1.
Whole-Course Application of Dexmedetomidine Combined with Ketorolac in Nonnarcotic Postoperative Analgesia for Patients with Lung Cancer Undergoing Thoracoscopic Surgery: A Randomized Control Trial.
Miao, Z, Wu, P, Wang, J, Zhou, FC, Lin, Y, Lu, XY, Lv, R, Hou, QH, Wen, QP
Pain physician. 2020;(2):E185-E193
Abstract
BACKGROUND Opioid-based postoperative analgesia provides adequate analgesia with much adverse effects and immunosuppression. Dexmedetomidine and ketorolac have properties of opioid-sparing, antiinflammation, and immune protection. OBJECTIVES To investigate the efficacy and safety of whole-course application of dexmedetomidine combined with ketorolac in nonnarcotic postoperative analgesia and its effect on inflammatory response and immune function in thoracoscopic surgery of lung cancer. STUDY DESIGN Double-blind, randomized control trial. SETTING The First Affiliated Hospital of Dalian Medical University, Dalian, Liaoning, China. METHODS Sixty patients scheduled for thoracoscopic surgery were enrolled and randomly divided into 2 groups to receive a combination of intraoperative usage of dexmedetomidine and postoperative patient-controlled intravenous analgesia of dexmedetomidine 0.1 µg/kg/h and ketorolac 3 mg/kg (DEX group) or only postoperative patient-controlled intravenous analgesia of sufentanil 1.5 µg/kg and ketorolac 3 mg/kg (SUF group) for 48 hours. Vital signs, postoperative Visual Analog Scale (VAS) score, Ramsay sedation score, patient-controlled analgesia pressing times, consumption of sufentanil and rescue drug, and complications were compared between the 2 groups. The levels of inflammatory factors and immune function were also compared. RESULTS A significant reduction in median blood pressures and heart rates within 48 hours after surgery and perioperative consumption of sufentanil were observed in the DEX group compared with the SUF group (P < 0.05). No statistically significant difference was found in VAS scores, patient-controlled analgesia pressing times, and rescue drug consumption between the 2 groups (P > 0.05). The incidence of nausea was significantly lower in the DEX group compared with the SUF group (P < 0.05). A significant decrease of interleukin (IL)-1 beta, IL-6, tumor necrosis factor (TNF)-alpha, and increased CD4+ and CD4+/CD8+ were observed in the DEX group compared with the SUF group at 24 and 48 hours after surgery (P < 0.05). There was no difference in the levels of CD8+ and natural killer cells between the 2 groups (P > 0.05). LIMITATIONS This study was limited by its sample size. CONCLUSIONS Whole-course application of dexmedetomidine combined with ketorolac in nonnarcotic postoperative analgesia provided adequate and safe postoperative analgesia, reduced sufentanil consumption, analgesia-related complications, alleviated inflammatory response, and immunosuppression compared with sufentanil-based analgesia in thoracoscopic surgery. KEY WORDS Dexmedetomidine, ketorolac, sufentanil, thoracoscopic surgery, postoperative analgesic, patient-controlled analgesia, inflammatory response, immune function.
2.
Comparison Between the Effects of Intravenous Morphine, Tramadol, and Ketorolac on Stress and Immune Responses in Patients Undergoing Modified Radical Mastectomy.
Bakr, MA, Amr, SA, Mohamed, SA, Hamed, HB, Abd El-Rahman, AM, Mostafa, MA, El Sherif, FA
The Clinical journal of pain. 2016;(10):889-97
Abstract
OBJECTIVES Analgesics had been suspected of impairing various immune functions either directly or indirectly. Our primary objective was to compare the effects of intravenous (IV) morphine, tramadol, and ketorolac on stress and immune responses in patients who underwent modified radical mastectomy. PATIENTS Sixty patients randomly assigned to receive IV morphine 5 mg (group M, n=20), tramadol 100 mg (group T, n=20), or ketorolac 60 mg (group K, n=20) at the end of surgery. METHODS Serum cortisol, prolactin were measured immediately, 40 minutes, and 24 hours postoperatively. Expressions of peripheral T lymphocytes (CD3, CD3CD4, CD3CD8) and natural killer cells (CD3, CD56) were measured as percentages of total lymphocytes by flow cytometry immediately, 90 minutes, and 24 hours postoperatively. RESULTS After 40 minutes, cortisol level increased but prolactin decreased significantly (P=0.001), then both decreased after 24 hours (P=0.001) compared with baseline within the 3 groups. CD3, CD4, CD8, and CD56 significantly decreased at 90 minutes and 24 hours (P≤0.033) compared with baseline in the 3 groups. CD4, CD8, and CD56 significantly decreased in group M, compared with group T and K (P≤0.016) and CD3, CD8, and CD56 in group T compared with group K at 90 minutes (P≤0.024) postoperatively. After 24 hours, CD4, and CD8 decreased in group M compared with group T (P≤0.048) and CD4 and CD56 in groups M and T compared with group K (P≤0.049). CONCLUSIONS IV morphine, tramadol, and ketorolac suppressed stress and immune responses. Ketorolac was the least immunosuppressive among the 3 drugs.
3.
Plasma levels of interleukin-6 and interleukin-10 are affected by ketorolac as an adjunct to patient-controlled morphine after abdominal hysterectomy.
Kim, MH, Hahm, TS
The Clinical journal of pain. 2001;(1):72-7
Abstract
OBJECTIVE Because morphine affects various immune functions, patient-controlled analgesia with morphine may further deteriorate the immune mechanisms after surgery. Therefore, the purpose of this study was to determine differences between morphine patient-controlled analgesia and a combination of morphine and ketorolac in interleukin-6 and interleukin-10 responses, and in analgesia and morphine-related side effects. DESIGN Prospective study. PATIENTS Twenty-two patients who underwent abdominal hysterectomy were classified randomly into two groups: (1) patient-controlled analgesia with morphine; and (2) patient-controlled analgesia with a combination of morphine and ketorolac. Blood samples to measure cytokines were collected at preoperatively, immediately postoperatively, and 2 hours, 4 hours, and 24 hours postoperatively. OUTCOME MEASURES Plasma was separated and frozen until the analysis of cytokines using enzyme-linked immunosorbent assays. Postoperative pain was assessed using a visual analog score. Sedation was checked based on a protocol developed at the Samsung Medical Center. RESULTS In the two groups, interleukin-6 increased immediately postoperatively, and it remained consistent for 24 hours. Interleukin-10 concentrations peaked at 2 hours postoperatively and progressively decreased. Cytokine concentrations between the two groups were significantly different for interleukin-6 24 hours postoperatively (p = 0.026) and for interleukin-10 4 hours postoperatively (p = 0.045). Total analgesic use was not different, but morphine consumption was significantly different (p = 0.037 at 4 hours postoperatively, p = 0.015 at 24 hours postoperatively). Pain scores, sedation, and side effects were unaffected by the patient-controlled analgesia regimen. CONCLUSIONS The authors conclude that supplementation using ketorolac plus administration of morphine modifies cytokine responses and may contribute to immune augmentations during postoperative periods.