CORRELATION BETWEEN CENTRAL VENOUS AND MIXED VENOUS OXYGEN SATURATION IN THE ELECTIVE ABDOMINAL AORTIC ANEURYSM SURGERY. KORELACIJA IZMEĐU SATURACIJA CENTRALNE VENSKE I MEŠANE VENSKE KRVI KISEONIKOM U ELEKTIVNOJ HIRURGIJI ANEURIZME

Background/Aim. The concept of utilizing central venous oxygen saturation (ScvO2) to calculate cardiac index (CI) remains controversial and neither precise nor generally applicable conclusion has been reached yet. We evaluated the relationship between ScvO2 and mixed venous oxygen saturation (SvO2) in elective surgery of the abdominal aorta. The adequacy of their interchangeability was tested by comparing cardiac indices (CI) calculated by two methods in patients that underwent major vascular surgery. The aim of this study was to test the correlation between ScvO2 and SvO2 in different time frames, in patients undergoing elective abdominal aortic aneurysm (AAA) surgery as well as to determine if the use of ScvO2 for calculating CI by the modified Fick equation, could be feasible and accurate surrogate for the values obtained by pulmonary artery catheter (PAC). Methods. This prospective observational study included 125 consecutive patients that underwent elective AAA surgery. The ScvO2 and SvO2 data, as well as CI values, were obtained and compared from samples taken in three different time frames: immediately after induction of general anesthesia (T0), immediately after admission in the intensive care unit (ICU; T1), and 8 h after admission in the ICU (T2). The Fick equation, used for CI estimation from ScvO2 (CI-F), for the purpose of this study, was simplified according to Walley. Results. There was good linear correlation between ScvO2 and SvO2 in all time frames and linear regression study revealed strongest coefficient of determination (R2 = 0.661) in T2 time-frame. There was no correlation between CI-F (i.e. CI calculated from ScvO2 by modified Fick equation) and CI (measured by PAC from SvO2) in any time-frame. Conclusion. The results of our study confirm that ScvO2 is a reliable substitute for SvO2 among patients undergoing elective surgery of the AAA. However, ScvO2 cannot be used as a surrogate to true SvO2 in the calculation of CI.


Introduction
Measurement of mixed venous oxygen saturation (SvO2) is useful indirect index of the entire body tissue oxygenation. 1 However, risk/benefit of the pulmonary artery catheter (PAC) placement remains controversial, and thus, its use has became somewhat unpopular. 2,3Routine use of the PAC in critically ill patients does not improve mortality and is associated with higher costs and complication rates. 4,5Insertion of a central venous catheter (CVC) in the superior vena cava (SVC), via the right internal jugular or subclavian vein, on the other side, remains standard of care in critically ill patients. 6Monitoring of central venous oxygen saturation (ScvO2) may be, therefore, the safer alternative to SvO2.Despite recent renewed interest in clinical applicability of serial ScvO2 measurements, there are no published data in the available literature describing the pattern of ScvO2 changes during major vascular surgery or possible relationships with outcome. 7,8rinciple objective of our study was to test the correlation between ScvO2 and SvO2 in different time frames, in patients undergoing elective abdominal aortic aneurysm (AAA) surgery.Additionally, we wanted to determine if calculating cardiac index (CI) using ScvO2, by modified Fick equation, could be feasible and accurate surrogate for the values obtained by PAC.

Methods
Prospective observational study included 125 consecutive patients, scheduled for the elective AAA surgery, between July 2015.and April 2016., at Clinic for Vascular and Endovascular Surgery, Clinical Center of Serbia.Patients with aortoiliac occlusive disease (Leriche ' s syndrome), cardiac or dialysis access shunt (fistula or graft) and emergent cases (ruptured AAA) were excluded from the study.Study protocol has been approved by the Ethical Committee of the Clinical Center of Serbia.Written informed consent was obtained from all patients before enrollment.All operations were performed with combined (peridural and general endotracheal) anesthesia.Patients were premedicated with 5mg i.m. midazolam (Dormicum, Roche) 45 minutes prior to anesthesia.Peridural catheter (Perifix, B.Braun Melsungen AG) was inserted under local anesthesia at Th10-L1, or L1-L2, or L2-L3 level, with patient in left recumbent position.Induction proceeded with 0.2 mg/kg midazolam and 0,6mg/kg rocuronium bromide (Esmeron, Merck Sharp & Dohme).Patients were connected to anesthesia apparatus (Primus, Dräger) and anesthesia was maintained with gas mixture O2/N2O (FiO2=0.5) and sevoflurane (Sevoran, AbbVie) in concentration of 0.8-1.5 Vol%, along with rocuronium bromide in total dose of 100mg.For analgesia, 6-8ml of 0.5% levobupivacain was given every 1.5h-2h via the peridural catheter.Operations were completed without any use of intravenous analgetics.Median laparotomy and transperitoneal approach to the abdominal aorta and classical inguinal approach to the femoral arteries were utilized.Abdominal aortic cross clamping was done below or above the origin of renal arteries, and occasionally above the origin of truncus coeliacus.Reconstruction of the abdominal aorta (AA) included interposition of either tubular (Ao graft interposition -GI) or " Y " Dacron graft (Ao-biilliac -AII, Aobifemoral -AFF).Postoperative analgesia was maintained with a bolus dose 6-8ml of 0,25%, levobupivacain, every 8h, via the peridural catheter.Lungs were mechanically ventilated (Evita, Dräger).Invasive monitoring included radial artery cannulation (Becton Dickinson off-on), for the measurement of systemic blood pressure and serial blood sampling for gas analyses (Radiometar ABL 90 flex).Insertion of the CVC (Arrow) was performed via the right internal jugular or subclavian vein and position of its tip in SVC, for ScvO2 measurements, subsequently verified by chest radiograph.In addition, the PAC (Swan-Ganz catheter, Arrow, 7F) was also inserted for SvO2, CO (cardiac output), CI measurements.Thermodilution CO and CI were obtained in triplicate and averaged.Samples from CVC and PAC were taken simultaneously in following time-frames: immediately after induction of general anesthesia (T0), immediately after admission in the ICU (T1), and 8h after admission in the ICU (T2).Fick equation, used for CI estimation from ScvO2 (CI-F), for the purpose of this study, was simplified according to Walley 7 : CI ≈ 100/Hgb x 1/ Sa 2-SvO2) where: CI = cardiac index (L/min/m 2 ); Hgb = hemoglobin (gram/L); SaO2 = arterial oxygen saturation (%) and ScvO2 = central venous oxygen saturation (%).Statistical analyses were performed using SPSS software v.23.0 (SPSS Inc., Chicago, IL, USA).Descriptive data for all groups and variables were expressed as mean ± SD for continuous measures, or percent of a group for discrete measures.A normal distribution was tested using the Koglomorov-Smirnov test.If the data were normally distributed, RM-ANOVA was used.Non-parametric data were analyzed using Fridman test.Post hoc analysis was performed using Bonferroni test (parametric data) and Wilcoxon test (non parametric data).Correlation of the CVC and PAC parameters was tested with Pearson (parametric data) and Spearman correlation coefficient (non parametric data).All reported p values were two-sided; differences were considered significant when p value was <0.05.

Results
Preoperative and intraoperative patient characteristics are summarized in Table 1.It is noteworthy emphasizing that majority of patients were in the seventh decade of life, with significant male predominance.Almost 95% were hypertensive and more than a half had some form of coronary artery disease.Intraabdominal reconstruction (i.e.GI and AII) with infrarenal clamp was possible in more than 90% cases.

TABLE 1.
Values of observed parameters (ScvO2,Sv 2 , CI, CI-F), obtained in three different time frames, are summarized in Table 2. Significant changes were registered for all of them, but intergroup significance was present only for ScvO2 and Sv 2 .
TABLE 2. Correlation between ScvO2 andSv 2 in different time frames is shown on Table 3.Since we established statistically significant correlation between observed parameters, a linear regression study was performed and the strongest coefficient of determination (R 2 =0.661) was found in T2 time-frame (Table 3, Figure 1C).These results have confirmed that ScvO2 could be reliable surrogate for Sv 2 , particularly 8 hours after admission in the ICU.TABLE 3. FIGURE 1. Unlike expected, there was no correlation between CI-F (i.e.CI calculated from ScvO2 by modified Fick equation and CI measured by C fromSv 2 in any time-frame (Table 4).TABLE 4.

Discusion
Interchangeability of ScvO2 and SvO2 values has been a matter of debate, primarily because of different sampling points and venous blood pools they represent (i.e.entire body for SvO2 and upper part of the body for ScvO2) 9 .Complex relationship of these two parameters is different in healthy and diseased persons.Thus, ScvO2 is slightly lower (76% vs. 78%) than SvO2 in healthy individuals, but in persons with cardiovascular instability, this relationship changes 10 .
The most valuable information is trend of either ScvO2 or SvO2 changes upon applied treatment.Renewed interest in ScvO2 monitoring came from the fact that lots of complications related to PAC insertion have been documented in the literature. 11ntravascular pressure could not provide an adequate insight in intravascular volume, which is, in turn, the only cardiac preload equivalent of 12 .Sandham et al. found no correlation between PAC guided therapy and outcome in non-cardiac surgical patients. 2cheinman and co-workers compared ScvO2 and SvO2 levels in different hemodynamic states. 11,12 hey found no significant difference in stabile patients and patients with heart failure (54.7% vs. 56.9%,p>0.1 and 61.8% vs. 58.2%,p<0.1 respectively).In patients with circulatory shock, this difference was significant (58.0% vs. 47.5%, p<0.001), due to poor left ventricular function and renal impairment. 13,14he degree of correlation between ScvO2 and Sv 2 was tested by numerous studies, regardless of patient's hemodynamic status.By doing so, they were unable to find the reasons for poor correlation observed.][17] Unlike previous, studies performed under experimentally controlled conditions found good correlation between ScvO2 and Sv 2, regardless of their absolute values. 18,19Also, some studies emphasized the importance of similarity of trends between two parameters, while others deny the reliability of ScvO2. 20,21,22f we keep on mind that ScvO2 depends on: hemoglobin levels, SaO2, CO, VO2 (oxygen consumption), body temperature, analgesic level and metabolic state, keeping all, except selected one constant, than ScvO2 value reflects the changes of the remaining.The relationship between ScvO2 and SvO2 is not simple.In healthy persons, absolute values of these parameters are similar, which is not necessarily true in critically ill patients.Absolute values of ScvO2 may be pathological even when it is high or low. 23ttempts to calculate CI from ScvO2 is not a new concept. 24In experimental studies, with dogs in different cardio-respiratory conditions, Reinhart et al. found a good correlation (r=0.97) between CI calculated using two different methods. 20 Goldman et al. 1968, performed similar study in human subjects. 24Since then, a lot of studies on human subjects in different medical conditions were designed to correlate ScvO2 and SvO2. 25,26uring hypovolemic circulatory disturbances, CI and ScvO2 showed better correlation with the extent of blood loss, than CVP, PCWP (pulmonary capillary wedge pressure), arterial pressure and heart rate.Interestingly, in spite of different absolute values, the trends of ScvO2 and SvO2 changes paralleled observed hemodynamic changes.Orthostatic hypotension is commonly used, as a model of the cardiovascular disturbances associated with hypovolemia in humans. 25,27Median ScvO2 fell from 75% to 60%, paralleling CO decrease from 4.3 to 2.7 L/min, at the onset of pre-syncope symptoms.However, unlike in experiments, in series of major trauma victims, there was no strong correlation of ScvO2 and SvO2 with the extent of blood loss. 27,28n septic patients, different trials could not find firm correlation between absolute values of ScvO2 and SvO2 29,30 , probably due to modified blood flow distribution and oxygen extraction (O2 ER) by brain and splanchnic tissues. 30,31In spite of this, variations in these two parameters usually occured in a parallel manner. 29,32 ybe the most extensively studied were the patterns of SvO2 and ScvO2 changes in cardiac failure and myocardial infarction.Goldman correlated derangements ScvO2 with severity of myocardial dysfunction and subsequent response to treatment, finding that levels below 45% usually indicate the onset of cardiogenic shock.While decrease of ScvO2 levels depicts the severity of disease 11 , trends are associated with CO and response to treatment. 33,34,35here are few papers describing SvO2 monitoring during the aortic surgery. 36,37Application and removal of aortic and femoral clamps produces complex SvO2 changes.Clamp removal and lower body reperfusion produce significant SvO2 decrease, not necessarily reflecting a need to change cardiovascular management.However, there are very few or no data, regarding ScvO2 monitoring during the abdominal aortic surgery.Kopterides and coworkers 37 investigated the significance of CVC tip position.When positioned 15cm away from the inlet of the right atrium, ScvO2 overestimated SvO2 by 8%.However, when the tip of the CVC was advanced deeper in the right atrium, ScvO2 becomes an excellent surrogate, overestimating SvO2 by only 1%.
Our study enrolled patients without PA and SVC (superior vena cava) catheterization under fluoroscopic guidance.So, both measurements, neither ScvO2 nor SvO2, were obtained under direct visualization of the catheter tips.Our subsequent analyses of the central line tip positions, in the ICU, showed that most of them were located in SVC or proximal right atrium (RA) or SVC-RA junction.This implies that blood samples were actually obtained from different places.We used the X-ray confirmation of the CVC tip position in the ICU, to exclude the patients in whom CVC was accidentally placed in the innominate vein.Thus, we intended to test the correlation between ScvO2 and SvO2 within more limited variations of ScvO2 values.It should be emphasized that it was our intention to adapt on "real-life" situation, without changing established perioperative protocols for the purposes of this study.On the other hand, PAC parameters (SvO2 and thermodilution CI) were obtained in triplicate and then averaged.Although our results have confirmed statistically significant linear correlation between ScvO2 and SvO2, almost paradoxically, the same was not true with CI-F and CI.The most logical explanation is that, in fact, we have used "different mathematics".Walley's simplification of Fick formula, using ScvO2 values to calculate CI-F, could not meet correlation criteria with thermodilution CI values obtained by PAC, using SvO2.The ability of ScvO2 measurement to estimate SvO2 is useful but still imperfect, depending on CVC catheter placement, patient anatomy and physiologic state.Importantly, ScvO2 is an increasingly less reliable substitute for SvO2 as the cardiac performance is worsened.This should always be kept in mind when interpreting ScvO2 measurements.When true SvO2 is essential, PAC placement remains the gold standard, since it provides more data than just a calculation of CI and many patients may still benefit from it.In that sense, significant linear correlation between ScvO2 and SvO2 in our study could be seen as a result of standardized and reliable team work, resulting in absence of significant perioperative hemodynamic disturbances and mayor blood loss, allowing early detubation (within 2 postoperative hours) and stabile spontaneous breathing in all patients.

Limitations of the study
Accuracy of ScvO2 measurement depends on CVC catheter placement, patient anatomy and physiologic state.Positioning of PAC and measurements was not always done by the same physician.

Conclusion
The results of our study confirm that ScvO2 is a reliable substitute for SvO2 among patients undergoing elective surgery of the abdominal aorta.It seems, when applied appropriately, measurement of either ScvO2 or SvO2 may provide a valuable guide to circulatory management in the early postoperative period.However, this is not always true.In our study ScvO2 cannot be used as a surrogate to true SvO2 in the calculation of CI.Further studies are needed to confirm our findings.In practice, ScvO2 seems especially useful in combination with vital signs and other relevant parameters.

Table legend :
*statistical significance; a RM ANOVA; b Fridman-s test; c Bonferroni test; d Wilcoxon-s test; 1 p=To and T1 comparison; 2 p= To and T2 comparison; 3 p= T1 and T2 comparison.