Microcirculation in the intensive care unit

Dubin, Arnaldo

doi:10.1590/S0103-507X2011000300001

EDITORIAL

Cátedra de Farmacología Aplicada, Facultad de Ciencias Médicas, Universidad Nacional de La Plata, La Plata, Argentina; Servicio de Terapia Intensiva, Sanatorio Otamendi y Miroli, Buenos Aires, Argentina

Corresponding author

The maintenance of tissue oxygenation is a main goal in the care of critically ill patients. Unfortunately, there is no gold standard for its monitoring. For many years, research was focused on the behavior of systemic oxygen-derived parameters. In this way, a large number of studies attempted to address the meaning of the different relationships between oxygen transport (DO₂) and consumption (VO₂).

Sepsis is characterized by abnormalities in oxygen extraction, but the significance of a plateau of VO₂ or a linear VO₂/DO₂ relationship (the so-called pathological dependency) remains uncertain.⁽¹⁾ Moreover, severe tissue hypoperfusion might be present even under conditions of normal or increased systemic and intestinal VO₂. In contrast, parallel changes in VO₂ and DO₂ might not be a pathological phenomenon but rather reflect the physiological behavior of the system, in which cardiac output and DO₂ are modified to satisfy changing oxygen demands. These parameters may in fact be misleading because of methodological drawbacks related to their measurements and calculations. Surrogates of VO₂/DO₂ such as central venous or mixed venous oxygen saturations are usually normal in ICU patients.⁽²⁾Consequently, its usefulness, if any, seems to be related only to patients who do not receive resuscitation.⁽³⁾

The development of gastrointestinal tonometry and the subsequent introduction of different forms of tissue capnometry were important steps in the monitoring of tissue perfusion. Gastrointestinal tonometry rapidly became a useful tool in basic research. In addition, and for the first time, a regional parameter was used to detect and to treat hypoperfusion in the critically ill.⁽⁴⁾ Despite a large body of evidence demonstrating their value, gastric tonometry and sublingual capnography are no longer used. Different methodological pitfalls as well as commercial issues could explain this situation.

In this issue of RBTI, two articles have been published reviewing recent advances in the monitoring of tissue oxygenation and perfusion.^(5,6)Both are comprehensive evaluations of emerging technologies that could potentially help clinicians to better understand, monitor and treat critically ill patients.

In the last few years, the direct evaluation of microcirculation was translated from the basic research laboratories to intensive care units. The advances in videomicroscopic techniques, first with OPS and later with the improved SDF imaging device, now make it possible to visualize the microcirculation of any mucosa without contrast injection, at the bedside.⁽⁷⁾ Dr. Penna et al. review recent basic and clinical research performed in sepsis with these techniques.⁽⁵⁾

A number of issues are worthy of comment: first, the main limitation for the clinical implementation of videomicroscopic techniques is the evaluation of the images. Beyond the cautions needed to properly record the videos of the microcirculation, the analysis is both cumbersome and time consuming. Measurements of density, velocity and heterogeneity are the main parameters to analyze.⁽⁸⁾ This can be done by the human eye or by the use of specific software. Future developments in this area should include new software that could rapidly provide objective information to clinicians.

In contrast to the hyperdynamic systemic circulation, the septic microcirculation is characterized mainly by hypoperfusion (decreased perfused capillary density, fraction of perfused capillaries and microvascular flow index) and increased heterogeneity.^(9,10) In contrast, capillaries with increased blood flow are absent in the sublingual microcirculation of septic patients. Data from our group -still unpublished- show that only 4% of capillaries of septic shock patients show red blood cell velocities higher than the 75th percentile of the velocities of the normal volunteers.

Another relevant issue related to the microcirculation in sepsis is the heterogeneous behavior of different microvascular beds. Although Verdant et al. showed a similar pattern of sublingual circulation and intestinal villi hypoperfusion, this experimental study has an important limitation.⁽¹¹⁾ The microcirculatory derangements were much more severe than those described in septic patients. Therefore, it is possible that a more critical condition affects every territory homogeneously. In contrast, in a model of endotoxemic shock, the normalization of systemic and intestinal hemodynamics by fluid resuscitation corrected the sublingual and ileal serosal microvascular alterations. Villi hypoperfusion, however, remained present.⁽¹²⁾ Accordingly, Boerma et al. showed a dissimilar behavior of sublingual and gut microcirculation in postoperative septic patients with intestinal ostomies. Consequently, different microcirculatory beds could behave differently.⁽¹³⁾

Although heterogeneity is present, strong evidence suggests that the monitoring of sublingual microcirculation in critically ill patients provides valuable information in terms of the severity of illness, outcome and monitoring of the treatment response.

In another review published in this issue of RBTI, Drs. Lima and Bakker comprehensively discussed the basics and new developments of near infrared spectroscopy (NIRS), with special emphasis regarding the monitoring of skeletal muscle oxygenation.⁽⁶⁾ Remarkably, NIRS allows for the continuous and non-invasive monitoring of tissue oxygen saturation (StO₂). Although these characteristics are appealing, values of StO₂ are only clearly reduced in low-flow states. In sepsis, in which cardiac output is usually normal or elevated, StO₂ values may not differ from those of normal volunteers. In contrast, the dynamic response of StO₂ provides relevant information. As a manifestation of the severe microvascular disorders in sepsis, the slope of the recovery of StO₂ (ΔStO₂) after an occlusion test sharply differentiates healthy from septic subjects and survivors from non-survivor septic patients.⁽¹⁴⁾ The ΔStO₂ reflects the adequacy of the reactive hyperemia. Reactive hyperemia is the increase in blood flow in response to a period of ischemia and reflects the ability to recruit the microcirculation. Accordingly, Georger et al. showed that the increase in mean arterial blood pressure from 54 ± 8 to 77 ± 9 mmHg improves ΔStO₂.⁽¹⁵⁾ This finding could be interpreted as an improvement in microvascular perfusion in response to the elevation of blood pressure above the lower limit of the autoregulation of blood flow.

In this way, it is expectable that different microcirculatory territories might display heterogeneous behaviors owing to characteristics of the underlying disease or to the response to treatment. Therefore, the monitoring of microcirculation should ideally be targeted to different microvascular beds. A complete approach should include sublingual SDF imaging, muscle ΔStO₂ and tissue capnometry. Several methodological problems, however, need to be addressed. Moreover, clinical trials aimed at improving the microcirculation should demonstrate the actual value of these approaches. In the meantime, sublingual microcirculation and muscle StO₂ remain attractive windows for improving our pathophysiologic knowledge.

REFERENCES

1. Cain SM. Supply dependency of oxygen uptake in ARDS: myth or reality? Am J Med Sci. 1984;288(3):119-24.
2. van Beest PA, Hofstra JJ, Schultz MJ, Boerma EC, Spronk PE, Kuiper MA. The incidence of low venous oxygen saturation on admission to the intensive care unit: a multi-center observational study in The Netherlands. Crit Care. 2008;12(2):R33.
3. Rivers E, Nguyen B, Havstad S, Ressler J, Muzzin A, Knoblich B, Peterson E, Tomlanovich M; Early Goal-Directed Therapy Collaborative Group. Early goal-directed therapy in the treatment of severe sepsis and septic shock. N Engl J Med. 2001;345(19):1368-77.
4. Gutierrez G, Palizas F, Doglio G, Doglio G, Wainsztein N, Gallesio A, et al. Gastric intramucosal pH as a therapeutic index of tissue oxygenation in critically ill patients. Lancet. 1992;339(8787):195-9.
5. Penna GL, Salgado DR, Japiassú AM, Kalichsztein M, Nobre GF, Vilella N, Bouskela. Avaliação da microcirculação: uma nova arma no manejo da sepse? Rev Bras Ter Intensiva. 2011;23(3): 352-7.
6. Lima A, Bakker J. Espectroscopia no infravermelho próximo para a monitorização da perfusão tecidual. Rev Bras Ter Intensiva. 2011;23(3):341-51.
7. Goedhart PT, Khalilzada M, Bezemer R, Merza J, Ince C. Sidestream Dark Field (SDF) imaging: a novel stroboscopic LED ring-based imaging modality for clinical assessment of the microcirculation. Opt Express. 2007;15(23):15101-14.
8. De Backer D, Hollenberg S, Boerma C, Goedhart P, Büchele G, Ospina-Tascon G, et al. How to evaluate the microcirculation: report of a round table conference. Crit Care. 2007;11(5):R101.
9. 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.
10. Trzeciak S, Dellinger RP, Parrillo JE, Guglielmi M, Bajaj J, Abate NL, Arnold RC, Colilla S, Zanotti S, Hollenberg SM; Microcirculatory Alterations in Resuscitation and Shock Investigators. Early microcirculatory perfusion derangements in patients with severe sepsis and septic shock: relationship to hemodynamics, oxygen transport, and survival. Ann Emerg Med. 2007;49(1):88-98, 98.e1-2.
11. Verdant CL, De Backer D, Bruhn A, Clausi CM, Su F, Wang Z, et al. Evaluation of sublingual and gut mucosal microcirculation in sepsis: a quantitative analysis. Crit Care Med. 2009;37(11):2875-81.
12. Dubin A, Edul VS, Pozo MO, Murias G, Canullán CM, Martins EF, et al. Persistent villi hypoperfusion explains intramucosal acidosis in sheep endotoxemia. Crit Care Med. 2008;36(2):535-42.
13. Boerma EC, Kuiper MA, Kingma WP, Egbers PH, Gerritsen RT, Ince C. Disparity between skin perfusion and sublingual microcirculatory alterations in severe sepsis and septic shock: a prospective observational study. Intensive Care Med. 2008;34(7):1294-8.
14. Creteur J, Carollo T, Soldati G, Buchele G, De Backer D, Vincent JL. The prognostic value of muscle StO₂ in septic patients. Intensive Care Med. 2007;33(9):1549-56.
15. Georger JF, Hamzaoui O, Chaari A, Maizel J, Richard C, Teboul JL. Restoring arterial pressure with norepinephrine improves muscle tissue oxygenation assessed by near-infrared spectroscopy in severely hypotensive septic patients. Intensive Care Med. 2010;36(11):1882-9.