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

Glenn Hernandez, Cecilia Luengo, Alejandro Bruhn, Eduardo Kattan, Gilberto Friedman, Gustavo A Ospina-Tascon, Andrea Fuentealba, Ricardo Castro, Tomas Regueira, Carlos Romero, Can Ince, Jan Bakker, Glenn Hernandez, Cecilia Luengo, Alejandro Bruhn, Eduardo Kattan, Gilberto Friedman, Gustavo A Ospina-Tascon, Andrea Fuentealba, Ricardo Castro, Tomas Regueira, Carlos Romero, Can Ince, Jan Bakker

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: Lactate; Microcirculation; Perfusion; Resuscitation; Septic shock.

Figures

Figure 1
Figure 1
Time-trend changes for selected perfusion parameters after normalization showing a biphasic recovery trend (see statistical analysis): A,lactate;B,capillary refill time (CRT);C,central venous-arterial pCO2gradient (P(cv-a)CO2).
Figure 2
Figure 2
Percentage of abnormal values for several perfusion and microcirculatory parameters in septic shock survivors. The evolution of these parameters at different time-points during the first 24 h of intensive care unit-based resuscitation is presented. PVD, perfused vessel density; PPV, proportion of perfused vessels; MFI, microvascular flow index; P(cv-a)CO2, central venous-arterial pCO2 gradient; CRT, capillary refill time.

References

    1. Hernandez G, Bruhn A, Castro R, Pedreros C, Rovegno M, Kattan E, Veas E, Fuentealba A, Regueira T, Ruiz C, Ince C. Persistent sepsis-induced hypotension without hyperlactatemia: is it really septic shock? J Crit Care. 2011;26(435):e9–e14.
    1. Palizas F, Dubin A, Regueira T, Bruhn A, Knobel E, Lazzeri S, Baredes N, Hernández G. Gastric tonometry versus cardiac index as resuscitation goals in septic shock: a multicenter, randomized, controlled trial. Crit Care. 2009;13:R44. doi: 10.1186/cc7767.
    1. Rivers E, Nguyen B, Havstad S, Ressler J, Muzzin A, Knoblich B, Peterson E, Tomlanovich M. Early goal-directed therapy in the treatment of severe sepsis and septic shock. N Engl J Med. 2001;345:1368–1377. doi: 10.1056/NEJMoa010307.
    1. Dellinger RP, Levy MM, Rhodes A, Annane D, Gerlach H, Opal SM, Sevransky JE, Sprung CL, Douglas IS, Jaeschke R, Osborn TM, Nunnally ME, Townsend SR, Reinhart K, Kleinpell RM, Angus DC, Deutschman CS, Machado FR, Rubenfeld GD, Webb S, Beale RJ, Vincent JL, Moreno R. Surviving sepsis campaign: international guidelines for management of severe sepsis and septic shock. Intensive Care Med. 2013;39:165–228. doi: 10.1007/s00134-012-2769-8.
    1. Green RS, Djogovic D, Gray S, Howes D, Brindley PG, Stenstrom R, Patterson E, Easton D, Davidow JS. Canadian association of emergency physicians sepsis guidelines: the optimal management of severe sepsis in Canadian emergency departments. CJEM. 2008;10:443–459.
    1. Lima A, Jansen TC, van Bommel J, Ince C, Bakker J. The prognostic value of the subjective assessment of peripheral perfusion in critically ill patients. Crit Care Med. 2009;37:934–938. doi: 10.1097/CCM.0b013e31819869db.
    1. Vallée F, Vallet B, Mathe O, Parraguette J, Mari A, Silva S, Samii K, Fourcade O, Genestal M. Central venous-to-arterial carbon dioxide difference: an additional target for goal-directed therapy in septic shock? Intensive Care Med. 2008;34:2218–2225. doi: 10.1007/s00134-008-1199-0.
    1. Sakr Y, Dubois MJ, De Backer D, Creteur J, Vincent JL. Persistent microcirculatory alterations are associated with organ failure and death in patients with septic shock. Crit Care Med. 2004;32:1825–1831. doi: 10.1097/01.CCM.0000138558.16257.3F.
    1. Hayes MA, Timmins AC, Yau EH, Palazzo M, Hinds CJ, Watson D. Elevation of systemic oxygen delivery in the treatment of critically ill patients. N Engl J Med. 1994;330:1717–1722. doi: 10.1056/NEJM199406163302404.
    1. Enrico C, Kanoore Edul VS, Vazquez AR, Pein MC, de la Hoz RAP, Ince C, Dubin A. Systemic and microcirculatory effects of dobutamine in patients with septic shock. J Crit Care. 2012;27:630–638. doi: 10.1016/j.jcrc.2012.08.002.
    1. Regueira T, Bruhn A, Hasbun P, Aguirre M, Romero C, Llanos O, Castro R, Bugedo G, Hernandez G. Intra-abdominal hypertension: incidence and association with organ dysfunction during early septic shock. J Crit Care. 2008;23:461–467. doi: 10.1016/j.jcrc.2007.12.013.
    1. Jones AE, Shapiro NI, Trzeciak S, Arnold RC, Claremont HA, Kline JA. Lactate clearance vs central venous oxygen saturation as goals of early sepsis therapy: a randomized clinical trial. JAMA. 2010;303:739–746. doi: 10.1001/jama.2010.158.
    1. Hernandez G, Bruhn A, Castro R, Regueira T. The holistic view on perfusion monitoring in septic shock. Curr Opin Crit Care. 2012;18:280–286. doi: 10.1097/MCC.0b013e3283532c08.
    1. Levy MM, Fink MP, Marshall JC, Abraham E, Angus D, Cook D, Cohen J, Opal SM, Vincent JL, Ramsay G. 2001 international sepsis definitions conference. Crit Care Med. 2003;31:1250–1256. doi: 10.1097/01.CCM.0000050454.01978.3B.
    1. Knaus WA, Draper EA, Wagner DP, Zimmerman JE. APACHE II: a severity of disease classification system. Crit Care Med. 1985;13:818–829. doi: 10.1097/00003246-198510000-00009.
    1. Vincent JL, Moreno R, Takala J, Willatts S, De Mendonça A, Bruining H, Reinhart CK, Suter PM, Thijs LG. The SOFA (sepsis-related organ failure assessment) score to describe organ dysfunction/failure: on behalf of the working group on sepsis-related problems of the European society of intensive care medicine. Intensive Care Med. 1996;22:707–710. doi: 10.1007/BF01709751.
    1. Hernandez G, Pedreros C, Veas E, Bruhn A, Romero C, Rovegno M, Neira R, Bravo S, Castro R, Kattan E, Ince C. Evolution of peripheral vs metabolic perfusion parameters during septic shock resuscitation: a clinical-physiologic study. J Crit Care. 2012;27:283–288. doi: 10.1016/j.jcrc.2011.05.024.
    1. Mesquida J, Masip J, Gili G, Artigas A, Baigorri F. Thenar oxygen saturation measured by near infrared spectroscopy as a noninvasive predictor of low central venous oxygen saturation in septic patients. Intensive Care Med. 2009;35:1106–1109. doi: 10.1007/s00134-009-1410-y.
    1. Shapiro NI, Arnold R, Sherwin R, O’Connor J, Najarro G, Singh S, Lundy D, Nelson T, Trzeciak SW, Jones AE. The association of near-infrared spectroscopy-derived tissue oxygenation measurements with sepsis syndromes, organ dysfunction and mortality in emergency department patients with sepsis. Crit Care. 2011;15:R223. doi: 10.1186/cc10463.
    1. De Backer D, Hollenberg S, Boerma C, Goedhart P, Büchele G, Ospina-Tascon G, Dobbe I, Ince C. How to evaluate the microcirculation: report of a round table conference. Crit Care. 2007;11:R101. doi: 10.1186/cc6118.
    1. Cornejo R, Downey P, Castro R, Romero C, Regueira T, Vega J, Castillo L, Andresen M, Dougnac A, Bugedo G, Hernandez G. High-volume hemofiltration as salvage therapy in severe hyperdynamic septic shock. Intensive Care Med. 2006;32:713–722. doi: 10.1007/s00134-006-0118-5.
    1. Marik PE, Monnet X, Teboul JL. Hemodynamic parameters to guide fluid therapy. Ann Intensive Care. 2011;1:1. doi: 10.1186/2110-5820-1-1. doi:10.1186/2110-5820-1-1.
    1. Balogh ZJ, Malbrain M. Resuscitation in intra-abdominal hypertension and abdominal compartment syndrome. Am Surg. 2011;77(Suppl 1):S31–S33.
    1. Cuzick J. A wilcoxon-type test for trend. Stat Med. 1985;4:87–90. doi: 10.1002/sim.4780040112.
    1. Bracht H, Hänggi M, Jeker B, Wegmüller N, Porta F, Tüller D, Takala J, Jakob SM. Incidence of low central venous oxygen saturation during unplanned admissions in a multidisciplinary intensive care unit: an observational study. Crit Care. 2007;11:R2. doi: 10.1186/cc5144.
    1. Van Beest PA, Hofstra HH, Schultz MJ, Boerma EC, Spronk PE, Kuiper MA. The incidence of low venous oxygen saturation on admission to the intensive care unit: a multi-centre observational study in The Netherlands. Crit Care. 2008;12:R33. doi: 10.1186/cc6811.
    1. Van Genderen ME, Lima A, Akkerhuis M, Bakker J, Van Bommel J. Persistent peripheral and microcirculatory perfusion alterations after out-of-hospital cardiac arrest are associated with poor survival. Crit Care Med. 2012;40:2287–2294. doi: 10.1097/CCM.0b013e31825333b2.
    1. Levy B. Lactate and shock state: the metabolic view. Curr Opin Crit Care. 2006;12:315–321. doi: 10.1097/01.ccx.0000235208.77450.15.
    1. Hernandez G, Regueira T, Bruhn A, Castro R, Rovegno M, Fuentealba A, Veas E, Berrutti D, Florez J, Kattan E, Martin C, Ince C. Relationship of systemic, hepatosplanchnic, and microcirculatory perfusion parameters with 6-hour lactate clearance in hyperdynamic septic shock patients: an acute, clinical-physiological, pilot study. Ann Intensive Care. 2012;2:44. doi: 10.1186/2110-5820-2-44.
    1. Jansen TC, Van Bommel J, Schoonderbeek FJ, Sleeswijk Visser SJ, Van der Klooster JM, Lima AP, Willemsen SP, Bakker J. Early lactate-guided therapy in intensive care unit patients: a multicenter, open-label, randomized controlled trial. Am J Respir Crit Care Med. 2010;182:752–761. doi: 10.1164/rccm.200912-1918OC.
    1. Ospina-Tascon G, Neves AP, Occhipinti G, Donadello K, Büchele G, Simion D, Chierego ML, Silva TO, Fonseca A, Vincent JL, De Backer D. Effects of fluids on microvascular perfusion in patients with severe sepsis. Intensive Care Med. 2010;36:949–955. doi: 10.1007/s00134-010-1843-3.
    1. Trzeciak S, McCoy JV, Phillip Dellinger R, Arnold RC, Rizzuto M, Abate NL, Shapiro NI, Parrillo JE, Hollenberg SM. Early increases in microcirculatory perfusion during protocol-directed resuscitation are associated with reduced multi-organ failure at 24 h in patients with sepsis. Intensive Care Med. 2008;34:2210–2217. doi: 10.1007/s00134-008-1193-6.
    1. Pottecher J, Deruddre S, Teboul JL, Georger JF, Laplace C, Benhamou D, Vicaut E, Duranteau J. Both passive leg raising and intravascular volume expansion improve sublingual microcirculatory perfusion in severe sepsis and septic shock patients. Intensive Care Med. 2010;36:1867–1874. doi: 10.1007/s00134-010-1966-6.
    1. De Backer D, Donadello K, Sakr Y, Ospina-Tascon G, Salgado D, Scolletta S, Vincent JL. Microcirculatory alterations in patients with severe sepsis: impact of time of assessment and relationship with outcome. Crit Care Med. 2013;41:791–799. doi: 10.1097/CCM.0b013e3182742e8b.
    1. Iwagami M, Yasunaga H, Doi K, Horiguchi H, Fushimi K, Matsubara T, Yahagi N, Noiri E. Postoperative polymyxin B hemoperfusion and mortality in patients with abdominal septic shock: a propensity-matched analysis. Crit Care Med. 2013;42:1187–1193. doi: 10.1097/CCM.0000000000000150.
    1. A randomized trial of protocol-based care for early septic shock. N Engl J Med. 2014;370:1683–1693. doi: 10.1056/NEJMoa1401602.
    1. Kaukonen KM, Bailey M, Suzuki S, Pilcher D, Bellomo R. Mortality related to severe sepsis and septic shock among critically ill patients in Australia and New Zealand, 2000-2012. JAMA. 2014;311:1308–1316. doi: 10.1001/jama.2014.2637.
    1. Hernandez G, Bruhn A, Luengo C, Regueira T, Kattan E, Fuentealba A, Florez J, Castro R, Aquevedo A, Pairumani R, McNab P, Ince C. Effects of dobutamine on systemic, regional and microcirculatory perfusion parameters in septic shock: a randomized, placebo-controlled, double-blind, crossover study. Intensive Care Med. 2013;39:1435–1443. doi: 10.1007/s00134-013-2982-0.
    1. Boerma EC, Koopmans M, Konijn A, Kaiferova K, Bakker AJ, Van Roon EN, Buter H, Bruins N, Egbers PH, Gerritsen RT, Koetsier PM, Kingma WP, Kuiper MA, Ince C. Effects of nitroglycerin on sublingual microcirculatory blood flow in patients with severe sepsis/septic shock after a strict resuscitation protocol: a double-blind randomized placebo controlled trial. Crit Care Med. 2010;38:93–100. doi: 10.1097/CCM.0b013e3181b02fc1.

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