Kido Kanta, Toda Shinichi, Shindo Yuki, Miyashita Hitoshi, Sugino Shigekazu, Masaki Eiji
Department of Dental Anesthesiology and Pain Management, Tohoku University Hospital, Sendai, Miyagi, Japan,
Department of Oral Medicine and Surgery, Division of Oral and Maxillofacial Surgery, Graduate School of Dentistry, Tohoku University, Sendai, Miyagi, Japan.
J Pain Res. 2019 Jan 17;12:377-385. doi: 10.2147/JPR.S177098. eCollection 2019.
Remifentanil is associated with acute opioid tolerance that can lead to increased postoperative consumption of opioid analgesics. The purpose of this study was to determine whether a low dose of ketamine prevents remifentanil-induced acute opioid tolerance and affects the neutrophil-lymphocyte ratio (NLR), a newly recognized biomarker of inflammation.
Forty patients undergoing orthognathic surgery were enrolled in this prospective, randomized, double-blind study and randomly assigned to intraoperative administration of one of the following anesthetic regimens: high-dose remifentanil (0.6 µg/kg/minute); low-dose remifentanil (0.2 µg/kg/minute); or high-dose remifentanil with ketamine (remifentanil 0.6 µg/kg/minute with 0.5 mg/kg ketamine just after induction followed by an intraoperative infusion of ketamine 5 µg/kg/minute until wound closure). Fentanyl by intravenous patient-controlled analgesia was used for postoperative pain control. Visual Analog Scale pain scores and fentanyl consumption were recorded in the first 24 hours postoperatively. Perioperative serum C-reactive protein level and NLR were also determined.
Baseline characteristics were similar in the three study groups. There were no between-group differences in Visual Analog Scale pain scores during the study period. The high-dose remifentanil group had a significantly higher requirement for fentanyl than the other two groups. Addition of ketamine did not affect the C-reactive protein level but increased the NLR; this increase was associated with decreased fentanyl consumption.
High-dose intraoperative remifentanil induced postoperative acute opioid tolerance that was prevented by infusion of low-dose ketamine. Ketamine increased the postoperative NLR associated with decreased fentanyl requirement for postoperative pain control.
瑞芬太尼与急性阿片类药物耐受性相关，可导致术后阿片类镇痛药消耗量增加。本研究的目的是确定低剂量氯胺酮是否能预防瑞芬太尼诱导的急性阿片类药物耐受性，并影响中性粒细胞与淋巴细胞比值（NLR），这是一种新发现的炎症生物标志物。
40例接受正颌手术的患者纳入这项前瞻性、随机、双盲研究，并随机分配接受以下麻醉方案之一的术中给药：高剂量瑞芬太尼（0.6μg/kg/分钟）；低剂量瑞芬太尼（0.2μg/kg/分钟）；或高剂量瑞芬太尼联合氯胺酮（诱导后立即给予瑞芬太尼0.6μg/kg/分钟和氯胺酮0.5mg/kg，随后术中输注氯胺酮5μg/kg/分钟直至伤口闭合）。术后疼痛控制采用静脉自控镇痛给予芬太尼。记录术后24小时内的视觉模拟评分疼痛分数和芬太尼消耗量。还测定围手术期血清C反应蛋白水平和NLR。
三个研究组的基线特征相似。研究期间视觉模拟评分疼痛分数在组间无差异。高剂量瑞芬太尼组对芬太尼的需求量显著高于其他两组。添加氯胺酮不影响C反应蛋白水平，但增加了NLR；这种增加与芬太尼消耗量减少相关。
术中高剂量瑞芬太尼诱导术后急性阿片类药物耐受性，低剂量氯胺酮输注可预防。氯胺酮增加了术后NLR，与术后疼痛控制所需芬太尼减少相关。
