1. Transfusion and Apheresis Science 45 (2011) 269–274
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Transfusion and Apheresis Science
journal homepage: www.elsevier.com/ locate/ transci
Acute normovolemic hemodilution
Giorgio Oriani a,⇑, Marco Pavesi b, Alessandro Oriani c, Ilaria Bollina a
a Servizio Anestesia ICSS, Milano, Italy
b Servizio Anestesia IRCCS, Policlinico San Donato, Milano, Italy
c Servizio Anestesia e Rianimazione IRCCS, San Raffaele, Milano, Italy
a r t i c l e i n f o
Keywords:
ANH
Low Ht physiology
Total hip arthroplasty
Hemodinamic parameters
a b s t r a c t
Acute normovolemic hemodilution (AHN) is a well known but poorly used ‘‘blood saving’’
method. The authors, based on their own experience and on the ‘‘low hematocrit’’ physiol-ogy,
present some concepts on AHN and a clinical experience to demonstrate the useful-ness
and affordability of this method. Consequently we offer several tools concerning
both the realization of AHN and the safe use of such dilution, suggesting simple and excit-ing
methods to determine if, when and how to apply this blood saving system.
2011 Elsevier Ltd. All rights reserved.
1. Introduction
Hemodilution (HD) is an acute dilution of erythrocytes
and plasma concentration, obtained through a partial
substitution of the blood with artificial colloids and/or iso-osmotic
cell-free fluids. The HD has to be defined ‘‘isovo-lemic’’
whenever the dilution affects the corpuscular part,
while the circulating blood volume remains stable. In this
case we can correctly think of the low hematocrit (Ht) with
all that this definition entails [1]. The term ‘‘Hypervolemic
HD’’ really means a dilution of the corpuscolated part with
a circulating blood volume implemented by plasma and/or
macromolecular solutions to increase the circulating vol-ume
(and a consequent lower Ht). Konrad Messmer first
began to consider HD as a blood sparing method in the
early 1970’s and published his clinical experiences in the
‘‘Intentional Hemodilution’’ book, upon which several
authors have based their training [2].
Although the first goal of ANH was to obtain autologous
blood amount and to reduce intra and postoperatory blood
losses, it was soon evident that such a dilution was linked
to positive effects on blood flow properties. An acute
hemodilution, causes blood flow changes both in macro
as in micro-circulation, strictly due to a new fluidity of
such a circulating fluid. Main determinants of blood fluid-ity
are Erythrocytes concentration (Ht), their deformability
and aggregability and plasma viscosity. Viscosity depends
on shear stress vs. shear rate (m = t/D) this means that
any increase in the hematocrit value carries an increase
in the blood viscosity. Shear rate and blood viscosity influ-ence
erythrocytes aggregability and deformability [3,4].
Erythrocyte dilution increases the blood fluidity giving bet-ter
deformability and aggregability in the circulatory sys-tem
[5]. Blood fluidity rise increases cardiac output and
consequently offers a better oxygen supply to organs and
tissues. The linear lowering of the Ht causes an exponential
improvement of the rheological blood properties, espe-cially
for an Ht between 45% and 30%. This last value is
considered the best compromise between blood oxygen
transport and blood fluidity [1–9].
Cardiac output improves for an increased blood ‘‘back to
the heart’’ and systolic volume, with normal heart rate [6].
This happens until normovolemia is observed and Ht does
not fall below 25% [10]. Tachycardia appears as a conse-quence
of hypovolemia, too low Ht and increased oxygen
demand. During ANH, like in the normal condition, blood
flow is uniformly distributed to the organs except in coro-nary
circulation [7]. For this reason ANH is contraindicated
⇑ Corresponding author. Address: C/o ICSS, Via Monreale 18, 20148
Milano, Italy. Tel.: +39 02 487851.
E-mail addresses: giorgio.oriani@grupposandonato.it, gorian@alice.it
(G. Oriani).
1473-0502/$ - see front matter 2011 Elsevier Ltd. All rights reserved.
doi:10.1016/j.transci.2011.10.006

2. 270 G. Oriani et al. / Transfusion and Apheresis Science 45 (2011) 269–274
where coronary flow is compromised like in cardiopatic
ischemic patients.
In our centre, we usually applied this procedure first of
all in orthopedic patients especially those submitted to hip
arthroplasty. In this study we have monitored patients
with Vigileo to control hemodynamic conditions and verify
whether reference parameters control allows to take
advantage in ANH, to make it safer and more efficient.
2. Methods
In our study, we evaluated the results obtained by two
groups of patients. A study group of 23 patients (12 males
and 11 females) and a control group of 24 patients (13 males
and 11 females). Any patient undergoing hip replacement or
revision hip surgery and has been submitted to an ANH pro-cedure.
Exclusion criteria reflected clinical conditions of risk
relative to a cardiopathic ischemic, valvulopathic and cere-brovascular
patients. In serious bronco pneumopathy, acute
and chronic renal insufficiency and coagulation deficit ANH
is also contraindicated. Each surgery was performed by the
same surgical staff and followed by the same anesthetist. It
was never necessary to give up the procedure due to compli-cations.
Study groups have been submitted to haematic
hemodynamic tests: basal Ht and Hb, volemic conditions,
blood amount to take off based on patient’s weight and
volemic mass, quantity of substitution fluids to reinfuse dur-ing
the dilution phase, Ht and Hb checks to determine the
safe timing of the whole procedure. During all procedures,
all patients were monitored for heart rate, invasive pressure,
ST variations, SatO2, diuresis and consciousness. A system of
hemodynamic monitoring slightly invasive has been used to
measure cardiac output, systemic, stroke volume variations
(SVV%), vascular resistance and venous central oximetry. At
the end of each deposit unit some hematic controls were
performed referring to electrolytes (to control quality of
the substitution), Ht and Hb (Anemia), pH, Sat02, PaO2, lac-tates
(to evaluate any lack in adequacy of metabolic require-ments).
Heart rate, mean AP, ST, CO, RVP,DO2, SVV% features
allowed the authors to be able to detect in advance any
warning for possible cardiac distress and to verify the ade-quacy
of compensation system. Continuously checking pa-tients’
consciousness allowed medical staff to keep
controlling an enough cerebral perfusion. Where changes
emerged the procedure was immediately suspended. By
applying the Gross formula it has been determined how
much blood could be taken off: EBV (Htr Htd)/Htm,
where EBV = estimated blood volume (approx. 7% of pa-tients’
weight), Htr = actual hematocrit value, Htd = value
to reach before surgery (estimated 30% according to Hint
studies), Htm = the difference between them. As specific
parameters were chosen: SVV (100%) as limit value for nor-volemia,
SatO2 (70%) as limit value in anemic situation of
compensation attempt in oxygen extraction and finally cen-tral
venous of lactates concentrations (2.0 mmol) as sign of
metabolic deviation from aerobic to anaerobic. Volume to
be reinfuse is calculated basing on a proportion of 1:2
(1000 ml blood = 2000 ml volemic substitution) with such
a ratio: 2/3 of crystalloids and 1/3 of colloids [11,12]. Blood
volumes have been evaluated basing on weight of volume
taken off, considering a proportion of 1:1 (mg:ml). The
autologous collection bags were filled up to obtain a volume
of 300–350 ml. A complete hemodynamic control has been
maintained during all operative and post-op period in awak-ening
area. During all surgical intervention some hematic
tests have been executed and blood intra-op losses have
been noted. During post surgical time have been collected
data referring to drain losses, blood tests, blood units (autol-ogous
vs. homologous) transfused, length of stay in hospital
and any arisen complications. All control group patients
underwent preoperative ANH procedure, applying the same
criteria and restrictions as in the study group. In the control
group a traditional system of monitoring, registering Ht and
Hb; pH, SatO2; PaO2, Fc, diuresis, and consciousness was ap-plied.
Vigileo monitoring system was not used for register-ing
CO, CI, SVV, SvO2, DO2.
3. Result analysis
In study group 59 years was the average age, 38% and
12.7 g/dl, respectively the average pre-op hematocrit and
Hb. In nine cases anesthesia was Loco-Regional (Spinal),
while the other 14 patients were treated by general anes-thesia.
This decision was based on single medical histories
and hematic values found at the anesthesiological evalua-tion.
In the control group, the average age was 51 years,
average basal hematocrit was 41% and 13.8 mg/dl was
average basal hemoglobin. In this group we applied loco-regional
anesthesia in 10 patients and general anesthesia
in the other 14 patients.
Average HT% value alters during different phases, start-ing
from basal values, followed by values registered after
first, second, third and fourth blood sampling (350 ml
each), and more just before reinfusion of blood, after rein-fusion
and finally at the moment of surgical room (Fig. 1).
The highlighted graph area shows the intra surgical proce-dure
period, when the lowest hematocrit value was
reached (24.3%). DO2 (ml/min) modifies its values during
different phases (Fig. 2), starting from basal to first, second,
third and fourth blood sampling, just before reinfusion of
blood, after reinfusion and finally at the moment of operat-ing
room discharge. DO2 values are indicated in ml/min.
During reinfusion phase it was reached the lowest DO2 va-lue
(448 ml/min). Stroke volume variations represent a
parameter that describes volemic condition. This value is
the average variation between the minimal and maximum
peak of sequential arterial pressure waves. This variability
depends by the effect of breath to reduce the back flow to
the heart. In particular, breath influence to circulation is
more evident in ipovolemic condition and less in normovo-lemic.
The lower is variation of artery peak and the value of
SVV more normovolemic the patient is normovolemic.
During all procedure average values fluctuated between
10% and 15%, reaching the highest level at the moment of
the second blood sampling (15%) and just before reinfusion
(14%) (Fig. 3). At the moment of surgical room discharge
the hemodynamic value reached is the same as before
beginning hemodilution procedure. Like SVV%, cardiac
index enables to evaluate patient’s hemodynamic condi-tions
and is related to an efficient circulatory system dur-ing
acute normovolemic hemodilution. It allows to check
patient’s conditions and to correct any wrongness it may

3. G. Oriani et al. / Transfusion and Apheresis Science 45 (2011) 269–274 271
Fig. 1. Representation of hematocrit modifications in the different phases.
Fig. 2. DO2 modifications during different phases of hemodilution procedure.
Fig. 3. Modifications of stroke volume variation (SVV%) in the different phases.

4. 272 G. Oriani et al. / Transfusion and Apheresis Science 45 (2011) 269–274
Fig. 4. Cardiac index modifications during different phases.
Fig. 5. Venous oxygen saturation (SvO2) fluctuations during each phase.
Fig. 6. Modifications of lactates (mMol/l) concentration during different phases of hemodilution procedure.

5. G. Oriani et al. / Transfusion and Apheresis Science 45 (2011) 269–274 273
Fig. 7. Transfusion risk in ANH group vs. control group.
occurs. Statistic results obtained show a fine stability dur-ing
first blood sampling, a fairly variation if a fourth blood
unit should be drawn and a strong instability just before
autologous blood reinfusion. When procedure is completed
values return as before (Fig. 4). Venous oxygen saturation
(SvO2) allows to check the peripheral oxygen extraction,
the last of human mechanisms to compensate for a tissue
deficit need. This parameter allows to verify the adequacy
of the patient’s metabolic balance when less oxygen is
delivered in tissues or there is a higher requirements of
the same. This parameter allows also to evaluate patient’s
conditions and to correct any errors that may occurs. It has
been verified that a progressive blood anemization, as re-sult
of autologous blood sampling, concurred to optimize
physiological system of compensation and tissue oxygen
requirements. In fact, during all the blood sampling phases
SvO2 increased, reaching a maximum of 79% during fourth
blood sampling while just before and during reinfusion
there has been an abrupt drop of values (68%). When the
patient was discharged from the surgical area, venous sat-uration
increased and reached 71% (Fig. 5). Lactates are
produced when cellular metabolism, in lack of oxygen,
changes from aerobic to anaerobic. Therefore their appear-ance
means that less oxygen than necessary is delivered to
tissues and, beyond a certain limit, a reduction of physio-logical
pH (acidosis) occurs. During first blood sampling,
lactates reached a positive level of 1 mmol/l, while during
reinfusion of autologous blood it was reached the highest
lactates value, near 3 mmol/L (Fig. 6). Study group patients,
undergone to ANH and monitored according to the proto-col,
have a lower risk to be transfused with homologous
blood than control group patients, also undergone to
ANH but monitored in a traditional way (Fig. 7).
4. Discussion
This technique, compared to the predeposits one, pre-sents
several advantages, while the latter could cause some
inconveniences for the patient. Hemodiluition has to be
done just before surgery. Its relatively simple and quick
preparation allows the same to be used both for elective
and emergency surgery, while the collected blood is kept
nearby the patient’s bed, minimizing costs for collecting,
maintenance and control the predeposit units. The mean-ing
of all these factors is that ANH can be considered as a
useful, effective and convenient method. Finally, ANH is ac-cepted
by most but not all of Jehovah’s Witnesses; in fact
blood should be constantly kept in contact with the circu-lation
and there should not be any continuous solutions
between blood way in and out of the body.
Monitoring during ANH has showed some adjunctive
hemodynamic parameters that guaranteed to maintain
normovolemic conditions during all procedure and sur-gery.
This has permitted to obtain an adequate correlation
between blood drawn and volemic reintegration. This is
showed by graphics in Figs. 3 and 4 in which an initial in-crease
in SVV% has been rapidly corrected and hasn’t influ-enced
cardiac index. DO2 curve (Fig. 2) and Ht% curve
(Fig. 3) show a similar trend during all the procedure. Evi-dently
entity of Ht% reduction isn’t been so deep to justify a
cardiac intervention (Fig. 4) to compensate DO2 reduction.
During anesthesia VO2 is minimal because all the body is at
rest. DO2 adequacy to VO2 is also confirmed by SvO2 (Fig. 5)
and lactates (Fig. 6).
All parameters maintain a constant trend until the
phase just before reinfusion of autologous blood (ANH).
Three particular factors happen in this moment: anesthesia
awakening, increasing volume anemia reduction by autol-ogous
blood reinfusion. After this critical phase almost all
parameters back to initial preoperatory values, only SvO2
(Fig. 5) falls down and lactates drops up (Fig. 6). Maybe this
is due to increase VO2 by anesthesia awakening.
Comparing study group with control group we have
noted that there is a very important difference. Control
group start with Ht values higher (41%) than those in study
group (38.2%). The final values are similar, respectively Ht
30.5% and Ht 30.7% but during postoperative period
control group patients have been transfused more than
the other group. This shows that information given by

6. 274 G. Oriani et al. / Transfusion and Apheresis Science 45 (2011) 269–274
monitoring improves benefits offered by ANH. In fact study
group patients have drawn an average of 450 ml more
blood than the other group. Moreover, monitoring permit-ted
an early identification of real ipovolemic conditions
and consented to treat them with adequate integrative
volumes.
5. Conclusion
Starting from the physiology of the low Ht, through
clinical experiences, we examine the whole procedure
and the peculiarities of ANH. The final result, in our opin-ion,
is a suggestion to apply such a procedure, well keeping
in mind that anemia does not mean hypovolemia and that
each step is equally important (consequences have to be
carefully examined!). The actual possibilities both in mon-itoring
and in drug use, certainly improves the safety we
always seek, and help to consider such a ANH as an old-young
system to safe blood in surgery.
Acknowledgment
The authors want to thank Dr. Isabella Oriani for help-ing
in translating.
References
[1] Duruble M, Martin Jl, Duvelleroy M. Effets théoretiques,
expèrimentaux et cliniques des variations de l’Hématocrite au
cours de l’hémodiluition. Ann Anesth Fr 1979;9:805–15.
[2] Messmer K. Hemodilution. Surg Clin N Am 1975;55:659–78.
[3] Messmer K, Sunder-Plassmann L, Kloverkon WP, Holper K.
Circulatory significance of hemodiution: rheological changes and
limitations. Adv Minorcirc 1972;4:1–77 [Karger, Basel].
[4] Chien S. The present state of blood rheology; in Messmer am
Schmid–Schoubein hemodilution. Theor Basis Clin Appl 1972:1–40
[Kager, Basel].
[5] Messmer K, Kreimeir U, Intaglietta M. Present state of international
Hemodiluition. Eur Surg Mes 1986;18:254–63.
[6] Kloverkorn WP, Richter S, Sebening F. Hemodilution in coronaryby-pass
operation. Biblioth Haematol 1981;47:297–302 [kunger, Basel].
[7] Schmid-Schonbein H, Messmer K, Rieger H. Hemodilution an flow
improvement. Biblioth Haematol 1981;47 [Kuger, Basel].
[8] Hint H. The pharmacology of dextran an physiological background of
the clinical use rheomacrodex. Acta Anaesth Belge 1968;19:119–38.
[9] Mirhashemi S, Messmer K, Intaglietta M. Tissue perfusion during
normovolemic hemodilution investigated by a hydraulic model of
cardiovascular system. Int S Microcrc Clin Exp 1987;6:123–36.
[10] Messmer KFW. Acceptable hematocrit levels in surgical patients.
World J Surg 1987;11:41–6.
[11] Anderson Westphal M, James MFM, Stocker R, Van Aken H.
Hydroxyethyl starches. Different products–different effects.
Anesthesiology 2009;111:187–202.
[12] Boldt J. Hydroxyethylstarch can be safely use in the intensive care
patient–the renal debate. Intensive Care Med 2009;35:1337–42.