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Anesthesiology:
doi: 10.1097/01.anes.0000296643.13634.41
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Hyperoxia-induced Decrease in Organ Blood Flow

Forkner, Ivy F. M.D.; Piantadosi, Claude A. M.D.; Charles, Hal C. Ph.D.; Scafetta, Nicola Ph.D.; Moon, Richard E. M.D.*

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In Reply:—

We thank Dr. Her for his comments on our article.1 He notes that a previous human study by Floyd et al. demonstrated that the magnitude of the decrease in cerebral blood flow (CBF) induced by 100% oxygen administration is more profound than that of the increase in arterial oxygen content,2 which seems to support the notion that hyperoxia can induce tissue hypoxia. This study, which used arterial spin labeled-perfusion magnetic resonance imaging, reported a 29-33% decrease in CBF during 100% oxygen breathing. If the 30% reduction were accurate, then Dr. Her may have a point. However, this reduction in CBF is significantly greater than what has been observed in other studies, in which the reduction has been on the order of 5–15%.3–5 Unfortunately the investigators in the Floyd et al. study made unwarranted assumptions. For instance, they assumed that T1 for blood was the same during air and oxygen breathing despite published data to the contrary.6 This component of the lumped constant in their calculation of CBF leads to a 36% difference based on the T1 of blood with air versus oxygen breathing. Further, they assumed T1 in tissue to be similar to that in blood and suggest that violations of this assumption would cause only a small error. This is clearly not the case and is the reason for the overestimation of changes in CBF found in their study. In a recent article by Bulte et al.,5 in which 100% oxygen reduced CBF less than 10%, the changes in relaxation times of blood and tissue with increased Fio2 are confounders of the arterial spin labeled technique, and that failure to accurately account for them when calculating perfusion will lead to gross overestimation of hyperoxia-induced blood flow changes.
We agree with Dr. Her that acute hypocapnia can be associated with markers of ischemia, such as impaired psychomotor performance, at least in the arterial Pco2 range 20–25 mmHg.7 However, our original manuscript included data showing that during spontaneous breathing, the tendency of 100% oxygen administration to cause hypocapnia is either very small or does not exist.1 Tissue Po2 regulates blood flow such that, although oxygen administration does induce vasoconstriction, there is a monotonically increasing relationship between arterial and tissue Po2.8–10 This has also been observed in the retina.11 In a pig study, the administration of 100% oxygen reduced retinal blood flow by 62% but increased periarteriolar and intervascular Po2.12 It is therefore unlikely that hyperoxia could contribute to retinal ischemia induced by an increase in intraocular pressure, and indeed there is direct evidence to the contrary.13
Oxygen administration also reduces coronary blood flow; however, in the study cited by Dr. Her,14 there is no evidence that the reduced coronary blood flow induced either ischemia or myocardial hypoxia.
With regard to Dr. Her’s comment on oxygen and postoperative wound infections, evidence suggests an inverse relationship between tissue Po2 and infection rate,15 and the bulk of evidence supports the use of supplemental perioperative oxygen to reduce wound infection rate.16,17 The study by Pryor and colleagues cited by Dr. Her,18 which failed to demonstrate a beneficial effect, has been criticized on methodological grounds.19,20
In summary, peripheral blood flow is regulated to maintain tissue oxygenation in the face of alterations in oxygen delivery. There is no evidence that the autoregulatory decrease in tissue blood flow during hypoxia induces tissue ischemia or hypoxia.
Ivy F. Forkner, M.D.
Claude A. Piantadosi, M.D.
Hal C. Charles, Ph.D.
Nicola Scafetta, Ph.D.
Richard E. Moon, M.D.*
*Center for Hyperbaric Medicine & Environmental Physiology, Duke University Medical Center, Durham, North Carolina. moon0002@mc.duke.edu
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References

1. Forkner IF, Piantadosi CA, Scafetta N, Moon RE: Hyperoxia-induced tissue hypoxia: A danger? Anesthesiology 2007; 106:1051–5

2. Floyd TF, Clark JM, Gelfand R, Detre JA, Ratcliffe S, Guvakov D, Lambertsen CJ, Eckenhoff RG: Independent cerebral vasoconstrictive effects of hyperoxia and accompanying arterial hypocapnia at 1 ATA. J Appl Physiol 2003; 95:2453–61

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11. Wangsa-Wirawan ND, Linsenmeier RA: Retinal oxygen: Fundamental and clinical aspects. Arch Ophthalmol 2003; 121:547–57

12. Riva CE, Pournaras CJ, Tsacopoulos M: Regulation of local oxygen tension and blood flow in the inner retina during hyperoxia. J Appl Physiol 1986; 61:592–8

13. Alder VA, Cringle SJ: Intraretinal and preretinal PO2 response to acutely raised intraocular pressure in cats. Am J Physiol 1989; 256:H1627–34

14. McNulty PH, Robertson BJ, Tulli MA, Hess J, Harach LA, Scott S, Sinoway LI: Effect of hyperoxia and vitamin C on coronary blood flow in patients with ischemic heart disease. J Appl Physiol 2007; 102:2040–5

15. Hopf HW, Hunt TK, West JM, Blomquist P, Goodson WH III Jensen JA, Jonsson K, Paty PB, Rabkin JM, Upton RA, von Smitten K, Whitney JD: Wound tissue oxygen tension predicts the risk of wound infection in surgical patients. Arch Surg 1997; 132:997–1004

16. Greif R, Akca O, Horn EP, Kurz A, Sessler DI: Supplemental perioperative oxygen to reduce the incidence of surgical-wound infection: Outcomes Research Group. N Engl J Med 2000; 342:161–7

17. Belda FJ, Aguilera L, Garcia de la Asuncion J, Alberti J, Vicente R, Ferrandiz L, Rodriguez R, Company R, Sessler DI, Aguilar G, Botello SG, Orti R: Supplemental perioperative oxygen and the risk of surgical wound infection: A randomized controlled trial. JAMA 2005; 294:2035–42

18. Pryor KO, Fahey TJ III, Lien CA, Goldstein PA: Surgical site infection and the routine use of perioperative hyperoxia in a general surgical population: A randomized controlled trial. JAMA 2004; 291:79–87

19. Dellinger EP: Increasing inspired oxygen to decrease surgical site infection: Time to shift the quality improvement research paradigm. JAMA 2005; 294:2091–2

20. Brasel K, McRitchie D, Dellinger P: Canadian Association of General Surgeons and American College of Surgeons Evidence Based Reviews in Surgery 21: The risk of surgical site infection is reduced with perioperative oxygen. Can J Surg 2007; 50:214–6

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Correction

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10.1097/01.anes.0000311262.15106.d4
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