Br. J. Surg. 1988, Vol.

75, August,
789-792 Blood transfusion and infectious
complications following colorectal
cancer surgery

Blood transfusion has been linked to clinical phenomena attributable to

P. 1. Tartter
Department of Surgery, Annenberg
25-60, The Mount Sinai Medical
Center, 7 Gustave L. Levy Place,
New York, N. Y. 10029, USA
Correspondence to: Dr P. I. Tartter
immune suppression. We prospectively studied the relationship between
perioperative blood transfusion and postoperative infectious
complications in 343 consecutive patients undergoing surgery for
colorectal cancer. Of the 134 patients who received transfusions 33
(24.6 per cent) developed infectious complications compared with 9
(4.3 per cent) of the 209 patients who did not receive blood (P<O.OOOI).
T h e mean number of units of blood received by patients who developed
infectious complications significantly exceeded the number for patients
without infectious complications (2.31 versus 0.74, P <O.OOOl). The
association of transfusion with infections was highly significant
(P <0.0001) a f e r controlling for age, sex, blood loss, procedure, tumour
differentiation, stage, admission haematocrit, duration of surgery, length
of the specimen and tumour size. Blood transfusion appears to be an
independent risk factor for postoperative infectious complications.
Keywords: Colorectal cancer, blood transfusions, infectious complications, operation

The competence of the immune system may be a significant
determinant of morbidity and mortality in the general surgical
patient. Pre-operative immune suppression manifested by
anergy to skin tests is associated with postoperative infection,
septicaemia, and death related to infection'. To naturally
occurring immune deficiency may be added certain iatrogenic
factors inherent in the operative procedure such as anaesthetic
agent^^.^, duration of surgery4, and the magnitude of the
procedures.
Recently another factor, perioperative blood transfusion, has
been implicated in postoperative immune suppression6.
Numerous studies in organ transplantation have demonstrated
prolonged survival of allografts by transfusion-induced immune
suppression. In addition, in cancer patients early recurrence and
poor prognosis are associated with perioperative blood
transfusion and attributed to immune suppression.
These observations lead to speculation that perioperative
blood transfusion, by inducing immune suppression, may
contribute to postoperative infections and septic mortality.
Multivariate studies have found that blood transfusion is an
independent risk factor for postoperative infections'-' and
organ system failure". The current study is our appraisal of the
association of perioperative blood transfusion with
postoperative infections in patients with colorectal cancer.
Patients and methods
A total of 343 consecutive patients were studied. None had pre-
operative evidence of liver or other metastases. Patients were identified
pre-operatively between 1 August 1983 and 31 July 1986. All patients
received bowel preparation with laxatives, enemas, oral neomycin and
erythromycin base, and intravenous cephazolin. Cephazolin was
continued for 24 h following surgery. A purulent exudate was accepted
as irrefutable evidence of wound infection. Urinary tract infection was
diagnosed when culture yielded more than 100000 pathogens/ml or
signs and symptoms of urinary tract infection were present in the
absence of other possible sources. Pneumonia was diagnosed by fever,
leucocytosis and infiltrate on chest X-ray. Intra-abdominal collections
were localized by ultrasonography and by computed tomographic
scanning when other studies failed to reveal a source for fever and
leucocytosis.
Supported by the Frieda and George Zinberg Foundation and N C I - N I H
Grant I ROI-CA-35.55841
Information was recorded on age, sex, operative procedure, size
of tumour, degree of differentiation, number of involved nodes, length
of specimen, stage, admission haematocrit, operative blood loss,
duration of operation, and blood transfusions administered during
hospitalization: pre-, intra-, and postoperatively. No patients received
chemotherapy or radiotherapy during the study.
The variables (e.g. age, sex, etc.) of the patients who developed
infectious complications were compared with the values for patients
who did not develop infectious complications. Student's t and x 2 tests
were used where appropriate. Multivariate analysis of the data was
accomplished using BMDP stepwise logistic regression software' ' J ~
run on an IBM 370 computer housed at the City University of New
York Computing Center. This program investigates the relationship
between a binary dependent variable such as infectious complication
and a set of independent variables which may be categorical (such as
operative procedure and sex) or interval-scaled (such as age, operative
blood loss, duration of procedure, etc.).
Results
Of the 343 patients studied, 42 (12.2per cent) developed infections
following surgery (Table 1). Thirteen patients (3.8 per cent)
developed wound infections and six (1.7 per cent) developed
intra-abdominal or pelvic collections. Three patients with wound
infections subsequently developed dehiscence of the abdominal
wound and died with multiple septic complications. One patient
with suspected pelvic collection after abdominoperineal
resection died from septic shock. Twelve patients had
postoperative urinary tract infections which resolved with
intravenous antibiotics. All patients in this study were routinely
catheterized with indwelling Foley balloon catheters before
Table 1 Source of infiction in the 343 patients studied
0'
n /a
Wound 13 3.8
Urine 12 3.5
Abdominopelvic 6 1.7
Pneumonia 6 1.7
Sepsis without source 4 1.2
Phlebitis 1 0.3
Total 42 12.2

0007-1323/88/080789-04%3.D0 0 1988 Butterworth & Co (Publishers) Ltd 789

Blood transfusion and infection in colorectal cancer surgery: P. I. Tartter

rabk 2 Comparison of patients with and without infectious infections and those who remained uninfected (Table2) revealed
zomplications significant differences in the number of units of blood received,
the distribution of the operative procedures, and the duration of
Not
Infected infected P surgery. Since progressive stage was not significantly associated
- with increasing risk of infection and, although significant by x2
Age 70 68 0.254 analysis, was not significant by the multivariate analysis to
Sex follow, it is not considered further.
Males 22 151 0.849 Right hemicolectomies, transverse colon resections, and
Fema Ies 20 150 anterior resections were associated with low risk of infection
Operation compared with 1&27 per cent for the remaining procedures.
Right hemicolectomy 4 63 However, transfused patients exhibited greater risk of infection
Transverse colectomy 0 10 than untransfused patients after every operation with the sole
Left hemicolectomy 9 33
Sigmoid resection 11 63 0003
exception of abdominoperineal resections (Table 3).
Anterior resection 2 79 The risk of infection for patients with procedures lasting less
Anterior resection with colostomy 8 29 than the mean of 174.4min was 8.3 per cent compared with
Abdominoperineal resection 7 19 16.7 per cent for more lengthy operations (x2= 13.371,
Subtotal colectomy 1 5 P < 0.0001). However, transfusion was significantly related to
Admission haematocrit 38.4 38.2 0842 infection among patients with both short and long operations
Specimen length (cm) 30 28 0.444 (Table 4 ) .
Duration of surgery (min) 193 172 0018 Blood transfusion was significantly associated with infection
Blood loss (dl) 5.7 5.1 0648 because 33 (24.6percent) of the 134 patients who received
Blood transfusions 2.3 1 0.74 < 0.001
Tumour size (ml) 22.3 19.5 0.317 transfusions developed infectious complications compared with
Nodes 1.6 1.1 0.138 nine (4.3 per cent) of the 209 patients who did not receive blood
Differentiation transfusions (Table 5). The mean number of blood transfusions
Well 160 24 among the patients with infectious complications significantly
Moderate 101 12 0200 exceeded those among patients without complications (2.31
Poor 17 6 versus 0.74, P<O~OoOl,Table 2). The administration of blood
Dukes’ classification was significantly ( P < 0.05) associated with low admission
A 3 38 haematocrit, high operative blood loss, bowel penetration
B, 1 30
by tumour (classification B, or greater), poor tumour
B* 17 87 < 0.001
differentiation, and lengthy specimens. However, none of these
c, 8 91
factors was associated with infectious complications ( P > 0.10).
c2 10 16
‘D’ 3 Blood transfusions were associated with infectious com-
plications when given pre-, intra-, or postoperatively (Table 5 ) .
P values are taken to three decimal places None of the transfused patients developed an infectious
Table 3 Association of infection with blood transfusion for each complication before receiving their first unit of blood. In
operative procedure addition, the risk of postoperative infection increased
progressively with the number of units of blood given, from
n Infections % 5 per cent without transfusion to 30 per cent with three or more
units of blood.
Right hemicolectomy
Transfused 26 4 15
Not transfused 41 0 0
Transverse colectomy Table 4 Association of infection with blood transfusion controlling for
Transfused 5 0 0 duration of procedure
Not transfused 5 0 0
Left hemicolectomy n Infections %
Transfused 21 8 38
Not transfused 21 1 5 Long procedures (> 174min)
Sigmoid resection Transfused 78 22 28
Transfused 19 8 42 Not transfused 84 5 6
Not transfused 55 3 5 Short procedures ( < 175 min)
Anterior resection Transfused 52 11 21
Transfused 18 1 6 Not transfused 129 4 3
Not transfused 63 1 2
Anterior resection with colostomy
Transfused 23 7 30
Not transfused 14 1 7
Abdominoperineal resection Table 5 Relationship of infection with blood transfusions given pre-
Transfused 16 4 25 operatively, intra-operatively and postoperatively
Not transfused 10 3 33
Subtotal colectomy n Infected %
Transfused 3 1 33
Not transfused 3 0 0 Pre-operative
Transfused 26 5 19
Not transfused 317 37 12
surgery. Six patients (1.7 per cent) developed pneumonia, one of Intra-operative
whom also had a cerebrovascular accident and myocardial Transfused 75 16 21
infarction but recovered and was discharged home. Four Not transfused 268 26 10
patients with fever, leucocytosis and positive blood cultures Postoperative
were successfully treated with intravenous antibiotics without a Transfused 58 18 31
source of infection being found. For two of these patients colon Not transfused 285 26 9
resection had included a splenectomy for iatrogenic injury. One Overall
patient developed septic phlebitis. Transfused 134 33 25
Not transfused 209 9 4
Univariate analysis comparing the patients who developed

790 Br. J. Surg., Vol. 75, No. 8, August 1988

 Blood transfusion and infection in colorectal cancer surgery: P. I. Tartter

Table 6 Multivariate analysis with infictious complication as the Table 7 Association of infection with blood transjkion controlling for
dependent variable admission haematocrit
~ ~-
Variable x2 P Degrees of freedom n Infections ”/,

Age 0.16 0.686 1 Low haematocrit (<38.3)

Sex <0.01 0.982 1 Transfused 88 19 22
Operation 10.74 0.150 7 Not transfused 71 0 0
Haematocr it 5.13 0.024 1 High haematocrit (> 382)
Duration o l surgery 0.04 0.839 1 Transfused 43 14 33
Estimated blood loss 0.07 0.790 1 Not transfused 141 9 6
Transfusions 30.54 <O~OOl 1
Tumour size 0.85 0.356 1
Nodes 2.36 0.125 1 Allogeneic transfusions of rats are followed by immune
Differentiation 0.18 0.669 1 and increased mortality from burn wound
Dukes’ classification 0.96 0,327 5 sepsisI6, intraperitoneal injections of Escherichia colil4, and
caecal ligation with puncture (D. C. Maidman et al.,
P values are taken to three decimal places
unpublished results) compared with rats given syngeneic blood.
Multivariate stepwise logistic regression was used to The available animal studies support the hypothesis that blood
combine variables, beginning with the most significant, into a transfusion-induced immune suppression increases suscepti-
model which will predict whether or not a patient will develop bility to infection and subsequent mortality.
an infectious complication (Table 6).After each variable is added The specific component of transfused blood responsible for
to the model, the significance of the remaining variables is immune suppression has not been identified. Red cells and their
recalculated, variables with Pc0.1 are added and those with components are immunosuppressive in uitro (references 16 and
P>0.15 are removed. The result of this analysis is that 17 and Tartter et al., unpublished results), possibly owing
admission haematocrit and whether or not the patient received to macrophage release of prostaglandin E (reference 18). The
blood transfusions were significantly related to the development reticulo-endothelial system is implicated by the observation that
of infectious complications. Admission haematocrit was transfused damaged red cells are sequestered by the spleen and
significantly related to infection only in the context of increase susceptibility to septic challenge’’. Transplant studies
transfusion: none of the patients with low admission have implicated leucocytes in the production of the transfusion
haematocrits (below the mean of 38.2) developed infectious effect in transplantation”. However, since blood storage
complications unless they were transfused (Table 7 ) .The risk of reduces the number of viable leucocytes and improves renal
infection among patients with low admission haematocrit was allograft survival”, and leucocyte extracts” and large volumes
11.9 per cent and 12.5 per cent for patients with normal of donor-specific serum prolong the survival of skin allograftsz3,
haematocrits. leucocyte-derived products present in the serum of the
Finally, we used the multivariate analysis to investigate the transfused blood may be the cause of transfusion-induced
relationship of transfusion to infection after consideration of all immune suppression. Plasma has been implicated in
of the other variables. After consideration of age, sex, blood loss, transfusion-associated cancer recurrence by tumour growth
procedure, tumour differentiation, stage, admission haemato- experiments in micez4 and by clinical studiesz5.
crit, duration of surgery, length of specimen, and tumour size, Unfortunately, it is currently impossible to prove that the
the association of blood transfusion with infectious observed clinical phenomena in humans are not due to viral
complications was highly significant (xz = 1849, P<OOoOl). contamination of transfused blood. Human cytomegalovirus
infections have long been associated with immune
suppression26J7 and post-transplantation infection is
Discussion common2*.The facility with which the clinical studies can be
This study implicates blood transfusion as a factor in the reproduced in animal models makes it unlikely that viral
development of postoperative infectious complications. The infections are the cause of these phenomena.
temptation is to attyibute the association of blood transfusion The effect of blood transfusion on transplants, malignancies
with infection to operative difficulty or trauma related to the and infections, even if all three are mediated by immune
severity of disease and reflected by the need for transfusion. The suppression, is unlikely to be mediated through the same arm of
lack of association of anaemia, stage, blood loss, specimen the immune system. Current dogma indicates that malignant
length and tumour size with infection, and the observation that cells are destroyed by separate systems from those that destroy
transfusion was associated with infection independent of the bacteria. Some have argued ‘before rational strategies can be
operative procedure and its duration suggest that some other evolved for minimizing the deleterious effects of blood
mechanism accounts for this association. In addition, two transfusion, it is essential that these mechanisms be clearly
studies of penetrating abdominal trauma have identified blood defined’6. We do not agree that clinical studies of blood
transfusion as an independent risk factor for postoperative components for surgery should be postponed until the immune
infections. A prospective multi-institutional study of patients system is unravelled. Proof that transfusion affects a given
with penetrating abdominal trauma observed that the number element of the immune system is at hand, but proving that a
of units of blood administered was significantly related to the given element of the immune system is responsible for
risk of operative infection independent of the number of organs postoperative infections or recurrent malignancies is difficult.
injured, colostomy formation, increased age, and shock on
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Br. J. Surg.. Vol. 75, No. 8, August 1988 791

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Paper accepted 20 March 1988

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792 Br. J. Surg., Vol. 75, No. 8, August 1988