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Table of Contents  
ORIGINAL ARTICLE
Year : 2022  |  Volume : 16  |  Issue : 2  |  Page : 272-277  

Correlation of the changing trends of ScvO2, serum lactate, standard base excess and anion gap in patients with severe sepsis and septic shock managed by Early Goal Directed Therapy (EGDT): A prospective observational study


1 Department of Anaesthesiology, Institute of Medical Sciences, Banaras Hindu University, Varanasi, Uttar Pradesh, India
2 Department of Obstetrics and Gynaecology, Institute of Medical Sciences, Banaras Hindu University, Varanasi, Uttar Pradesh, India
3 Department of Cardiology, Medical College, Kolkata, West Bengal, India
4 Department of Anaesthesiology, Division of Critical Care Medicine, Institute of Medical Sciences, Banaras Hindu University, Varanasi, Uttar Pradesh, India
5 Executive Director, AIIMS, Bathinda, Punjab, India

Date of Submission02-Apr-2021
Date of Decision27-Feb-2022
Date of Acceptance11-Jul-2022
Date of Web Publication21-Oct-2022

Correspondence Address:
Dr. Bikram Kumar Gupta
Department of Anaesthesiology, Institute of Medical Sciences, Banaras Hindu University, Varanasi - 221 005, Uttar Pradesh
India
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/aer.aer_52_21

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   Abstract 

Background: To observe the correlation of central venous oxygen saturation (ScvO2), serum lactate, standard base excess (SBE), and anion gap (AG) in septic and septic shock patients resuscitated with early goal-directed therapy (EGDT). Materials and Methods: A review was made of 130 severe septic shock patients (15–65 years) according to the consensus conference criteria admitted in intensive care unit. Blood samples were obtained from arterial and central venous line for ScvO2, serum lactate, SBE, and AG on admission and after achieving all aims of EGDT i.e.; mean arterial pressure >65 mmHg, central venous pressure = 8–12 mmHg, ScvO2 >70%, and urine output >0.5 mL.kg−1.h−1, and on 12 and 24 h. The statistical analysis was done using SPSS for windows version 16 software. For comparison, Pearson test was used. A P < 0.05 was considered as statistically significant. Results: There were a positive correlation between ScvO2 and SBE, a negative correlation between ScvO2 and AG, a negative correlation between ScvO2 and lactate, a negative correlation between SBE and AG, a negative correlation between AG and lactate, and a negative correlation between SBE and lactate. The ScvO2 was initially low but was in an improving trend after a resuscitative period, SBE was initially low and correction of SBE was linear. AG was high in the beginning and goes on decreasing after resuscitation. Lactate level was also high initially and in decreasing trend after a resuscitative period. Conclusions: ScvO2 and SBE are correlated and can be used as a surrogate marker. ScvO2 and AG are related but not absolutely codependent. ScvO2 and lactate are correlated but they are not absolutely codependent. SBE and AG are correlated and can be used as a surrogate marker. AG and lactate are not related to each other. Hence, AG cannot be considered as a surrogate for lactate testing. SBE and lactate are related and can be used as a surrogate marker.

Keywords: Anion gap, lactate, sepsis, septic shock, standard base excess, venous oximetry


How to cite this article:
Sneha K, Mhaske VR, Saha KK, Gupta BK, Singh DK. Correlation of the changing trends of ScvO2, serum lactate, standard base excess and anion gap in patients with severe sepsis and septic shock managed by Early Goal Directed Therapy (EGDT): A prospective observational study. Anesth Essays Res 2022;16:272-7

How to cite this URL:
Sneha K, Mhaske VR, Saha KK, Gupta BK, Singh DK. Correlation of the changing trends of ScvO2, serum lactate, standard base excess and anion gap in patients with severe sepsis and septic shock managed by Early Goal Directed Therapy (EGDT): A prospective observational study. Anesth Essays Res [serial online] 2022 [cited 2022 Dec 5];16:272-7. Available from: https://www.aeronline.org/text.asp?2022/16/2/272/359351


   Introduction Top


Sepsis is defined as life-threatening organ dysfunction caused by a deregulated host response to infection where organ dysfunction is identified as an acute change in total quick sequential organ failure assessment score ≥2 consequent to infection. Septic shock is a subset of sepsis in which underlying circulatory and cellular/metabolic abnormalities are profound enough to substantially increase mortality.[1] Early goal-directed therapy (EGDT) proposed by Rivers et al. in 2001 found that early aggressive management of hemodynamics targeting a balance of oxygen consumption and delivery resulted in a significant reduction in mortality (absolute risk reduction by 16%) as compared to the standard therapy.[2] Recently, three large studies, the ProCESS, ARISE, and ProMISe, have challenged the benefit of this approach in improving survival in severe sepsis.[3],[4],[5] Contrary to the results of these three studies, in a recent meta-analysis of 13 studies, it was found that EGDT did improve mortality with a relative risk reduction of 17%.[6] In EGDT, The precocious match between oxygen consumption and delivery is achieved with central venous oxygen saturation (ScvO2) ≥70%. As regards the metabolic consequences of shock and hemodynamic management, there are other simple monitoring tools such as unmeasured anions (UA) through anion gap (AG), serum lactate levels, and standard base excess (SBE) that can be used in critical illness.[7],[8],[9],[10] Calculation of the SBE and the AG is commonly used to identify the presence and to analyze the cause of metabolic acidosis in critically ill patients. An AG >17 defines the presence of UA; critically ill patients with increased AG and metabolic acidosis are often assumed to have increased plasma lactate, which is associated with a higher risk of death than normal lactate concentrations. When measured at admission and within the 1st day of intensive care unit (ICU) stay, these variables are important outcome markers in conventionally resuscitated patients.[7] However, to the best of our knowledge, there are few clinical studies testing interventions based on serum lactate level or SBE[11] and there are no studies showing correlation of the changing trends of ScvO2, serum lactate, SBE, and AG in patients with sepsis and septic shock managed by EGDT. The aim of this study was to compare ScvO2, serum lactate levels, SBE, and AG evolution between surviving and nonsurviving patients of sepsis and septic shock that underwent early goal-directed hemodynamic therapy.


   Materials and Methods Top


After ethical research committee approval (Dean/2015-16/EC/1563 dated December 30, 2015), written informed consent was taken from the guardians of each patient, for participation in the study and use of the patient data for research and educational purposes. All the procedures adapted follows the guidelines laid down in the Declaration of Helsinki.(1964) A single-centred, prospective, observational study was conducted for a period of 18 months, from January 2015 to June 2017, in the ICU of the division of critical care medicine, in our tertiary care hospital. The study included newly admitted adult patients, aged 20–80 years, either with medical or surgical ailments, who were clinically suspected with infection from any source fulfilling at least two criteria of systemic inflammatory response syndromes (SIRS) and requiring blood, urine, or endotracheal culture. While those who were already diagnosed with culture reports at primary care setups, or with pregnancy, morbid obesity, trauma, burn, cardiomyopathy with ejection fraction <40%, neutropenia, or immunosuppression were excluded from the study. Dropouts included patients with no indication of antimicrobials or culture or had early discharge or left against medical advice or those who died before investigated, were excluded.

Enrollment of 130 eligible patients was done consecutively whenever there was clinical suspicion of having sepsis or SIRS during their hospital stay. They were shifted to the ICU and managed according to the EGDT protocol and Surviving Sepsis Campaign guidelines. Data were retrieved from our prospectively collected database. The following data were collected: age, gender, Acute physiology and chronic health evaluation II score, serum procalcitonin, and baseline vitals. Blood samples were obtained at admission; all patients were monitored with an arterial and central venous line; after this initial period every procedure, such as fluid challenges, inotropic agents, and vasopressors, was checked with blood samples for ScvO2, serum lactate, SBE, and AG. After reaching a ScvO2 ≥70%, (or in the absence of such response, but with a higher reached ScvO2), new blood samples were collected after 12 h then at 24 h. Data compatible with a fully resuscitated patient retrieved from the database were the establishment of a plateau, that is, a steady level without great variations above or under the current value. ScvO2 was obtained through the gas analysis of blood drawn from the central venous catheter. The SBE, AG, and serum lactate levels were obtained through the arterial blood analysis gained from the arterial line at the same time of central venous blood sample collection as described above. Central venous catheter position was previously verified, and possible complications were ruled out with a chest X-ray. All blood samples were analyzed in a Roche gas analyzer, and to determine the SBE value, the Van Slyke method was used. The trends of ScvO2, serum lactate level, AG, and SBE were correlated.

Statistical analysis

The statistical software SPSS version 22.0 (Armonk, NY: IBM Corp. released 2013) and Pearson correlation were used, taking P < 0.05 as a significant level. Bonferroni correction for continuity was applied when necessary.


   Results Top


During 18 months, 130 patients were observed. General characteristics and their mean values as well as baseline values of ScvO2, AG, SBE, and lactate are shown in [Table 1].
Table 1: Baseline values of general characteristics

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Then, samples for ScvO2, AG, SBE, and lactate were taken at different time intervals and correlation analysis was done. A total of six samples from each patient were taken, i.e., after fluid bolus (at 30 mL.kg−1), after achieving central venous pressure (CVP), mean arterial pressure (MAP), and ScvO2 target, and then 12 hourly up to 24 h, respectively.

Baseline correlation

The positive correlation was observed between ScvO2 and SBE (r = 0.462, P = 0) and negative correlation between ScvO2 and serum lactate (r = −0.481, P = 0). The negative correlation was observed between SBE and serum lactate (r = −0.45, P = 0). The negative correlation was observed between ScvO2 and AG (r = −0.172, P = 0.05). The negative correlation was observed between SBE and AG (r = −0.244, P = 0.005). All the correlations were statistically significant (P < 0.05). The negative correlation was observed between serum lactate and AG (r = −0.059, P = 0.502). This correlation was statistically not significant [Table 2]. After adequate fluid resuscitation, again correlation analysis was done.
Table 2: Baseline correlation of central venous oxygen saturation, standard base excess, anion gap, and lactate

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After fluid resuscitation

The positive correlation was observed [Table 3] between ScvO2 and SBE (r = 0.149, P = 0.092) and negative correlation between ScvO2 and serum lactate (r = −0.2, P = 0.023). The negative correlation was observed between SBE and serum lactate (r = −0.374, P = 0). The positive correlation was observed between ScvO2 and AG (r = 0.054, P = 0.541). This was not statistically significant. The negative correlation was observed between SBE and AG (r = −0.329, P = 0). This was statistically significant. The negative correlation was observed between serum lactate and AG (r = −0.055, P = 0.5); this was not statistically significant.
Table 3: Correlations of variables after fluid resuscitation

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Correlation analysis after achieving target CVP, MAP, and ScvO2, at 12 h then 24 h is shown in [Table 4], [Table 5], [Table 6], [Table 7], [Table 8], [Table 9], respectively. Correlation of variables at different interval by line diagram and Bar Chart in [Figure 1] and [Figure 2] respectively.
Table 4: Correlations of variables after achieving target central venous pressure

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Table 5: Correlations of variables after achieving target mean arterial pressure

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Table 6: Correlations of variables after achieving target central venous oxygen saturation

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Table 7: Correlations of variables when urine output >0.5 ml/kg/h

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Table 8: Correlation of variables after 12 h of admission

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Table 9: Correlation of variables after 24 h of admission

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Figure 1: Line diagram showing correlation of variables at different intervals. CVP = Central venous pressure, MAP = Mean arterial pressure, ScvO2 = Central oxygen saturation

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Figure 2: Bar charts showing correlation of variables at different intervals. ScvO2 = Central venous oxygen saturation, SBE = Standard base excess, AG = Anion gap, CVP = Central venous pressure, MAP = Mean arterial pressure

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   Discussion Top


Earlier studies were done on the correlation of changing trends of ScvO2, serum lactate, and base excess, some had shown results similar to our finding, and some studies do not support our finding. Adams et al.[12] evaluated all emergency department (ED) patients for sepsis and found AG and serum lactate are related, but they are not absolutely codependent. From this study and our study, it appears that AG cannot be considered as a surrogate for lactate testing. Berkman et al.,[13] recruited 1419 patients of septic shock to the ED of Boston hospital and concluded that Ag is a good but not excellent screening test to help identify elevated lactate in an ED population at risk of sepsis. Park et al.[14] conducted the study in the medical and surgical ICU of the Hospital of the University of Sao Paulo in Brazil in September 2004–November 2005. They concluded acidosis resolution was attributable to a decrease in strong ion gap and lactate level [Table 3]. Park et al.[11] conducted a retrospective study in ICU of a university tertiary hospital where 65 consecutive severe sepsis and septic shock patients are observed without any intervention in the treatment by the authors of this report. They observed that the ScvO2 of both groups was above 70% after the resuscitative period, excluding the 2nd day of the nonsurvivors group (69.8%). After the 2nd day, the ScvO2 was significantly higher in the survivors' group (P < 0.001). SBE was initially low in both groups, but from the 2nd day on, the correction of SBE was significantly more successful and linear in the survivor group (P < 0.001). Lactate levels were similar during the evolution of both groups. They concluded that although evaluative SBE and serum lactate level are still outcome markers in severe sepsis and septic shock patients resuscitated with EGDT, other studies must be performed to clarify if hemodynamic interventions based on SBE and serum lactate level could be reliable to improve clinical outcomes in severe sepsis and septic shock patients. Our findings of the correlation between SBE and serum lactate were consistent with that of abovementioned studies. Mahajan et al.[15] performed a prospective observational cohort study over 8 months (November 2012 until June 2013) in the medical and surgical ICU and high dependency units of a tertiary care hospital in India. They concluded that there was no evidence of a change in ScvO2 (P = 0.063) values overtime. Lactate significantly decreased overtime (P < 0.001) with the rate of decrease more pronounced in survivors than nonsurvivors (P < 0.001). Our finding of lack of correlation between ScvO2 and serum lactate is consistent with that of the above finding. Pongmanee and Vattanavanit.[16] found that in patients with septic shock, lactate and AG showed a strong correlation with each other, whereas lactate and BE showed a moderate correlation with each other. Thus, these biomarkers can be used interchangeably to help determine septic shock earlier in patients.

Merits

Our study is important in the following parameters criteria used by us are widely studied and are used in various studies including Indian studies. We compared all the variables on various parameters. We correlated all the variables interclass and intraclass. The bias in the study was minimal. The study is able to give valuable information regarding the trend of one variable that can predict the trend of other variables.

Limitations

Above merits should be considered within limits of our study as our setup is tertiary center hence seriously ill subjects are seen mostly but patients rarely come from the direct community, i.e., most of them are referred cases from some private hospitals so most of them either have stared resuscitation or already in very deteriorated condition so patient bias cannot be ruled out hence, limit the generalizability of the findings. Normal matched controls were not taken in the study. Furthermore, we did not use a definite antibiotic protocol common to all patients for treatment, so the bias due to treatment heterogeneity cannot be ruled out. Seven discrete time points were chosen for the evaluation of the various parameters. Continuous monitoring of these parameters and measuring changes with specific interventions would have been more relevant. We could not follow the trend of these parameters after 24 h.

Future directions

The identification of these specific parameters and to have a better understanding we need studies with good sample size and follow-up studies for generalizing the results.


   Conclusion Top


ScvO2 and SBE are correlated and can be used as a surrogate marker. ScvO2 and AG are related but not absolutely co-dependent. ScvO2 and lactate are correlated but they are not absolutely co-dependent. SBE and AG are correlated and can be used as a surrogate marker. AG and lactate are not related to each other. Hence, AG cannot be considered as a surrogate for lactate testing. SBE and lactate are related and can be used as a surrogate marker.

Acknowledgment

The authors are thankful to the patients' guardians for their consent and the department of medicine and anesthesia and nursing officers for their support in the study. The guardians reviewed the study findings and gave written permission to the authors to publish the article.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.



 
   References Top

1.
Singer M, Deutschman CS, Seymour CW, Shankar-Hari M, Annane D, Bauer M, et al. The Third International Consensus definitions for sepsis and septic shock (Sepsis-3). JAMA 2016;315:801-10.  Back to cited text no. 1
    
2.
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.  Back to cited text no. 2
    
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ProCESS Investigators, Yealy DM, Kellum JA, Huang DT, Barnato AE, Weissfeld LA, et al. A randomized trial of protocol-based care for early septic shock. N Engl J Med 2014;370:1683-93.  Back to cited text no. 3
    
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ARISE Investigators, ANZICS Clinical Trials Group, Peake SL, Delaney A, Bailey M, Bellomo R, et al. Goal-directed resuscitation for patients with early septic shock. N Engl J Med 2014;371:1496-506.  Back to cited text no. 4
    
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Mouncey PR, Osborn TM, Power GS, Harrison DA, Sadique MZ, Grieve RD, et al. Trial of early, goal-directed resuscitation for septic shock. N Engl J Med 2015;372:1301-11.  Back to cited text no. 5
    
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Gu WJ, Wang F, Bakker J, Tang L, Liu JC. The effect of goal-directed therapy on mortality in patients with sepsis – Earlier is better: A meta-analysis of randomized controlled trials. Crit Care 2014;18:570.  Back to cited text no. 6
    
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Smith I, Kumar P, Molloy S, Rhodes A, Newman PJ, Grounds RM, et al. Base excess and lactate as prognostic indicators for patients admitted to intensive care. Intensive Care Med 2001;27:74-83.  Back to cited text no. 7
    
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Balasubramanyan N, Havens PL, Hoffman GM. Unmeasured anions identified by the Fencl-Stewart method predict mortality better than base excess, anion gap, and lactate in patients in the pediatric Intensive Care Unit. Crit Care Med 1999;27:1577-81.  Back to cited text no. 8
    
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Bakker J, Gris P, Coffernils M, Kahn RJ, Vincent JL. Serial blood lactate levels can predict the development of multiple organ failure following septic shock. Am J Surg 1996;171:221-6.  Back to cited text no. 9
    
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Marecaux G, Pinsky MR, Dupont E, Kahn RJ, Vincent JL. Blood lactate levels are better prognostic indicators than TNF and IL-6 levels in patients with septic shock. Intensive Care Med 1996;22:404-8.  Back to cited text no. 10
    
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Park M, Azevedo LC, Maciel AT, Pizzo VR, Noritomi DT, da Cruz Neto LM. Evolutive standard base excess and serum lactate level in severe sepsis and septic shock patients resuscitated with early goal-directed therapy: Still outcome markers? Clinics (Sao Paulo) 2006;61:47-52.  Back to cited text no. 11
    
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Adams BD, Bonzani TA, Hunter CJ. The anion gap does not accurately screen for lactic acidosis in emergency department patients. Emerg Med J 2006;23:179-82.  Back to cited text no. 12
    
13.
Berkman M, Ufberg J, Nathanson LA, Shapiro NI. Anion gap as a screening tool for elevated lactate in patients with an increased risk of developing sepsis in the Emergency Department. J Emerg Med 2009;36:391-4.  Back to cited text no. 13
    
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Park M, Taniguchi LU, Noritomi DT, Libório AB, Maciel AT, Cruz-Neto LM. Clinical utility of standard base excess in the diagnosis and interpretation of metabolic acidosis in critically ill patients. Braz J Med Biol Res 2008;41:241-9.  Back to cited text no. 14
    
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Mahajan RK, Peter JV, John G, Graham PL, Rao SV, Pinsky MR. Patterns of central venous oxygen saturation, lactate and veno-arterial CO2 difference in patients with septic shock. Indian J Crit Care Med 2015;19:580-6.  Back to cited text no. 15
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16.
Pongmanee W, Vattanavanit V. Can base excess and anion gap predict lactate level in diagnosis of septic shock? Open Access Emerg Med 2018;10:1-7.  Back to cited text no. 16
    


    Figures

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    Tables

  [Table 1], [Table 2], [Table 3], [Table 4], [Table 5], [Table 6], [Table 7], [Table 8], [Table 9]



 

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