Neumann Caroline, Leitner Margit, Bloos Frank, Lange Dorothea, Bogatsch Holger, Annane Djillali, Fleuriet Jerôme, Briegel Josef, Bauer Michael
Department of Anaesthesiology and Intensive Care Medicine, Jena University Hospital, Am Klinikum 1, 07747, Jena, Germany.
Department of Anaesthesiology, LMU University Hospital, LMU Munich, Marchioninistraße 15, 81377, Munich, Germany.
Infection. 2025 May 30. doi: 10.1007/s15010-025-02569-x.
Sepsis requires stratification for host-directed therapies through the discovery of adequate biomarkers enabling prediction of outcomes and treatment responses. Adrenomedullin has previously demonstrated potential for prognostic enrichment. This study aimed to assess associations of bioactive adrenomedullin (bio-ADM) levels at ICU admission and sepsis outcomes and to evaluate the potential of bio-ADM as marker to identify subgroups of patients with moderate disease severity that might benefit from hydrocortisone treatment.
We used data from the HYPRESS trial (NCT00670254) to investigate, if bio-ADM is useful to predict sepsis outcomes (septic shock, 90- and 180-day mortality) and benefit or harm by hydrocortisone treatment. Optimal cut-offs for outcome predictions were determined by Youden's index. Logistic regression was used to assess bio-ADM subgroups and treatment interaction.
Bio-ADM levels differed significantly in patients with or without septic shock within 14 days (p = 0.011). While the area under the ROC curve (AUC) was only 0.603 (CI 0.531-0.676), patient subgrouping using bio-ADM levels showed significantly higher cumulative incidence of septic shock within 14 days in the subgroup of patients with bio-ADM levels ≥ 37 pg/mL (p < 0.001). The odds ratio for the development of septic shock in this group was 4.67 (95% CI 1.53, 20.3, p = 0.016). A bio-ADM cut-off of ≥ 136 pg/mL was predictive for 90-day (OR 8.21, 95% CI 2.46-27.9, p < 0.001) and 180-day mortality (OR 4.87, 95% CI 1.49-16.0, p = 0.008). Hydrocortisone therapy did not reduce the incidence of septic shock (OR 1.59, 95% CI 0.37-8.15, p = 0.54), 90-day (OR 1.53, p = 0.23) or 180-day mortality (OR 1.41, p = 0.25), regardless of bio-ADM stratification (interaction term p = 0.58 for septic shock; p = 0.31 for 90-day mortality; p = 0.51 for 180-day mortality).
Whereas bio-ADM levels are associated with sepsis outcomes, our data do not indicate usefulness of the marker to identify patients potentially benefitting from hydrocortisone therapy.
脓毒症需要通过发现合适的生物标志物进行分层，以指导针对宿主的治疗，从而预测预后和治疗反应。此前研究表明肾上腺髓质素具有预后富集的潜力。本研究旨在评估重症监护病房（ICU）入院时生物活性肾上腺髓质素（bio-ADM）水平与脓毒症预后的相关性，并评估bio-ADM作为标志物识别疾病严重程度中等且可能从氢化可的松治疗中获益的患者亚组的潜力。
我们使用了HYPRESS试验（NCT00670254）的数据，以研究bio-ADM是否有助于预测脓毒症预后（感染性休克、90天和180天死亡率）以及氢化可的松治疗的益处或危害。通过约登指数确定预后预测的最佳临界值。采用逻辑回归评估bio-ADM亚组和治疗相互作用。
14天内发生或未发生感染性休克的患者，其bio-ADM水平差异显著（p = 0.011）。虽然ROC曲线下面积（AUC）仅为0.603（95%CI 0.531 - 0.676），但使用bio-ADM水平进行患者亚组分析显示，bio-ADM水平≥37 pg/mL的患者亚组在14天内感染性休克的累积发生率显著更高（p < 0.001）。该组发生感染性休克的比值比为4.67（95%CI 1.53, 20.3, p = 0.016）。bio-ADM临界值≥136 pg/mL可预测90天（OR 8.21, 95%CI 2.46 - 27.9, p < 0.001）和180天死亡率（OR 4.87, 95%CI 1.49 - 16.0, p = 0.008）。无论bio-ADM分层情况如何，氢化可的松治疗均未降低感染性休克的发生率（OR 1.59, 95%CI 0.37 - 8.15, p = 0.54）、90天（OR 1.53, p = 0.23）或180天死亡率（OR 1.41, p = 0.25）（感染性休克的交互项p = 0.58；90天死亡率的交互项p = 0.31；180天死亡率的交互项p = 0.51）。
虽然bio-ADM水平与脓毒症预后相关，但我们的数据并未表明该标志物对识别可能从氢化可的松治疗中获益的患者有用。
