Archived Comments for:
Survival time in severe hemorrhagic shock after perioperative hemodilution is longer with PEG-conjugated human serum albumin than with HES 130/0.4: a microvascular perspective
Creagh-Brown and Evans’ main concern as noted in their commentary of our paper is the use of an animal model where the microcirculation of connective tissue is investigated instead of clinically more relevant organs such as the viscera. In addition one major point of criticism is the severity of the protocol where after slow replacement of 50% of blood volume (acute normovolemic hemodilution, ANH) with either PEG-albumin or HES 130/0.4, 60% of circulating volume was removed thus simulating severe surgical hemorrhage. Animals were then observed for a further hour in terms of microvascular parameters such as functional capillary density (FCD), arteriolar and venular diameter, red blood cell velocity and blood flow. Whereas all animals receiving PEG-albumin survived the protocol, none of the HES animals completed the hemorrhage phase of the protocol.
The purpose of the study was to investigate whether there was any effect on survival time by using either HES or PEG-albumin and whether there was any difference in microvascular capillary perfusion by using one or the other study solution. The main point of interest was to investigate whether a plasma expander works under extreme conditions even though they might be rare and usually won’t develop in a clinical setting. The experimental protocol chosen is severe enough to immediately see the effect of perturbations such as hemodilution not only in terms of survival but also regarding physiological changes like FCD and blood flow. One might also consider the fact that a plasma expander that stabilizes hemodynamics under extreme conditions provides an additional margin of safety as under less severe circumstances smaller amounts of the material will sufficiently restore hemodynamic parameters.
We agree with Creagh-Brown and Evans that the skin microcirculation is not representative for the microcirculation of internal organs such as the viscera, liver or heart. During shock, vessels of the skin vasoconstrict shift blood towards more crucial organs such as the heart, brain or liver. Nevertheless Kerger et al., 1996 (1) demonstrated that maintenance of FCD was the only critical microvascular parameter correlated with survival in a model of severe hemorrhagic shock in the hamster window chamber. In view of this very important finding it seems justifiable to draw conclusions from data acquired in the hamster skinfold. Furthermore this is the only animal model where the microcirculation can be studied in an awake animal without having to deal with the side effects of anesthesia.
In conclusion the data for PEG-albumin are promising, even though we agree that the working mechanism still needs to be further investigated.
Judith Martini
Ananda K.
Seetharama A Acharya
Marcos Intaglietta
Amy G. Tsai
REFERENCE:
1. Kerger H, Saltzman DJ, Menger MD, Messmer K, and Intaglietta M. Systemic and subcutaneous microvascular pO2 dissociation during 4-h hemorrhagic shock in conscious hamsters. Am J Physiol 270: H827-H836, 1996.
Critical Care
The promise of next generation colloids
4 July 2008
Creagh-Brown and Evans’ main concern as noted in their commentary of our paper is the use of an animal model where the microcirculation of connective tissue is investigated instead of clinically more relevant organs such as the viscera. In addition one major point of criticism is the severity of the protocol where after slow replacement of 50% of blood volume (acute normovolemic hemodilution, ANH) with either PEG-albumin or HES 130/0.4, 60% of circulating volume was removed thus simulating severe surgical hemorrhage. Animals were then observed for a further hour in terms of microvascular parameters such as functional capillary density (FCD), arteriolar and venular diameter, red blood cell velocity and blood flow. Whereas all animals receiving PEG-albumin survived the protocol, none of the HES animals completed the hemorrhage phase of the protocol.
The purpose of the study was to investigate whether there was any effect on survival time by using either HES or PEG-albumin and whether there was any difference in microvascular capillary perfusion by using one or the other study solution. The main point of interest was to investigate whether a plasma expander works under extreme conditions even though they might be rare and usually won’t develop in a clinical setting. The experimental protocol chosen is severe enough to immediately see the effect of perturbations such as hemodilution not only in terms of survival but also regarding physiological changes like FCD and blood flow. One might also consider the fact that a plasma expander that stabilizes hemodynamics under extreme conditions provides an additional margin of safety as under less severe circumstances smaller amounts of the material will sufficiently restore hemodynamic parameters.
We agree with Creagh-Brown and Evans that the skin microcirculation is not representative for the microcirculation of internal organs such as the viscera, liver or heart. During shock, vessels of the skin vasoconstrict shift blood towards more crucial organs such as the heart, brain or liver. Nevertheless Kerger et al., 1996 (1) demonstrated that maintenance of FCD was the only critical microvascular parameter correlated with survival in a model of severe hemorrhagic shock in the hamster window chamber. In view of this very important finding it seems justifiable to draw conclusions from data acquired in the hamster skinfold. Furthermore this is the only animal model where the microcirculation can be studied in an awake animal without having to deal with the side effects of anesthesia.
In conclusion the data for PEG-albumin are promising, even though we agree that the working mechanism still needs to be further investigated.
Judith Martini
Ananda K.
Seetharama A Acharya
Marcos Intaglietta
Amy G. Tsai
REFERENCE:
1. Kerger H, Saltzman DJ, Menger MD, Messmer K, and Intaglietta M. Systemic and subcutaneous microvascular pO2 dissociation during 4-h hemorrhagic shock in conscious hamsters. Am J Physiol 270: H827-H836, 1996.
Competing interests
none.