Abstract
Purpose
Standard resuscitation practice for shock states mandates use of high flow, high concentration oxygen. However, this may induce microvascular constriction and potentially impair regional oxygen delivery. We thus investigated the impact of varying inspired oxygen concentrations in a rat model of progressive haemorrhage.
Methods
Tissue oxygen tension (the balance between local O2 supply and demand) was measured in four different organ beds (liver, renal cortex, muscle, bladder), with concurrent assessment of cardiorespiratory function and organ perfusion in a spontaneously breathing, anaesthetised rat model. 10% aliquots of circulating blood volume were removed at 15 min intervals until death. Different oxygen fractions in the gas mixture (0.15–1.0) were administered following 20% blood removal. A control group consisted of normovolaemic animals breathing varying oxygen fractions.
Results
Survival times following progressive haemorrhage were similar in animals breathing room air (98 ± 10 min), 60% O2 (102 ± 6 min) or 100% O2 (90 ± 4 min), but significantly worse in those breathing 15% O2 (52 ± 8 min, P < 0.01). Significant derangements of blood pressure, aortic blood flow and lactataemia were observed in both hypoxaemic and hyperoxaemic groups compared to normoxaemic animals. Breathing 100% O2 increased arterial PO2 sevenfold and tPO2 approximately threefold over baseline values during normovolaemia and mild haemorrhage (20% blood volume removal). However, with progressive haemorrhage, and despite maintained PaO2 values, tissue PO2 fell in line with the decrease in global oxygen delivery.
Conclusion
Hypoxaemia and hyperoxaemia both compromised haemodynamics and biochemical markers of organ perfusion during severe, progressive haemorrhage. This may carry implications for resuscitation practice.
Similar content being viewed by others
References
Bitterman H, Reissman P, Bitterman N, Melamed Y, Cohen L (1991) Oxygen therapy in hemorrhagic shock. Circ Shock 33:183–191
Barth E, Bassi G, Maybauer DM, Simon F, Groger M, Oter S, Speit G, Nguyen CD, Hasel C, Moller P, Wachter U, Vogt JA, Matejovic M, Radermacher P, Calzia E (2008) Effects of ventilation with 100% oxygen during early hyperdynamic porcine fecal peritonitis. Crit Care Med 36:495–503
Garner WL, Downs JB, Reilley TE, Frolicher D, Kargi A, Fabri PJ (1989) The effects of hyperoxia during fulminant sepsis. Surgery 105:747–751
Cheung PY, Obaid L, Emara M, Brierley Y, Johnson ST, Chan GS, Jewell L, Korbutt G, Bigam DL (2008) Cardio-renal recovery of hypoxic newborn pigs after 18%, 21% and 100% reoxygenation. Intensive Care Med 34:1114–1121
Tsai AG, Cabrales P, Winslow RM, Intaglietta M (2003) Microvascular oxygen distribution in awake hamster window chamber model during hyperoxia. Am J Physiol Heart Circ Physiol 285:H1537–H1545
Rosser DM, Stidwill RP, Jacobson D, Singer M (1995) Oxygen tension in the bladder epithelium rises in both high and low cardiac output endotoxemic sepsis. J Appl Physiol 79:1878–1882
Rosser DM, Stidwill RP, Jacobson D, Singer M (1996) Cardiorespiratory and tissue oxygen dose response to rat endotoxemia. Am J Physiol 271:H891–H895
Hou H, Grinberg OY, Taie S, Leichtweis S, Miyake M, Grinberg S, Xie H, Csete M, Swartz HM (2003) Electron paramagnetic resonance assessment of brain tissue oxygen tension in anesthetized rats. Anesth Analg 96:1467–1472
Vollmar B, Conzen PF, Kerner T, Habazettl H, Vierl M, Waldner H, Peter K (1992) Blood flow and tissue oxygen pressures of liver and pancreas in rats: effects of volatile anesthetics and of hemorrhage. Anesth Analg 75:421–430
Whitehouse T, Stotz M, Taylor V, Stidwill R, Singer M (2006) Tissue oxygen, hemodynamics in renal medulla, cortex, corticomedullary junction during hemorrhage-reperfusion. Am J Physiol Renal Physiol 291:F647–F653
Dyson A, Stidwill R, Taylor V, Singer M (2007) Tissue oxygen monitoring in rodent models of shock. Am J Physiol Heart Circ Physiol 293:526–533
Knudson MM, Lee S, Erickson V, Morabito D, Derugin N, Manley GT (2003) Tissue oxygen monitoring during hemorrhagic shock and resuscitation: a comparison of lactated Ringer’s solution, hypertonic saline dextran, and HBOC-201. J Trauma 54:242–252
Nordin A, Mildh L, Makisalo H, Harkonen M, Hockerstedt K (1998) Hepatosplanchnic and peripheral tissue oxygenation during treatment of hemorrhagic shock: the effects of pentoxifylline administration. Ann Surg 228:741–747
Kram HB, Appel PL, Fleming AW, Shoemaker WC (1986) Conjunctival and mixed-venous oximeters as early warning devices of cardiopulmonary compromise. Circ Shock 19:211–220
Shoemaker WC, Fink S, Ray CW, McCartney S (1984) Effect of hemorrhagic shock on conjunctival and transcutaneous oxygen tensions in relation to hemodynamic and oxygen transport changes. Crit Care Med 12:949–952
Tremper KK, Waxman K, Shoemaker WC (1979) Effects of hypoxia and shock on transcutaneous PO2 values in dogs. Crit Care Med 7:526–531
Gottrup F, Gellett S, Kirkegaard L, Hansen ES, Johansen G (1989) Effect of hemorrhage and resuscitation on subcutaneous, conjunctival, and transcutaneous oxygen tension in relation to hemodynamic variables. Crit Care Med 17:904–907
Drucker W, Pearce F, Glass-Heidenreich L, Hopf H, Powell C, Ochsner MG, Frankel H, Murray D, Nelson M, Champion H, Rozycki G, Silva J, Malcolm D, DeNobile J, Harviel D, Rich N, Hunt TK (1996) Subcutaneous tissue oxygen pressure: a reliable index of peripheral perfusion in humans after injury. J Trauma 40:S116–S122
Vallet B, Lund N, Curtis SE, Kelly D, Cain SM (1994) Gut and muscle tissue PO2 in endotoxemic dogs during shock and resuscitation. J Appl Physiol 76:793–800
Boekstegers P, Weidenhofer S, Pilz G, Werdan K (1991) Peripheral oxygen availability within skeletal muscle in sepsis and septic shock: comparison to limited infection and cardiogenic shock. Infection 19:317–323
Peitzman AB, Billiar TR, Harbrecht BG, Kelly E, Udekwu AO, Simmons RL (1995) Hemorrhagic shock. Curr Probl Surg 32:925–1002
Boura C, Caron A, Longrois D, Mertes PM, Labrude P, Menu P (2003) Volume expansion with modified hemoglobin solution, colloids, or crystalloid after hemorrhagic shock in rabbits: effects in skeletal muscle oxygen pressure and use versus arterial blood velocity and resistance. Shock 19:176–182
Schlichtig R, Kramer DJ, Boston JR, Pinsky MR (1991) Renal O2 consumption during progressive hemorrhage. J Appl Physiol 70:1957–1962
Thurau K, Boylan JW (1976) Acute renal success. The unexpected logic of oliguria in acute renal failure. Am J Med 61:308–315
Rousseau A, Bak Z, Janerot-Sjoberg B, Sjoberg F (2005) Acute hyperoxaemia-induced effects on regional blood flow, oxygen consumption and central circulation in man. Acta Physiol Scand 183:231–240
Milone SD, Newton GE, Parker JD (1999) Hemodynamic and biochemical effects of 100% oxygen breathing in humans. Can J Physiol Pharmacol 77:124–130
Pasgaard T, Stankevicius E, Jorgensen MM, Ostergaard L, Simonsen U, Frobert O (2007) Hyperoxia reduces basal release of nitric oxide and contracts porcine coronary arteries. Acta Physiol (Oxf) 191:285–296
Mak S, Egri Z, Tanna G, Colman R, Newton GE (2002) Vitamin C prevents hyperoxia-mediated vasoconstriction and impairment of endothelium-dependent vasodilation. Am J Physiol Heart Circ Physiol 282:H2414–H2421
Dallinger S, Dorner GT, Wenzel R, Graselli U, Findl O, Eichler HG, Wolzt M, Schmetterer L (2000) Endothelin-1 contributes to hyperoxia-induced vasoconstriction in the human retina. Invest Ophthalmol Vis Sci 41:864–869
Jackson WF (1989) Arteriolar oxygen reactivity is inhibited by leukotriene antagonists. Am J Physiol 257:H1565–H1572
Messina EJ, Sun D, Koller A, Wolin MS, Kaley G (1994) Increases in oxygen tension evoke arteriolar constriction by inhibiting endothelial prostaglandin synthesis. Microvasc Res 48:151–160
Forkner IF, Piantadosi CA, Scafetta N, Moon RE (2007) Hyperoxia-induced tissue hypoxia: a danger? Anesthesiology 106:1051–1055
Floyd TF, Clark JM, Gelfand R, Detre JA, Ratcliffe S, Guvakov D, Lambertsen CJ, Eckenhoff RG (2003) Independent cerebral vasoconstrictive effects of hyperoxia and accompanying arterial hypocapnia at 1 ATA. J Appl Physiol 95:2453–2461
McNulty PH, Robertson BJ, Tulli MA, Hess J, Harach LA, Scott S, Sinoway LI (2007) Effect of hyperoxia and vitamin C on coronary blood flow in patients with ischemic heart disease. J Appl Physiol 102:2040–2045
Yu M, Morita SY, Daniel SR, Chapital A, Waxman K, Severino R (2006) Transcutaneous pressure of oxygen: a noninvasive and early detector of peripheral shock and outcome. Shock 26:450–456
Yu M, Chapital A, Ho HC, Wang J, Takanishi D Jr (2007) A prospective randomized trial comparing oxygen delivery versus transcutaneous pressure of oxygen values as resuscitative goals. Shock 27:615–622
Goeckenjan G, Strasser K (1977) Relation of transcutaneous to arterial PO2 in hypoxaemia, normoxaemia and hyperoxaemia. Investigations in adults with normal circulation and in patients with circulatory insufficiency. Biotelemetry 4:77–87
O’connor PM, Anderson WP, Kett MM, Evans RG (2006) Renal preglomerular arterial-venous O2 shunting is a structural anti-oxidant defence mechanism of the renal cortex. Clin Exp Pharmacol Physiol 33:637–641
Ba ZF, Wang P, Koo DJ, Cioffi WG, Bland KI, Chaudry IH (2000) Alterations in tissue oxygen consumption and extraction after trauma and hemorrhagic shock. Crit Care Med 28:2837–2842
Meier J, Kemming GI, Kisch-Wedel H, Blum J, Pape A, Habler OP (2004) Hyperoxic ventilation reduces six-hour mortality after partial fluid resuscitation from hemorrhagic shock. Shock 22:240–247
Takasu A, Stezoski SW, Stezoski J, Safar P, Tisherman SA (2000) Mild or moderate hypothermia, but not increased oxygen breathing, increases long-term survival after uncontrolled hemorrhagic shock in rats. Crit Care Med 28:2465–2474
Takasu A, Prueckner S, Tisherman SA, Stezoski SW, Stezoski J, Safar P (2000) Effects of increased oxygen breathing in a volume controlled hemorrhagic shock outcome model in rats. Resuscitation 45:209–220
Douzinas EE, Livaditi O, Andrianakis I, Prigouris P, Paneris P, Villiotou V, Betrosian AP (2008) The effect of hypoxemic resuscitation from hemorrhagic shock on blood pressure restoration and on oxidative and inflammatory responses. Intensive Care Med 34:1133–1141
Her C (2008) Hyperoxia-induced decrease in organ blood flow. Anesthesiology 108:168–169
Acknowledgments
This work was funded by the UK Medical Research Council and Integrative Pharmacological Fund. This work was undertaken at UCLH/UCL who receive a proportion of funding from the UK Department of Health’s NIHR Biomedical Research Centre’s funding scheme. We thank Oxford Optronix for kindly providing the tPO2 probes.
Author information
Authors and Affiliations
Corresponding author
Additional information
This article is discussed in the editorial available at: doi:10.1007/s00134-009-1576-3.
Rights and permissions
About this article
Cite this article
Dyson, A., Stidwill, R., Taylor, V. et al. The impact of inspired oxygen concentration on tissue oxygenation during progressive haemorrhage. Intensive Care Med 35, 1783–1791 (2009). https://doi.org/10.1007/s00134-009-1577-2
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s00134-009-1577-2