Human Cardiovascular and Metabolic Response to Acute, Severe Isovolemic Anemia

Abstract

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 (TO 2 ) as assessed by oxygen consumption (V O 2 ), plasma lactate concentration, and ST changes on electrocardiogram.Results.-Acute, isovolemic reduction of Hb concentration decreased systemic vascular resistance and TO 2 and increased heart rate, stroke volume, and cardiac index (each PϽ.001). We did not find evidence of inadequate oxygenation: V O 2 increased slightly from a mean (SD) of 3.07 (0.44) mL of oxygen per kilogram per minute (mL O 2 •kg −1 •min −1 ) to 3.42 (0.54) mL O 2 •kg −1 •min −1 (PϽ.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 TO 2 , as assessed by lack of change of V O 2 and plasma lactate concentration. Analysis of Holter readings suggests that at this Hb concentration in this resting healthy population, myocardial ischemia would occur infrequently.

Plasma methemoglobin as a potential biomarker of anemic stress in humans

“…1). Second, the increase in DeoxyHb in local vascular beds, secondary to increased oxygen extraction, 23,24 would favour the production of NO from nitrite with MetHb as the byproduct (Fig. 2).…”

“…These proposed mechanisms may be particularly favoured during anemia since local production of NO would be supported by an increase in tissue oxyHb extraction which is known to occur in anemic vascular beds. 23,24 For example, in the brain, acute anemia increases Hb O 2 extraction from *30% (Hb * 140 gÁL -1 ) to *50% (Hb * 50 gÁL -1 ), 23 while brain microvascular PO 2 decreases from *70 to *50 mmHg. 6,7 As such, methemoglobin (MetHb) production may be favoured in anemic vascular beds.…”

Transfusion medicine and solid organ transplant – Update and review of some current issues

“…By inducing a moderate isovolemic anemia during surgery, the blood lost is diluted in concentration. 16 ANH spares not only the red cell mass but platelets and clotting factors as well. ANH offers following advantages over preoperative autologous donation (PAD).…”

Assessment and treatment of preoperative anemia: Continuing Professional Development

“…Cellular detection of tissue hypoxia triggers an increase in autonomic responses that result in acute increases in cardiac output and reduction in systemic vascular resistance to optimize tissue oxygen delivery. 24 Concurrently, oxygen extraction is increased, mediated, in part, by a right shift in the oxyhemoglobin dissociation curve. The increased cardiac output is distributed differentially in a hierarchical manner such that critically vital organs (brain, heart) receive proportionally more oxygen relative to less vital organs (kidney, gut).…”

“…4,24,25 These responses include an increase in cardiac output with organ specific vasodilation to reduce systemic vascular resistance and maintain global oxygen delivery. Despite these compensatory cardiovascular responses, evidence suggests that brain oxygen delivery is inadequate during severe anemia (Hb * 50 to 60 gÁL -1 ), resulting in reduced brain tissue PO 2 and increased hypoxic cellular responses.…”