Counterpoint: Should Lactate Clearance Be Substituted for Central Venous Oxygen Saturation as Goals of Early Severe Sepsis and Septic Shock Therapy? No
2011; Elsevier BV; Volume: 140; Issue: 6 Linguagem: Inglês
10.1378/chest.11-2563
ISSN1931-3543
AutoresEmanuel P. Rivers, Ronald Elkin, Chad Cannon,
Tópico(s)Cardiac, Anesthesia and Surgical Outcomes
ResumoIn 2001, early goal-directed therapy (EGDT) resulted in a 16% reduction in hospital mortality and, post hoc, a higher lactate clearance in severe sepsis and septic shock.1Rivers E Nguyen B Havstad S Early Goal-Directed Therapy Collaborative Group et al.Early goal-directed therapy in the treatment of severe sepsis and septic shock.N Engl J Med. 2001; 345: 1368-1377Crossref PubMed Scopus (7748) Google Scholar Multiple studies have confirmed the validity and generalizability of EGDT, resulting in its adoption into the Surviving Sepsis Campaign Guidelines.2Rivers EP Point: adherence to early goal-directed therapy: does it really matter? Yes. After a decade, the scientific proof speaks for itself.Chest. 2010; 138: 476-485Abstract Full Text Full Text PDF PubMed Scopus (34) Google Scholar, 3Dellinger RP Levy MM Carlet JM International Surviving Sepsis Campaign Guidelines Committee American Association of Critical-Care Nurses American College of Chest Physicians American College of Emergency Physicians Canadian Critical Care Society European Society of Clinical Microbiology and Infectious Diseases European Society of Intensive Care Medicine European Respiratory Society International Sepsis Forum Japanese Association for Acute Medicine Japanese Society of Intensive Care Medicine Society of Critical Care Medicine Society of Hospital Medicine Surgical Infection Society World Federation of Societies of Intensive and Critical Care Medicine et al.Surviving Sepsis Campaign: international guidelines for management of severe sepsis and septic shock: 2008.Crit Care Med. 2008; 36: 296-327Crossref PubMed Scopus (3952) Google Scholar Nguyen et al4Nguyen HB Rivers EP Knoblich BP et al.Early lactate clearance is associated with improved outcome in severe sepsis and septic shock.Crit Care Med. 2004; 32: 1637-1642Crossref PubMed Scopus (839) Google Scholar, 5Nguyen HB Loomba M Yang JJ et al.Early lactate clearance is associated with biomarkers of inflammation, coagulation, apoptosis, organ dysfunction and mortality in severe sepsis and septic shock.J Inflamm (Lond). 2010; 7: 6Crossref PubMed Scopus (123) Google Scholar examined early lactate clearance and found a significant retrospective association with inflammation, apoptosis, coagulation, organ dysfunction, and mortality. Following this rationale, Jones et al6Jones AE Shapiro NI Trzeciak S Arnold RC Claremont HA Kline JA Emergency Medicine Shock Research Network (EMShockNet) Investigators Lactate clearance vs central venous oxygen saturation as goals of early sepsis therapy: a randomized clinical trial.JAMA. 2010; 303: 739-746Crossref PubMed Scopus (792) Google Scholar modified the EGDT protocol in 2010 using a noninferiority study design and concluded that lactate clearance is equivalent to central venous oxygen saturation (Scvo2) in the management of individual patients.Before applying the findings of Jones et al6Jones AE Shapiro NI Trzeciak S Arnold RC Claremont HA Kline JA Emergency Medicine Shock Research Network (EMShockNet) Investigators Lactate clearance vs central venous oxygen saturation as goals of early sepsis therapy: a randomized clinical trial.JAMA. 2010; 303: 739-746Crossref PubMed Scopus (792) Google Scholar to one's next patient, compare the baseline characteristics, early hemodynamic patterns, and therapeutic interventions between those of Jones et al6Jones AE Shapiro NI Trzeciak S Arnold RC Claremont HA Kline JA Emergency Medicine Shock Research Network (EMShockNet) Investigators Lactate clearance vs central venous oxygen saturation as goals of early sepsis therapy: a randomized clinical trial.JAMA. 2010; 303: 739-746Crossref PubMed Scopus (792) Google Scholar and the EGDT study.1Rivers E Nguyen B Havstad S Early Goal-Directed Therapy Collaborative Group et al.Early goal-directed therapy in the treatment of severe sepsis and septic shock.N Engl J Med. 2001; 345: 1368-1377Crossref PubMed Scopus (7748) Google Scholar Further, review the complexities of lactate kinetics and the weaknesses of a noninferiority study design.7Piaggio G Elbourne DR Altman DG Pocock SJ Evans SJ CONSORT Group Reporting of noninferiority and equivalence randomized trials: an extension of the CONSORT statement.JAMA. 2006; 295: 1152-1160Crossref PubMed Scopus (1024) Google Scholar Based on these facts, it is clear that lactate clearance and Scvo2 are not equivalent, but complementary goals for the individual patient.The Hemodynamic Phases of Severe Sepsis and Septic ShockThe early stages of sepsis are accompanied by circulatory insufficiency that results from hypovolemia, vasomotor dysfunction, myocardial depression, and increased metabolic demands. In the systemic oxygen delivery (Do2)-dependent (hypodynamic) phase, a decrease in Do2 results in a decrease in Scvo2/mixed venous oxygen saturation (Svo2) and usually an increase in systemic oxygen extraction (OER) or 1 − Scvo2/Svo2 (Fig 1,8Kruse J Lactic acidosis, part 1: understanding pathogenesis and causes. As mechanisms are elucidated, some assumptions are being revised.J Crit Illness. 1999; 14: 456-466Google Scholar Table 1). When the limits of the OER (anaerobic threshold) are reached, lactate is produced, signifying the development of global tissue hypoxia (GTH). There is significant individual variation in the anaerobic threshold leading to variable lactate production.9Levraut J Ichai C Petit I Ciebiera JP Perus O Grimaud D Low exogenous lactate clearance as an early predictor of mortality in normolactatemic critically ill septic patients.Crit Care Med. 2003; 31: 705-710Crossref PubMed Scopus (102) Google Scholar This gives rise to why some patients may require normal or elevated Do2 in order to resolve GTH (decreased Scvo2/Svo2 and increased lactate) (Fig 1, Table 1). GTH is associated with increased morbidity and mortality if not adequately treated.10Astiz ME Rackow EC Kaufman B Falk JL Weil MH Relationship of oxygen delivery and mixed venous oxygenation to lactic acidosis in patients with sepsis and acute myocardial infarction.Crit Care Med. 1988; 16: 655-658Crossref PubMed Scopus (99) Google Scholar, 11Rivers EP Kruse JA Jacobsen G et al.The influence of early hemodynamic optimization on biomarker patterns of severe sepsis and septic shock.Crit Care Med. 2007; 35: 2016-2024Crossref PubMed Scopus (170) Google Scholar Because GTH can occur with normal vital signs, it has been termed "cryptic shock."12Rady MY Rivers EP Nowak RM Resuscitation of the critically ill in the ED: responses of blood pressure, heart rate, shock index, central venous oxygen saturation, and lactate.Am J Emerg Med. 1996; 14: 218-225Abstract Full Text PDF PubMed Scopus (192) Google Scholar GTH or cardiovascular insufficiency is a significant part of the natural history of sepsis and responsible for the sudden cardiopulmonary deterioration seen in 12% to 21% of patients.13Brun-Buisson C Doyon F Carlet J French ICU Group for Severe Sepsis et al.Incidence, risk factors, and outcome of severe sepsis and septic shock in adults. A multicenter prospective study in intensive care units.JAMA. 1995; 274: 968-974Crossref PubMed Google Scholar, 14Carr GE Edelson DP Yuen TC et al.In-hospital cardiac arrest among patients with coexisting pneumonia: a report from the American Heart Association's Get With The Guidelines–Resuscitation Program.Am J Respir Crit Care Med. 2011; 183: A6339Google Scholar EGDT is associated with a 50% reduction in this adverse event, an issue not addressed by Jones et al.6Jones AE Shapiro NI Trzeciak S Arnold RC Claremont HA Kline JA Emergency Medicine Shock Research Network (EMShockNet) Investigators Lactate clearance vs central venous oxygen saturation as goals of early sepsis therapy: a randomized clinical trial.JAMA. 2010; 303: 739-746Crossref PubMed Scopus (792) Google ScholarTable 1Hemodynamic Phases of SepsisStageHemodynamic PictureSBPCVPTreatment and CommentsBHypovolemiaVariable↓VolumeMyocardial suppressionVariable↑Correct anemia, inotropic therapyAResuscitated, compensated, and vasodilatoryVariableNormalVasopressors, low-dose corticosteroidsCSupranormal Do2 dependencyVariable↑ to normalIncreased o2 after augmentation of Do2DImpairment of tissue O2 utilizationVariableNormalr-APCDecreased o2VariableNormalResuscitatedCVP = central venous pressure; Do2 = systemic oxygen delivery; r-APC = recombinant activated protein C; SBP = systolic BP; SvO2 = mixed venous oxygen saturation; o2 = oxygen consumption. Open table in a new tab With adequate volume therapy and myocardial reserve, a hyperdynamic or compensated phase follows. During this compensated phase, Do2 is in the normal or elevated range, systemic oxygen consumption (o2) is increased, and vascular resistance is generally decreased. In contrast to the hypodynamic phase (patients in the Rivers et al1Rivers E Nguyen B Havstad S Early Goal-Directed Therapy Collaborative Group et al.Early goal-directed therapy in the treatment of severe sepsis and septic shock.N Engl J Med. 2001; 345: 1368-1377Crossref PubMed Scopus (7748) Google Scholar study), Jones et al6Jones AE Shapiro NI Trzeciak S Arnold RC Claremont HA Kline JA Emergency Medicine Shock Research Network (EMShockNet) Investigators Lactate clearance vs central venous oxygen saturation as goals of early sepsis therapy: a randomized clinical trial.JAMA. 2010; 303: 739-746Crossref PubMed Scopus (792) Google Scholar enrolled patients in this phase with a lower systolic BP, normal central venous pressure (CVP), normal Scvo2, lower lactate levels, and triple the frequency of vasopressor dependence (Fig 1; Table 1, Table 2). These patients also had corresponding Simplified Acute Physiology Score II scores and predicted mortality that was nearly 14% lower than that in patients receiving EGDT (34.8% vs 48.4%) and other studies.2Rivers EP Point: adherence to early goal-directed therapy: does it really matter? Yes. After a decade, the scientific proof speaks for itself.Chest. 2010; 138: 476-485Abstract Full Text Full Text PDF PubMed Scopus (34) Google ScholarTable 2Comparison of Clinical Variables Between Jones et al6Jones AE Shapiro NI Trzeciak S Arnold RC Claremont HA Kline JA Emergency Medicine Shock Research Network (EMShockNet) Investigators Lactate clearance vs central venous oxygen saturation as goals of early sepsis therapy: a randomized clinical trial.JAMA. 2010; 303: 739-746Crossref PubMed Scopus (792) Google Scholar and Rivers et al1Rivers E Nguyen B Havstad S Early Goal-Directed Therapy Collaborative Group et al.Early goal-directed therapy in the treatment of severe sepsis and septic shock.N Engl J Med. 2001; 345: 1368-1377Crossref PubMed Scopus (7748) Google ScholarJones et al6Jones AE Shapiro NI Trzeciak S Arnold RC Claremont HA Kline JA Emergency Medicine Shock Research Network (EMShockNet) Investigators Lactate clearance vs central venous oxygen saturation as goals of early sepsis therapy: a randomized clinical trial.JAMA. 2010; 303: 739-746Crossref PubMed Scopus (792) Google ScholarRivers et al1Rivers E Nguyen B Havstad S Early Goal-Directed Therapy Collaborative Group et al.Early goal-directed therapy in the treatment of severe sepsis and septic shock.N Engl J Med. 2001; 345: 1368-1377Crossref PubMed Scopus (7748) Google ScholarLactate ClearanceScvo2 GuidedStandard TherapyEGDTComorbidities Congestive heart failure……30.236.7 Coronary artery disease……23.526.5 Liver disease……23.523.1 Alcohol use……38.738.5Baseline hemodynamics Lactate, naNo statistical significance. mmol/L3.9±3.14.2±3.16.9±4.57.7±4.7 CVP,aNo statistical significance. mm Hg11±6.511±6.26.1±7.75.3±9.3 Systolic BP,aNo statistical significance. mm Hg91±24.692±21.0109±34106±36 Scvo2aNo statistical significance.…74±12.349.2±13.348.6±11.2Treatments (0-6-h ranges) RBC transfusions7318.564.1 P Value.2…< .001… VasopressorsaNo statistical significance.727530.327.4 Inotropes350.813.7 P Value.57…< .001… Mechanical ventilationaNo statistical significance.272653.853.06 h hemodynamics Lactate, mmol/L……4.9±4.74.3±4.2 P Value.01 Lactate clearance (0–6 h)……2944.2 P Value.01 CVP, mm Hg……11.8±6.813.8±4.4 P Value.007 Scvo2……66.0±15.577.3±10.0 P Value< .001Sudden cardiopulmonary collapse……21.010.3 P Value.02SAPS II scores (baseline)aNo statistical significance.44.8±18.444.1±17.348.8±11.151.2±11.1Predicted mortality (approximate)34.832.848.448.7Actual in-hospital mortality231746.530.5 P ValueNS….009…Data are presented as mean ± SD or %. EGDT = early goal-directed therapy; NS = not significant; SAPS = Simplified Acute Physiology Score; Scvo2 = central venous oxygen saturation. See Table 1 legend for expansion of other abbreviations.a No statistical significance. Open table in a new tab Pathological Do2 dependency is a result of a progressive impairment of OER, which is accompanied by a markedly increased Scvo2/Svo2 (venous hyperoxia) and a hyperdynamic circulation. When Do2 is insufficient, o2 decreases, and increased lactate levels accompany venous hyperoxia. The phase of tissue dysoxia can be the result of microcirculatory dysfunction causing maldistribution of blood flow or mitochondrial dysfunction with defects in substrate utilization. In this phase, improvement in Do2 may not result in improvement in o2.Sepsis may consist of four hemodynamic phases where a decreased Scvo2/Svo2 always precedes the appearance of lactate, making them complementary and nonexclusive end points, (Fig 1, Table 1). These hemodynamic phases are not always distinct and may overlap depending on the timing and quality of the resuscitation. By characterizing these phases in hemodynamic outcome studies, future trials can be conducted with the appropriate research design and interpreted with clarity, facilitating generalizability and external validation in clinical management.15Sevransky JE Nour S Susla GM Needham DM Hollenberg S Pronovost P Hemodynamic goals in randomized clinical trials in patients with sepsis: a systematic review of the literature.Crit Care. 2007; 11: R67Crossref PubMed Scopus (46) Google ScholarLactate Kinetics Are Complex and Limit the Interpretation of Lactate Levels and Lactate Clearance in the Individual PatientLactate elevation may indicate stress-induced upregulation in epinephrine-stimulated sodium-potassium adenosine triphosphatase activity in skeletal muscle and inhibition of pyruvate metabolism rather than, or in addition to, the traditionally implicated cellular hypoxia. Other confounding influences may include exogenous lactate sources (Ringers lactate or packed RBC transfusions), lactate shuttles and transport, delayed washout from underperfused tissue, variable lactate clearance by a number of organs, and dilution (large-volume resuscitations) (Fig 2). These interactions are not in a steady state and depend on the pathophysiology, timing, and quality of the resuscitation in the individual case.16Mizock BA The hepatosplanchnic area and hyperlactatemia: A tale of two lactates.Crit Care Med. 2001; 29: 447-449Crossref PubMed Scopus (27) Google ScholarFigure 2The kinetics, diagnostic, and therapeutic clinical scenarios of lactate. EGDT = early goal-directed therapy; PRBC = packed RBC; ScvO2 = central venous oxygen saturation. See Figure 1 legend for expansion of other abbreviation.View Large Image Figure ViewerDownload Hi-res image Download (PPT)Normal lactate levels occur in up to 45% of cases of septic shock, and although there is significant variability, the associated mortality can be up to 52%.9Levraut J Ichai C Petit I Ciebiera JP Perus O Grimaud D Low exogenous lactate clearance as an early predictor of mortality in normolactatemic critically ill septic patients.Crit Care Med. 2003; 31: 705-710Crossref PubMed Scopus (102) Google Scholar, 17Hernandez G Castro R Romero C et al.Persistent sepsis-induced hypotension without hyperlactatemia: is it really septic shock?.J Crit Care. 2010; 26 (435e14): 435.e9Abstract Full Text Full Text PDF Scopus (66) Google Scholar, 18Dugas A Joyce N et al.Prevalence and characteristics of non-lactate and lactate expressors in septic shock [abstract].Crit Care Med. 2009; 37: A227Crossref Scopus (60) Google Scholar, 19Cannon CM Multicenter Severe Sepsis and Septic Shock Collaborative Group The GENESIS Project (GENeralization of Early Sepsis InterventionS): a multicenter quality improvement collaborative.Acad Emerg Med. 2010; 17: 1258Crossref Google Scholar In fact, many patients develop multisystem organ failure and die without ever having increased lactate levels.9Levraut J Ichai C Petit I Ciebiera JP Perus O Grimaud D Low exogenous lactate clearance as an early predictor of mortality in normolactatemic critically ill septic patients.Crit Care Med. 2003; 31: 705-710Crossref PubMed Scopus (102) Google Scholar Thus, lactate has limitations as a tool for risk stratification and as a guide for resuscitation in individual patients. In the Jones et al6Jones AE Shapiro NI Trzeciak S Arnold RC Claremont HA Kline JA Emergency Medicine Shock Research Network (EMShockNet) Investigators Lactate clearance vs central venous oxygen saturation as goals of early sepsis therapy: a randomized clinical trial.JAMA. 2010; 303: 739-746Crossref PubMed Scopus (792) Google Scholar study, the lactate clearance goal was at least 10% at ≥2 h or normality of both initial and subsequent lactates. Nguyen et al,20Nguyen HB Rivers EP Havstad S et al.Critical care in the emergency department: a physiologic assessment and outcome evaluation.Acad Emerg Med. 2000; 7: 1354-1361Crossref PubMed Scopus (136) Google Scholar however, found an optimal lactate clearance cutoff of <10% after 6 h of intervention to have a sensitivity of 44.7%, specificity of 84.4%, and accuracy of only 67.6% for predicting in-hospital mortality. Additionally, lactate clearance was less predictive of outcome in septic shock, the predominant feature of the patients in the Jones et al6Jones AE Shapiro NI Trzeciak S Arnold RC Claremont HA Kline JA Emergency Medicine Shock Research Network (EMShockNet) Investigators Lactate clearance vs central venous oxygen saturation as goals of early sepsis therapy: a randomized clinical trial.JAMA. 2010; 303: 739-746Crossref PubMed Scopus (792) Google Scholar study. Because of the variable expression of lactate, its complicated kinetics, and the limited accuracy of lactate clearance, Nguyen et al20Nguyen HB Rivers EP Havstad S et al.Critical care in the emergency department: a physiologic assessment and outcome evaluation.Acad Emerg Med. 2000; 7: 1354-1361Crossref PubMed Scopus (136) Google Scholar did not recommend lactate clearance as a sole therapeutic end point. Serum lactate levels may rise or fluctuate during therapy. Of patients with increased initial lactate levels, 41% have delayed peak values (20±12 h) after the initial presentation.11Rivers EP Kruse JA Jacobsen G et al.The influence of early hemodynamic optimization on biomarker patterns of severe sepsis and septic shock.Crit Care Med. 2007; 35: 2016-2024Crossref PubMed Scopus (170) Google Scholar, 17Hernandez G Castro R Romero C et al.Persistent sepsis-induced hypotension without hyperlactatemia: is it really septic shock?.J Crit Care. 2010; 26 (435e14): 435.e9Abstract Full Text Full Text PDF Scopus (66) Google Scholar Of patients with normal initial lactates, 15% will later demonstrate elevations. These patients have abnormal Scvo2 (66.7%±8.6%) at baseline compared with their counterparts with normal levels.17Hernandez G Castro R Romero C et al.Persistent sepsis-induced hypotension without hyperlactatemia: is it really septic shock?.J Crit Care. 2010; 26 (435e14): 435.e9Abstract Full Text Full Text PDF Scopus (66) Google Scholar Lactate levels over time can increase (negative clearance), stay the same, or decrease (positive clearance) after intervention (Fig 2). Not only is the direction of clearance important but also the magnitude of change. There are significantly different clinical and outcome implications in patients whose lactate levels decrease from 10 to 9 mmol/L vs 4 to 3.6 mmol/L. Although both represent clearance of 10%, the implications for illness severity and prognostic significance are much different.What if the Patient Requires More Than Fluid and Vasopressors and the Lactate Is Still High?Optimization of preload (CVP) and afterload (mean arterial pressure) were addressed by Jones et al6Jones AE Shapiro NI Trzeciak S Arnold RC Claremont HA Kline JA Emergency Medicine Shock Research Network (EMShockNet) Investigators Lactate clearance vs central venous oxygen saturation as goals of early sepsis therapy: a randomized clinical trial.JAMA. 2010; 303: 739-746Crossref PubMed Scopus (792) Google Scholar; however, the remaining components of EGDT, including optimizing Do2 (oxygen carrying capacity [supplemental oxygen and hemoglobin], cardiac output) and decreasing o2 (mechanical ventilation and sedation) to prevent delayed cardiopulmonary complications, were not elicited or examined.15Sevransky JE Nour S Susla GM Needham DM Hollenberg S Pronovost P Hemodynamic goals in randomized clinical trials in patients with sepsis: a systematic review of the literature.Crit Care. 2007; 11: R67Crossref PubMed Scopus (46) Google Scholar Over the past decade, numerous studies have validated the clinical utility of Scvo2 in recognizing supply dependency, need for a transfusion, detection of myocardial dysfunction, response to oxygen and mechanical ventilation, early cardiopulmonary complications, and overall influence on mortality. To establish noninferiority, lactate clearance has to be appropriately examined in these scenarios in order to be generalizable to all hemodynamic phases of sepsis and these facets of care.7Piaggio G Elbourne DR Altman DG Pocock SJ Evans SJ CONSORT Group Reporting of noninferiority and equivalence randomized trials: an extension of the CONSORT statement.JAMA. 2006; 295: 1152-1160Crossref PubMed Scopus (1024) Google Scholar The discrepancy between Scvo2-triggered interventions in the Rivers et al1Rivers E Nguyen B Havstad S Early Goal-Directed Therapy Collaborative Group et al.Early goal-directed therapy in the treatment of severe sepsis and septic shock.N Engl J Med. 2001; 345: 1368-1377Crossref PubMed Scopus (7748) Google Scholar study vs the 30 interventions (10% of patients) guided by lactate clearance reflects significant differences in hemodynamic phases, patient populations, and frequency and timing of interventions (Fig 2). This undermines the conclusion of equivalency from a noninferiority research design.7Piaggio G Elbourne DR Altman DG Pocock SJ Evans SJ CONSORT Group Reporting of noninferiority and equivalence randomized trials: an extension of the CONSORT statement.JAMA. 2006; 295: 1152-1160Crossref PubMed Scopus (1024) Google Scholar Patients more likely to require inotropes (congestive heart failure or coronary artery disease) or patients with reduced lactate clearance (liver failure) were not described by Jones et al6Jones AE Shapiro NI Trzeciak S Arnold RC Claremont HA Kline JA Emergency Medicine Shock Research Network (EMShockNet) Investigators Lactate clearance vs central venous oxygen saturation as goals of early sepsis therapy: a randomized clinical trial.JAMA. 2010; 303: 739-746Crossref PubMed Scopus (792) Google Scholar (Table 2). This lower number of interventions reflects a lower illness severity compared with other studies,2Rivers EP Point: adherence to early goal-directed therapy: does it really matter? Yes. After a decade, the scientific proof speaks for itself.Chest. 2010; 138: 476-485Abstract Full Text Full Text PDF PubMed Scopus (34) Google Scholar the possibility of poor compliance to the protocol, or a study design that is not equivalent to EGDT. The threefold greater use of vasopressors by Jones et al6Jones AE Shapiro NI Trzeciak S Arnold RC Claremont HA Kline JA Emergency Medicine Shock Research Network (EMShockNet) Investigators Lactate clearance vs central venous oxygen saturation as goals of early sepsis therapy: a randomized clinical trial.JAMA. 2010; 303: 739-746Crossref PubMed Scopus (792) Google Scholar may have resulted in higher lactate levels (catecholamines), CVP (increased afterload and venous tone), and Scvo2 (decreased OER). As a result, triggers for more fluid administration, RBC transfusion, inotropes, and mechanical ventilation may have been obscured by catecholamines. In this vasodilatory phase of sepsis, one would expect a higher use of corticosteroids3Dellinger RP Levy MM Carlet JM International Surviving Sepsis Campaign Guidelines Committee American Association of Critical-Care Nurses American College of Chest Physicians American College of Emergency Physicians Canadian Critical Care Society European Society of Clinical Microbiology and Infectious Diseases European Society of Intensive Care Medicine European Respiratory Society International Sepsis Forum Japanese Association for Acute Medicine Japanese Society of Intensive Care Medicine Society of Critical Care Medicine Society of Hospital Medicine Surgical Infection Society World Federation of Societies of Intensive and Critical Care Medicine et al.Surviving Sepsis Campaign: international guidelines for management of severe sepsis and septic shock: 2008.Crit Care Med. 2008; 36: 296-327Crossref PubMed Scopus (3952) Google Scholar; however, they were only used in 37% and 35% of eligible patients in the lactate clearance and Scvo2 groups, respectively.Real-World Clinical PracticeCentral venous catheterization is recommended for patients with septic shock, and this was indeed the practice in the Jones et al6Jones AE Shapiro NI Trzeciak S Arnold RC Claremont HA Kline JA Emergency Medicine Shock Research Network (EMShockNet) Investigators Lactate clearance vs central venous oxygen saturation as goals of early sepsis therapy: a randomized clinical trial.JAMA. 2010; 303: 739-746Crossref PubMed Scopus (792) Google Scholar study. However, this study often is misinterpreted to imply that lactate clearance precludes the need for central venous catheterization altogether. This could result in a delay in a safer route for administration of vasopressors and achievement of EGDT goals within 6 h. The Surviving Sepsis Campaign recommendations include intermittent or continuous Scvo2 sampling.3Dellinger RP Levy MM Carlet JM International Surviving Sepsis Campaign Guidelines Committee American Association of Critical-Care Nurses American College of Chest Physicians American College of Emergency Physicians Canadian Critical Care Society European Society of Clinical Microbiology and Infectious Diseases European Society of Intensive Care Medicine European Respiratory Society International Sepsis Forum Japanese Association for Acute Medicine Japanese Society of Intensive Care Medicine Society of Critical Care Medicine Society of Hospital Medicine Surgical Infection Society World Federation of Societies of Intensive and Critical Care Medicine et al.Surviving Sepsis Campaign: international guidelines for management of severe sepsis and septic shock: 2008.Crit Care Med. 2008; 36: 296-327Crossref PubMed Scopus (3952) Google Scholar It is a simple matter to add intermittent Scvo2 to lactate measurements in the absence of continuous monitoring. Bundle compliance and socioeconomic costs improve significantly with continuous monitoring.21Ising P Smith TW Simpson SQ Effect of intermittent vs continuous ScvO2 monitoring on sepsis bundle compliance and mortality [abstract].Chest. 2009; 136: 21SAbstract Full Text Full Text PDF Google ScholarConclusionsScvo2 provides immediate feedback to the o2/Do2 relationship but requires interpretation that depends on the phase of sepsis. Lactate is a delayed indicator of tissue perfusion and is subject to complex kinetics that are never clear in the individual case. Lactate levels may be normal or fluctuate, leading to inappropriate risk stratification and therapy. Lactate clearance and Scvo2, therefore, are complementary and not mutually exclusive end points. In 2001, early goal-directed therapy (EGDT) resulted in a 16% reduction in hospital mortality and, post hoc, a higher lactate clearance in severe sepsis and septic shock.1Rivers E Nguyen B Havstad S Early Goal-Directed Therapy Collaborative Group et al.Early goal-directed therapy in the treatment of severe sepsis and septic shock.N Engl J Med. 2001; 345: 1368-1377Crossref PubMed Scopus (7748) Google Scholar Multiple studies have confirmed the validity and generalizability of EGDT, resulting in its adoption into the Surviving Sepsis Campaign Guidelines.2Rivers EP Point: adherence to early goal-directed therapy: does it really matter? Yes. After a decade, the scientific proof speaks for itself.Chest. 2010; 138: 476-485Abstract Full Text Full Text PDF PubMed Scopus (34) Google Scholar, 3Dellinger RP Levy MM Carlet JM International Surviving Sepsis Campaign Guidelines Committee American Association of Critical-Care Nurses American College of Chest Physicians American College of Emergency Physicians Canadian Critical Care Society European Society of Clinical Microbiology and Infectious Diseases European Society of Intensive Care Medicine European Respiratory Society International Sepsis Forum Japanese Association for Acute Medicine Japanese Society of Intensive Care Medicine Society of Critical Care Medicine Society of Hospital Medicine Surgical Infection Society World Federation of Societies of Intensive and Critical Care Medicine et al.Surviving Sepsis Campaign: international guidelines for management of severe sepsis and septic shock: 2008.Crit Care Med. 2008; 36: 296-327Crossref PubMed Scopus (3952) Google Scholar Nguyen et al4Nguyen HB Rivers EP Knoblich BP et al.Early lactate clearance is associated with improved outcome in severe sepsis and septic shock.Crit Care Med. 200
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