Biomarkers in sepsis-looking for the Holy Grail or chasing a mirage!

Table 6 Adrenomedullin and pro adrenomedullin for prognosis of sepsis

Ref.	Type of study	Patient population	Aim	No. of patients	Results	Conclusion of study
Christ-Crain et al[34], 2006	Prospective observational	Adult patients with CAP	To evaluate the value of Pro ADM levels for severity assessment and outcome prediction in CAP	302	Pro ADM levels (as compared to CRP and leukocyte count) increased with increasing severity of CAP (calculated through PSI score). Pro ADM levels at admission significantly higher 2.1 (1.5 to 3) nmol/L compared to survivors 1 (0.6 to 1.6) nmol/L; P < 0.001. AUC for proADM was 0.76 (95%CI: 0.71–0.81)-significantly higher than PCT, CRP, TLC	Pro ADM is a useful biomarker for risk stratification in patients with CAP
Charles et al[60], 2017	Prospective cohort	Adults	To assess the prognostic value of PCT, MR pro ADM, copeptin and CT proendothelin1 concentrations	173	Day 1 MR-ProADM levels significantly higher in non survivors [8.6 (5.9) vs 4.4 (3.9)] nmol/L; P < 0.0001	Day 1 MR-ProADM is a good predictor of short term clinical outcome as compared with others
Li et al[36], 2018	Meta-Analysis	Adults	To evaluate the ability of adrenomedullin and Pro Adm to predict mortality in septic patients	13 studies; 2556 patients	Increased AM or Pro ADM levels are associated with increased mortality (pooled RR = 3.31; 95%CI: 2.31-4.75); AUC 0.8 (95%CI: 0.77-0.84)	AM and Pro ADM may be used as prognostic markers in sepsis
Chen and Li[61], 2013	Observational	Adults	To evaluate the prognostic value of adrenomedullin in septic patients and compare it with PCT and MEDS	837	Mean levels (at admission of AM were 28.66 ± 6.05 ng/L in 100 healthy controls, 31.65 ± 6.47 ng/L in 153 systemic inflammatory response syndrome patients, 33.24 ± 8.59 ng/L in 376 sepsis patients, 34.81 ± 8.33 ng/L in 210 severe sepsis patients, and 45.15 ± 9.87 ng/L in 98 septic shock patients. The differences between the 2 groups were significant. ADM levels significantly higher in non survivors; AUC for in hospital mortality-AM-0.773; PCT-0.701; MEDS-0.721	Adrenomedullin is valuable prognostic biomarker for septic patients in ED
Caironi et al[62], 2017	Observational	Adults	To evaluate the role of Bio ADM	956	Plasma bio ADM (day 1) was higher in and associated with higher 90 d mortality, multi organ failures, extent of haemodynamic support and serum lactate time course over the 1st wk. Bio ADM trajectory during the 1st wk of treatment predicted 90 d mortality; Reduction to levels below 110 pg/ml at day 7 was associated with reduction in 90 d mortality	Bio ADM levels may help individualize haemodynamic support therapy in septic patients
Elke et al[63], 2018	Secondary analysis of RCT	Adults	To evaluate role of MR Pro Adm compared to conventional biomarkers (PCT, CRP, lactate) and clinical scores to identify disease severity in sepsis	1089	MR Pro Adm had strongest association with mortality and high disease severity; A decreasing concentration of PCT by ≥ 20 % from baseline to day 1 or ≥ 50 % from baseline to day 4 but a persisting high level of Pro Adm had significantly increased mortality risk [HR (95%CI)-19 (8-45.9) and 43.1 (10.1-184)]	MR Pro Adm assesses disease severity and treatment response more accurately than conventional biomarkers and scores

AM: Adrenomedullin; AUC: Area under the receiver operator characteristic curve; Bio ADM: Bio adrenomedullin; CAP: Community acquired pneumonia; CRP: C-reactive protein; MEDS: Mortality in Emergency Department Score; MR pro ADM: Mid Regional Pro adrenomedullin; PCT: Procalcitonin; Pro ADM: Pro adrenomedullin; PSI: Pneumonia severity Index; TLC: Total leukocyte count.