Cecconi, M

Pinsky, MR

Vallet, B

English

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B. ValletM. R. PinskyM. CecconiResuscitation of patients with septic shock:please ‘‘mind the gap’’!Received: 30 May 2013Accepted: 7 June 2013Published online: 29 June 2013 The Author(s) 2013. This article is published with open access atSpringerlink.comB. Vallet ())Department of Anesthesiology and Critical Care MedicineUniversity Hospital of Lille, Univ Nord de France, Lille, Francee-mail: benoit.vallet@chru-lille.frTel.: ?33-3-20444447Fax: ?33-3-20444440M. R. PinskyDepartment of Critical Care Medicine, University of Pittsburgh,Pittsburgh, PA, USAM. CecconiDepartment of Intensive Care Medicine, St George’s HealthcareNHS Trust and St George’s University of London, London, UKVan Beest et al. [1] performed a post hoc analysis of 53patients with severe sepsis or septic shock to investigatethe interchangeability of mixed and central venous-to-arterial carbon dioxide (CO2) differences (mvaCO2gapand cvaCO2gap, respectively) and the relation betweenthe cvaCO2gap (‘‘pCO2gap’’ or the ‘‘gap’’), cardiac index(CI), and outcome. The authors observed a strong agree-ment between pCO2 measured from either mixed venousor central venous sites with relatively small limits ofagreement. The authors claim that combining ScvO2values, as easily obtained from a central venous catheter,as a surrogate for global tissue hypoxia, and pCO2gap as asurrogate for CI, obtained from the same central venouscatheter, may be useful in assessing cardiovascular stateduring resuscitation in critically ill patients. We cannotagree more and propose thereafter a tentative ‘‘ScvO2-cvaCO2gap-guided protocol’’ (Fig. 1). Cuschieri et al. [2]previously demonstrated in a mixed population of criti-cally ill patients that the relationships between themvaCO2gap or the cvaCO2gap and the CI were equiva-lent. Since central venous blood is readily available froma central venous catheter, whereas mixed venous bloodrequires a pulmonary artery catheter, the cvaCO2gap, asan easily available clinical monitoring tool, is attractive.At ICU admission, 24 patients in the van Beest et al. studyhad a pCO2gap greater than 0.8 kPa (or 6 mmHg). Per-sistence of such a large pCO2gap after 24 h of treatmentwas predictive of higher mortality.These data are in line with results of Valle´e et al. [3]who prospectively tested this hypothesis in 56 septicshock patients resuscitated to an ScvO2 greater than 70 %(according to the Rivers’ study results [4]). They foundthat patients who still had altered tissue perfusion(assessed by serum lactate levels greater than 2 mmol L-1) in spite of a normalized ScvO2 displayed a largecvaCO2gap (greater than 6 mmHg). CO2 is the endproduct of aerobic metabolism and its concentration in thevenous blood reflects the global tissue blood flow relativeto metabolic demand. Since CO2 is about 20 times moresoluble than O2 the likelihood of it diffusing out ofischemic tissues and into the venous effluent is great,making it a very sensitive marker of hypoperfusion. Thus,in situations where an O2 diffusion barrier exists (result-ing from non-functional and obliterated capillaries),‘‘masking’’ poor O2 extraction (O2ER) and increasedtissue O2 debt, CO2 still diffuses to the venous effluent,‘‘unmasking’’ the low perfusion state for the clinicianwhen venous-to-arterial CO2 difference is evaluated.Consistently Valle´e et al. [3] evidenced that patients withhigh cvaCO2gap values had lower lactate clearance andCI values, and presented a significant lower decrease inSepsis-related Organ Failure Assessment score thanpatients with a low cvaCO2gap. Thus, the cvaCO2gapIntensive Care Med (2013) 39:1653–1655DOI 10.1007/s00134-013-2998-5 EDITORIALrepresents a useful complementary tool to identifypatients who remain inadequately resuscitated when the70 % ScvO2 threshold value has been reached.The obvious limitation of ScvO2 is therefore that nor-mal/high values cannot discriminate whether delivery isadequate or in excess to demand. High ScvO2 profileshave even been shown to be related to elevated bloodlactate concentration and poor survival rates [5].Although ScvO2 may thus not miss any global oxygendelivery (DO2) disorder, it may remain ‘‘blind’’ to localperfusion disorders, which abound in sepsis because ofimpaired microcirculation. Under conditions where O2uptake (VO2) does not meet O2 demand, tissue dysoxiaoccurs, leading to organ failure and death. The crucialpoint here is that these tissues might remain howeveraccessible to conventional therapeutic hemodynamicmanagement (inotropes and fluid infusion).Whether the resultant effect on pCO2 gap depends inprinciple on the flow state or anaerobic CO2 productionwas tested by Vallet et al. [6] in an experimental model ofisolated limb in which ischemic hypoxia (IH) and hypoxichypoxia (HH) were compared. The authors demonstratedthat when DO2 was reduced beyond its critical thresholdin IH (dysoxia), this was associated with an increasedlimb venous-to-arterial pCO2gap [6]. Conversely, inHH, pCO2gap did not increase in spite of a marked VO2and VCO2 reduction, clearly evidencing the gap as amarker of adequacy of venous blood flow to remove CO2produced rather than a marker of tissue hypoxia ordysoxia.In conclusion, determining the gap during resuscitationof critically ill patients is useful when deciding when tostop resuscitation despite persistent evidence of organischemia and an ScvO2 of greater than 70 % (see Fig. 1,Table 1). All forms of circulatory stress are potentiallyassociated with hyperlactatemia, but hyperlactatemia isnot a discriminatory factor in defining the cause of thatstress. A goal of a gap lower than 6 could be a usefulcomplementary tool to evaluate the adequacy of bloodflow to global metabolic demand. In this regard it can helpto titrate inotropes in order to adapt DO2 to VCO2, or tochoose between hemoglobin correction or fluid/inotropeFig. 1 The ScvO2-cvaCO2gap-guided protocol. ScvO2 venous central O2 saturation, cvCO2gap central venous-to-arterial pCO2difference, SaO2 arterial O2 saturation, CI cardiac index, SVV stroke volume variability, PPV pulse pressure variabilityTable 1 Lactate-ScvO2-cvaCO2gap as shock diagnostic toolsShock type Lactate O2ER ScvO2 cvaCO2gapCardiogenic hypovolemic HI HI LO HIAnemic hypoxemic HI HI LO LODistributive HI LO HI HICytopathic HI LO HI LOScvO2 venous central O2 saturation, cvCO2gap central venous-to-arterial pCO2 difference, O2ER O2 extraction ratio, HI high, LO low1654infusion. Whatever way you use it or like it, from mixedor central venous, in patients with septic shock, please‘‘mind the gap’’!Conflicts of interest None.Open Access This article is distributed under the terms of theCreative Commons Attribution Noncommercial License whichpermits any noncommercial use, distribution, and reproduction inany medium, provided the original author(s) and the source arecredited.References1. Van Beest PA, Lont MC, Holman ND,Loef B, Kuiper MA, Boerma EC (2013)Central venous-arterial pCO2 differenceas a tool in resuscitation of septicpatients. Intensive Care Med39:1034–10392. Cuschieri J, Rivers EP, Donnino MW,Katilius M, Jacobsen G, Nguyen HB,Pamukov N, Horst HM (2005) Centralvenous-arterial carbon dioxide differenceas an indicator of cardiac index.Intensive Care Med 31:818–8223. Valle´e F, Vallet B, Mathe O, ParraguetteJ, Mari A, Silva S, Samii K, Fourcade O,Genestal M (2008) Central venous-to-arterial carbon dioxide difference: anadditional target for goal-directedtherapy in septic shock? Intensive CareMed 34:2218–22254. Rivers E, Nguyen B, Havstad S, ResslerJ, Muzzin A, Knoblich B, Peterson E,Tomlanovich M, Early Goal-DirectedTherapy Collaborative Group (2001)Early goal-directed therapy in thetreatment of severe sepsis and septicshock. N Engl J Med 345:1368–13775. Puskarich MA, Trzeciak S, Shapiro NI,Arnold RC, Heffner AC, Kline JA, JonesAE, Emergency Medicine ShockResearch Network (EMSHOCKNET)(2012) Prognostic value and agreementof achieving lactate clearance or centralvenous oxygen saturation goals duringearly sepsis resuscitation. Acad EmergMed 19:252–2586. Vallet B, Teboul JL, Cain S, Curtis S(2000) Venoarterial CO2 differenceduring regional ischemic or hypoxichypoxia. J Appl Physiol 89:1317–13211655

Central venous-arterial pCO2 difference as a tool in resuscitation of septic patients.

Central venous-toarterial carbon dioxide difference: an additional target for goal-directed therapy in septic shock? Intensive Care Med 34:2218–2225 4. Rivers

Resuscitation of patients with septic shock: please "mind the gap"!

B. Vallet

M. R. Pinsky

M. Cecconi

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Intensive Care Medicine

Resuscitation of patients with septic shock: please “mind the gap”!

http://dx.doi.org/10.1007/s00134-013-2998-5

Resuscitation of patients with septic shock: please "mind the gap"!

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