The study protocol was approved by the National Ethics Committee of Slovenia; informed consent was obtained from all patients or their relatives. The study was performed during the period between October 2004 and June 2006. Following initial heamodynamic resuscitation, heart examination was performed in all patients admitted to our intensive care unit (ICU) using transthoracic ultrasound (Hewlett-Packard HD 5000; Hewlett-Packard, Andover, MA, USA). In patients with primary heart disease, low cardiac output and no signs of hypovolaemia, right heart catheterization with a pulmonary artery floating catheter (Swan-Ganz CCOmboV CCO/SvO₂/CEDV; Edwards Lifesciences, Irvine, CA, USA) was performed at the descretion of the treating physician. The site of insertion was confirmed by the transducer waveform, the length of catheter insertion and chest radiography. Systemic arterial pressure was measured invasively using radial or femoral arterial catheterization.

Patients with severe left heart failure due to primary heart disease (left ventricular systolic ejection fraction < 40%, pulmonary artery occlusion pressure > 18 mmHg) were included. The patients were prospectively divided into two groups; group A included patients without severe sepsis or septic shock and group B included patients with additional severe sepsis or septic shock. Severe sepsis and septic shock were defined according to the 1992 American College of Chest Physicians and the Society of Critical Care Medicine consensus conference definitions 12.

All patients received standard treatment for localized infection, severe sepsis and septic or cardiogenic shock, including source control, fluid infusion, catecholamine infusion, replacement and/or support therapy for organ failure, intensive control of blood glucose and corticosteroid substitution therapy, in accordance to current Surviving Sepsis Campaign Guidelines 13. Mechanically ventilated patients were sedated with midazolam and/or propofol infusion, and no paralytic agents were used.

Fifteen healthy volunteers served as a control group.

In ten patients from group A and eight patients from group B, StO₂ and SvO₂ (Vigilance CEDV; Edwards Lifesciences) were continuously monitored and recorded every 15 minutes for one hour to study agreement between trends in measured variables.

Data are expressed as mean ± standard deviation. Student's t-test, Kolmogorov-Smirnov Z test and χ² test (Yates correction) were applied to analyze data (SPSS 10.0 for Windows™; SPSS Inc., Cary, NC, USA). One-way analysis of variance with Dunnett T3 test for post-hoc multiple comparisons were used to compare muscle tissue StO₂ between healthy volunteers and both groups. Spearman correlation test was applied to determine correlation. To compare muscle tissue StO₂ and SvO₂, bias, systemic disagreement between measurements (mean difference between two measurements) and precision (the random error in measuring [standard deviation of bias]) were calculated 14. The 95% limits of agreement were arbitrarily set, in accordance with Bland and Altman 15, as the bias ± 2 standard deviations. P < 0.05 (two-tailed) was considered statistically significant.

We previously detected high StO₂ and slow deceleration in StO₂ during stagnant ischaemia in septic patients 11. Our data were in concordance with a previous report from De Blasi and coworkers 16. Studies in animals and patients with sepsis confirmed the presence of increased tissue oxygen tension 17. However, tissue oxygen consumption slows down in sepsis, and this correlates with the severity of sepsis 18. Reduced cellular use/extraction of oxygen may be the problem rather than tissue hypoxia per se, because an increase in tissue oxygen tension is normally observed 19. The high StO₂ levels seen in our patients with additional severe sepsis or septic shock support this hypothesis. Mitochondrial dysfunction has been implicated by Ince and Sinaasappel 20. This mitochondrial alteration was also shown to correlate with outcome in sepsis and septic shock 21.

The high StO₂/low SvO₂, seen in severe sepsis and septic shock, suggest blood flow redistribution. Thenar muscle StO₂ probably correlates with central venous oxygen saturation (ScvO₂), which is measured in a mixture of blood from head and both arms. In healthy resting individuals ScvO₂ is slightly lower than SvO₂ 22. Blood in the inferior vena cava has high oxygen content because the kidneys do not utilize much oxygen but receive a high proportion of cardiac output 23. As a result, inferior vena caval blood has higher oxygen content than blood from the upper body, and SvO₂ is greater than ScvO₂.

This relationship changes in the presence of cardiovascular instability. Scheinman and coworkers 24 performed the earliest comparison of ScvO₂ and SvO₂ in both haemodynamically stable and shocked patients. In stable patients ScvO₂ was similar to SvO₂. In patients with failing heart ScvO₂ was slightly higher than SvO₂ and in shock patients the difference between SvO₂ and ScvO₂ was even more pronounced (47.5 ± 15.11% and 58.0 ± 13.05%, respectively; P < 0.001). Lee and coworkers 25 described similar findings. Other, more detailed studies in mixed groups of critically ill patients designed to test whether the ScvO₂ measurements could substitute for SvO₂ demonstrated problematic large confidence limits 26 and poor correlation between the two values 27.

Most authors attribute this pattern to changes in the distribution of cardiac output that occur in the presence of haemodynamic instability. In shock states, blood flow to the splanchnic and renal circulations falls, whereas flow to the heart and brain is maintained 28. This results in a fall in the oxygen content of blood in the inferior vena cava. As a consequence, in shock states the normal relationship is reversed and ScvO₂ is greater than SvO₂ 232425. Consequently, when using ScvO₂ (or probably StO₂) as a treatment goal, the relative oxygen consumption of the superior vena cava system may remain stable at a time when oxidative metabolism of vital organs, such as the splanchnic region, may reach a level at which flow-limited oxygen consumption occurs, together with marked decrease in oxygen saturation. In this situation StO₂ provides a falsely favourable impression of adequate body perfusion, because of the inability to detect organ ischemia in the lower part of the body.

In the present study three patients with septic shock had skeletal muscle StO₂ of 75% or less (under the lower bound of the 95% confidence interval for the mean StO₂ in control individuals); they were all in septic shock (lactate value > 2.5 mmol/l) with low cardiac index (< 2.0 l/min per m²). These patients were probably in an early under-resuscitated phase of septic shock. Low numbers of septic patients with low StO₂ values did not allow us to study the agreement between StO₂ and SvO₂ in such patients; however, there was a wide range in StO₂ values with SvO₂ below 65%. Additional research is necessary to study muscle skeletal StO₂ in under-resuscitated septic patients.

Our data are supported by previous work conducted by Boekstegers and coworkers 29, who measured the oxygen partial pressure distribution in biceps muscle. They found low peripheral oxygen availability in cardiogenic shock compared with sepsis. In cardiogenic shock skeletal muscle partial pressure of oxygen correlated with systemic DO₂ (r = 0.59, P < 0.001) and systemic vascular resistance (r = 0.74, P < 0.001). No correlation was found between systemic oxygen transport variables and skeletal muscle partial oxygen pressure in septic patients. These measurements were taken in the most common cardiovascular state in sepsis; this is in contrast to hypodynamic shock, which is only present in the very final stages of sepsis or in patients without adequate volume replacement 30. In a subsequent study, those authors showed that even in the final state of hypodynamic septic shock, leading to death, the mean muscle partial oxygen pressure did not decrease to under 4.0 kPa before circulatory standstill took place 31.

In a human validation study 32 a significant correlation between NIRS-measured StO₂ and venous oxygen saturation (r = 0.92, P < 0.05) was observed; the venous effluent was obtained from a deep forearm vein that drained the exercising muscle. StO₂ was minimally affected by skin blood flow. Changes in limb perfusion affect StO₂; skeletal muscle StO₂ decreases during norepinephrine and increases during nitroprusside infusion.

In shock with preserved or even increased oxygen extraction, such as haemorrhagic shock, StO₂ (as measured by NIRS in skeletal muscle, stomach and liver) correlated with systemic DO₂ in a pig model 33. Changes in skeletal muscle oxygen partial pressure were confirmed during haemorrhagic shock and resuscitation 34. Continuous monitoring of skeletal muscle StO₂ is already used in trauma patients, in whom it identifies the severity of shock 35. Basal skeletal muscle StO₂ can track systemic DO₂ during and after resuscitation of trauma patients 36.

StO₂ overestimated SvO₂ (bias -2.5%) in the present study. This may be due to the NIRS method, which does not discriminate between compartments. It provides a global assessment of oxygenation in all vascular compartments (arterial, venous and capillary) in sample volume of underlying tissue. This is major limitation of the present study. The noninvasive measurement of only venous oxygen saturation is complicated by the fact that isolation of the contribution of venous compartment to the noninvasive optical signal is not straightforward. New methods like near-infrared spiroximetry, which measures venous oxygen saturation in tissue from the near-infrared spectrum of the amplitude of respiration-induced absorption oscillations, may lead to the design of a noninvasive optical instrument that can provide simultaneous and real-time measurements of local arterial, tissue and venous oxygen saturation 37.

In low flow states, in which controversies regarding monitoring persist 38, it appears logical to make use of both macro- and microcirculatory parameters to guide resuscitation efforts 39. A large prospective study is currently being performed to evaluate the utility of additional StO₂ regional monitoring to guide tissue oxygenation, in addition to the early goal-directed therapy proposed by Rivers and coworkers 40.