Hemodilution and intravenous perflubron emulsion as an alternative to blood transfusion: effects on tissue oxygenation during profound hemodilution in anesthetized dogs

Häbler, O.; Kleen, M.; Hutter, Jörg; Podtschaske, Armin; Tiede, M.; Kemming, Gregor; Welte, M.; Corso, Carlos Otávio; Batra, Sanjay; Keipert, Peter E.; Faithfull, N. S.; Meßmer, K.

doi:10.1046/j.1537-2995.1998.38298193096.x

Cited by 78 publications

(57 citation statements)

References 16 publications

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“…To date, this latter phase remains firmly within the purvey of blood transfusion medicine; however, alternative oxygen-carrying volume fluids such as modified hemoglobins (Hbs) and fluorocarbons have emerged in the past decade. Few of these materials have been objectively analyzed in terms of their transport properties at the level of the microscopic blood vessels, where the actual exchange of oxygen takes place, to determine if their properties lead to adequate transport processes at the cellular/tissue level (8).…”

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confidence: 99%

Oxygen delivery and consumption in the microcirculation after extreme hemodilution with perfluorocarbons

Cabrales¹,

Tsai²,

Frangos³

et al. 2004

American Journal of Physiology-Heart and Circulatory Physiology

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Intaglietta. Oxygen delivery and consumption in the microcirculation after extreme hemodilution with perfluorocarbons. Am J Physiol Heart Circ Physiol 287: H320 -H330, 2004; 10.1152/ajpheart.01166.2003.-The oxygen transport capacity of fluorocarbons was investigated in the hamster chamber window model microcirculation to determine the rate at which oxygen is delivered to the tissue in conditions of extreme hemodilution [hematocrit (Hct) 11%]. Hydroxyethlyl starch (HES 200; 200 kDa molecular mass) was used as a plasma expander for two isovolemic hemodilutions performed with 10% HES 200 until a Hct of 65%. A third step reduced the Hct to 75% of baseline and was performed with either HES 200 or a 60% perfluorocarbon (PFC) emulsion. Comparisons of HES 200-only-hemodiluted animals versus 4.2 g/kg PFC emulsion-hemodiluted animals were made at 21% and 100% normobaric oxygen ventilation. It was found that systemic and microvascular oxygen delivery was 25% and 400% higher in the PFC animals compared with HES 200 animals, respectively, showing that PFCs deliver oxygen to the tissue when combined with hyperoxic ventilation in the present experiments, with no evidence of vasoconstriction or impaired microvascular function. Oxygen ventilation (100%) led to a positive base excess for the PFC group (5.5 Ϯ 2.5 mmol/l) versus a negative balance (Ϫ0.8 Ϯ 1.4 mmol/l) for the HES 200 group, suggesting that microvascular findings corresponded to systemic events. hyperoxia; functional capillary density; oxygen-carrying capacity; blood substitutes; tissue oxygen delivery THE CORRECTION OF BLOOD LOSSES usually begins with the normalization of blood volume. The continued decrease of red blood cell (RBC) concentration is followed by the restoration of oxygen-carrying capacity. To date, this latter phase remains firmly within the purvey of blood transfusion medicine; however, alternative oxygen-carrying volume fluids such as modified hemoglobins (Hbs) and fluorocarbons have emerged in the past decade. Few of these materials have been objectively analyzed in terms of their transport properties at the level of the microscopic blood vessels, where the actual exchange of oxygen takes place, to determine if their properties lead to adequate transport processes at the cellular/tissue level (8).Fluorocarbons have been investigated by different approaches that extended to phase 3 clinical trials (9). These materials carry oxygen, are synthetic, and, in principle, are available in very large quantities at modest costs. This has tantalized investigators, medical practitioners, and business enterprises, because it could, in principle, lead to a convenient, largely available, and pathogen-free oxygen carrier. However, fluorocarbons only become miscible with water when emulsified with phospholipids (derived from egg yolk) and therefore are not completely synthetic. Furthermore, whereas Hb carries oxygen via a reversible chemical reaction, fluorocarbons carry oxygen as a function of their solubility; therefore, at the PO 2 s prevailing in the microcirc...

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confidence: 99%

Oxygen delivery and consumption in the microcirculation after extreme hemodilution with perfluorocarbons

Cabrales¹,

Tsai²,

Frangos³

et al. 2004

American Journal of Physiology-Heart and Circulatory Physiology

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“…In particular, a reduction of Hb crit could be achieved by hypothermia (moderate reduction of body core temperature reduces total body O 2 demand [18]), infusion of norepinephrine (stabilization of CPP during hemodilution [19]), infusion of artificial O 2 carriers (maintenance of CaO 2 despite reduced hematocrit [20,21]) and continuous NMB (lowering skeletal muscular O 2 demand [22]). …”

Section: Discussionmentioning

confidence: 99%

The Limit of Anemia Tolerance during Hyperoxic Ventilation with Pure Oxygen in Anesthetized Domestic Pigs

et al. 2013

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Background: During acellular replacement of an acute blood loss, hyperoxic ventilation (HV) increases the amount of O₂ physically dissolved in the plasma and thereby improves O₂ supply to the tissues. While this effect could be demonstrated for HV with inspiratory O₂ fraction (FiO₂) 0.6, it was unclear whether HV with pure oxygen (FiO₂ 1.0) would have an additional effect on the physiological limit of acute normovolemic anemia. Methods: Seven anesthetized domestic pigs were ventilated with FiO₂ 1.0 and subjected to an isovolemic hemodilution protocol. Blood was drawn and replaced by a 6% hydroxyethyl starch (HES) solution (130/0.4) until a sudden decrease of total body O₂ consumption (VO₂) indicated the onset of O₂ supply dependency (primary endpoint). The corresponding hemoglobin (Hb) concentration was defined as ‘critical Hb' (Hb_crit). Secondary endpoints were parameters of myocardial function, central hemodynamics, O₂ transport and tissue oxygenation. Results: HV with FiO₂ 1.0 enabled a large blood-for-HES exchange (156 ± 28% of the circulating blood volume) until Hb_crit was met at 1.3 ± 0.3 g/dl. After termination of the hemodilution protocol, the contribution of O₂ physically dissolved in the plasma to O₂ delivery and VO₂ had significantly increased from 11.7 ± 2 to 44.2 ± 9.7% and from 29.1 ± 4.2 to 66.2 ± 11.7%, respectively. However, at Hb_crit, cardiovascular performance was found to have severely deteriorated. Conclusion: HV with FiO₂ 1.0 maintains O₂ supply to tissues during extensive blood-for-HES exchange. In acute situations, where profound anemia must be tolerated (e.g. bridging an acute blood loss until red blood cells become available for transfusion), O₂ physically dissolved in the plasma becomes an essential source of oxygen. However, compromised cardiovascular performance might require additional treatment.

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“…In several experimental studies, a decrease in Hb crit demonstrated that anemia tolerance is increased by (1) hypothermia (moderate reduction of body core temperature reduces total body O 2 demand [16]), (2) hyperoxic ventilation (bioavailability of physically dissolved O 2 is excellent in profound anemia [12,17,18]), (3) infusion of norepinephrine (stabilization of coronary perfusion pressure during hemodilution [13]), and (4) artificial O 2 carriers (maintenance of CaO 2 despite reduced hematocrit [19,20]). In contrast, anemia tolerance is decreased by (1) hypovolemia (reduction of microcirculatory O 2 supply), (2) profound anesthesia (pharmacologic reduction of the cardiac output response to hemodilution [21,22]) and (3) by coronary artery disease (reduced coronary flow reserve [23]).…”

Section: Discussionmentioning

confidence: 99%

Neuromuscular Blockade with Rocuronium Bromide Increases the Tolerance of Acute Normovolemic Anemia in Anesthetized Pigs

et al. 2011

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Background: The patient’s individual anemia tolerance is pivotal when blood transfusions become necessary, but are not feasible for some reason. To date, the effects of neuromuscular blockade (NMB) on anemia tolerance have not been investigated. Methods: 14 anesthetized and mechanically ventilated pigs were randomly assigned to the Roc group (3.78 mg/kg rocuronium bromide followed by continuous infusion of 1 mg/kg/min, n = 7) or to the Sal group (administration of the corresponding volume of normal saline, n = 7). Subsequently, acute normovolemic anemia was induced by simultaneous exchange of whole blood for a 6% hydroxyethyl starch solution (130/0.4) until a sudden decrease of total body O₂ consumption (VO₂) indicated a critical limitation of O₂ transport capacity. The Hb concentration quantified at this time point (Hb_crit) was the primary endpoint of the protocol. Secondary endpoints were parameters of hemodynamics, O₂ transport and tissue oxygenation. Results: Hb_crit was significantly lower in the Roc group (2.4 ± 0.5 vs. 3.2 ± 0.7 g/dl) reflecting increased anemia tolerance. NMB with rocuronium bromide reduced skeletal muscular VO₂ and total body O₂ extraction rate. As the cardiac index increased simultaneously, total body VO₂ only decreased marginally in the Roc group (change of VO₂ relative to baseline –1.7 ± 0.8 vs. 3.2 ± 1.9% in the Sal group, p < 0.05). Conclusion: Deep NMB with rocuronium bromide increases the tolerance of acute normovolemic anemia. The underlying mechanism most likely involves a reduction of skeletal muscular VO₂. During acellular treatment of an acute blood loss, NMB might play an adjuvant role in situations where profound stages of normovolemic anemia have to be tolerated (e.g. bridging an unexpected blood loss until blood products become available for transfusion).

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Hemodilution and intravenous perflubron emulsion as an alternative to blood transfusion: effects on tissue oxygenation during profound hemodilution in anesthetized dogs

Cited by 78 publications

References 16 publications

Oxygen delivery and consumption in the microcirculation after extreme hemodilution with perfluorocarbons

Oxygen delivery and consumption in the microcirculation after extreme hemodilution with perfluorocarbons

The Limit of Anemia Tolerance during Hyperoxic Ventilation with Pure Oxygen in Anesthetized Domestic Pigs

Neuromuscular Blockade with Rocuronium Bromide Increases the Tolerance of Acute Normovolemic Anemia in Anesthetized Pigs

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