Tissue oxygen tension (PTO2) is the directly measured local partial pressure of oxygen in a specific tissue. It may be thought of as the local expression of global oxygen delivery (DO2) in a particular tissue. Tissue oxygen tension is the balance between oxygen perfusion and oxygen consumption in the tissue at a given time. In tissues with stable oxygen consumption, PTO2 reflects tissue perfusion more precisely than traditional clinical indices such as mean arterial pressure, cardiac output, urine output, skin temperature, or skin capillary refill.
Tissue oxygen tension may be measured in any tissue of interest, but values in peripheral subcutaneous tissue are the most widely reported. Its vascular bed is susceptible to vasoconstrictive influences, being the first vascular bed compromised when circulatory homeostasis is threatened and the last replenished during recovery.1 Subcutaneous tissue oxygen consumption is a relatively constant, low amount (approximately 1 ml kg1 min1, compared with overall body average of approximately 4 ml kg1 min1); thus PTO2 in s.c. tissue is a highly sensitive indicator of tissue perfusion. Importantly, s.c. tissue is easily accessible for measurement techniques, and is invariably involved when surgical wound infection occurs.1 2
Measurement techniques
Tissue oxygen tension may be measured by polarographic or dynamic fluorescence quenching methods. The original polarographic technique, described over 20 yr ago, remains popular. An oxygen-permeable, silastic catheter (internal diameter 0.8 mm) is introduced via a 14 G i.v. cannula into the s.c. tissue of the deltoid region of the upper arm or the surgical wound. Hypoxic saline, obtained by bubbling nitrogen gas through normal saline for 510 min, is introduced into the silastic tube. This is allowed to equilibrate with tissue oxygen for 1520 min, then the saline is sampled for oxygen tension.1
Modern refinements of this technique involve using a purpose-built, microcatheter located within a s.c., saline-filled tonometer, on a 15 cm probe (CC1-SB, Licox Medical Systems, Integra Neurosciences, Hamps, UK). The oxygen sensor is enclosed within a cylindrical polyethylene tube, which is permeable to oxygen when in contact with tissue. Two polarographic electrodes (silver and gold) lie within the polyethylene tube, which is also filled with an electrolyte solution. The proximal end of the probe is closed by an electrical cable connection, which is attached to a digital, bedside monitor displaying real-time PTO2 values every 2 s.3 These probes use revoxode technology, that is the chemical reaction at the electrode tips is reversible, unlike standard Clark electrodes, where these electrolytic reactions are irreversible. This means that there is no calibration drift as time passes, ensuring accurate measurement over a period of days. Sensitivity and offset are preserved within a narrow range (5%) over a 5-day period of operation.4 Calibration data for these revoxode probes are individually determined during manufacture and are stored on a smart card, specific for an individual probe. Revoxode probes average the heterogeneous local tissue oxygen tension values over their probe area, eliminating any random positioning error of the microprobe sensors. Sensors interface with a laptop PC, allowing data to be recorded on a continuous basis and stored electronically.
A newer technique promises more flexible measurements at lower cost. Oxygen molecules have the property of quenching the fluorescence and phosphorescence of certain luminophores. First described by Kautsky in 1939, this effect is called dynamic fluorescence quenching. Collision of an oxygen molecule with a fluorophore in its excited state leads to a non-radiative transfer of energy. The degree of fluorescence quenching relates to the frequency of collisions, and therefore to the concentration, pressure, and temperature of the oxygen-containing media. The fluorescence intensity can be expressed in terms of the SternVolmer equation, where fluorescence is related quantitatively to the partial pressure of oxygen:5
where I0 is the intensity of fluorescence at zero pressure of oxygen, I is the intensity of fluorescence at a pressure P of oxygen, and k is the SternVolmer constant.
Fibre-optic oxygen sensors use the fluorescence of a ruthenium complex to measure the partial pressure of oxygen. A pulsed, blue Light Emitting Diode (LED) sends light, at approximately 475 nm, to an optical fibre. The optical fibre carries the light to a probe, consisting of a thin layer of a hydrophobic sol-gel material. The ruthenium complex is trapped in the sol-gel matrix. Light from the LED excites the ruthenium complex at the probe tip, which fluoresces, emitting energy at approximately 600 nm. If the excited ruthenium complex encounters an oxygen molecule, the excess energy is transferred to the oxygen molecule in a non-radiative transfer, decreasing or quenching the fluorescence signal. The degree of quenching correlates with the oxygen partial pressure in the sample. This is detected by the probe and carried through the optical fibre to a spectrometer. The data are converted to a digital form, which may be displayed on a PC. The probe may be safely sterilized in ethylene oxide and reused. It is manufactured as an 18 G diameter, so inserting it into tissue is akin to having an 18 G cannula inserted.6
Key role of anaesthesia in PTO2 and surgical wound healing
While there is ongoing interest in measuring PTO2 in malignant tumours in order to define hypoxic cell radioresistance, the principal clinical significance of PTO2 is that it is the final common pathway by which many diverse factors influence surgical wound healing (Fig. 1). Successful surgical wound healing requires resistance to infection, which depends mainly on oxidative killing of organisms by neutrophils. Tissue oxygen tension is an especially important determinant of postoperative wound healing, because the bactericidal ability of neutrophils is directly related to PTO2.7 Moreover, PTO2 also influences collagen deposition, which reflects wound tensile strength. Indeed, the incidence of surgical wound infection is dependent on wound s.c. tissue oxygen tension. Supra-normal arterial oxygen tension levels, achieved by administering supplemental perioperative oxygen, have been demonstrated to half the incidence of surgical wound infection from 11 to 5% by increasing PTO2.8
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Regional anaesthesia
Epidural anaesthesia and analgesia attenuate the stress response to surgery, promote systemic vasodilatation, and provide superior analgesia compared with parenteral methods of analgesia. A prospective, randomized, blind clinical study tested the hypothesis that epidural anaesthesia and analgesia increase wound tissue oxygen tension compared with conventional i.v. morphine analgesia. Patients undergoing major abdominal surgery (n=32) were randomized to receive combined general and epidural anaesthesia with postoperative patient-controlled epidural analgesia (epidural group, n=16), or general anaesthesia (GA) alone with postoperative patient-controlled intravenous analgesia (i.v. group, n=16). An oxygen sensor and a temperature sensor were placed subcutaneously in the wound before closure. Wound tissue oxygen tension (PTO2) and temperature were measured continuously for 24 h. Despite epidural patients being more hypothermic at the end of surgery (35.7 (0.3) vs 36.3 (0.5)°C, P=0.004), they had significantly higher mean PTO2 over the 24-h period, compared with the i.v. group (8.5(1.9) vs 6.8(2.0) kPa, mean (SD), 95% CI difference, 3.0 to 0.7, P=0.02). Visual Analogue Scale pain scores at rest and moving were significantly lower in the epidural group at all times.13 Whether this observation is a result of vasodilatation, superior pain relief provided by the epidural, or some other mechanism, is unknown.
Other regional anaesthesia techniques may also influence PTO2. Patients undergoing mastectomy and immediate latissimus dorsi (LD) breast reconstruction with GA and paravertebral anaesthesia combined, followed by continuous infusion paravertebral postoperative analgesia, had decreased pain and increased LD flap tissue oxygen tension for 24 h postoperatively, compared with patients having this procedure under GA alone with postoperative i.v. opioid analgesia.14 The difference between patients receiving paravertebral anaesthesia compared with GA alone was higher than has been observed in epidural studies (mean (SD) difference, 4.1 (1.1) kPa), which may reflect differences in muscle tissue oxygen tension in the LD muscle flap compared with s.c. tissue oxygen tension measurements in other studies.
Other possible applications of PTO2
Although PTO2 has been established as being inversely related to the true outcome measure of surgical wound infection,7 a variety of studies have speculated on a wider role for PTO2. More than a decade ago, a small study found that low intraoperative PTO2 (<2.1 kPa) was predictive of adverse clinical outcome in patients undergoing colorectal surgery, compared with patients who had higher PTO2 values.15 In a prospective, observational study, patients after cardiopulmonary bypass and patients with systemic sepsis syndrome were subjected to a 20 min episode of upper limb ischaemia and reperfusion. Tissue oxygen tension and microvascular flow were measured using polarographic microelectrodes. Patients with sepsis syndrome had a greater decline of PTO2 after ischaemia and slower recovery after reperfusion.16 An experimental study of PTO2 in the mucosal colonic surfaces of rat models demonstrated that addition of a nitric oxide inhibitor reduced PTO2 by 45%, which was reversed by addition of L-arginine, a substrate for nitric oxide synthesis.17 These data suggest that nitric oxide is central to the local mechanism by which PTO2 is regulated. A small study has suggested that recovery of PTO2 is delayed in patients with major trauma, despite apparently adequate resuscitation.18 Therefore, there is evidence that PTO2 is influenced by the systemic inflammatory response syndrome and might have a prognostic role or be useful in guiding therapy.
Cardiopulmonary bypass (CPB) activates the systemic inflammatory response, and invites comparison with coronary revascularization without cardiopulmonary bypass (off-pump coronary artery bypass, OPCAB), which was first undertaken over 30 yr ago. Off-pump coronary revascularization surgery reduces the systemic inflammatory response induced by CPB and the early postoperative catecholamine requirement. A prospective, cohort study of 10 consecutive patients undergoing OPCAB compared with 10 having conventional CPB tested the hypothesis that OPCAB would be associated with increased PTO2 compared with surgery using conventional CPB. All patients had a tissue oxygen sensor implanted longitudinally into the subcutaneous tissue of the leg in the saphenous vein harvest wound. Data were collected from closure of the saphenous vein wound for 20 h postoperatively. Although OPCAB patients had significantly fewer coronary arteries grafted, postoperative PTO2 was significantly higher in OPCAB patients throughout the 20-h study period. Absolute mean differences ranged from 2.3 kPa in the first 2 h (14.4 (2.3) vs 12.1 (2.4) in OPCAB and CPB, respectively, P=0.04) to 4.6 kPa at 810 h (14.0 (3.5) vs 9.3 (2.7), P=0.007). In contrast, there were no significant differences in arterial oxygen tension, pH, or serum lactate values over this period.19 A reduction in the CPB-induced inflammatory response in OPCAB patients is probably the major explanatory factor.
Hypercapnia in the intraoperative period has been shown recently to increase PTO2 in volunteers and in patients undergoing GA, in a dose-dependent fashion. This is thought to be attributable to increased cardiac index in addition to local vasodilatation.20 21 The Outcomes Research Group, primarily responsible for defining the role of PTO2 in anaesthesia and surgical wound healing,8 10 1214 1921 is currently investigating the role of mild, intraoperative hypercapnia on actual wound infection rates in patients undergoing colorectal surgery. If such an outcome was validated, while not quite heralding a return of carbon dioxide cylinders to our anaesthetic machines, it could change our practice to permit a degree of intraoperative hypercapnia in surgical patients. Future studies on the role of PTO2 in determining the adequacy of tissue perfusion in the critically ill are also warranted.
Summary
Directly measured PTO2 is the local partial pressure of oxygen in a specific tissue and is perhaps the most reliable quantitative index of tissue perfusion currently available. Measurement technology is based on the principles of the polarographic cell and on dynamic fluorescence quenching. Tissue oxygen tension is of central importance in surgical wound infection and healing, because the bactericidal activity of neutrophils is dependent on PTO2 values at the time of contamination, that is the intraoperative period. While surgical and patient factors are important determinants of surgical wound healing, the anaesthetist has a central role in maximizing PTO2 by maintaining normothermia, using supplemental oxygen, and optimizing fluid balance and analgesia. Regional anaesthetic techniques, in particular epidural and paravertebral anaesthesia, increase PTO2 levels by a mechanism that is currently unknown. Work is ongoing on other factors by which PTO2 may be influenced by the anaesthetist, including hypercapnia, while a role for PTO2 in guiding therapy and predicting outcome in the critically ill, septic patient remains to be defined.
J. Ragheb
D. J. Buggy*
National University of Ireland, Dublin and Mater Misericordiae Hospital
Dublin 7
Ireland
*Corresponding author. E-mail: donal.buggy{at}nbsp.ie; anaes{at}mater.ie
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