From the Department of Medicine.
Center for Personalized Therapeutics.
Anesth Analg. 2022 Nov 1;135(5):929-940. doi: 10.1213/ANE.0000000000005951. Epub 2022 Feb 25.
Pharmacogenomics, which offers a potential means by which to inform prescribing and avoid adverse drug reactions, has gained increasing consideration in other medical settings but has not been broadly evaluated during perioperative care.
The Implementation of Pharmacogenomic Decision Support in Surgery (ImPreSS) Trial is a prospective, single-center study consisting of a prerandomization pilot and a subsequent randomized phase. We describe findings from the pilot period. Patients planning elective surgeries were genotyped with pharmacogenomic results, and decision support was made available to anesthesia providers in advance of surgery. Pharmacogenomic result access and prescribing records were analyzed. Surveys (Likert-scale) were administered to providers to understand utilization barriers.
Of eligible anesthesiology providers, 166 of 211 (79%) enrolled. A total of 71 patients underwent genotyping and surgery (median, 62 years; 55% female; average American Society of Anesthesiologists (ASA) score, 2.6; 58 inpatients and 13 ambulatories). No patients required postoperative intensive care or pain consultations. At least 1 provider accessed pharmacogenomic results before or during 41 of 71 surgeries (58%). Faculty were more likely to access results (78%) compared to house staff (41%; P = .003) and midlevel practitioners (15%) ( P < .0001). Notably, all administered intraoperative medications had favorable genomic results with the exception of succinylcholine administration to 1 patient with genomically increased risk for prolonged apnea (without adverse outcome). Considering composite prescribing in preoperative, recovery, throughout hospitalization, and at discharge, each patient was prescribed a median of 35 (range 15-83) total medications, 7 (range 1-22) of which had annotated pharmacogenomic results. Of 2371 prescribing events, 5 genomically high-risk medications were administered (all tramadol or omeprazole; with 2 of 5 pharmacogenomic results accessed), and 100 genomically cautionary mediations were administered (hydralazine, oxycodone, and pantoprazole; 61% rate of accessing results). Providers reported that although results were generally easy to access and understand, the most common reason for not considering results was because remembering to access pharmacogenomic information was not yet a part of their normal clinical workflow.
Our pilot data for result access rates suggest interest in pharmacogenomics by anesthesia providers, even if opportunities to alter prescribing in response to high-risk genotypes were infrequent. This pilot phase has also uncovered unique considerations for implementing pharmacogenomic information in the perioperative care setting, and new strategies including adding the involvement of surgery teams, targeting patients likely to need intensive care and dedicated pain care, and embedding pharmacists within rounding models will be incorporated in the follow-on randomized phase to increase engagement and likelihood of affecting prescribing decisions and clinical outcomes.
药物基因组学提供了一种告知处方和避免药物不良反应的潜在手段，在其他医疗环境中得到了越来越多的关注，但在围手术期护理中尚未得到广泛评估。
手术中药物基因组决策支持的实施（ImPreSS）试验是一项前瞻性、单中心研究，包括预随机化试验和随后的随机阶段。我们描述了试验阶段的发现。计划接受择期手术的患者进行药物基因组检测，在手术前为麻醉提供者提供决策支持。分析药物基因组检测结果和处方记录。向提供者发放了（李克特量表）调查问卷，以了解利用障碍。
在符合条件的麻醉学提供者中，211 名中有 166 名（79%）参与。共有 71 名患者接受了基因分型和手术（中位数年龄 62 岁；55%为女性；平均美国麻醉师协会（ASA）评分 2.6；58 例住院患者和 13 例门诊患者）。没有患者需要术后重症监护或疼痛咨询。至少有 1 名提供者在 71 例手术中的 41 例（58%）手术前或手术中查看了药物基因组学结果。与住院医师（41%；P=0.003）和中级从业者（15%）相比，教员更有可能查看结果（78%）（P<0.0001）。值得注意的是，除了 1 名基因上增加了长时间呼吸暂停风险的患者接受了琥珀酰胆碱（没有不良后果）外，所有给予的术中药物都具有良好的基因组结果。考虑到术前、恢复、整个住院期间和出院时的综合处方，每位患者的处方中位数为 35 种（范围 15-83）总药物，其中 7 种（范围 1-22）有注释的药物基因组学结果。在 2371 次给药事件中，给予了 5 种药物基因组学高风险药物（均为曲马多或奥美拉唑；其中 5 种药物基因组学结果中有 2 种），并给予了 100 种药物基因组学谨慎药物（肼屈嗪、羟考酮和泮托拉唑；结果的访问率为 61%）。提供者报告说，尽管结果通常易于访问和理解，但不考虑结果的最常见原因是因为他们尚未将访问药物基因组学信息作为其正常临床工作流程的一部分。
我们的结果访问率试点数据表明麻醉提供者对药物基因组学的兴趣，即使由于高风险基因型而改变处方的机会很少。这一试点阶段还发现了在围手术期护理环境中实施药物基因组信息的独特考虑因素，包括增加手术团队的参与、针对可能需要重症监护和专门疼痛护理的患者，以及将药剂师纳入查房模式等新策略，将纳入后续的随机阶段，以增加参与度并有可能影响处方决策和临床结果。
