Maurene Viele

What can we learn about the need for transfusion from patients who refuse blood? The experience with Jehovah's Witnesses

BACKGROUND: A transfusion threshold of 7 g per dL (70 g/L) of hemoglobin has been proposed for patients, although scant human data are available to support this recommendation.

Acute severe isovolemic anemia impairs cognitive function and memory in humans.

Background Erythrocytes are transfused to prevent or treat inadequate oxygen delivery resulting from insufficient hemoglobin concentration. Previous studies failed to find evidence of inadequate systemic oxygen delivery at a hemoglobin concentration of 5 g/dl. However, in those studies, sensitive, specific measures of critical organ function were not used. This study tested the hypothesis that acute severe decreases of hemoglobin concentration alters human cognitive function. Methods Nine healthy volunteers, age 29 ± 5 yr (mean ± SD), were tested with verbal memory and standard, computerized neuropsychologic tests before and after acute isovolemic reduction of their hemoglobin to 7, 6, and 5 g/dl and again after transfusion of their autologous erythrocytes to return their hemoglobin concentration to 7 g/dl. To control for duration of the experiment, each volunteer also completed the same tests on a separate day, without alteration of hemoglobin, at times of the day approximately equivalent to those on the experimental day. Results No test showed any change in reaction time or error rate at hemoglobin concentration of 7 g/dl compared with the data at the baseline hemoglobin concentration of 14 g/dl. Reaction time, but not error rate, for horizontal addition and digit–symbol substitution test (DSST) increased at hemoglobin 6 g/dl (mean horizontal addition, 19%; 95% confidence interval [CI], 4–34%; mean DSST, 10%; 95% CI, 4–17%) and further at 5 g/dl (mean horizontal addition, 43%; 95% CI, 6–79%; mean DSST, 18%; 95% CI, 4–31%). Immediate and delayed memory was degraded at hemoglobin 5 g/dl but not at 6 g/dl. Return of hemoglobin to 7 g/dl returned all tests to baseline, except for the DSST, which significantly improved, and returned to baseline the following morning after transfusion of all autologous erythrocytes. Conclusion Acute reduction of hemoglobin concentration to 7 g/dl does not produce detectable changes in human cognitive function. Further reduction of hemoglobin level to 6 and 5 g/dl produces subtle, reversible increases in reaction time and impaired immediate and delayed memory. These are the first prospective data to demonstrate subtle degraded human function with acute anemia of hemoglobin concentrations of 6 and 5 g/dl. This reversibility of these decrements with erythrocyte transfusion suggests that our model can be used to test the efficacy of erythrocytes, oxygen therapeutics, or other treatments for acute anemia.

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

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 &bgr;-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 ± 2.0 ml O2 · kg−1 · min−1; all P < 0.001). Oxygen consumption (VO2; 3.0 ± 0.5 to 3.4 ± 0.6 ml O2 · kg−1 · min−1;P < 0.05) and plasma lactate concentration (0.50 ± 0.10 to 0.62 ± 0.16 mM;P < 0.05; 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 · kg−1 · min−1; all P < 0.01 vs. before esmolol). VO2 (3.2 ± 0.6 ml O2 · kg−1 · min−1;P > 0.05) and plasma lactate (0.66 ± 0.14 mM;P > 0.05) 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 · 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.

Oxygen Reverses Deficits of Cognitive Function and Memory and Increased Heart Rate Induced by Acute Severe Isovolemic Anemia

Background Erythrocytes are transfused to improve oxygen delivery and prevent or treat inadequate oxygenation of tissues. Acute isovolemic anemia subtly slows human data processing and degrades memory, increases heart rate, and decreases self-assessed energy level. Erythrocyte transfusion is efficacious in reversing these effects of acute anemia. We tested the hypothesis that increasing arterial oxygen pressure (Pao2) to 350 mmHg or greater would supply sufficient oxygen to be equivalent to augmenting hemoglobin concentration by 2–3 g/dl and thus reverse the effects of acute anemia. Methods Thirty-one healthy volunteers, aged 28 ± 4 yr (mean ± SD), were tested with verbal memory and standard, computerized neuropsychologic tests before and twice after acute isovolemic reduction of their hemoglobin concentration to 5.7 ± 0.3 g/dl. Two sets of tests were performed in randomized order at the lower hemoglobin concentration: with the volunteer breathing room air or oxygen. The subject and those administering the tests and recording the results were unaware which gas was administered. As an additional control for duration of the experiment, 10 of these volunteers also completed the same tests on a separate day, without alteration of hemoglobin concentration, at times of the day similar to those on the experimental day. Heart rate, mean arterial blood pressure, and self-assessed sense of energy were recorded at the time of each test. Results Reaction time for digit-symbol substitution test increased, delayed memory was degraded, mean arterial pressure and energy level decreased, and heart rate increased at a hemoglobin concentration of 5.7 g/dl (all P < 0.05). Increasing Pao2 to 406 ± 47 mmHg reversed the digit-symbol substitution test result and the delayed memory changes to values not different from those at the baseline hemoglobin concentration of 12.7 ± 1.0 g/dl, and decreased heart rate (P < 0.05). However, mean arterial pressure and energy level changes were not altered with increased Pao2 during acute anemia. Conclusion The authors confirmed that acute isovolemic anemia subtly slows human reaction time, degrades memory, increases heart rate, and decreases energy level. The findings of this study support the hypothesis that increasing Pao2 to 350 mmHg or greater by breathing oxygen reverses all of these effects of acute anemia except for decreased energy.

Electrocardiographic ST-segment changes during acute, severe isovolemic hemodilution in humans.

BackgroundControversy 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. MethodsFifty-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. ResultsDuring 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. ConclusionWith 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.

How we treat: management of life-threatening primary postpartum hemorrhage with a standardized massive transfusion protocol

Management of massive, life‐threatening primary postpartum hemorrhage in the labor and delivery service is a challenge for the clinical team and hospital transfusion service. Because severe postpartum obstetrical hemorrhage is uncommon, its occurrence can result in emergent but variable and nonstandard requests for blood products. The implementation of a standardized massive transfusion protocol for the labor and delivery department at our institution after a maternal death caused by amniotic fluid embolism is described. This guideline was modeled on a existing protocol used by the trauma service mandating emergency release of 6 units of group O D– red cells (RBCs), 4 units of fresh frozen or liquid plasma, and 1 apheresis unit of platelets (PLTs). The 6:4:1 fixed ratio of uncrossmatched RBCs, plasma, and PLTs allows the transfusion service to quickly provide blood products during the acute phase of resuscitation and allows the clinical team to anticipate and prevent dilutional coagulopathy. The successful management of three cases of massive primary postpartum hemorrhage after the implementation of our new massive transfusion protocol in the maternal and fetal medicine service is described.

Recombinant Human Hemoglobin Does Not Affect Renal Function in Humans Analysis of Safety and Pharmacokinetics

BACKGROUND Recombinant human hemoglobin (OptroD; rHb1.1) is a genetically engineered protein produced in Escherichia coli. The two alpha-globin polypeptides are genetically joined, resulting in a stable tetramer that does not dissociate into dimers or monomers. Historically, infusion in humans of acellular hemoglobin preparations has resulted in renal toxicity. This study was performed to evaluate the safety and pharmacokinetics of rHb1.1 when infused in humans. METHODS After giving informed consent, 48 healthy male volunteers were randomly assigned to receive either 0.015-0.32 g/kg 5% rHb1.1 (n = 34) or an equivalent amount of 5% human serum albumin (HSA; n = 14) infused intravenously over 0.8-1.9 h. Serum creatinine, creatinine clearance, urine N-acetyl-beta-glucosaminidase, and serum rHb1.1 concentrations were measured before and at timed intervals after infusion. RESULTS Postinfusion urine N-acetyl-beta-glucosaminidase activity did not exceed preinfusion values at any interval in either group. Serum creatinine did not differ from preinfusion values at 1 day, 2-3 days, or 7 days after infusion for either group. Creatinine clearance increased significantly for the HSA group 12 h after infusion (138 +/- 16 ml/min, means +/- SE) and in the rHb1.1 group 1 day after infusion (112 +/- 5 ml/min; P < 0.05). Values for creatinine clearance did not differ from preinfusion values for either group at any other postinfusion interval; serum creatinine and creatinine clearance did not differ between groups at any time. The amount of hemoglobin excreted in the urine did not exceed approximately 0.04% of the administered rHb1.1 dose in any volunteer. Plasma clearance of rHb1.1 decreased and half-life increased as a function of increasing plasma concentration (e.g., the half-life was 2.8 h at a plasma concentration of 0.5 mg/ml and 12 h at 5 mg/ml). The incidence of gastrointestinal symptoms, fever, and chills was greater after infusion of rHb1.1 than after HSA (P < 0.05). CONCLUSIONS No evidence for rHb1.1-mediated nephrotoxicity was observed in volunteers given doses of rHb1.1 as large as 0.32 g/kg. Because the clearance of rHb1.1 varies inversely with its concentration, additional studies with larger doses are necessary to determine the half-life expected in clinical use. Administration of rHb1.1 to conscious humans is associated with some side effects, such as gastrointestinal upset, fever, chills, headache, and backache.

Fatigue during acute isovolemic anemiain healthy, resting humans

BACKGROUND: Transfusion guidelines recommend that clinicians assess patients for signs and symptoms of anemia before the transfusion of RBCs. However, studies of signs and symptoms associated with acute isovolemic anemia are limited. The objective of this study was to determine whether acute reduction of Hb concentration to 5 g per dL would result in fatigue, tachycardia, or hypotension in resting, young, healthy, isovolemic humans, and whether changes were reversible with RBC transfusion.

Heart rate increases linearly in response to acute isovolemic anemia

BACKGROUND : The cardiovascular response to acute isovolemic anemia in humans is thought to differ from that of other species. Studies of anesthetized humans have found either no change or a decreased heart rate. A previous study showed that in 32 healthy unmedicated humans, heart rate increased during acute isovolemic anemia. The hypothesis that heart rate in humans increases in response to acute isovolemic anemia and that the increase is affected by gender was tested.

How we treat: transfusion medicine support of obstetric services

BACKGROUND: Obstetric services depend on the transfusion service (TS) to provide diagnostic testing and blood component therapy for clinical care pathways.