Targeting skeletal muscle tissue oxygenation (StO2) in adults with severe sepsis and septic shock: a randomised controlled trial (OTO-StS Study)

Olivier Nardi, Elizabeth Zavala, Claude Martin, Serafim Nanas, Thomas Scheeren, Andrea Polito, Xavi Borrat, Djillali Annane, Olivier Nardi, Elizabeth Zavala, Claude Martin, Serafim Nanas, Thomas Scheeren, Andrea Polito, Xavi Borrat, Djillali Annane

Abstract

Objective: Evaluation of the ratio of oxyhaemoglobin to total haemoglobin in skeletal muscle (StO2) using near-infrared spectroscopy may aid in the monitoring of patients with sepsis. This study assessed the benefits and risks of targeting StO2 in adults with severe sepsis or septic shock.

Design: A European randomised controlled trial was performed on two parallel groups.

Setting: Five intensive care units (ICU) in France, Greece, Spain and Germany were used for the study.

Participants: A total of 103 adults with severe sepsis or septic shock on ICU admission were randomised (54 subjects in the experimental arm and 49 subjects in the control arm).

Interventions: Haemodynamic management using an algorithm that was adapted from the 2004 Surviving Sepsis Campaign guidelines with (experimental arm) or without (control arm) targeting an StO2 value greater than 80% at a minimum of two different sites.

Outcomes: The primary outcome was a composite: 7-day all-cause mortality or worsening of organ function, defined as a positive difference in Sepsis-related Organ Failure Assessment (SOFA) score between day 7 and randomisation (ie, delta SOFA >0). Secondary endpoints: 30-day mortality, duration of mechanical ventilation and vasopressor therapy up to 30 days from randomisation.

Results: The study ended prematurely due to lack of funding after enrolment of 103/190 patients. Eighteen patients (33.3%) in the experimental arm and 14 (28.6%, P=0.67) in the control arm died or exhibited delta SOFA >0 on day 7. The mean number of days on mechanical ventilation was 12.2±10.6 in the experimental group and 7.6±7.9 in the control group (P=0.03). Thirty-one (57%) patients in the experimental arm and 14 (29%) patients in the control arm received red cells by day 7 (P=0.01).

Conclusion: Despite the limitation related to premature termination, this study provides no data to support the routine implementation of resuscitation protocols incorporating StO2 >80% at two or more muscle sites as a target. StO2-guided therapy may be associated with prolonged use of mechanical ventilation and an increased number of red blood cell transfusions.

Trial registration number: NCT00167596; Results.

Keywords: microcirculation; near infrared spectrometry; organ dysfunction; sepsis; shock.

Conflict of interest statement

Competing interests: None declared.

© Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

Figures

Figure 1
Figure 1
Haemodynamic treatment algorithm. CVP, central venous pressure; Ht, haematocrit; MBP, mean blood pressure.
Figure 2
Figure 2
Study flow diagram.
Figure 3
Figure 3
Kaplan-Meier survival estimates. Shown is the probability of survival for participants according to randomisation arm at 30 days.

References

    1. Mesquida J, Gruartmoner G, Espinal C. Skeletal muscle oxygen saturation (StO2) measured by near-infrared spectroscopy in the critically ill patients. Biomed Res Int 2013;2013:1–8. 10.1155/2013/502194
    1. Scheeren TW, Schober P, Schwarte LA. Monitoring tissue oxygenation by near infrared spectroscopy (NIRS): background and current applications. J Clin Monit Comput 2012;26:279–87. 10.1007/s10877-012-9348-y
    1. Colin G, Nardi O, Polito A, et al. . Masseter tissue oxygen saturation predicts normal central venous oxygen saturation during early goal-directed therapy and predicts mortality in patients with severe sepsis. Crit Care Med 2012;40:435–40. 10.1097/CCM.0b013e3182329645
    1. Shapiro NI, Arnold R, Sherwin R, et al. . 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 10.1186/cc10463
    1. Vorwerk C, Coats TJ. The prognostic value of tissue oxygen saturation in emergency department patients with severe sepsis or septic shock. Emerg Med J 2012;29:699–703. 10.1136/emermed-2011-200160
    1. 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;111:366–71. 10.1097/ALN.0b013e3181aae72d
    1. De Backer D, Donadello K, Cortes DO. Monitoring the microcirculation. J Clin Monit Comput 2012;26:361–6. 10.1007/s10877-012-9383-8
    1. Dellinger RP, Levy MM, Carlet JM, et al. . Surviving sepsis campaign: international guidelines for management of severe sepsis and septic shock: 2008. Crit Care Med 2008;36:296–327. 10.1097/01.CCM.0000298158.12101.41
    1. Dellinger RP, Levy MM, Rhodes A, et al. . Surviving sepsis campaign: international guidelines for management of severe sepsis and septic shock: 2012. Crit Care Med 2013;41:580–637. 10.1097/CCM.0b013e31827e83af
    1. De Backer D, Creteur J, Dubois MJ, et al. . The effects of dobutamine on microcirculatory alterations in patients with septic shock are independent of its systemic effects. Crit Care Med 2006;34:403–8. 10.1097/01.CCM.0000198107.61493.5A
    1. Sakr Y, Chierego M, Piagnerelli M, et al. . Microvascular response to red blood cell transfusion in patients with severe sepsis. Crit Care Med 2007;35:1639–44. 10.1097/01.CCM.0000269936.73788.32
    1. Nardi O, Polito A, Aboab J, et al. . StO₂ guided early resuscitation in subjects with severe sepsis or septic shock: a pilot randomised trial. J Clin Monit Comput 2013;27:215–21. 10.1007/s10877-013-9432-y
    1. Bone RC, Balk RA, Cerra FB, et al. . Definitions for sepsis and organ failure and guidelines for the use of innovative therapies in sepsis. Chest 1992;101:1644–55. 10.1378/chest.101.6.1644
    1. Dellinger RP, Carlet JM, Masur H, et al. . Surviving sepsis campaign guidelines for management of severe sepsis and septic shock. Crit Care Med 2004;32:858–73. 10.1097/01.CCM.0000117317.18092.E4
    1. Knaus WA, Zimmerman JE, Wagner DP, et al. . APACHE-acute physiology and chronic health evaluation: a physiologically based classification system. Crit Care Med 1981;9:591–7. 10.1097/00003246-198108000-00008
    1. McCabe WA, Jackson GG. Gram negative bacteremia. I. Etiology and ecology. Arch Intern Med 1962;110:847–55.
    1. Le Gall JR, Lemeshow S, Saulnier F. A new Simplified Acute Physiology Score (SAPS II) based on a European/North American multicenter study. JAMA 1993;270:2957–63. 10.1001/jama.1993.03510240069035
    1. Vincent JL, Moreno R, Takala J, et al. . 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;22:707–10.
    1. Bassler D, Briel M, Montori VM, et al. . Stopping randomized trials early for benefit and estimation of treatment effects: systematic review and meta-regression analysis. JAMA 2010;303:1180–7. 10.1001/jama.2010.310
    1. Rivers E, Nguyen B, Havstad S, et al. . Early goal-directed therapy in the treatment of severe sepsis and septic shock. N Engl J Med 2001;345:1368–77. 10.1056/NEJMoa010307
    1. Hayes MA, Timmins AC, Yau EH, et al. . Elevation of systemic oxygen delivery in the treatment of critically ill patients. N Engl J Med 1994;330:1717–22. 10.1056/NEJM199406163302404
    1. Hébert PC, Wells G, Blajchman MA, et al. . A multicenter, randomized, controlled clinical trial of transfusion requirements in critical care. N Engl J Med Overseas Ed 1999;340:409–17. 10.1056/NEJM199902113400601
    1. Mouncey PR, Osborn TM, Power GS, et al. . Trial of early, goal-directed resuscitation for septic shock. N Engl J Med 2015;372:1301–11. 10.1056/NEJMoa1500896
    1. Peake SL, Delaney A, Bailey M, et al. . Goal-directed resuscitation for patients with early septic shock. N Engl J Med 2014;371:1496–506. 10.1056/NEJMoa1404380
    1. Yealy DM, Kellum JA, Huang DT, et al. . A randomized trial of protocol-based care for early septic shock. N Engl J Med 2014;370:1683–93. 10.1056/NEJMoa1401602
    1. Neto AS, Pereira VG, Manetta JA, et al. . Association between static and dynamic thenar near-infrared spectroscopy and mortality in patients with sepsis: a systematic review and meta-analysis. J Trauma Acute Care Surg 2014;76:226–33. 10.1097/TA.0b013e3182a9221f
    1. Nardi O, Gonzalez H, Fayssoil A, et al. . Masseter muscle oxygen saturation is associated with central venous oxygen saturation in patients with severe sepsis. J Clin Monit Comput 2010;24:289–93. 10.1007/s10877-010-9247-z
    1. Pareznik R, Knezevic R, Voga G, et al. . Changes in muscle tissue oxygenation during stagnant ischemia in septic patients. Intensive Care Med 2006;32:87–92. 10.1007/s00134-005-2841-8
    1. Creteur J, Carollo T, Soldati G, et al. . The prognostic value of muscle StO2 in septic patients. Intensive Care Med 2007;33:1549–56. 10.1007/s00134-007-0739-3
    1. Bezemer R, Lima A, Myers D, et al. . Assessment of tissue oxygen saturation during a vascular occlusion test using near-infrared spectroscopy: the role of probe spacing and measurement site studied in healthy volunteers. Crit Care 2009;13(Suppl 5):S4 10.1186/cc8002
    1. Creteur J. Muscle StO2 in critically ill patients. Curr Opin Crit Care 2008;14:361–6. 10.1097/MCC.0b013e3282fad4e1
    1. Annane D. Thenar tissue oxygen saturation monitoring: noninvasive does not mean simple or accurate!. Crit Care Med 2011;39:1828–9. 10.1097/CCM.0b013e31821b8153
    1. Vincent JL, de Mendonça A, Cantraine F, et al. . Use of the SOFA score to assess the incidence of organ dysfunction/failure in intensive care units: results of a multicenter, prospective study. Working group on "sepsis-related problems" of the European Society of Intensive Care Medicine. Crit Care Med 1998;26:1793–80.
    1. Moreno R, Vincent JL, Matos R, et al. . The use of maximum SOFA score to quantify organ dysfunction/failure in intensive care. Results of a prospective, multicentre study. Working Group on Sepsis related Problems of the ESICM. Intensive Care Med 1999;25:686–96.
    1. Ferreira FL, Bota DP, Bross A, et al. . Serial evaluation of the SOFA score to predict outcome in critically ill patients. JAMA 2001;286:1754–8. 10.1001/jama.286.14.1754
    1. Singer M, Deutschman CS, Seymour CW, et al. . The Third International Consensus Definitions for Sepsis and Septic Shock (Sepsis-3). JAMA 2016;315:801–10. 10.1001/jama.2016.0287
    1. Colbert JF, Schmidt EP. Endothelial and Microcirculatory Function and Dysfunction in Sepsis. Clin Chest Med 2016;37:263–75. 10.1016/j.ccm.2016.01.009

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