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    Avaliação do efeito da s(+)cetamina associada a remifentanila na dor e hiperalgesia pós-operatória em colecistectomia videolaparoscópica: estudo randomizado, duplo-cego
    (Universidade Federal de São Paulo (UNIFESP), 2014-11-26) Leal, Plinio da Cunha [UNIFESP]; Sakata, Rioko Kimiko [UNIFESP]; Universidade Federal de São Paulo (UNIFESP)
    The use of remifentanil results in short-term analgesic effect and is related to the phenomenon of opioid induced hyperalgesia. Some mechanisms have been proposed to explain the phenomenon of hyperalgesia, including the activation of N-methyl-Daspartate (NMDA). The association of blocking NMDA receptor, S(+)ketamine, to remifentanil can promote better analgesia and longer duration. The aim of this study was to determine if the association of ketamine to remifentanil promotes better postoperative analgesia and reduces postoperative hyperalgesia, evaluated with algometer, monofilaments and cytokine dosage. Methods: The study was a prospective, randomized, double-blind clinical trial, including 60 patients ≥ 18 years of age submitted to laparoscopic cholecystectomy. Anesthesia was induced with remifentanil (1 μg.Kg-1), propofol and atracurium. Patients in G1 received remifentanil (0.4 μg.Kg-1.min-1) and ketamine (5 μg.Kg-1.min-1); patients in G2 received remifentanil (0.4 μg.Kg-1.min-1) and normal saline. The dose was increased or decreased as needed. The infusion of the solutions was continued until skin closure. Postoperative pain was treated with morphine PCA. The parameters evaluated were: time to first PCA complementation; total morphine consumption in 24 h; intensity of postoperative pain; hyperalgesia using algometer and monofilaments; allodynia using soft brush; extent of hyperalgesia using a 300g monofilament; and inflammatory respose through interleukin 6, 8 and 10 dosage. Adverse effects were noted. Results: There was no difference in demographic characteristics between the groups, as well as the duration of surgery, anesthesia and time to awakening. There was no statistically significant difference in time for the morphine dose requirement between G1 (18 min) and G2 (15 min), or in pain intensity at the evaluation period. There was no statistically significant difference between groups in the dose of remifentanil, as well as the total dose of morphine consumption (27.4 ± 18.3 mg for G1 and 27.7 ± 12.9 mg for G2). There was a statistically significant difference in hyperalgesia evaluated with monofilaments in the thenar eminence of the hand 24 hours after surgery (p = 0.019, student's t test), with a lower sensitivity threshold seen in patients in group 2. No statistically significant difference was observed in hyperalgesia evaluated with algometer, allodynia with soft brush or in the extent of hyperalgesia. There was no statistical difference in interleukin 6, 8 and 10 dosage between the groups at the evaluation times. Regarding adverse effects, there was a statistically significant difference in visual changes, sedation and vomiting, with a higher rate in G1. Conclusions: The association of ketamine (5 μg.kg- 1.min-1) to remifentanil for laparoscopic cholecystectomy did not change postoperative pain intensity, time to first supplementary analgesia or total dose of morphine in 24 hours, although it was promoted a reduction in hyperalgesia evaluated using monifilaments in the thenar eminence of the hand 24 hours after surgery; there was no statistical difference in hyperalgesia seen using a algometer, allodynia using a soft brush and in IL-6, IL-8 e IL-10 dosage