Iatrogenic hemodilution: a possible cause for avoidable blood transfusions?
Perel Critical Care
Iatrogenic hemodilution: a possible cause for avoidable blood transfusions?
Azriel Perel 0
0 Department of Anaesthesiology and Intensive Care, Sheba Medical Center, Tel Aviv University , Tel Aviv 52621 , Israel
A restrictive approach to blood transfusions is recommended by most current guidelines [1, 2]. Others suggest that in some patients a more liberal transfusion strategy may be beneficial . However, the extensive discussions regarding the appropriate transfusion threshold have not adequately addressed the potential impact of iatrogenic hemodilution on the hemoglobin (Hb) level during dynamic clinical conditions that necessitate fluid administration [4, 5]. This editorial will attempt to describe the frequent occurrence of iatrogenic hemodilution and its potential impact on decisions to transfuse blood.
Anemia; Blood transfusion; Hemodilution; Hemoglobin; Fluid administration; Goal-directed therapy
The effect of fluid administration on the hemoglobin concentration
Fluid administration may result in a beneficial increase
in microvascular flow (and perfusion pressure) with a
global increase in oxygen delivery (DO2) and cellular
oxygenation in conditions of relative volume deficit (e.g.,
distributive shock in sepsis). Fluid administration may
also cause a relative, but not absolute, reduction in
hemoglobin (Hb) concentration (“dilutional anemia”).
Such iatrogenic hemodilution may cause a paradoxical
decrease in DO2 due to the resulting decrease in Hb
concentration, as observed in patients who have received
more colloids as part of perioperative goal-directed
therapy (GDT) [
] and in critically ill patients who did [
did not [
] increase their cardiac output following fluid
loading. In patients in septic shock who received large
amounts of fluids as part of the original early GDT
protocol, a decrease of 30% in hematocrit was uniformly
observed 3 h into the resuscitation, possibly explaining
the very high incidence of blood transfusions in this
group of patients [
]. From a very rough analysis of
these and other studies in surgical and critically ill
patients, it seems that the administration of 500 ml of
fluids may acutely decrease the Hb concentration by
about 1 g/dl, or about 8% [
]. A similar degree of
hemodilution was observed in healthy volunteers in whom
sequential Hb measurements were used to assess the
impact of crystalloid administration [
]. It should be
noted that the microcirculation of healthy individuals
may respond differently to macrocirculatory
derangements than that of surgical patients, and may differ
further in critically ill patients with systemic inflammation.
The potential impact of hemodilution on blood transfusions
It is well established that iatrogenic hemodilution may
lead to increased blood transfusion due to dilutional
coagulopathy and increased surgical bleeding. However,
the resulting decrease in Hb levels may reach values
below the acceptable transfusion threshold, and thus
prompt clinicians to order blood transfusions in the
absence of significant bleeding [
]. This phenomenon
should be considered as a potential unintended
consequence of the administration of large amounts of fluids.
In one of the largest randomized controlled trials
(RCTs) on GDT, the incidence of blood transfusions was
double (22 vs 11%) in the GDT group patients, who
received nearly twice the amount of colloids compared to
the control group, even though the same transfusion
threshold (Hb > 8 g/dl) was used for both groups [
The most feasible explanation for this clinically relevant
and statistically significant difference (p = 0.04 based on
a chi square test), which was not calculated nor
discussed in the article [
], is that more patients in the
GDT group reached Hb levels below the transfusion
threshold due to hemodilution, prompting physicians to
order blood transfusions. Other RCTs have also reported
that patients in the GDT group, who received
significantly more colloid boluses, received significantly more
blood transfusions [
] and had significantly higher
blood loss  compared to the standard therapy group.
In another study, the administration of more colloids led
to lower Hb and DO2 values at the end of surgery
(hemodilution being the responsible mechanism according
to the authors themselves), and an associated trend of
increased intraoperative blood loss [
]. In another
prospective study comparing patients before and after the
adoption of a GDT protocol, a pulse pressure
variationguided protocol was associated with less fluid
administration, significantly higher Hb values after surgery, less
blood transfusions, and decreased morbidity [
seems, therefore, that the administration of greater
amounts of fluids within a GDT protocol is frequently
associated with more blood transfusions. It should be
noted, however, that when fluid administration restores
a depleted blood volume due to previous hemorrhage,
the fall in Hb concentration may in fact reflect true (and
not dilutional) anemia (Fig. 1a).
Continuous non-invasive monitoring of
hemoglobin (“SpHb”) may detect the
development of iatrogenic hemodilution
Although questions have been raised regarding the
absolute accuracy of continuous non-invasive measurement
of Hb concentration (SpHb) [
], this parameter may be
a useful trend monitor in the management of severe
perioperative bleeding [
]. By offering real-time visibility
of changes in Hb levels, SpHb monitoring may also
detect real-time development of iatrogenic hemodilution in
non-bleeding patients. Figure 1a and b depict trends
from hepatic and spinal surgery, respectively, both
known for significant changes in blood volume and
frequent need for blood transfusions. In both cases, a
significant decrease in SpHb to about 7.5 g/dL (dashed
lines in Fig. 1a, b) is observed following the
administration of large amounts of fluids. Simultaneously, there is
a gradual and significant decrease in the
Plethysmographic Variability Index (PVI), a dynamic parameter of
fluid responsiveness, which is due to the increase in the
effective blood volume. In some cases, the observed
acute decrease in SpHb, in the absence of active
bleeding, may help the clinician to reconsider the decision to
administer blood transfusion. In addition, a gradual
decrease in the SpHb in the absence of active bleeding
should also prompt clinicians to re-examine their fluid
The administration of large amounts of intravenous
fluids may cause iatrogenic hemodilution and, at times,
even a paradoxical decrease in DO2. The associated
decrease in Hb values to below the acceptable transfusion
threshold may lead to avoidable blood transfusions.
Perioperative GDT protocols that lead to the intentional
administration of more fluids seem to be associated with
more blood transfusions. By being able to reflect the
development of acute iatrogenic hemodilution in real time,
continuous monitoring of SpHb may be potentially
helpful in identifying fluid overload and in the decision to
GDT: Goal-directed therapy; Hb: Hemoglobin; PVI: Plethysmographic
Variability Index; RCT: Randomized controlled trial; SpHb: Continuous
noninvasively measured hemoglobin
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to Pulsion/GETINGE, Munich, Germany.
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