








































Anesthesia eJournal
Volume 2 Issue 2 2014

AEJ

Educated Hand Publishing LLC 
“The Science Behind the Art”  

 Anesthesia eJournal - Online
ISSN 2333-2611

Abstract

Perioperative Management To Prevent Allogeneic Blood Transfusion In Liver Surgery

Robbin Rabbani, CRNA, MS
Michele E. Gold, CRNA, PhD

Affiliations:
This article was written by Robbin as student at USC. Correspondence: Robbinra@usc.edu 
Michele E. Gold, CRNA, PhD is program director, Program of Nurse Anesthesia in the Keck School of Medicine of the University of Southern California, Los Angeles. Correspon-
dence: mgold@usc.edu

Considerable surgical blood loss is a recognized complication of hepatic surgery. Allogeneic blood 
product transfusion can be used to treat anemia related to surgery. However, research has shown 
that transfusing blood products exposes the patient to multiple risk factors. Methods of surgical 
and anesthetic management of blood loss such as establishing acute normovolemic hemodilution 
and maintaining low central venous pressure can prevent the need for a transfusion. This case 
study outlines the use of acute normovolemic hemodilution and low central venous pressure to 
prevent allogeneic blood transfusion in a patient undergoing hepatic resection. 

Keywords:
Allogeneic transfusion; central venous pressure, hemodilution, hepatic resection, hepatectomy.

Acknowledgments
The authors thank Ben Lindsey, CRNA, MS, for his guidance and encouragement in this case and for his continued 
efforts to educate future certified registered nurse anesthetists at the University of Southern California.

INTRODUCTION
Advances in the operative and anesthetic techniques of hepatic resection have decreased associated 

morbidity and mortality. Administration of allogeneic blood products to correct anemia and coagulopathy 
is routine in this surgical population, although adverse events occur with significant frequency. 
Immunosuppression, infection, transfusion reactions, and early recurrence of cancer have all been 
associated with allogeneic blood transfusions.1-3 The incidence of these complications may be as high as 
1 in 2000 units of red blood cells (RBC) transfused. Furthermore, the incidence of transfusion errors has 
been estimated at 1 in 14,000 units of blood transfused.4 

Anesthesia practitioners must focus on careful perioperative management to reduce RBC loss and 
prevent allogeneic blood transfusions. Techniques traditionally used to prevent allogeneic transfusion 
during hepatic resection include clamping the major hepatic vessels, decreasing retrograde hepatic 
blood flow, and diluting the circulating RBC concentration.1,2 In this case report, acute normovolemic 
hemodilution (ANH) and maintenance of a low central venous pressure (CVP) were implemented to 
reduce the concentration of RBC lost, decrease overall blood loss, and prevent allogeneic blood transfusion.

mailto:Robbinra@usc.edu
mailto:mgold@usc.edu


Anesthesia eJournal                         www.anesthesiaejournal.com
Volume 2 Issue 2 2014 

CASE SUMMARY
A 53-year-old woman with an American Society of 

Anesthesiologists (ASA) Physical Status 3 presented for 
open surgical resection of a liver mass. She was 163 cm tall 
and weighed 83 kg. Her medical history included type 2 
diabetes mellitus, hypertension, and rectal cancer. Preoperative 
medications were metformin and valsartan. The patient’s surgical 
history included transrectal excision of rectal cancer in 2009. 
Preoperative laboratory values were as follows: hemoglobin 
13.4g/dL, hematocrit (HCT) 40.2%, blood urea nitrogen 13 mg/
dL, creatinine 0.66 mg/dL, glucose 162 mg/dL, protime (PT) 
10.4 seconds, international normalized ratio 1.0, and partial 
thromboplastin time (PTT) 28 seconds. The chest x-ray showed 
no acute disease; the electrocardiogram (ECG) showed a possible 
inferior infarct. A myocardial perfusion scan was performed after 
the ECG. The scan showed normal perfusion, ventricle size, and 
ejection fraction and no wall motion abnormalities. The ECG 
results did not clinically correlate with the perfusion scan, and the 
patient was cleared for surgery.  The preoperative vital signs were: 
heart rate 106 beats per minute, blood pressure 116/80 mm Hg, 
respiratory rate 19 breaths per minute, and temperature 36.6°C.

The patient was given 2 mg midazolam intravenously (IV) 
before entering the operating room. Standard ASA monitors 
were connected to the patient, and a face mask delivering 6 L/
min oxygen was applied. The patient was placed in a seated 
position, and the regional anesthesia team inserted a thoracic 
epidural at the level of T8 without complications. The patient was 
positioned supine, pre-oxygenated for 5 minutes, and induced 
with 100 mg lidocaine, 100 mcg fentanyl, 150 mg propofol, and 
10 mg cisatracurium. A 7.0-mm endotracheal tube (ETT) was 
inserted into the trachea. General anesthesia was maintained with 
desflurane 5%-6% inspired concentration in a mixture of 0.5 L/
min oxygen and 0.5 L/min air.

A 20-gauge right radial arterial catheter and a 7F triple-
lumen central venous catheter (CVC) were placed under sterile 
conditions. The CVP was transduced through the CVC. The 
patient was placed in a 15-degree Trendelenburg position. Two 
citrate phosphate dextrose (CPD) bags were attached to the CVC 
for phlebotomy. About 700 mL blood were collected between 
both bags, which were stored in a cooler and agitated periodically 
to prevent clotting. Albumin 5% (500 mL) and plasmalyte (600 
mL) were administered IV over 30 minutes. Post-phlebotomy 
and hemodilution lab specimens were processed in the main 
hospital laboratory and resulted in HGB 11.5 g/dL and HCT 
35%. Before the intraparenchymal dissection, the surgeon 
clamped the hepatic arteries and portal vein. During resection, 
CVP was maintained at ≤4 mm Hg with administration of a 
nitroglycerin (NTG) infusion. As blood loss increased, IV fluids 
and phenylephrine were needed to maintain the blood pressure 
within 10%-20% of preoperative values. Total administration 
of NTG was 2100 mcg, and administration of phenylephrine 
was 2450 mcg. Total IV fluid administration was 3 L crystalloid 
and 500 mL albumin. Total blood loss for the operation was 
estimated at 500 mL, and urine output was 250 mL. 

Before extubation, 700 mL whole blood in the CPD bags were 
transfused to the patient over 30 minutes, and the phenylephrine 
infusion was adjusted downward and turned off. Epidural 
morphine (3 mg) was administered before tracheal extubation. 

Return of neuromuscular function was determined by train-
of-four monitoring with 4/4 twitches and sustained tetany. 
The patient met extubation criteria to maintain spontaneous 
ventilation, and the ETT was removed. The patient was 
transferred to the postanesthesia care unit (PACU) with 6 L/
min oxygen administered via face mask. After 30 minutes in 
the PACU, the blood pressure began to decline but responded 
to administration of 500 mL normal saline. The patient did not 
complain of pain. 

To prevent further decline in blood pressure, epidural infusion 
of local anesthetic was not initiated. After 30 minutes in the 
PACU, the patient reported pain at the surgical site. She was 
given IV hydromorphone for pain management in the PACU 
and throughout her hospitalization. Postoperative hematology 
results in the PACU were HBG 8.7 g/dL and HCT 25.5%. On 
postoperative day 2, the patient’s HGB increased to 9.0 g/dL 
and HCT to 26.1%. The epidural was used only for morphine 
administration at the end of surgery and was discontinued 
on postoperative day 3 with no sequelae. No allogeneic blood 
products were transfused during hospitalization.
DISCUSSION

Hepatic resection is the preferred management for malignant 
and benign masses of the liver.3 Over the past few decades, 
advances in intraoperative management have reduced morbidity 
and mortality associated with this surgical population.3 However, 
acute blood loss remains a significant challenge for both surgeons 
and anesthetists. Often, these losses result in the transfusion of 
allogeneic blood products.2 Serious complications such as renal 
injury, immunosuppression, sepsis, hemolytic reactions, acute 
lung injury, and infection can occur after these transfusions.4,5 To 
prevent these complications, anesthetic management should focus 
on interventions to minimize surgical blood loss. In this case, the 
following plan was implemented to accomplish this goal: before 
incision, ANH would be used and, during liver parenchymal 
resection, CVP would be maintained at ≤4 mm Hg. 

Establishment of ANH involves the removal of blood cells, 
resulting in RBC dilution and lower HGB and HCT, followed 
by return of the patient’s original blood concentrated with 
RBCs and coagulation factors. By replacing the blood that was 
removed with colloid or crystalloid, the blood lost is diluted. 
This results in a decrease in the number of lost RBCs during 
intraoperative bleeding and maintains intravascular volume 
and cardiac output.3,6 Transfusing blood at the end of surgery 
can increase RBC count, restore blood volume, and improve 
coagulability.4 For this patient, 2 CPD bags were used to remove 
about 700-800 mL. However, larger volumes of blood can be 
safely removed during ANH.3,6,7 Hemodilution to HGB levels 
of 8.0 g/dL can easily be achieved if the patient’s hemodynamic 
status is maintained during the procedure. The amount of blood 
that needs to be removed to achieve a target HGB or HCT can 
be estimated by applying the equation in Figure 1.3,6 Substituting 
the patient’s pre- and post-phlebotomy HCT confirms that the 
estimated amount of blood removed in the 2 CPD bags was 
accurate. 

The effectiveness of ANH in reducing allogeneic blood 
transfusion has been debated. Table 1 includes a number of 
studies for review. A 2004 meta-analysis reviewed 42 randomized 
controlled trials using ANH and concluded that there was no 



Anesthesia eJournal                         www.anesthesiaejournal.com
Volume 2 Issue 2 2014 

significant reduction in the incidence or relative risk of allogeneic 
blood transfusion. The volume of blood transfused in the ANH 
group was significantly less than in the usual-care groups. 
Although the volume of blood transfused was decreased by 1-2 
units, it did not affect the incidence of allogeneic transfusion.8 
However, this meta-analysis had limitations; most of the studies 
were not conducted in the United States, and only 12 had the 
outcome evaluator blinded to the study group. In addition, only 
one study was specific to hepatic surgery. A 2002 study specific 
to ANH in hepatic surgery showed a significant increase in the 
incidence of allogeneic transfusion when ANH was not used.9 
Four patients in the ANH group received an allogeneic blood 
transfusion, compared with 14 patients in the control group. Half 
the patients in the control group received only 1 unit of blood. 
This could have been avoided by using ANH.9 

In 2006, the ASA conducted a research review and published 
its guidelines for perioperative blood transfusion. The ASA 
concluded that there is statistically significant evidence to 
support using ANH to reduce perioperative allogeneic blood 
transfusion.10 More recent research also supports these findings. 
Jarnagin et al, who studied patients undergoing hepatic resection,  
demonstrated a 50% reduction in RBC transfusion using ANH.3 

Guo’s 2013 study compared 30 elderly patients undergoing 
hepatic resection randomly assigned to either ANH or a 
control group.7 This study also identified a significant decrease 
in blood transfusion in the ANH group by more than 100 mL 
RBC. Although fibrinogen was decreased and PT/PTT were 
prolonged after ANH, these values were within normal limits and 
improved to values similar to the control group after transfusion 
of homologous blood.7 ANH facilitated a reduction in the 
concentration of RBCs lost, and  allogeneic blood transfusion was 
not necessary, possibly due to ANH therapy.

 Maintenance of a low CVP (≤5 mm Hg) has been identified 
as a potential means to reduce blood loss during hepatic 
resection.2,11 A low CVP results in a decrease in retrograde 
pressure and flow through the dissected liver parenchyma. The 
surgical steps involved in hepatic resection include an initial 
clamping of the hepatic arteries and portal vein, causing total 
hepatic inflow occlusion before parenchymal dissection. The 
increase in pressure from the retrograde blood flow into the 
hepatic veins increases bleeding through the hepatic sinusoids. 
Lowering the CVP can reduce these pressures and blood flow 
to the liver to decrease overall blood loss (Table 2). A research 
trial to evaluate this phenomenon studied two groups of 50 
patients undergoing hepatic resection (CVP ≤5 mm Hg or CVP 
>5 mm Hg). Demographic data and transfusion thresholds 
were equivalent in both groups. The low CVP group recorded a 
roughly 80% reduction in blood loss and significantly fewer blood 
transfusions.11 Multiple methods can be used to reduce CVP 
while maintaining normotension. 

A 2006 study of 50 patients undergoing hepatic resection 
used IV NTG infusion and the Trendelenburg position, limited 
IV fluid administration, and used IV furosemide to maintain 
CVP at 2-4 mm Hg. Compared with the control group, the 
low CVP group had a 69% reduction in blood loss and a 32% 
reduction in allogeneic transfusion.12 In 2008, a trial of 46 
patients used similar methods to reduce CVP to 2-4 mm Hg. 
This trial evaluated the volume of intraoperative blood loss and 
blood product administration and monitored renal function to 
postoperative day 7. The low CVP group demonstrated a 49% 
reduction in intraoperative blood loss and a 44% decrease in 
volume of blood product administration compared with the 
control group. There were no differences in postoperative renal 
function in either group.13 In this case, CVP was maintained at 
≤4 mm Hg using both the Trendelenburg position and IV NTG 
infusion. These interventions may have been responsible for the 
lower intraoperative blood losses. 

When altering a patient’s hemodynamic status with ANH 
and lower CVP, the impact on comorbidities must be addressed. 
In this case, the patient’s hypertension was well controlled, 
without signs of compromised perfusion, as evidenced by a 
preoperative normal myocardial perfusion scan and normal 
chemistry values. An NTG infusion adjusted to a rate of 25 mcg/
min was effective at reducing the CVP to ≤4 mm Hg. As surgical 
blood losses increased, the NTG infusion was discontinued 
and a phenylephrine infusion adjusted to 60 mcg/min, which 
maintained blood pressure at 89/48 to 115/60 mm Hg. 

Constant communication between the surgeon and anesthetist 
enabled vigilant monitoring of current and anticipated blood 
losses, which informed decisions on vasoactive therapies and 
return of the patient’s blood. When the vasopressor infusion 
was used to support blood pressure and the hepatic resection 
was completed, a decision was made to re-transfuse the patient. 
As blood pressure returned to baseline levels, the phenylephrine 
drip was discontinued. To reduce postoperative pain, the epidural 
was activated during incision closure with 3 mg morphine. The 
anesthetic management goals to maintain the patient’s CVP at ≤4 
mm Hg and blood pressure within 20% of the baseline were met 
throughout the surgery. 

ANH and maintenance of low CVP reduced surgical blood loss 
and precluded the administration of allogeneic blood transfusion 
during hepatic resection. Current evidence supports the use of 
these methods in hepatic surgery.1-3,6,10,11,14 The intraoperative 
management of hepatic resection should include ANH and 
low CVP to reduce the concentration of surgical RBC losses 
and overall intraoperative blood loss. These interventions can 
prevent exposing the patient to allogeneic blood products and the 
associated risks and complications.

Estimate amount of blood to 
be removed

VL = EBV x ((Hi – Hf)/Hav)

Apply equation to pre- and 
post-phlebotomy lab values

VL = (65 x 83) ([40.2 – 35.0] / 37.6) = 746 mL of blood removed

Figure  1.
EBV, estimated blood volume; Hi, initial hematocrit; Hf, target hematocrit after hemodilution; Hav, average between Hi and HF; 
VL, total volume to be removed.



Anesthesia eJournal                         www.anesthesiaejournal.com
Volume 2 Issue 2 2014 

Table 1. Methodology and outcomes of studies on use of acute normovolemic hemodilution during hepatic resection.

Author and date Methodology Outcomes
Segal et al - 20048 Meta-analysis of 42 trials: 18 cardiac surgeries, 13 

orthopedic procedures, 4 radical prostatectomies, 3 
spine surgeries, 2 aortic surgeries, 1 thoracic surgery, 
and 1 liver resection

No significant decrease in  relative risk of receiving allogeneic 
blood transfusion (P = 0.3). Total volume of allogeneic blood 
transfused intraoperatively and postoperatively was significantly 
less in ANH group (P <0.001)

Matot et al - 20029 Prospective RCT of 78 patients undergoing hepatic 
surgery for tumor excision. Control group (n=39) 
did not undergo ANH therapy; ANH therapy group 
(n=39) underwent phlebotomy (HCT = 24%). Fluid 
administration was controlled in both groups to 
prevent increases in CVP values. Indication for 
blood transfusion was standardized in both groups to 
HCT = 20%

Intraoperative blood loss, CVP, and urine output were similar 
in both groups. 14 patients in control group received allogeneic 
blood transfusion, compared with 4 patients in ANH group (P = 
0.014). 50% of patients in control group were transfused only 1 
unit of blood. There were no differences in HCT, creatinine, PT, 
and pH between control group and ANH group

Jarnagin et al - 20083 Prospective RCT of 130 patients undergoing hepatic 
surgery comparing ANH with standard anesthetic 
management (65 patients/group). Target diluted 
HGB = 8.0 mg/dL. Low CVP was standardized in 
both groups. Transfusion trigger was HGB < 7.0 g/
dL in both groups.

50% reduction in transfusion of allogeneic red cells and fresh 
frozen plasma in ANH group (P <0.05). 66.6% of standard 
management patients with ≥1500 mL blood loss were transfused 
intraoperatively compared with none in ANH group (P <0.01). 
Results showed 85% reduction in allogeneic transfusion 
requirement

Guo et al - 20137 Prospective RCT of 30 patients aged 60-70 
undergoing hepatic surgery for tumor excision. 
Patients were randomly assigned to ANH group or 
control group (15 patients/group). Blood samples 
were drawn 5 times: before induction (T1), 30 
min after ANH (T2), 1 hour after surgery start 
(T3), immediately after surgery (T4), and 24 hours 
after surgery (T5). ANH group target HCT = 28%. 
Transfusion threshold HGB = 8 g/dL or HCT = 25%

Intraoperative blood losses were similar in both groups. Volume 
of blood transfusion was significantly less in ANH group (350.5 
± 70.7 mL vs 457.8 ± 181.3 mL; P <0.05). Compared with data 
before ANH, PT and PTT were significantly prolonged in ANH 
group for times T2 and T3 (values were still within normal 
limits). Concentration of fibrinogen was significantly reduced 
after ANH (within lower limit). Fibrinogen values increased 
after transfusion of homologous blood removed by ANH

ANH, acute normovolemic hemodilution; CVP, central venous pressure; HCT, hematocrit; HGB, hemoglobin; PPT, partial thrombo-
plastin time; PT, protime; RCT, randomized controlled trial.

Table 2. Methodology and outcomes of studies on maintenance of low central venous pressure during hepatic resection.

Author and date Methodology Outcomes
Jones et al – 199811 Prospective trial with 100 patients undergoing 

hepatic resection. Patients were categorized into 2 
groups: CVP ≤5 and CVP >5. Transfusion threshold 
was HGB =10 g/dL for both groups

Median blood loss for CVP ≤5 = 200 mL; median blood loss for 
CVP >5 = 1000 mL (P = 0.0001). Group with CVP ≤5, 2 patients 
received blood transfusion compared with group with CVP >5 
had 25 patients that received blood transfusion (P = 0.0008)

Wang et al – 200612 Prospective RCT with 50 patients undergoing 
hepatic resection classified equally into low CVP 
group (CVP = 2-4 mm Hg and SBP >90 mm Hg) 
and control group (no CVP lowering). CVP was 
maintained in  low CVP group by using Trende-
lenburg position, limiting fluid volume, IV NTG 
infusion, and IV furosemide if necessary. Transfu-
sion thresholds were equivalent for both groups, at 
8.0 g/dL

Total blood loss was significantly lower in low CVP group com-
pared with control group (P <0.01) (904 mL vs 2329 mL). 56% 
of patients in control group received blood transfusion com-
pared with 24% in low CVP group (P <0.05). Low CVP group 
had significantly shorter hospital stays (P <0.05). Postoperative 
complications were equivalent in both groups. There were no 
differences in postoperative hepatic and renal functions

Liu et al - 200813 Prospective RCT of 46 patients undergoing liver 
resection classified equally into  low CVP group 
(CVP = 2-4 mm Hg, SBP >90 mm Hg, and mean 
blood pressure >60 mm Hg) and control group (no 
CVP lowering). CVP was controlled in low CVP 
group by using Trendelenburg position, limiting 
fluid volume administration, and IV NTG infusion 
and IV furosemide. Transfusion threshold was same 
for both groups, at HGB <8.0 g/dL

Total intraoperative blood loss was significantly less in low CVP 
group (P <0.01) (375 mL vs 733 mL). RBC transfusion was 
significantly less in low CVP group, with average 206 mL vs 
365 mL in control group (P <0.05). 7 patients in  low CVP group 
required blood transfusion vs 13 patients in control group. There 
were no changes in BUN or creatinine on postoperative days 1, 
3, or 7

BUN, blood urea nitrogen; CVP, central venous pressure; IV, intravenous; NTG, nitroglycerin; RBC, red blood cell; SBP, systolic 
blood pressure.



Anesthesia eJournal                         www.anesthesiaejournal.com
Volume 2 Issue 2 2014 

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