Journal of Hepato-Biliary-Pancreatic Surgery

, Volume 16, Issue 1, pp 69–74

Assessment of blood-products use as predictor of pulmonary complications and surgical-site infection after hepatectomy for hepatocellular carcinoma

  • Hiroaki Shiba
  • Yuji Ishii
  • Yuichi Ishida
  • Shigeki Wakiyama
  • Taro Sakamoto
  • Ryusuke Ito
  • Takeshi Gocho
  • Tadashi Uwagawa
  • Shoichi Hirohara
  • Yoshiaki Kita
  • Takeyuki Misawa
  • Katsuhiko Yanaga
ORIGINAL ARTICLE

Abstract

Background

In perioperative management after hepatectomy, some patients require fresh frozen plasma (FFP) to treat coagulopathy associated with blood loss. However, several studies have suggested a correlation between blood products and pulmonary complications or surgical-site infection (SSI).

Methods

The subjects were 99 patients who underwent hepatectomy for hepatocellular carcinoma without plasma exchange for postoperative liver failure in the Department of Surgery, Jikei University Hospital, between January 2000 and December 2006. We investigated the association of 16 factors including age; gender; preoperative ICGR15; type of resection; concomitant resection of other digestive organs; duration of operation; blood loss; hepatitis virus status; postoperative minimum platelet count, maximum serum total bilirubin (max T-Bil), minimum serum albumin, or minimum prothrombin time; and the dose of red-blood-cell concentration (RC), FFP, platelet concentration, or albumin given in relation to postoperative pulmonary complications and SSI.

Results

In univariate analysis, pulmonary complications were correlated with gender (P = 0.012), max T-Bil (P = 0.043), dose of RC given (P = 0.007), dose of FFP given (P < 0.001), and dose of albumin given (P < 0.001). In multivariate analysis, pulmonary complications were correlated with FFP given (P = 0.031) and albumin given (P = 0.020), while the incidence of SSI was not correlated with any factors.

Conclusion

Excessive FFP and albumin administration may cause pulmonary complications after hepatectomy.

Keywords

Fresh frozen plasma Hepatectomy Hepatocellular carcinoma Pulmonary complication Surgical-site infection 

Introduction

In Japan, blood products such as fresh frozen plasma (FFP) and albumin have been administered rather liberally after hepatectomy for hepatocellular carcinoma (HCC) to maintain plasma osmotic pressure and coagulation factor levels [1, 2] because appropriate guidelines for blood-products transfusion had not yet been established [3, 4, 5, 6]. Then, in 1999, the guidelines for administration of blood preparations were released from the Japanese Ministry of Health and Welfare [7]. Indications of FFP use have been limited to reduce consumption of FFP.

Several studies have suggested the involvement of FFP in pulmonary complications and surgical-site infections (SSI) after surgery [8, 9]. In recent years, the use of FFP has partially been replaced by albumin preparations. However, there are no standardized guidelines for the use of albumin preparations [10, 11, 12, 13]. On the other hand, in perioperative management of hepatectomy for HCC, coagulopathy and albumin composition dysfunction by concomitant chronic liver disease are not unusual, and administration of blood components may be essential. Therefore, the usefulness and risk of blood-products use in perioperative management of hepatectomy for HCC needs to be evaluated. In this study, we retrospectively investigated factors pertinent to pulmonary complications and SSI after hepatectomy for HCC to clarify risk factors for such complications, with special reference to perioperative blood-products use.

Methods

Between January 2000 and December 2006, 101 patients underwent hepatectomy for HCC in the Department of Surgery, Jikei University Hospital. Of these, two patients who required plasma exchange for postoperative liver failure were excluded, and the remaining 99 patients were studied. Generally, the extent of hepatectomy was determined based on ICGR15 before surgery and hepatic reserve, as described by Makuuchi et al. [14]. The use of blood products was determined by attending surgeons, and the dose of blood products given was judged based on intraoperative blood loss, and postoperative hemoglobin level, platelet count, serum albumin level, and prothrombin time (PT).

We investigated the association of pulmonary complications and SSI with the following 16 factors: age; gender; preoperative ICGR15; type of resection; concomitant resection of other digestive organs; duration of operation; blood loss; hepatitis virus status; postoperative data of minimum platelet count (min Plt), maximum serum total bilirubin (max T-Bil), minimum serum albumin (min Alb), or minimum prothrombin time (min PT); and the dose of red-blood-cell concentration (RC), FFP, platelet concentration (PC), or albumin given. Pulmonary complications were defined as postoperative pneumonia; postoperative respiratory failure with pyrexia, dyspnea, and a pulmonary infiltrate on chest X-rays; or pleural effusion that required thoracentesis. SSI was defined as surgical wound infection with purulent discharge and bacterial isolation, or abdominal abscess with pyrexia. The type of resection was classified into two types: anatomical hepatectomy (extended lobectomy, lobectomy, segmentectomy, or subsegmentectomy) and limited partial resection.

Statistical analysis

The data are expressed as mean ± SD. Univariate analysis was performed using non-paired Student’s t test and χ2 test. Multivariate analysis was performed using logistic-regression analysis. A P value <0.05 was regarded as significant.

Results

Type of resection, postoperative complications, and patient characteristics

Types of resection are listed in Table 1 and postoperative complications in Table 2. Postoperative complications developed in 33 of the 99 patients (33.3%), including pulmonary complications in 13, SSI in 13, and hospital death due to respiratory failure in 1 patient (1.1%). Patient characteristics are listed in Table 3.
Table 1

Types of resection

Type of resection

Number

Anatomical hepatic resection

 Extended right lobectomy

3

 Extended left lobectomy

2

 Right lobectomy

12

 Left lobectomy

2

 Posterior segmentectomy

3

 Lateral segmentectomy

5

 Subsegmentectomy

6

 Caudate lobectomy

2

Limited partial resection

64

Table 2

Postoperative complications after hepatectomy

Complications

Number

SSI

 Surgical wound infection

12

 Intraperitoneal abscess

1

Pulmonary complication

 Postoperative pneumonia

9

 Respiratory failure

3

 Pleural effusion

1

Others

 Bile leakage

6

 Hepatic failure

1

 Small-bowel obstraction

2

 Intractable ascites

1

 Upper gastrointestinal hemorrhage

1

SSI Surgical site infection

Table 3

Patient characteristics

Variable

Data

Age (years)

61.2 ± 11.1

Gender (male:female)

84:15

ICGR15 (%)

14.2 ± 9.4

Type of resection (anatomical:partial)

35:64

Resection of digestive organs (yes:no)

6:93

Duration of operation (min)

287.7 ± 120.3

Blood loss (g)

1,097.4 ± 1,222.5

Hepatitis virus (HBV:HCV:no)

39:43:17

Max T-Bil (mg/dl)

1.8 ± 1.0

Min PT (%)

69.7 ± 12.9

Min Plt (×103/μl)

115.8 ± 46.0

Min Alb (g/dl)

3.0 ± 0.4

RC given (units)

1.9 ± 3.9

FFP given (units)

8.2 ± 14.5

PC given (units)

1.5 ± 5.8

Albumin given (g)

49.9 ± 99.3

HBV Hepatitis B virus, HCV hepatitis C virus, max T-Bil maximum serum postoperative total bilirubin, min PT minimum postoperative prothrombin time, min Plt minimum postoperative platelet, min Alb minimum postoperative serum albumin, RC red-blood-cell concentration, FFP fresh frozen plasma, PC platelet concentration

Data are mean ± SD unless otherwise stated

Association between clinical variables and postoperative SSI

Table 4 lists the relationship between clinical variables and SSI after hepatectomy for HCC. In univariate analysis, the incidence of SSI did not correlate with any factors.
Table 4

Univariate analysis of clinical variables and SSI after hepatectomy

Factor

SSI

P value (univariate)

Yes (= 13)

No (n = 86)

Age (years)

59.5 ± 8.0

61.4 ± 11.4

0.553

Gender (male:female)

13:0

71:15

0.102

ICGR15 (%)

14.3 ± 6.0

14.1 ± 9.8

0.971

Type of resection (anatomical:partial)

5:8

30:56

0.801

Resection of digestive organs (yes:no)

1:12

5:81

0.791

Duration of operation (min)

325.8 ± 116.0

282.0 ± 120.6

0.223

Blood loss (g)

1,188.8 ± 1,171.9

1,083.6 ± 1,236.0

0.774

Hepatitis virus (HBV:HCV:no)

4:6:3

35:37:14

0.736

Max T-Bil (mg/dl)

2.2 ± 1.3

1.7 ± 1.0

0.109

Min PT (%)

69.5 ± 15.5

69.8 ± 12.5

0.951

Min Plt (×103/μl)

110.1 ± 45.4

116.6 ± 46.3

0.634

Min Alb (g/dl)

2.9 ± 0.4

3.1 ± 0.4

0.230

RC given (units)

2.0 ± 3.8

1.9 ± 3.9

0.937

FFP given (units)

15.2 ± 23.2

7.1 ± 12.6

0.063

PC given (units)

1.5 ± 5.5

1.5 ± 5.9

0.961

Albumin given (g)

78.8 ± 200.2

45.5 ± 74.5

0.261

SSI Surgical site infection, HBV hepatitis B virus, HCV hepatitis C virus, max T-Bil maximum postoperative serum total bilirubin, min PT minimum postoperative prothrombin time, min Plt minimum postoperative platelet, min Alb minimum postoperative serum albumin, RC red-blood-cell concentration, FFP fresh frozen plasma, PC platelet concentration

Association between clinical variables and postoperative pulmonary complications

Table 5 lists the relationship between clinical variables and pulmonary complications after hepatectomy for HCC. In univariate analysis, pulmonary complication was more common in females (P = 0.012) and associated with higher max T-Bil (P = 0.043), and dose of RC given (P = 0.007), FFP given (P < 0.001) and albumin given (P < 0.001). In multivariate analysis, dose of FFP given (P = 0.031) and albumin given (P = 0.020) were associated with pulmonary complications (Table 6), which suggests that excessive FFP or albumin use may cause pulmonary complications. Table 7 lists the clinical parameters of 13 patients with postoperative pulmonary complications.
Table 5

Univariate analysis of clinical variables and postoperative pulmonary complications after hepatectomy

Factor

Pulmonary complications

P value (univariate)

Yes (n = 13)

No (n = 86)

Age (years)

64.5 ± 8.3

60.6 ± 11.3

0.245

Gender (male:female)

8:5

76:10

0.012

ICGR15 (%)

13.8 ± 7.2

14.2 ± 9.7

0.874

Type of resection (anatomical:partial)

6:7

29:57

0.382

Resection of digestive organs (yes:no)

0:13

6:80

0.326

Duration of operation (min)

331.2 ± 132.9

281.2 ± 117.8

0.164

Blood loss (g)

1,647.6 ± 1,858.2

1,014.2 ± 1,087.3

0.082

Hepatitis virus (HBV:HCV:no)

6:5:2

33:38:15

0.867

Max T-Bil (mg/dl)

2.3 ± 1.6

1.7 ± 0.9

0.043

Min PT (%)

63.4 ± 13.5

70.7 ± 12.6

0.068

Min Plt (×103/μl)

113.3 ± 71.3

116.1 ± 41.9

0.840

Min Alb (g/dl)

3.0 ± 0.5

3.0 ± 0.4

0.682

RC given (units)

4.6 ± 6.6

1.5 ± 3.2

0.007

FFP given (units)

26.8 ± 25.2

5.3 ± 9.6

<0.001

PC given (units)

3.1 ± 7.5

1.2 ± 5.5

0.286

Albumin given (g)

179.8 ± 211.7

30.2 ± 45.4

<0.001

HBV Hepatitis B virus, HCV hepatitis C virus, max T-Bil maximum postoperative serum total bilirubin, min PT minimum postoperative prothrombin time, min Plt minimum postoperative platelet, min Alb minimum postoperative serum albumin, RC red-blood-cell concentration, FFP fresh frozen plasma, PC platelet concentration

Table 6

Multivariate analysis of clinical variables and postoperative pulmonary complications after hepatectomy

Factor

Odds ratio (95% CI)

P value (multivariate)

Gender (female)

4.986 (0.889–27.956)

0.068

Max T-Bil (mg/dl)

0.405 (0.122–1.345)

0.140

RC given (units)

0.968 (0.760–1.232)

0.791

FFP given (units)

1.089 (1.008–1.177)

0.031

Albumin given (g)

1.015 (1.002–1.027)

0.020

Max T-Bil Maximum postoperative serum total bilirubin, FFP fresh frozen plasma

Table 7

Clinical variables of patients with postoperative pulmonary complications

Age (years)

Gender

ICGR15 (%)

Type of resection

Resection of digestive organs

Duration of operation (min)

Blood loss (g)

Hepatitis virus

Max T-Bil (mg/dl)

Min PT (%)

Min Plt (×103/μl)

Min Alb (g/dl)

RC given (units)

FFP given (units)

PC given (units)

Albumin given (g)

64

M

16

Anatomical

No

290

1,104

HCV

2.1

58

42

2.7

0

40

20

12.5

57

M

8

Anatomical

No

400

2,650

HBV

1.1

63

292

3.2

4

21

0

62.5

57

M

13

Partial

No

195

225

HBV

1.1

82

122

3.4

0

0

0

0

74

F

18

Anatomical

No

330

4,500

HCV

6.6

58

85

3.4

20

64

0

212.5

67

F

34

Partial

No

135

475

HCV

2.8

37

70

2.5

4

48

0

275

66

M

8

Anatomical

No

330

610

No

3.2

66

122

2.5

4

24

0

362.5

76

M

15

Anatomical

No

300

1,300

HBV

2.3

64

113

3.0

2

12

0

50

76

F

7

Partial

No

490

4,235

No

2.5

57

92

3.4

12

24

20

200

71

M

12

Anatomical

No

585

5,230

HCV

2.1

72

54

4.1

14

40

0

325

66

F

15

Partial

No

410

250

HCV

1.3

66

73

2.6

0

0

0

100

58

M

16

Partial

No

210

10

HBV

0.9

87

210

3.2

0

0

0

0

53

M

10

Partial

No

450

730

HBV

3.5

49

80

2.8

0

75

0

737.5

53

F

7

Partial

No

180

100

HBV

1

66

117

2.6

0

0

0

0

HBV Hepatitis B virus, HCV hepatitis C virus, max T-Bil maximum postoperative serum total bilirubin, min PT minimum postoperative prothrombin time, min Plt minimum postoperative platelet, min Alb minimum postoperative serum albumin, RC red-blood-cell concentration, FFP fresh frozen plasma, PC platelet concentration

Discussion

In 1985, the Hospital Transfusion Committee in the United States recommended criteria for blood-products administration [15]. In Europe and in the United States, blood-products administration has been minimized for many years [16, 17, 18, 19]. In Japan, on the other hand, the use of FFP transfusion has been rather liberal to maintain the circulating plasma volume and supplement the coagulation factors. In Japan, the guidelines for administration of blood preparations were established by the Ministry of Health and Welfare in 1999 [7]. FFP transfusion is limited to supplementing coagulation factors, while albumin preparation is recommended to supplement plasma protein. This practice did reduce the usage of FFP. Japanese guidelines for administration of blood preparations advocate that FFP should be indicated for patients with a PT value of 30% or less and an activated partial thromboplastin time value 1.5 times higher than the reference value established at each hospital. In addition, FFP should be indicated when the volume of blood loss during surgery corresponds to 100% or more of the circulating blood volume. To maintain the circulating plasma volume, isotonic albumin preparations should be administered. For protein source supplementation, intravenous hyperalimentation or enteral nutrition is indicated. Various plasma fraction preparations have been developed and administered, which contribute to sparing the use of FFP.

Excessive intraoperative blood loss and blood transfusion affect postoperative complications and prognoses [2, 20, 21], and recent studies have reported a relationship between allogenic blood transfusion and immunomodulatory effects [22, 23, 24, 25, 26]. Concerning the mechanism for immunosuppressive effects of blood transfusion, soluble HLA class I molecules and soluble Fas-ligands released by leukocytes in blood-transfusion preparations inhibit the activity of NK cells and cytotoxic T cells, which reduce immune capacity, inducing postoperative infectious diseases such as postoperative pneumonia and wound infection [8, 26, 27, 28, 29, 30, 31]. Since blood preparations are derived from donations, massive administration of blood preparations should be avoided.

Nevertheless, in perioperative management of hepatectomy for HCC, it is sometimes necessary to supplement blood components following extensive blood loss and hepatic dysfunction. Administration of blood products including FFP and albumin preparation at an optimal dose may be important to prevent postoperative complications. Changes in the condition during or after hepatectomy differ among patients with hepatopathy such as liver cirrhosis; such patients often require blood products including FFP and albumin preparation therapy. Criteria should be established for the use of blood products in hepatic surgery for cirrhotic patients and in perioperative management, so that complications of hepatic resection can be minimized. Based on these guidelines, conditions requiring transfusion during hepatectomy or in perioperative management and side effects of blood products use should be reviewed, and criteria for administering blood products must be established.

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Copyright information

© Springer 2008

Authors and Affiliations

  • Hiroaki Shiba
    • 1
  • Yuji Ishii
    • 1
  • Yuichi Ishida
    • 1
  • Shigeki Wakiyama
    • 1
  • Taro Sakamoto
    • 1
  • Ryusuke Ito
    • 1
  • Takeshi Gocho
    • 1
  • Tadashi Uwagawa
    • 1
  • Shoichi Hirohara
    • 1
  • Yoshiaki Kita
    • 1
  • Takeyuki Misawa
    • 1
  • Katsuhiko Yanaga
    • 1
  1. 1.Department of SurgeryJikei University School of MedicineMinatoJapan

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