Several randomised controlled clinical studies have shown improved morbidity and mortality in high-risk surgical patients with perioperative optimisation of haemodynamics using strict treatment protocols in the single-centre setting 123. The haemodynamic endpoints in goal-directed studies have been based on values derived from the pulmonary artery catheter 1234, oesophageal Doppler 5678910, or (very recently) lithium indicator dilution and pulse power analysis 11. Central venous oxygen saturation (ScvO₂) and mixed venous oxygen saturation (SvO₂) have been proposed to be indicators of the oxygen supply/demand relationship. However, the relationship between SvO₂ and ScvO₂ remains controversial 12. Venous oxygen saturations differ among organ systems because different organs extract different amounts of oxygen. It is therefore conceivable that venous oxygen saturation depends on the site of measurement 13. Redistribution of blood flow and alterations in regional oxygen demand (for example, in shock, severe head injury, general anaesthesia, as well as microcirculatory disorders) may affect the difference between ScvO₂ and SvO₂. Although ScvO₂ principally reflects the relationship of oxygen supply and demand, mainly from the brain and the upper part of the body 13, it correlates reasonably well with concomitantly measured SvO₂ 1213, which is more dependent on changes in oxygen extraction in the gastrointestinal tract.

In patients with severe sepsis and septic shock, early ScvO₂-driven haemodynamic treatment was found to reduce mortality 14. More recently, low postoperative ScvO₂ values were associated with an increased risk of complications in high-risk surgical patients 11. Despite increasing evidence of beneficial effects on outcome, goal-directed therapies are not widely used in clinical practice. The reasons are a lack of demonstrated effect in large multicentre studies, the need for postoperative intensive care resources, the necessity of instituting complex protocols, as well as the need for monitoring techniques that are not routinely used in these specific patient groups. Using the ScvO₂ as a potential target variable for haemodynamic optimisation is attractive because central venous catheterisation is routinely used in high-risk patients undergoing major surgery, ScvO₂ can be screened, pre-emptive treatment is possible, and no major changes are necessary for the infrastructure in the operation area.

The present investigation was a pilot study designed to assess the incidence of low perioperative ScvO₂ in high-risk surgical patients and the association of low ScvO₂ with outcome in a multicentre setting. The aim was to evaluate whether the association of ScvO₂ and postoperative complications in a strictly protocolised, interventional single-centre study on goal-directed haemodynamic management in high-risk surgical patients 11 could be confirmed in a purely observational, multicentre setting. Specifically, this pilot study was designed to clarify (a) the recruitment rate of patients scheduled for major surgery in a multicentre setting, (b) the range of perioperative ScvO₂ in such patients, (c) the number of postoperative complications, and (d) the potential association between ScvO₂ and complications. With these data, it should be possible to define whether a trial with goal-directed therapy using ScvO₂ as a target is reasonable to conduct.

Two university hospitals in Finland and one in Switzerland participated in the study. The study was approved by the appropriate ethics committee for each institution, and written informed consent was obtained from each patient. Patients were screened for inclusion and exclusion criteria between September 20 and December 20, 2004.

Of 218 screened patients, 60 patients fulfilled requirements for both inclusion and exclusion criteria and gave written informed consent (21 females, 39 males). Their mean age was 72 ± 10 years, and simplified acute physiology score (SAPS II) was 32 ± 12. In two centres, all patients were elective surgical cases, whereas in the third centre, 12 out of 21 patients were emergencies. Demographics and outcome data as well as indications for laparatomy stratified for the three centres are indicated in Table 1. Mean SAPS II scores in the three centres were 30, 26, and 40, respectively, and the associated mortality rates were 0%, 6%, and 24%, respectively.

As compared with preoperative values, ScvO₂ was lower immediately after surgery. Haemoglobin decreased (preoperative 110 ± 19 g/l versus 102 ± 17 g/l immediately after surgery, p = 0.003).

Overall length of stay in the ICU/HDC was 1.0 (0 to 1) days, and hospital LOS was 10.5 (8 to 14) days (observation period 28 days). Six patients died (28-day mortality 10%); three of them were emergency cases (28-day mortality in emergency cases 25%).

Sixty-seven postoperative complications were recorded in 32 patients (20 cardiorespiratory, 23 surgical, 19 infectious, and 5 other; between 1.0 and 1.3 per patient per centre). Univariate analysis identified nine variables associated with postoperative complications (Table 2). Six of them were ScvO₂ variables (Figure 1a,b). Additionally, haemoglobin (111 ± 18 versus 105 ± 23 g/l, p = 0.018), SAPS II (27 ± 11 versus 45 ± 26, p = 0.003), and hospital LOS (10 [8 to 12] versus 14 [10 to 17] days, p = 0.001) were associated with postoperative complications.

After multivariate analysis, mean ScvO₂ value (OR 1.23 [95% CI 1.01 to 1.50], p = 0.037), hospital LOS (OR 0.75 [95% CI 0.59 to 0.94], p = 0.012), and SAPS II (OR 0.90 [95% CI 0.82 to 0.99], p = 0.029) were independently associated with postoperative complications. ROC curves for these variables are displayed in Figure 2. The areas under the ScvO₂ and SAPS II, but not LOS, ROC curves were significantly different from 0.5 (p = 0.004 and 0.002, respectively). The optimal value of mean ScvO₂ for discriminating between patients who did or did not develop complications was 73% (sensitivity 72%, specificity 61%). The relation between ScvO₂ and hospital LOS in survivors and non-survivors is displayed in Figure 3.

The main finding of this study was that in the multicentre setting, low ScvO₂ during the peri- and postoperative period was associated with an increased risk of postoperative complications in high-risk patients undergoing major surgery. Our results support the feasibility of testing ScvO₂ as a target variable to improve outcome in high-risk surgery. The criteria to define patients at high risk were pragmatic and clinically oriented and resulted in a sufficient recruitment rate. Furthermore, despite the relative heterogeneity of the patient population, ScvO₂ had a reasonable predictive value for postoperative complications.

Pearse et al. 11 found that low minimum ScvO₂ values during the first eight postoperative hours were associated with increased risk of postoperative complications. Their findings come from a strictly protocolised, interventional single-centre study on goal-directed haemodynamic management in high-risk surgical patients. Our results further confirm the association between ScvO₂ and postoperative complications in a purely observational, multicentre setting. Furthermore, intraoperatively, we were able to demonstrate a significant difference in ScvO₂ between patients who did and did not develop complications. Taken together, the present study and that of Pearse et al. suggest that the overall peri- and postoperative course of ScvO₂ should be taken into account if ScvO₂-targeted interventions are considered for testing in large-scale clinical trials.

Despite the relative similarity of the participating centres and the presence of comparable infrastructures for postoperative care, the hospital LOS varied widely between the centres. The reason for this is certainly multifactorial and likely to include, among other things, care processes within the individual centres, discharge policies, and variations in local health care organisation. These variations were likely to dilute any association between ScvO₂ and length of stay in the relatively small sample size. Hence, we used clinically relevant predefined complications as the main outcome measure. The hospital mortality in the present study was comparable with the recent study of Pearse et al. 11 and clearly lower than what would be expected from several previous studies on high-risk surgery. Due to the small sample size and different proportions of emergency patients, relevant between-centre comparisons cannot be made.

The prognostic significance of ScvO₂ less than 65% has been demonstrated in myocardial infarction 15, trauma 16, severe sepsis 17, and cardiac failure 18. However, the only interventional trial of ScvO₂ conducted so far used a target of 70% 14. In the study of Pearse et al. 11, a level of 65% seemed to discriminate best between patients with and without complications. This may be related to the lower tissue oxygen delivery in surgical patients as compared with patients with sepsis. Despite complex physiology, the association between ScvO₂ and outcome after major surgery seems to be similar to the association between cardiac index and outcome or between oxygen delivery and outcome 19202122.

The best cutoff for ScvO₂ in predicting complications in our study was 73%. This corresponds well with the mean ScvO₂ of 75% found by Pearse et al. 11 in patients who did not develop complications. The observed cutoff value of ScvO₂ should be interpreted with some caution due to the sample size. Nevertheless, the somewhat higher best cutoff of ScvO₂ for predicting complications in our study could be related to the fact that our study was observational, whereas Pearse et al. used protocolised treatment. When using protocols, the fluctuation in ScvO₂ is likely to be reduced. This may also explain why in our study the mean ScvO₂, rather than the minimum ScvO₂, had predictive value.

In our study, the perioperative mean of ScvO₂ was 74% in patients who did not develop postoperative complications. This is comparable with previous measurements in healthy subjects 23 and in patients after surgery 1122 but is higher than in patients with favourable outcome after severe sepsis, trauma, cardiac failure, or myocardial infarction 15161718. Accordingly, targets for ScvO₂ in future prospective trials should probably be adapted to the specific study groups.

We believe that our results encourage trials with goal-directed therapy using ScvO₂ as a target in high-risk surgery patients. Based on our data and in agreement with results from others 11, target values should be in the range of 70% to 75%, and values less than 65% should be strictly avoided. In patients with cardiac failure or trauma, lower targets (at approximately 65%) may be appropriate 1516.

Obviously, in a multicentre approach, the inclusion of 60 patients with an observed 28-day mortality of 10% is enough to be able to demonstrate a benefit in terms of complication rate but not in terms of length of stay and mortality. To demonstrate a relative reduction in 28-day mortality of 34% (as in the study of Rivers et al. 14, with a beta error of 80% and an alpha error of 5%, the sample size in a patient group similar to that in this study would be 85 for both groups. Although the risk factors for postoperative complications agree well with previous studies, the small sample size for the multivariate analysis should be considered in interpreting our results.

Because oxygen demands are normally well controlled during general anaesthesia, efforts to increase ScvO₂ should target oxygen delivery (arterial oxygen saturation, haemoglobin, and cardiac output). In fact, in this trial, preoperative haemoglobin concentrations were significantly lower in patients with complications as compared with patients without. To avoid sudden drops in ScvO₂ as a consequence of the combination of hypovolaemia and anaemia during surgical bleeding, it may be prudent to correct low (<10 g/dl) preoperative haemoglobin concentrations.

A drop in ScvO₂ was noted between the end of surgery and the first readings in the ICU. This finding is consistent with previous findings on ScvO₂ 11 and SvO₂ 1921 in surgical patients. Both decreased systemic oxygen delivery and increased oxygen consumption may have contributed. Pearse et al. 11 reported unchanged cardiac output in the postoperative period. If this was the same in our patients, oxygen delivery still could have decreased due to the significantly lower postoperative haemoglobin concentrations. Postoperative oxygen consumption is determined by various factors, including pain, emergence from anaesthesia, body temperature, and shivering. To avoid low postoperative ScvO₂, all of these factors may have to be controlled.

In our study, low ScvO₂ was frequently observed in patients during and after major surgery and was related to postoperative complications. In prospective trials using ScvO₂ as a goal, the specific patient group has to be taken into account when target levels are defined.

• Low ScvO₂ perioperatively is related to increased risk of postoperative complications in high-risk surgery.

• Trials with goal-directed therapy using ScvO₂ as a target in high-risk surgery patients are warranted.

HDC = high-dependency care; ICU = intensive care unit; LOS = length of stay; OR = odds ratio; ROC = receiver operator characteristic; SAPS II = simplified acute physiology score; ScvO₂ = central venous oxygen saturation; SvO₂ = mixed venous oxygen saturation.

The authors declare that they have no competing interests. No author received individual funding in connection with this study.

HB performed programming of databases for all centres, data acquisition, data analysis, calculation of statistics and manuscript revision. VE, DI, SL, IP, CR, and AV provided data acquisition and manuscript revision. MH carried out data acquisition and interpretation and manuscript revision. SMJ participated in the study design and coordination, performed the measurements, and wrote a first draft of the manuscript. HL and SN recruited patients, performed data acquisition, data analysis and interpretation, and manuscript revision. KM and PM carried out patient recruitment, data acquisition, and manuscript revision. MN and ER performed data interpretation and manuscript revision. JT provided study conception and design, data interpretation, and manuscript revision. All authors were given the opportunity to read and approve the final manuscript.

The Collaborative Study Group on Perioperative ScvO₂ Monitoring is composed of authors from three centres:

Bern:

Hendrik Bracht¹, Verena Eigenmann², Matthias Haenggi¹, Daniel Inderbitzin³, Stephan M Jakob¹ (co-principal investigator), Stefanie Loher¹, Christine Raeber¹, Jukka Takala¹ (coordinating investigator), Andreas Vogt⁷

Kuopio:

Kimmo Mäkinen⁵, Pekka Miettinen⁵, Minna Niskanen⁶, Ilkka Parviainen⁶ (co-principal investigator)

Tampere:

Heli Leppikangas⁴, Silvia Nunes⁴, Esko Ruokonen⁴ (co-principal investigator)

¹Department of Intensive Care Medicine, University Hospital Bern, CH-3010 Bern, Switzerland

²Department of Cardiovascular Surgery, University Hospital Bern, CH-3010 Bern, Switzerland

³Department of Visceral and Transplantation Surgery, University Hospital Bern, CH-3010 Bern, Switzerland

⁴Department of Intensive Care, Tampere University Hospital, P.O. Box 2000, 33521 Tampere, Finland

⁵Department of Surgery, Kuopio University Hospital, P.O. Box 1777, 70211 Kuopio, Finland

⁶Department of Anesthesia and Intensive Care Medicine, Kuopio University Hospital, P.O. Box 1777, 70211 Kuopio, Finland

⁷Department of Anesthesiology, University Hospital Bern, CH-3010 Bern, Switzerland