REVIEW CURRENT OPINION The holistic view on perfusion monitoring in septic shock Glenn Hernandez, Alejandro Bruhn, Ricardo Castro, and Tomas Regueira Purpose of review To review recent evidence concerning the interactions between hemodynamic and perfusion parameters during septic shock resuscitation, and to propose some basic foundations for a more comprehensive perfusion assessment. Recent findings Several recent studies have expanded our knowledge about the physiologic determinants and limitations of currently used perfusion parameters such as central venous oxygen saturation and lactate. Macrohemodynamic, metabolic, peripheral and microcirculatory parameters tend to change in parallel in response to fluid loading during initial resuscitation. In contrast, perfusion markers are poorly correlated in patients who evolve with a persistent circulatory dysfunction. Therefore, assessment of perfusion status based solely on a single parameter can lead to inaccurate or misleading conclusions. Summary All individual perfusion parameters have extensive limitations to adequately reflect tissue perfusion during persistent sepsis-related circulatory dysfunction. A multimodal approach integrating macrohemodynamic, metabolic, peripheral and eventually microcirculatory perfusion parameters may overcome those limitations. This approach may also provide a thorough understanding on the predominant driving forces of hypoperfusion, and lead to physiologically oriented interventions. Keywords central venous oxygen saturation, fluid challenge, lactate, microcirculation, tissue perfusion INTRODUCTION mutually exclusive protocols [5,18]. As a result, the lack of an integrative comprehensive approach is A fundamental challenge in septic shock resuscita- && tion is to evaluate tissue perfusion [1,2]. Macrohe- evident, with notable exceptions [7 ,24]. This trend modynamic [3], metabolic [4&,5,6,7&&], peripheral contrasts with more holistic approaches in other [8,9&], regional [10,11,12&&] and microcirculatory settings, such as the multimodal monitorization pro- parameters [13–16] have been utilized to evaluate posed for neurocritical patients [25]. either perfusion status or resuscitation success. In this article, we will review recent evidence However, because of the extreme complexity of concerning the relationship between hemodynamic sepsis-related circulatory dysfunction, none of and perfusion parameters during septic shock resus- these markers have earned universal acceptance citation, and propose some basic foundations for an as the unique parameter to be considered as integrative perfusion assessment. the hallmark to guide septic shock resuscitation [3,5,6,9&,17,18]. During the last decades several potential resusci- tation targets have been explored. Among them, we Departamento de Medicina Intensiva, Pontificia Universidad Catolica de can mention supernormal hemodynamic objectives Chile, Santiago, Chile && [19], gastric tonometry [10,18], lactate [5,7 ], Correspondence to Glenn Hernandez, MD, Departamento de Medicina mixed (SvO2) or central venous oxygen saturations Intensiva, Pontificia Universidad Catolica de Chile, Marcoleta 367, (ScvO2) [20,21], and more recently, sublingual micro- Santiago 8320000, Chile. Tel: +56 2 3543972; e-mail: glennguru@ circulatory flow [22], peripheral perfusion [9&]and gmail.com & venous-arterial pCO2 gradient ( p(cv-a)CO2) [6,23 ]. Curr Opin Crit Care 2012, 18:280–286 Unfortunately, they have been tested in rather DOI:10.1097/MCC.0b013e3283532c08 www.co-criticalcare.com Volume 18 Number 3 June 2012 Copyright © Lippincott Williams & Wilkins. Unauthorized reproduction of this article is prohibited. The holistic view on perfusion monitoring Hernandez et al. AQ1 points during initial resuscitation in 41 patients KEY POINTS with septic shock [9&]. We found that capillary refill All individual perfusion parameters have extensive time, lactate and heart rate improved in parallel limitations to adequately reflect tissue perfusion during during 6 h of fluid-based resuscitation. In a previous persistent sepsis-related circulatory dysfunction. landmark study, ScvO2 and lactate exhibited a com- parable recovery trend during early resuscitation Assessment of perfusion status based solely on a single [20]. A more recent study, by Ait-Oufella et al. parameter can lead to inaccurate or && misleading conclusions. [35 ], demonstrates that the opposite is also true. A worsening peripheral perfusion was associated A multimodal approach integrating to increasing hyperlactatemia in refractory septic macrohemodynamic, metabolic, peripheral, and shock patients. eventually microcirculatory perfusion parameters might These data taken together suggest an intricate overcome those limitations. relationship between macrohemodynamics, per- fusion parameters and microcirculatory flow indices. All these elements are affected by hypovo- lemia and tend to improve in parallel in fluid- INITIAL CIRCULATORY DYSFUNCTION responsive patients. Their relative changes, though, AND RESPONSE TO EARLY are not well correlated. The beneficial effects RESUSCITATION of fluids may be explained by an increase in cardiac Although many mechanisms are involved in the output, a decrease in the neurohumoral response pathogenesis of sepsis-related circulatory dysfunc- to hypovolemia, and by direct effects at the micro- tion [26,27,28&,29], hypovolemia is clearly the pre- circulatory level [26]. The clinical expression dominant factor in preresuscitated patients early on of these effects is variable according to several after hospital admission [30&]. Depending on the preexisting factors such as preload responsiveness, severity and time course of hypovolemia, patients the magnitude of adrenergic induced redistribu- may exhibit an impaired peripheral perfusion, tive vasoconstriction, or local microvascular dys- hyperlactatemia, low ScvO2, and altered microcir- function. culatory flow, whether or not they are hypotensive. The fundamental challenge in this phase is rapid A couple of studies have explored the relation- and complete reversal of the low-flow state secon- ship between hemodynamic and perfusion para- dary to hypovolemia. Simple, readily available and meters in this preresuscitative phase. Trzeciak validated monitoring tools such as subjective per- et al. [31] found an early significant correlation ipheral perfusion and lactate can be used to guide between macrohemodynamic parameters, lactate this process. Normalization of these parameters and microcirculatory flow alterations. Payen et al. indicates a successful reversal of initial circulatory [32] confirmed these findings in 43 septic shock dysfunction. Such an approach was recently dem- patients undergoing initial resuscitation. They onstrated to be as effective as ScvO2-guided resusci- found that microvascular reactivity assessed by near- tation, but appears as more practical for the pre-ICU infrared spectroscopy (NIRS)-derived techniques setting [5]. However, a significant proportion was correlated to cardiac index and lactate levels. of patients may develop a persistent circulatory The cornerstone of initial resuscitation is fluid dysfunction characterized by variable degrees of loading. A series of dynamic studies evaluated the volume-refractory hypotension and/or perfusion effects of a fluid challenge in this setting. Pottecher abnormalities. et al. [33&&] observed an improvement in sublingual microcirculatory perfusion after fluid adminis- tration in septic shock patients. Interestingly, PERSISTENT CIRCULATORY improvement in microcirculatory flow correlated DYSFUNCTION AFTER INITIAL significantly to changes in global hemodynamics. RESUSCITATION In another septic shock study, early fluid loading Persistent circulatory dysfunction after fluid resus- improved mean arterial pressure, cardiac index, citation can be expressed through diverse clinical SvO2 or ScvO2 values, lactate levels, pulse pressure profiles. In our opinion, at least three distinct hemo- variation and microcirculatory flow in parallel [34]. dynamic patterns can be recognized at this stage: Other studies explored the time course of overt or classic septic shock (vasopressor require- changes in several perfusion parameters during early ments and hypoperfusion) [36], cryptic shock (per- septic shock resuscitation confirming previous find- sistent hypoperfusion without hypotension) [37&], ings. Our group evaluated changes in metabolic and and a state of persistent sepsis-related hypotension peripheral perfusion parameters at different time without hypoperfusion [38&] (Fig. 1). 1070-5295 ß 2012 Wolters Kluwer Health | Lippincott Williams & Wilkins www.co-criticalcare.com 281 Copyright © Lippincott Williams & Wilkins. Unauthorized reproduction of this article is prohibited. Cardiopulmonary monitoring Initial circulatory dysfunction Initial fluid resusciation Persistent Resolved√ circulatory dysfunction Persistent hypotension without hypoperfusion VP Cryptic shock HP Classic shock VP HP FIGURE 1. Clinical patterns which can be recognized in patients with persistent sepsis-related circulatory dysfunction. HP, hypoperfusion; VP, vasopressers. In contrast to the preresuscitative phase, more correlation between systemic hemodynamics and complex mechanisms may lead the pathogenesis of thenar basal StO2 or its recovery slope after a vas- persistent circulatory dysfunction [27,39]. Vascular cular occlusion test assessed by NIRS. Other experi- dysfunction induces vasoplegia, capillary leak and ences have found no association between ScvO2 and