Department of Anesthesiology, 535 East 70th Street, New York, NY 10021, USA.
J Bone Joint Surg Am. 2012 Dec 5;94(23):2120-7. doi: 10.2106/JBJS.K.00995.
The perioperative inflammatory response as measured by elevated levels of interleukin-6 (IL-6) has been linked to acute respiratory distress syndrome, postoperative confusion, and fever. Because of the extent of surgery,patients undergoing bilateral total knee arthroplasty may be at high risk of complications. We had found a significant decrease in IL-6 in patients having bilateral total knee replacement who received two doses of 100 mg of hydrocortisone eight hours apart; however, by twenty-four hours, IL-6 levels were equal to those in the group that received a placebo. In the present study, we investigated whether the administration of three doses would reduce IL-6 levels at twenty-four hours and affect other outcomes such as desmosine level, a marker of lung injury.
After institutional review board approval, a total of thirty-four patients (seventeen patients and seventeen control subjects) were enrolled in this double-blind, randomized, placebo-controlled study. Three doses of intravenous hydrocortisone (100 mg) or placebo were given eight hours apart. Urinary desmosine levels were obtained at baseline and at one and three days postoperatively. The level of IL-6 was measured at baseline and at six, ten, twenty-four, and forty-eight hours postoperatively. Pain scores, presence of fever, and functional outcomes were recorded.
The level of IL-6 increased in both groups, but was significantly higher in the control group, peaking at twenty-four hours (mean and standard deviation, 623.74 ± 610.35 pg/mL versus 148.13 ± 119.35 pg/mL; p = 0.006). Urinary desmosine levels significantly increased by twenty-four hours in the control group, but remained unchanged in the study group (134.75 ± 67.88 pmol/mg and 79.45 ± 46.30 pmol/mg, respectively; p = 0.006). Pain scores at twenty-four hours were significantly lower in the study group (1.4 ± 0.9 versus 2.4 ± 1.2; p = 0.01) as was the presence of fever (11.8%versus 47.1%; p = 0.03). Range of motion at the knee was significantly greater in the study group (81.6 ± 11.6 versus 70.6 ± 14.0 in the right knee [p = 0.02] and 81.4 ± 11.3 versus 73.4 ± 9.4 in the left knee [p = 0.03]).
Hydrocortisone (100 mg) given over three doses, each eight hours apart, decreased and maintained a lower degree of inflammation with bilateral total knee replacement as measured by IL-6 level. Corticosteroids decreased the prevalence of fever, lowered visual analog pain scores, and improved knee motion. The significantly lower values of desmosine in the study group suggest that this treatment may be protective against lung injury.
白细胞介素-6（IL-6）水平升高与急性呼吸窘迫综合征、术后意识混乱和发热有关。由于手术范围广泛，接受双侧全膝关节置换术的患者可能存在发生并发症的高风险。我们发现，接受两次 100mg 氢化可的松治疗的双侧全膝关节置换患者的 IL-6 显著下降；然而，到 24 小时时，IL-6 水平与接受安慰剂的患者相同。在本研究中，我们研究了给予三剂是否会降低 24 小时时的 IL-6 水平并影响其他结果，如肺损伤标志物 Desmosine 水平。
在机构审查委员会批准后，共纳入 34 名患者（17 名患者和 17 名对照者）参与这项双盲、随机、安慰剂对照研究。每隔 8 小时静脉给予三剂 100mg 氢化可的松或安慰剂。在基线和术后 1 天和 3 天采集尿 Desmosine 水平。在基线和术后 6、10、24 和 48 小时测量 IL-6 水平。记录疼痛评分、发热情况和功能结局。
两组的 IL-6 水平均升高，但对照组升高更显著，在 24 小时时达到峰值（均值和标准差，623.74±610.35pg/ml 比 148.13±119.35pg/ml；p=0.006）。对照组的尿 Desmosine 水平在 24 小时时显著升高，但研究组不变（分别为 134.75±67.88pmol/mg 和 79.45±46.30pmol/mg；p=0.006）。研究组在 24 小时时的疼痛评分显著较低（1.4±0.9 比 2.4±1.2；p=0.01），发热发生率也较低（11.8%比 47.1%；p=0.03）。研究组膝关节活动度明显更大（右侧膝关节 81.6±11.6 比 70.6±14.0 [p=0.02]，左侧膝关节 81.4±11.3 比 73.4±9.4 [p=0.03]）。
每 8 小时给予三剂 100mg 氢化可的松可降低并维持双侧全膝关节置换术患者的炎症程度，通过 IL-6 水平衡量。皮质类固醇降低了发热的发生率，降低了视觉模拟疼痛评分，并改善了膝关节运动。研究组 Desmosine 的显著较低值表明，这种治疗可能对肺损伤具有保护作用。
