|Year : 2023 | Volume
| Issue : 1 | Page : 10-17
Utility of lactate, central venous oxygen saturation, and the difference in venous and arterial CO2 partial pressures (delta pCO2) levels in quantifying microcirculatory failure: A single-center prospective observational study
Emrullah Ayguler, Genco Ali Gençay, Demet Demirkol
Department of Pediatric Intensive Care, Istanbul Faculty of Medicine, Istanbul University, Istanbul, Turkey
|Date of Submission||02-Apr-2022|
|Date of Decision||21-Nov-2022|
|Date of Acceptance||12-Dec-2022|
|Date of Web Publication||20-Jan-2023|
Prof. Demet Demirkol
Department of Pediatric Intensive Care, Istanbul Faculty of Medicine, Topkapi, Turgut Özal Millet Cd, 34093, Fatih, Istanbul
Source of Support: None, Conflict of Interest: None
Background: The aim of the study was to evaluate the utility of lactate, central venous oxygen saturation (ScvO2), and the difference in venous and arterial CO2 partial pressures (delta pCO2) levels and their relationship with the prognosis of critically ill children with circulatory failure in the pediatric intensive care unit (PICU).
Subjects and Methods: Thirty children with circulatory failure who were admitted to the PICU of a tertiary university hospital between January 15 and November 1, 2020, were evaluated in this prospective observational study. Lactate levels, ScVO2, and delta pCO2 levels were evaluated on admission and at hours 4, 12, and 24 (T0, T4, T12, T24) in the PICU.
Results: The mortality of the children with circulatory failure was 30% (n = 9). Arterial and venous lactate levels were highly correlated at T0, T4, T12, T24 (P < 0.001; P < 0.001; P < 0.001; P < 0.001, respectively). Nonsurvivors had always higher arterial lactate levels (T0, T4, T12, T24) (P = 0.019, P = 0.007, P = 0.002, P = 0.0003, respectively) and higher delta pCO2 at T0 (P = 0.039) when compared with survivors. Receiver operating characteristic analysis showed that T0 arterial lactate levels (area under the curve [AUC] 0.788, P = 0.019), T24 arterial lactate (AUC 0.918, P < 0,001), and T0 delta pCO2 levels (AUC 0,741, P = 0.039) and were predictive of mortality.
Conclusions: Lactate remains the most important marker of microcirculatory dysfunction in critically ill children with circulatory failure. Delta pCO2 may be an additional marker of microcirculatory dysfunction in critically ill children.
Keywords: Delta CO2, lactate, central venous oxygen saturation
|How to cite this article:|
Ayguler E, Gençay GA, Demirkol D. Utility of lactate, central venous oxygen saturation, and the difference in venous and arterial CO2 partial pressures (delta pCO2) levels in quantifying microcirculatory failure: A single-center prospective observational study. J Pediatr Crit Care 2023;10:10-7
|How to cite this URL:|
Ayguler E, Gençay GA, Demirkol D. Utility of lactate, central venous oxygen saturation, and the difference in venous and arterial CO2 partial pressures (delta pCO2) levels in quantifying microcirculatory failure: A single-center prospective observational study. J Pediatr Crit Care [serial online] 2023 [cited 2023 Mar 24];10:10-7. Available from: http://www.jpcc.org.in/text.asp?2023/10/1/10/368231
| Introduction|| |
Tissue perfusion is disrupted during circulatory failure. When left untreated, shock and damage at the cellular level can occur. During treatment for circulatory failure, in some children, macrohemodynamic goals are reached while circulatory failure persists at the cellular level., Therefore, microcirculation should be evaluated in addition to macrohemodynamic parameters. An ideal parameter for hemodynamic monitoring would be one that determines the severity of circulatory compromise, points to the underlying pathophysiology, aids the clinician in choosing the most appropriate therapy, and thus guides treatment.
Many guidelines recommend that microcirculation be evaluated with mixed venous oxygen saturation (SvO2), central venous oxygen saturation (ScvO2), and lactate levels. Target levels have been suggested., However, the aforementioned variables have their shortcomings and do not suffice as a sole parameter to quantify tissue perfusion.
Carbon dioxide (CO2) levels may change much faster than lactate kinetics., Variables based on tissue carbon dioxide (PtCO2) levels may provide insight into blood flow at the macroscopic and microscopic levels as well as the presence of anaerobic cellular respiration., The three principal determinants of PtCO2 are partial pressure of arterial CO2 (PaCO2), CO2 production (VCO2) and tissue blood flow. Under normal conditions, an increase in tissue metabolism (and VCO2) is balanced by an increase in perfusion. Thus, an increase in PtCO2 with a stable PaCO2 shows a disruption of tissue perfusion. When blood flow decreases (ischemic hypoxia), cellular O2 content also decreases. The ensuing anaerobic metabolism increases lactic acid production and the difference in venous and arterial CO2 partial pressures. Therefore, delta pCO2 is significantly correlated with microcirculatory dysfunction.,
The threshold value for delta pCO2 is 0.8 kPa (6 mmHg). Mortality was shown to be increased in septic children with delta pCO2 above 6 mmHg.,,, High values of delta pCO2 were shown to be associated with low cardiac output (CO), low SvO2, low lactate clearance, and increased lactate levels.,,
Studies on the significance of delta pCO2 in determining the state of tissue perfusion and prognosis in children are scarce. In this study, we aimed to evaluate the utility of lactate, ScvO2, and delta pCO2 levels and their relationship with the prognosis of critically ill children with circulatory failure in the pediatric intensive care unit (PICU).
| Materials and Methods|| |
Children who were admitted to the PICU with circulatory failure between January 15 and November 1, 2020, were evaluated in this prospective observational study. Ethical approval was obtained from the Ethics Board for Clinical Studies at University, Faculty of Medicine (Approval number: 2020/45). In our PICU, children who need invasive blood pressure monitoring or frequent blood sampling, but have sufficient peripheral vascular access have arterial lines placed. Children who are on high-dose vasopressors or infusions that require central access have central venous lines placed. Children between the ages of 1 month and 18 years, who had central venous and peripheral arterial lines placed in keeping with the aforementioned indications were enrolled in the study and simultaneous arterial and venous blood gas analysis was done on admission (T0), at hour 4 (T4), hour 12 (T12) and hour 24 (T24) of admission to evaluate lactate, ScvO2, and delta pCO2 levels. Children who only had an arterial or a central venous line were excluded.
The diagnosis of circulatory failure was based on the section on cardiovascular failure in the pediatric logistic organ dysfunction (PELOD) score. Children younger than 1 month or older than 18 years, children with insufficient samples and data (transfer, mortality in the first 24 h, etc.,) in hospital records were excluded.
Central venous access was obtained via the jugular, subclavian and femoral veins while arterial access was obtained via the brachial or femoral arteries. No additional interventions, laboratory studies, therapeutic procedures, and treatment changes were performed for the study. Indication for admission, underlying diseases, age (in months), physical examination findings, and vital signs were recorded. Glasgow coma score (GCS) was recorded using the values before sedation and analgesia in children receiving such medications. If the patient was intubated and sedated on admission, if GCS before admission was unknown, and if the clinical course did not prompt consideration for acute neurologic injury, GCS was not included in the analyses.
Laboratory testing and evaluation
Patient data were recorded prospectively during the first 24 h of the study. Delta pCO2 was calculated by subtracting arterial pCO2 from venous pCO2. Blood gas samples were analyzed using the ABL800 FLEX blood gas Analyzer (Radiometer Medical ApS, 2700 Brønshøj, Denmark, 2020).
Evaluation of treatment information
Respiratory support was recorded as invasive mechanical ventilation (IMV), noninvasive ventilation, and high-flow nasal cannula, and the total duration of respiratory support was recorded. IMV and vasoactive treatment were recorded at T0 and T24. Vasoactive inotropic score (VIS) was calculated for children on vasoactive medications at T24, using the following formula: VIS = dopamine dose (mcg/kg.min) + dobutamine dose (mcg/kg. min) + (100 × epinephrine dose [mcg/kg.min]) + (100 × norepinephrine dose [mcg/kg.min]) + (10 × milrinone dose [mcg/kg.min]) + (10000 × vasopressin dose [U/kg.min]). The need for extracorporeal membrane oxygenation (ECMO) and renal replacement therapy (RRT) was recorded.
Mortality and morbidity scoring
Time to PICU discharge and mortality were recorded. Pediatric risk of mortality-III (PRISM III), PELOD-2, and pediatric sequential organ failure assessment (pSOFA) scores were calculated. Sepsis was diagnosed and the number of organ failures (NOF) was determined according to the pediatric sepsis consensus group criteria. NOFs were calculated using the criteria for six systems, namely, cardiovascular, hepatic, renal, respiratory, hematologic, and neurologic systems.
Grouping of the children
Children were grouped as survivors and nonsurvivors. Length of stay in the PICU, duration of vasoactive and respiratory support, NOF, delta pCO2, lactate and ScvO2 levels, PRISM-III, PELOD-2, pSOFA scores, and VIS at T24 were compared.
Lactate threshold was 2 mmol/L, delta pCO2 threshold was 6 mmHg, and ScvO2 threshold was 65% in this study.,
Data were analyzed using the Statistical Package for Social Sciences Software version 21.0 (IBM Corp., Armonk, NY, USA). Continuous variables were presented as median and interquartile range; categorical data were presented as numbers and percentages. Continuous data were compared using the Mann–Whitney U and Kruskal–Wallis tests; categorical data were compared using the Chi-squared test. Spearman rank test and Bland–Altman plots were used to determine if arterial and venous lactate levels are correlated and in agreement. Survival analysis was performed using the cox regression method. A P < 0.05 was considered statistically significant.
| Results|| |
Thirty children who had both arterial and central venous lines placed according to the aforementioned indications were enrolled in the study. Demographic features are summarized in [Table 1]. The most common cause of circulatory failure was sepsis (n = 24, 80%) [Figure 1]. Other causes have been summarized.
An infectious agent was identified in 17 children, namely, Escherichia coli in 29.4% (n = 5), Klebsiella pneumoniae in 17.6% (n = 3), Methicillin-resistant coagulase-negative Staphylococcus (n = 3), severe acute respiratory syndrome coronavirus 2 in 11.7% (n = 2), Haemophilus influenzae in 5.8% (n = 1), Pseudomonas aeruginosa in 5.8% (n = 1), Streptococcus pneumoniae in 5.8% (n = 1), and alpha-hemolytic streptococcus in 5.8% (n = 1). Twenty-two children (73.3%) needed IMV, 80% of the children (n = 24) received vasoactive agents, 43% (n = 13) needed RRT, and 6.7% (n = 2) needed ECMO support.
Microcirculatory parameters of the children in the study are summarized in [Table 2]. Arterial and venous lactate levels were highly correlated at T0, T4, T12, and T24 (rho = 0.965, P < 0.001; rho = 0.967, P < 0.001; rho: 0.943, P < 0.001; rho = 0.953, P < 0.001, respectively) and median arterial and venous lactate levels were found to be similar at T0, T4, T12, T24 (P = 0.657, P = 0.416, P = 0.594, P = 0.573, respectively). On Bland–Altman plots, arterial and venous lactate levels at T0, T12, and T24 were found to be similar (P = 0.15, P = 0.36, P = 0.97, respectively) but there was a minor, albeit statistically significant difference at T4, with venous lactate being 0.3 mmol/L higher than arterial lactate at T4 (P = 0.022). In children with elevated lactate levels (lactate >2.0 mmol/L), arterial and venous lactate levels were in agreement at T0, T4, T12, T24 (P = 0.492, P = 0.221, P = 0.488, P = 0.386, respectively). Microcirculatory parameters are summarized in [Table 2].
Mortality was 30% (n = 9) in our study. Nonsurvivors had higher T24 PRISM-III, PELOD-2, pSOFA, VIS, and NOF than survivors (P = 0.0001, P = 0.0002, P = 0.0002, P = 0.001, P = 0.006, respectively). Different parameters among survivors and nonsurvivors are summarized in [Table 3].
Nonsurvivors had higher arterial lactate levels at all times (T0, T4, T12, T24) when compared with survivors (P = 0.019, P = 0.007, P = 0.002, P = 0.0003, respectively) [Table 4]. Central venous lactate levels were higher in nonsurvivors at all times (T0, T4, T12, T24) (P = 0.014, P = 0.009, P = 0.001, P = 0.0002, respectively). A central venous lactate level higher than the threshold of "2 mmol/L" was found to be associated with mortality at all times (T0, T4, T12, T24) (P = 0.046, P = 0.046, P = 0.025, P = 0.002, respectively). Lactate levels were ≥2 mmol/L at T0 in 88.9% (n = 8) of nonsurvivors and 52.5% (n = 11) of survivors (P = 0.057). Trends in heart rate, mean arterial pressure, delta pCO2, and lactate are shown in [Figure 2].
|Figure 2: The associations of delta pCO2 and arterial lactate levels with clinical variables|
Click here to view
|Table 4: Lactate, central venous oxygen saturation and delta partial pressure of carbon dioxide levels in survivors and nonsurvivors|
Click here to view
Nonsurvivors had lower ScvO2 values at T0, T4, T12, and T24, but the difference did not reach statistical significance [Table 4]. A ScvO2 level lower than the threshold of 65% was not found to be associated with mortality at T0, T4, and T12, while it was found to be associated with mortality at T24 (P = 0.035).
Median Delta pCO2 at T0 was significantly higher in nonsurvivors (P = 0.039) [Table 4]. Nonsurvivors had higher median delta pCO2 levels at T4, T12, and T24, but the difference did not reach statistical significance. Delta pCO2 at T4 was higher in nonsurvivors with a nonsignificant difference (P = 0.06). More nonsurvivors had delta pCO2 values higher than the threshold of "6 mmHg" than survivors at T0, T4, and T12, but the difference did not reach statistical significance.
Receiver operating characteristic (ROC) analysis showed T0 arterial lactate levels (area under the curve [AUC] 0.775, P = 0.019), T24 arterial lactate (AUC 0.918, P < 0.001), and T0 delta pCO2 levels (AUC 0.741, P = 0.039) were found to be predictive of mortality [Table 5], [Figure 3] and [Figure 4].
|Figure 3: ROC analysis for lactate, delta pCO2 and ScvO2 at admission. ROC: Receiver operating characteristic, ScvO2: Central venous oxygen saturation|
Click here to view
|Figure 4: ROC analysis for lactate, delta pCO2 and ScvO2 at 24th h. ROC: Receiver operating characteristic, ScvO2: Central venous oxygen saturation|
Click here to view
|Table 5: T0 receiver operating characteristic analysis, T24 receiver operating characteristic analysis|
Click here to view
| Discussion|| |
Lactate is a substrate, biomarker, source of energy, and the main modulator of cellular bioenergetics under physiologic stress. During circulatory failure, anaerobic metabolism predominates, clearance of lactate in the liver, kidneys, and skeletal muscle is decreased and lactic acidosis occurs. A number of studies have found an association between lactate levels above 4 mmol/L and mortality.,, Bai et al. noted higher lactate levels in the 1st 2 h of PICU admission among nonsurvivors than survivors in their study of 1109 general population of critically ill children (6.6 mmol/L vs. 3.1 mmol/L; P < 0.001). Fernández-Sarmiento et al. have reported higher lactate levels among nonsurvivors in their study with 67 children who were diagnosed with septic shock during their stay in the PICU (P = 0.02). Similarly, in our study, lactate levels ≥2 mmol/L were shown to be associated with mortality.
In the present study, arterial and central venous lactate levels were similar at all times, with the exception of T4 when venous lactate was 0.3 mmol/L higher than arterial lactate. The 0.3 mmol/L difference was not considered clinically relevant. Most reports suggest good agreement between arterial and central venous lactate levels, among both adults and children.,,,, This was observed in the present study as well. The authors suggested that the agreement between arterial and central venous lactate should be evaluated in larger studies, preferably studies that include more children with elevated lactate.
There are a variety of reasons for elevated lactate levels such as adrenergic response, mitochondrial dysfunction, liver failure, metabolic disorders, lymphoproliferative diseases, and drugs. It is of utmost importance to determine if lactate is elevated due to hypoperfusion and plan treatment. Ancillary markers of perfusion such as ScvO2 and delta pCO2 can be used to diagnose hypoperfusion-related elevated lactate. Waldauf et al. have suggested that delta pCO2 can be used to avoid unnecessary fluid and inotrope administration in adults with elevated lactate. Similarly, Wittayachamnankul et al. have suggested that in patients with elevated lactate and ScvO2 <70%, fluids, and inotropes should be employed if delta pCO2 ≥6 mmHg while more oxygen (O2) should be provided, and hemoglobin levels should be increased if delta pCO2 is <6 mmHg. Increased delta pCO2 values have been associated with lower CO, lower SvO2, lower lactate clearance, and higher lactate levels and mortality in adult studies. The authors have found increased delta pCO2 levels on admission to be associated with mortality. Lactate levels were always higher among nonsurvivors, and more nonsurvivors had lactate levels >2 mmol/L, with a nonsignificant difference in the present study (P = 0.057).
ScvO2 reflects the relationship between the delivery of O2 (DO2) and the consumption of O2 (VO2). Early goal-directed therapy protocol recommends that ScvO2 be kept ≥70%. The European Society of Pediatric and Neonatal Intensive Care recommends that ScvO2 be measured and kept higher than 65% in children with shock. However, there are contradictory studies that suggest that associate both high ScvO2 and low ScvO2 with mortality,, Therefore, ScvO2-based treatment has been removed from the Surviving Sepsis Campaign guidelines., In our study, the median ScvO2 was lower in nonsurvivors. However, the difference was not significant and ScvO2 level was not found to be correlated with mortality.
The authors found delta pCO2 on admission to be associated with mortality, with 37.5% mortality in children with delta pCO2 ≥6 mmHg at T0 and 21% mortality in children with delta pCO2 <6 mmHg at T0. Our findings are in keeping with previous studies. Vallée et al. have found similar acute physiology and chronic health evaluation scores and sequential organ failure assessment scores in adults with elevated and normal delta pCO2 values (P = 0.68 and P = 0.95, respectively). Chen et al. have evaluated 48 children with septic shock and found no correlation between delta pCO2 ≥6 mmHg and PRISM-III score. In their study of 67 children with shock, Fernández-Sarmiento et al. have found delta pCO2 to be less sensitive than lactate in predicting multiple organ failure (29% and 51%, respectively).
Arterial lactate levels and delta pCO2 were found to be predictive of mortality in ROC analysis while ScvO2 was not predictive. Fernández-Sarmiento et al. have found that lactate was more predictive of multiple organ failure than ScvO2 and delta pCO2.
The strengths of this study include its prospective design that includes a heterogeneous PICU patient population with a variety of causes of circulatory failure with no missing data.
The study has significant limitations because of its small sample size and single-center design, which limits the generalizability of our findings.
| Conclusions|| |
Lactate is the most important marker of the severity of circulatory dysfunction in critically ill children with circulatory failure. In situations where lactate cannot adequately demonstrate microcirculatory function, delta pCO2 should be evaluated.
Financial support and sponsorship
Conflicts of interest
There are no conflicts of interest.
| References|| |
Ospina-Tascón GA, Bautista-Rincón DF, Umaña M, Tafur JD, Gutiérrez A, García AF, et al.
Persistently high venous-to-arterial carbon dioxide differences during early resuscitation are associated with poor outcomes in septic shock. Crit Care 2013;17:R294.
Fernández-Sarmiento J, Carcillo JA, Díaz Del Castillo AME, Barrera P, Orozco R, Rodríguez MA, et al.
Venous-arterial CO (2) difference in children with sepsis and its correlation with myocardial dysfunction. Qatar Med J 2019;2019:18.
Singh Y, Villaescusa JU, da Cruz EM, Tibby SM, Bottari G, Saxena R, et al.
Recommendations for hemodynamic monitoring for critically ill children-expert consensus statement issued by the cardiovascular dynamics section of the European society of paediatric and neonatal intensive care (ESPNIC). Crit Care 2020;24:620.
Dellinger RP, Levy MM, Rhodes A, Annane D, Gerlach H, Opal SM, et al.
Surviving sepsis campaign: International guidelines for management of severe sepsis and septic shock: 2012. Crit Care Med 2013;41:580-637.
Jones AE, Shapiro NI, Trzeciak S, Arnold RC, Claremont HA, Kline JA, et al.
Lactate clearance vs central venous oxygen saturation as goals of early sepsis therapy: A randomized clinical trial. JAMA 2010;303:739-46.
Hernandez G, Bruhn A, Castro R, Regueira T. The holistic view on perfusion monitoring in septic shock. Curr Opin Crit Care 2012;18:280-6.
Ospina-Tascón GA, Hernández G, Cecconi M. Understanding the venous-arterial CO(2) to arterial-venous O(2) content difference ratio. Intensive Care Med 2016;42:1801-4.
Ospina-Tascón GA, Umaña M, Bermúdez WF, Bautista-Rincón DF, Valencia JD, Madriñán HJ, et al.
Can venous-to-arterial carbon dioxide differences reflect microcirculatory alterations in patients with septic shock? Intensive Care Med 2016;42:211-21.
Ospina-Tascón GA, Umaña M, Bermúdez W, Bautista-Rincón DF, Hernandez G, Bruhn A, et al.
Combination of arterial lactate levels and venous-arterial CO2 to arterial-venous O 2 content difference ratio as markers of resuscitation in patients with septic shock. Intensive Care Med 2015;41:796-805.
Du W, Liu DW, Wang XT, Long Y, Chai WZ, Zhou X, et al.
Combining central venous-to-arterial partial pressure of carbon dioxide difference and central venous oxygen saturation to guide resuscitation in septic shock. J Crit Care 2013;28:5.e1-5.
De Backer D, Durand A. Monitoring the microcirculation in critically ill patients. Best Pract Res Clin Anaesthesiol 2014;28:441-51.
Mallat J, Benzidi Y, Salleron J, Lemyze M, Gasan G, Vangrunderbeeck N, et al.
Time course of central venous-to-arterial carbon dioxide tension difference in septic shock patients receiving incremental doses of dobutamine. Intensive Care Med 2014;40:404-11.
Vallée F, Vallet B, Mathe O, Parraguette J, Mari A, Silva S, et al.
Central venous-to-arterial carbon dioxide difference: An additional target for goal-directed therapy in septic shock? Intensive Care Med 2008;34:2218-25.
Mallat J, Pepy F, Lemyze M, Gasan G, Vangrunderbeeck N, Tronchon L, et al.
Central venous-to-arterial carbon dioxide partial pressure difference in early resuscitation from septic shock: A prospective observational study. Eur J Anaesthesiol 2014;31:371-80.
Chen R, Zhang Y, Cui Y, Miao H, Xu L, Rong Q. Central venous-to-arterial carbon dioxide difference in critically ill pediatric patients with septic shock. Zhonghua Er Ke Za Zhi 2014;52:918-22.
Wittayachamnankul B, Chentanakij B, Sruamsiri K, Chattipakorn N. The role of central venous oxygen saturation, blood lactate, and central venous-to-arterial carbon dioxide partial pressure difference as a goal and prognosis of sepsis treatment. J Crit Care 2016;36:223-9.
Mallat J, Vallet B. Difference in venous-arterial carbon dioxide in septic shock. Minerva Anestesiol 2015;81:419-25.
Al Duhailib Z, Hegazy AF, Lalli R, Fiorini K, Priestap F, Iansavichene A, et al.
The Use of central venous to arterial carbon dioxide tension gap for outcome prediction in critically Ill patients: A systematic review and meta-analysis. Crit Care Med 2020;48:1855-61.
Pollack MM, Patel KM, Ruttimann UE. PRISM III: An updated pediatric risk of mortality score. Crit Care Med 1996;24:743-52.
Karam O, Demaret P, Duhamel A, Shefler A, Spinella PC, Stanworth SJ, et al.
Performance of the PEdiatric logistic organ dysfunction-2 score in critically ill children requiring plasma transfusions. Ann Intensive Care 2016;6:98.
Matics TJ, Sanchez-Pinto LN. Adaptation and validation of a pediatric sequential organ failure assessment score and evaluation of the sepsis-3 definitions in critically Ill children. JAMA Pediatr 2017;171:e172352.
Goldstein B, Giroir B, Randolph A, International Consensus Conference on Pediatric Sepsis. International pediatric sepsis consensus conference: Definitions for sepsis and organ dysfunction in pediatrics. Pediatr Crit Care Med 2005;6:2-8.
Evans L, Rhodes A, Alhazzani W, Antonelli M, Coopersmith CM, French C, et al.
Surviving sepsis campaign: International guidelines for management of sepsis and septic shock 2021. Intensive Care Med 2021;47:1181-247.
Hernandez G, Bellomo R, Bakker J. The ten pitfalls of lactate clearance in sepsis. Intensive Care Med 2019;45:82-5.
Weiss SL, Peters MJ, Alhazzani W, Agus MSD, Flori HR, Inwald DP, et al.
Surviving sepsis campaign international guidelines for the management of septic shock and sepsis-associated organ dysfunction in children. Pediatr Crit Care Med 2020;21:e52-106.
Bai Z, Zhu X, Li M, Hua J, Li Y, Pan J, et al.
Effectiveness of predicting in-hospital mortality in critically Ill children by assessing blood lactate levels at admission. BMC Pediatr 2014;14:83.
Scott HF, Brou L, Deakyne SJ, Kempe A, Fairclough DL, Bajaj L. Association between early lactate levels and 30-day mortality in clinically suspected sepsis in children. JAMA Pediatr 2017;171:249-55.
Fernández Sarmiento J, Araque P, Yepes M, Mulett H, Tovar X, Rodriguez F. Correlation between arterial lactate and central venous lactate in children with sepsis. Crit Care Res Pract 2016;2016:7839739.
Velissaris D, Karamouzos V, Pantzaris ND, Kyriakopoulou O, Gogos C, Karanikolas M. Relation between central venous, peripheral venous and arterial lactate levels in patients with sepsis in the emergency department. J Clin Med Res 2019;11:629-34.
Middleton P, Kelly AM, Brown J, Robertson M. Agreement between arterial and central venous values for pH, bicarbonate, base excess, and lactate. Emerg Med J 2006;23:622-4.
Jose JM, Cherian A, Bidkar PU, Mohan VK. The agreement between arterial and venous lactate in patients with sepsis. Int J Clin Pract 2021;75:e14296.
Réminiac F, Saint-Etienne C, Runge I, Ayé DY, Benzekri-Lefevre D, Mathonnet A, et al.
Are central venous lactate and arterial lactate interchangeable? A human retrospective study. Anesth Analg 2012;115:605-10.
Waldauf P, Jiroutkova K, Duska F. Using PCO (2) gap in the differential diagnosis of hyperlactatemia outside the context of sepsis: A physiological review and case series. Crit Care Res Pract 2019;2019:5364503.
Diaztagle Fernández JJ, Rodríguez Murcia JC, Sprockel Díaz JJ. Venous-to-arterial carbon dioxide difference in the resuscitation of patients with severe sepsis and septic shock: A systematic review. Med Intensiva 2017;41:401-10.
Rivers E, Nguyen B, Havstad S, Ressler J, Muzzin A, Knoblich B, et al.
Early goal-directed therapy in the treatment of severe sepsis and septic shock. N Engl J Med 2001;345:1368-77.
de Oliveira CF, de Oliveira DS, Gottschald AF, Moura JD, Costa GA, Ventura AC, et al.
ACCM/PALS haemodynamic support guidelines for paediatric septic shock: An outcomes comparison with and without monitoring central venous oxygen saturation. Intensive Care Med 2008;34:1065-75.
Boulain T, Garot D, Vignon P, Lascarrou JB, Desachy A, Botoc V, et al.
Prevalence of low central venous oxygen saturation in the first hours of intensive care unit admission and associated mortality in septic shock patients: A prospective multicentre study. Crit Care 2014;18:609.
Textoris J, Fouché L, Wiramus S, Antonini F, Tho S, Martin C, et al.
High central venous oxygen saturation in the latter stages of septic shock is associated with increased mortality. Crit Care 2011;15:R176.
[Figure 1], [Figure 2], [Figure 3], [Figure 4]
[Table 1], [Table 2], [Table 3], [Table 4], [Table 5]