Perioperative Blood Transfusion and Postoperative Mortality
Carson JL, Duff A, Berlin JA, Lawrence VA, Poses RM, Huber EC, O'Hara DA, Noveck H, Strom BL;
JAMA. 1998;279:199-205. [ see abstract below ]
Human Cardiovascular and Metabolic Response to Acute, Severe Isovolemic Anemia
Weiskopf RB, Viele MK, Feiner J, Kelley S, Lieberman J, Noorani N, Leung JM, Fisher DM, Murray WR, Toy P, Moore MA; JAMA. 1998;279:217-221. [ see abstract below ]
Two peer-reviewed articles appear in a single issue of the Journal of the American Medical Association related to the level of anemia in patients which can be safely tolerated without transfusion. In the first of these two articles, Carson et al begin by pointing out that the practice of transfusing patients for a hemoglobin level less than 100 grams per liter or a hematocrit less than 0.30 is no longer uniformly accepted. This is primarily because of the lack of sufficient studies on the efficacy of red blood cell transfusion to establish clear guidance in this area.
The authors note that only five randomized clinical trials, including a total of 207 patients, have contrasted various hematocrits at which transfusion was initiated, yet no differences in mortality or morbidity were documented between the high and low transfusion thresholds. Not only did these studies reflect too few patients to sufficiently evaluate the effect of lower transfusion triggers on clinically important outcomes, but the studies did not control for risk factors for death or evaluate the effects of hemoglobin concentrations other lower than 100 grams per liter.
Carson et al evaluated 30 and 90 day postoperative mortality in patients with hip fractures, comparing those who received preoperative and postoperative transfusions with similar patients who did not receive transfusions. In this specific study, involving a total of 8,787 consecutive hip fracture patients aged 60 years or older undergoing surgery, these authors found no evidence that transfusion improved survival, despite chronic disease and hemoglobin concentrations as low as 80 grams per liter. In an effort to examine the potential limitations of their study, the authors attempted to identify and control for factors associated with transfusion status and death, examining a large array of co-morbid conditions, including several widely used clinical indices predictive of short-term mortality, intraoperative events, surgical procedure and types of anesthesia.
Additionally, the authors point to possible limitations in their study. First, the data were collected retrospectively, yet they are unlikely to be biased in the three primary study variables: transfusion status, hemoglobin level, and postoperative death. Second, although this report is the largest sample size reported to date in this subject, it may still be of insufficient size to provide adequate power to distinguish the relationship of transfusion to mortality. Third, the authors note that factors such as morbidity, re-admission to the hospital, speed of recovery and functional status may prove to be influenced more by transfusion than mortality. Fourth, the data collection period of 11 years and the geographic distribution over 20 hospitals in four geographic areas might add variability to the interpretation of the morbidity statistics associated with transfusion, however, the authors note that they found no correlation among these factors. Finally, the authors remind us that measurement artifacts can skew the interpretation of transfusion-related data, and most importantly, caution that results from the population studied in this particular article not be extrapolated to other patient populations without appropriate considerations.
The second of these studies, by Weiskopf et al, examined the effects of acute isovolemic reduction of blood hemoglobin concentrations to 50 grams per liter in conscious, healthy, resting humans. They found that this treatment did not result in detectable inadequate systemic T02. Similar to the precautions referenced in the study by Carson et al, these authors remind the reader that their subjects were healthy, resting and supine and, thus, these results should not be extrapolated to conditions associated with higher oxygen demand, decreased ability to mount appropriate cardiac compensation, or decreased capacity to upwardly modulate a specific organ or tissue blood flow.
ABSTRACT Perioperative Blood Transfusion and Postoperative Mortality (Carson et al)
Context: The risks of blood transfusion have been studied extensively but the benefits and the hemoglobin concentration at which patients should receive a transfusion have not.
Objective: To determine the effect of perioperative transfusion on 30- and 90-day postoperative mortality.
Design: Retrospective cohort study.
Setting: A total of 20 US hospitals between 1983 and 1993.
Participants: A total of 8787 consecutive hip fracture patients, aged 60 years or older, who underwent surgical repair.
Main Outcome Measures: Primary outcome was 30-day postoperative mortality; secondary
outcome was 90-day postoperative mortality. The "trigger" hemoglobin level was defined as the
lowest hemoglobin level prior to the first transfusion during the time period or, for patients in the
nontranfused group, as the lowest hemoglobin level during the time period.
Results: Overall 30-day mortality was 4.6% (n=402; 95% confidence interval [CI], 4.1%-5.0%); overall 90-day mortality was 9.0% (n=788; 95% CI, 8.4%-9.6%). A total of 42% of patients (n=3699) received a postoperative transfusion. Among patients with trigger hemoglobin levels between 80 and 100 g/L (8.0 and 10.0 g/dL), 55.6% received a transfusion, while 90.5% of patients with hemoglobin levels less than 80 g/L (8.0 g/dL) received postoperative transfusions. Postoperative transfusion did not influence 30- or 90-day mortality after adjusting for trigger hemoglobin level, cardiovascular disease, and other risk factors for death: for 30-day mortality, the adjusted odds ratio (OR) was 0.96 (95% CI, 0.74-1.26); for 90-day mortality, the adjusted hazard ratio was 1.08 (95% CI, 0.90-1.29). Similarly, 30-day mortality after surgery did not differ between those who received a preoperative transfusion and those who did not (adjusted OR, 1.23; 95% CI, 0.81-1.89).
Conclusions: Perioperative transfusion in patients with hemoglobin levels 80 g/L (8.0 g/dL)
or higher did not appear to influence the risk of 30- or 90-day mortality in this elderly population.
At hemoglobin concentrations of less than 80 g/L (8.0 g/dL), 90.5% of patients received a
transfusion, precluding further analysis of the association of transfusion and mortality.
Human Cardiovascular and Metabolic Response to Acute, Severe Isovolemic Anemia
(Weiskopf et al)
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 venou 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 (VO2), 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: VO2 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 VO2 and plasma lactate concentration. Analysis of Holter readings suggests that
at this Hb concentration in this resting healthy population, myocardial ischemia would occur
infrequently.
