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Highly Accessed Letter

Tissue hypoxia during acute hemorrhage

Philippe Haouzi

Author Affiliations

Division of Pulmonary and Critical Care Medicine, Penn State University College of Medicine, Penn State Hershey Medical Center, 500 University Drive, Hershey, PA 17033, USA

Critical Care 2013, 17:423  doi:10.1186/cc12519

See related commentary by Calzia et al.,

The electronic version of this article is the complete one and can be found online at:

Published:28 March 2013

© 2013 BioMed Central Ltd


Calzia and colleagues argue [1] that tissue hypoxia in a rat model of hemorrhage that led to an oxygen deficit of 120 ml/kg with hyperlactacidemia [2] may be modest, and may not affect hydrogen sulfide oxidation since '... the arterial oxygen partial pressure was still normal ...' [1]. This contention requires clarification.

A relative hyperventilation is the rule in most experimental models of hemorrhage [2,3], since the reduction in oxygen uptake/consumption V ˙ O 2 is always larger than that in alveolar ventilation V ˙ A . Alveolar oxygen partial pressure therefore increases during hemorrhage, as it is the ratio between V ˙ O 2 and V ˙ A (and not the absolute level of V ˙ A ) that dictates the partial pressure of oxygen in the alveolar gas (PAO2):

PA O 2  =  PI O 2 - k V ˙ O 2 / V ˙ A

This tells us very little about the level of tissue hypoxia.

In all of the models used to study an acute hemorrhage, the baseline oxygen delivery rate ( D O 2 = Q ˙ C a O 2 ) is three to four times higher than V ˙ O 2 , despite a large discrepancy in V ˙ O 2 per kilogram between a 500 g rat, a 20 kg pig or a human being: cardiac output, DO2 and V ˙ O 2 do share a similar allometric function with body weight, so that the blood oxygen content is the same in most species. Q ˙ drops dramatically during hemorrhage, reducing DO2. The level of DO2 decreases up to 10 times while V ˙ O 2 drops by four times regardless of the size of animal chosen [3,4] so that both DO2 and V ˙ O 2 reach one-third of the baseline metabolic rate at the end of a severe hemorrhage! This should certainly lead to one of the most severe forms of tissue hypoxia - with normal arterial blood oxygen partial pressure - unless a decrease in oxygen demand contributes significantly to the reduction in V ˙ O 2 induced by the decline in DO2. Indeed, although the relationship between DO2 and V ˙ O 2 is similar across species, the meaning of a reduction in V ˙ O 2 can greatly differ among animal models according to their ability to decrease the oxygen demand [3,5] - a phenomenon present during hemorrhage in small mammals [3]. It is eventually this ability to modify oxygen demand during a hemorrhage, in keeping with DO2, which controls the level of tissue hypoxia, and not the absolute levels of PaO2, DO2 or V ˙ O 2 .


CaO2: concentration (content) of oxygen in the arterial gas; DO2: rate of oxygen delivery ( Q ˙ C a O 2 ) ; PAO2: partial pressure of oxygen in the alveolar gas; PIO2: partial pressure of oxygen in the inspired gas; Q ˙ : cardiac output; V ˙ A : alveolar ventilation; V ˙ O 2 : oxygen uptake/consumption.

Competing interests

The author declares that they have no competing interests.


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