Improved short-term survival with polyethylene glycol modified hemoglobin liposomes in critical normovolemic anemia

Pape, Andreas; Kertscho, H.; Meier, Jens; Horn, Oliver; Laout, M.; Steche, M; Lossen, Mischa; Theisen, A.; Zwißler, Bernhard; Häbler, O.

doi:10.1007/s00134-008-1082-z

Cited by 23 publications

(21 citation statements)

References 36 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: 73%

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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: 73%

“…In our previous experimental studies, critical normovolemic anemia was associated with 100% mortality if no further treatment (e.g. elevation of FiO 2 , transfusion of red blood cells, administration of catecholamines, infusion of artificial O 2 carriers) was instantaneously initiated at Hb crit [12,13,14,15]. …”

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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“…However, a couple of experimental models have simulated the scenario of acute normovolemic anemia requiring transfusion of allogeneic RBCs to maintain adequate tissue oxygenation. Overall, the results of these studies demonstrate the potential of several LEH-formulations to provide adequate tissue oxygenation in situations with critically impaired O 2 -transport capacity [10,18,22,71]. Whether these findings will translate to clinical benefit still remains to be elucidated.…”

Section: Liposome Encapsulated Hemoglobinmentioning

confidence: 79%

“…[85] However, these effects could be maintained for a longer time in dogs transfused with autologous RBCconcentrates [71].…”

Section: Liposome Encapsulated Hbmentioning

confidence: 99%

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Pape¹,

Häbler²

2010

Tissue Engineering

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“…elevation of FiO 2 , transfusion of red blood cells or infusion of artificial O 2 carriers), hemodilution to Hb crit is associated with 100% mortality [14,15,16]. Hb crit therefore reflects the limit of anemia tolerance at the level of the whole organism by averaging VO 2 of all organs.…”

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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Improved short-term survival with polyethylene glycol modified hemoglobin liposomes in critical normovolemic anemia

Abstract: In this present experimental study the infusion of a PEG-modified LEH provided adequate tissue oxygenation, hemodynamic stability, and a prolongation of survival time after critical anemia. However, these effects were sustained for only a short period of time.

Cited by 23 publications

References 36 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

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

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