Off-pump coronary artery bypass grafting (OP-CABG) surgery without the use of cardiopulmonary bypass (CPB) has come into practice for surgical treatment of Coronary artery disease (CAD) to reduce the post-operative systemic inflammatory response and post-operative morbidity. However, manipulation of the beating heart during OP-CABG surgery brings significant fluctuations in the patients haemodynamics leading to occult hypo-perfusion and 'Global tissue hypoxia' (GTH) -a decrease in oxygen utilization associated with anaerobic metabolism.

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Introduction
Off-pump coronary artery bypass grafting (OP-CABG) surgery
without the use of cardiopulmonary bypass (CPB) has come into
practice for surgical treatment of Coronary artery disease (CAD)
to reduce the post-operative systemic inflammatory response and
post-operative morbidity. However, manipulation of the beating
heart during OP-CABG surgery brings significant fluctuations in
the patients haemodynamics leading to occult hypo-perfusion
and ‘Global tissue hypoxia’ (GTH) -a decrease in oxygen utilization
associated with anaerobic metabolism [1].
About 10% of these patients suffer organ failure with GTH after
cardiac surgery, which is associated with a prolonged ICU stay [2].
GTH is not recognized using routinely monitored vital parameters
such as urine output, mean arterial pressure, pulse-oximetry and
others [3]. ScVO2 and lactate are the bio-markers which indicate
microcirculatory failure and tissue hypoperfusion. They have a
well-defined role in guiding the clinicians to initiate and optimize
early haemodynamic treatment and resolution of hypoperfusion
in critically ill patients and those with sepsis [4]. They have also
independently proved to be potential early predictors of morbidity
and mortality. However, studies simultaneously addressing both
ScVO2 and lactate as potential early predictors of morbidity and
mortality in cardiac surgery are still lacking. The purpose of this
study is to evaluate the hypothesis whether measurement of ScVO2
and blood lactate, individually or in combination would predict the
outcome of patients undergoing elective OP-CABG in our hospital.
Materials and Methods
This study was conducted in our institution from September
2014 to September 2015 after the institutional Ethical Committee
approval. Consecutive patients undergoing elective OP-CABG who
fulfilled the inclusion criteria without any exclusion criteria were
Namratha1
, Dinesh Kumar2
* and Nalini Kotekar1
1
Department of anaesthesia, JSS super specialty hospital and medical college, JSS University, India
2
Department of Cardiac, thoracic and vascular anaesthesia, JSS super specialty hospital and medical college, JSS university, India
*Corresponding author: Dinesh Kumar, Assistant professor, Department of Cardiac, thoracic and vascular anaesthesia, JSS super specialty hospital and
medical college, JSS university, Mysore -570011, Karnataka, India, Tel: +919663237722; Email:
Submission: January 05, 2018; Published: January 19, 2018
Does Serum Lactate and Central Venous Saturation
Predict Perioperative Outcomes in Patients
Undergoing Off-Pump CABG
Research Article Open J Cardiol Heart Dis
Copyright © All rights are reserved by Dinesh Kumar.
CRIMSONpublishers
http://www.crimsonpublishers.com
Abstract
Background: Lactate and Central venous oxygen saturation (ScVO2) are well-known bio-markers for the adequacy of oxygen delivery to tissues.
Both are used in intensive care units (ICU) and following major surgery to predict outcome. Our aim was to study whether low ScVO2 (≤65%) and
high lactate (≥3mmol/L) when used alone or in combination predict post-operative morbidity, mortality and prolonged duration of ICU stay following
elective off-pump Coronary artery bypass grafting (OP-CABG).
Methods: This is a prospective observational study of sixty patients aged between 40 and 80 years undergoing elective OP-CABG was conducted
from September 2014 to September 2015. Lactate and ScVO2 were measured at three fixed intervals -at induction (T1), ICU admission (T2) and 12
hours after induction (T3). The association of these parameters at all three time intervals with morbidity and duration of ICU stay were studied using
univariate and multivariate Logistic regression analysis. Sensitivity, Specificity, Positive Predictive value (PPV), Negative Predictive value (NPV), and
Diagnostic accuracy were calculated using 2 X 2 contingency table.
Results: High Lactate at induction (T1), low ScVO2 at 12 hours after induction (T3) and the combined index ( high Lactate with low ScVO2)
measured at ICU admission (T2) were found to predict post-operative major morbidity with an odds ratio (OR) of 10.797, 4.696 and 44.444 respectively.
Combined index at T2 had 97.56% specificity and PPV of 90.91%.
Conclusion: High Lactate and low ScVO2 are associated with post-operative morbidity both independently and as a combined index. An abnormal
combined index measured at ICU admission is the most reliable predictor of morbidity following elective OP-CABG surgery.
Keywords: Lactate; Central venous oxygen saturation; Off-pump CABG
ISSN 2578-0204

2. How to cite this article: Namratha, Dinesh K, Nalini K. Does Serum Lactate and Central Venous Saturation Predict Perioperative Outcomes in Patients
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selected for the study and a written informed consent was obtained.
A thorough pre-anesthetic evaluation was performed and the
following data were collected age, sex, height, weight, Euro score
II, pre-op requirement of Intra-aortic Balloon pump (IABP), serum
creatinine, hemoglobin, Co-morbidities, pre-operative ejection
fraction.
All the patients underwent OP-CABG under general anaesthesia
with endotracheal intubation and controlled ventilation. With strict
asepsis, Central line (7F, 16cms triple lumen, Arrow) in the right
internal jugular vein was secured under local anaesthesia before
induction. All venous blood samples for measuring serum lactate
and central venous saturation was collected from the distal port of
triple lumen. Anaesthesia was administered as per our institutional
protocol. Induction was done with oxygen, Sevoflurane-2%,
Fentanyl 10ug/kg, Midazolam 0.05mg/kg, Propofol 2mg/kg and
Pancuronium 0.1mg/kg for endotracheal intubation. Standard
monitoring included 12-lead electrocardiogram with ST analysis,
invasive arterial pressure, pulse oximetry, end-tidal carbon
dioxide, central venous pressure, nasopharyngeal temperature
and urine output. Trans-oesophageal echocardiography (TEE)
was used to monitor the left ventricular function, regional wall
motion abnormality and to calculate the cardiac output and
systemic vascular resistance. The position of the tip of the triple
lumen central venous catheter was confirmed to be at the superior
venacava (SVC) and right atrium (RA) junction by TEE. Isoflurane
1%, Air: O2 (FiO2=0.6) was used for maintenance along with
Dexmedetomidine (0.3ug/kg/hr) and Morphine (20ug/kg/hr)
infusion. Neuromuscular blockade was achieved with Vecuronium.
Coronary artery bypass grafting was performed off pump by
stabilizing the heart with Octopus and Atmos suction apparatus
while grafting. Left internal mammary artery was used for grafting
leftanteriordescendingarteryandotherarteriesweregraftedusing
saphenous vein grafts. All patients were admitted post-operatively
to ICU, electively ventilated and received standard post-operative
care. Blood samples from the right internal Jugular central venous
catheter were collected using vacutainer tubes for measuring
central venous saturation and lactate. First sample was obtained
after induction (T1), the second sample was obtained at ICU
admission (T2) and the third was obtained 12hours after induction
(T3). The samples were sent for venous blood gas analysis, ScVO2
and lactate values were obtained (Blood gas analyzer ABL 800).
Patients were considered to have major morbidity if they develop
renal failure (serum creatinine more than twice the pre-operative
value) and requirement of dialysis, a high inotropic requirement
in first 48hrs (Vasoactive Inotropic score >15), the requirement
of Intra-aortic balloon pump (IABP), low cardiac output (MAP
<65mmHg and urine output <0.5ml/kg/hr), infection, sepsis and
other complications (stroke, respiratory distress syndrome) were
recorded. Based on the outcome, the patients included in the study
were divided into Group M having major morbidity and Group N
having no morbidity. Mortality at 30 days following surgery was
evaluated by a telephonic call to the patient relative.
ScVO2 and Lactate values measured at induction (T1), at ICU
admission (T2) and12 hours after induction (T3) were defined
as Low ScVO2 (≤65%) or normal ScVO2 (>65%), high Lactate
(≥3mmol/L) or normal Lactate (<3mmol/L) and abnormal
combined index (lactate ≥3mmol/L and ScVO2 ≤65%) or normal
combined index (Lactate <3mmol/L and ScVO2>65%).
Data was analyzed by IBM SPSS software version 22.0. A p
value <0.05 was considered significant. Continuous variables were
expressed as Mean±Standard Deviation. Categorical variables were
expressed as Number (n) or Percentage (%). The Independent
t-test was used to compare continuous variables and Chi-square
test was used to compare categorical variables between two groups.
Univariate/multivariate Logistic regression analysis was used to
test the association of high lactate, low ScVO2 and an abnormal
combined index with major morbidity. Sensitivity, Specificity,
Positive Predictive value, Negative Predictive value, and Diagnostic
accuracy of high Lactate, low ScVO2 and abnormal combined
index as predictors of major morbidity were calculated using 2X2
contingency table.
Inclusion criteria
1. Age - 40-80 years, male and female patients
2. Patients undergoing off pump CABG with triple vessel
disease with ejection fraction >30%.
Exclusion criteria
1. Emergency surgery
2. Coexisting valvular heart disease
3. Preoperative COPD/cardiogenic shock/renal failure
4. Ejection fraction <30%
5. Patients with Left Main Coronary Artery (LMCA) lesion
6. Unwilling to give consent
7. Central venous catheter tip couldn’t be visualized with
TEE.
8. Patients lost to follow-up.
Results
Sixty patients with coronary artery disease who underwent
elective off-pump CABG from 2014 to 2015 satisfying the eligibility
criteria were included in this prospective observational study.
Based on the post-operative morbidity they were divided into two
groups. As shown in Table 1 the demographic parameters in both
the group-M and group-N were comparable except the Euroscore
which was higher in group-M. Out of the sixty patients, 19 patients
(31.66%) belonged to the group M who developed major post-
operative morbidity. Three (5%) patients had renal failure and
required dialysis, sixteen (26.66%) patients required high inotropic
support in first 48hours, four (6.66%) patients required intra-aortic
balloon pump and two (3.33%) of them developed an infection
and sepsis. Patients who developed sepsis and subsequent multi-
organ dysfunction accounted for the mortality of two (3.33%)

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How to cite this article: Namratha, Dinesh K, Nalini K. Does Serum Lactate and Central Venous Saturation Predict Perioperative Outcomes in Patients
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patients during the post-operative ICU care. The perioperative risk
assessment parameter used in our study, Euroscore II [5] was found
to be a good predictor of post-operative outcome in our study (p
=0.003).
Table 1: Demographic parameters of the patients with morbidity (Group M) and without morbidity (Group N).
GROUP N (41) GROUP M (19)
P value
Mean Median S D Mean Median SD
AGE 60.85 63.00 8.36 63.68 62.00 9.23 0.2
HEIGHT (cm) 160.37 162.00 9.37 159.53 161.00 9.05 0.8
WEIGHT (kg) 65.17 65.00 9.10 62.21 60.00 9.13 0.3
BMI (kg/m2
) 25.37 25.40 4.21 24.36 24.57 3.38 0.4
BSA (m2
) 1.68 1.69 0.13 1.64 1.61 0.16 0.4
Hb (g/dL) 12.97 13.10 1.79 12.69 12.80 2.10 0.6
EF (%) 53.00 60.00 10.21 47.68 45.00 9.97 0.07
EUROSCOREII 1.33 1.18 0.55 2.25 2.11 1.15 0.003
SC (mg/dL) 0.93 0.90 0.19 1.11 1.00 .38 0.02
Independent t test, BMI: Body Mass Index; BSA: Body Surface Area; Hb: Hemoglobin; EF: Ejection Fraction; SC: Serum Creatinine.
Table 2: Association between lactate, ScVO2 and combined index with morbidity at induction (T1), at ICU admission (T2) and 12hours
after induction (T3) (LOGISTIC REGRESSION ANALYSIS).
SEM P Value OR (95%CI)
At induction
(T1)
Lactate 0.798 0.034 5.405(1.132-25.807)
ScVO2
0.611 0.679 1.287(0.389-4.260)
Combined index 0.918 0.072 5.200 (0.861-31.421)
At ICU admission
(T2)
ScVO2 0.663 0.274 2.065 (0.563-7.577)
Lactate 0.685 0.001 10.797 (2.822-41.312)
Combined index 1.112 0.001 44.444 (5.029-392.815)
12hours after Induction
(T3)
ScVO2
0.673 0.022 4.696 (1.256-17.560)
Lactate 0.807 0.037 5.389 (1.109-26.198)
Combined index 1.119 0.005 23.333 (2.605-208.979)
SEM: Standard Error of Mean; OR: Odds Ratio; CI: Confidence Interval.
P <0.05 -significant
Table 3: Validity of ScVO2, lactate and combined index measured at various time intervals -at induction (T1), at ICU admission (T2)
and 12 hours after induction (T3).
ScVO2
≤65% Sensitivity Specificity PPV NPV Diagnostic Accuracy
T1 47.3% 65.85% 39.13% 72.97% 60%
T2 63.16% 63.41% 44.44% 78.79% 63.33%
T3 78.95% 60.98% 48.39% 86.21% 66.67%
Lactate ≥3mmol/L Sensitivity Specificity PPV NPV Diagnostic Accuracy
T1 31.58% 92.68% 66.67% 74.51% 73.33%
T2 63.16% 87.8% 70.59% 83.72% 80%
T3 36.84% 92.68% 70% 76% 75%
Combined Index Sensitivity Specificity PPV NPV Diagnostic Accuracy
T1 21.05% 95.12% 66.67% 72.22% 71.67%
T2 52.63% 97.56% 90.91% 81.63% 83.33%
T3 36.84% 97.56% 87.5% 76.92% 78.33%
NPV: Negative Predictive Value; PPV: Positive Predictive Value.
At induction (T1), Lactate was independently associated with
major morbidity (p = 0.034). High Lactate at the induction was
found to predict morbidity independently with an odds ratio of
5.405 (95%CI, 1.132-25.807). (Table 2) at ICU admission (T2),
Lactate and the combined index were found to be associated with
major morbidity (p =0.001) with an odds ratio of 10.797 and 44.444
respectively. (Table 2) at 12hrs after induction (T3), lactate and
ScVO2 both independently and as a combined index were associated

4. How to cite this article: Namratha, Dinesh K, Nalini K. Does Serum Lactate and Central Venous Saturation Predict Perioperative Outcomes in Patients
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with major morbidity. Lactate (p=0.037) and ScVO2 (p=0.022) were
independently associated with major morbidity with an odds ratio
of 4.696 and 5.389 respectively. The combined index (p=0.005)
positively correlated with major morbidity with an odds ratio of
23.333. (Table 2) low ScVO2, high lactate and abnormal combined
index as predictors of morbidity were studied at all the three time
intervals for sensitivity, specificity, positive predictive value (PPV),
negative predictive value (NPV) and diagnostic accuracy using the
2X2 contingency table. (Table 3) High Lactate measured at all three
time intervals (T1, T2, T3) had an NPV between 74.51% at T1 to
83.72% at T2. ScVO2 as predictor of morbidity was found to have a
higher NPV of 86.21% at T3. However, PPV for Lactate was found to
range from 66.67% at T1 and 70.59% at T2. ScVO2 at T3 had a PPV
of 48.49%. A combined index (ScVO2<65% and Lactate >3mmol/
dL) had a PPV of 90.91% with an NPV of 81.63% when measured at
ICU admission (T2).
Discussion
Cardiac and high risk surgeries are known to be associated
with global tissue hypoxia (GTH) due to low cardiac output,
anaemia, bleeding, CPB and large volume shift perioperatively. OP-
CABG in particular is associated with haemodynamic instability
and GTH intraoperatively and in post-operative ICU care if not
managed properly [6]. In our study, nineteen out of sixty patients
(31.6%) developed post-operative major morbidity. Ten among
these patients (52.63%) had a low MAP or decreased urine output
recorded in first 48 hours. Failure of conventional indicators like
urine output and MAP to indicate GTH has led to usage of bio-
markers like ScVO2 and Lactate [7]. High blood lactate levels and
low ScVO2 have independently proved to be bio-markers of GTH
and potential early predictors of morbidity and mortality. However,
there are studies showing blood lactate level and ScVO2 are also
influenced by many factors and cannot be independently used as
early predictors of morbidity and mortality in cardiac surgery. So
we studied Lactate and ScVO2 as the combined index predict major
morbidity and mortality. We found that low ScVO2 (< 65%) at 12
hours after induction (T3) was associated with major morbidity
[odds ratio =4.696 (95% CI, 1.256-17.560)] with 78.95% sensitivity
and 60.98% specificity (Table 2). This was in agreement with the
observation by Pearse et al. [8] in which low ScVO2 (<64.4%) was
found to be associated with morbidity with a sensitivity of 67%
and specificity of 56%. A drop in ScVO2 commonly occurs without
change in cardiac index, which is due to various factors like pain,
emergence, body temperature and shivering, but not hypoperfusion
[8]. The low ScVO2 observed at induction (T1) and at ICU admission
(T2) in our study, which was not associated with post-operative
morbidity may be attributed to the increased oxygen extraction due
to these factors rather than decreased perfusion.
According to Ranucci et al. [9] and Maillet et al. [10] Lactate
>3mmol/L was found to be associated with mortality and morbidity
in patients undergoing cardiac surgery on CPB [9,10]. Similarly, in
our study, the lactate value of >3mmol/L at all three time intervals
were found to predict major morbidity. (Table 2) with an odds ratio
of 5.405 (95% CI, 1.132-25.807) at T1, 10.797 (95% CI, 2.822-
41.312) at T2 and 5.389 (95% CI, 1.109-26.198) at T3.
Graph 1: Scatter plot of patient distribution according to cutoff values 65% (ScVO2) and 3mmol/L (lactate) measured at ICU
admission (T2).
Lactate production is not always suggestive of tissue hypoxia.
Type B hyperlactemia is dependent on various other causes like
the inability of tissues to consume oxygen, and not related to tissue
hypoxia. However, Lactate coupled with low ScVO2 is suggestive of
tissue hypoperfusion (type A hyperlactemia) [11].When ScVO2 and
lactate in combination is used, the clinician may be able to decide if
an elevated lactate is due to hypoperfusion or not. In our study an
abnormal combined index at T2 (ICU admission) and T3 (12hours

5. Open Journal of Cardiology & Heart Diseases
How to cite this article: Namratha, Dinesh K, Nalini K. Does Serum Lactate and Central Venous Saturation Predict Perioperative Outcomes in Patients
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later) was found to predict post-operative major morbidity (Table
2) with an odds ratio of 44.444 (95% CI, 5.029-392.815) and
23.333 (95% CI, 2.605-208.979) respectively. The combined index
measured at ICU admission had a specificity of 97.56% and a
PPV of 90.91%, which was higher than that of Lactate and ScVO2
considered individually in predicting outcome (Table 3). Similar
results were obtained in the study by Ranucci et al. [9] in which
combined index of Lactate and ScVO2 was found to have a higher
specificity (99%) and a lower positive predictive value (89%) as
compared to our study in predicting mortality and morbidity [9].
The study group was graphically represented as a scatter plot
showing the patient distribution according to the cut offs of 65%
for ScVO2 and 3mmol/L for Lactate in Graph 1. Low ScVO2 (≤65%)
with normal Lactate (<3mmol/L) represented by the patients in
lower left quadrant may be interpreted as a condition of increased
oxygen-extraction rate, sufficient for covering the consumption
(VO2). On prolonged inadequate delivery, a progressive increase in
bloodlactatewasfound,asamarkerofanaerobicenergyproduction.
UpperleftquadrantinGraph1havingLactate≥3mmol/LwithScVO2
≤65% (abnormal combined index) therefore, can be interpreted as
hyperlactemia (Type A) which is only due to tissue hypoxia. Out of
eleven patients placed in this quadrant, ten (90.90%) patients had
major morbidity. This also explains the higher PPV (90.91%) and
accuracy (83.33%) of the combined index (both lactate and ScVO2)
in comparison to individual indices (ScVO2 or lactate alone) in our
study.
Limitation
The sample size was small and a single center study. Therefore,
the reliability of the results and thus the applicability in practice
will need to be validated further by a larger trial. The PA catheter
was not used to measure the cardiac output and systemic vascular
resistance in post-operative ICU care. Therefore, low cardiac output
in ICU was diagnosed based on clinical acumen, mean arterial
pressure (MAP) and urine output and managed with inotropes.
So Inotrope requirement and LCOS as one of the factors in major
morbidity may not be accurate. A low incidence of 30 day mortality
(two among sixty patients) in our study was not adequate to analyze
its association with lactate or ScVO2.
Conclusion
Our study supports routine measurement of both ScVO2 and
Lactate (combined index) in detecting global tissue hypoxia in
patients undergoing elective off-pump CABG. At ICU admission,
the combined index was found to have highest specificity and
PPV in our study. Detection of low ScVO2 (≤65%) along with high
Lactate (≥3mmol/L) should be considered a warning signal for
inadequate tissue perfusion. Early detection and interventions to
improve tissue oxygenation prevent the degree of hypoperfusion,
development of post-operative major morbidity and organ failure
resulting in improved outcome. High lactate and low central
venous saturation as a combined index are a better predictor of
major morbidity and mortality in patients undergoing off pump
cardiac surgery. A goal directed therapy using these bio-markers
may decrease the postoperative morbidity and duration of ICU and
hospital stay.
Author Contributions
Dr Namratha G C: Data collection and manuscript preparation.
Dr Dinesh Kumar: Conceptualization of idea, Data analysis and
manuscript preparation.
Dr Nalini Kotekar: Conceptualization of idea, Data analysis and
manuscript preparation.
Acknowledgement
We acknowledge Dr Sumanth for his inputs on statistics.
We also like to acknowledge the cooperation of patients and
anaesthesiologist.
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