Circulating bioactive adrenomedullin as a marker of sepsis, septic shock and critical illness

Abstract

Background Biomarkers can be of help to understand critical illness and to identify and stratify sepsis. Adrenomedullin is a vasoactive hormone, with reported prognostic and potentially therapeutic value in sepsis. The primary aim of this study was to investigate the association of circulating bioactive adrenomedullin (bio-ADM) levels at intensive care unit (ICU) admission with mortality in sepsis patients and in a general ICU population. Secondary aims included the association of bio-ADM with organ failure and the ability of bio-ADM to identify sepsis. Methods In this retrospective observational study, adult patients admitted to one of four ICUs during 2016 had admission bio-ADM levels analysed. Age-adjusted odds ratios (OR) with 95% CI for log-2 transformed bio-ADM, and Youden’s index derived cut-offs were calculated. The primary outcome was 30-day mortality, and secondary outcomes included the need for organ support and the ability to identify sepsis. Results Bio-ADM in 1867 consecutive patients were analysed; 632 patients fulfilled the sepsis-3 criteria of whom 267 had septic shock. The median bio-ADM in the entire ICU population was 40 pg/mL, 74 pg/mL in sepsis patients, 107 pg/mL in septic shock and 29 pg/mL in non-septic patients. The association of elevated bio-ADM and mortality in sepsis patients and the ICU population resulted in ORs of 1.23 (95% CI 1.07–1.41) and 1.22 (95% CI 1.12–1.32), respectively. The association with mortality remained after additional adjustment for lactate in sepsis patients. Elevated bio-ADM was associated with an increased need for dialysis with ORs of 2.28 (95% CI 2.01–2.59) and 1.97 (95% CI 1.64–2.36) for the ICU population and sepsis patients, respectively, and with increased need of vasopressors, OR 1.33 (95% CI 1.23–1.42) (95% CI 1.17–1.50) for both populations. Sepsis was identified with an OR of 1.78 (95% CI 1.64–1.94) for bio-ADM, after additional adjustment for severity of disease. A bio-ADM cut-off of 70 pg/mL differentiated between survivors and non-survivors in sepsis, but a Youden’s index derived threshold of 108 pg/mL performed better. Conclusions Admission bio-ADM is associated with 30-day mortality and organ failure in sepsis patients as well as in a general ICU population. Bio-ADM may be a morbidity-independent sepsis biomarker.

The diagnostic and prognostic value of mature and total adrenomedullin for sepsis: a prospective, observational study

“…This could be explained by the sensitivity of the assay used in each study, indicating that the cut-off values obtained by different assay methods may be different. Recently, Lundberg et al [20] reported a Yuden's index cut-off of 45 pg mL -1 for predicting the 28-day sepsis-related mortality in their sepsis cohort, which was as low as in the present study.…”

“…In some previous studies, the levels of total AM were assessed and their utility in diagnosing sepsis was compared with those of other chemical biomarkers, such as CRP, PCT, lactate, and PSEP [8,9,18,20,[24][25][26]. We found that among all the clinical parameters examined, the diagnostic accuracy for sepsis on the rst day of ICU admission was the highest for total AM, and that of mature AM was the second highest.…”

“…In our study, the cut-off level of mature AM for the diagnosis of sepsis was approximately 31.2 pg mL -1 , and its AUC was 0.848, with a sensitivity of 88.1% and a speci city of 67.9%. Other investigators have also reported that the ability of mature AM to identify patients with sepsis was modest because an AUC of 0.76 and a Youden's index derived cut-off of 37 pg mL -1 generated a sensitivity of 61% and a speci city of 80% [20]. These cut-off values of mature AM were close, indicating that the values of about 30 pg mL -1 could be applicable to diagnose sepsis, which is a novel nding for mature AM.…”

Plasma proenkephalin A 119–159 and dipeptidyl peptidase 3 on admission after cardiac arrest help predict long-term neurological outcome

“…13 The 99th percentile of bio-ADM is 43 pg/mL in a normal population. 27 In DPP3 samples of 355 healthy subjects, the 97.5th percentile was 43 ng/mL (personal communication with SpingoTec GmbH).…”

“…26 A study by Lundberg et al found admission bio-ADM to be associated with 30-day mortality and organ failure in sepsis patients as well as in a general ICU population. 27…”