Association and dissociation of microcirculation and macrocirculation in critically ill patients with shock
Editorial Commentary

Association and dissociation of microcirculation and macrocirculation in critically ill patients with shock

Yu-Chang Yeh, Ching-Tang Chiu

Department of Anesthesiology, National Taiwan University Hospital, Taipei

Correspondence to: Yu-Chang Yeh, MD, PhD. No 7, Chung Shan South Road, Taipei. Email:

Received: 14 September 2019; Accepted: 15 October 2019; Published: 13 December 2019.

doi: 10.21037/jeccm.2019.10.05

Pitfalls of macrocirculation

Early goal-directed therapy with maintenance of adequate central venous pressure (CVP), mean arterial pressure (MAP), and central venous oxygen saturation (ScvO2) fails to improve survival (1-3) in patients with shock, which emphasizes the fact that normal values of macrocirculation parameters may be inadequate to prevent shock.

Poor macrocirculation is associated with poor microcirculation, but microcirculatory dysfunction may exist despite the normalization of macrocirculation. CVP is affected and limited by several factors (4). The predictability of fluid responsiveness of CVP is low (5). Increased CVP may reduce renal perfusion (6). In addition, maintaining a high MAP with high dose vasopressor may cause excessive vasoconstriction, which may lead to a reduced number of perfused small vessels in the tissue (7). However, maintaining a high MAP by using adequate dose of vasopressor in patients with a past history of hypertension may improve microcirculation (8,9). Furthermore, during disseminated intravascular coagulation, microthrombosis may occlude tissue microvascular blood flow and result in shunting of the microvascular blood flow, which may eventually lead to a falsely high ScvO2. Because of the frequent dissociation between microcirculation and systemic hemodynamics, only direct measurement of the microcirculation in different tissues may indicate microcirculatory dysfunction in patients with shock exhibiting normal macrocirculation parameters.

Techniques for clinical microcirculation research

Several methods can be used to measure or evaluate microvascular perfusion (10). Laser Doppler is used to measure the velocity of red blood cells (RBCs) (11). Near-infrared spectroscopy (NIRS) is used to measure tissue oxygen saturation (12). Microvascular reactivity can be evaluated using laser Doppler or NIRS (13). Laser speckle imaging is used to compare the perfusion intensity of microvascular blood flow and reveal the heterogeneity of microcirculation (14). Videomicroscopy is used to measure the density of perfused small vessels and evaluate the microvascular blood flow classification (15-17). The sublingual area is most frequently used to evaluate and measure the microcirculation in clinical studies. The most frequently used microcirculation parameters include total small vessel (less than 20 µm) density (TSVD), blood flow classification of small vessels, perfused small vessel density (PSVD), proportion of perfused small vessels (PPV), microvascular flow index (MFI) score, and heterogeneity index (HI) (18). The quality of microcirculation videos is crucial for correct evaluation of the microcirculation (19).

Microcirculatory dysfunction in critically ill patients with shock

In patients with sepsis or septic shock, microvascular blood flow is altered; microcirculatory dysfunction is more severe in non-survivors than in survivors (20). Various damages may result in microcirculatory dysfunction in patients with septic shock. Hypovolemia, loss of vascular reactivity and autoregulation, and microthrombosis reduce the density of perfused small vessels and may lead to shunting of oxygen from the hypoperfused area to the hyperperfused area. Systemic inflammations may cause glycocalyx degradation and manifest capillary leakage and subsequent tissue edema. Although excessive use of vasopressors may reduce the density of perfused small vessels, adequate use of vasopressors may be required to increase microvascular perfusion (8). In patients with sepsis and septic shock, microcirculatory dysfunction was more severe in the 28-day nonsurvivor group than in the 28-day survivor group (21). In patients with surgical or traumatic hemorrhagic shock, our previous study revealed that early TSVD and PSVD are correlated with the lactate level 24 h after surgery (22). Tachon et al. found that the sublingual microcirculation was impaired for at least 72 h after restoration of the macrocirculation in patients with traumatic hemorrhagic shock (23). In patients with cardiogenic shock, decreased cardiac output impairs microvascular perfusion, and subsequent systemic inflammation may result in further impairment of microcirculation (24). In patients with out-of-hospital cardiac arrest, persistent microcirculatory dysfunction is associated with poor survival (25). For patients on venoarterial extracorporeal membrane oxygen (VA-ECMO) life support, microcirculatory dysfunction is more severe in non-survivors than in survivors (26,27). Akin et al. used sublingual microcirculation as a novel potential marker to identify successful weaning from VA-ECMO (28).

Limitations of microcirculation in clinical practice

There exist several limitations of using microcirculation in clinical practice and shock resuscitation. First, the unavailability of expensive devices and time-consuming analysis of microcirculation videos limit the possibility of frequent microcirculation monitoring for every patient. Second, some microcirculation parameters are semi-quantified and time-consuming. High adherence to the consensus and internal validation in the study group are crucial to maintain a high-quality examination of microcirculation. A new, real-time, and automated analysis software for microcirculatory videos is required. Third, most microcirculation studies can only measure the tissue surface in several specific areas. However, the microcirculation in the deeper layers of the tissue and in different organs may not always correlate with the microcirculation in the investigated area. The kidneys and intestine are vulnerable to hypoperfusion in patients with different types of shock. Novel techniques or specific biomarkers are required to investigate the microcirculation in the kidneys and intestine.

How to resuscitate microcirculation without information of microcirculation parameters?

Increasing cardiac output, early fluid supplementation, adequate use of vasopressors, careful transfusion of RBCs, avoid excessive vasoconstriction, and blood purification are strategies to improve PSVD and microvascular blood flow (29). However, during the unavailability of a device to evaluate the microcirculation, substitute parameters may be helpful. Several measurements are suggested to represent microcirculation, including lactate levels (30), the gap between the venous and arterial carbon dioxide (31), and capillary filling time (32).


Normal values of macrocirculation parameters may be inadequate for shock resuscitation. The first step is to combine several macrocirculation parameters for appropriate decision—to guide the resuscitation of systemic hemodynamics. The second step is to evaluate the microcirculation or use substitute measurement to resuscitate the microcirculation. New techniques and software are required for timely evaluation and resuscitation of the microcirculation to maintain adequate tissue perfusion.




Conflicts of Interest: The authors have no conflicts of interest to declare.

Ethical Statement: The authors are accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved.


  1. ARISE Investigators, ANZICS Clinical Trials Group, Peake SL, et al. Goal-directed resuscitation for patients with early septic shock. N Engl J Med 2014;371:1496-506. [Crossref] [PubMed]
  2. Mouncey PR, Osborn TM, Power GS, et al. Trial of early, goal-directed resuscitation for septic shock. N Engl J Med 2015;372:1301-11. [Crossref] [PubMed]
  3. ProCESS Investigators, Yealy DM, Kellum JA, et al. A randomized trial of protocol-based care for early septic shock. N Engl J Med 2014;370:1683-93. [Crossref] [PubMed]
  4. Rhodes A, Evans LE, Alhazzani W, et al. Surviving Sepsis Campaign: International Guidelines for Management of Sepsis and Septic Shock: 2016. Crit Care Med 2017;45:486-552. [Crossref] [PubMed]
  5. Marik PE, Monnet X, Teboul JL. Hemodynamic parameters to guide fluid therapy. Ann Intensive Care 2011;1:1. [Crossref] [PubMed]
  6. Chen X, Wang X, Honore PM, et al. Renal failure in critically ill patients, beware of applying (central venous) pressure on the kidney. Ann Intensive Care 2018;8:91. [Crossref] [PubMed]
  7. Dubin A, Pozo MO, Casabella CA, et al. Increasing arterial blood pressure with norepinephrine does not improve microcirculatory blood flow: a prospective study. Crit Care 2009;13:R92. [Crossref] [PubMed]
  8. Fiorese Coimbra KT, de Freitas FGR, Bafi AT, et al. Effect of Increasing Blood Pressure With Noradrenaline on the Microcirculation of Patients With Septic Shock and Previous Arterial Hypertension. Crit Care Med 2019;47:1033-40. [Crossref] [PubMed]
  9. Thooft A, Favory R, Salgado DR, et al. Effects of changes in arterial pressure on organ perfusion during septic shock. Crit Care 2011;15:R222. [Crossref] [PubMed]
  10. De Backer D, Durand A. Monitoring the microcirculation in critically ill patients. Best Pract Res Clin Anaesthesiol 2014;28:441-51. [Crossref] [PubMed]
  11. Boyle NH, Roberts PC, Ng B, et al. Scanning laser Doppler is a useful technique to assess foot cutaneous perfusion during femoral artery cannulation. Crit Care 1999;3:95-100. [Crossref] [PubMed]
  12. Crookes BA, Cohn SM, Bloch S, et al. Can near-infrared spectroscopy identify the severity of shock in trauma patients? J Trauma 2005;58:806-13; discussion 813-6. [Crossref] [PubMed]
  13. Creteur J, Carollo T, Soldati G, et al. The prognostic value of muscle StO2 in septic patients. Intensive Care Med 2007;33:1549-56. [Crossref] [PubMed]
  14. Legrand M, Bezemer R, Kandil A, et al. The role of renal hypoperfusion in development of renal microcirculatory dysfunction in endotoxemic rats. Intensive Care Med 2011;37:1534-42. [Crossref] [PubMed]
  15. Balestra GM, Bezemer R, Boerma EC, et al. Improvement of sidestream dark field imaging with an image acquisition stabilizer. BMC Med Imaging 2010;10:15. [Crossref] [PubMed]
  16. Dubin A. Physiology and technology hand in hand for clinical imaging of the microcirculation. Intensive Care Med 2009;35:1815. [Crossref] [PubMed]
  17. Milstein DMJ, Romay E, Ince C. A novel computer-controlled high resolution video microscopy imaging system enables measuring mucosal subsurface focal depth for rapid acquisition of oral microcirculation video images. Intensive Care Med 2012;38:S271.
  18. De Backer D, Hollenberg S, Boerma C, et al. How to evaluate the microcirculation: report of a round table conference. Crit Care 2007;11:R101. [Crossref] [PubMed]
  19. Ince C, Boerma EC, Cecconi M, et al. Second consensus on the assessment of sublingual microcirculation in critically ill patients: results from a task force of the European Society of Intensive Care Medicine. Intensive Care Med 2018;44:281-99. [Crossref] [PubMed]
  20. De Backer D, Creteur J, Preiser JC, et al. Microvascular blood flow is altered in patients with sepsis. Am J Respir Crit Care Med 2002;166:98-104. [Crossref] [PubMed]
  21. Shih CC, Liu CM, Chao A, et al. Matched Comparison of Microcirculation Between Healthy Volunteers and Patients with Sepsis. Asian J Anesthesiol 2018;56:14-22. [PubMed]
  22. Yeh YC, Wang MJ, Chao A, et al. Correlation between early sublingual small vessel density and late blood lactate level in critically ill surgical patients. J Surg Res 2013;180:317-21. [Crossref] [PubMed]
  23. Tachon G, Harrois A, Tanaka S, et al. Microcirculatory alterations in traumatic hemorrhagic shock. Crit Care Med 2014;42:1433-41. [Crossref] [PubMed]
  24. Ashruf JF, Bruining HA, Ince C. New insights into the pathophysiology of cardiogenic shock: the role of the microcirculation. Curr Opin Crit Care 2013;19:381-6. [Crossref] [PubMed]
  25. Lehmann C, Cerny V, Abdo I, et al. Microcirculation diagnostics and applied studies in circulatory shock - research from the bench to the bedside. Clin Hemorheol Microcirc 2012;52:131-9. [Crossref] [PubMed]
  26. Yeh YC, Lee CT, Wang CH, et al. Investigation of microcirculation in patients with venoarterial extracorporeal membrane oxygenation life support. Crit Care 2018;22:200. [Crossref] [PubMed]
  27. Kara A, Akin S, Dos Reis Miranda D, et al. Microcirculatory assessment of patients under VA-ECMO. Crit Care 2016;20:344. [Crossref] [PubMed]
  28. Akin S, Dos Reis Miranda D, Caliskan K, et al. Functional evaluation of sublingual microcirculation indicates successful weaning from VA-ECMO in cardiogenic shock. Crit Care 2017;21:265. [Crossref] [PubMed]
  29. Shapiro NI, Angus DC. A review of therapeutic attempts to recruit the microcirculation in patients with sepsis. Minerva Anestesiol 2014;80:225-35. [PubMed]
  30. Jansen TC, van Bommel J, Schoonderbeek FJ, et al. Early lactate-guided therapy in intensive care unit patients: a multicenter, open-label, randomized controlled trial. Am J Respir Crit Care Med 2010;182:752-61. [Crossref] [PubMed]
  31. Ospina-Tascón GA, Umana M, Bermudez WF, et al. Can venous-to-arterial carbon dioxide differences reflect microcirculatory alterations in patients with septic shock? Intensive Care Med 2016;42:211-21. [Crossref] [PubMed]
  32. Hernández G, Ospina-Tascon GA, Damiani LP, et al. Effect of a Resuscitation Strategy Targeting Peripheral Perfusion Status vs Serum Lactate Levels on 28-Day Mortality Among Patients With Septic Shock: The ANDROMEDA-SHOCK Randomized Clinical Trial. JAMA 2019;321:654-64. [Crossref] [PubMed]
doi: 10.21037/jeccm.2019.10.05
Cite this article as: Yeh YC, Chiu CT. Association and dissociation of microcirculation and macrocirculation in critically ill patients with shock. J Emerg Crit Care Med 2019;3:60.