Severe Anemia Well-Tolerated in Normal Volunteers
April 1, 1998 3 minutes read
Severe Anemia Well-Tolerated in Normal Volunteers
ABSTRACT & COMMENTARY
Synopsis: Acute reduction of hemoglobin to 5 g/dL resulted in a slight increase in oxygen uptake (3.07-3.42 mL O2/kg/min) and no evidence of anaerobic metabolism in 11 normal volunteers and 21 normal patients prior to elective surgery. This was accomplished by a compensatory reduction in peripheral resistance and increases in heart rate, stroke volume, and cardiac index.
Source: Weiskopf RB, JAMA 1998;279(3): 217-221.
The theory of "critical" oxygen delivery-the point at which oxygen uptake becomes dependent on delivery-remains unproven in critical care medicine. A "critical" point in the oxygen delivery-oxygen use curve, below which oxygen use by the tissues is supply-dependent, can be demonstrated in animal models, but there is little evidence that it occurs in humans. Assuming that this pathological process is present in patients with shock has led to using vasoactive substances in critically ill patients to drive oxygen delivery to high levels, often in patients with already elevated cardiac outputs and normal blood pressures. This study demonstrates the usual responses of normal patients to profound anemia and an anemia-induced decrease in oxygen delivery.
Thirty-two non-smoking individuals without evidence of cardiac, pulmonary, or liver disease were incrementally bled to a hemoglobin of 5 g/dL. Cardiac and oxygen transport variables were determined using a pulmonary artery catheter placed under light sedation. Measurements and interventions were performed with the individuals awake. Intravascular volume was maintained with infusions of 5% albumin solution. Continuous arterial pressure and elecrocardiogram recording was maintained, and S-T segments on the electrocardiogram were analyzed for signs of ischemia.
Average heart rate rose from 58 to 92 beats per minute and cardiac index increased from 3.0 to 5.7 L/min/m2, linearly following the fall in hemoglobin concentration. Oxygen uptake rose slightly during induction of anemia. Oxygen delivery declined gradually until the final measurement, when it fell significantly to under 11 mL O2/kg/min (from 13.5 mL O2/kg/min). Mixed venous oxygen saturation paralleled oxygen delivery reaching a nadir of 69% (down from an initial 76%). Plasma lactate remained normal at less than 1 mmol/L throughout the experiment. No ischemia-related ECG changes were seen. No patient experienced any subjective symptoms suggestive of ischemia.
No critical value of oxygen delivery was seen in this group of normal humans studied at rest. Values as low as 6.5 mL O2/kg/min occurred in one person without evidence of decreased oxygen uptake. This study supports withholding transfusions in patients remaining at rest without cardiovascular disease at even lower hemoglobin levels than are currently recommended (i.e., 7 g/dL).
COMMENT BY CHARLES G. DURBIN, Jr., MD, FCCM
This remarkable study demonstrates the large margin of safety and effectiveness of compensatory cardiovascular responses that normal humans are capable of mounting to tolerate acute anemia. These individuals were normal (although several were older than age 60) supine and at rest. None had experienced a period of shock, and all were maintained with normal cardiac preload. Thus, these benign results are not freely applicable to critically ill patients under stress, and they add little to our understanding of what is an appropriate hemoglobin or level of oxygen delivery in critically ill or injured patients.
To the contrary, the results in this group of normal people suggests that hemoglobin levels should be maintained at least at a level of 12 g/dL in the critically ill, since a linear increase in heart rate and stroke volume was seen below this level. This would remove one stress from an already challenged system and allow for compensation for other stresses.
The failure to demonstrate "critical" oxygen delivery in normal individuals at hemoglobin concentrations of 5 g/dL is not surprising. This is an important study supporting withholding of transfusions in otherwise healthy individuals who are not under critical stress.
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