Preview

Regional blood circulation and microcirculation

Advanced search

Microcirculation disorders in patients with severe COVID-19 and development of bacterial sepsis

https://doi.org/10.24884/1682-6655-2021-20-4-52-61

Abstract

It is believed that microcirculation dysfunction in sepsis primarily caused by damage of the endothelium by infectious agents and pro-inflammatory cytokines. Mechanisms of impaired microcirculation in the severe course of COVID-19 and sepsis likely to be similar. However, there are few reports studied microcirculation disorders in patients with COVID-19, and their results are sometimes contradictory. Objective. To assess the microcirculation of patients with severe Covid-19 and the development of bacterial sepsis using nail bed microscopy and laser Doppler flowmetry. Materials and methods. 16 intensive care unit COVID-19 patients subsequently diagnosed with bacterial sepsis were examined. Patients underwent vital capillaroscopy and an occlusive test using laser Doppler flowmetry. The average rate of capillary blood flow, the size of the perivascular zone, the density of capillaries, the presence of intravascular aggregates, the increase in the amplitude of the maximum post-occlusive blood flow and the average value of postocclusive blood flow relative to the initial one were valuated. Additionally, the level of serum proadrenomedullin was evaluated. Studies were performed on the day of admission and in dynamics. Results. By the capillaroscopy analysis, microcirculation disorders were detected in the form of a decrease in the linear speed of capillary blood flow (<400 μm/s), an extention of the perivascular zone (>100 μm), the circulation of microaggregates; the absence of postocclusive hyperemia was determined by an occlusive test. Secondary bacterial infection led to an even greater aggravation of microcirculation disorders: an increase of the perivascular zone, the progression of intravascular aggregation resulting in microthrombosis with a decrease of the density of the capillary network (according to capillaroscopy), as well as a sharp decrease of amplitude maximal increment of blood flow of post-осclusive circulation at the time of an occlusive sample. We also revealed a trend of negative correlation between the level of serum proadrenomedullin and the maximum increase in blood flow during the occlusive test. Conclusion. The secondary bacterial infection in patients with COVID-19 leads to a significant aggravation of microcirculation disorders with the development of perfusion deficiency and interstitial edema. The increased plasma proadrenomedullin level supports the concept of the significant role of endothelial dysfunction in the pathogenesis of severe COVID-10 and bacterial sepsis.

About the Authors

E. E. Ladozhskaya-Gapeenko
Pavlov University
Russian Federation

Ladozhskaya-Gapeenko Ekaterina E. – anesthesiologist of Anesthesiology and Intensive Care Unit № 2, Junior Researcher of the Scientific and Clinical Center of Anesthesiology and Intensive Care

6-8, L’va Tolstogo street, Saint Petersburg, 197022



K. N. Khrapov
Pavlov University
Russian Federation

Khrapov Kirill N. – Doctor of Medical Sciences, Professor of Anesthesiology and Intensive Care Department, Chief Researcher of Anesthesiology Department of Research Clinical Center of Anesthesiology and Intensive Care

6-8, L’va Tolstogo street, Saint Petersburg, 197022



N. N. Petrishchev
Pavlov University
Russian Federation

Petrishchev Nikolay N. – Doctor of Medical Sciences, Professor of the Department pathophysiology with a course of clinical pathophysiology, Head of the Center for Laser Medicine of Scientific and Educational Institute of Biomedicine

6-8, L’va Tolstogo street, Saint Petersburg, 197022



Yu. S. Polushin
Pavlov University
Russian Federation

Polushin Yury S. – Academician of RAS, Professor, Head of Anesthesiology and Intensive Care Department, Head of Research Clinical Center of Anesthesiology and Intensive Care

6-8, L’va Tolstogo street, Saint Petersburg, 197022



I. V. Shlyk
Pavlov University
Russian Federation

Shlyk Irina V. – Doctor of Medical Sciences, Professor of Anesthesiology and Intensive Care Department, Deputy Head of Research Clinical Center of Anesthesiology and Intensive Care, Deputy Head Physician of University Clinic in Anesthesiology and Intensive Care

6-8, L’va Tolstogo street, Saint Petersburg, 197022



References

1. Lam C, Tyml K, Martin C, Sibbald W. Microvascular perfusion is impaired in a rat model of normotensive sepsis // J Clin Invest. 1994;(94):2077–2083.

2. Pons S, Fodil S, Azoulay E, Zafrani L. The vascular endothelium: the cornerstone of organ dysfunction in severe SARSCoV-2 infection // Crit Care. 2020;24(1):353. Doi: 10.1186/s13054-020-03062-7; PMID: 32546188; PMCID: PMC7296907.

3. Sakr Y, Dubois MJ, De Backer D, Creteur J, Vincent JL. Persistent microcirculatory alterations are associated with organ failure and death in patients with septic shock // Crit Care Med. 2004;(32):1825–1831.

4. Vincent JL, De Backer D. Microvascular dysfunction as a cause of organ dysfunction in severe sepsis // Crit Care. 2005;9(Suppl 4):S9–12.

5. Ince C. The microcirculation is the motor of sepsis. Crit Care 9 Suppl 4: S13–S19, 2005. 60.

6. Bateman RM, Sharpe MD, Ellis CG. Bench-to-bedside review: microvascular dysfunction in sepsis-hemodynamics, oxygen transport, and nitric oxide // Crit Care. 2003;(7):359–373.

7. Ince C. Hemodynamic coherence and the rationale for monitoring the microcirculation // Crit Care. 2015;(19 (Suppl. 3)):S8.

8. Nakajima Y, Baudry N, Duranteau J, Vicaut E. Microcirculation in intestinal villi: a comparison between hemorrhagic and endotoxin shock // Am J Respir Crit Care Med. 2001;164(8 Pt 1):1526–15230.

9. Trzeciak S, Dellinger RP, Parrillo JE,Guglielmi M, Bajaj J, Abate NL, Arnold RC, Colilla S, Zanotti S, Hollenberg SM. Early microcirculatory perfusion derangements in patients with severe sepsis and septic shock: relationship to hemodynamics, oxygen transport, and survival. Ann Emerg Med. 2007;(49):88–98.

10. Bateman RM, Walley KR. Microvascular resuscitation as a therapeutic goal in severe sepsis // Crit Care. 2005;(9(Suppl 4)):S27-S32.

11. Harrois A, Dupic L, Duranteau J: Targeting the microcirculation in resuscitation of acutely unwell patients // Curr Opin Crit Care. 2011;(17):303–307.

12. Nencioni A, Trzeciak S, Shapiro NI: The microcirculation as a diagnostic and therapeutic target in sepsis // Intern Emerg Med. 2009,(4):413–418.

13. Trzeciak S, Cinel I, Phillip Dellinger R, Shapiro NI, Arnold RC, Parrillo JE, Hollenberg SM; Microcirculatory Alterations in Resuscitation and Shock (MARS) Investigators: Resuscitating the microcirculation in sepsis: the central role of nitric oxide, emerging concepts for novel therapies, and challenges for clinical trials // Acad Emerg Med. 2008;(15):399–413.

14. Brell B, Temmesfeld-Wollbrück B, Altzschner I, et al. Adrenomedullin reduces Staphylococcus aureus alpha-toxininduced rat ileum microcirculatory damage // Crit Care Med. 2005;(33):819–826.

15. 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;(22):1693–1711.

16. Kitamura K, Kangawa K, Eto T. Adrenomedullin and PAMP: discovery, structures, and cardiovascular functions // Microsc Res Tech. 2002;(57):3–13.

17. Piccioni А., Saviano А., Cicchinelli S., Valletta F., et al. Proadrenomedullin in Sepsis and Septic Shock: A Role in the Emergency Department // Francesco Franceschi Medicina (Kaunas). 2021;57(9):920. Doi: 10.3390/medicina57090920.

18. Abou-Arab O., Beyls C., Khalipha A. Microvascular flow alterations in critically ill Covid-19 patients: A prospective study // PLoS One. 2021;16(2):e0246636. Doi: 10.1371/journal.pone.0246636; PMID: 33556081; PMCID: PMC7870020.

19. Hutchings S.D., Watchorn J., Trovato F. et al. Microcirculatory, Endothelial, and Inflammatory Responses in Critically Ill Patients With Covid-19 Are Distinct From Those Seen in Septic Shock: A Case Control Study // Shock. 2021; 55(6):752–758. Doi: 10.1097/SHK.0000000000001672. PMID: 33021572.

20. Dubin A, Kanoore Edul VS, Caminos Eguillor JF, Ferrara G. Monitoring Microcirculation: Utility and Barriers – A Point-of-View Review // Vasc Health Risk Manag. 2020;(16):577–589. Doi: 10.2147/VHRM.S242635; PMID: 33408477; PMCID: PMC7780856.

21. Miranda M, Balarini M, Caixeta D, Bouskela E. Microcirculatory dysfunction in sepsis: pathophysiology, clinical monitoring, and potential therapies // Am J Physiol Heart Circ Physiol. 2016;311(1):H24–35. Doi: 10.1152/ajpheart.00034.2016; PMID: 27106039.

22. Pozo MO, Kanoore Edul VS, Ince C, Dubin A. Comparison of different methods for the calculation of the microvascular flow index // Crit Care Res Pract. 2012;(2012):102483. Doi: 10.1155/2012/102483; PMID: 22593824; PMCID: PMC3347715.

23. Belenkov Yu.N., Privalova E.V., Danilogorskaia Iu.A.,Shchendrygina A.A. Structural And Functional Changes In Capillary Microcirculation In Patients With Cardiovascular Diseases (Arterial Hypertension, Coronary Heart Disease, Chronic Heart Failure) Observed During Computer Videocapillaroscopy // Cardiology and cardiovascular surgery. 2012;5(2):49–56. (In Russ.).

24. Ladozhskaya-Gapeenko EE, Khrapov KN, Polushin YuS, Shlyk IV, Petrishchev NN, Vartanova IV. Microcirculation disorders in patients with severe COVID-19 // Messenger of Anesthesiology and Resuscitation. 2021;18(4):7–19. (In Russ.). Doi: 10.21292/2078-5658-2021-18-4-7-19.

25. Natalello G, De Luca G, Gigante L, Campochiaro C, De Lorenzis E, Verardi L, Paglionico A, Petricca L, Martone AM, Calvisi S, Ripa M, Cavalli G, Della-Torre E, Tresoldi M, Landi F, Bosello SL, Gremese E, Dagna L. Nailfold capillaroscopy findings in patients with coronavirus disease 2019: Broadening the spectrum of COVID-19 microvascular involvement // Microvasc Res. 2021;(133):104071. Doi: 10.1016/j.mvr.2020.104071; PMID: 32949574; PMCID: PMC7494493.

26. Rovas A., Osiaevi I, Buscher K et al. Microvascular dysfunction in Covid-19: the MYSTIC study // Angiogenesis. 2021;24(1):145–157. Doi: 10.1007/s10456-020-09753-7; PMID: 33058027; PMCID: PMC7556767.

27. Kanoore Edul V.S., Caminos Eguillor J.F., Ferrara G. et al. Microcirculation alterations in severe Covid-19 pneumonia // J Crit Care. 2021;(61):73–75. Doi: 10.1016/j.jcrc.2020.10.002. PMID: 33096349; PMCID: PMC7568145.

28. Damiani E, Carsetti A, Casarotta E et al. Microvascular alterations in patients with SARS-COV-2 severe pneumonia // Ann. Intensive Care. 2020;(10):60. Doi: 10.1186/s13613-020-00680-w.

29. De Backer D, Creteur J, Preiser JC, Dubois MJ, Vincent JL. Microvascular blood flow is altered in patients with sepsis // Am J Respir Crit Care Med. 2002; 166(1):98–104. Doi: 10.1164/rccm.200109-016oc; PMID: 12091178.

30. Spanos A, Jhanji S, Vivian-Smith A, Harris T, Pearse RM. Early microvascular changes in sepsis and severe sepsis // Shock. 2010;(33):387–391.

31. Ghiadoni L, Versari D, Giannarelli C, et al. S. Noninvasive diagnostic tools for investigating endothelial dysfunction // Curr Pharm Des. 2008;14(35):3715–3722. Doi: 10. 2174/138161208786898761; PMID: 19128224.

32. De Blasi RA, Palmisani S, Alampi D, Mercieri M, Romano R, Collini S, Pinto G. Microvascular dysfunction and skeletal muscle oxygenation assessed by phasemodulation near-infrared spectroscopy in patients with septic shock // Intensive Care Med. 2005;(31):1661–1668.

33. Pareznik R, Knezevic R, Voga G, Podbregar M (2006) Changes in muscle tissue oxygenation during stagnant ischemia in septic patients // Intensive Care Med. 2006;(32):87–92.

34. Draisma A, Bemelmans R, van der Hoeven JG, Spronk P, Pickkers P. Microcirculation and vascular reactivity during endotoxemia and endotoxin tolerance in humans // Shock. 2009;(31):581–585.

35. Trzeciak S, McCoy JV, Phillip DR, Arnold RC, Rizzuto M, Abate NL, Shapiro NI, Parrillo JE, Hollenberg SM. Early increases in microcirculatory perfusion during protocoldirected resuscitation are associated with reduced multi-organ failure at 24 h in patients with sepsis // Intensive Care Med. 2008;(34):2210–2217.


Review

For citations:


Ladozhskaya-Gapeenko E.E., Khrapov K.N., Petrishchev N.N., Polushin Yu.S., Shlyk I.V. Microcirculation disorders in patients with severe COVID-19 and development of bacterial sepsis. Regional blood circulation and microcirculation. 2021;20(4):52-61. (In Russ.) https://doi.org/10.24884/1682-6655-2021-20-4-52-61

Views: 917


Creative Commons License
This work is licensed under a Creative Commons Attribution 4.0 License.


ISSN 1682-6655 (Print)
ISSN 2712-9756 (Online)