Human Cardiovascular and Metabolic Response to Acute, Severe Isovolemic Anemia

Document Type



Faculty of Health Sciences, East Africa


Context.— Although concern over the risks of red blood cell transfusion has resulted in several practice guidelines for transfusion, lack of data regarding the physiological effects of anemia in humans has caused uncertainty regarding the blood hemoglobin (Hb) concentration requiring treatment.

Objective.— To test the hypothesis that acute isovolemic reduction of blood Hb concentration to 50 g/L in healthy resting humans would produce inadequate cardiovascular compensation and result in tissue hypoxia secondary to inadequate oxygen transport.

Design.— Before and after interventional study.

Setting.— Academic tertiary care medical center.

Participants.— Conscious healthy patients (n=11) prior to anesthesia and surgery and volunteers not undergoing surgery (n=21).

Interventions.— Aliquots of blood (450-900 mL) were removed to reduce blood Hb concentration from 131 (2) g/L to 50 (1) g/L [mean (SE)]. Isovolemia was maintained with 5% human albumin and/or autologous plasma. Cardiovascular parameters, arterial and mixed venous oxygen content, oxyhemoglobin saturation, and arterial blood lactate were measured before and after removal of each aliquot of blood. Electrocardiogram and, in a subset, Holter monitor were monitored continuously.

Main Outcome Measures.— "Critical" oxygen delivery (TO2) as assessed by oxygen consumption (O2), plasma lactate concentration, and ST changes on electrocardiogram.

Results.— Acute, isovolemic reduction of Hb concentration decreased systemic vascular resistance and TO2 and increased heart rate, stroke volume, and cardiac index (each P<.001). We did not find evidence of inadequate oxygenation: O2 increased slightly from a mean (SD) of 3.07 (0.44) mL of oxygen per kilogram per minute (mL O2·kg−1·min−1) to 3.42 (0.54) Ml O2·kg−1·min−1 (P<.001) and plasma lactate concentration did not change (0.81 [0.11] mmol/L to 0.62 [0.19] mmol/L;P=.09). Two subjects developed significant ST changes on Holter monitor: one apparently related to body position or activity, the other to an increase in heart rate (at an Hb concentration of 46-53 g/L); both occurred in young women and resolved without sequelae.

Conclusions.— Acute isovolemic reduction of blood Hb concentration to 50 g/L in conscious healthy resting humans does not produce evidence of inadequate systemic TO2, as assessed by lack of change of O2 and plasma lactate concentration. Analysis of Holter readings suggests that at this Hb concentration in this resting healthy population, myocardial ischemia would occur infrequently.

THE MOST COMMON indication for the transfusion of red blood cells is to augment the oxygen-carrying capacity of the blood of an anemic patient. The potential for blood components to transmit infectious disease has produced concern and "guidelines," "practice parameters," or "standards" delineating conditions under which it is appropriate to transfuse red blood cells.1-4 Formulation of these documents has been hindered by the lack of data defining the hemoglobin (Hb) concentration in humans that does not allow for adequate oxygen transport (TO2) and that initiates tissue hypoxia.

Accordingly, we acutely decreased the Hb concentration of 32 healthy resting humans to test the hypothesis that a blood Hb concentration of 50 g/L would result in tissue hypoxia secondary to inadequate TO2. We did not conduct these studies with the subjects performing any activity that would thereby increase oxygen consumption (O2). Consequently, our results are applicable only to humans at rest.


This work was published before the author joined Aga Khan University.


JAMA The Journal of the American Medical Association