When to stop septic shock resuscitation: clues from a dynamic perfusion monitoring

Hernandez et al. Annals of Intensive Care 2014, 4:30 http://www.annalsofintensivecare.com/content/4/1/30 RESEARCH Open Access When to stop septic shock resuscitation: clues from a dynamic perfusion monitoring Glenn Hernandez1*, Cecilia Luengo2, Alejandro Bruhn1, Eduardo Kattan1, Gilberto Friedman3, Gustavo A Ospina-Tascon4, Andrea Fuentealba1, Ricardo Castro1, Tomas Regueira1, Carlos Romero2, Can Ince5 and Jan Bakker5 Abstract Background: The decision of when to stop septic shock resuscitation is a critical but yet a relatively unexplored aspect of care. This is especially relevant since the risks of over-resuscitation with fluid overload or inotropes have been highlighted in recent years. A recent guideline has proposed normalization of central venous oxygen saturation and/or lactate as therapeutic end-points, assuming that these variables are equivalent or interchangeable. However, since the physiological determinants of both are totally different, it is legitimate to challenge the rationale of this proposal. We designed this study to gain more insights into the most appropriate resuscitation goal from a dynamic point of view. Our objective was to compare the normalization rates of these and other potential perfusion-related targets in a cohort of septic shock survivors. Methods: We designed a prospective, observational clinical study. One hundred and four septic shock patients with hyperlactatemia were included and followed until hospital discharge. The 84 hospital-survivors were kept for final analysis. A multimodal perfusion assessment was performed at baseline, 2, 6, and 24 h of ICU treatment. Results: Some variables such as central venous oxygen saturation, central venous-arterial pCO2 gradient, and capillary refill time were already normal in more than 70% of survivors at 6 h. Lactate presented a much slower normalization rate decreasing significantly at 6 h compared to that of baseline (4.0 [3.0 to 4.9] vs. 2.7 [2.2 to 3.9] mmol/L; p < 0.01) but with only 52% of patients achieving normality at 24 h. Sublingual microcirculatory variables exhibited the slowest recovery rate with persistent derangements still present in almost 80% of patients at 24 h. Conclusions: Perfusion-related variables exhibit very different normalization rates in septic shock survivors, most of them exhibiting a biphasic response with an initial rapid improvement, followed by a much slower trend thereafter. This fact should be taken into account to determine the most appropriate criteria to stop resuscitation opportunely and avoid the risk of over-resuscitation. Keywords: Septic shock; Perfusion; Resuscitation; Lactate; Microcirculation Background Several clinical studies have demonstrated that persistent impairment of perfusion-related physiological variables is associated with increased mortality in septic shock patients [1-3]. Therefore, current guidelines recommend normalization of relevant physiologic variables such as lactate and/or central venous oxygen saturation (ScvO2) as resuscitation goals, basically through oxygen transport * Correspondence: 1 Departamento de Medicina Intensiva, Facultad de Medicina, Pontificia Universidad Católica de Chile, Marcoleta 367, Santiago 8320000, Chile Full list of author information is available at the end of the article (DO2) optimization [4,5]. In addition, peripheral perfusion, central venous-arterial pCO2 gradient (P(cv-a)CO2), and microcirculatory abnormalities have also been linked to morbidity or mortality and suggested as potential complementary targets [6-8]. However, the issue of when to stop resuscitation has become more relevant in recent years as the risks of overresuscitation have also been increasingly highlighted. In fact, pursuing complete normalization of all potential perfusion-related goals with repeated attempts to increase DO2 could eventually result in severe adverse effects such as fluid overload, pulmonary edema, intra-abdominal © 2014 Hernandez et al.; licensee Springer. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited. Hernandez et al. Annals of Intensive Care 2014, 4:30 http://www.annalsofintensivecare.com/content/4/1/30 hypertension, cardiac arrhythmias, and myocardial ischemia, thus possibly increasing morbidity and mortality [9-11]. From a physiological point of view, the problem is far more complex. For instance, it is not known if all perfusion-related variables are equally sensitive to DO2 optimization [12], a factor that could critically influence their specific normalization rates. Besides, parameters traditionally considered as reflecting tissue perfusion like lactate are also mechanistically determined by non-flow dependent or mixed mechanisms [13]. This may result in a wide variability on individual recovery time courses after optimization of DO2 depending on the predominant pathogenic mechanism. The practical aspect is that if a more likely flow-dependent parameter is selected as a goal (such as P(cv-a)CO2 or ScvO2), it may normalize earlier than a less flow-dependent one such as lactate. In other words, from a theoretical point of view, the resuscitation length could vary dramatically depending on these considerations leading eventually to the risk of over-resuscitation if the selected goal exhibits an intrinsic slow normalization rate. To address this subject, we designed a prospective study to evaluate the specific normalization rates of several perfusion-related variables in a cohort of consecutive septic shock patients subjected to protocolized resuscitation and multimodal perfusion assessment. We a priori decided to include only ultimately hospital-surviving patients for analysis to provide a relevance perspective to persistent abnormalities after initial resuscitation. Methods Setting We conducted a prospective observational study from July 2011 to November 2012 in a mixed 16-bed ICU at our university hospital. The institutional review board of our university approved this study and waived the need of an informed consent because of the observational nature of the study (Comité de Etica en Investigación, Facultad de Medicina, Pontificia Universidad Católica de Chile; approval number 11-113). Patient selection We included all consecutive adult patients admitted to the ICU with septic shock diagnosis according to the 2001 consensus definition [14], with a basal arterial lactate >2 mmol/L and full commitment for resuscitation. Protocol and measurements Patients were studied for the first 24 h following initiation of ICU-based resuscitation and were followed until death or hospital discharge. Clinical and demographic data and severity scores [15,16] were collected for each patient at baseline (at inclusion = 0 h). Page 2 of 9 The following measurements as part of a mu (...truncated)