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Keywords:

  • Arteriolar constriction;
  • Hyperoxia;
  • Oxygen;
  • Oxygen transport;
  • Tissue oxygenation

SUMMARY

  1. Top of page
  2. SUMMARY
  3. INTRODUCTION
  4. HYPEROXIC VENTILATION AS A RESCUE THERAPY FOR MYOCARDIAL INFARCTION
  5. HYPEROXIC VENTILATION DURING INFLAMMATION AND SEPSIS
  6. HYPEROXIC VENTILATION DURING MODERATE ANEMIA
  7. HYPEROXIC VENTILATION DURING EXTREME, CRITICAL ANEMIA
  8. HYPEROXIC VENTILATION DURING SEVERE HEMORRHAGIC SHOCK
  9. HYPEROXIC VENTILATION DURING EXTREME METHEMOGLOBINEMIA
  10. CONCLUSION
  11. REFERENCES

Application of high inspiratory oxygen concentrations is an established method to improve arterial oxygen content, oxygen transport and tissue oxygenation. However, in the past years a considerable amount of data have emerged challenging this approach: hyperoxic ventilation (ventilation with pure oxygen, HV) and subsequent hyperoxemia have been accused of inducing unfavorable effects on microcirculation and tissue perfusion, resulting in regional tissue hypoxia. Interestingly, these disadvantegous properties of HV seem to occur predominantly in patients with physiological hemoglobin concentrations and probably play a minor role in anemic patients. In animal experiments the effect of HV on tissue oxygenation and on outcome of several severe pathologic conditions essentially depends on the hemoglobin concentration: HV failed to have a considerable impact on survival of severe hypovolemia or methemoglobinemia (physiological hemoglobin concentration), whereas it convincingly improves outcome of severe normovolemic anemia. The present review discusses a perspective on the effects of HV at different hemoglobin concentrations and its potential to improve oxygen transport and tissue oxygenation especially during moderate and severe anemia.


INTRODUCTION

  1. Top of page
  2. SUMMARY
  3. INTRODUCTION
  4. HYPEROXIC VENTILATION AS A RESCUE THERAPY FOR MYOCARDIAL INFARCTION
  5. HYPEROXIC VENTILATION DURING INFLAMMATION AND SEPSIS
  6. HYPEROXIC VENTILATION DURING MODERATE ANEMIA
  7. HYPEROXIC VENTILATION DURING EXTREME, CRITICAL ANEMIA
  8. HYPEROXIC VENTILATION DURING SEVERE HEMORRHAGIC SHOCK
  9. HYPEROXIC VENTILATION DURING EXTREME METHEMOGLOBINEMIA
  10. CONCLUSION
  11. REFERENCES

Oxygen (O2) is by far the most commonly used pharmacon in anesthesiology and intensive care. Obviously every patient is receiving O2 during general surgery or during a contingently necessary stay at the intensive care unit. According to the package leaflet medical O2 can be used for treatment of many different kinds of hypoxia or hypoxemia (Package leaflet Sauerstoff medical, Air Liquide, Düsseldorf, Germany; SachNr: 770.31115, Rev. 3): the aim of this measure is either to increase arterial oxygen partial pressure (pO2) in case of hypoxia, or to increase arterial oxygen content (CaO2) in case of hypoxemia. The increase of CaO2 is usually mediated (i) to a small extent by an increase of hemoglobin bound oxygen and (ii) to an much greater extent by an increase of physically dissolved oxygen (Figure 1).1–4 Due to this immediate and simple increase of CaO2, the application of pure oxygen has been implemented into many different emergency algorithms and guidelines. This approach is deduced from the conception that an increase of CaO2 will automatically result in an immediate amelioration of tissue oxygenation.

image

Figure 1. Arterial oxygen content (CaO2) depending on arterial oxygen partial pressure (paO2). Dashed line: physically dissolved oxygen; solid line: hemoglobin bound oxygen; dotted line: sum of physically dissolved and hemoglobin bound oxygen.

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However, this is not true for all situations where oxygen is applied. In 1972 Duling et al. demonstrated that a supranormal arterial pO2 (hyperoxia) results in a decline of microvascular blood flow.5–7 This phenomenon is provoked by general arteriolar constriction, which is basically mediated by 20-HETE, a metabolite of arachidonic acid metabolism.8 This arteriolar constriction results in a reduction of functional capillary density and cardiac output at physiological hemoglobin concentrations (Figure 2).9–15 Furthermore, microvascular blood flow is reallocated and previously homogeneously perfused tissues become perfused more heterogeneously.14,16,17 As a consequence, afore normally perfused tissues are increasingly involved by compromised perfusion.14 Surprisingly, up to now no evidence exists that ventilation with pure O2 can significantly increase oxygen delivery (DO2): all studies addressing the effects of hyperoxic ventilation on oxygen transport failed to demonstrate a significant increase of calculated DO2 despite a significant increase of CaO2.18–20

image

Figure 2. Oxygen response of aparenchymal arteriols of the hamster cheek pouch in situ (intravital microscopy). Arteriols were suffused with a normal saline solution equilibrated to different oxygen partial pressures (x-axis). The mean arteriolar diameter is depicted on the y-axis. Adapted from Duling.7

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Despite these unfavorable findings, hyperoxic ventilation is used as a rescue therapy for many different pathologies. Thereby, the effects and the effectiveness of hyperoxic ventilation differ depending on the situation where this measure is used.

HYPEROXIC VENTILATION AS A RESCUE THERAPY FOR MYOCARDIAL INFARCTION

  1. Top of page
  2. SUMMARY
  3. INTRODUCTION
  4. HYPEROXIC VENTILATION AS A RESCUE THERAPY FOR MYOCARDIAL INFARCTION
  5. HYPEROXIC VENTILATION DURING INFLAMMATION AND SEPSIS
  6. HYPEROXIC VENTILATION DURING MODERATE ANEMIA
  7. HYPEROXIC VENTILATION DURING EXTREME, CRITICAL ANEMIA
  8. HYPEROXIC VENTILATION DURING SEVERE HEMORRHAGIC SHOCK
  9. HYPEROXIC VENTILATION DURING EXTREME METHEMOGLOBINEMIA
  10. CONCLUSION
  11. REFERENCES

Oxygen has been used in the treatment of myocardial infarction (MI) and acute coronary syndromes for over 100 years.21 The rationale for this longstanding use is the belief that hyperoxic ventilation should increase oxygen delivery to the ischemic myocardium, thereby reducing the size of MI and improving clinical outcomes. However, concern has been expressed that the routine use of supplemental oxygen in MI might not improve outcome but may potentially cause harm.22,23 Despite this conflicting evidence, contemporary international guidelines recommend the routine use of supplemental oxygen in the treatment of MI.24,25 However, a recent review and meta-analysis concluded that there is a lack of evidence to support the routine prescription of high-flow oxygen therapy in patients with uncomplicated MI.26 Furthermore, a pessimistic interpretation of the available data might even exclude supplementary oxygen from the therapeutic routine in this situation.26 The fear of potential harm with high concentration oxygen therapy results from its known hemodynamic effects. In patients with MI, hyperoxia reduces cardiac output and stroke volume, and increases the mean arterial pressure and systemic vascular resistance. As a consequence, in most of the cases hyperoxic ventilation does not increase oxygen transport, as the reduction in nutritive organ blood flow is in excess of the increase in oxygen content.26,27 Furthermore, hyperoxic ventilation is a major determinant of artery regulatory tone. The magnitude of the reduction in coronary blood flow with hyperoxia might be substantial in patients with MI.28 Moreover, hyperoxia-induced formation of radical oxygen species might essentially affect myocardial tissue integrity and by that promote tissue damage.29

HYPEROXIC VENTILATION DURING INFLAMMATION AND SEPSIS

  1. Top of page
  2. SUMMARY
  3. INTRODUCTION
  4. HYPEROXIC VENTILATION AS A RESCUE THERAPY FOR MYOCARDIAL INFARCTION
  5. HYPEROXIC VENTILATION DURING INFLAMMATION AND SEPSIS
  6. HYPEROXIC VENTILATION DURING MODERATE ANEMIA
  7. HYPEROXIC VENTILATION DURING EXTREME, CRITICAL ANEMIA
  8. HYPEROXIC VENTILATION DURING SEVERE HEMORRHAGIC SHOCK
  9. HYPEROXIC VENTILATION DURING EXTREME METHEMOGLOBINEMIA
  10. CONCLUSION
  11. REFERENCES

Formation of radical oxygen species might even play a more pronounced role during inflammation and sepsis: the systemic inflammatory response syndrome (SIRS) and septic shock are associated with oxidative stress resulting from enhanced formation of reactive oxygen species (ROS) and nitrogen species, whereby ROS production is directly related to oxygen tension.30,31 As a consequence, hyperoxia might theoretically aggravate tissue injury during SIRS and sepsis. It has been demonstrated for ischemia/reperfusion-induced SIRS that in this situation hyperoxic ventilation can induce severe tissue damage and by that organ failure of several organs by ROS induction.32 However, on the other side the effect of hyperoxic ventilation on tissue oxygenation during SIRS and septic shock might essentially depend on the interaction of hyperoxic conditions with the inflammation-related bioavailability of NO. It has been demonstrated by Cabrales and co-workers that decreased NO availability magnifies the vasoactive responses of the microcirculation to changes in oxygen supply, reducing the supply to the tissue by increasing oxygen vessel wall consumption.33 As a consequence, during SIRS and sepsis with increased NO bioavailability hyperoxic ventilation seems to have the ability to improve oxygen transport and tissue oxygenation.34 It has been demonstrated that hyperoxia during fecal peritonits does not affect lung mechanics or gas exchange, does not aggravate oxidative or nitrosative stress, redistributes cardiac output in favor of the hepatosplanchnic organs, improves direct aerobic glucose oxidaton rate and renal function, attenuates renal function, attenuates metabolic acidosis and reduces apoptosis in liver and lung.34 However, it remains an open question whether these conclusions are applicable in conditions of decreased NO bioavaliabiity, such as those associated with latent, present or induced endothelial dysfunction.

HYPEROXIC VENTILATION DURING MODERATE ANEMIA

  1. Top of page
  2. SUMMARY
  3. INTRODUCTION
  4. HYPEROXIC VENTILATION AS A RESCUE THERAPY FOR MYOCARDIAL INFARCTION
  5. HYPEROXIC VENTILATION DURING INFLAMMATION AND SEPSIS
  6. HYPEROXIC VENTILATION DURING MODERATE ANEMIA
  7. HYPEROXIC VENTILATION DURING EXTREME, CRITICAL ANEMIA
  8. HYPEROXIC VENTILATION DURING SEVERE HEMORRHAGIC SHOCK
  9. HYPEROXIC VENTILATION DURING EXTREME METHEMOGLOBINEMIA
  10. CONCLUSION
  11. REFERENCES

Hyperoxic arteriolar constriction and the associated microcirculatory failure most distinctively emerge at physiological hemoglobin concentrations. As a consequence, microcirculatory failure is absent during moderate anemia (Hb 8 g/dL).18,35 It seems as if the actual hemoglobin concentration plays a key role for the changes of vascular tone during hyperoxia.

In contrast to the dysregulation of the microcirculation at physiological hemoglobin concentrations, this effect seems to be diminished after preceding normovolemic hemodilution (i.e. 1:1 exchange of blood with an isooncotic colloidal solution) to a hemoglobin concentration of 7 g/dL.18 The increase of blood flow velocity and the increase of shear stress at the endothelium during hemodilution result in NO-mediated vasodilation.36 This hemodilution-induced vasodilation compensates for hyperoxia-induced arteriolar constriction, and as a consequence a maldistribution of blood flow cannot be observed.1

It has been demonstrated that the hemodilution-induced decline of systemic vascular resistance re-increases after the onset of hyperoxic ventilation without reaching its baseline level (Figure 3).1,18 Despite its low solubility in plasma, physically dissolved oxygen becomes an biologically relevant oxygen source in this situation, which covers up to 75% of whole body VO2.18–20,37,38

image

Figure 3. Schematic depiction of changes in arteriolar diameter when hyperoxia is performed (i) in subjects with physiological hemoglobin concentrations (left side), or (ii) in hemodiluted subjects (right side). Hemodilution-induced vasodilatation compensates for hyperoxia-induced vasoconstriction.

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It has been demonstrated in several animal experiments that animals ventilated with pure oxygen tolerate considerably lower hemoglobin concentrations than animals ventilated with room air.18,39–41 The resulting hyperoxemia creates a margin of safety for myocardial,18,41,42 intestinal37 and cerebral tissue oxygenation.43,44

However, in the majority of cases these effects have only been investigated for physiological hemoglobin concentrations and for uncritical anemia (Hb 8–10 g/dL).45,46 It cannot be excluded that at such ‘high’ hemoglobin concentrations a hemoglobin-based margin of safety compensates for potentially negative effects of hyperoxemia (microcirculatory failure, a decline of cardiac output, no effect on DO2, formation of O2-radicals). It has been completely unknown for a long time, whether during critical anemia (Hb ∼3 g/dL) – i.e. in absence of any margin of safety for tissue oxygenation – these toxic effects of hyperoxemia might become essential for the outcome of an organism, and that the hyperoxia-induced microcirculatory failure might result in lethal organ failure in this situation.

HYPEROXIC VENTILATION DURING EXTREME, CRITICAL ANEMIA

  1. Top of page
  2. SUMMARY
  3. INTRODUCTION
  4. HYPEROXIC VENTILATION AS A RESCUE THERAPY FOR MYOCARDIAL INFARCTION
  5. HYPEROXIC VENTILATION DURING INFLAMMATION AND SEPSIS
  6. HYPEROXIC VENTILATION DURING MODERATE ANEMIA
  7. HYPEROXIC VENTILATION DURING EXTREME, CRITICAL ANEMIA
  8. HYPEROXIC VENTILATION DURING SEVERE HEMORRHAGIC SHOCK
  9. HYPEROXIC VENTILATION DURING EXTREME METHEMOGLOBINEMIA
  10. CONCLUSION
  11. REFERENCES

During acute anemia tissue oxygenation is not endangered as long as the critical hemoglobin concentration has not been reached. The critical hemoglobin concentration (Hbcrit) is defined as that hemoglobin where oxygen demand of the tissues can no longer be satisfied. Without treatment generalized tissue hypoxia develops within a short period of time.

Determination of Hbcrit

The individual Hbcrit can be determined by detection of a decline of previously stable VO2 values. At physiological hemoglobin concentrations 3–4 times more oxygen is delivered by the circulation than is actually needed by the tissues (‘luxury DO2’).47 As a consequence, oxygen demand can be satisfied over a large range of normovolemic anemia although DO2 is continuously declining.48 Finally, during extreme hemodilution ‘luxury DO2’ is completely exhausted and in this situation DO2 and VO2 balance each other. If this degree of dilution is exceeded, DO2 declines below O2-demand of organs and tissues and as a consequence VO2 (constant so far) begins to decline.49 This decline of VO2 has to be interpreted as an indicator of severe tissue hypoxia (Figure 4). The continuous registration of VO2 via a metabolic monitor and the immediate detection of an acute VO2-decline enables one to detect significant tissue hypoxia individually and contemporarily – independently from the actual hemoglobin concentration.49 The corresponding DO2 is called ‘critical’ DO2 (DO2crit) and in analogy the corresponding hemoglobin concentration is called ‘critical’ Hb (Hbcrit). A computer software especially designed for this purpose can be used to detect a significant decline of VO2 automatically according to a preset standard (‘DeltaCrit System’).49

image

Figure 4. Dependency of oxygen consumption (VO2) on oxygen delivery (DO2) during normovolemic anemia. Despite an initial decrease of DO2, VO2 remains stable over a long period (DO2 is independent of VO2). If a critical hemoglobin concentration (Hbcrit) is reached, VO2 starts to decrease because of critical restriction (DO2 dependent on VO2).

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Hyperoxic ventilation at Hbcrit

At hemoglobin concentrations above Hbcrit any restriction of oxygen transport does not necessarily result in tissue hypoxia as a margin of safety for tissue oxygenation still exists. Therefore, it is difficult to detect ‘harm’ of hyperoxia in the sense of a reduction of nutritive organ blood flow. However, if Hbcrit is reached any additional restriction of tissue perfusion should result in severe tissue hypoxia and by that in an increase of mortality.

In a recent study 14 anesthetized piglets ventilated on room air were hemodiluted with hydroxyethyl starch (HAES 6%, MW 200,000, Braun Melsungen, Melsungen, Germany) until their individual critical hemoglobin concentration had been reached. After detection of Hbcrit animals were either observed without any further intervention (control group), or were ventilated with pure oxygen (hyperoxia group).50

All animals of the control group died within 3 hours, whereas 6 of 7 animals of the hyperoxia group survived the six-hour observation period (Figure 5A). The onset of hyperoxic ventilation in the hyperoxia group was accompanied by a stabilization of macrohemodynamics, an increase of mean arterial blood pressure, and an increase of coronary perfusion pressure. Even in this situation, ventilation with pure O2 did not result in an increase of DO2. This protocol was the first to demonstrate that ventilation with pure O2 significantly increases survival in the presence of critical dilutional anemia, and as a consequence can be recommended as a first-line measurement in this situation. Potential toxic effects of hyperoxic ventilation on microvascular perfusion seem to be negligible regarding the main outcome parameter ‘survival rate’.

image

Figure 5. Experimental protocol of the three studies described in detail and Kaplan–Meier plot of the according survival rates observed for normoxic (solid line) and hyperoxic (dashed line) ventialtion during (A) extreme normovolemic anemia, (B) hemorrhagic shock and (C) severe methemoglobinemia. Hyperoxic ventilation increases six-hour survival rate for extreme normovolemic anemia and for hemorrhagic shock, but fails to improve the six-hour survival rate of severe methemoglobinemia.

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Furthermore, direct measurement of tissue oxygen partial pressure and in vivo registration of microvascular terminal vessels corroborate these speculations.14,35 While ventilation with pure oxygen results in microcirculatory failure at physiological hemoglobin concentrations, this effect is diminished during moderate anemia,18 and furthermore does not result in significant local restrictions of tissue oxygen supply during extreme anemia.50

HYPEROXIC VENTILATION DURING SEVERE HEMORRHAGIC SHOCK

  1. Top of page
  2. SUMMARY
  3. INTRODUCTION
  4. HYPEROXIC VENTILATION AS A RESCUE THERAPY FOR MYOCARDIAL INFARCTION
  5. HYPEROXIC VENTILATION DURING INFLAMMATION AND SEPSIS
  6. HYPEROXIC VENTILATION DURING MODERATE ANEMIA
  7. HYPEROXIC VENTILATION DURING EXTREME, CRITICAL ANEMIA
  8. HYPEROXIC VENTILATION DURING SEVERE HEMORRHAGIC SHOCK
  9. HYPEROXIC VENTILATION DURING EXTREME METHEMOGLOBINEMIA
  10. CONCLUSION
  11. REFERENCES

Although ventilation with pure oxygen increases survival rate of critical normovolemic anemia, the same might not be necessarily true for hypovolemic anemia. Indeed, a similar effect of hyperoxic ventilation on survival has not been demonstrated throughout for acute hypovolemic anemia (hemorrhagic shock).51–53

Distinctive blood loss during hemorrhagic shock is accompanied by a reduction of ventricular stroke volume and by a reduction of cardiac output, both mediated by baroreceptors of the carotis sinus and the aortic arch. The consecutive decline of mean arterial pressure results in a sympathoadrenergic compensatory reaction. This compensatory mechanism is made up of an activation of the sympathic myocardial and circulatory innervation by a postganglionic release of norepinephrine as well as a maximum stimulation of the adrenal medulla with the subsequent systemic release of epinephrine and norepinephrine. The compensatory mechanisms of normovolemic anemia (dilutional anemia) and hypovolemic anemia (hemorrhagic shock) differ essentially: while the reduction of the circulating red cell mass during normovolemic anemia is compensated for by generalized vasodilation with an consecutive increase of cardiac output and nutritive organ blood flow, compensation of hemorrhagic shock consists of peripheral vasoconstriction and centralization of the circulation.

These differences in compensatory mechanisms might explain why the influence of hyperoxemia as sole therapeutic option never had any verifiable effect on the survival rate of severe hemorrhagic shock51–54: the combination of hyperoxic arteriolar constriction and shock-induced peripheral hypoperfusion seems to constrain tissue oxygenation to such an extent that the additional amount of physically dissolved oxygen has no longer a positive influence on survival rate. However, there is only little evidence to decide whether the combination of hyperoxic ventilation and partial substitution of the blood volume lost with erythrocyte free solutions (with a subsequent induction of dilutional anemia) results in an amelioration of the survival rate.

In a recent animal model focusing on the effects of hyperoxic ventilation during hypovolemic anemia, hemorrhagic shock was induced in 14 anesthetized piglets by controlled exsanguination until a mean arterial pressure of 35–40 mmHg was reached.55 This blood pressure was maintained for 1 hour and thereafter the plasma volume withdrawn was replaced by hydroxyethyl starch. Thereupon, seven animals were observed for up to 6 hours without any further intervention (control group), whereas the other seven animals were ventilated with pure O2 (hyperoxia group).

While 5 of the 7 animals of the control group died within the six-hour observation period all animals of the hyperoxia group survived the six-hour observation period (Figure 5B). Ventilation with pure oxygen in the hyperoxia group stabilized macrohemodynamics (especially blood pressure and cardiac output) and resulted in a significant amelioration of tissue oxygenation (increase of tissue oxygen partial pressure). In contrast to previous study protocols (hyperoxemia during hemorrhagic shock without concomitant volume substitution), it was demonstrated, for the first time, that ventilation with pure oxygen as a supplemental measure to volume substitution is an effective therapeutic option during severe hemorrhage. Again potential toxic effects of hyperoxemia on the microcirculation can be disregarded in view of survival rate. Despite ongoing hypovolemia it seems as if moderate dilutional anemia at least partially compensates for the vasoactive properties of oxygen.50

Ventilation with 100% oxygen led to an immediate, significant increase of mean arterial pressure, a phenomenon that has been described for animals and humans since a long time period.56 The increase in mean arterial blood pressure resulted presumably from vasoconstriction in skeletal muscle. It has been demonstrated in recent animal studies that oxygen did not change the vascular resistance in the renal and superior mesenteric beds, and induced a significant increase in blood flow to the renal artery, superior mesenteric artery and the small bowel,57 a result that has especially been demonstrated for acute normovolemic anemia.13 The differential effect of oxygen on regional vascular resistance was followed by an increase in splanchnic and renal blood flow ‘at the expense’ of the hindquarter. Thus, inhalation of oxygen probably induces a shift of blood from the peripheral muscular bed to regions of the body with lower vascular resistance (e.g. to the kidney and splanchnic viscera). Redistribution of blood flow to the renal and splanchnic vascular beds during hemorrhagic shock may be an important mechanism underlying the beneficial effects of oxygen in this condition. However, it can be speculated that this effect might play a minor role at physiological hemoglobin concentrations, but up to date this topic has not been elucidated completely.

HYPEROXIC VENTILATION DURING EXTREME METHEMOGLOBINEMIA

  1. Top of page
  2. SUMMARY
  3. INTRODUCTION
  4. HYPEROXIC VENTILATION AS A RESCUE THERAPY FOR MYOCARDIAL INFARCTION
  5. HYPEROXIC VENTILATION DURING INFLAMMATION AND SEPSIS
  6. HYPEROXIC VENTILATION DURING MODERATE ANEMIA
  7. HYPEROXIC VENTILATION DURING EXTREME, CRITICAL ANEMIA
  8. HYPEROXIC VENTILATION DURING SEVERE HEMORRHAGIC SHOCK
  9. HYPEROXIC VENTILATION DURING EXTREME METHEMOGLOBINEMIA
  10. CONCLUSION
  11. REFERENCES

The results of the studies presented prove that hyperoxic induced microcirculatory failure can be diminished or even prevented, if concurrently microvascular perfusion is increased by anemia-induced vasodilation. These results have been approved for moderate and extreme normovolemic dilutional anemia as well as for hypovolemic anemia with survival models and the aid of several imaging techniques (e.g. intravital microscopy).14,58 However, it remains unclear whether the application of O2 during a critical restriction of tissue oxygenation at physiological hemoglobin concentrations could result in a deterioration of the survival rate, as it can be speculated that without concomitant anemia-induced vasodilatation the negative effects of hyperoxic ventilation (arteriolar constriction, reduction of nutritive organ blood flow, microcirculatory failure) might overweigh the positive effects on macrohemodynamics and oxygen transport. In a recent study the effects of hyperoxic ventilation on survival rate during acute, critical methemoglobinemia were tested. Methemoglobinemia reduces arterial oxygen content without any change of the amount of red blood cells or the arterial oxygen partial pressure (paO2). Viscosity as the main determinant of the rheological properties of blood remains unchanged.59–62

In this model critical methemoglobinemia was induced in 14 anesthetized pigs ventilated on room air by injection of 4-dimethylaminophenol (4-DMAP). Concurrently, oxygen carrying amount of hemoglobin declined from 9.4 to 3.4 g/dL by an increase of the percental proportion of methemoglobin to 60%. VO2 determined by indirect calorimetry declined by 10–22% as an indicator for severe supply dependency due to insufficient global oxygen supply. Thereafter, animals were either observed without any further intervention for 6 hours (control group) or ventilated with pure oxygen (hyperoxia group). The main outcome parameter of this study was again the six-hour survival rate in both groups.

In contrast to the aforementioned studies (shock, hemodilution) hyperoxic ventilation failed to increase the six-hour survival rate in severe methemoglobinemia. Admittedly, mean survival time could be improved significantly from 105 ± 30 to 210 ± 64 minutes by this measure (Figure 5C). Furthermore, no difference between the two groups could be observed for all relevant parameters of macrohemodynamics, oxygen transport and tissue oxygenation. Ventilation with pure oxygen at physiological hemoglobin concentrations, physiological hematocrit, physiological blood viscosity and a contemporaneous critical reduction of arterial oxygen content only resulted in a negligible amelioration of oxygen transport and tissue oxygenation, and by that survival.

These results can be interpreted as indirect proof for the hypothesis that the efficacy of hyperoxic ventilation is directly correlated to hemoglobin, blood viscosity, shear stress and resulting anemia-induced vasodilation.

CONCLUSION

  1. Top of page
  2. SUMMARY
  3. INTRODUCTION
  4. HYPEROXIC VENTILATION AS A RESCUE THERAPY FOR MYOCARDIAL INFARCTION
  5. HYPEROXIC VENTILATION DURING INFLAMMATION AND SEPSIS
  6. HYPEROXIC VENTILATION DURING MODERATE ANEMIA
  7. HYPEROXIC VENTILATION DURING EXTREME, CRITICAL ANEMIA
  8. HYPEROXIC VENTILATION DURING SEVERE HEMORRHAGIC SHOCK
  9. HYPEROXIC VENTILATION DURING EXTREME METHEMOGLOBINEMIA
  10. CONCLUSION
  11. REFERENCES

The results described enable judgment of the efficacy and the peril of hyperoxic ventilation: Ventilation with pure oxygen resulting in consecutive hyperoxemia has the ability to ameliorate survival rate of critical normovolemic and critical hypovolemic anemia. The anemia-induced vasodilation compensates for hyperoxia-induced arteriolar constriction to such an extent that a ‘net-vasoconstriction’ with subsequent microcirculatory failure is prevented. The vasoconstrictive component of hyperoxemia might even result in stabilization of macrohemodynamics and especially myocardial perfusion and function. If hyperoxic ventilation is applied during a critical restriction of oxygen transport capacity of blood without a concomitant reduction of blood viscosity (methemoglobinemia) efficacy of this measure is diminished. This is an indirect proof for the theory that arteriolar induced microcirculatory failure especially occurs at physiologic hemoglobin concentrations with unmodified rheology of blood. As a consequence, the initially described paradox of an aggravation of tissue oxygenation despite an amelioration of O2-transport capacity has to be put into perspective. One of the most important prerequisites for the efficacy of hyperoxic ventilation is the presence of generalized vasodilation as can be noticed during all kinds of dilutional anemia.

Summing up, it can be deduced that the application of hyperoxic ventilation should be accompanied by an amelioration of outcome during moderate and critical normovolemic dilutional anemia. In the clinical situation of ongoing blood loss, where normovolemia is ensured by adapted infusion of cristalloids and colloids, hyperoxic ventilation and concomitant hyperoxemia is an easily applicable and extremely effective measure to create a margin of safety for tissue oxygenation and organ function. This hyperoxia-induced increase of anemia tolerance possibly might enable a reduction of transfusion rate, as well as a reduction of the transfusion-associated risks and costs. Although hyperoxic ventilation can be used to create a margin of safety for tissue oxygenation at different hemoglobin concentrations any long-term usage of hyperoxic ventilation is not advised.

REFERENCES

  1. Top of page
  2. SUMMARY
  3. INTRODUCTION
  4. HYPEROXIC VENTILATION AS A RESCUE THERAPY FOR MYOCARDIAL INFARCTION
  5. HYPEROXIC VENTILATION DURING INFLAMMATION AND SEPSIS
  6. HYPEROXIC VENTILATION DURING MODERATE ANEMIA
  7. HYPEROXIC VENTILATION DURING EXTREME, CRITICAL ANEMIA
  8. HYPEROXIC VENTILATION DURING SEVERE HEMORRHAGIC SHOCK
  9. HYPEROXIC VENTILATION DURING EXTREME METHEMOGLOBINEMIA
  10. CONCLUSION
  11. REFERENCES