Alfitian Jonas, Riedel Bernhard, Ismail Hilmy, Ho Kwok M, Xie Sophia, Zimmer Philipp, Kammerer Tobias, Wijeysundera Duminda N, Cuthbertson Brian H, Schier Robert
University of Cologne, Faculty of Medicine and University Hospital Cologne, Department for Anesthesiology and Intensive Care Medicine, Germany.
Department of Anaesthesia, Perioperative Medicine and Pain Medicine, Peter MacCallum Cancer Centre, Australia.
EClinicalMedicine. 2023 Sep 28;64:102223. doi: 10.1016/j.eclinm.2023.102223. eCollection 2023 Oct.
Poor functional capacity has been identified as an important modifiable risk factor for postoperative complications. Cardiopulmonary exercise testing (CPET) provides objective parameters of functional capacity (e.g., oxygen consumption at peak exercise, peak VO), with significant prognostication for postoperative complications. However, sex-specific thresholds for functional capacity to predict surgical risk are yet to be established. Therefore, we performed a analysis of the international, multicentre, prospective observational METS (Measurement of Exercise Tolerance before Surgery) study to evaluate if sex-specific thresholds of peak VO improve risk prediction of postoperative complications.
We undertook a analysis (HREC/71824/PMCC) of the METS study, which was performed between March 2013 and March 2016. We investigated whether sex-specific differences exist for CPET-derived parameters and associated thresholds for predicting postoperative complications in this large cohort of patients that had major non-cardiac surgery (n = 1266). Logistic regression models were analyzed for the association of low peak VO with moderate-to-severe in-hospital postoperative complications. Optimal sex-specific peak VO thresholds were obtained by maximizing the Youden index of receiver operating characteristic (ROC) curves. Finally, multivariable logistic regression models tested the resulting sex-specific thresholds against the established non-sex-specific peak VO threshold (14 mL kg min) adjusted for clinically relevant features such as comorbidities and surgical complexity. Models were evaluated by bootstrapping optimism-corrected area under the ROC curve and the net reclassification improvement index (NRI).
Female patients (n = 480) had a lower mean (SD) peak VO than males (16.7 (4.9) mL kg min versus 21.2 (6.5) mL kg min, p < 0.001) and a lower postoperative complication rate (10.4% versus 15.3%; p = 0.018) than males (n = 786). The optimal peak VO threshold for predicting postoperative complications was 12.4 mL kg min for females and 22.3 mL kg min for males, respectively. In the multivariable regression model, low non-sex-specific peak VO did not independently predict postoperative complications. In contrast, low sex-specific peak VO was an independent predictor of postoperative complications (OR 2.29; 95% CI: 1.60, 3.30; p < 0.001). The optimism-corrected AUC-ROC of the sex-specific model was higher compared with the non-sex-specific model (0.73 versus 0.7; DeLong's test: p = 0.021). The sex-specific model classified 39% of the patients more correctly than the baseline model (NRI = 0.39; 95% CI: 0.24, 0.55). In contrast, the non-sex-specific model only classified 9% of the patients more correctly when compared against the baseline model (NRI = 0.09; 95% CI: -0.04, 0.22).
Our data report sex-specific differences in preoperative CPET-derived functional capacity parameters. Sex-specific peak VO thresholds identify patients at increased risk for postoperative complications with a higher discriminatory ability than a sex-unspecific threshold. As such, sex-specific threshold values should be considered in preoperative CPET to potentially improve risk stratification and to guide surgical decision-making, including eligibility for surgery, preoperative optimization strategies (prehabilitation) or seeking non-surgical options.
There was no funding for the present study. The original METS study was funded by Canadian Institutes of Health Research, Heart and Stroke Foundation of Canada, Ontario Ministry of Health and Long-Term Care, Ontario Ministry of Research, Innovation and Science, UK National Institute of Academic Anaesthesia, UK Clinical Research Collaboration, Australian and New Zealand College of Anaesthetists, and Monash University.
功能能力差已被确定为术后并发症的一个重要可改变风险因素。心肺运动试验（CPET）提供了功能能力的客观参数（如运动峰值时的耗氧量、峰值VO），对术后并发症具有重要的预后价值。然而，预测手术风险的功能能力的性别特异性阈值尚未确立。因此，我们对国际多中心前瞻性观察性METS（术前运动耐量测量）研究进行了分析，以评估峰值VO的性别特异性阈值是否能改善术后并发症的风险预测。
我们对2013年3月至2016年3月期间进行的METS研究进行了分析（HREC/71824/PMCC）。我们调查了在这一大群接受重大非心脏手术的患者（n = 1266）中，CPET得出的参数以及预测术后并发症的相关阈值是否存在性别差异。对低峰值VO与中度至重度院内术后并发症的关联进行了逻辑回归模型分析。通过最大化受试者工作特征（ROC）曲线的约登指数获得最佳性别特异性峰值VO阈值。最后，多变量逻辑回归模型针对根据合并症和手术复杂性等临床相关特征调整后的既定非性别特异性峰值VO阈值（14 mL·kg⁻¹·min⁻¹），对得出的性别特异性阈值进行了测试。通过自举法对ROC曲线下的乐观校正面积和净重新分类改善指数（NRI）对模型进行评估。
女性患者（n = 480）的平均（标准差）峰值VO低于男性（16.7（4.9）mL·kg⁻¹·min⁻¹对21.2（6.5）mL·kg⁻¹·min⁻¹，p < 0.001），术后并发症发生率也低于男性（10.4%对15.3%；p = 0.018）（男性n = 786）。预测术后并发症的最佳峰值VO阈值女性为12.4 mL·kg⁻¹·min⁻¹，男性为22.3 mL·kg⁻¹·min⁻¹。在多变量回归模型中，低非性别特异性峰值VO不能独立预测术后并发症。相比之下，低性别特异性峰值VO是术后并发症的独立预测因素（OR 2.29；95% CI：1.60，3.30；p < 0.001）。性别特异性模型的乐观校正AUC-ROC高于非性别特异性模型（0.73对0.7；德龙检验：p = 0.021）。性别特异性模型比基线模型更正确地分类了39%的患者（NRI = 0.39；95% CI：0.24，0.55）。相比之下，非性别特异性模型与基线模型相比仅更正确地分类了9%的患者（NRI = 0.09；95% CI：-0.04，0.22）。
我们的数据报告了术前CPET得出的功能能力参数存在性别差异。性别特异性峰值VO阈值比非性别特异性阈值具有更高的辨别能力，可识别术后并发症风险增加的患者。因此，在术前CPET中应考虑性别特异性阈值，以潜在地改善风险分层并指导手术决策，包括手术资格、术前优化策略（术前康复）或寻求非手术选择。
本研究无资金支持。原METS研究由加拿大卫生研究院、加拿大心脏与中风基金会、安大略省卫生与长期护理部、安大略省研究、创新与科学部、英国国家学术麻醉研究所、英国临床研究合作组织、澳大利亚和新西兰麻醉师学院以及莫纳什大学资助。
