at 6 hours ( P < 0.05). VAS scores were significantly lower at 12, 18, and 24 hours after surgery in group KI compared with group KS ( P < 0.05).

          Conclusion

          A 0.5 mg/kg dose of ketamine given at approximately 15 minutes before surgery by the intravenous route provided analgesia for 24 hours after surgery in patients undergoing appendectomy.

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          Most cited references 26

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          Ketamine and postoperative pain--a quantitative systematic review of randomised trials.

          Ketamine, an N-methyl-D-aspartate receptor antagonist, is known to be analgesic and to induce psychomimetic effects. Benefits and risks of ketamine for the control of postoperative pain are not well understood. We systematically searched for randomised comparisons of ketamine with inactive controls in surgical patients, reporting on pain outcomes, opioid sparing, and adverse effects. Data were combined using a fixed effect model. Fifty-three trials (2839 patients) from 25 countries reported on a large variety of different ketamine regimens and surgical settings. Sixteen studies tested prophylactic intravenous ketamine (median dose 0.4 mg/kg, range (0.1-1.6)) in 850 adults. Weighted mean difference (WMD) for postoperative pain intensity (0-10 cm visual analogue scale) was -0.89 cm at 6 h, -0.42 at 12 h, -0.35 at 24 h and -0.27 at 48 h. Cumulative morphine consumption at 24 h was significantly decreased with ketamine (WMD -15.7 mg). There was no difference in morphine-related adverse effects. The other 37 trials tested in adults or children, prophylactic or therapeutic ketamine orally, intramuscularly, subcutaneously, intra-articulary, caudally, epidurally, transdermally, peripherally or added to a PCA device; meta-analyses were deemed inappropriate. The highest risk of hallucinations was in awake or sedated patients receiving ketamine without benzodiazepine; compared with controls, the odds ratio (OR) was 2.32 (95%CI, 1.09-4.92), number-needed-to-harm (NNH) 21. In patients undergoing general anaesthesia, the incidence of hallucinations was low and independent of benzodiazepine premedication; OR 1.49 (95%CI 0.18-12.6), NNH 286. Despite many published randomised trials, the role of ketamine, as a component of perioperative analgesia, remains unclear.
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            Adding ketamine to morphine for intravenous patient-controlled analgesia for acute postoperative pain: a qualitative review of randomized trials.

            In experimental trials, ketamine has been shown to reduce hyperalgesia, prevent opioid tolerance, and lower morphine consumption. Clinical trials have found contradictory results. We performed a review of randomized, double-blinded clinical trials of ketamine added to opioid in i.v. patient-controlled analgesia (PCA) for postoperative pain in order to clarify this controversy. Our primary aim was to compare the effectiveness and safety of postoperative administered ketamine in addition to opioid for i.v. PCA compared with i.v. PCA with opioid alone. Studies were identified from the Cochrane Library 2003, MEDLINE (1966-2009), and EMBASE (1980-2009) and by hand-searching reference lists from review articles and trials. Eleven studies were identified with a total of 887 patients. Quality and validity assessment was performed on all trials included using the Oxford Quality Scale with an average quality score of 4.5. Pain was assessed using visual analogue scales or verbal rating scales. Six studies showed significant improved postoperative analgesia with the addition of ketamine to opioids. Five studies showed no significant clinical improvement. For thoracic surgery, the addition of ketamine to opioid for i.v. PCA was superior to i.v. PCA opioid alone. The combination allows a significant reduction in pain score, cumulative morphine consumption, and postoperative desaturation. The benefit of adding ketamine to morphine in i.v. PCA for orthopaedic or abdominal surgery remains unclear. Owing to huge heterogeneity of studies and small sample sizes, larger double-blinded randomized studies showing greater degree of homogeneity are required to confirm these findings.
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              A comparison of gabapentin and ketamine in acute and chronic pain after hysterectomy.

              Gabapentin and ketamine are popular analgesic adjuvants for improving perioperative pain management. We designed this double-blind, placebo-controlled study to test and compare the preventive effects of perioperative ketamine and gabapentin on early and chronic pain after elective hysterectomy. Sixty patients undergoing abdominal hysterectomy were randomly assigned to 1 of the following 3 groups: control group received oral placebo capsules and bolus plus infusion of saline; ketamine group received oral placebo capsules and, before incision, 0.3 mg/kg IV bolus and 0.05 mgxkg(-1)xh(-1) infusion of ketamine until the end of surgery; and gabapentin group received oral gabapentin 1.2 g and bolus plus infusion of saline. The anesthetic technique was standardized, and the postoperative assessments included verbal rating scales for pain and sedation, IV morphine usage, quality of recovery assessment, recovery of bowel function, resumption of normal activities, and patient satisfaction with their pain management. Patients were questioned at 1, 3, and 6 mo after surgery for chronic postoperative pain. Postoperative pain scores were significantly lower in the gabapentin group compared with the ketamine and control groups, and patient-controlled analgesia morphine use was significantly reduced in both treatment groups (versus control group) (P < 0.001). Total patient-controlled analgesia morphine use was decreased by 35% and 42% in the ketamine and gabapentin groups, respectively, compared with the control group (P < 0.001). Patient satisfaction with pain treatment was significantly improved in the ketamine and gabapentin groups compared with the control group (P < 0.001). The incidence of incisional pain and related pain scores at the 1-, 3-, and 6-mo follow-up were significantly lower in the gabapentin group compared with the ketamine and control groups (P < 0.001). Gabapentin and ketamine are similar in improving early pain control and in decreasing opioid consumption; however, gabapentin also prevented chronic pain in the first 6 postoperative months.
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                Author and article information

                Journal
                J Pain Res
                J Pain Res
                Journal of Pain Research
                Dove Medical Press
                1178-7090
                2012
                30 December 2011
                : 5
                : 1-6
                Affiliations
                Anesthesiology and Critical Care Research Center, Isfahan University of Medical Sciences, Isfahan, Iran
                Author notes
                Correspondence: Mohammadreza Safavi, Anesthesiology and Critical Care Research Center, Isfahan University of Medical Sciences, Isfahan, Iran, Tel +98 91 3315 2416, Email safavi@ 123456med.mui.ac.ir
                Article
                jpr-5-001
                10.2147/JPR.S26476
                3273401
                22328829
                © 2012 Honarmand et al, publisher and licensee Dove Medical Press Ltd.

                This is an Open Access article which permits unrestricted noncommercial use, provided the original work is properly cited.

                Categories
                Original Research

                Anesthesiology & Pain management

                ketamine, postoperative, analgesia, pain, appendectomy

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