Department of Anesthesiology and Perioperative Medicine, Mayo Clinic, Phoenix, AZ, USA.
Department of Orthopedic Surgery, Mayo Clinic, Phoenix, AZ, USA.
Clin Orthop Relat Res. 2024 Feb 1;482(2):291-300. doi: 10.1097/CORR.0000000000002767. Epub 2023 Aug 18.
Pharmacogenomics is an emerging and affordable tool that may improve postoperative pain control. One challenge to successful pain control is the large interindividual variability among analgesics in their efficacy and adverse drug events. Whether preoperative pharmacogenomic testing is worthwhile for patients undergoing TKA is unclear.
QUESTIONS/PURPOSES: (1) Are the results of preoperative pharmacogenetic testing associated with lower postoperative pain scores as measured by the Overall Benefit of Analgesic Score (OBAS)? (2) Do the results of preoperative pharmacogenomic testing lead to less total opioids given? (3) Do the results of preoperative pharmacogenomic testing lead to changes in opioid prescribing patterns?
Participants of this randomized trial were enrolled from September 2018 through December 2021 if they were aged 18 to 80 years and were undergoing primary TKA under general anesthesia. Patients were excluded if they had chronic kidney disease, a history of chronic pain or narcotic use before surgery, or if they were undergoing robotic surgery. Preoperatively, patients completed pharmacogenomic testing (RightMed, OneOME) and a questionnaire and were randomly assigned to the experimental group or control group. Of 99 patients screened, 23 were excluded, one before randomization; 11 allocated patients in each group did not receive their allocated interventions for reasons such as surgery canceled, patients ultimately undergoing spinal anesthesia, and change in surgery plan. Another four patients in each group were excluded from the analysis because they were missing an OBAS report. This left 30 patients for analysis in the control group and 38 patients in the experimental group. The control and experimental groups were similar in age, gender, and race. Pharmacogenomic test results for patients in the experimental group were reviewed before surgery by a pharmacist, who recommended perioperative medications to the clinical team. A pharmacist also assessed for clinically relevant drug-gene interactions and recommended drug and dose selection according to guidelines from the Clinical Pharmacogenomics Implementation Consortium for each patient enrolled in the study. Patients were unaware of their pharmacogenomic results. Pharmacogenomic test results for patients in the control group were not reviewed before surgery; instead, standard perioperative medications were administered in adherence to our institutional care pathways. The OBAS (maximum 28 points) was the primary outcome measure, recorded 24 hours postoperatively. A two-sample t-test was used to compare the mean OBAS between groups. Secondary measures were the mean 24-hour pain score, total morphine milligram equivalent, and frequency of opioid use. Postoperatively, patients were assessed for pain with a VAS (range 0 to 10). Opioid use was recorded preoperatively, intraoperatively, in the postanesthesia care unit, and 24 hours after discharge from the postanesthesia care unit. Changes in perioperative opioid use based on pharmacogenomic testing were recorded, as were changes in prescription patterns for postoperative pain control. Preoperative characteristics were also compared between patients with and without various phenotypes ascertained from pharmacogenomic test results.
The mean OBAS did not differ between groups (mean ± SD 4.7 ± 3.7 in the control group versus 4.2 ± 2.8 in the experimental group, mean difference 0.5 [95% CI -1.1 to 2.1]; p = 0.55). Total opioids given did not differ between groups or at any single perioperative timepoint (preoperative, intraoperative, or postoperative). We found no difference in opioid prescribing pattern. After adjusting for multiple comparisons, no difference was observed between the treatment and control groups in tramadol use (41% versus 71%, proportion difference 0.29 [95% CI 0.05 to 0.53]; nominal p = 0.02; adjusted p > 0.99).
Routine use of pharmacogenomic testing for patients undergoing TKA did not lead to better pain control or decreased opioid consumption. Future studies might focus on at-risk populations, such as patients with chronic pain or those undergoing complex, painful surgical procedures, to test whether pharmacogenomic results might be beneficial in certain circumstances.
Level I, therapeutic study.
药物基因组学是一种新兴的、具有成本效益的工具，可能有助于改善术后疼痛控制。成功控制疼痛的一个挑战是，在疗效和不良药物事件方面，各种镇痛药的个体间差异很大。对于接受 TKA 的患者，术前药物基因组学检测是否有价值尚不清楚。
问题/目的：（1）总体镇痛评分（Overall Benefit of Analgesic Score，OBAS）是否与术后疼痛评分较低有关？（2）是否减少了给予的总阿片类药物量？（3）是否改变了阿片类药物的处方模式？
本随机试验的参与者于 2018 年 9 月至 2021 年 12 月入选，如果他们年龄在 18 至 80 岁之间，且正在接受全身麻醉下的初次 TKA。如果患者患有慢性肾脏病、术前有慢性疼痛或阿片类药物使用史，或正在接受机器人手术，则将其排除在外。术前，患者完成药物基因组学检测（RightMed，OneOME）和问卷调查，并随机分配到实验组或对照组。在 99 名筛选出的患者中，有 23 名因各种原因被排除，其中包括手术取消、患者最终接受脊髓麻醉以及手术计划改变。每个组中还有另外四名患者因缺少 OBAS 报告而被排除在分析之外。这使得对照组有 30 名患者，实验组有 38 名患者纳入分析。对照组和实验组在年龄、性别和种族方面相似。实验组的患者在手术前由药剂师审查药物基因组学检测结果，药剂师根据临床团队的建议为患者推荐围手术期药物。药剂师还根据临床药物基因组学实施联盟的指南，评估每个入组患者的药物基因相互作用和药物剂量选择。患者不知道自己的药物基因组学检测结果。对照组的患者在手术前没有审查药物基因组学检测结果，而是按照我们的机构护理途径给予标准的围手术期药物。OBAS（最高 28 分）是主要的观察指标，在术后 24 小时记录。采用两样本 t 检验比较两组之间的平均 OBAS。次要观察指标为 24 小时平均疼痛评分、总吗啡毫克当量和阿片类药物使用频率。术后，患者用视觉模拟评分法（range 0 to 10）评估疼痛。记录术前、术中、麻醉后恢复室和麻醉后恢复室出院后 24 小时的阿片类药物使用情况。记录根据药物基因组学检测结果改变围手术期阿片类药物使用情况，并记录术后疼痛控制的处方模式变化。还比较了有和没有从药物基因组学检测结果确定的各种表型的患者的术前特征。
两组的 OBAS 平均值无差异（对照组的平均±标准差为 4.7±3.7，实验组为 4.2±2.8，平均差异为 0.5[95%置信区间 -1.1 至 2.1]；p=0.55）。两组患者的总阿片类药物用量在各时间点（术前、术中或术后）均无差异。我们没有发现阿片类药物处方模式的差异。在进行多次比较调整后，治疗组和对照组在曲马多的使用上也没有差异（41%与 71%，比例差异 0.29[95%置信区间 0.05 至 0.53]；名义 p=0.02；调整后 p>0.99）。
对于接受 TKA 的患者，常规使用药物基因组学检测并没有带来更好的疼痛控制或减少阿片类药物的使用。未来的研究可能集中在高危人群，如慢性疼痛患者或接受复杂、疼痛手术的患者，以测试在某些情况下药物基因组学结果是否有益。
I 级，治疗性研究。
