Transcutaneous oximetry in clinical practice: consensus statements from an expert panel based on evidence.

Transcutaneous oximetry (PtcO2) is finding increasing application as a diagnostic tool to assess the peri-wound oxygen tension of wounds, ulcers, and skin flaps. It must be remembered that PtcO2 measures the oxygen partial pressure in adjacent areas of a wound and does not represent the actual partial pressure of oxygen within the wound, which is extremely difficult to perform. To provide clinical practice guidelines, an expert panel was convened with participants drawn from the transcutaneous oximetry workshop held on June 13, 2007, in Maui, Hawaii. Important consensus statements were (a) tissue hypoxia is defined as a PtcO2 <40 mm Hg; (b) in patients without vascular disease, PtcO2 values on the extremity increase to a value >100 mm Hg when breathing 100% oxygen under normobaric pressures; (c) patients with critical limb ischemia (ankle systolic pressure of < or =50 mm Hg or toe systolic pressure of < or =30 mm Hg) breathing air will usually have a PtcO2 <30 mm Hg; (d) low PtcO2 values obtained while breathing normobaric air can be caused by a diffusion barrier; (e) a PtcO2 <40 mm Hg obtained while breathing normobaric air is associated with a reduced likelihood of amputation healing; (f) if the baseline PtcO2 increases <10 mm Hg while breathing 100% normobaric oxygen, this is at least 68% accurate in predicting failure of healing post-amputation; (g) an increase in PtcO2 to >40 mm Hg during normobaric air breathing after revascularization is usually associated with subsequent healing, although the increase in PtcO2 may be delayed; (h) PtcO2 obtained while breathing normobaric air can assist in identifying which patients will not heal spontaneously.

Wound oxygen levels during hyperbaric oxygen treatment in healing wounds.

Hyperbaric oxygen (HBO2) increases wound oxygen delivery, but few data quantify wound oxygen levels over the course of healing. We characterized these changes during and after HBO2 treatment in a rat wound model. The treatment group (n=7) received 2.0 ATA HBO2, 90 minutes BID for 15 days. Control rats (n=5) were only exposed to HBO2 during measurement. On days 5, 10, and 15, wound pO2 was measured before, during, and for an hour after HBO2 treatment. Both the peak pO2 and the pO2 one hour after HBO2 treatment were significantly greater than baseline on all days in both the treatment (p < .01) and control group (p < .05). The peak pO2 during HBO2 exposure and one hour after decreased significantly in the treatment group on day 15 compared to day 5 (p <.01, p <.05 respectively). No significant differences were found in pO2 values between days within the control group. These results demonstrate that both the peak wound oxygen levels and duration of elevation change significantly throughout the course of HBO2 treatment.

UHMS position statement: topical oxygen for chronic wounds.

A small body of literature has been published reporting the application of topical oxygen for chronic non-healing wounds . Frequently, and erroneously, this form of oxygen administration has been referred to as "topical hyperbaric oxygen therapy" or even more erroneously "hyperbaric oxygen therapy." The advocates of topical oxygen claim several advantages over systemic hyperbaric oxygen including decreased cost, increased safety, decreased complications and putative physiologic effects including decreased free radical formation and more efficient delivery of oxygen to the wound surface. With topical oxygen an airtight chamber or polyethylene bag is sealed around a limb or the trunk by either a constriction/tourniquet device or by tape and high flow (usually 10 liters per minute) oxygen is introduced into the bag and over the wound. Pressures just over 1.0 atmospheres absolute (atm abs) (typically 1.004 to 1.013 atm abs) are recommended because higher pressures could decrease arterial/capillary inflow. The premise for topical oxygen, the diffusion of oxygen into the wound adequate to enhance healing, is attractive (though not proven) and its delivery is certainly less complex and expensive than hyperbaric oxygen. When discussing the physiology of topical oxygen, its proponents frequently reference studies of systemic hyperbaric oxygen suggesting that mechanisms are equally applicable to both topical and systemic high pressure oxygen delivery. In fact, however, the two are very different. To date, mechanisms of action whereby topical oxygen might be effective have not been defined or substantiated. Conversely, cellular toxicities due to extended courses of topical oxygen have been reported, although, again these data are not conclusive, and no mechanism for toxicity has been examined scientifically. Generally, collagen production and fibroblast proliferation are considered evidence of improved healing, and these are both enhanced by hyperbaric oxygen therapy. Paradoxically, claims of decreased collagen production and fibroblast inhibition in wounds subjected to topical oxygen have been reported in studies of topical oxygen as a benefit of topical oxygen therapy. The literature on topical oxygen is mostly small case series or small controlled but not randomized trials. Moreover, the studies generally are not aimed at specific ulcer types, but rather at "chronic wounds." This non-specific approach is recognized as a major design flaw in any study of therapies designed to improve impaired wound healing. The only randomized trial for topical oxygen in diabetic foot ulcers actually showed a tendency toward impaired wound healing in the topical oxygen group. Contentions that topical oxygen is superior to hyperbaric oxygen are not proven. There are potentially plausible mechanisms that support both possibly beneficial and detrimental effects of topical oxygen therapy, and thus well designed and executed basic science research and clinical trials are clearly needed. There is some ongoing research in regard to the role of topical oxygen at established wound laboratories. Neither CMS nor other third party payors recognize or reimburse for topical oxygen. Therefore, the policy of the Undersea and Hyperbaric Medical Society in regard to topical oxygen is stated as follows: 1. Topical oxygen should not be termed hyperbaric oxygen since doing so either intentionally or unintentionally suggests that topical oxygen treatment is equivalent or even identical to hyperbaric oxygen. Published documents reporting experience with topical oxygen should clearly state that topical oxygen not hyperbaric oxygen is being employed. 2. Mechanisms of action or clinical study results for hyperbaric oxygen cannot and should not be co-opted to support topical oxygen since hyperbaric oxygen therapy and topical oxygen have different routes and probably efficiencies of entry into the wound and their physiology and biochemistry are necessarily different. 3. The application of topical oxygen cannot be recommended outside of a clinical trial at this time based on the volume and quality of scientific supporting evidence available, nor does the Society recommend third party payor reimbursement. 4. Before topical oxygen can be recommended as therapy for non-healing wounds, its application should be subjected to the same intense scientific scrutiny to which systemic hyperbaric oxygen has been held.

The role of nitric oxide in subcutaneous and transmural gut tissue oxygenation.

The influence of inhibiting the nitric oxide (NO) synthetase on tissue perfusion as indicated by tissue oxygen tensions was determined. Tissue oxygen probes were placed subcutaneously and on serosal and mucosal surfaces of colon of anesthetized adult rats. After a control period, the inhibitor of NO formation, N(G)-nitro-L-arginine methyl ester (L-NMMA), was given intravenously and followed 20 min later by infusion of substrate for NO synthetase, L-arginine. Mean arterial blood pressure (MAP), subcutaneous tissue oxygen tension (P(SQ)O2), serosal tissue oxygen tension (P SO(2)), and mucosal tissue oxygen tension (P(M)O2) were simultaneously measured. Baseline values for the measured parameters were MAP = 95 + or - 9 mmHg, P(SQ)O2 = 61 + or - 7 mmHg, P(S)O2 65 + or - 7 mmHg, and P(M)02 = 9 + or - 2 mmHg. The infusion of L-NMMA induced a significant increase in MAP to 123 + or - 7 mmHg (p < .001) and P(SQ)O2 to 72 + or - 7 mmHg (p < .001). P(S)O2 did not change significantly from baseline after L-NMMA infusion. A significant decrease in P(M)O2 to 4 + or - 2 mmHg was noted after L-NMMA infusion (p < .001). The administration of L-arginine promptly returned all measured parameters to baseline levels within 10 min of infusion. A transmural P(O2) gradient exists across the colon with P(M)O2 far lower than P(S)O2. P(SQ)O2 approximates P(S)O2 at baseline and P(S)O2 is not altered by inhibition of the NO synthetase. The 45% reduction in mucosal PO2 after L-NMMA, which was reversed by L-arginine infusion, suggests that nitric oxide participates in splanchnic vasomotor control with a preferential effect in the mucosal vasculature. The observed decrease in mucosal PO2 observed after inhibition of NO production is similar to the worsened hypoxia previously measured during hemorrhagic shock. Further work clarifying the local control mechanisms of gut tissue P02 can direct therapies to increase gut tissue oxygenation.

Postoperative pain management.

OBJECTIVES: To examine the relationship between analgesia and clinical outcome and to review new methods of delivering opioid analgesics and new pharmacologic analgesic agents. DATA SOURCES: A computer-assisted search of the literature on postoperative pain management, and a review of those areas in which new approaches have led to a change in clinical practice. RESULTS: Current research focuses on the ability of analgesia to decrease perioperative complications. Recent advances allow enhanced postoperative analgesia with a low incidence of side effects. Administration of opioids via a patient-controlled device or via an epidural catheter yields excellent analgesia with a low rate of side effects compared with intramuscular opioids. Several non-narcotic, parenteral drugs, including ketorolac tromethamine and alpha 2-adrenergic agonists are now available. These drugs decrease opioid requirement, and thus the rate of serious side effects, including respiratory depression. Moreover, because these drugs act at sites other than opioid receptors, they may enhance the quality of analgesia at the same time they decrease opioid requirement. CONCLUSIONS: New technology and new agents allow more rational management of postoperative pain. Use of these techniques results in increased patient satisfaction and may improve clinical outcome.

Transmural gut oxygen gradients in shocked rats resuscitated with heparan.

OBJECTIVES: To develop a reproducible model to measure transmural gut tissue PO2, to determine the gradient from serosa to mucosa during normovolemia and hypovolemia, and to determine the effect of resuscitation with heparan sulfate (danaparoid sodium) on this gradient. DESIGN: Fluorescent tissue oxygen sensors were placed onto serosal and mucosal surfaces of rat colon. Hemorrhagic shock was induced using a fixed pressure (mean arterial pressure, 40 mm Hg) model and resuscitated with either saline solution or heparan. RESULTS: Control animals had stable mean (+/- SD) serosal and mucosal tissue oxygen tensions (PO2) of 64 +/- 4 and 10 +/- 2 mm Hg, respectively. In shocked animals, baseline serosal PO2 decreased to 37 +/- 2 mm Hg at a mean (+/- SD) of 19 +/- 7 minutes after the initiation of hemorrhage. Mucosal values decreased to a minimum of 4 +/- 2 mm Hg at 45 +/- 15 minutes after the initiation of hemorrhage. Serosal PO2 returned to baseline during resuscitation in both control and heparan-resuscitated animals. Mucosal PO2 did not return to baseline in the shock/no heparan group. In the heparan-resuscitated animals, however, mucosal PO2 increased above baseline (13 +/- 3 mm Hg at 3 hours after completion of hemorrhage). CONCLUSIONS: A transmural gradient of PO2 exists across the colon with mucosal PO2 far lower than serosal PO2. Both serosal and mucosal PO2 decrease during hypovolemia. During hypovolemia, the PO2 of the entire gut wall is in a range in which phagocytic killing is impaired by hypoxia. Heparan improved mucosal PO2 and it may restore and/or protect gut function by oxygen-related mechanisms.

Perioperative collagen deposition in elderly and young men and women.

HYPOTHESIS: Women deposit more collagen after major abdominal surgery than men. DESIGN: A post hoc analysis of data obtained from 2 prospective, randomized, double-blind clinical trials. SETTING: University hospital general surgical service. PATIENTS: One hundred sixteen patients undergoing colon resection. MAIN OUTCOME MEASURES: Protein and hydroxyproline (collagen) deposition during the first 7 postoperative days in expanded polytetrafluoroethylene implants positioned subcutaneously. RESULTS: On univariate analysis, men and women deposited comparable amounts of collagen (257 +/- 120 vs 281 +/- 117 ng/mm, respectively). When potential confounding factors were entered into a generalized mixed-effects model, only the interaction between age and sex was a significant factor (P = .047). Collagen deposition decreased with age in men, being 317 +/- 133 ng/mm in men younger than 45 years, but only 238 +/- 113 ng/mm in those older than 45 years (P = .03). In contrast, collagen deposition was virtually identical in women younger than 45 years (280 +/- 133 ng/mm) and in those older than 45 years (281 +/- 110 ng/mm). Only 3 of these women were receiving hormone replacement therapy. CONCLUSIONS: Collagen deposition after surgery decreased significantly with age in men, while remaining unchanged in women. Younger men and women deposited similar amounts of collagen. Therefore, older men made less collagen after surgery than older women, perhaps explaining the consistent observation that wound dehiscence is twice as common in men than in women. Our results differ from previous studies conducted in healthy, nonsurgical volunteers, which showed that (1) young women made significantly more collagen than young men and (2) collagen deposition was reduced in postmenopausal women, but deposition returned to premenopausal values with hormone replacement therapy. Differences between our results and those reported previously likely stem from the populations studied. In particular, multiple perioperative factors decrease collagen deposition, which apparently obscures the differences observed previously in healthy, unstressed volunteers.

Cigarette smoking decreases tissue oxygen.

Subcutaneous wound-tissue oxygen (PsqO2) tension in eight volunteers fell rapidly and significantly in response to smoking, and remained low for 30 to 50 minutes. Sham "smoking" had no effect. These data suggest that a typical "pack-per-day" smoker experiences tissue hypoxia during a significant portion of each day. The degree of hypoxia found in these subjects has been associated with poor wound healing in animal and human studies. The onset and duration of tissue hypoxia paralleled the well-established plasma pharmacokinetics of nicotine. This suggests that peripheral vasoconstriction, induced by the adrenergic effects of nicotine, may contribute to the observed decrease in PsqO2.

Wound hypoxia and acidosis limit neutrophil bacterial killing mechanisms.

BACKGROUND: "Respiratory burst" activity, ie, O2- production, is dependent on PO2, temperature, pH, and glucose concentrations within the physiologic range. OBJECTIVES: To determine whether environmental conditions characteristic of wounds may limit human neutrophil respiratory burst metabolism and to clarify the degree to which bactericidal oxidant production depends on local PO2. METHODS: Human blood and wound neutrophils were stimulated with phorbol myristate acetate. Oxygen consumption and superoxide production were measured over a range of 30 to 300 mm Hg PO2, 0 to 40 mmol/L glucose, pH 6.0 to 8.0, and 30 degrees C to 37 degrees C. The apparent Michaelis Menten constant for oxidant production with respect to PO2 was calculated. RESULTS: Oxygen consumption and O2- production were dependent on PO2 throughout the range tested. Half-maximal oxidant production occurred in the range of 45 to 80 mm Hg PO2 and maximal at PO2 higher than 300 mm Hg. These data agree with the highest previous estimates. Oxidant generation was also dependent on pH, temperature, and glucose concentration, but to a lesser extent. CONCLUSIONS: Leukocyte bacterial killing capacity as measured by oxygen consumption and superoxide production are substantially impaired at the low oxygen tensions often found in wounds. Changes in pH, temperature, and glucose concentration have lesser but nonetheless significant consequences. The data provide a plausible mechanism for the vulnerability of some wounds to infection and for the previous finding that increasing oxygen tension at wound sites enhances bactericidal function. Thus, the data serve as a basis for future studies on prevention of wound infection.

Subcutaneous perfusion and oxygen during acute severe isovolemic hemodilution in healthy volunteers.

HYPOTHESIS: Acute severe isovolemic anemia (to a hemoglobin [Hb] concentration of 50 g/L) does not decrease subcutaneous wound tissue oxygen tension (PsqO(2)). SETTING: University hospital operating room and inpatient general clinical research center ward. SUBJECTS: Twenty-five healthy, paid volunteers. METHODS: Subcutaneous oxygen tension and subcutaneous temperature (Tsq) were measured continuously during isovolemic hemodilution to an Hb level of 50 g/L. In 14 volunteers (initially well-perfused), "normal" perfusion (Tsq >34.4 degrees C) was achieved by hydration and systemic warming prior to starting isovolemic hemodilution, while in 11 volunteers (perfusion not controlled [PNC]), no attempt was made to control perfusion prior to hemodilution. MAIN OUTCOME MEASURES: Measurements of PsqO(2), Tsq, and relative subcutaneous blood flow (flow index). RESULTS: While PsqO(2), Tsq, and flow index were significantly lower in PNC vs well-perfused subjects at baseline, there was no significant difference between them at the Hb of 50 g/L (nadir). Subcutaneous PO(2) did not decrease significantly in either group. Arterial PO(2) was not different between the groups, and did not change significantly over time; Tsq and flow index increased significantly from baseline to nadir Hb in both groups. CONCLUSIONS: The level of PsqO(2) was maintained at baseline levels during hemodilution to Hb 50 g/L in healthy volunteers, whether they were initially well-perfused or mildly underperfused peripherally. Given the significant increase in Tsq and flow index, this resulted from a compensatory increase in subcutaneous blood flow sufficient to maintain oxygen delivery. Wound healing depends to a large extent on tissue oxygen delivery, and these data suggest that even severe anemia by itself would not be sufficient to impair wound healing. Thus, transfusion of autologous packed red blood cells solely to improve healing in surgical patients with no other indication for transfusion is not supported by these results.