Tissue saturation measurement - exciting prospects, but standardisation and reference data still needed

Sepsis and shock result in disturbances in microcirculatory perfusion and tissue oxygen utilisation that may not be reflected in global measures of haemodynamics. Near-infrared spectroscopy enables measurement of tissue oxygen saturation (StO2) and provides information on local microvascular and mitochondrial function. This measure could be incorporated with existing targets of goal-directed therapy to provide an integrated approach to haemodynamic resuscitation of both the macro- and microcirculation in various shock states. However, key methodological factors must be addressed before widespread clinical application.

In the previous issue of Critical Care, Možina and Podbregar report that changes in thenar muscle tissue saturation (StO 2 ) in response to vascular occlusion can be used to predict discrepancy between central (ScvO 2 ) and mixed (SvO 2 ) venous oxygen saturation in patients with combined severe left ventricular failure and sepsis [1].
On fi rst read this study is conceptually diffi cult. Essentially, ScvO 2 is a surrogate marker of SvO 2 and is widely used to assess adequacy of oxygen delivery, and to guide the initial resuscitation of septic patients [2]. Trends in ScvO 2 may refl ect those in SvO 2 , but alterations in oxygen extraction and redistribution of blood fl ow away from peripheral and splanchnic circulations in various shock states may cause clinically important diff er ences between these values [3]. In these circumstances ScvO 2 may be maintained despite abnormally low SvO 2 and signifi cant tissue hypoxia. Th e current study suggests a means to identify these discrepancies which may be useful in the management of sepsis/septic shock, particularly in patients with complex haemodynamic distur bances. However, several issues relating to methodo logical factors require further consideration.
Microcirculatory perfusion and tissue oxygen utilization are aff ected by sepsis and shock [4]. Th ese derangements can be studied non-invasively using near-infrared spectroscopy, a technique that is able to determine the oxygenation status of tissue haemoglobin. Decreased StO 2 refl ects the presence of severe hypoperfusion and has been used clinically to guide resuscitation during hypovolaemic shock [5]. Unfortunately, in sepsis/septic shock absolute values of StO 2 do not reliably diff erentiate patients from healthy individuals [6].
Th e discriminatory power and predictive ability of StO 2 can, however, be improved by measuring the response to an ischaemic challenge. Th e vascular occlusion test (VOT) is a provocative test in which StO 2 is measured at a peripheral site (such as the thenar eminence) whilst a transient rapid vascular occlusion is performed for either a defi ned time interval or until a pre-defi ned StO 2 value is reached. Th e VOT-derived StO 2 trace can be divided into four phases -baseline, ischemia, reperfusion, and hyperemia -and parameters can be measured for each of these. Th ese include: rate of deoxygenation (DeO 2 ), measured from the StO 2 downslope during the ischaemic phase -this is generally considered to refl ect local muscle metabolism and mitochondrial oxygen consumption [7]; and rate of reoxygenation (ReO 2 ), measured from the StO 2 upslope during reperfusion -this is the time required to wash out stagnant blood and is thought to refl ect the reactivity of the microcirculation [8].
Studies suggest that the response to the VOT diff ers in sepsis, with a slower DeO 2 during cuff occlusion and a prolonged ReO 2 during reperfusion when compared to healthy individuals [9,10]. Furthermore, it seems that VOT refl ects severity of illness and is sensitive to intervention with activated protein C [8,11]. According

Abstract
Sepsis and shock result in disturbances in microcirculatory perfusion and tissue oxygen utilisation that may not be refl ected in global measures of haemodynamics. Near-infrared spectroscopy enables measurement of tissue oxygen saturation (StO 2 ) and provides information on local microvascular and mitochondrial function. This measure could be incorporated with existing targets of goal-directed therapy to provide an integrated approach to haemodynamic resuscitation of both the macro-and microcirculation in various shock states. However, key methodological factors must be addressed before widespread clinical application.
to the current study it may also have a role in guiding resuscitation and optimisation of haemodynamics.
Th ese fi ndings are exciting, but at present enthusiasm must be tempered. Firstly, there are wide variations in StO 2 and VOT-derived parameters dependent upon probe position and probe size [12]. Secondly, the VOT procedure has yet to be standardized; currently, diff erent types and degrees of defl ation thresholds (for example, absolute StO 2 of 40% or 50% versus duration of 3 minutes, 4 minutes, 5 minutes) are employed [13]. Th irdly, context-specifi c ranges for VOT-derived StO 2 parameters need to be estab lished in health to ensure correct interpretation of responses in pathological states. High quality data are also needed on the VOT parameter values for diff erent levels of disease severity, and indeed for diff erent diseases. Finally, the mechanisms underlying diff erences in StO 2 response observed in sepsis need to be fully characterized.
Dynamic StO 2 monitoring is a promising technique with the potential to provide a non-invasive 'biopsy' of microvascular and mitochondrial function. Used in conjunc tion with global measures of oxygen delivery it could provide an integrated approach to haemodynamic resuscitation of both the macro-and microcirculation in various shock states. Furthermore, it may have utility in determining disease severity, outcome prediction, assessment of the biological eff ects of interventions, and in guiding future research. However, as with all new technologies it is essential that operating characteristics are robustly defi ned and that the limitations are fully appreciated before wider application to the clinical setting.

Competing interests
MT has received StO 2 equipment in support of research from Hutchinson Technology Inc.