Best Practice & Research Clinical Anaesthesiology 27 (2013) 201207

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Best Practice & Research Clinical Anaesthesiology

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The oxygen supplydemand balance: A monitoring challenge

Krisztin Tnczos, MD, Clinical Director of Neuro-trauma Intensive Care Unit, Zsolt Molnr, MD, PhD, Clinical Professor of Anaesthesiology and Critical Care, Head of Department *
Department of Anaesthesia and Intensive Therapy, University of Szeged, 6, Semmelweis St, 6725 Szeged, Hungary

Keywords: oxygen delivery oxygen consumption central venous oxygen saturation mixed venous oxygen saturation

The principal task of acute critical care is to avoid or correct oxygen debt by increasing oxygen delivery (DO2) and/or decreasing oxygen consumption (VO2). The most commonly used methods to assess the relationship of adequate delivery and consumption are mixed venous oxygen saturation and its surrogate, central venous oxygen saturation (ScvO2). The purpose of this article is to review the values and limitations of the two parameters and evaluate the clinical use of ScvO2 in certain clinical scenarios, such as anaemia and transfusion, hypovolaemia, major surgery, septic shock, and in difcult-to-wean patients. 2013 Elsevier Ltd. All rights reserved.

Oxygen is one of the major essentials required for sustaining life. The primary goal of the cardiorespiratory system is to deliver adequate oxygen to the tissues to meet their metabolic requirements. The adequacy of tissue oxygenation is determined by the balance between the rate of oxygen transport to the tissues (oxygen delivery, DO2) and the rate at which the oxygen is used by the tissues (oxygen consumption, VO2) [1]. Standard formulae to determine DO2 and VO2 are: DO2 [ SV HR Hb 1:34 SaO2 D 0:003 PaO2 [ CO CaO2 VO2 [ CO CaO2 L Hb 1:34 SvO2 D 0:003 PvO2 [ CO CaO2 L CvO2 where DO2 is oxygen delivery, SV is stroke volume, HR is heart rate, Hb is haemoglobin, SaO2 is Hb arterial oxygen saturation, PaO2 is arterial oxygen partial pressure, CO is cardiac output, CaO2 is arterial
* Corresponding author. Tel.: 36 62545168. E-mail addresses: tkrisztian78@gmail.com (K. Tnczos), zsoltmolna@gmail.com, z_molnar@hotmail.com (Z. Molnr). 1521-6896/$ see front matter 2013 Elsevier Ltd. All rights reserved. http://dx.doi.org/10.1016/j.bpa.2013.06.001

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oxygen content, VO2 is oxygen consumption, SvO2 is Hb mixed venous oxygen saturation, PvO2 is venous oxygen partial pressure and CvO2 is venous oxygen content. From the above formulae, DO2 at rest can be calculated: CO [ 70 ml 72=min [ 5 l minL1 CaO2 [ 150 g lL1 1:34 ml 1 D 0:003 100 mmHg [ 201:3 ml lL1 DO2 w 1000 ml minL1 VO2 at rest is: CvO2 [ 150 g lL1 1:34 ml 0:75 D 0:003 40 mmHg [ 150:87 VO2 [ 5 l minL1 201:3 ml lL1 L 150:87 ml lL1 w 250 ml minL1 OxygenextractionO2 ER [ VO2 =DO2 100250 ml minL1 =1000 ml minL1 100 [ 25% In the critically ill and in the perioperative period, there is often an imbalance between delivery and consumption. DO2 may be inadequate considering arterial oxygen content and/or CO may be reduced [2,3]. The circulation can compensate to some extent, but after a critical threshold severe oxygen debt and shock may occur [4]. The principal task of acute critical care is to avoid or correct oxygen debt by increasing DO2 and/or decreasing VO2. Furthermore, knowing when increasing DO2 has restored tissue perfusion and no further increase is necessary is an important question in order to avoid harm that can be caused by unnecessary over-resuscitation. Perhaps the most commonly used methods to assess global VO2 are SvO2 and its surrogate, central venous oxygen saturation (ScvO2). Mixed venous oxygen saturation Mixed venous sampling is performed by gentle aspiration of blood from the distal port of an unwedged pulmonary artery catheter (PAC). This ensures complete admixture of blood from superior and inferior venae cavae and the coronary sinus. SvO2 is measured either intermittently by co-oximetry on mixed venous samples or continuously by bre-optic reectance oximetry using a modied catheter. According to the above-specied physiological changes, measurement of SvO2 can be an indirect index of tissue oxygenation in the entire body [5]. However, the risk/benet of the placement of a PAC remains controversial. Several studies have reported no favourable impact on survival in patients with this type of catheter; hence, the use of the PAC has become somewhat unpopular [6,7]. By contrast, insertion of a central venous catheter in the superior vena cava via the internal jugular or the subclavian vein is considered standard care in critically ill patients. Similar to SvO2, the measurement of ScvO2 has been advocated in order to detect global tissue hypoxia [4]. Monitoring of ScvO2 may be therefore an attractive alternative to that of SvO2. Central venous oxygen saturation ScvO2 is an easily obtained parameter via the central venous catheter already in situ in most critically ill patients and it is often used as a marker of the balance between DO2 and VO2. Measurement of ScvO2 indicates the level of venous oxygenation of the brain and the upper part of the body. The normal value varies between 73% and 82% [8]. Because of the different level of measurement (entire body in the case of SvO2 4 brain and the upper part of the body with ScvO2), there has been considerable debate on the interpretation of ScvO2 values as compared to SvO2. Most of the studies that have analysed the relationship between ScvO2 and SvO2 have shown that ScvO2 is an average of 5% higher than SvO2 and is considered a reasonable surrogate marker in the clinical setting [911]. However, recent clinical trials, mainly on septic patients, were unable to show satisfactory agreement between ScvO2 and SvO2. This could in part be explained

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by modications of blood-ow distribution and oxygen extraction (O2ER) by brain and splanchnic tissues [12]. It appears that ScvO2 and SvO2 are not numerically equivalent but the variations in these two parameters usually occur in a parallel manner [13]. The main factors, which inuence ScvO2, are haemoglobin (Hb), SaO2, CO and VO2. Theoretically, if three of these factors are kept constant the value of ScvO2 reects the changes of the latter. There are multiple physiologic, pathologic and therapeutic factors which inuence venous oxygen saturation. These are summarised in Fig. 1[14]. One of the important features of venous saturation is that it can be pathologic when it is high and also when it is low. In a recent large cohort of septic patients in the emergency department, it was found that mortality was 40% in patients admitted with an ScvO2 <70% but it was almost as high, 34%, in patients with high initial ScvO2 of >90% [15]. Finally, one has to bear in mind that ScvO2 should be measured in the superior vena cava. In a heterogeneous patient population, it was found that there were very wide limits of agreement between ScvO2 measured in the superior vena cava as compared to results from the inferior vena cava; therefore, femoral venous oxygen saturation should not be used as a surrogate for ScvO2 [16]. The current place of ScvO2s in clinical practice ScvO2 as a transfusion trigger One of the most common causes of inadequate DO2 in the perioperative setting is anaemia requiring red blood cell transfusions [17]. It has recently been suggested that the Hb level should not be the only factor on which the indication of the need for transfusion is based [18,19]. According to the TRICC (Transfusion Requirements in Critical Care) trial, patients with Hb levels above 10 g dl1 require rarely transfusion while red blood cell donation is usually necessary if the Hb level is below 7 mg dl1 [20]. There is however a clear need for additional parameters in patients with Hb levels between 7 and 10 g dl1. Clinicians use different tools ranging from simple clinical signs (confusion, tachycardia, ST-segment elevation/depression and diuresis) to invasive haemodynamic measurements (ScvO2, O2ER and central venous-to-arterial carbon dioxide difference) in order to obtain information on anaemia-related altered O2ER and hence the need for blood administration [21]. One of the potentially useful physiological parameters is ScvO2. It was found during haemorrhage in animal and human experimental models that ScvO2 may be useful for the identication of patients with occult or ongoing clinically signicant blood loss [22,23]. In bleeding conditions, an ScvO2 value of w70% has been used as a goal to therapeutic intervention in attempts at improving DO2 [21]. In a

Fig. 1. Mixed venous saturations in the critically ill. SvO2, mixed venous saturation; ScvO2, central venous oxygen saturation; DO2, oxygen delivery; VO2, oxygen consumption. See text for explanation.

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prospective human interventional study, it was found that acute isovolaemic anaemia of Hb of 50 g l1 in conscious healthy resting humans did not produce haemodynamic instability, but oxygen imbalance was accompanied by a signicant drop in mixed venous saturation [24]. These results were reinforced by a retrospective analysis of a prospective observational study in which ScvO2 was found to be a good indicator of transfusion [25]. The results of our animal study on isovolaemic haemodilution gave further evidence that anaemia-induced change in oxygen balance can be monitored by ScvO2 [26]. According to the above-mentioned studies, it seems that ScvO2 better identies the point when compensatory mechanisms fail and DO2 begins to decline, as compared to the Hb concentration alone. A low level of Hb does not necessarily lead to oxygen debt in haemodynamically stable, anaesthetised, ventilated patients, while oxygen imbalance may occur in agitated, pyrexial patients with normal Hb level. These ndings are in accord with the idea that compensatory changes in CO and other parameters of DO2 make Hb concentration alone a less sensitive marker of oxygen balance and for the need for therapeutic intervention to increase DO2. ScvO2 could therefore be important in helping to avoid hypoxia and tissue injury under such circumstances, while helping to more accurately guide blood transfusions. Therefore, we believe that not only the Hb level but also ScvO2 and other physiological signs of oxygen debt (confusion, angina, low diuresis, serum lactate level, etc.) should be taken into account before using red blood cells in order to reduce the number of unnecessary transfusions. Protocolising transfusion and adopting protocols for every patient are therefore difcult, because of its multimodal features. Nevertheless, applying the above-mentioned approach of including physiological indicators of oxygen debt in the decision making may help us in individualising transfusion therapy. ScvO2 as an indicator of hypovolaemia A common cause for decreased CO in the intensive care unit (ICU) is hypovolaemia. Diagnosing hypovolaemia is an everyday challenge in critical care. Although diagnosis may prove difcult, early recognition of hypovolaemia is of utmost importance. By the time macro-haemodynamic changes manifest, the microcirculation may already be damaged [3]. Furthermore, on the one hand early uid resuscitation can save lives, but on the other hand a cumulative positive uid balance is an independent factor of mortality [27]. Up until now, there has been no consensus either on the most accurate haemodynamic indicator of hypovolaemia, or on the end points for optimal uid therapy [28,29]. Many recent studies have suggested that uid therapy should be based on dynamic (such as CO, pulse pressure variation and SV variation) rather than static haemodynamic variables (such as central venous pressure (CVP) and pulmonary artery occlusion pressure), because they are better predictors of uid responsiveness in ICU patients. However, pulse pressure variation and SV variation are limited to patients who are fully ventilated and have no arrhythmias [22,30]. Although it is not strictly a haemodynamic variable, in certain clinical conditions a ScvO2 value of w70% has been used as a therapeutic end point to improve DO2 [23]. In a recent study, it was found that a 4% increase in ScvO2 after uid challenge had >80% sensitivity and specicity in predicting volume responsiveness at the bedside in critically ill patients [31]. ScvO2 and major surgery As the two most common complications in the perioperative setting are bleeding/anaemia and hypovolaemia, it seems logical to assume that ScvO2 may be a good resuscitation end point during and after major surgery. In a single-centre study, patients in the ScvO2-directed therapy group had fewer postoperative complications and were hospitalised for shorter periods than the patients in the control group [32]. In a prospective, randomised controlled trial, a therapeutic strategy designed to detect and reverse tissue hypoxia (diagnosed by an increase of O2ER) was used after major abdominal surgery. The intervention group received therapy to maintain O2ER <27% after predened goals for arterial pressure, urine output and CVP had been achieved. Early treatment according to O2ER reduced organ failures and hospital stay [33].

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ScvO2 and severe sepsis/septic shock Global tissue hypoxia as a result of an overwhelming systemic inammatory response is a frequent and important complication of sepsis and may lead to multiple organ dysfunction syndrome [34]. Treatment strategies that are aimed at restoring tissue perfusion by improving the balance between DO2 and VO2 may prevent the development of organ dysfunction syndrome and thus improve the outcome of septic patients. Rivers and his colleagues reported that in patients with severe sepsis, early goal-directed intervention guided by continuous monitoring of ScvO2, CVP and mean arterial pressure (MAP) reduced mortality from 46.5% to 30.5% at the 28th day [35]. Several studies using early goaldirected therapy (EGDT) end points (CVP 812 mmHg, MAP 65 mmHg and ScvO2 70%) suggest that this multimodal approach is a useful strategy in the treatment of sepsis [36,37]. However, the EGDT-based protocol aiming at correcting low ScvO2 levels through a titrated resuscitation has recently been criticised. Recent data suggest that patients with initially high ScvO2 values may also have adverse outcomes [15,38], probably due to impaired oxygen utilisation. High ScvO2 values may thus represent an inability of the cells to extract oxygen or microcirculatory shunting in sepsis [39]. Therefore, additional measures are necessary to help evaluate high ScvO2 values, such as central venous-toarterial CO2 gap, or by applying advanced invasive haemodynamic monitoring. Discussing these issues is beyond the scope of this article. ScvO2 in difcult-to-wean patients During the weaning procedure, the increased respiratory workload (due to the increased respiratory muscle oxygen consumption) may lead to an imbalance between DO2 and VO2. The consequential low ScvO2 can indicate the exhaustion of the patient and thus may predict extubation failure. The aim of a multicentre, clinical study performed in three medicalsurgical ICUs was to evaluate the predictive value of ScvO2 to detect extubation failure in difcult-to-wean patients. A signicant lower central venous saturation was found during the spontaneous breathing trial in patients with extubation failure. According to this trial, ScvO2 may be a valuable parameter to be included in weaning protocols of difcult-to-wean patients and may also serve as a useful tool to assist the weaning process in mechanically ventilated patients [40]. Summary Avoiding and treating oxygen debt in critically ill patients is without doubt one of the most important tasks of our work. Unfortunately, there is no gold standard for the assessment of oxygen debt. Although ScvO2 is not a perfect surrogate of SvO2, it is easy to measure and can be of great value in several clinical settings. Interpretation of ScvO2 may be more complicated when its value is high, which may require its evaluation together with other measures of anaerobic metabolism and might also be an indication for advanced haemodynamic monitoring. Nevertheless, it can be measured easily and quickly and can be an early warning sign of oxygen debt; therefore, its routine measurement should be included in our everyday practice. Practice points     ScvO2 correlates well with oxygen demand/supply (VO2/DO2). Low values mean impaired DO2. Low values may help in decision-making in transfusion and uid therapy. High values should be taken seriously in septic shock and may necessitate the commencement of invasive haemodynamic monitoring.  Dynamic changes in ScvO2 (i.e., during a spontaneous breathing trial) may refer to the patients reserves.

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Research agenda  In haemodynamically stable brain-injured patients, the role of ScvO2 in monitoring the severity of brain damage and as a prognostic factor has rationale, but very limited data are available.  The relationship between high ScvO2 and measures of anaerobic metabolism (such as venous-to-arterial CO2-gap, lactate, etc.) should be studied further.  <XS_FFU> The dynamic changes of ScvO2 during increased oxygen demand (such as weaning, mobilisation, etc.) as a measure of the patients DO2 reserves are another very interesting eld that deserves further studies.  The value of the continuous measurement of ScvO2 in certain clinical scenarios such as highrisk surgery and suspected bleeding (gastrointestinal, postoperative, etc.) should also be investigated in clinical trials.

Conict of interest None. References

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