<?xml version="1.0" encoding="UTF-8"?>
<!DOCTYPE article PUBLIC "-//NLM//DTD JATS (Z39.96) Journal Publishing DTD v1.3 20210610//EN" "JATS-journalpublishing1-3.dtd">
<article article-type="research-article" dtd-version="1.3" xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance" xml:lang="ru"><front><journal-meta><journal-id journal-id-type="publisher-id">microcirculation</journal-id><journal-title-group><journal-title xml:lang="ru">Регионарное кровообращение и микроциркуляция</journal-title><trans-title-group xml:lang="en"><trans-title>Regional blood circulation and microcirculation</trans-title></trans-title-group></journal-title-group><issn pub-type="ppub">1682-6655</issn><issn pub-type="epub">2712-9756</issn><publisher><publisher-name>Academician I.P. Pavlov First St. Petersburg State Medical University</publisher-name></publisher></journal-meta><article-meta><article-id pub-id-type="doi">10.24884/1682-6655-2021-20-4-52-61</article-id><article-id custom-type="elpub" pub-id-type="custom">microcirculation-1010</article-id><article-categories><subj-group subj-group-type="heading"><subject>Research Article</subject></subj-group><subj-group subj-group-type="section-heading" xml:lang="ru"><subject>ОРИГИНАЛЬНЫЕ СТАТЬИ (КЛИНИЧЕСКИЕ ИССЛЕДОВАНИЯ)</subject></subj-group><subj-group subj-group-type="section-heading" xml:lang="en"><subject>ORIGINAL ARTICLES (CLINICAL INVESTIGATIONS)</subject></subj-group></article-categories><title-group><article-title>Нарушения микроциркуляции у больных с тяжелым течением COVID-19, осложненным бактериальным сепсисом</article-title><trans-title-group xml:lang="en"><trans-title>Microcirculation disorders in patients with severe COVID-19 and development of bacterial sepsis</trans-title></trans-title-group></title-group><contrib-group><contrib contrib-type="author" corresp="yes"><name-alternatives><name name-style="eastern" xml:lang="ru"><surname>Ладожская-Гапеенко</surname><given-names>Е. Е.</given-names></name><name name-style="western" xml:lang="en"><surname>Ladozhskaya-Gapeenko</surname><given-names>E. E.</given-names></name></name-alternatives><bio xml:lang="ru"><p>Ладожская-Гапеенко Екатерина Евгеньевна – врач анестезиолог-реаниматолог отделения анестезиологии и реанимации № 2, младший научный сотрудник Научно-клинического центра анестезиологии и реаниматологии</p><p>197022, Санкт-Петербург, ул. Льва Толстого, д. 6-8</p></bio><bio xml:lang="en"><p>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</p><p>6-8, L’va Tolstogo street, Saint Petersburg, 197022</p></bio><email xlink:type="simple">ulfkote@mail.ru</email><xref ref-type="aff" rid="aff-1"/></contrib><contrib contrib-type="author" corresp="yes"><name-alternatives><name name-style="eastern" xml:lang="ru"><surname>Храпов</surname><given-names>К. Н.</given-names></name><name name-style="western" xml:lang="en"><surname>Khrapov</surname><given-names>K. N.</given-names></name></name-alternatives><bio xml:lang="ru"><p>Храпов Кирилл Николаевич – д-р мед. наук, профессор кафедры анестезиологии и реаниматологии, главный научный сотрудник Научно-клинического центра анестезиологии и реаниматологии</p><p>197022, Санкт-Петербург, ул. Льва Толстого, д. 6-8</p></bio><bio xml:lang="en"><p>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</p><p>6-8, L’va Tolstogo street, Saint Petersburg, 197022</p></bio><email xlink:type="simple">khrapov.kirill@mail.ru</email><xref ref-type="aff" rid="aff-1"/></contrib><contrib contrib-type="author" corresp="yes"><name-alternatives><name name-style="eastern" xml:lang="ru"><surname>Петрищев</surname><given-names>Н. Н.</given-names></name><name name-style="western" xml:lang="en"><surname>Petrishchev</surname><given-names>N. N.</given-names></name></name-alternatives><bio xml:lang="ru"><p>Петрищев Николай Николаевич – д-р мед. наук, профессор кафедры патофизиологии с курсом клинической патофизиологии, руководитель центра лазерной медицины Научно-образовательного института биомедицины</p><p>197022, Санкт-Петербург, ул. Льва Толстого, д. 6-8</p></bio><bio xml:lang="en"><p>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</p><p>6-8, L’va Tolstogo street, Saint Petersburg, 197022</p></bio><email xlink:type="simple">lasmed@yandex.ru</email><xref ref-type="aff" rid="aff-1"/></contrib><contrib contrib-type="author" corresp="yes"><name-alternatives><name name-style="eastern" xml:lang="ru"><surname>Полушин</surname><given-names>Ю. С.</given-names></name><name name-style="western" xml:lang="en"><surname>Polushin</surname><given-names>Yu. S.</given-names></name></name-alternatives><bio xml:lang="ru"><p>Полушин Юрий Сергеевич – д-р мед. наук, профессор, академик РАН , заведующий кафедрой анестезиологии и реаниматологии, руководитель научно-клинического центра анестезиологии и реаниматологии</p><p>197022, Санкт-Петербург, ул. Льва Толстого, д. 6-8</p></bio><bio xml:lang="en"><p>Polushin Yury S. – Academician of RAS, Professor, Head of Anesthesiology and Intensive Care Department, Head of Research Clinical Center of Anesthesiology and Intensive Care</p><p>6-8, L’va Tolstogo street, Saint Petersburg, 197022</p></bio><email xlink:type="simple">polushin1@gmail.com</email><xref ref-type="aff" rid="aff-1"/></contrib><contrib contrib-type="author" corresp="yes"><name-alternatives><name name-style="eastern" xml:lang="ru"><surname>Шлык</surname><given-names>И. В.</given-names></name><name name-style="western" xml:lang="en"><surname>Shlyk</surname><given-names>I. V.</given-names></name></name-alternatives><bio xml:lang="ru"><p>Шлык Ирина Владимировна – д-р мед. наук, профессор кафедры анестезиологии и реаниматологии, зам. руководителя Научно-клинического центра анестезиологии и реаниматологии, зам. главного врача университетской клиники по анестезиологии и реаниматологии</p><p>197022, Санкт-Петербург, ул. Льва Толстого, д. 6-8</p></bio><bio xml:lang="en"><p>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</p><p>6-8, L’va Tolstogo street, Saint Petersburg, 197022</p></bio><email xlink:type="simple">irina_shlyk@mail.ru</email><xref ref-type="aff" rid="aff-1"/></contrib></contrib-group><aff-alternatives id="aff-1"><aff xml:lang="ru"><institution>Федеральное государственное бюджетное образовательное учреждение высшего образования «Первый Санкт-Петербургский государственный медицинский университет имени академика И. П. Павлова» Министерства здравоохранения Российской Федерации</institution><country>Россия</country></aff><aff xml:lang="en"><institution>Pavlov University</institution><country>Russian Federation</country></aff></aff-alternatives><pub-date pub-type="collection"><year>2021</year></pub-date><pub-date pub-type="epub"><day>09</day><month>01</month><year>2022</year></pub-date><volume>20</volume><issue>4</issue><fpage>52</fpage><lpage>61</lpage><permissions><copyright-statement>Copyright &amp;#x00A9; Ладожская-Гапеенко Е.Е., Храпов К.Н., Петрищев Н.Н., Полушин Ю.С., Шлык И.В., 2022</copyright-statement><copyright-year>2022</copyright-year><copyright-holder xml:lang="ru">Ладожская-Гапеенко Е.Е., Храпов К.Н., Петрищев Н.Н., Полушин Ю.С., Шлык И.В.</copyright-holder><copyright-holder xml:lang="en">Ladozhskaya-Gapeenko E.E., Khrapov K.N., Petrishchev N.N., Polushin Y.S., Shlyk I.V.</copyright-holder><license xml:lang="ru" license-type="creative-commons-attribution" xlink:href="https://creativecommons.org/licenses/by/4.0/" xlink:type="simple"><license-p>Данная работа распространяется под лицензией Creative Commons Attribution 4.0.</license-p></license><license xml:lang="en" license-type="creative-commons-attribution" xlink:href="https://creativecommons.org/licenses/by/4.0/" xlink:type="simple"><license-p>This work is licensed under a Creative Commons Attribution 4.0 License.</license-p></license></permissions><self-uri xlink:href="https://www.microcirc.ru/jour/article/view/1010">https://www.microcirc.ru/jour/article/view/1010</self-uri><abstract><p>Считается, что дисфункция микроциркуляции при сепсисе возникает главным образом в результате повреждения эндотелия инфекционными агентами и провоспалительными цитокинами. Вероятно, механизмы нарушения микроциркуляции при тяжелом течении COVID-19 и сепсисе могут быть схожими. Однако исследований, при которых изучали нарушения микроциркуляции у пациентов с COVID-19, в настоящее время не так много, и их результаты порой противоречивы. Цель – оценить состояние микроциркуляции у больных с тяжелым течением COVID-19 и развитием бактериального сепсиса c помощью микроскопии ногтевого ложа и лазерной допплеровской флоуметрии. Материалы и методы. В отделении реанимации обследованы 16 пациентов с COVID-19, у которых впоследствии диагностирован бактериальный сепсис. Пациентам выполняли витальную капилляроскопию и окклюзионную пробу с использованием лазерной допплеровской флоуметрии. Оценивали среднюю скорость капиллярного кровотока, размер периваскулярной зоны, плотность капилляров, наличие внутрисосудистых агрегатов, прирост амплитуды максимального постокклюзионного кровотока и среднего значения постокклюзионного кровотока относительно исходного. Дополнительно оценивали сывороточную концентрацию проадреномедуллина. Исследования выполняли в день поступления и в динамике. Результаты. При капилляроскопии у пациентов были выявлены нарушения микроциркуляции в виде снижения линейной скорости капиллярного кровотока (&lt;400 мкм/с), увеличения размера периваскулярной зоны (&gt;100 мкм), циркуляции микроагрегатов, при окклюзионной пробе определялось отсутствие постокклюзионной гиперемии. Присоединение бактериальной инфекции приводило к еще бóльшему усугублению нарушений микроциркуляции: увеличению периваскулярной зоны, прогрессию внутрисосудистой агрегации с исходом в микротромбоз с уменьшением плотности капиллярной сети (по данным капилляроскопии), а также резкому снижению амплитуды максимального прироста кровотока постокклюзионного кровотока при окклюзионной пробе. Также выявлена тенденция к отрицательной корреляции между уровнем сывороточного проадреномедуллина и максимального прироста кровотока при окклюзионной пробе. Заключение. Присоединение бактериальной инфекции у больных с COVID-19 приводит к значительному усугублению нарушений микроциркуляции с развитием явлений дефицита перфузии и интерстициального отека. Повышенная концентрация проадреномедуллина в плазме крови подтверждает концепцию о значении эндотелиальной дисфункции в патогенезе тяжелого течения COVID-19 и бактериального сепсиса.</p></abstract><trans-abstract xml:lang="en"><p>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 (&lt;400 μm/s), an extention of the perivascular zone (&gt;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.</p></trans-abstract><kwd-group xml:lang="ru"><kwd>капилляроскопия</kwd><kwd>микроциркуляция</kwd><kwd>сепсис</kwd><kwd>COVID-19</kwd><kwd>лазерная допплеровская флоуметрия</kwd><kwd>окклюзионная проба</kwd><kwd>дисфункция микроциркуляции</kwd></kwd-group><kwd-group xml:lang="en"><kwd>capillaroscopy</kwd><kwd>microcirculation</kwd><kwd>sepsis</kwd><kwd>COVID-19</kwd><kwd>laser Doppler flowmetry</kwd><kwd>occlusion test</kwd><kwd>microcirculation disfunction</kwd></kwd-group></article-meta></front><back><ref-list><title>References</title><ref id="cit1"><label>1</label><citation-alternatives><mixed-citation xml:lang="ru">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.</mixed-citation><mixed-citation xml:lang="en">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.</mixed-citation></citation-alternatives></ref><ref id="cit2"><label>2</label><citation-alternatives><mixed-citation xml:lang="ru">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.</mixed-citation><mixed-citation xml:lang="en">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.</mixed-citation></citation-alternatives></ref><ref id="cit3"><label>3</label><citation-alternatives><mixed-citation xml:lang="ru">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.</mixed-citation><mixed-citation xml:lang="en">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.</mixed-citation></citation-alternatives></ref><ref id="cit4"><label>4</label><citation-alternatives><mixed-citation xml:lang="ru">Vincent JL, De Backer D. Microvascular dysfunction as a cause of organ dysfunction in severe sepsis // Crit Care. 2005;9(Suppl 4):S9–12.</mixed-citation><mixed-citation xml:lang="en">Vincent JL, De Backer D. Microvascular dysfunction as a cause of organ dysfunction in severe sepsis // Crit Care. 2005;9(Suppl 4):S9–12.</mixed-citation></citation-alternatives></ref><ref id="cit5"><label>5</label><citation-alternatives><mixed-citation xml:lang="ru">Ince C. The microcirculation is the motor of sepsis. Crit Care 9 Suppl 4: S13–S19, 2005. 60.</mixed-citation><mixed-citation xml:lang="en">Ince C. The microcirculation is the motor of sepsis. Crit Care 9 Suppl 4: S13–S19, 2005. 60.</mixed-citation></citation-alternatives></ref><ref id="cit6"><label>6</label><citation-alternatives><mixed-citation xml:lang="ru">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.</mixed-citation><mixed-citation xml:lang="en">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.</mixed-citation></citation-alternatives></ref><ref id="cit7"><label>7</label><citation-alternatives><mixed-citation xml:lang="ru">Ince C. Hemodynamic coherence and the rationale for monitoring the microcirculation // Crit Care. 2015;(19 (Suppl. 3)):S8.</mixed-citation><mixed-citation xml:lang="en">Ince C. Hemodynamic coherence and the rationale for monitoring the microcirculation // Crit Care. 2015;(19 (Suppl. 3)):S8.</mixed-citation></citation-alternatives></ref><ref id="cit8"><label>8</label><citation-alternatives><mixed-citation xml:lang="ru">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.</mixed-citation><mixed-citation xml:lang="en">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.</mixed-citation></citation-alternatives></ref><ref id="cit9"><label>9</label><citation-alternatives><mixed-citation xml:lang="ru">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.</mixed-citation><mixed-citation xml:lang="en">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.</mixed-citation></citation-alternatives></ref><ref id="cit10"><label>10</label><citation-alternatives><mixed-citation xml:lang="ru">Bateman RM, Walley KR. Microvascular resuscitation as a therapeutic goal in severe sepsis // Crit Care. 2005;(9(Suppl 4)):S27-S32.</mixed-citation><mixed-citation xml:lang="en">Bateman RM, Walley KR. Microvascular resuscitation as a therapeutic goal in severe sepsis // Crit Care. 2005;(9(Suppl 4)):S27-S32.</mixed-citation></citation-alternatives></ref><ref id="cit11"><label>11</label><citation-alternatives><mixed-citation xml:lang="ru">Harrois A, Dupic L, Duranteau J: Targeting the microcirculation in resuscitation of acutely unwell patients // Curr Opin Crit Care. 2011;(17):303–307.</mixed-citation><mixed-citation xml:lang="en">Harrois A, Dupic L, Duranteau J: Targeting the microcirculation in resuscitation of acutely unwell patients // Curr Opin Crit Care. 2011;(17):303–307.</mixed-citation></citation-alternatives></ref><ref id="cit12"><label>12</label><citation-alternatives><mixed-citation xml:lang="ru">Nencioni A, Trzeciak S, Shapiro NI: The microcirculation as a diagnostic and therapeutic target in sepsis // Intern Emerg Med. 2009,(4):413–418.</mixed-citation><mixed-citation xml:lang="en">Nencioni A, Trzeciak S, Shapiro NI: The microcirculation as a diagnostic and therapeutic target in sepsis // Intern Emerg Med. 2009,(4):413–418.</mixed-citation></citation-alternatives></ref><ref id="cit13"><label>13</label><citation-alternatives><mixed-citation xml:lang="ru">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.</mixed-citation><mixed-citation xml:lang="en">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.</mixed-citation></citation-alternatives></ref><ref id="cit14"><label>14</label><citation-alternatives><mixed-citation xml:lang="ru">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.</mixed-citation><mixed-citation xml:lang="en">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.</mixed-citation></citation-alternatives></ref><ref id="cit15"><label>15</label><citation-alternatives><mixed-citation xml:lang="ru">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.</mixed-citation><mixed-citation xml:lang="en">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.</mixed-citation></citation-alternatives></ref><ref id="cit16"><label>16</label><citation-alternatives><mixed-citation xml:lang="ru">Kitamura K, Kangawa K, Eto T. Adrenomedullin and PAMP: discovery, structures, and cardiovascular functions // Microsc Res Tech. 2002;(57):3–13.</mixed-citation><mixed-citation xml:lang="en">Kitamura K, Kangawa K, Eto T. Adrenomedullin and PAMP: discovery, structures, and cardiovascular functions // Microsc Res Tech. 2002;(57):3–13.</mixed-citation></citation-alternatives></ref><ref id="cit17"><label>17</label><citation-alternatives><mixed-citation xml:lang="ru">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.</mixed-citation><mixed-citation xml:lang="en">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.</mixed-citation></citation-alternatives></ref><ref id="cit18"><label>18</label><citation-alternatives><mixed-citation xml:lang="ru">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.</mixed-citation><mixed-citation xml:lang="en">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.</mixed-citation></citation-alternatives></ref><ref id="cit19"><label>19</label><citation-alternatives><mixed-citation xml:lang="ru">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.</mixed-citation><mixed-citation xml:lang="en">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.</mixed-citation></citation-alternatives></ref><ref id="cit20"><label>20</label><citation-alternatives><mixed-citation xml:lang="ru">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.</mixed-citation><mixed-citation xml:lang="en">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.</mixed-citation></citation-alternatives></ref><ref id="cit21"><label>21</label><citation-alternatives><mixed-citation xml:lang="ru">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.</mixed-citation><mixed-citation xml:lang="en">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.</mixed-citation></citation-alternatives></ref><ref id="cit22"><label>22</label><citation-alternatives><mixed-citation xml:lang="ru">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.</mixed-citation><mixed-citation xml:lang="en">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.</mixed-citation></citation-alternatives></ref><ref id="cit23"><label>23</label><citation-alternatives><mixed-citation xml:lang="ru">Структурные и функциональные изменения микроциркуляторного русла на уровне капилляров у больных сердечно-сосудистыми заболеваниями (артериальная гипертензия, ишемическая болезнь сердца, хроническая сердечная недостаточность) / Ю. Н. Беленков, Е. В. Привалова, Ю. А. Данилогорская, А. А. Щендрыгина // Кардиология и сердечно-сосудистая хир. 2012. – Т. 5, № 2. С. 49–56.</mixed-citation><mixed-citation xml:lang="en">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.).</mixed-citation></citation-alternatives></ref><ref id="cit24"><label>24</label><citation-alternatives><mixed-citation xml:lang="ru">Ладожская-Гапеенко Е. Е., Храпов К. Н., Полушин Ю. С. и др. Нарушения микроциркуляции у больных с тяжелым течением COVID-19 // Вестн. анестезиологии и реаниматологии. – 2021. – Т. 18, № 4. – С. 7–19.</mixed-citation><mixed-citation xml:lang="en">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.</mixed-citation></citation-alternatives></ref><ref id="cit25"><label>25</label><citation-alternatives><mixed-citation xml:lang="ru">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.</mixed-citation><mixed-citation xml:lang="en">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.</mixed-citation></citation-alternatives></ref><ref id="cit26"><label>26</label><citation-alternatives><mixed-citation xml:lang="ru">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.</mixed-citation><mixed-citation xml:lang="en">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.</mixed-citation></citation-alternatives></ref><ref id="cit27"><label>27</label><citation-alternatives><mixed-citation xml:lang="ru">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.</mixed-citation><mixed-citation xml:lang="en">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.</mixed-citation></citation-alternatives></ref><ref id="cit28"><label>28</label><citation-alternatives><mixed-citation xml:lang="ru">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.</mixed-citation><mixed-citation xml:lang="en">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.</mixed-citation></citation-alternatives></ref><ref id="cit29"><label>29</label><citation-alternatives><mixed-citation xml:lang="ru">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.</mixed-citation><mixed-citation xml:lang="en">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.</mixed-citation></citation-alternatives></ref><ref id="cit30"><label>30</label><citation-alternatives><mixed-citation xml:lang="ru">Spanos A, Jhanji S, Vivian-Smith A, Harris T, Pearse RM. Early microvascular changes in sepsis and severe sepsis // Shock. 2010;(33):387–391.</mixed-citation><mixed-citation xml:lang="en">Spanos A, Jhanji S, Vivian-Smith A, Harris T, Pearse RM. Early microvascular changes in sepsis and severe sepsis // Shock. 2010;(33):387–391.</mixed-citation></citation-alternatives></ref><ref id="cit31"><label>31</label><citation-alternatives><mixed-citation xml:lang="ru">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.</mixed-citation><mixed-citation xml:lang="en">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.</mixed-citation></citation-alternatives></ref><ref id="cit32"><label>32</label><citation-alternatives><mixed-citation xml:lang="ru">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.</mixed-citation><mixed-citation xml:lang="en">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.</mixed-citation></citation-alternatives></ref><ref id="cit33"><label>33</label><citation-alternatives><mixed-citation xml:lang="ru">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.</mixed-citation><mixed-citation xml:lang="en">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.</mixed-citation></citation-alternatives></ref><ref id="cit34"><label>34</label><citation-alternatives><mixed-citation xml:lang="ru">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.</mixed-citation><mixed-citation xml:lang="en">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.</mixed-citation></citation-alternatives></ref><ref id="cit35"><label>35</label><citation-alternatives><mixed-citation xml:lang="ru">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.</mixed-citation><mixed-citation xml:lang="en">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.</mixed-citation></citation-alternatives></ref></ref-list><fn-group><fn fn-type="conflict"><p>The authors declare that there are no conflicts of interest present.</p></fn></fn-group></back></article>
