A Review of the Clinical Significance of Tissue Hypoxia Measurements in Lower Extremity Wound Management

Abstract

The aim of this paper is to review techniques that are currently available to measure tissue hypoxia in order to benefit the management of wounds. Direct measurement of tissue partial oxygen pressure (PO₂) is invasive and therefore unappealing in clinical practice. Several techniques (PET scans, MRI derived techniques) are primarily applicable to research rather than clinical applications. Imaging techniques (duplex ultrasonography, arteriography, MRI techniques) are recommended only as part of the workup for revascularisation. Techniques that assess local perfusion include clearance methods, transcutaneous O₂ and CO₂ pressure measurement, and laser Doppler flowmetry and imaging. These techniques permit interpretation of altered perfusion states. Each technique offers subtly different information concerning microvascular function. All these techniques require strict protocols to derive reliable data. The potential of the promising near infrared reflectance spectroscopy (NIRS) technique is yet to be determined.

Keywords

wound healing peripheral arterial disease tissue oxygen pressure transcutaneous oxygen pressure laser Doppler flowmetry near infrared reflectance spectroscopy

Get full access to this article

View all access options for this article.

References

Theopold C. , Yao F. , Ericksson E. Cutaneous tissue engineering and lower extremity wounds (part 1). Int J Low Extrem Wounds 2004;3(2):80-86.

Mani R. Science of measurements in wound healing. Wound Repair Regen 1999;6(5):330-334.

Ouriel K. Peripheral arterial disease. Lancet 2001;358:1257-64.

Krentz A. , Mani R. , Shearman CP

Peripheral arterial disease in diabetes: time for a co-ordinated approach to management. Br J Diabetes

Vasc Dis 2003 ;3(2):92-97.

Markowitz JS , Gutteman E. , Glen M. , Margolis DM Risk of amputation in patients with diabetic foot ulcers: a claims based study. Wound Repair Regen 2006;14(1):11-17.

Baumberger JP , Godfriend RB Determination of arterial oxygen tension in man by equilibration trough intact skin. Fed Proc 1951;10:10-11.

Clark LC Jr , Wolf R. , Granger D. Continuous recording of blood oxygen tensions by polarography. J Appl Physiol 1953;6: 189-193.

Clark LC Jr. Monitor and control of blood and tissue oxygen tension . Trans Am Soc Artif Intern Org. 1956;2:41-46.

Huch R. , Lubbers DW , Huch A. Quantitative continuous measurement of partial oxygen pressure on the skin of adults and newborn babies. Pflugers Arch 1972;337:185-198.

10.

Huch A. , Huch R. , Hollmann G. , Hockerts T. Transcutaneous PO2 of volunteers during hyperbaric oxygenation . Biotelemetry 1977;4:88-100.

11.

Eberhard P. , Mindt W. , Jahn F. , Hammacher K. Oxygen monitoring of newborns by skin electrodes. Correlation between arterial and cutaneously determined PO2. In: Bruley DF , Bicher HI , editors. Advances in experimental medicine and biology. New York : Plenum Press; 1973. pp. 1097-1101.

12.

Eberhard P. , Mindt W. , Jann F. , Hammacher K. Continuous PO2 monitoring in the neonate by skin electrodes. Med Biol Eng 1975 ;13:436-442.

13.

Hohenauer L. Transcutaneous monitoring of PO2 (TcPO2) in sick newborn babies: three years of clinical experience. In: Huch A , Huch R , Lucey JF , editors. Continuous transcutaneous blood gas monitoring . New York: Alan R. Liss; 1979. pp. 375-376.

14.

Montgomery H. , Horowitz O. Oxygen tension of tissues by polarographic method. J Clin Invest 1953;29:1120-1130.

15.

Shoemaker WC , Vidyssagar D. Physiological and clinical significance of PTCO2 measurements. Crit Care Med 9:689-690.

16.

Brantigan JW , Ziegler EC , Hynes KM , Dunn KL , Albo D. Tissue gases during hypovolemic shock. J Appl Physiol 1974;31:117-122.

17.

Dennhardt R. , Ricke MF , Huch A. , Huch R. Transcutaneous PO2 monitoring in anaesthesia. Eur J Intens Care Med 1976;2:29-33.

18.

Podolsky S. , Baraff LJ , Geeher E. Transcutaneous oximetry measurements during acute blood loss. Ann Emerg Med 1982;11: 523-525.

19.

Kram HB , Shoemaker WC Diagnosis of major peripheral arterial trauma by transcutaneous oxygen monitoring . Am J Surg 1984;147:776-780.

20.

Eickhoff JH , Engell HC Transcutaneous oxygen tension measurement on the foot in normal subjects and in patients with peripheral arterial disease admitted for vascular surgery. Scand J Clin Lab Invest 1981;41:742-748.

21.

Ratlift DA , Clyne Cac , Chant Adb , Webster Jhh. Prediction of amputation wound healing: the role of transcutaneous PO 2 assessment. Br J Surg 1984;71:219-222.

22.

White RA , Nolan L. , Harley D. , Shoemaker WC Noninvasive evaluation of peripheral vascular disease using transcutaneous oxygen tension. Am J Surg 1982;144:68-75.

23.

Wyss CA , Matsen FA Iii , Simmons CW , Burgess EM Transcutaneous oxygen tension measurements on limbs of diabetic and nondiabetic patients with peripheral vascular disease. Surgery 1984;95:339-345.

24.

Achauer BM , Black KS , Litke DK Transcutaneous PO2 in flaps: a new method of survival prediction . Plast Reconstr Surg 1980;65:738-745.

25.

Serafin D. , Lesence CB , Mullen RY , Georgiade NG Transcutaneous PO2 monitoring for assessing viability and predicting survival of skin flaps: experimental and clinical correlations. J Microsurg 1981;2:165-178.

26.

Sheffield PJ , Workman WT Noninvasive tissue oxygen measurements in patients administered normobaric and hyperbaric oxygen by mask. Hyperb Oxygen 1985;6:47-62.

27.

Abbot NC , Swanson Beck J. , Carnochan FM , Spence VA , James PB Estimating skin respiration from transcutaneous PO2/PCO2 at 1 and 2 atm abs on normal and inflamed skin. J Hyperb Med 1990;5:91-102.

28.

Wattel F. , Mathieu D. , Neviere R. Transcutaneous oxygen pressure measurements. A useful technique to appreciate the oxygen delivery to tissues. J Hyperbaric Med 1991;6:269-281.

29.

Hart GB , Meyer GW , Strauss MB , Messina VJ Transcutaneous partial pressure of oxygen measured in a monoplace hyperbaric chamber at 1.15 and 2 atm abs oxygen. J Hyperb Med 1990;5:223-229.

30.

Dowd Gse , Linge K. , Bentley G. Measurement of transcutaneous oxygen pressure in normal and ischaemic skin . J Bone Joint Surg 1983;65:79-83.

31.

Evans Nts , Naylor Pfd. The systemic oxygen supply to the surface of the human skin. Respir Physiol 1967;3:21-37.

32.

Franzeck UK , Talke P. , Berstein EF , Golbrandon FL , Fronek A. Transcutaneous PO2 measurements in health and peripheral arterial occlusive disease. Surgery 1982;91:153-163.

33.

Hauser CJ , Shoemaker WC Use of a transcutaneous PO2 regional perfusion index to quantify tissue perfusion in peripheral vascular disease. Ann Surg 1983;197:337-343.

34.

Ledermann HP , Heidecker HG , Schulte AC , Thalhammer C. , Aschwanden M. , Jaeger KA , Scheffler K. , Bilecen D. Calf muscles imaged at BOLD MR: correlation with TCPO2 and flowmetry measurements during ischemia and reactive hyperemia—initial experience. Radiology 2006;241:477-84.

35.

Agache P. , Lucas A. , Agache A. Influence of age on transcutaneous oxygen pressure. In: Leveque JL , Agache P , editors. Aging skin properties and function changes. New York: Marcel Dekker; 1992:125-132.

36.

Breuer Hwm , Breuer J. , Berger M. Transcutaneous oxygen pressure measurements in type I diabetic patients for early detection of functional diabetic microangiopathy. Eur J Clin Invest 1988;18:454-459.

37.

Ubbink DT , Tulevski II , den Hartog D. , Koelemay MJ , Legemate DA , Jacobs MJ The value of non-invasive techniques for the assessment of critical limb ischaemia . Eur J Vasc Endovasc Surg 1997;13:296-300.

38.

Ratliff DA , Clyne Cac , Chant Adb , Webster Jhh. Prediction of amputation wound healing: the role of transcutaneous PO 2 assessment. Br J Surg 1984;71(3):219-222.

39.

Hauser CJ , Klein SR , Hehringer CM et al. Superiority of transcutaneous oximetry in non-invasive vascular diagnosis in patients with diabetes. Arch Surg 1984;119:690.

40.

Karanfilian RG , Lynch TG , Zirul VT , Padberg FT , Jamil Z. , Hobson RW The value of laser Doppler velocimetry and transcutaneous oxygen tension determination in predicting healing of ischemic forefoot ulcerations and amputations in diabetic and nondiabetic patients . J Vasc Surg 1986;4:511-516.

41.

Pecoraro RE , Ahroni JH , Boyko EJ , Stensel VL Chronology and determinants of tissue repair in diabetic lower-extremity ulcers. Diabetes 1991;40:1305-1313.

42.

Kalani M. , Brismar K. , Fagrell B. , Ostergren J. , Jorneskog G. Transcutaneous oxygen tension and toe blood pressure as predictors for outcome of diabetic foot ulcers. Diabetes Care 1999 ;22:147-51.

43.

Becker F. , Raoux MH , Brenot R. , David M. Predictive value of TcPO2 in chronical severe ischemia of lower limbs. Int J Microcir Clin Exp 1988 ;7:261-271.

44.

Harward TR , Volny J. , Golbranson F. , Bernstein EF , Fronek A. Oxygen inhalation-induced transcutaneous PO2 changes as a predictor of amputation level. J Vasc Surg 1985;2:220-7.

45.

European Consensus Jury. Second European consensus on critical ischemia. Circulation 1991;84(IV):21-26.

46.

Norgren L. , Hiatt WR , Dormandy JA , Nehler MR , Harris KA , Fowkes FG ; on behalf of the TASC II Working Group. Inter-society consensus for the management of peripheral arterial disease (TASC II). J Vasc Surg 2007;45:S5-S67.

47.

de Graaff JC , Ubbink DT , Legemate DA , Tijssen JG , Jacobs MJ Evaluation of toe pressure and transcutaneous oxygen measurements in management of chronic critical leg ischemia: a diagnostic randomized clinical trial. J Vasc Sur 2003 ;38:528-34.

48.

Bunt TJ , Holloway GA TcPO2 as an accurate predictor of therapy in limb salvage . Ann Vasc Surg 1996;10:224-7.

49.

Ray SA , Buckenham TM , Belli AM , Taylor RS , Dormandy JA The predictive value of laser Doppler fluxmetry and transcutaneous oximetry for clinical outcome in patients undergoing revascularisation for severe leg ischemia. Eur J Vasc Endovasc Surg 1997;13:54-9.

50.

Ubbink DT , Spincemaille GH , Reneman RS , Jacobs MJ Prediction of imminent amputation in patients with non-reconstructable leg ischaemia by means of microcirculatory investigations. J Vasc Surg 1999;30:114-21.

51.

Caselli A. , Latini V. , Lapenna A. , Di Carlo S. , Pirozzi F. , Benvenuto A. , Uccioli L. Transcutaneous oxygen tension monitoring after successful revascularization in diabetic patients with ischaemic foot ulcers. Diabet Med 2005;22:460-5.

52.

Depairon M. , Krahenbuhl B. , Vaucher J. Determination of the amputation level by transcutaneous PO2 measurement and distal arterial systolic pressure. J Mal Vasc 1986;11:229-34.

53.

Bacharach JM , Rooke TW , Osmundson PJ , Gloviczki P. Predictive value of transcutaneous oxygen pressure and amputation success by use of supine and elevation measurements . J Vasc Surg 1992;15:558-63.

54.

Slagsvold CE , Kvernebo K. , Slungaard U. , Kroese AJ Pre- and postischemic transcutaneous oxygen tension measurements and the determination of amputation level in ischemic limbs. Acta Chir Scand 1989;155:527-31.

55.

Wutschert R. , Bounameaux H.

Determination of amputation level in ischemic limbs: reappraisal of the measurement of TcPO2

Diabetes Care 1997;20:1315-8.

56.

Poredos P. , Rakovec S. , Guzic-Salobir B. Determination of amputation level in ischaemic limbs using TcPO 2 measurement. Vasa 2005;34:108-12.

57.

Kranke P. , Bennett M. , Roeckl-Wiedmann I. , Debus S. Hyperbaric oxygen therapy for chronic wounds. Cochrane Database Syst Rev 2004;CD004123.

58.

Wattel F. , Mathieu D. , Coget JM , Billard V. Hyperbaric oxygen therapy in chronic vascular wound management. Angiology 1990;42:59-65.

59.

Wattel F. , Mathieu D. , Fossati F. , Neviere R. , Coget JM Hyperbaric oxygen in the treatment of diabetic foot. Undersea Biomed Res 1990;17(suppl):160-161.

60.

European Committee for Hyperbaric Medicine. Recommendation of the 7th European consensus conference on hyperbaric medicine. Eur J Underwater Hyp Med 2005;6:29-40.

61.

Saiman M. , Glantzounis GK , Yang W. , Myint F. , Hamilton G. , Seifalian AM Measurement of critical lower limb tissue hypoxia by coupling chemical and optical techniques. Clin Sci (Lond) 2005;108:159-65.

62.

Melillo E. , Ferrari M. , Balbarini A. , Pedrinelli R.

Transcutaneous oxygen and carbon dioxide levels with iloprost administration in diabetic critical limb ischemia. Vasc Endovascular

Surg 2006; 40:303-11.

63.

McCollum PT , Spence VA , Walker WF Circumferential skin blood flow measurements in the ischaemic limb. Br J Surgery 1985;72:310-312.

64.

Holstein P. , Dovey A. , Lassen NA Wound healing in below knee amputations in relation to skin perfusion pressure. Acta Orthop Scand 1979;50:49-58.

65.

Mani R. Non invasive techniques for monitoring cutaneous perfusion. In: Spence VA , Tooke JE , editors. Practical aspects of skin blood flow. London: Churchill Livingstone; 1985 . pp. 57-62.

66.

Riva C. , Ross B. , Benedek GB Laser Doppler measurements of blood flow in capillary tubes and retinal arteries . Invest Ophthalmol 1972;11:936-944.

67.

Stern MD In vivo evaluation of microcirculation by coherent light scattering. Nature 1975;254:56-58.

68.

Holloway GA Jr , Watkins DW Laser Doppler measurement of cutaneous blood flow. J Invest Dermatol 1977;69:306-309.

69.

Nilsson GE , Tenland T. , Oberg PA A new instrument for continuous measurement of tissue blood flow by light beating spectroscopy. IEEE Trans Biomed Eng 1980;27:1-8.

70.

Bonner RF , Clem TR , Bowen PD Laser Doppler continuous real-time monitor of pulsatile and mean blood flow in tissue microcirculation. In: Chen SH , Chu B , Nossal R , editors. Scattering techniques applied to supramolecular and non-equilibrium systems. New York: Plenum Press ; 1981. pp. 685-701.

71.

Bonner R. , Nossal R. Model for laser Doppler measurements of blood flow in tissue. Appl Optics 1981;20:2097-2107.

72.

Saumet JL , Dittmar A. , Leftheriotis G. Non invasive measurement of skin blood flow: comparison between plethysmography, laser Doppler flowmeter and heat thermal clearance method. Int J Microc Clin Exp 1986;5:73-83.

73.

Fagrell B. Advances in microcirculation network evaluation: an update. Int J Microcirc 1995;15(suppl 1):34-40.

74.

Bircher A. , De Boer EM , Agner T. , Wahlberg JE , Serup J. Guidelines for measurement of cutaneous blood flow by laser Doppler flowmetry. A report from the standardization group of the European society of contact dermatitis. Contact Dermatitis 1994;30:65-72.

75.

Iabichella ML , Melillo E. , Mosti G. A review of microvascular measurements in wound healing. Int J Low Extrem Wounds 2006 ;5(3):181-199.

76.

Pape SA , Skouras CA , Byrne PO An audit of the use of laser Doppler imaging (LDI) in the assessment of burns of intermediate depth. Burns 2001;27:233-9.

77.

Jöbsis FF Noninvasive, infrared monitoring of cerebral and myocardial oxygen sufficiency and circulatory parameters. Science 1977;198:1264-1267.

78.

Piantadosi CA , Comfort BJ Development and validation of multiwavelength algorithms for in vivo near infrared spectroscopy. In: Chance B , editor. Photon migration in tissues. New York: Plenum Press; 1989. pp. 69-82.

79.

Simonson SG , Piantadosi CA Near-infrared spectroscopy: clinical applications . Crit Care Clin 1996;12:1019-1029.

80.

Kragelj R. , Jarm T. , Miklavcic D. Reproducibility of parameters of postocclusive reactive hyperemia measured by near infrared spectroscopy and transcutaneous oximetry. Ann Biomed Eng 2000;28:168-73.

81.

Kooijman HM , Hopman MT , Colier WN , van der Cliet JA , Oeseburg B. Near infrared spectroscopy for noninvasive assessment of claudication. J Surg Res 1997;72:1-7.

82.

Comerota AJ , Throm RC , Kelly P. , Jaff M. Tissue (muscle) oxygen saturation (StO 2): a new measure of symptomatic lower-extremity arterial disease. J Vasc Surg 2003;38:724-9.

83.

Ubbink DT , Koopman B. Near-infrared spectroscopy in the routine diagnostic work-up of patients with leg ischaemia. Eur J Vasc Endovasc Surg 2006 ;31:394-400.