Proadrenomedullin in the Management of COVID-19 Critically Ill Patients in Intensive Care Unit: A Systematic Review and Meta-Analysis of Evidence and Uncertainties in Existing Literature

Abstract

Mid-regional proadrenomedullin (MR-proADM) is a new biomarker of endothelial damage and its clinical use is increasing in sepsis and respiratory infections and recently in SARS-CoV-2 infection. We conducted a systematic review and meta-analysis to clarify the use of MR-proADM in severe COVID-19 disease. After Pubmed, Embase, and Scopus search, registries, and gray literature, deduplication, and selection of full-texts, we found 21 studies addressing the use of proadrenomedullin in COVID-19. All the studies were published between 2020 and 2022 from European countries. A total of 9 studies enrolled Intensive Care Unit (ICU) patients, 4 were conducted in the Emergency Department, and 8 had mixed populations. Regarding the ICU critically ill patients, 4 studies evaluating survival as primary outcome were available, of which 3 reported completed data. Combining the selected studies in a meta-analysis, a total of 252 patients were enrolled; of these, 182 were survivors and 70 were non-survivors. At the admission to the ICU, the average MR-proADM level in survivor patients was 1.01 versus 1.64 in non-survivor patients. The mean differences of MR-proADM values in survivors vs. non-survivors was −0.96 (95% CI from −1.26, to −0.65). Test for overall effect: Z = 6.19 (p < 0.00001) and heterogeneity was I2 = 0%. MR-proADM ICU admission levels seem to predict mortality among the critical COVID-19 population. Further, prospective studies, focused on critically ill patients and investigating a reliable MR-proADM cut-off, are needed to provide adequate guidance to its use in severe COVID-19.

Effectiveness of mid-regional pro-adrenomedullin, compared to other biomarkers (including lymphocyte subpopulations and immunoglobulins), as a prognostic biomarker in COVID-19 critically ill patients: New evidence from a 15-month observational prospective study

“…This prospective, observational study, on a cohort of over 200 critically ill ICU-COVID-19 patients, confirms the validity of the biomarker MR-proADM in predicting mortality (9,15). Its values, measured within the first 48 h of ICU admission, proved to be significantly higher in patients with a fatal outcome and revealed an ability to discriminate between surviving and non-surviving patients better than other biomarkers commonly used in ICU, such as PCT, C-RP, LDH, and D-dimer.…”

“…For survival analysis, we used the Kaplan-Meier method, considering a period of 28 days. A log-rank test was used to assess the differences between survival curves considering the MR-proADM cutoff value of 1.5 nmol/L according to available studies on MR-proADM in patients with severe COVID-19 admitted to ICUs (9).…”

“…It could even be able to predict SARS-CoV2-induced mortality, although the pathological mechanism underlying this correlation has not been fully clarified. In fact, most studies had limited dimensions and were designed in the context of a pandemic emergency, with heterogenicity of objectives and contexts (2,9).…”

“…In an intensive care unit (ICU) setting, the evidence seems to be particularly limited. A recent systematic review and meta-analysis designed to clarify the use of MR-proADM in severe COVID-19 disease included 21 studies, published between 2020 and 2022 from European countries, addressing the use of pro-adrenomedullin in COVID-19 (9). The analysis included data from 252 patients, only in the ICU setting.…”

Biomarkers as Prognostic Predictors and Therapeutic Guide in Critically Ill Patients: Clinical Evidence

“…They do not mention other biomarkers, but there are some not included in the guidelines that may be very useful in the future, as we have seen in the perioperative context. We would highlight MR ProADM and Bio ADM since they have already been studied in the perioperative period [ 134 ], and their use as a marker of endothelial dysfunction [ 135 ] and congestion [ 136 ] makes them very attractive in this context.…”