Diaspirin crosslinked hemoglobin enables extreme hemodilution beyond the critical hematocrit

Meisner, Franz; Kemming, Gregor; Häbler, O.; Kleen, M.; Tillmanns, Jochen; Hutter, Jörg; Bottino, Daniel; Thein, E.; Meier, Jens; Wojtczyk, Christoph J.; Pape, Andreas; Meßmer, K.

doi:10.1097/00003246-200104000-00030

Cited by 47 publications

(29 citation statements)

References 29 publications

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“…Consistently, the value of Hb crit in the Roc group (2.4 ± 0.5 g/dl) is comparable to that described in paralyzed animals [13,15,16,17,18,19], while the values of Hb crit obtained in nonparalyzed animals are similar to Hb crit observed in the Sal group [4,12]. …”

Section: Discussionsupporting

confidence: 87%

“…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%

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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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Section: Discussionsupporting

confidence: 87%

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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“…Measurements of organ surface PO 2 using Clark-type electrodes have been established in several studies as a suitable instrument for assessing tissue oxygenation in a variety of organs (7,17,19,21). PO 2muc measurements require diffusion of O 2 through mucosal epithelial cells to the electrode were O 2 is consumed in a complex redox reaction (16).…”

Section: Discussionmentioning

confidence: 99%

Jejunal tissue oxygenation and microvascular flow motion during hemorrhage and resuscitation

Pajk

Schwarz

Knotzer

et al. 2002

American Journal of Physiology-Heart and Circulatory Physiology

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“…After moderate hemodilution, the increase of CO and microvascular blood flow, due to reduced blood viscosity, maintained oxygen supply to the tissues. Sufficient oxygenation of the tissues is limited by the functional reserve of the heart, as at a given hematocrit an increase in cardiac output is needed to deliver oxygen needs 30,31 . However, continuing the progressive hemodilution regulatory mechanisms tend to fail, even with PFCOC emulsion combined with hyperoxia.…”

Section: Discussionmentioning

confidence: 99%

Delaying Blood Transfusion in Experimental Acute Anemia With Perfluorocarbon Emulsion

Cabrales¹,

Briceño²

2012

Survey of Anesthesiology

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Background-To avoid unnecessary blood transfusions, physiologic transfusion triggers, rather than exclusively hemoglobin-based transfusion triggers have been suggested. The objective of this study was to determine systemic and microvascular effects of using a perfluorocarbon-based oxygen carrier (PFCOC) to maintaining perfusion and oxygenation during extreme anemia.Methods-The hamster (weight 55-65 g) window chamber model was used. Two isovolemic hemodilution steps were performed using 10% hydroxyethyl starch at normoxic conditions to hematocrit of 19% (5.5 g Hb /dl), point where the transfusion trigger was reached. Two additional hemodilution exchanges using the PFCOC (Oxycyte™, Synthetic Blood International, Inc. Costa Mesa, CA) and increasing fraction of inspired oxygen to 1.0 were performed to reduce hematocrit to 11% (3.8 g Hb /dl) and 6% (2.0 g Hb /dl), respectively. No control group was used in the study, as this level of hemodilution is lethal with conventional plasma expanders. Systemic parameters, microvascular perfusion, functional capillary density and oxygen tensions across the microvascular network were measured.Results-At 6% hematocrit, the PFCOC maintained mean arterial pressure, cardiac output, systemic oxygen delivery and consumption. As hematocrit was lowered from 11% to 6%, functional capillary density, calculated microvascular oxygen delivery and consumption decreased, and oxygen extraction ratio was close to 100%. Peripheral tissue oxygenation was not predicted by systemic oxygenation.Conclusions-PFCOC in conjunction with hyperoxia was able to sustain organ function, and partially provide systemic oxygenation during extreme anemia over the observation period. The PFCOC can work as a bridge until red blood cells are available for transfusion, or where additional oxygen is required, notwithstanding possible limitations in peripheral tissue oxygenation.

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Diaspirin crosslinked hemoglobin enables extreme hemodilution beyond the critical hematocrit

Cited by 47 publications

References 29 publications

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

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

Jejunal tissue oxygenation and microvascular flow motion during hemorrhage and resuscitation

Delaying Blood Transfusion in Experimental Acute Anemia With Perfluorocarbon Emulsion

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