International Journal of Urology

(2002)

9,

210–214

Original Article

Blackwell Science, LtdOxford, UKIJU

International Journal of Urology0919-81722002 The Japanese Urological Association

94April 2002454

Autologous blood transfusion in RRPM Morioka

et al.10.1046/j.0919-8172.2002.00454.x

Original Article210214BEES SGML

Correspondence: Masaaki Morioka

MD

, Department ofUrology, Kawasaki Medical School, 577 Matsushima,Kurashiki 701-0192, Japan.Email: moriokam@med.kawasaki-m.ac.jp

Received 26 March 2001; accepted 19 November 2001.

Efficacy of preoperative donation of autologous blood in patients undergoing radical retropubic prostatectomy

MASAAKI MORIOKA, TOKUNORI YAMAMOTO, YOJI FURUKAWA, KEIGO KINUGAWA, ATSUSHI SONE, YOSHIMASA JO, TAKAKAZU MATSUKI, TAKASHI NAKAJIMA, TAKAO KOIDE AND HIROYOSHI TANAKA

Department of Urology, Kawasaki Medical School, Kurashiki, Japan

Abstract

Background

: Radical retropubic prostatectomy (RRP) has resulted in substantial blood loss and thefrequent need for homologous blood transfusion. In this study, the efficacy of autologous bloodtransfusion, from medical and financial perspectives, was evaluated in patients undergoing RRP.

Methods

: Between 1994 and 2000, 80 patients with localized prostate cancer underwent RRP in ourinstitute. Based on informed consent, preoperative donation of autologous blood (PDA) wasperformed in 65 out of 80 patienets. Four or six units were donated during the first 3 years; however,donation units were reduced to a maximum of 4 units since 1997 onwards. The discard rate ofdonated blood and frequency of homologous transfusion were examined. Changes of hematocrit (Ht)and hemoglobin (Hb) levels through donation and surgery and important factors that may affectpostoperative levels of Ht and Hb were evaluated in 56 patients receiving 4-unit donations.

Results

: Overall, 2 or 4 units of donated blood were discarded in four patients and homologoustransfusion was required in two patients. In 56 patients receiving 4-unit donation, the mean Ht levelat predonation was 43.3%. Following donation, this decreased to 35.7%. The administration ofrecombinant human erythropoietin (rHuEpo) relieved declining Ht levels following donation, butchanges in Ht levels after surgery were minor. Important factors related to postoperative decline ofHt and Hb levels were operative time and blood loss.

Conclusions

: The program of 4-unit PDA can be performed safely without rHuEpo injection, and itis useful to reduce the risk of requiring homologous transfusion. However, more efficient programsto relieve patient burden and to reduce medical cost are needed.

Key words

blood donation units, medical cost, preoperative donation of autologous blood, radical retropubic prostatectomy, recombinant human erythropoietin.

Introduction

In line with the development of the anatomical approachto radical retropubic prostatectomy (RRP),

1

morbidityof the procedure has decreased. However, the operationhas resulted in substantial blood loss. Several reportsdocumenting excellent surgical results,

2,3

including

blood loss of less than 1 L, have appeared. However, therisk of requiring homologous blood transfusion is stillpresent in 8–30% of patients.

2–5

Autologous bloodtransfusion (ABT) has been used in order to avoid com-plications associated with homologous transfusion suchas infection (viral hepatitis, human immunodeficiencyvirus), immunological suppression and allogenic sensi-tization. In Japan, government policy prefers the use ofABT in elective surgery; moreover, the use of recombi-nant human erythropoietin (rHuEpo) has been approvedin patients receiving in excess of 4 units (800 mL) ofautologous donation. In this study we analyzed the 7-year experience of preoperative donation of autologousblood (PDA) in patients undergoing RRP.

Autologous blood transfusion in RRP 211

Methods

Between May 1994 and December 2000, 80 patientswith clinically localized prostate cancer underwent RRPwith pelvic lymph node dissection in the Departmentof Urology, Kawasaki Medical School. The program ofPDA was adopted in 65 out of 80 cases, based oninformed consent of ABT. Patients with a low hemat-ocrit (Ht) level (

<

35%) or active viral hepatitis wereexcluded from the program. During the first 3 years, 4 or6 units of autologous blood were collected over a 3-weekperiod, and rHuEpo was used in 12 out of 13 cases.Donation units were reduced to a maximum of 4 unitssince 1997 onwards, and 19 out of 52 patients donatedwithout rHuEpo injection during the past 4 years. Oralferrous compounds were administered in all patients.

The frequency of homologous transfusion and dis-card rate of donated blood was examined. Changes of Htand hemoglobin (Hb) levels through donation and sur-gery were analyzed in 56 patients with 4-unit donation(Table 1). The schedule of 4-unit donation involved thecollection of 2 units once per week on two occasions.The interval of final donation and surgery ranged from 2to 17 days (median: 6 days). Following the control ofbleeding, donated blood was transfused in the operatingroom and/or in the ward within 24 h after surgery. Therelationships between changes in Ht and Hb levels andseveral parameters, including the use of rHuEpo, oper-ative time and estimated blood loss, were analyzed. Sta-tistical analyses were performed by paired or non-paired

t

-test for measured data. Fisher’s exact test was used fordichotomous data. Differences were considered statisti-cally significant when the

P

value was

≤

0.05.

Results

Two or four units of donated blood were discarded infour out of 65 patients (6.2%); moreover, homologoustransfusion was required in two cases (Table 1). Back-ground factors in 56 patients receiving 4-unit donationare summarized in Table 2. Recombinant human eryth-ropoietin was used in 38 patients and was not used inthe remaining 18 patients. Operative time varied from130 to 295 min (median: 180 min; mean: 191 min) andmedian blood loss was 970 mL. Four units of donatedblood was returned to 54 patients. The two exceptionsinvolved discarding two units of donated blood as aresult of Ht levels exceeding 40% following the returnof two units of donated blood. Two other patientsrequired two and four units of homologous blood. Theneed for homologous transfusion in these patients wasattributed to excessive blood loss (1800 and 2400 mL)and coronary risk. A positive correlation between oper-ative time and blood loss was identified (

r

=

0.609;

P

<

0.0001) in the present study.Mean levels of Ht and Hb at predonation were 43.3%

and 14.6 g/dL, respectively. After 4-unit donation, meanHt and Hb levels significantly declined to 35.7% and12.5 g/dL, respectively. The decreases in Ht and Hblevels following 4-unit donation were 7.7

±

3.9% and2.1

±

0.9 g/dL, respectively (mean

±

SD). However, thedecline in Ht and Hb levels after surgery was minor dueto transfusion of donated blood. Ht and Hb levels soonrecovered at 8–14 days postoperatively (36.0

±

4.4% and11.7

±

1.6 g/dL, respectively), corresponding to day ofdischarge (Table 3).

In order to examine the effect of rHuEpo on Ht andHb levels, 56 patients were divided into two groupsaccording to the use or non-use of rHuEpo. Operativetime and medical cost were the significant distinguish-ing factors between the two groups. Ht and Hb levelsfollowing donation did not differ from one another;however, the decline from predonation levels was sig-nificantly relieved in patients receiving rHuEpo injec-tion. Autologous blood donation and transfusion coststotaled 38 000 Japanese yen per 4 units. In contrast,rHuEpo costs were 35 000 Japanese yen per 24 000 IU.Consequently, the typical rHuEpo dose for 4-unit dona-tion totaled 70 000 Japanese yen (Table 4).

Levels of Ht and Hb at predonation, the use ofrHuEpo, operative time, patient age and blood lossduring surgery were evaluated as parameters that mayaffect postoperative Ht and Hb levels. Operative time(

>

180 min) and estimated blood loss (

>

1 L) were sig-nificant factors with respect to declines in Ht and Hblevels; the use of rHuEpo, predonation Ht levels andpatient age were not (Table 5).

Table 1

The use of autologous and homologous bloodaccording to the number of donation units

No. donation units 2 3 4 6 Total

Autologous blood usedUnits 4 3 220† 30‡ 257No. patients 2 1 56 6 65

rHuEpo used 0 1 38 6 45

Homologous blood usedUnits 0 0 6 0 6No. patients 0 0 2 0 2

rHuEpo, recombinant human erythropoietin. † donatedblood was discarded in two cases, each 2 units; ‡ donatedblood was discarded in two cases, one case 2 and one case4 units.

212 M Morioka

et al

.

Discussion

Despite the improvement of the RRP surgical technique,this procedure has continued to result in substantialblood loss, causing risk of homologous blood transfu-

sion in 8–30% of patients.

2–5

In our institute, five out of15 patients (33%) undergoing RRP during the sameperiod without PDA required 2 or 4 units of homologoustransfusion. In the group without PDA, median bloodloss and operative time were 810 mL and 200 min,respectively. These background factors did not differfrom patients with PDA; however, the risk for homolo-gous blood transfusion was significantly higher inpatients without PDA than those with PDA (

P

=

0.0037,Fisher’s exact test). Fortunately, complications associ-ated with homologous transfusion or prolonged hospitalstays were not seen in the five patients who requiredhomologous blood.

In elective surgery, ABT programs have been used toavoid risks associated with homologous transfusion.ABT is comprised of three methods: PDA, the hemodi-lution method (acute normovolemic hemodilution,ANH

6,7

), and the cell-saver system.

8

PDA and ANH arecommon procedures in oncologic surgery. The impact ofPDA in patients undergoing RRP was evaluated in the1990s. It was determined that 2 or 4 units of PDAresulted in risk reduction of homologous blood transfu-sion to 0–8%.

3–5,9

However, the impact of PDA inpatients undergoing RRP was considered inefficient dueto a lack of cost-effectiveness and a high discard rate ofdonated blood (up to 20–50%).

3,4,8

In recent years, an

Table 3

Change of hematocrit (Ht) and hemoglobin (Hb)levels in patients with 4-unit donation (

n

=

56)

Time of examination Ht (%)mean

±

SDHb (g/dL)mean

±

SD

Pre-donation 43.3

±

3.5 14.6

±

1.3Before surgery 35.7

±

4.2* 12.5

±

1.4*Decline from predonation

to before surgery7.7

±

3.9 2.1

±

0.9

POD 1 33.9

±

3.7† 11.1

±

1.3†POD 3–7 34.1

±

4.9‡ 11.2

±

1.7‡POD 8–14 (at discharge) 36.0

±

4.4§ 11.7

±

1.6§

POD, postoperative day. * Predonation

vs

before surgery:

P

<

0.0001 (Ht, Hb); † before surgery

vs

POD 1:

P

=

0.0021(Ht),

P

=

0.0002 (Hb); ‡ POD 1

vs

POD 3–7:

P

=

0.7815(Ht),

P

=

0.7904 (Hb); §POD 3–7

vs

POD 8–14:

P

<

0.0001(Ht),

P

=

0.0009 (Hb). (

P

values were calculated by paired

t

-test.)

Table 2

Background of patients receiving 4-unit donation (

n

=

56)

Parameter Range (median) Details

Age (years) 53–78 (69) 67.3

±

6.4 (mean

±

SD)Clinical stage T1b, 1c: 19; T2: 31; T3: 6Preoperative PSA level (ng/mL; Tandem-R) 4.3–42.6 (10.4)

<

10 ng: 2510–19.9 ng: 19

≥

20 ng: 12Dose of rHuEpo (IU) 6000–48 000 (48 000) rHuEpo used: 38 (68%)

rHuEpo not used: 18 (32%)Interval of final donation and surgery (days) 2–17 (6) 2–6 days: 34 (61%)

7–14 days: 20 (36%)

≥

15 days: 2 (3%)Operative time (min)† 130–295 (180)

≤

180 min: 30 (53.5%)181–240 min: 21 (37.5%)

≥

241 min: 5 (9%)Estimated blood loss (mL)‡ 340–2400 (970)

<

1000 mL: 29 (51.8%)1000–1499 mL: 16 (28.6%)

≥

1500 mL: 11 (19.6%)Transfused blood (units) 2–4 (4) Discarded autologous blood: 2 patients

(3.6%; each 2 units)Homologous blood transfused: 2 patients

(3.6%; 2 and 4 units, respectively)

† Correlation coefficient of operative time and blood loss:

r

=

0.609 (

P

<

0.0001); ‡ estimated blood loss: contained suction urine during surgery.

Autologous blood transfusion in RRP 213

Table 5

Parameters that may affect postoperative decline of hematocrit (Ht) and hemoglobin (Hb) levels in patients with 4-unit donation (

n

=

56)

Parameter Decline from predonation to POD 3–7

Ht (%)mean

±

SD

P

value† Hb (g/dL)mean

±

SD

P

value†

Operative time

≤

180 min (

n

=

30) 7.4

±

4.6 0.0025 2.7

±

1.5 0.0010

>

180 min (

n

=

26) 11.3

±

4.4 4.2

±

1.6Estimated blood loss

<

1000 mL (

n

=

29) 7.3

±

4.2 0.0016 2.7

±

1.4 0.0014

≥

1000 mL (

n

=

27) 11.4

±

4.6 4.2

±

1.6rHuEpo used

Yes (

n

=

38) 9.1

±

4.8 0.7911 3.4 ± 1.7 0.8635No (n = 18) 9.8 ± 5.0 3.5 ± 1.7

Ht level at predonation< 43% (n = 25) 7.9 ± 4.4 0.0640 2.9 ± 1.4 0.0530≥ 43% (n = 31) 10.4 ± 4.9 3.8 ± 1.8

Age (years)< 70 (n = 3) 9.2 ± 4.6 0.8491 3.4 ± 1.7 0.9800≥ 70 (n = 25) 9.4 ± 5.1 3.4 ± 1.7

POD, postoperative day. † P values were calculated by non-paired t-test.

Table 4 Impact of recombinant human erythropoietin (rHuEpo) on hematocrit (Ht) and hemoglobin (Hb) levels in patientswith 4-unit donation (n = 56)

Parameter rHuEpo used (n = 38)mean ± SD

rHuEpo not used (n = 18)mean ± SD

P value

Age (years) 67.6 ± 6.2 66.7 ± 6.7 0.6205Medical cost for ABT (Japanese yen)† 100 073 ± 17 726 39 871 ± 214 < 0.0001Operative time (min) 200 ± 41 172 ± 31 0.0081Estimated blood loss (mL) 1103 ± 503 968 ± 384 0.2732Discarded blood 2 patients (5.3%), each 2 units 0 (0%) 0.8256‡Homologous blood used 2 patients (5.3%), 2 and 4 units 0 (0%) 0.8256‡Pre-donation

Ht (%) 43.0 ± 3.2 44.0 ± 3.9 0.3215Hb (g/dL) 14.5 ± 1.2 14.8 ± 1.3 0.3700

Before surgeryHt (%) 36.2 ± 3.8 34.5 ± 4.7 0.1763Hb (g/dL) 12.2 ± 1.2 12.9 ± 1.7 0.3468

Decline from predonation to before surgeryHt (%) 6.8 ± 4.0 9.6 ± 3.2 0.0072Hb (g/dL) 1.8 ± 0.8 2.8 ± 0.9 0.0351

POD 3–7Ht (%) 33.8 ± 4.4 34.8 ± 5.7 0.5256Hb (g/dL) 11.0 ± 1.5 11.5 ± 1.9 0.3414

ABT, autologous blood transfusion; POD, postoperative day. †Medical cost includes all charges concerned in the ABTprogram, such as storage, transfusion, laboratory tests, rHuEpo and oral ferrous compounds; ‡calculated by Fisher’s exact test(other P values were calculated by non-paired t-test).

intraoperative hemodilution protocol has been evaluatedas a possible substitute due to its cost-effectiveness.6,7

However, ANH possesses a potential risk of homolo-gous transfusion in 20% of cases. A combination ofANH and 2 units PDA are recommended.4,6,7

In the present study, significant factors affectingpostoperative Ht and Hb levels were operative time andestimated blood loss, as per previous reports.3,5 None ofthe patients experiencing less than 1500 mL blood lossor short operative time (within 180 min) required fur-

214 M Morioka et al.

ther homologous blood. Our program of 4-unit donationwas considered efficient with respect to its ability toreduce risk of homologous transfusion to 3.6%. How-ever, two problems remained: (i) significant decline inHt and Hb levels following PDA (7.7 ± 3.9% and2.1 ± 0.9 g/dL, respectively); and (ii) medical costs asso-ciated with ABT, particularly the cost of rHuEpo. InJapan, rHuEpo use has been approved in adult patientswith autologous blood donation in excess of 4 units.Additionally, the usual dose of rHuEpo for 4-unit dona-tion costs 70 000 Japanese yen. In contrast, medicalcosts associated with ABT totals 38 000 Japanese yenper 4 units; however, these expenses cannot be chargedunless donated blood is returned to patients. In thepresent investigation, the discard rate of donated bloodwas quite low (3.6%) in comparison to that documentedin other countries.3,4,8 This low discard rate may beattributed to the insurance system in Japan. In fact, Htlevels at 3–7 days following surgery were relativelyhigher (34.1 ± 4.9%) than those observed in previousreports (28–30%).5,7 Our data suggest that donatedblood was returned exceeding medical needs. Conse-quently, 4-unit donation was considered excessive forthe majority of patients from the perspectives of medi-cal evidence and cost-effectiveness.

In conclusion, the program of 4-unit PDA can be per-formed safely without rHuEpo injection, and it is effi-cient to reduce a risk of homologous blood transfusion.However, more efficient programs in order to relievepatient burden with respect to PDA, to minimize post-operative anemia and to reduce medical costs areneeded. A recently reported program, the combinationof 2 units PDA and the hemodilution method,4,6,7 may beone of the useful alternatives.

References

1 Walsh PC. Anatomic radical retropubic prostatectomy.In: Walsh, PC, Retik, AB, Vaughan, ED Jr, Wein, AJ(eds). Campbell’s Urology, 7th edn. WB Saunders,Philadelphia 1998; 2565–88.

2 Yamada AH, Lieskovsky G, Skinner DG, Schulman I,Groshen S, Chen SC. Impact of autologous bloodtransfusion on patients undergoing radical prostatec-tomy using hypotensive anesthesia. J. Urol. 1993; 149:73–6.

3 Goad JR, Eastham JA, Fitzgerald KB et al. Radicalretropubic prostatectomy: Limited benefit of autologousblood donation. J. Urol. 1995; 154: 2103–9.

4 Nash PA, Schrepferman CG, Rowland RG et al. Theimpact of pre-donated autologous blood and intra-operative isovolemic haemodilution on the outcome oftransfusion in patients undergoing radical retropubicprostatectomy. Br. J. Urol. 1996; 77: 856–60.

5 Goh M, Kleer CG, Kielczewski P, Wojno KJ, Kim K,Oesterling JE. Autologous blood donation prior to ana-tomical radical retropubic prostatectomy: Is it neces-sary? Urology 1997; 49: 569–74.

6 Monk TG, Goodnough LT, Brecher ME et al. Acutenormovolemic hemodilution can replace preoperativeautologous blood donation as a standard of care forautologous blood procurement in radical prostatectomy.Anesth. Analg. 1997; 85: 953–8.

7 Monk TG, Goodnough LT, Brecher ME, Colberg JW,Andriole GL, Catalona WJ. A prospective randomizedcomparison of three blood conservation strategies forradical prostatectomy. Anesthesiology 1999; 91: 24–33.

8 Gilbert JB, Malkowicz SB, Wein AJ. Cell saver andradical retropubic prostatectomy: Analysis of cost-effectiveness. Urology 1995; 46: 542–4.

9 Goodnough LT, Grishaber DO, Birkmeyer JD, MonkTG, Catalona WJ. Efficacy and cost-effectiveness ofautologous blood predeposit in patients undergoingradical prostatectomy procedures. Urology 1994; 44:226–31.