This work and investigation sure to follow will undoubtedly provide new insights into the pathophysiology of sepsis and the potential for a novel therapeutic target.
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Has the Cat Got Your Tongue Evaluation of Circulation by Microcirculation.pdf
This work and investigation sure to follow will undoubtedly provide new insights into the pathophysiology of sepsis and the potential for a novel therapeutic target.
This work and investigation sure to follow will undoubtedly provide new insights into the pathophysiology of sepsis and the potential for a novel therapeutic target.
920 www.ccmjournal.org March 2013 Volume 41 Number 3
This work and investigation sure to follow will undoubtedly provide new insights into the pathophysiology of sepsis and the potential for a novel therapeutic target. REFERENCES 1. Martin GS, Mannino DM, Eaton S, et al: The epidemiology of sepsis in the United States from 1979 through 2000. N Engl J Med 2003; 348:1546 1554 2. Dellinger RP, Levy MM, Carlet JM, et al: Surviving Sepsis Campaign: International guidelines for management of severe sepsis and septic shock. Crit Care Med 2008; 36:295327 3. Vincent JL, Opal SM, Marshall JC: Ten reasons why we should NOT use severity scores as entry criteria for clinical trials or in our treat- ment decisions. Crit Care Med 2010; 38:283287 4. Pierrakos C, Vincent JL: Sepsis biomarkers: A review. Crit Care 2010; 14:R15 5. Janz DR, Bastarache JA, Peterson JF: Association Between Cell-Free Hemoglobin, Acetaminophen, and Mortality in Patients With Sepsis: An Observational Study. Crit Care Med 2013; 41:784790 6. Larsen R, Gozzelino R, Jeney V, et al: A central role for free heme in the pathogenesis of severe sepsis. Sci Transl Med 2010; 2:51ra71 7. Reiter CD, Wang X, Tanus-Santos JE, et al: Cell-free hemoglobin lim- its nitric oxide bioavailability in sickle-cell disease. Nat Med 2002; 8:13831389 8. Boutaud O, Moore KP, Reeder BJ, et al: Acetaminophen inhibits hemoprotein-catalyzed lipid peroxidation and attenuates rhabdomyol- ysis-induced renal failure. Proc Natl Acad Sci USA 2010; 107:2699 2704 9. Rivers E, Nguyen B, Havstad S, et al; Early Goal-Directed Therapy Collaborative Group: Early goal-directed therapy in the treatment of severe sepsis and septic shock. N Engl J Med 2001; 345:1368 1377 10. Gaieski DF, Mikkelsen ME, Band RA, et al: Impact of time to antibiot- ics on survival in patients with severe sepsis or septic shock in whom early goal-directed therapy was initiated in the emergency depart- ment. Crit Care Med 2010; 38:10451053 11. Lee BH, Inui D, Suh GY, et al; Fever and Antipyretic in Critically ill pa- tients Evaluation (FACE) Study Group: Association of body tempera- ture and antipyretic treatments with mortality of critically ill patients with and without sepsis: Multi-centered prospective observational study. Crit Care 2012; 16:R33 D e Backer et al describe the value of assessing sublin- gual microcirculation for estimating the outcome in patients with severe sepsis in this issue of Critical Care Medicine (1). Microvascular dysfunction seems to be the key element of the pathogenesis of septic shock. The causes of this dysfunction may lie in the occurrence of generalized micro- vascular thrombosis (2). This thrombosis may prevent bacteria in the tissues from trafcking to the systemic circulation via the capillaries. However, when this microvascular thrombo- sis is generalizing, microvascular dysfunction with extensive tissue ischemia may result in organ failure and even death. On the other hand, global hemodynamic parameters are de- ranged in patients suffering from septic shock (3). The ques- tion is whether these global hemodynamic measures are as- sociated with regional hemodynamics and vice versa. Indeed, hemodynamic monitoring of septic patients is impeded by the discrepancy between the macrohemodynamics and the mi- crocirculation of internal organs. Microcirculation dysfunc- tion does not correlate with the internal organs circulation because of the highly heterogeneous micro circulation struc- ture and function in different sites (4). Furthermore, despite therapeutic correction of systemic oxygen delivery variables, regional hypoxia and oxygen extraction decits persist. The determination of microvascular dysfunction may not only be a prognostic parameter but also help guiding therapeutic measures in patients with septic shock. The development of new technologies such as capillary microscopy, laser Doppler, intravital videomicroscopy, or- thogonal polarization spectral (OPS), and sidestream darkeld imaging (SDF) enabled microcirculation monitoring. The lat- ter two have been used in the study by De Backer et al (1). Overall, physicianscientists using one of these possibilities try to connect micro circulatory imbalance with global hemody- namic dysfunction and outcome. For instance, tissue oxygen saturation (StO 2 ) in septic shock patients as measured by tissue spectroscopy was signicantly lower in the nonsurvivors than in the survivors. In detail, StO 2 values < 78% were associated with increased mortality at day 28 (5). Interestingly, StO 2 cor- relates with central venous saturation (ScvO 2 ) in normotensive patients with severe sepsis or septic shock (6). ScvO 2 correlates with the cardiac index in patients suffering from septic shock (7). Thus, we can seemingly derive an association between the microcirculation and a parameter from global hemo- dynamics from this study. Besides the oxygen tension, tissue hypercarbia as measured in the ear lobe has also been shown Has the Cat Got Your Tongue? Evaluation of Circulation by Microcirculation* Martijn van Griensven, MD, PhD Department of Trauma Surgery Klinikum rechts der Isar Technical University Munich Munich, Germany *See also p. 791. Key Words: hemodynamics; microcirculation; sepsis; shock; tissue oxygenation The author has not disclosed any potential conflicts of interest. Copyright 2013 by the Society of Critical Care Medicine and Lippincott Williams & Wilkins DOI: 10.1097/CCM.0b013e3182770e61 Editorials Critical Care Medicine www.ccmjournal.org 921 to be correlated with microcirculatory alterations in septic patients (8). Sublingual capnometry resulted in similar results (9). Regional microcirculatory blood ow is the main determinant of sublingual carbon dioxide partial pressure. No association with systemic carbon dioxide partial pressure could be detected. Furthermore, during the early phase of re- suscitated severe sepsis and septic shock, there appears to be no correlation between sublingual microcirculatory alterations and the central-to-toe temperature differences (10). All of the above mentioned methods represent simple, noninvasive methods to monitor microcirculatory alterations in septic patients. Most of the studies underline the idea of a dispersive nature of blood ow under conditions of sepsis between microcirculatory and systemic hemodynamics. This is corroborated by the study of De Backer et al (1) using OPS and SDF sublingual microcirculation imaging. They presented a large cohort of patients having undergone measurements of their microcirculation. Unfortunately, the patients were included in different studies, and the measurements presented were only performed at the start of the respective studies during an extended period of time. Therefore, the outcome may not only depend on early microcirculatory function but also on interventions performed. Nevertheless, the measurements are very valuable as pathologic values are shown upon admission to the ICU. Thus, these methods may be helpful in determining the status of the patients. Two different methods of measurement have been usedOPS and SDFwhich can be discussed as being a disadvantage as well as an advantage. It may be argued that the results are obtained by different methods and cannot be compared completely. On the other hand, although two different methods were used, overall valid conclusions could be drawn. Thus, it would not make a difference which method is being used in a clinical setting. The ndings indicate that microcirculation is dysfunctional in severe sepsis despite relatively normal global hemodynamic parameters. Especially the proportion of perfused small vessels (PPVs) was the most strongly associated with outcome (area under the curve = 0.818) (1). PPV and lactate levels were independent determinants of the outcome of severe sepsis in the early phase. The authors also investigated 48 patients 48 hrs after onset of severe sepsis. In these patients, PPV alterations were not as pronounced anymore. Therefore, it is important to determine the microcirculatory status as early as possible to be able to prioritize therapy. Microcirculatory recruitment is needed to ensure adequate microcirculatory perfusion and the oxygenation of tissue cells. Therapy must include focused recruitment of hypoxic-shunted microcirculatory compartments. It has been shown that clinical application of these devices is feasible. It is important that the measurements are readily avail- able and interpretable without the need of extensive calcula- tions. In that case, this tool of determining the microcirculatory status in the sublingual or thenar area will be a valuable piece in diagnosing and in the prognosis of (severe) sepsis. Especially, as the microcirculatory status is not reected by global hemo- dynamic parameters. REFERENCES 1. De Backer D, Donadello K, Sakr Y, et al: Microcirculatory Alterations in Patients With Severe Sepsis: Impact of Time of Assessment and Relationship With Outcome. Crit Care Med 2013; 41:791799 2. Dixon B: The role of microvascular thrombosis in sepsis. Anaesth In- tensive Care 2004; 32:619629 3. Quezado ZM, Natanson C: Systemic hemodynamic abnormalities and vasopressor therapy in sepsis and septic shock. Am J Kidney Dis 1992; 20:214222 4. Bateman RM, Sharpe MD, Ellis CG: Bench-to-bedside review: Micro- vascular dysfunction in sepsishemodynamics, oxygen transport, and nitric oxide. Crit Care 2003; 7:359373 5. Leone M, Blidi S, Antonini F, et al: Oxygen tissue saturation is lower in nonsurvivors than in survivors after early resuscitation of septic shock. Anesthesiology 2009; 111:366371 6. Mesquida J, Masip J, Gili G, et al: Thenar oxygen saturation measured by near infrared spectroscopy as a noninvasive predictor of low cen- tral venous oxygen saturation in septic patients. Intensive Care Med 2009; 35:11061109 7. Perner A, Haase N, Wiis J, et al: Central venous oxygen saturation for the diagnosis of low cardiac output in septic shock patients. Acta Anaesthesiol Scand 2010; 54:98102 8. Valle F, Mateo J, Dubreuil G, et al: Cutaneous ear lobe Pco at 37C to evaluate microperfusion in patients with septic shock. Chest 2010; 138:10621070 9. Creteur J, De Backer D, Sakr Y, et al: Sublingual capnometry tracks microcirculatory changes in septic patients. Intensive Care Med 2006; 32:516523 10. Boerma EC, Kuiper MA, Kingma WP, et al: Disparity between skin per fusion and sublingual microcirculatory alterations in severe sepsis and septic shock: A prospective observational study. Intensive Care Med 2008; 34:12941298