Role of Central and Mixed Venous Oxygen Saturation Measurement in Perioperative Care

Searches of the MEDLINE and Cochrane CENTRAL databases from January 1968 to December 2008 were performed by both authors using the following search terms: (venous saturation OR venous oximetry OR Svo²OR Scvo²) AND (surgery OR surgical OR \ *operative OR operation). Only articles published in English were included, but no restrictions were placed on source. A further online search was then carried out using the Google Scholar search engine by using the following key words: venous saturation, venous oximetry, surgery, Scvo², Svo². The resulting abstracts were screened to identify relevant investigations in adult patients undergoing major surgery. Studies were excluded if they had not been published in a peer-reviewed journal. Bibliographies of relevant articles were also screened. Manuscripts were screened initially by title and then by abstract before obtaining the full text of relevant articles.

The terms central (Scvo²) and mixed venous oxygen saturation (Svo²) refer to the hemoglobin saturation of blood in the superior vena cava and proximal pulmonary artery, respectively.16Rearrangement of the Fick equation illustrates that venous oxygen content is determined by arterial oxygen content, oxygen consumption and cardiac output.17The quantity of dissolved oxygen is small under standard conditions; therefore, the more conveniently measured variable of hemoglobin saturation is preferred. This is summarized in the equation below, where CO refers to cardiac output, Cao²refers to arterial oxygen content, Cvo²refers to venous oxygen content, and Vo²refers to oxygen consumption.

Where oxygen supply is insufficient to meet metabolic requirements, increased tissue oxygen extraction results in a decrease in the oxygen content of effluent venous blood. Venous oxygen saturation therefore reflects the balance between global oxygen delivery (Do²) and global oxygen consumption (Vo²).18Vo²and Do²both fluctuate significantly during the perioperative period, and it is of particular importance to recognize that changes in venous saturation may reflect a variety of physiologic and pathologic changes (fig. 1). The safe use of venous saturation as a therapeutic goal depends on the prompt recognition of the cause of any derangement. Regional variations in Do²and Vo²are also commonplace and clinically relevant differences in the oxygen content of venous blood are to be expected in different parts of the circulation.19–22In common with other global physiologic variables, the apparent simplicity of a single variable is often associated with a lack of sensitivity to detect regional abnormalities in an apparently stable patient. There is little published data describing the normal value of venous saturation in health. Although commonly quoted as 70%, the available data suggest this may vary from 70% to 80% in healthy individuals.23,24Values of Svo²and Scvo²may often be as low as 65% in hospital in-patients before elective surgery.25 

Global oxygen delivery is determined by cardiac output and the oxygen content of arterial blood as shown in the equation below,26where Do²refers to oxygen delivery and CO to cardiac output where the Bunsen solubility coefficient for O²at 37°C is 0.02.27 

Adequate tissue oxygen delivery therefore depends on the adequacy of both respiratory and cardiovascular function. If oxygen consumption, hemoglobin concentration, and arterial saturation remain constant, changes in Svo²are therefore directly proportional to those in cardiac output; this relationship has been demonstrated in several studies in man.24,28In a study of healthy volunteers, orthostatic hypotension resulted in a decrease in cardiac output from 4.3 to 2.7 l min⁻¹at the onset of presyncopal symptoms.24Over the same time period, Scvo²decreased from 75% at baseline to 60%.24A clinical series of patients undergoing one-lung ventilation demonstrated that cardiac output increased in response to sudden decreases in arterial saturation; as a consequence, Svo²remained unchanged.28Several reports describe reduced venous saturation in patients with a reduced cardiac output due to myocardial infarction and/or heart failure.29–34Changes in Scvo²and Svo²in these circumstances reflect both the severity of hemodynamic disturbances and response to treatment.29–32 

The affinity of hemoglobin for oxygen is affected by the partial pressure of oxygen (fig. 2). It may be anticipated from the oxyhemoglobin dissociation curve that, at higher partial pressures of oxygen, increases in Po²will result in only small increases in hemoglobin saturation. At lower partial pressures, such as those typical of venous blood, the same incremental rise in Po²will result in a greater increase of hemoglobin saturation due to the greater oxygen affinity of deoxyhemoglobin.35Consequently, the change in venous saturation in response to a step change in fractional inspired oxygen concentration may differ considerably from simultaneous changes in arterial hemoglobin saturation. Clinical and laboratory investigations have shown that an increase in fractional inspired oxygen concentration results in a greater increase in oxygen saturation of venous than arterial blood.36,37The administration of supplemental oxygen may therefore be sufficient to rectify significant abnormalities in venous saturation even though these abnormalities may not specifically result from alveolar hypoxia. In situations where Scvo²or Svo²values are being used as hemodynamic endpoints for the administration of intravenous fluid or inotropic therapies, an increase in venous saturation resulting from an increase in fractional inspired oxygen concentration may be misinterpreted as an indication of adequate hemodynamic resuscitation. The potential for such simple interventions to mask the effects of shock emphasizes the importance of a detailed understanding of venous oximetry.

Few studies have explored the relationship between Vo²and venous saturation during the perioperative period. This may reflect poor recognition of the importance of Vo²as a determinant of venous saturation. Considerable changes in oxygen consumption may occur during the perioperative period. Increases in Vo²resulting from pain, anxiety, or shivering may all result in a decrease in venous saturation,38–42whereas the corresponding treatments may rectify such derangements.43Experimental data suggests that the extent of such derangements may correlate with the magnitude of oxidative stress.44General anesthesia results in a decrease in Vo²through reductions in general motor activity, work of breathing, neuronal activity, and body temperature. These changes are the result of anesthesia itself as well as neuromuscular blockade and invasive ventilation.45–49Volatile anesthetic agents decrease the basal metabolic rate, with reductions in sympathetic tone and cardiac output being more pronounced at higher doses.50Intravenous hypnotics such as benzodiazepines appear to exert similar effects on metabolic demand by blunting the sympathetic neurohumoral response,51,52and intravenous anesthetic agents such as propofol similarly reduce metabolic demand, with the probable exception of ketamine, which usually increases myocardial inotropy by increasing general sympathetic activity.53,54Sympatheticolytic agents such as clonidine reduce perioperative Vo².55,56Reductions in neuronal oxygen consumption occur with the administration of volatile anesthetic agents, barbiturates, benzodiazepines, and propofol.57–61Opiates may similarly reduce perioperative Vo².62–65Neuraxial blockade has both sympatheticolytic and analgesic effects,66,67but we are unaware of reports specifically describing effects on Vo².

While the determinants of Scvo²and Svo²are very similar, the relationship between the two variables is complex and they cannot be used interchangeably.68–73Regional variations in the balance between Do²and Vo²result in differences in the hemoglobin saturation of blood in the superior and inferior vena cavae.74Streaming of caval blood continues within the right atrium and ventricle and complete mixing only occurs during ventricular contraction. The drainage of myocardial venous blood directly into the right atrium via  the coronary sinus and cardiac chambers via  the Thebesian veins results in further discrepancies.16Consequently, Svo²reflects the balance between oxygen supply and demand averaged across the entire body but Scvo²is affected disproportionately by changes in the upper body.74In healthy individuals, Scvo²is usually 2–5% less than Svo²,16largely because of the high oxygen content of effluent venous blood from the kidneys.22This relationship changes during periods of hemodynamic instability because blood is redistributed to the upper body at the expense of the splanchnic and renal circulations.75In shock states, therefore, the observed relationship between Scvo²and Svo²may reverse, and the absolute value of Scvo²may exceed that of Svo²by up to 20%.73This lack of numerical equivalence has been demonstrated in various groups of critically ill patients, including those with cardiogenic, septic and hemorrhagic shock.31,68–70,76–78This has also been demonstrated in patients undergoing general anesthesia for cardiac71,72,79and noncardiac surgery.69,80Although trends in Scvo²may closely reflect those of Svo², absolute values differ and the variables cannot be used interchangeably.68–72This observation is sometimes cited in support of continued use of the pulmonary artery catheter. However, there is no evidence to suggest one variable is of greater clinical value than the other. As the use of the pulmonary artery catheter declines, measurement of Scvo²is usually more convenient than Svo², although Scvo²measurements cannot be cannot be used to calculate Vo²or shunt fraction.72 

Cardiac catheterization was first performed in 1929 by Werner Forssmann, a major advance that allowed the measurement of Svo²and hence application of Fick’s principle to measure cardiac output.81,82However, it was not until 1970 that the introduction of the balloon-tipped pulmonary artery catheter facilitated the routine clinical measurement of Svo².81Reports of the clinical utility of Scvo²predate those of Svo²by several years.29,33Measurement of venous saturation may be performed either intermittently by blood sampling and cooximetry or continuously through the use of a spectrophotometric catheter.

Cooximetry involves the measurement of hemoglobin saturation by spectrophotometry by using widely available blood gas analysis technology. The differences in light absorption spectra between oxygenated and deoxygenated hemoglobin allow calculation of the hemoglobin saturation of blood. This also allows the identification of other forms of hemoglobin such as methemoglobin and carboxyhemoglobin. Cooximetry is a reliable and well-established technique. However, in clinical practice it may be inconvenient to make frequent measurements by using this approach. Specific errors result from sample contamination, delayed measurement, and sampling from the incorrect site.83,84As with any form of venous oximetry, interpretation errors may arise due to intracardiac shunts, tricuspid regurgitation, and catheter misplacement.84When taking blood samples, syringe aspiration should be gentle enough to avoid high negative pressure that may increase the aspiration of pulmonary capillary blood and hence produce falsely high readings for oxygen saturation.

The introduction of optical fiber technology has allowed the continuous measurement of venous saturation by spectrophotometry using indwelling pulmonary artery or central venous catheters. The major benefit of this approach is the provision of continuous data allowing the detection of sudden fluctuations in venous saturation, which are common during the perioperative period.85,86The principle disadvantages of this technology are the additional cost and signal drift, although the latter can be addressed by recalibration. Advances in the technology have addressed the problem of interference from other optically active compounds such carboxyhemoglobin and bilirubin.

Abnormalities of venous saturation are common during and after major surgery and are associated with an increased incidence of postoperative complications.87–91Reductions in Scvo²and Svo²also have prognostic significance in heart failure, trauma, and sepsis.92–95These observations are no surprise, given the wide range of pathologic abnormalities that affect venous saturation in the perioperative period.87–89 

Two studies have been performed in noncardiac surgical patients with complementary findings. In the first observational study of 117 patients, the lowest recorded value of Scvo²in the early postoperative period was independently associated with subsequent complications, the optimal cut-off for the lowest Scvo²value being 64.4%.87Interestingly, a considerable decrease in Scvo²was observed within the first hour after surgery, possibly as a consequence of increased Vo²after the cessation of general anesthesia (fig. 3). In a further multicenter observational study of 60 patients, the mean value of Scvo²was found to be reduced at various time points throughout the perioperative period in patients who developed complications.88The optimal cutoff value in this study for the mean  Scvo²value was 73%. These investigations not only provide strong evidence to support the role of Scvo²as a therapeutic target, but they are also highly consistent in suggesting the most appropriate target value to be an Scvo²value of approximately 75%. However, these findings do not indicate how venous saturation should be used as a therapeutic goal. A range of factors influence Vo², Do², and therefore venous saturation during the perioperative period, not all of which are pathologic in nature. The most appropriate therapy to achieve a venous saturation endpoint may vary.

Alterations in Svo²have been described in patients undergoing cardio-thoracic surgery, although no reports of changes in Scvo²were identified.89–91Derangements in Svo²occur before any changes in mean arterial pressure or heart rate are observed,96and they appear to correlate well with changes in cardiac index.86Early work in patients undergoing both cardiac and pulmonary surgery demonstrated that sustained reductions in Svo²below 65% were associated with a higher incidence of complications, particularly arrhythmias.97Increases in oxygen extraction ratio, derived through measurement of Svo², have also been associated with postoperative organ failure and prolonged intensive care stay.90,91,98During lung transplantation, changes in Svo²reflected adverse clinical events, although this series is too small to support any more detailed conclusions.99During cardiopulmonary bypass, Svo²may prove a more specific indicator of global oxygen delivery; pump flow (or cardiac output) and metabolic rate are generally constant in these circumstances.100,101 

The effects of hypovolemia on venous saturation have been described in both animals and humans.73,102,103Fluctuations in Svo²and Scvo²closely mirror periods of hemorrhage and subsequent resuscitation in anesthetized dogs.73,102A case series of ten victims of mainly penetrating trauma described similar changes in Svo².103Venous saturation may provide a useful indication of the severity of blood loss that is more reliable than conventional cardiovascular variables such as heart rate and arterial and central venous pressure.102,103A single small case series describes the use of normal levels of Svo²as therapeutic target in trauma patients in which the authors suggest a survival benefit.104However, the study has a number of limitations, and the data do not appear to support such conclusions.

Our literature search identified only one interventional trial using Scvo²as a therapeutic goal in perioperative care.105This was a multicenter trial of 135 patients undergoing major abdominal (including aortic) surgery. All patients received fluid challenges, dobutamine up to 15 μg · kg⁻¹· min⁻¹and blood transfusions to achieve predefined goals for arterial pressure, urine output, and central venous pressure.105These same therapies were administered in the intervention group to achieve the additional goal of an estimated oxygen extraction ratio of less than 27%, the value of which was calculated using intermittent measurements of Scvo². Trial interventions were continued until an unspecified time on the first postoperative day. Dobutamine was administered more frequently and in greater doses to the Scvo²group (2.6 ± 4.0 μg · kg⁻¹· min⁻¹vs.  0.4 ± 2.2 μg · kg⁻¹· min⁻¹; P = 0.001). Volumes of intravenous fluid and transfused blood were similar in the two groups, although fluid challenges were commenced earlier stage in the Scvo²group. Fewer patients in the Scvo²group developed organ failure (8 of 68 patients [11.8%]vs.  20 of 67 patients [29.8%]; P < 0.05). The duration of hospital stay was also reduced in the Scvo²group (11.3 ± 3.8 days vs.  13.4 ± 6.1 days; P < 0.05), whereas mortality was low in both groups (2.9% vs.  3.0%; absolute values not reported). This was an important investigation with encouraging findings. However, there are some limitations that prevent full interpretation of the results. The report provides little information regarding the standardization of interventions that are frequent confounders in trials of this size. In particular, there is little or no description of those interventions likely to limit excessive Vo². These include anesthesia, analgesia, temperature maintenance, postoperative sedation, ventilation, and other aspects of postoperative critical care. It is unclear why the investigators chose to use estimated oxygen extraction ratio as a hemodynamic goal rather than absolute values of Scvo². Although this may reduce the effects of alveolar hypoxemia as a confounder, the use of Scvo²to calculate oxygen extraction ratio is considered unreliable.68,73,76,80,106In common with a number of similar trials, the small sample size limits the generalizability of the findings.11–13Although the multicenter design offsets this somewhat, much larger trials are clearly needed to resolve the question of effectiveness in routine clinical practice.

In an earlier study of patients undergoing peripheral vascular surgery, the use of Svo²as a therapeutic endpoint for inotropic therapy was not associated with any change in outcome.107Patients undergoing aortic reconstruction or limb salvage procedures were admitted to intensive care 12 hours preoperatively for pulmonary artery catheter placement. Initial values of Svo²were surprisingly low but responded significantly in the intervention group (59.1% to 68.8%). However, final Svo²values were similar in the two groups (70.0% vs.  70.1%) perhaps explaining the similar outcomes.

Polonen et al.  randomized 196 patients undergoing elective cardiac surgery to a protocol involving the administration of intravenous fluid and inotropic therapy to attain a target Svo²of at least 70% in the first 8 h after surgery.108Dobutamine was administered in doses of up to 15 μg · kg⁻¹· min⁻¹where the target Svo²was not achieved with intravenous fluid alone. Control group patients were administered intravenous fluid and dobutamine to meet goals for pulmonary artery occlusion pressure, cardiac index, arterial pressure, and hematocrit. Svo²was similar in the two groups at baseline (control group 67 ± 6% vs.  Svo²group 67 ± 6%), but there were greater improvements in Svo²in the Svo²group (control group 69 ± 5% vs.  Svo²group 71 ± 4%; P < 0.001). Svo²-guided therapy was associated with a reduction in both hospital stay (7 [5–8] days vs.  6 [5–7] days; P < 0.05) and the number of patients developing complications (11 patients [5.6%]vs.  2 patients [1.0%]; P < 0.01). It is uncertain whether such a small mean difference in Svo²of 2% is a true reflection of these improved clinical outcomes. In common with other trials, the intervention protocol principally targeted Svo²by increasing Do². In addition, the authors report measures in all patients that would have minimized excessive Vo². These include postoperative sedation and ventilation that was discontinued only when the patient was normothermic and hemodynamically stable. Hemodynamic therapy to attain a target value for Svo²is more appropriate in this context as confounding causes of decreased venous saturation are minimized. This treatment approach is possible after cardiac surgery where postoperative intensive care admission is a standard of care; this is not always the case for high-risk noncardiac surgery.2,3 

Scvo²and Svo²reflect important pathophysiological changes in oxygen delivery and consumption that occur during the perioperative period. The most appropriate clinical interventions to rectify abnormalities of venous saturation may therefore vary widely. Supplemental oxygen, respiratory support, blood products, intravenous fluid, inotropic therapy, anesthesia, analgesia, sedation, and rewarming are all commonly used perioperative interventions that affect venous oxygen saturation. Small clinical trials suggest that the use of venous saturation as a therapeutic goal for hemodynamic therapy may reduce postoperative complication rates. However, these studies are not large enough to demonstrate a mortality benefit and are poorly generalizable. Further research is required to establish the most appropriate treatment algorithms for the use of Scvo²and Svo²in perioperative care. Large, prospective, randomized control trials should then be undertaken to confirm the effects of such an approach on clinical outcomes.