EUROANESTHESIA 2008 Copenhagen, Denmark, 31 May - 3 June 2008 CENTRAL VENOUS OXYGEN SATURATION (SCVO 2 ): INTEREST AND LIMITATIONS

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1 EUROANESTHESIA 2008 Copenhagen, Denmark, 31 May - 3 June 2008 CENTRAL VENOUS OXYGEN SATURATION (SCVO 2 ): INTEREST AND LIMITATIONS 12RC2 SHAHZAD SHAEFI 1 RUPERT M. PEARSE 2 1 Department of Anesthesia and Critical Care, Harvard Medical School, Boston, USA 2 Intensive Care Unit, Royal London Hospital, London, UK Saturday, May 31, :00-14:45 Room C1-M3 Central venous oxygen saturation (ScvO 2 ) is the term used to describe the haemoglobin saturation of blood in the superior vena cava. Mixed venous saturation (SvO 2 ) is a related value describing the saturation of blood in the proximal pulmonary artery. The earliest clinical report of the use of ScvO 2 data was in the clinical assessment of cardiogenic shock in patients admitted to hospital following myocardial infarction [1]. Since that time various authors have utilised ScvO 2 and SvO 2 as therapeutic goals in clinical trials, initially without success. More recently, however, improved understanding of the clinical relevance of ScvO 2 data has enabled its use in protocols which have resulted in significant improvements in outcome [2]. As a result there is renewed interest in the use of ScvO 2 during periods of critical illness as well as following major surgery. As with all forms of clinical monitoring, it is essential to grasp the physiological basis for the use of ScvO 2 in order to ensure any changes in treatment are appropriate. The aim of this refresher course lecture is to give an account of the physiology of ScvO 2 and explain both the strengths and limitations of the use of this variable in clinical practice. MEASUREMENT OF SCVO 2 The saturation of blood haemoglobin with oxygen is measured by spectrophotometry, either by intermittent blood sampling and blood gas analysis or continuously by an indwelling fibreoptic catheter. The main benefits of this technique are that it is a comparatively simple and less invasive than alternative forms of monitoring. ScvO 2 measurement by intermittent blood sampling is more economical although this approach will fail to identify any fluctuations between measurements which may be of clinical relevance. The main sources of measurement error are catheter malposition, use of diluted or unhomogenised blood samples, or artefact which arises when a fibreoptic catheter is in contact with the vessel wall. PHYSIOLOGY OF SCVO 2 The determinants of the oxygen content of venous blood are the delivery of oxygen to the tissues (DO 2 ) and its consumption by the tissues (VO 2 ). DO 2 is determined by the oxygen content in arterial blood and cardiac output (CO), whilst VO 2 is affected by a range of factors which relate to tissue respiration (see Table 1). This relationship may be expressed by re-arranging the Fick equation: CvO 2 = CaO 2 VO 2 /CO where CvO 2 and CaO 2 are the oxygen contents in venous and arterial blood. These oxygen contents are determined by the concentration of oxygenated haemoglobin in the blood and its dissolved oxygen content. At standard atmospheric pressure, the quantity of dissolved oxygen is very small and it is acceptable and more convenient simply to measure haemoglobin saturation. The normal value of ScvO 2 has been given as 70% [3]. However, there is little published data describing the normal value. It is more logical to assume a normal range for ScvO 2, rather than one discrete value. The available data suggest ScvO 2 varies between 70% and 80% in healthy subjects. However, values below 65% are not unusual amongst hospital in-patients who are not critically ill. The value of ScvO 2 will reflect the physiology of the entire body and should be regarded as a global indicator of the balance between tissue oxygen delivery and consumption. It is also important to realise that a global measurement of this kind may fail to detect significant regional abnormalities. An important consequence of regional differences in VO 2 and DO 2 is the effect on venous saturation in different sites. The choice of sampling site will, therefore, have a significant effect on the measured value of ScvO 2. In health, blood in the inferior vena cava has a high oxygen content because the kidneys do not utilise much oxygen but receive a high proportion of cardiac output. As a result, inferior vena caval blood has a higher oxygen content than blood from the upper body. In shock states, blood flow to the splanchnic and renal circulations falls, whilst flow to the heart and brain is maintained. This results in a fall in the oxygen content of blood in the inferior vena cava. Venous saturation differs between sampling sites and the magnitude of this

2 difference will be affected by the presence and degree of circulatory shock. ScvO 2 should therefore only be measured using a catheter with its tip sited in the superior vena cava. Measurement of ScvO 2 using a femoral venous catheter is very unreliable and not recommended. Similarly, ScvO 2 cannot be used for the calculation of intra-pulmonary shunt (Qs/Qt) or VO 2. Only SvO 2 can be reliably used for this purpose. TABLE 1. FACTORS INFLUENCING MIXED AND CENTRAL VENOUS SATURATION THE EFFECT OF ACUTE ILLNESS AND TREATMENT ON SCVO 2 BLOOD OXYGEN CONTENT (CAO 2 ) Alveolar hypoxia and inspired oxygen concentration (FiO 2 ) Alveolar hypoxia and changes in FiO 2 will have important effects on blood oxygen partial pressure and, therefore, the value of ScvO 2 and must be considered when interpreting data. As might be predicted from the shape of the oxyhaemoglobin dissociation curve, decreased blood oxygen content will have a more profound effect on ScvO 2 than SaO 2. At high partial pressures, an increase in PO 2 will produce only a small increase in haemoglobin saturation. However, at lower partial pressures, considerable increases in saturation will occur because oxygen molecules will bind more readily to deoxygenated haemoglobin. This is illustrated by the sigmoid shape of the oxyhaemoglobin dissociation curve (see Figure 1). Consequently, an increase in PO 2 has a much greater effect on haemoglobin saturation of venous blood in the range of 50% - 75% than arterial blood saturating in the range of % [4]. FIGURE 1 Oxyhaemoglobin dissociation curve: in well oxygenated arterial blood, a change in PO 2 may have a small effect on SaO 2, while in venous blood the same change PO 2 may result in large variations in ScvO

3 Haemoglobin concentration Changes in haemoglobin concentration would also be expected to affect venous saturation through a reduction in blood oxygen content and, therefore, DO 2. Studies have demonstrated considerable reductions in ScvO 2 during haemorrhagic shock [5], although to what extent this relates to a reduced cardiac output in addition to reduced oxygen carrying capacity is unclear. In a study of major trauma victims, a value of ScvO 2 < 65% was not only a useful indicator of severity of blood loss but proved more reliable than conventional observations (heart rate, blood pressure, central venous pressure) [6]. However, blood transfusion may not immediately restore oxygen carrying capacity because red cell function in stored blood may be impaired by a number of mechanisms. CARDIAC OUTPUT AND TISSUE PERFUSION Changes in cardiac output (CO) will result in changes in ScvO 2. In clinical practice, reductions in cardiac output are common and produce decreases in ScvO 2 which may be marked. The most important causes of decreased cardiac output are hypovolaemia and cardiac failure, although orthostatic hypotension may result in reductions in ScvO 2 with the onset of pre-syncopal symptoms [7]. Similarly, the changes in ScvO 2 in response to fluid resuscitation and inotropic therapy may provide a valuable treatment end-point. One of the earliest descriptions of ScvO 2 measurement was reported by Goldman in 1968 in patients with myocardial infarction [1]. Derangements in ScvO 2 correlated with the severity of myocardial dysfunction and subsequent response to treatment. While a 60% threshold identified a number of patients suffering from occult heart failure, reductions in ScvO 2 to below 45% were generally associated with cardiogenic shock. Recent work has identified derangements in microvascular perfusion during the peri-operative period and periods of critical illness. These changes result in heterogeneity of microvascular flow whereby some capillaries remain unperfused while increased blood flow in others results in oxygen shunting through the microcirculation and, therefore, impaired utilisation. This will result in a pathological increase in venous saturation although this phenomenon generally co-exists with other pathophysiological processes which decrease ScvO 2. As a consequence, the ScvO 2 related effects of poor microvascular perfusion may be masked by good systemic oxygen delivery or offset by reductions resulting from poor DO 2. Similar difficulties arise with the interpretation of the effects of cytopathic hypoxia (see below). OXYGEN CONSUMPTION (VO 2 ) Changing motor activity is an obvious cause of changes in oxygen consumption which may be reflected in a deceased ScvO 2. Perhaps the most important example of this is the increased work of breathing in a patient with respiratory failure. Other common causes include shivering, seizures and chest physiotherapy all of which may result in very significant increases in VO 2. Similarly, clinical interventions may result in significant decreases in VO 2 and, therefore, increases in ScvO 2. These include invasive and non-invasive ventilation and muscle relaxants; changes in conscious level are also likely to be of great importance. General anaesthesia, sedation and analgesia may substantially decrease VO 2 with a consequent increase in ScvO 2. Conversely, increases in VO 2 associated with delirium and agitation would be expected to result in a decrease in ScvO 2 which would have prognostic significance. Finally, cytopathic hypoxia (derangements in cellular respiration) due to sepsis or poisoning may also result in pathological increases in ScvO 2. SCVO 2 IN CLINICAL PRACTICE SEPSIS In the most important study in this field to date, Rivers and colleagues utilised ScvO 2 to guide cardiovascular management in early severe sepsis and septic shock [2]. Patients were randomised to receive either 6 h of standard care, or fluid and inotropic support to achieve a target for ScvO 2 of 70% (goal-directed therapy). As a result, in-hospital mortality was reduced from 47% in the control group to 31% in the intervention group (RR 0.58 ( ); p=0.009). The authors attribute this outcome improvement to a substantial reduction in episodes of sudden cardiovascular collapse. Immediately following the trial period, patients receiving goaldirected therapy had higher mean ScvO 2, lower serum lactate and lower mean APACHE II scores indicating less severe organ dysfunction. In this case, the treatment algorithm focused on optimal haemodynamic resuscitation utilizing ScvO 2 as a treatment end-point. However, the algorithm also emphasized aspects of routine treatment in both intervention and control groups. Such measures included sedation and invasive ventilation which will have contributed to a reduction in VO 2. Although the difference in care between the groups primarily related to haemodynamic therapy, the control of excessive VO 2 was also an integral aspect of the care of those patients

4 MIXED GROUPS OF CRITICALLY ILL PATIENTS In an observational study of 98 consecutive unplanned admissions to ICU, patients with an ScvO 2 < 60% at admission had higher mortality, but changes in ScvO 2 during the first 6 h were not predictive of length of hospital stay or mortality [8]. However, there are no reports describing the use of ScvO 2 to guide clinical interventions in this population. The efficacy of ScvO 2 -guided treatment in septic patients is likely to relate to improved early resuscitation of hypovolaemia. The wider use of ScvO 2 -guided therapy in unselected critically ill patients late in their presentation is unlikely to alter outcome. The causes of ScvO 2 derangements in this population will be diverse and a simplified treatment protocol may not address every pathological cause of decreased (or increased) ScvO 2. Evidence from a large multi-centre trial in which SvO 2 -guided haemodynamic therapy did not alter outcome supports this argument [9]. THE PERI-OPERATIVE PERIOD Two studies report significant reductions in ScvO 2 following major non-cardiac surgery [10, 11]. In the first of these, the lowest measured value of ScvO 2 in each patient was independently associated with postoperative complications (OR 0.94 [ ]; p=0.007), with an optimal cut-off value of 64.4% for prediction of complications [10]. The mean ScvO 2 of patients who did not develop postoperative complications was 75%. Interestingly, significant postoperative fluctuations in ScvO 2 occurred even when cardiac output and DO 2 remained unchanged, suggesting that clinically significant reductions in ScvO 2 were also associated with increased VO 2. A subsequent multi-centre observational study confirmed the finding that reductions in ScvO 2 are associated with increased postoperative complication rates [11]. Similarly, the optimal mean ScvO 2 value to discriminate between patients who did or did not develop complications was 73%. Although of great interest, these studies do not show that specific interventions to increase ScvO 2 will improve outcome. Further interventional trials are required before the routine peri-operative use of ScvO 2 as a treatment end-point can be recommended. This suggestion is supported by the inconsistent findings of interventional trials utilising mixed venous saturation (SvO 2 ) as a haemodynamic goal. In cardiac surgical patients postoperative haemodynamic therapy to achieve a target for SvO 2 of 70% was associated a decreased incidence of postoperative complications and the duration of hospital stay [12]. However, in peripheral vascular surgery, a pre- and postoperative goal directed haemodynamic therapy protocol designed to achieve an SvO 2 of 65% did not alter outcome despite a greater increase in SvO 2 in the intervention group [13]. TRAUMA Reductions in ScvO 2 associated with haemorrhage have been described in both animal and human studies. In animal studies, fluctuations in ScvO 2 mirror periods of haemorrhage and subsequent resuscitation. ScvO 2 may, therefore, have a role in the evaluation of patients with traumatic shock when conventional clinical data can be unreliable. However, in clinical studies, the correlation between ScvO 2 and the extent of blood loss is weaker than in experimental studies. At present there are no clinical trials of ScvO 2 -guided interventions in trauma patients and use as a treatment end-point in this population is not currently recommended. CONCLUSION When used appropriately, measurement of ScvO 2 may provide a valuable indication of disease severity and response to treatment. ScvO 2 monitoring is convenient as it is cheaper and less invasive than SvO 2 or cardiac output measurement. However, whilst cardiac output is an important determinant of ScvO 2, factors which influence VO 2 should be given equal emphasis when this parameter is used in clinical practice. Factors such as agitation, shivering, pain and increased work of breathing may all result in significant reductions in ScvO 2 whilst interventions including invasive ventilation, anaesthesia and sedation may have the opposite eff e c t. Determinants of blood oxygen content, in particular FiO 2, may also hamper interpretation of ScvO 2 data. Whilst the absolute value of ScvO 2 may not be as important as the trend in response to treatment, this parameter should only be measured using a catheter with the tip located in the superior vena cava

5 KEY LEARNING POINTS Central venous saturation (ScvO 2 ) may be a useful tool in clinical practice ScvO 2 may be measured by intermittent blood sampling and blood gas analysis or continuously using a spectrophotometric catheter The value of ScvO 2 is affected as much by oxygen consumption as oxygen delivery Studies show that derangements in ScvO 2 have prognostic significance in the critically ill and following major surgery More research is needed to inform the use of ScvO 2 as a treatment goal REFERENCES 1. Goldman RH, Klughaupt M, Metcalf T, et al. Measurement of central venous oxygen saturation in patients with myocardial infarction. Circulation 1968; 38: Rivers E, Nguyen B, Havstad S, et al. Early goal-directed therapy in the treatment of severe sepsis and septic shock. New Engl J Med 2001; 345: Morgan T, Venkatesh B. Monitoring oxygenation. In: Oh s Intensive Care Manual, 5 th edn. Bersten A, Soni N, Oh T, eds. London: Butterworth-Heinemann, 2003: Ho K, Harding R, Chamberlain J. The impact of arterial oxygen tension on venous saturation in circulatory failure. Shock 2008; 29: Reinhart K, Rudolph T, Bredle DL, et al. Comparison of central-venous to mixed-venous oxygen saturation during changes in oxygen supply/demand. Chest 1989; 95: Scalea TM, Hartnett R, Duncan A, et al. Central venous oxygen saturation: a useful clinical tool in trauma patients. J Trauma 1990; 30: Madsen P, Iversen H, Secher NH. Central venous oxygen saturation during hypovolaemic shock in humans. Scan J Clin Lab Invest 1993; 53: Bracht H, Hänggi M, Jeker B, et al. Incidence of low central venous oxygen saturation during unplanned admissions in a multidisciplinary intensive care unit: an observational study. Critical Care 2007; 11: R2. 9. Gattanoni L, Brazzi L, Pelosi P, et al. A trial of goal-orientated hemodynamic therapy in critically ill patients. SvO2 Collaborative Group. New Engl J Med 1995; 333: Pearse RM, Dawson D, Fawcett J, et al. Changes in central venous saturation after major surgery, and association with outcome. Crit Care 2005; 9: R Collaborative Study Group on Perioperative ScvO2 Monitoring. Multicentre study on peri- and postoperative central venous oxygen saturation in high-risk surgical patients. Crit Care 2006; 10: R Polonen P, Ruokonen E, Hippelainen M, Poyhonen M, Takala J. A prospective, randomized study of goal-oriented hemodynamic therapy in cardiac surgical patients. Anesth Analg 2000; 90: Ziegler DW, Wright JG, Choban PS, Flancbaum L. A prospective randomized trial of preoperative optimization of cardiac function in patients undergoing elective peripheral vascular surgery. Surgery 1997; 122: