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Item Open Access Epidural ketamine for postoperative analgesia(Springer Verlag, 1998-02) Sandler, Alan, N.; Schmid, Roger; Katz, JoelTwo factors have increased interest in ketamine for postoperative analgesia. The first was the discovery of the N-Methyl-D-asparrate (NMDA) receptor and its role in central pain processing and spinal cord neural plasticity.1 Ketamine is one of two clinically useful NMDA receptor antagonists available (the other is dextromethorphan). Ketamine binds non-competitively to the PCI, (phencyclidine) recognition site in the NMDA receptor channel2. In addition, interest in the concept of preemptive analgesia makes ketamine a natural candidate for investigation of ...Item Open Access Postoperative Morphine Use and Hyperalgesia Are Reduced by Preoperative but Not Intraoperative Epidural Analgesia: Implications for Preemptive Analgesia and the Prevention of Central Sensitization(Lippincott, Williams and Wilkins, 2003) Katz, Joel; Cohen, Lorenzo; Schmid, Roger; Chan, Vincent; Wowk, AdaroseBackground: The aim of this study was to evaluate the postoperative morphine-sparing effects and reduction in pain and secondary mechanical hyperalgesia after preincisional or postincisional epidural administration of a local anesthetic and an opioid compared with a sham epidural control. Methods: Patients undergoing major gynecologic surgery by laparotomy were randomly assigned to three groups and studied in a double-blinded manner. Group 1 received epidural lidocaine and fentanyl before incision and epidural saline 40 min after incision. Group 2 received epidural saline before incision and epidural lidocaine and fentanyl 40 min after incision. Group 3 received a sham epidural control (with saline injected into a catheter taped to the back) before and 40 min after incision. All patients underwent surgery with general anesthesia. Results: One hundred forty-one patients completed the study (group 1, n = 45; group 2, n = 49; group 3, n = 47). Cumulative patient-controlled analgesia morphine consumption at 48 h was significantly lower (P = 0.04) in group 1 (89.8 ± 43.3 mg) than group 3 (112.5 ± 71.5 mg) but not group 2 (95.4 ± 60.2 mg), although the hourly rate of morphine consumption between 24 and 48 h after surgery was significantly lower (P < 0.0009) in group 1 (1.25 ± 0.02 mg/h) than group 2 (1.41 ± 0.02 mg/h). Twenty-four hours after surgery, the visual analog scale pain score on movement was significantly less intense (P = 0.005) in group 1 (4.9 ± 2.2 cm) than group 3 (6.0 ± 2.6 cm) but not group 2 (5.3 ± 2.5 cm), and the von Frey pain threshold near the wound was significantly higher (P = 0.03) in group 1 (6.4 ± 0.6 log mg) than in group 3 (6.1 ± 0.8 log mg) but not group 2 (6.2 ± 0.7 log mg). Conclusions: Preincisional administration of epidural lidocaine and fentanyl was associated with a significantly lower rate of morphine use, lower cumulative morphine consumption, and reduced hyperalgesia compared with a sham epidural condition. These results highlight the importance of including a standard treatment control group to avoid the problems of interpretation that arise when two-group studies of preemptive analgesia (preincisional vs. postsurgery) fail to find the anticipated effects.Item Open Access Pre-emptive analgesia using intravenous fentanyl plus low-dose ketamine for radical prostatectomy under general anesthesia does not produce short-term or long-term reductions in pain or analgesic use(Elsevier, 2004) Katz, Joel; Schmid, Roger; Snijdelaar, Dirk G.; Coderre, Terence; McCartney, Colin J. L.; Wowk, AdaroseThe aim of the study was to evaluate post-operative pain and analgesic use after pre-operative or post-incisional i.v. fentanyl plus low dose i.v. ketamine vs. a standard treatment receiving i.v. fentanyl but not ketamine. Men undergoing radical prostatectomy under general anesthesia were randomly assigned in a double-blinded manner to one of three groups. Patients received i.v. fentanyl before incision followed by an i.v. bolus dose (0.2 ml kg−1) and an i.v. infusion (0.0025 ml kg−1 min−1) of 1 mg ml−1 ketamine (group 1) or normal saline (groups 2 and 3). Seventy minutes after incision, patients received i.v. fentanyl followed by an i.v. bolus dose (0.2 ml kg−1) and an i.v. infusion (0.0025 ml kg−1 min−1) of saline (groups 1 and 3) or ketamine (group 2). Pain, von Frey pain thresholds, and cumulative morphine consumption using patient-controlled analgesia (PCA) were assessed up to 72 h after surgery. 143 patients completed the study (group 1, n=47; group 2, n=50; group 3, n=46). Cumulative PCA morphine (mean±SD) did not differ significantly among groups (group 1, 92.3±45.9 mg; group 2, 107.2±58.4 mg; group 3, 103.6±50.4 mg; P=0.08 for groups 1 vs. 2, and groups 1 vs. 3). On day 3, the hourly rate (mean±SEM) of morphine consumption was significantly lower (P<0.0009) in group 1 (0.61±0.013 mg h−1) than group 2 (0.86±0.011 mg h−1) and group 3 (0.89±0.008 mg h−1). Pain scores and von Frey pain thresholds did not differ significantly among groups. Two-week and 6-month follow-ups did not reveal significant group differences in pain incidence, intensity, disability or mental health. Pre-operative, low-dose administration of i.v. ketamine did not result in a clinically meaningful reduction in pain or morphine consumption when compared with post-incisional administration of ketamine or a saline control conditionItem Open Access The Stability of a Ketamine-Morphine Solution(Lippincott, Williams and Wilkins, 2002) Schmid, Roger; Koren, Gideon; Klein, Julia; Katz, JoelRecent advances in acute pain mechanisms and management have implicated the N-methyl D-aspartate receptor-ion channel complex in the development of postoperative hyperalgesia and acute opioid tolerance. N-methyl D-aspartate receptor antagonists such as ketamine have been used increasingly in clinical studies in an effort to minimize acute postoperative pain and reduce opioid requirements. A mixture of ketamine and an opioid administered in the same solution and syringe would be a practical and useful technique for postoperative epidural analgesia, continuous IV infusion, or patient-controlled IV analgesia. We investigated the stability of a morphine sulfate and racemic ketamine solution in saline at pH 5.5–7.5 over a period of 4 days. Our study demonstrates that the ketamine-morphine mixture at a clinically relevant concentration seems to be stable at room temperature, at a wide range of pH values, for at least 4 days.