Subcutaneous Perfusion and Oxygen During Acute Severe Isovolemic Hemodilution in Healthy Volunteers

Hypothesis Acute severe isovolemic anemia (to a hemoglobin [Hb] concentration of 50 g/L) does not decrease subcutaneous wound tissue oxygen tension (PsqO2). Setting University hospital operating room and inpatient general clinical research center ward. Subjects Twenty-five healthy, paid volunteers. Methods Subcutaneous oxygen tension and subcutaneous temperature (Tsq) were measured continuously during isovolemic hemodilution to an Hb level of 50 g/L. In 14 volunteers (initially well-perfused), normal perfusion (Tsq \u3e34.4°C) was achieved by hydration and systemic warming prior to starting isovolemic hemodilution, while in 11 volunteers (perfusion not controlled [PNC]), no attempt was made to control perfusion prior to hemodilution. Main Outcome Measures Measurements of PsqO2, Tsq, and relative subcutaneous blood flow (flow index). Results While PsqO2, Tsq, and flow index were significantly lower in PNC vs well-perfused subjects at baseline, there was no significant difference between them at the Hb of 50 g/L (nadir). Subcutaneous PO2 did not decrease significantly in either group. Arterial PO2 was not different between the groups, and did not change significantly over time; Tsq and flow index increased significantly from baseline to nadir Hb in both groups. Conclusions The level of PsqO2 was maintained at baseline levels during hemodilution to Hb 50 g/L in healthy volunteers, whether they were initially well-perfused or mildly underperfused peripherally. Given the significant increase in Tsq and flow index, this resulted from a compensatory increase in subcutaneous blood flow sufficient to maintain oxygen delivery. Wound healing depends to a large extent on tissue oxygen delivery, and these data suggest that even severe anemia by itself would not be sufficient to impair wound healing. Thus, transfusion of autologous packed red blood cells solely to improve healing in surgical patients with no other indication for transfusion is not supported by these results

Critical Oxygen Delivery in Conscious Humans Is Less Than 7.3 ml O2· kg−1· min

Background The critical level of oxygen delivery (DO2) is the value below which DO2 fails to satisfy the metabolic need for oxygen. No prospective data in healthy, conscious humans define this value. The authors reduced DO2 in healthy volunteers in an attempt to determine the critical DO2. Methods With Institutional Review Board approval and informed consent, the authors studied eight healthy, conscious volunteers, aged 19-25 yr. Hemodynamic measurements were obtained at steady state before and after profound acute isovolemic hemodilution with 5% albumin and autologous plasma, and again at the reduced hemoglobin concentration after additional reduction of DO2 by an infusion of a beta-adrenergic antagonist, esmolol. Results Reduction of hemoglobin from 12.5+/-0.8 g/dl to 4.8+/-0.2 g/dl (mean +/- SD) increased heart rate, stroke volume index, and cardiac index, and reduced DO2 (14.0+/-2.9 to 9.9+/-20 ml O2 x kg(-1) x min(-1); all P\u3c0.001). Oxygen consumption (VO2; 3.0+/-0.5 to 3.4+/-0.6 ml O2 x kg(-1) x min(-1); P\u3c0.05) and plasma lactate concentration (0.50+/-0.10 to 0.62+/-0.16 mM; P\u3c0.05; n = 7) increased slightly. Esmolol decreased heart rate, stroke volume index, and cardiac index, and further decreased DO2 (to 7.3+/-1.4 ml O2 x kg(-1) x min(-1); all P\u3c0.01 vs. before esmolol). VO2 (3.2+/-0.6 ml O2 x kg(-1) x min(-1); P\u3e0.05) and plasma lactate (0.66+/-0.14 mM; P\u3e0.05) did not change further. No value of plasma lactate exceeded the normal range. Conclusions A decrease in DO2 to 7.3+/-1.4 ml O2 x kg(-1) min(-1) in resting, healthy, conscious humans does not produce evidence of inadequate systemic oxygenation. The critical DO2 in healthy, resting, conscious humans appears to be less than this value

Human Cardiovascular and Metabolic Response to Acute, Severe Isovolemic Anemia

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\u3c.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\u3c.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

Electrocardiographic ST-segment Changes during Acute, Severe Isovolemic Hemodilution in Humans

Background Controversy exists regarding the lowest blood hemoglobin concentration that can be safely tolerated. The authors studied healthy resting humans to test the hypothesis that acute isovolemic reduction of blood hemoglobin concentration to 5 g/dl would produce an imbalance in myocardial oxygen supply and demand, resulting in myocardial ischemia. Methods Fifty-five conscious healthy human volunteers were studied. Isovolemic removal of aliquots of blood reduced blood hemoglobin concentration from 12.8 +/- 1.2 to 5.2 +/- 0.5 g/dl (mean +/- SD). Removed blood was replaced simultaneously with intravenous fluids to maintain constant isovolemia. Hemodynamics and arterial oxygen content (Cao2) were measured before and after removal of each aliquot of blood. Electrocardiographic (ECG) changes were monitored continuously using a Holter ECG recorder for detection of myocardial ischemia. Results During hemodilution, transient, reversible ST-segment depression developed in three subjects as seen on the electrocardiogram during hemodilution. These changes occurred at hemoglobin concentrations of 5-7 g/dl while the subjects were asymptomatic. Two of three subjects with ECG changes had significantly higher heart rates than those without ECG changes at the same hemoglobin concentrations. When evaluating the entire study period, the subjects who had ECG ST-segment changes had significantly higher maximum heart rates than those without ECG changes, despite having similar baseline values. Conclusion With acute reduction of hemoglobin concentration to 5 g/dl, ECG ST-segment changes developed in 3 of 55 healthy conscious adults and were suggestive of, but not conclusive for, myocardial ischemia. The higher heart rates that developed during hemodilution may have contributed to the development of an imbalance between myocardial supply and demand resulting in ECG evidence of myocardial ischemia. However, these ECG changes appear to be benign because they were reversible and not accompanied by symptoms