Can venous-to-arterial carbon dioxide differences reflect microcirculatory alterations in patients with septic shock?

Gustavo A Ospina-Tascón, Mauricio Umaña, William F Bermúdez, Diego F Bautista-Rincón, Juan D Valencia, Humberto J Madriñán, Glenn Hernandez, Alejandro Bruhn, César Arango-Dávila, Daniel De Backer, Gustavo A Ospina-Tascón, Mauricio Umaña, William F Bermúdez, Diego F Bautista-Rincón, Juan D Valencia, Humberto J Madriñán, Glenn Hernandez, Alejandro Bruhn, César Arango-Dávila, Daniel De Backer

Abstract

Purpose: Septic shock has been associated with microvascular alterations and these in turn with the development of organ dysfunction. Despite advances in video microscopic techniques, evaluation of microcirculation at the bedside is still limited. Venous-to-arterial carbon dioxide difference (Pv-aCO2) may be increased even when venous O2 saturation (SvO2) and cardiac output look normal, which could suggests microvascular derangements. We sought to evaluate whether Pv-aCO2 can reflect the adequacy of microvascular perfusion during the early stages of resuscitation of septic shock.

Methods: Prospective observational study including 75 patients with septic shock in a 60-bed mixed ICU. Arterial and mixed-venous blood gases and hemodynamic variables were obtained at catheter insertion (T0) and 6 h after (T6). Using a sidestream dark-field device, we simultaneously acquired sublingual microcirculatory images for blinded semiquantitative analysis. Pv-aCO2 was defined as the difference between mixed-venous and arterial CO2 partial pressures.

Results: Progressively lower percentages of small perfused vessels (PPV), lower functional capillary density, and higher heterogeneity of microvascular blood flow were observed at higher Pv-aCO2 values at both T0 and T6. Pv-aCO2 was significantly correlated to PPV (T0: coefficient -5.35, 95 % CI -6.41 to -4.29, p < 0.001; T6: coefficient, -3.49, 95 % CI -4.43 to -2.55, p < 0.001) and changes in Pv-aCO2 between T0 and T6 were significantly related to changes in PPV (R (2) = 0.42, p < 0.001). Absolute values and changes in Pv-aCO2 were not related to global hemodynamic variables. Good agreement between venous-to-arterial CO2 and PPV was maintained even after corrections for the Haldane effect.

Conclusions: During early phases of resuscitation of septic shock, Pv-aCO2 could reflect the adequacy of microvascular blood flow.

Keywords: Microcirculation; Microcirculatory blood flow; Septic shock; Venous-to-arterial carbon dioxide difference.

Figures

Fig. 1
Fig. 1
Percentage of small vessels perfused (PPV), functional capillary density (FCD), and heterogeneity index (HI) for the predefined Pv-aCO2 groups. Box plots depicting differences in PPV, FCD, and HI for predefined Pv-aCO2 groups (group 1, <6.0 mmHg; group 2, 6.0–9.9 mmHg; group 3, ≥10 mmHg) at both T0 (a) and T6 (b). Kruskal–Wallis test, p < 0.001. *Post hoc Mann–Whitney analysis adjusted for multiple comparisons; p < 0.05 for group 1 vs. 2 and 1 vs. 3, **post hoc Mann–Whitney analysis adjusted for multiple comparisons; p < 0.05 for group 2 vs. 3. Boxes denote interquartile range, horizontal line in the boxes represents the median values, and whiskers extend 1.5 times the interquartile range above and below the 25th and 75th percentiles. PPV percentage of small vessels perfused, Pv-aCO2 venous-to-arterial carbon dioxide difference, FCD functional capillary density, HI heterogeneity index
Fig. 2
Fig. 2
Scatter plots showing the correlation of variations observed between changes in venous-to-arterial CO2 partial pressure differences (∆ Pv-aCO2) and a changes in percentage of small vessels perfused (∆ PPV) between measurements performed at T0 and T6 (R2 = 0.42, p < 0.001) and b changes in cardiac output (∆ cardiac output) between measurements performed at T0 and T6 (R2 = 0.01, p = 0.45)
Fig. 3
Fig. 3
Scatter plots depicting the relationships between the percentage of small vessels perfused (PPV) at T0 and a the venous-to-arterial CO2 partial pressure difference (Pv-aCO2), b the venous-to-arterial CO2 content difference (Pv-aCO2), and c the venous-to-arterial CO2 to arterial-venous O2 content difference ratio (Cv-aCO2/Da-vO2). Coefficient of determination (R2) was calculated to assess the strength of correlations

References

    1. Vincent JL, De Backer D. Circulatory shock. N Engl J Med. 2013;369:1726–1734. doi: 10.1056/NEJMra1208943.
    1. Cecconi M, De Backer D, Antonelli M, Beale R, Bakker J, Hofer C, Jaeschke R, Mebazaa A, Pinsky MR, Teboul JL, Vincent JL, Rhodes A. Consensus on circulatory shock and hemodynamic monitoring. Task force of the European Society of Intensive Care Medicine. Intensive Care Med. 2014;40:1795–1815. doi: 10.1007/s00134-014-3525-z.
    1. Bellomo R, Reade MC, Warrillow SJ. The pursuit of a high central venous oxygen saturation in sepsis: growing concerns. Crit Care. 2008;12:130. doi: 10.1186/cc6841.
    1. Yealy DM, Kellum JA, Huang DT, Barnato AE, Weissfeld LA, Pike F, Terndrup T, Wang HE, Hou PC, LoVecchio F, Filbin MR, Shapiro NI, Angus DC, Investigators P. A randomized trial of protocol-based care for early septic shock. N Engl J Med. 2014;370:1683–1693. doi: 10.1056/NEJMoa1401602.
    1. Peake SL, Bailey M, Bellomo R, Cameron PA, Cross A, Delaney A, Finfer S, Higgins A, Jones DA, Myburgh JA, Syres GA, Webb SA, Williams P, ARISE Investigators, for the Australian and New Zealand Intensive Care Society Clinical Trials Group Australasian resuscitation of sepsis evaluation (ARISE): a multi-centre, prospective, inception cohort study. Resuscitation. 2009;80:811–818. doi: 10.1016/j.resuscitation.2009.03.008.
    1. Mouncey PR, Osborn TM, Power GS, Harrison DA, Sadique MZ, Grieve RD, Jahan R, Harvey SE, Bell D, Bion JF, Coats TJ, Singer M, Young JD, Rowan KM, Investigators PT. Trial of early, goal-directed resuscitation for septic shock. N Engl J Med. 2015;372:1301–1311. doi: 10.1056/NEJMoa1500896.
    1. van Beest PA, Hofstra JJ, Schultz MJ, Boerma EC, Spronk PE, Kuiper MA. The incidence of low venous oxygen saturation on admission to the intensive care unit: a multi-center observational study in the Netherlands. Crit Care. 2008;12:R33. doi: 10.1186/cc6811.
    1. Ospina-Tascón GA, Bautista-Rincón DF, Umaña M, Tafur JD, Gutiérrez A, García AF, Bermúdez W, Granados M, Arango-Dávila C, Hernández G. Persistently high venous-to-arterial carbon dioxide differences during early resuscitation are associated with poor outcomes in septic shock. Crit Care. 2013;17:R294. doi: 10.1186/cc13160.
    1. van Beest PA, Lont MC, Holman ND, Loef B, Kuiper MA, Boerma EC. Central venous-arterial pCO2 difference as a tool in resuscitation of septic patients. Intensive Care Med. 2013;39:1034–1039. doi: 10.1007/s00134-013-2888-x.
    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. Grundler W, Weil MH, Rackow EC. Arteriovenous carbon dioxide and pH gradients during cardiac arrest. Circulation. 1986;74:1071–1074. doi: 10.1161/01.CIR.74.5.1071.
    1. Weil MH, Rackow EC, Trevino R, Grundler W, Falk JL, Griffel MI. Difference in acid-base state between venous and arterial blood during cardiopulmonary resuscitation. N Engl J Med. 1986;315:153–156. doi: 10.1056/NEJM198607173150303.
    1. Zhang H, Vincent JL. Arteriovenous differences in PCO2 and pH are good indicators of critical hypoperfusion. Am Rev Respir Dis. 1993;148:867–871. doi: 10.1164/ajrccm/148.4_Pt_1.867.
    1. Van der Linden P, Rausin I, Deltell A, Bekrar Y, Gilbart E, Bakker J, Vincent JL. Detection of tissue hypoxia by arteriovenous gradient for PCO2 and pH in anesthetized dogs during progressive hemorrhage. Anesth Analg. 1995;80:269–275.
    1. Groeneveld AB, Vermeij CG, Thijs LG. Arterial and mixed venous blood acid-base balance during hypoperfusion with incremental positive end-expiratory pressure in the pig. Anesth Analg. 1991;73:576–582.
    1. Teboul JL, Mercat A, Lenique F, Berton C, Richard C. Value of the venous-arterial PCO2 gradient to reflect the oxygen supply to demand in humans: effects of dobutamine. Crit Care Med. 1998;26:1007–1010. doi: 10.1097/00003246-199806000-00017.
    1. Bakker J, Vincent JL, Gris P, Leon M, Coffernils M, Kahn RJ. Veno-arterial carbon dioxide gradient in human septic shock. Chest. 1992;101:509–515. doi: 10.1378/chest.101.2.509.
    1. Mecher CE, Rackow EC, Astiz ME, Weil MH. Venous hypercarbia associated with severe sepsis and systemic hypoperfusion. Crit Care Med. 1990;18:585–589. doi: 10.1097/00003246-199006000-00001.
    1. Vallet B, Teboul JL, Cain S, Curtis S. Venoarterial CO(2) difference during regional ischemic or hypoxic hypoxia. J Appl Physiol. 2000;89:1317–1321.
    1. Dubin A, Estenssoro E, Murias G, Pozo MO, Sottile JP, Barán M, Piacentini E, Canales HS, Etcheverry G. Intramucosal-arterial Pco2 gradient does not reflect intestinal dysoxia in anemic hypoxia. J Trauma. 2004;57:1211–1217. doi: 10.1097/01.TA.0000107182.43213.4B.
    1. De Backer D, Creteur J, Preiser JC, Dubois MJ, Vincent JL. Microvascular blood flow is altered in patients with sepsis. Am J Respir Crit Care Med. 2002;166:98–104. doi: 10.1164/rccm.200109-016OC.
    1. De Backer D, Ospina-Tascon G, Salgado D, Favory R, Creteur J, Vincent JL. Monitoring the microcirculation in the critically ill patient: current methods and future approaches. Intensive Care Med. 2010;36:1813–1825. doi: 10.1007/s00134-010-2005-3.
    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. Creteur J, De Backer D, Sakr Y, Koch M, Vincent JL. Sublingual capnometry tracks microcirculatory changes in septic patients. Intensive Care Med. 2006;32:516–523. doi: 10.1007/s00134-006-0070-4.
    1. Dubin A, Edul VS, Pozo MO, Murias G, Canullan CM, Martins EF, Ferrara G, Canales HS, Laporte M, Estenssoro E, Ince C. Persistent villi hypoperfusion explains intramucosal acidosis in sheep endotoxemia. Crit Care Med. 2008;36:535–542. doi: 10.1097/01.CCM.0000300083.74726.43.
    1. Horan TC, Andrus M, Dudeck MA. CDC/NHSN surveillance definition of health care-associated infection and criteria for specific types of infections in the acute care setting. Am J Infect Control. 2008;36:309–332. doi: 10.1016/j.ajic.2008.03.002.
    1. Levy MM, Fink MP, Marshall JC, Abraham E, Angus D, Cook D, Cohen J, Opal SM, Vincent JL, Ramsay G, SCCM/ESICM/ACCP/ATS/SIS 2001 SCCM/ESICM/ACCP/ATS/SIS International Sepsis Definitions Conference. Crit Care Med. 2003;31:1250–1256. doi: 10.1097/01.CCM.0000050454.01978.3B.
    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 SA, Beale RJ, Vincent JL, Moreno R, Surviving Sepsis Campaign Guidelines Committee including The Pediatric Subgroup Surviving Sepsis Campaign: international guidelines for management of severe sepsis and septic shock, 2012. Crit Care Med. 2013;41:580–637. doi: 10.1097/CCM.0b013e31827e83af.
    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. Wu L, Tiwari MM, Messer KJ, Holthoff JH, Gokden N, Brock RW, Mayeux PR. Peritubular capillary dysfunction and renal tubular epithelial cell stress following lipopolysaccharide administration in mice. Am J Physiol Renal Physiol. 2007;292:F261–F268. doi: 10.1152/ajprenal.00263.2006.
    1. Fink T, Heymann P, Taha-Melitz S, Taha A, Wolf B, Rensing H, Volk T, Mathes AM. Dobutamine pretreatment improves survival, liver function, and hepatic microcirculation after polymicrobial sepsis in rat. Shock. 2013;40:129–135. doi: 10.1097/SHK.0b013e31829c361d.
    1. Bateman RM, Tokunaga C, Kareco T, Dorscheid DR, Walley KR. Myocardial hypoxia-inducible HIF-1alpha, VEGF, and GLUT1 gene expression is associated with microvascular and ICAM-1 heterogeneity during endotoxemia. Am J Physiol Heart Circ Physiol. 2007;293:H448–H456. doi: 10.1152/ajpheart.00035.2007.
    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. Moore JP, Dyson A, Singer M, Fraser J. Microcirculatory dysfunction and resuscitation: why, when, and how. Br J Anaesth. 2015;115:366–375. doi: 10.1093/bja/aev163.
    1. Ince C. The rationale for microcirculatory guided fluid therapy. Curr Opin Crit Care. 2014;20:301–308. doi: 10.1097/MCC.0000000000000091.
    1. Zuurbier CJ, van Iterson M, Ince C. Functional heterogeneity of oxygen supply-consumption ratio in the heart. Cardiovasc Res. 1999;44:488–497. doi: 10.1016/S0008-6363(99)00231-X.
    1. Stein JC, Ellis CG, Ellsworth ML. Relationship between capillary and systemic venous PO2 during nonhypoxic and hypoxic ventilation. Am J Physiol. 1993;265:H537–H542.
    1. Goldman D, Bateman RM, Ellis CG. Effect of decreased O2 supply on skeletal muscle oxygenation and O2 consumption during sepsis: role of heterogeneous capillary spacing and blood flow. Am J Physiol Heart Circ Physiol. 2006;290:H2277–H2285. doi: 10.1152/ajpheart.00547.2005.
    1. Walley KR. Heterogeneity of oxygen delivery impairs oxygen extraction by peripheral tissues: theory. J Appl Physiol. 1996;81:885–894.
    1. De Backer D, Creteur J, Dubois MJ, Sakr Y, Koch M, Verdant C, Vincent JL. The effects of dobutamine on microcirculatory alterations in patients with septic shock are independent of its systemic effects. Crit Care Med. 2006;34:403–408. doi: 10.1097/01.CCM.0000198107.61493.5A.
    1. Edul VS, Enrico C, Laviolle B, Vazquez AR, Ince C, Dubin A. Quantitative assessment of the microcirculation in healthy volunteers and in patients with septic shock. Crit Care Med. 2012;40:1443–1448. doi: 10.1097/CCM.0b013e31823dae59.
    1. Ospina-Tascon GA, Umana M, Bermudez W, Bautista-Rincon DF, Hernandez G, Bruhn A, Granados M, Salazar B, Arango-Davila C, De Backer D. Combination of arterial lactate levels and venous-arterial CO2 to arterial-venous O2 content difference ratio as markers of resuscitation in patients with septic shock. Intensive Care Med. 2015;41:796–805. doi: 10.1007/s00134-015-3720-6.
    1. Jakob SM, Groeneveld AB, Teboul JL. Venous-arterial CO2 to arterial-venous O2 difference ratio as a resuscitation target in shock states? Intensive Care Med. 2015;41:936–938. doi: 10.1007/s00134-015-3778-1.
    1. Cuschieri J, Rivers EP, Donnino MW, Katilius M, Jacobsen G, Nguyen HB, Pamukov N, Horst HM. Central venous-arterial carbon dioxide difference as an indicator of cardiac index. Intensive Care Med. 2005;31:818–822. doi: 10.1007/s00134-005-2602-8.
    1. Vandenbroucke JP. Observational research, randomised trials, and two views of medical science. PLoS Med. 2008;5:e67. doi: 10.1371/journal.pmed.0050067.
    1. Pearce N. Registration of protocols for observational research is unnecessary and would do more harm than good. Occup Environ Med. 2011;68:86–88. doi: 10.1136/oem.2010.058917.

Source: PubMed

Sponsor e collaboratori

Condizioni mediche

Interventi farmacologici

3
Sottoscrivi