The informative value of proadrenomedullin in patients with severe COVID-19
https://doi.org/10.21292/2078-5658-2020-17-6-31-38
Abstract
Subjects and methods. The retrospective study included 37 patients (n = 37) diagnosed with severe viral pneumonia (SARS-CoV2) who were treated in the intensive care unit of Pavlov First Saint Petersburg State Medical University. To assess the significance of PADM as a biomarker of bacterial infection, patients were divided into two groups: the group of patients with viral pneumonia without sepsis (n = 24) and the group of those who developed sepsis and septic shock complicating the course of the new coronavirus infection (n = 13). PADM was assessed as a criterion for the severity of the disease in the groups of deceased (n = 19) and survivors (n = 18). Data were statistically processed in the computer mathematics system R, version 3.6.2, the prognostic significance of PADM was assessed using linear regression.
Results. The median PADM in the group without sepsis was higher than the reference value – 1.1 (0.5; 4.3) nmol/L, in patients with sepsis that complicated the course of viral pneumonia – 2.8 (1.1; 5.7) nmol/L (p = 0.0019). Significant differences were revealed between the baseline levels of PADM in patients with different outcomes: in the surviving group, the median was 0.99 (0.5; 3.14) nmol/L, and in the group of deceased – 2.70 (0.94; 5.86 ) nmol/L. In surviving patients, the changes in PADM levels had a linear distribution throughout the entire period of stay in the intensive care unit. In deceased patients, within 20 days before death, PADM tended to grow significantly and reached its maximum by the time of the outcome.
Conclusion. The assessment of the PADM blood level can be used to clarify the addition of a bacterial infection in patients with pneumonia caused by the SARS-CoV2 virus. The study of changes in its level makes it possible to objectify the prediction of the course of COVID-19 – favorable or unfavorable. Data accumulation is required to clarify specific PADM values that predict the outcome in COVID-19 patients.
About the Authors
D. A. MalininaRussian Federation
Darya A. Malinina Post Graduate Student of Anesthesiology and Intensive Care Department, Emergency Physician of Anesthesiology and Intensive Care Unit no. 1 of Research Clinical Center of Anesthesiology and Intensive Care
I. V. Shlyk
Russian Federation
Irina V. Shlyk Doctor of Medical Sciences, Professor of Anesthesiology and Intensive Care Department, Deputy Head of Anesthesiology and Intensive Care Research Clinical Center,
Deputy Chief Doctor of University Clinic in Anesthesiology and Intensive Care
Yu. S. Polushin
Russian Federation
Yury S. Polushin Academician of RAS, Professor, Head of Anesthesiology and Intensive Care Department, Head of Anesthesiology and Intensive Care Research Clinical Center
A. A. Аfanasiev
Russian Federation
Aleksey A. Аfanasiev Candidate of Medical Sciences, Assistant of Anesthesiology and Intensive Care Department, Head of Anesthesiology and Intensive Care Department no. 1 of Research Clinical Center of Anesthesiology and Intensive Care
O. V. Stanevich
Russian Federation
Oksana V. Stanevich Infectious Diseases Specialist
E. A. Bakin
Russian Federation
Evgeniy A. Bakin Candidate of Technical Sciences, Senior Researcher of Raisa Gorbacheva Memorial Research Institute for Pediatric Oncology, Hematology and Transplantation
References
1. Rudnov V.А., Moldovanov А.V., Аstafieva M.N. et al. The clinical significance of proadrenomedulin level in blood in sepsis patients. Messenger of Anesthesiology and Resuscitation, 2019, vol. 16, no. 5, pp. 36-42. (In Russ.) doi: 10.21292/2078-5658-2019-16-5-36-42.
2. Andaluz-Ojeda D., Cicuéndez R., Calvo D. et al. Sustained value of proadrenomedullin as mortality predictor in severe sepsis. J. Infect., 2015, vol. 71, no. 1, pp. 136‒139. https://doi.org/10.1016/j.jinf.2015.02.002.
3. Bunton D.C., Petrie M.C., Hillier C. et al. The clinical relevance of adrenomedullin: a promising profile? Pharmacology & Therapeutics, 2004, vol. 103, no. 3, pp. 179‒201. https://doi.org/10.1016/j.pharmthera.2004.07.002.
4. Chen Y.X., Li C.S. Prognostic value of adrenomedullin in septic patients in the ED. Amer. J. Emerg. Med., 2013, vol. 31, no. 7, pp. 1017‒1021. https://doi.org/10.1016/j.ajem.2013.03.017.
5. Christ-Crain M., Morgenthaler N.G., Struck J. et al. Mid-regional pro-adrenomedullin as a prognostic marker in sepsis: an observational study. Crit. Care, 2005, vol. 9, no. 6, pp. R816. https://doi.org/10.1186/cc3885.
6. Christ-Crain M., Morgenthaler N.G., Stolz D. et al. Pro-adrenomedullin to predict severity and outcome in community-acquired pneumonia [ISRCTN04176397]. Crit. Care, 2006, vol. 10, no. 3, pp. R96. https://doi.org/10.1186/cc4955.
7. Eto T. A review of the biological properties and clinical implications of adrenomedullin and proadrenomedullin N-terminal 20 peptide (PAMP), hypotensive and vasodilating peptides. Peptides, 2001, vol. 22, no. 11, pp. 1693‒1711. https://doi.org/10.1016/s0196-9781(01)00513-7.
8. Fay M.P., Proschan M. Wilcoxon ‒ Mann ‒ Whitney or t-test? On assumptions for hypothesis tests and multiple interpretations of decision rules. Stat. Surv., 2010, no. 4, pp. 1-39.
9. Hinson J.P., Kapas S., Smith D.M. Adrenomedullin, a multifunctional regulatory peptide. Endocrine Rev., 2000, vol. 21, no. 2, pp. 138‒167. https://doi.org/10.1210/edrv.21.2.0396.
10. Jougasaki M., Burnett J.C.Jr. Adrenomedullin: potential in physiology and pathophysiology. Life Sci., 2000, vol. 66, no. 10, pp. 855‒872. https://doi.org/10.1016/S0024-3205(99)00358-6.
11. Kato J., Tsuruda T., Kitamura K. et al. Adrenomedullin: a possible autocrine or paracrine hormone in the cardiac ventricles. Hypertens. Res., 2003, vol. 26, pp. S113‒S119. https://doi.org/10.1161/01.hyp.31.1.505.
12. Kitamura K., Kangawa K., Kawamoto M. et al. Adrenomedullin: a novel hypotensive peptide isolated from human pheochromocytoma. Biochem. Biophys. Res. Communicat., 1993, vol. 192, no. 2, pp. 553‒560. https://doi.org/10.1006/bbrc.1993.1451.
13. Marino R., Struck J., Maisel A.S. et al. Plasma adrenomedullin is associated with short-term mortality and vasopressor requirement in patients admitted with sepsis. Crit. Care, 2014, vol. 18, no. 1, pp. R34. 14https://doi.org/10.1186/cc13731.
14. Martinez A., Pio R., Zipfel P.F. et al. Mapping of the adrenomedullin-binding domains in human complement factor H. Hypertens. Res., 2003, vol. 26, pp. S55‒S59. https://doi.org/10.1291/hypres.26.s55.
15. Mendenhall W.M., Sincich T.L. Statistics for Engineering and the Sciences. CRC Press, 2016, ISBN 9781498731850.
16. Montrucchio G., Sales G., Rumbolo F. et al. Effectiveness of mid-regional pro-adrenomedullin (MR-proADM) as prognostic marker in COVID-19 critically ill patients: an observational prospective study. 2020. https://doi.org/10.21203/rs.3.rs-56715/v1.
17. Nishio K., Akai Y., Murao Y. et al. Increased plasma concentrations of adrenomedullin correlate with relaxation of vascular tone in patients with septic shock. Crit. Care Med., 1997, vol. 25, no. 6, pp. 953‒957. https://doi.org/10.1164/ajrccm.160.1.9810006.
18. Pio R., Martinez A., Unsworth E.J. et al. Complement factor H is a serum-binding protein for adrenomedullin, and the resulting complex modulates the bioactivities of both partners. J. Biol. Chemistry, 2001, vol. 276, no. 15, pp. 12292‒12300. https://doi.org/10.1074/jbc.M007822200.
19. Singer M., Deutschman C.S., Seymour C.W. et al. The third international consensus definitions for sepsis and septic shock (Sepsis-3). Jama, 2016, vol. 315, no. 8, pp. 801‒810. https://doi.org/10.1001/jama.2016.0287.
20. Stolz D., Christ-Crain M., Morgenthaler N.G. et al. Plasma pro-adrenomedullin but not plasma pro-endothelin predicts survival in exacerbations of COPD. Chest, 2008, vol. 134, no. 2, pp. 263‒272. https://doi.org/10.1378/chest.08-0047.
21. Struck J., Morgenthaler N.G., Bergmann A. et al. Identification of an adrenomedullin precursor fragment in plasma of sepsis patients. Peptides, 2004, vol. 25, no. 8, pp. 1369‒1372. https://doi.org/10.1016/j.peptides.2004.06.019.
22. Team R.C., DC.R. A language and environment for statistical computing. Vienna, Austria. R Foundation for Statistical Computing, 2012. Available: https://www. R-project. org. 2019.
23. Wickham H. ggplot2: elegant graphics for data analysis. Springer, 2016, 213 р. doi 10.1007/978-0-387-98141-3.
Review
For citations:
Malinina D.A., Shlyk I.V., Polushin Yu.S., Аfanasiev A.A., Stanevich O.V., Bakin E.A. The informative value of proadrenomedullin in patients with severe COVID-19. Messenger of ANESTHESIOLOGY AND RESUSCITATION. 2020;17(6):31-38. (In Russ.) https://doi.org/10.21292/2078-5658-2020-17-6-31-38