Intraoperative minimal acute normovolemic hemodilution in patients undergoing coronary artery bypass surgery.

Abstract

Efficacy of minimal acute normovolemic hemodilution (ANH) in avoiding homologous blood transfusion during cardiovascular surgery remains controversial. Postoperative bleeding and transfusion remain a source of morbidity and cost after open heart operations. Our objective was to evaluate the impact of minimal ANH on blood transfusion requirements during open cardiovascular surgery using cardiopulmonary bypass (CPB).
This study was a randomized controlled trial. One hundred one patients scheduled for elective coronary artery bypass graft (CABG) under cardiopulmonary bypass in October 2007 through March 2008 in Imam Khomeini hospital were randomly assigned to a control group (standard care, no = 47) or an ANH or study group (no = 54). We used minimal ANH (representing 10% of patients' blood volume). Mean 490 +/- 50 mL of fresh autologous blood was removed after induction of anesthesia and reinfused at the end of CPB. The blood transfusion guidelines were uniformly applied to all patients.
Significant decrease in the number of red blood cell units transfused per patient per group (1.39 +/- 1.0 and 2.551.9 +/- units; p < 0.0001) in the ANH group versus the control group was observed. Conversely, chest tube output, postoperative hematocrits, and platelet count did not differ between two groups. Percentage of patients in whom allogeneic red blood cells were transfused was 44% in study group versus 76% in control group; (p < 0.01). No patient was transfused with platelet concentrates or fresh frozen plasma.
Minimal ANH is safe and cost effective and its routine use in eligible patients is therefore justified. Intraoperative autologous blood donation in CABG surgery decreased perioperative allogeneic blood requirement. However, the removal and reinfusion of about one unit autologous blood had no effect on postoperative bleeding or platelet count.

Full text

Page 1

423
M.E.J. ANESTH 20 (3), 2009
INTRAOPERATIVE MINIMAL ACUTE NORMOVOLEMIC
HEMODILUTION IN PATIENTS UNDERGOING
CORONARY ARTERY BYPASS SURGERY
AlirezA MAhoori1*, FArhAd heshMAti2*, heydAr NorooziNiA2*;
hAMid MehdizAdeh3#; shAhyAd sAlehi3#
ANd MojtAbA rohANi4*
Abstract
Background & Objective: Efficacy of minimal acute normovolemic hemodilution (ANH)
in avoiding homologous blood transfusion during cardiovascular surgery remains controversial.
Postoperative bleeding and transfusion remain a source of morbidity and cost after open heart
operations. Our objective was to evaluate the impact of minimal ANH on blood transfusion
requirements during open cardiovascular surgery using cardiopulmonary bypass (CPB).
Methods: This study was a randomized controlled trial. One hundred one patients scheduled
for elective coronary artery bypass graft (CABG) under cardiopulmonary bypass in October 2007
through March 2008 in Imam Khomeini hospital were randomly assigned to a control group
(standard care, no = 47) or an ANH or study group (no = 54). We used minimal ANH (representing
10% of patients’ blood volume). Mean 490 ±50 mL of fresh autologous blood was removed after
induction of anesthesia and reinfused at the end of CPB. The blood transfusion guidelines were
uniformly applied to all patients.
Results: Significant decrease in the number of red blood cell units transfused per patient per
group (1.39 ± 1.0 and 2.551.9± units; p < 0.0001) in the ANH group versus the control group was
observed. Conversely, chest tube output, postoperative hematocrits, and platelet count did not differ
between two groups. Percentage of patients in whom allogeneic red blood cells were transfused
was 44% in study group versus 76% in control group; (p < 0.01). No patient was transfused with
platelet concentrates or fresh frozen plasma.
Conclusions: Minimal ANH is safe and cost effective and its routine use in eligible patients
is therefore justified. Intraoperative autologous blood donation in CABG surgery decreased
perioperative allogeneic blood requirement. However, the removal and reinfusion of about one
unit autologous blood had no effect on postoperative bleeding or platelet count.
Key words: Transfusion, Autologous, Hemodilution, Coronary Artery Bypass Graft.
Presented at the 15th International Congress of Iranian Heart Association, Oct.31-Nov.3, 2006, Tehran Iran.
* From the Division of Cardiovascular Anesthesia, Urmia University of Medical Sciences, Urmia, Iran.
1. MD, Assist. Prof. in Anesthesiology, Fellowship in Cardiac Anesthesia.
2. MD, Assoc. Prof. in Anesthesiology, Fellowship in Cardiac Anesthesia.
4. MD, Anesthesiologist.
From the Division of Cardiac Surgery, Urmia University of Medical Sciences, Urmia, Iran.
3. MD, Assist. Prof. in Cardiac Surgery.
Corresponding author: Heydar Noroozinia MD, Assoc. Prof.; Dept. of Cardiovascular Anesthesia, Imam Khomeini Hospital,
Urmia, Iran. E-mail ar_mahoori@yahoo.com

Page 2

A. MAHOORI ET. AL
424
Introduction
Autologous blood transfusion was employed
as early as 1818, and preoperative blood donation
was used in the 19301. In recent years, the potential
benefits of avoiding homologous blood transfusion and
optimizing oxygen delivery in vital organs have led to a
renewed interest for autologous blood transfusion and
acute normovolemic hemodilution (ANH) in major
surgery26-.
Primary reasons for autologous blood transfusion
employment are, avoidance of complications related
to allogeneic blood transfusion, and conservation
of blood resources. The introduction of complex
operative procedures such as: cardiac surgery and
organ transplantation, has led to search and attention
for alternatives to allogeneic transfusion.
Coronary artery bypass graft surgery (CABG) is
one of the most frequently performed major operations
and is highly effective in improving life expectancy
and quality of life in patients with coronary artery
disease7. Although the number of surgical procedures
will continue to decline along with the advances in
interventional cardiology, the proportion of higher-risk
patients requiring complex surgical procedures will
likely continue to increase in the near future8.
In these types of surgeries, as with other
autologous transfusion techniques, ANH can be used
to reduce the need for allogeneic blood transfusion.
There are additional benefits of ANH that are not
common to other autologous transfusion modalities.
When the blood is kept in the same operating room,
the chances of clerical error are eliminated. On the
other hand, because blood collected by ANH is stored
at room temperature and is usually returned to the
patient within eight hours of collection, there is little
deterioration of platelets or coagulation factors1.
Recently, various studies have demonstrated
cardio-protective effects of acute normovolemic
hemodilution in cardiac
cardiopulmonary bypass (CPB), and in addition to
conventional myocardial preservation techniques,
preoperative ANH achieved further cardiac protection
in patients undergoing
revascularization and severe aortic stenosis9-10.
surgeries under
on-pump myocardial
In some studies that ANH was employed during
CABG, net blood loss, amount of reinfused shed blood,
postoperative blood requirements, the percentage of
patients who received allogeneic blood and the number
of blood units transfused per patients, were less in the
ANH group1113-. Despite the fact that some believe that
preoperative or intraoperative collection of platelet-rich
plasma during cardiopulmonary bypass surgery may
improve hemostasis and decrease allogeneic exposures,
others however have found no benefit, and various
studies have questioned the efficacy of intraoperative
acute normovolemic hemodilution (ANH) in reducing
bleeding and the need for allogeneic transfusions in
cardiac surgery and its capacity to reduce perioperative
allogeneic transfusion remains controversial1415-.
The effect of "minimal" ANH on postoperative
blood requirements have not been studied, the aim
of the present study was to evaluate the effects of a
"minimal" ANH in elective, coronary artery bypass
graft.
Methods and Materials
After approval by the local Ethics Committee,
written informed consent was obtained from all patients
scheduled for elective CABG and thought to meet the
eligibility criteria.
Exclusion criteria were left main coronary artery
stenosis; left ventricular ejection fraction less than
40%; anemia (hematocrit <34% and hemoglobin <11.5
g/dL); pump time >2.5h; need for reoperation; history
of hematological disorders; advanced chronic renal
failure (serum creatinine >2 mg/dL); active chronic
hepatitis; or cirrhosis.
One hundred one patients to undergoe CABG
surgery in October 2007 through March 2008 in our
hospital were included in this prospective, randomized
controlled trial to evaluate the merits and practicability
of autologous blood transfusion.
By using a computer-generated random-number
sequence, the 101 patients were prospectively
randomized to one of the two groups: the ANH group
(no = 54) and the standard care group (no = 47).
All patients had same protocol for anesthesia

Page 3

M.E.J. ANESTH 20 (3), 2009
425
INTRAOPERATIVE MINIMAL ACUTE NORMOVOLEMIC HEMODILUTION IN PATIENTS UNDERGOING
CORONARY ARTERY BYPASS SURGERY
gastroepiploic artery were not used in any patient.
After achieving a nasopharyngeal temperature
37°C, weaning from CPB was performed by standard
hemodynamic measurements. The pump flow was
gradually reduced while the heart was progressively
filled in order to optimize the preload-recruitable
stroke volume and to reach a mean arterial pressure
more than 70 mm Hg. The heart was electrically paced
if it failed to maintain a heart rate more than 60 beats/
min. Inotropes were not routinely administered during
weaning from CPB.
At the end of CPB, protamine was administered
to neutralize circulating heparin, and then in the
ANH group, the whole autologous blood volume was
reinfused. Allogeneic Packed red blood cells (PRBC)
were transfused with hemoglobin <10 g/dL and
hematocrit <30%.
Before closure of the chest, mediastinal and
pleural drains were positioned, and low-grade suction
was instituted.
Hemoglobin, and platelet count, were measured
in blood samples obtained before the induction of
anesthesia; at arrival in the intensive care unit (ICU)
after completion of the reinfusion of autologous blood;
24 and 48 h after surgery; and before discharge from the
cardiac intensive care unit. During surgery, hematocrit,
hemoglobin and electrolytes and blood gasses were
monitored in serial samples drawn for blood gas
determinations (nova biomedical, phox plus).
All data were analyzed using statistical software
(version 16 for Windows; SPPS; Chicago, IL). Values
were expressed as mean (±SD). Dichotomous variables
were compared by the x2 statistic or Fisher exact
test, as appropriate, and quantitative variables were
compared with unpaired Student t test. Differences
were considered statistically significant with p values
less than 0.05.
Results
Demographic, preoperative characteristics and
operative data are shown in Table 1. No significant
differences were observed between groups with regard
to age, sex, body surface area, and preoperative left
ventricular ejection fraction.
and surgery. On the morning of operation, the patients
were premedicated with morphine, 5µg/kg. Standard
monitorings such as pulse oximetry, leads II and V5 of
the ECG for heart rate and automated ST-segment trend
analysis, continuous measurements of central venous
pressures and mean arterial, end-tidal capnography,
bispectral index analysis of the EEG (BIS A-2000
XP; Aspect Medical Systems;) and nasopharyngeal
temperature were performed perioperatively.
Balanced anesthesia with propofol, fentanyl,
midazolam, isoflurane, and pipecuronium was
performed in all patients. Inhaled isoflurane (0.5 to 1%
in the pre-bypass period), was administered to enhance
cardiac protection before aortic clamping (anesthetic
preconditioning). In the two groups, a similar depth of
anesthesia was obtained by targeting bispectral EEG
values between 40 and 60 arbitrary units.
In the ANH group, we used minimal ANH
(representing 10% of patients' blood volume)1. After
the induction of anesthesia and before systemic
heparinization, blood was withdrawn from a central
vein by gravity into citrate-phosphate-dextrose
collection bags. Simultaneous gelatin solution (1
mL for each 1 mL of blood withdrawn) was infused
through a 16-gauge peripheral catheter on the opposite
arm. The autologous blood was labeled and stored at
the room temperature and reinfused intraoperatively
when the transfusion criteria were met.
Cardiopulmonary bypass (CPB) and myocardial
preservation strategies were uniform among the two
participating surgeons. After heparinization (300 IU/
kg), CPB including a membrane oxygenator and a
circuit primed with a 2-L normal saline solution was
performed using non-pulsatile flow (2.2 to 2.5 L/min/
m2) and hypothermia (28 to 30°C). An α stat control
for acid-base management was applied, and mean
arterial pressure was targeted between 50 and 80 mm
Hg with pharmacologic and pump flow manipulation
as necessary.
All patients were operated on in our Institution
with standardized techniques. The left internal
mammary artery (LIMA) was isolated through an
extra-pleural approach in all patients for left anterior
descending artery (LAD) graft. The saphenous vein
also was used for other grafts. The radial and the

Page 4

A. MAHOORI ET. AL
426
Also, the number of grafted coronary arteries, as
well as the duration of aortic cross-clamping and CPB,
preoperative hemoglobin, hematocrit and platelet
count, were comparable (Table 2). Mean removal of
blood in the ANH group was 490 ±50 mL. No patient
in the ANH group experienced complications related
to normovolemic blood withdrawal.
Hemoglobin
and postoperatively did not differ among groups.
Significant decrease in the number of red blood cell
units transfused per patient (1.39 ± 1.0 and 2.55±1.9
units; p < 0.0001) in the ANH group versus the control
group was observed (Fig. 1). Conversely, chest tube
output, postoperative hemoglobin and platelet count
did not differ between two groups, but a significantly
larger number of patients in the control group required
allogeneic transfusions.
concentration preoperatively
The total number of PRBC units transfused was
significantly more in the control group (120 vs. 75; P =
0.001). Percentage of patients in whom allogeneic red
blood cells were transfused was 44% in study group
Table 2
Postoperative data and perioperative allogeneic blood
transfusions*
VariableANH group
no = 54
Control
group
no = 47
P Value
Chest tube drainage,
mL/48h
871±48975±59 NS
Hemoglobin (g/dl) 10±1 11±1 NS
Platelet count (mm3) 170804±69178428±70NS
Patients transfused with
PRBC (n, %)
23, 44#
35, 76 0.0001
No. of PRBC transfused
per patient (n)
1.39 ± 1.0#
2.55±1.90.0001
Total FFP (U)00NS
Total Platelet
concentrate (U)
00 NS
Total number of PRBC
transfused (n)
75#
120 0.001
* Data are expressed as mean±SD unless otherwise indicated.
# p < 0.05 between two groups.
PRBC = packed red blood cells; FFP= fresh frozen plasma.
Table 1
Demographic data, Preoperative and operative characteristics of patients*
Variable ANH group
no = 54
55±12
46/8 (17.3)
67.45
1.8±0.14
46±6
13.7±1
40±4
230981±62
Control group
no = 47
58±9
40/7 (17.5)
71.90
1.7±0.19
47±6
13.2±1
39±4
257361±10
P Value
Age (y)
Sex: male/female (%)
Weight (kg)
BSA (m2)
LVEF (%)
Hemoglobin (g/dl)
Hematocrit (%)
Platelet count (mm3)
Preoperative treatment
0.149
0.991
0.224
0.148
0.725
0.069
0.089
0.123
ß blockers (%)
ACE inhibitors (%)
Diuretics (%)
Aspirin (%)
60
31
16
78
62
31
18
79
0.654
0.996
0.256
0.086
0.137
0.898
0.46
-
Grafted coronary arteries (n)
Duration of CPB (min)
Aortic clamp (min)
Removed autologous blood
* Data are presented as mean (95% confidence interval) unless otherwise indicated.
ANH = acute normovolemic hemodilution, BSA = body surface area;
LVEF = left ventricular ejection fraction.
3±0.8
75±21
116±29
490±50
3±0.7
75±25
121±31
-

Page 5

M.E.J. ANESTH 20 (3), 2009
427
INTRAOPERATIVE MINIMAL ACUTE NORMOVOLEMIC HEMODILUTION IN PATIENTS UNDERGOING
CORONARY ARTERY BYPASS SURGERY
more than three units whereas in the ANH group no
patient received more than three unit of PRBC.
All patients in each group who required re-
exploration for excessive bleeding were excluded
from study. No patient was transfused with platelet
concentrates or fresh frozen plasma (FFP).
versus 76% in control group; (p < 0.01). Fig. 2 shown
the total allogeneic blood exposure or number of patients
who received between 0-5 units PRBC in two study
groups. Thirteen patients in the ANH group, versus 4
patients in the control group, did not require any PRBC
transfusions. In the control group ten patients received
Fig. 1
Packed red blood cell units transfused per patient
* 1.39 ± 1.0 in the ANH group versus 2.55±1.9 units in the control group (p<0.05).
ANH = acute normovolemic hemodilution.
Fig. 2
Total allogeneic blood exposure in the two groups (0-5 units PRBC)
* p<0.05
PRBC = packed red blood cells; ANH = acute normovolemic hemodilution.

PRBC = packed red blood cells; ANH = acute normovolemic hemodilution.
13
4
17
7
14
10
10
16
0
5
0
5
0
5
10
15
20
25
30
35
40
45
50
Patients (nb)
0 1 2 3 4 5
Packed Red Blood Cell Units (nb)
ANH group Control group
*