The Safety of Continuous Hepatic Inflow

Occlusion During Major liver Resection

Douglas Quan and William J . Wall
To evaluate the safety of temporary hepatic inflow
occlusion during major liver resection, we re-
viewed 71 consecutive noncirrhotic patients who
underwent elective liver resection using this tech-
nique. There were 27 males and 44 females (mean
age, 54.4 years), the majority of whom had hepatic
malignancies. There were 31 right hepatectomies,
21 left hepatectomies, and 19 extended right
hepatectomies. Ischemic injury of the liver was
assessed using changes in postoperative liver
function tests and patient outcome was assessed
using morbidity and mortality rates. After prelimi-
nary ligation of the blood supply to the lobe to be
removed, global hepatic ischemia was produced
by temporary occlusion of the main portal vein
and hepatic artery proper white the liver paren-
chyma was divided. The average duration of in-
flow occlusion was 59 minutes (range, 25 to 90
he most significant operative hazard during
T major liver resection is hemorrhage. Bleeding is
expected, and it is common to lose moderate to large
volumes of blood.' The amount of blood loss has an
impact on morbidity and mortality. Several studies
have documented a correlation between large volume
transfusion during liver resection and poor patient
o~tcome. ~- ~ It has also been suggested that there is an
association between the risk of cancer recurrence and
the amount of perioperative blood transf~si on.~.~ In
addition to those considerations, there are the gen-
eral risks of transmission of disease and the strain on
blood bank resources when large volumes of blood
are consumed. Thus, there are many reasons to
minimize blood loss during hepatic surgery.
To reduce blood loss in patients undergoing liver
resection, it has been suggested that portal and
arterial flow to the liver should be temporarily
occluded when the hepatic parenchyma is di-
vided.8-10 This approach is based on the same
principle as Pringle's description in 1908 of portal
triad compression to control bleeding from an in-
jured liver. '' However, inflow occlusion has not
become routine because of the concern that signifi-
cant ischemic injury of the nonresected liver could
result. '
To determine the safety of continuous inflow
occlusion during major liver resection, weretrospec-
tively studied the postoperative course of all patients
minutes). There was no operative mortality, and
no patient developed liver failure. The liver en-
zymes reached their peak on the first postopera-
tive day (mean aspartate aminotransferase [AST]
level, 283 f 227 IU/L; mean alanine aminotransfer-
ase [ALT] level, 269 2 238 IU/L) and they returned
to normal by 7 days. The most common postopera-
tive complications were related to the chest,
wound, and urinary tract. The mean intraoperative
transfusion was 3.4 f 2.6 U of packed red blood
cells, and 0.94 -c 2.13 U of fresh frozen plasma.
We conclude that continuous hepatic inflow occlu-
sion for periods of 1 hour during major liver
resection is safe and well-tolerated when there is
no underlying parenchymal liver disease.
Copyright 0 1996 by the American Association for
the Study of Liver Diseases
who underwent major hepatic resection using this
technique at our center.
Patients and Methods
Seventy-one consecutive major liver resections using continuous
inflow occlusion performed on a single surgical semce in patients
with noncirrhotic livers between 1984 and 1993 were remewed.
There were 44 females and 27 males ranging in agefrom25 years
to 76 years (mean age, 54.4 2 14.2 years). The indications for liver
resection are listed in Table 1. Metastatic colon cancer was the
most common indication, accounting for 35 of 50 resections for
malignancy There were 2 1 resections for benign disease. The types
of liver resection were as follows: 31 right hepatectomies, 21 left
hepatectomies, and 19 extended right hepatectomies (right lobe
plus medial segment of left lobe). Patients who had fibrotic or
cirrhotic livers or who had significant gross fatty change in the liver
were not considered as candidates for inflow occlusion.
During the surgery the patients had monitoring of arterial
pressure, central venous pressure, and urine output Blood was
transfused intraoperatively on the basis of measured losses and
hemodynamics.
From the Department of Surgery, University Hospital, London,
Ontario, Canada.
Addrezs reprint requests to: WilliamJ . Wall, MD, FRCS(C),
Department of Surgery, University Hospital, London, Ontano, N6A
SA.5, Canada.
Copyright 0 1996 by theAmerican Association for the Study of
Liver Diseases
1074-3022/96/0202-000I $3.00/0
Liver Transplantation and Surgery, Vol2, No 2 (March), 1996: pp991 04
99
100 Quan and Wall
Table 1. Indications for Liver Resection
Diagnosis Number of Patients
Metastatic malignancy 36
Cavernous hemangioma 8
Primary liver malignancy 9
Cholangiocarcinoma 5
Hepatic adenorna 4
Focal nodular hyperplasia 2
Bile duct cystadenoma 2
lntrahepatic stones 2
Other 3
Total 71
I I
The operative technique was the same in all cases. Bilateral
subcostal incisions were used with an occasional upper midline
extension to the xiphoid process. After complete mobilization of
the lobe of the liver to be removed, the corresponding branch of
the portal vein, hepatic artery, and bile duct in the porta hepatis
was ligated and divided. The venous drainage of the lobe to be
resected was then similarly ligated for either right or left hepatecto-
mies. For extended right hepatectomies the right hepatic vein was
ligated but ligation of the middle hepatic vein was left until the
hepatic parenchyma had been divided. The main portal vein and
hepatic artery proper were temporarily occluded while the liver
parenchyma was transected. The artery was occluded with a Drake
aneurysmclip and the portal vein was occluded by a tourniquet
tape. The resections were performed along anatomic planes,
according to the description by Bismuth et al of partial hepatec-
t~my. ~ For right or left hepatectomies, the line of parenchymal
division was the plane joining the gallbladder fossa with the
retrohepatic cava. The line between vascularized and devascular-
ized liver was clearly evident after ligation of the blood supply of
the lobe to be removed. In cases of extended right lobectomy the
line of parenchymal diwsion was approximately 2 cmto the right
of the falciformligament. Preliminary hilar ligatlon of the vessels to
the right lobe was performed and the feeding vessels to the medial
segment of the left lobe were taken within the liver parenchyma
when the liver was transected. The gallbladder was removed in all
cases. The Cavitron ultrasonic dissector (Valley Lab, Richmond
Hill, Canada) was used to divide the liver. Vascular and biliary
tributaries encountered during the parenchymal division were
ligated with hemoclips or chromic catgut ligatures.
Arterial and portal inflow was restored after completion of the
resection. Bleeding fromthe raw edge of the liver after restoration
of blood flow was controlled with chromic catgut sutures or
topical hemostatic agents (gelfoamsoaked in topical thrombln).
Liver enzymes (aspartate aminotransferase [.&TI, alanine amino-
transferase [ALT] and alkaline phosphatase [ALPI), and serum
bilirubin levels and prothrombin time (PT) were monitored during
the first postoperative week. I t was part of the routine postopera-
tivemanagement to give1 or 2 U of 25% albumin daily for the first
5 days after surgery. Drains were removed between 5 and 7 days if
no bile was evident in the drainage. The patients were kept on
intravenous fluids that included 5% glucose until they were able to
eat.
Statistical analysis was camed out using Students t-test, x L
test, analysis of variance, and linear regression using Stawiew
WSuperANOVA (Abacus Concepts Inc, Berkeley, CAI. Values are
expressed as mean ? SD unless orhewise indicated.
Results
The 30-day operative mortality rate was zero, and all
patients were discharged from hospital. Overall, 15
patients (2 lo/,) experienced 16 postoperative compli-
cations (Table 2). More than half of the complica-
tions were infections related to the chest, wound, or
urinary tract. One patient developed a subphrenic
abscess after a right hepatectomy that was success-
fully treated with percutaneous drainage. One patient
had a bile leak that was controlled by the drain
placed at the time of surgery. The bile leak closed
spontaneously after 9 days of drainage. One patient
developed an inhibitor to factor V postoperatively,
which was thought to be caused by an idiosyncratic
reaction to topical thrombin placed on the raw liver
edge during the surgery.14 Postoperative morbidity
was not significantly associated with age, gender or
diagnosis (benign versus malignant; P >.05).
The average postoperative hospitalization stay was
14.2 2 8.0 days (range, 7 to 49 days; median, 12
days), Two patients had prolonged postoperative
stays of 48 and 49 days. The first patient required a
prostatectomy for urinary retention after the liver
surgery, and he subsequently developed a pulmonary
embolism. The second patient developed pulmonary
insufficiency and the adult respiratory distress syn-
drome and needed assisted ventilation for 1 week
after the hepatic resection. She made a slow but
complete recovery.
The mean duration of inflow occlusion was 59 I+_
Table 2. Postoperative Complications
Complication Number of Patients
Wound infection
Urinary infection
Pneumonia
Pulmonary embolism
ARDS
Subphrenic abscess
Bile leak
Urinary retention
Total
3
3
3
2
1
1
1
1
15
Liver Ischemia During Partial Hepatectomy
101
15 minutes (median, 60 minutes; range, 25 to 90
minutes). The mean intraoperative blood transfusion
was 3.4 * 2.6 U of packed red blood cells (median, 3
U; range, 0 to 19 U). Three patients required no
transfusion. Only one patient required more than
eight U of blood. This patient had a large angiosar-
coma that was intimate with the retrohepatic vena
cava, and when the tumor and the liver were being
mobilized, an opening was inadvertently made into
the inferior vena cava that resulted in sudden,
massive blood loss. Duration of inflow occlusion did
not correlate with the amount of transfusion (r2 =
0,001). The mean intraoperative transfusion of fresh
frozen plasma was 0.94 f 2.13 U.
Transient elevation occurred in the AST and ALT
levels during the first 7 postoperative days. The
enzymes reached their peak on the first postoperative
day and then decreased to preoperative levels by 7
days (Figs 1 and 2). The alkaline phosphatase
decreased slightly during the first 3 days after surgery
and began to increase by the fourth day (Fig 3). The
level of enzymes did not significantly correlate with
the duration of inflow occlusion (r2 =0.079 and
0.090 for AST and ALT, respectively) nor did they
correlate with the postoperative complications listed
in Table 2. The same was true for the serum bilirubin.
Hyperbilirubinemia was common in the immediate
postoperative period and the average serum bilirubin
level was still approximately three times normal by
the end of the first postoperative week (Fig 4).
However, no cases of prolonged jaundice were ob-
served.
The mean preoperative PT was 10.2 seconds. I t
was slightly prolonged on the first and second
400
PF ? E O P I 2 3 4 5 6 7
DAY
Figure 1. Mean (+SD) AST levels in 71 patients
who underwent major liver resection (normal, 10
to 30 IU/L).
PREOP I 2 3 4 5 6 7
DAY
Figure 2. Mean (+SD) ALT levels in 71 patients
(normal, 5 to 30 IU/L).
postoperative days (12.5 seconds and 12.6 seconds,
respectively), but the difference was not statistically
significant.
Discussion
The safety and success of liver resection depends
upon effective control of bleeding during surgery and
the ability of the nonresected lobe to sustain life in
the immediate postoperative period and regenerate to
a normal volume within a few months from surgery.
In this study of major liver resections, continuous
vascular inflow occlusion resulted in modest blood
loss, and the changes in liver function tests after
surgery did not suggest that it caused any significant
ischemic injury to the liver. There were no manifesta-
0 1 I I I I I I I
PREOP I 2 3 4 5 6 7
DAY
Figure 3. Mean (+SD) alkaline phosphatase lev-
els (normal, 18t o 113 IU/L).
102 Quan and Wall
/
loor
tions of liver insufficiency, and although the rate of
liver regeneration after surgery was not documented,
the clinical course of the patients did not suggest that
there was any impairment of the regenerative re-
sponse. Neither ascites nor prolonged jaundice were
observed in the postoperative period. Inflow occlu-
sion did not seem to have caused any adverse effects
in this series of patients. The complications that
occurred were typical of those that are commonly
reported after liver or other major abdominal surgery
and there was no evidence that inflow occlusion was
causally related to any of them.2-5
The concept of an exquisite sensitivity of the liver
to ischemia originated in experiments in dogs more
than 4 decades The canine model of liver
ischemia does not directly reflect human physiology
because of the unique hepatic vein sphincters in dogs
and the presence of bacteria in their portal blood that
resulted in hepatic gangrene after ligation of the
hepatic artery. It was erroneously assumed that the
human liver was similar, and the warning was given
that the liver should not be subjected to warm
ischemia for periods of more than 15 or 20 min-
utes.12
In 1978, Huguet et a18reported 9 patients who
had both portal and caval occlusion for an average of
38 minutes without mortality. Stimulated by that
report, westudied experimental hepatic ischemia in
a pig model.16 Those experiments and data from
Nordlinger et all7 showed that the porcine liver could
tolerate periods of normothermic inflow occlusion
(with simultaneous portal decompression) for 90 to
120 minutes. Extension of the ischemic period to
180 minutes resulted in greater physiological and
clinical abnormalities, and some of the animals did
not survive.18 Based on those experiments and the
handful of reported clinical cases until that time, we
began using inflow occlusion during major liver
resections. Over the past 10 years there have been
sporadic reports, mainly from the same centers, that
have shown that the human liver has considerable
tolerance for ischemia at normal body temperature.8-
Reported experiences indicate that it is safe to
use inflow occlusion for 60 minutes, and our results
show that it is possible to use inflow occlusion for as
long as 90 minutes without producing serious liver
injury.
Significant bleeding may occur at any of three
stages during liver resection. The first is during the
initial mobilization of the lobe to be resected. Prob-
lematic bleeding may occur at this stage if a vascular
tumor is present that is adherent to adjacent struc-
tures, ie, diaphragm, retrohepatic cava, retroperito-
neal tissues, etc. The second is when the liver is
divided and intrahepatic vessels are secured. Bleed-
ing at this stage is most likely to be reduced by inflow
occlusion. The third stage of bleeding occurs from
the raw edge of the liver after completion of the
resection, when blood flow is restored. The technical
advantage of a relatively bloodless field during the
second stage has permitted accurate and secure
control of vascular tributaries such that significant
bleeding from the raw edge, after inflow is restored, is
minimal. Thus, we have not found it necessary to
reinstitute inflow occlusion during the third stage.
There are several variations on the theme of inflow
occlusion, and the modifications include intermit-
tent inflow occlusion, total vascular exclusion, and
hypothermic vascular exclusion. Intermittent as op-
posed to continuous inflow occlusion has been
recommended by some to give the liver a periodic
drink with the intention of reducing the possibility
of ischemic injury. Intermittent release at 5- to
20-minute intervals has been reported with good
results.20~21 Our results suggest that this approach is
unnecessary. Indeed, there is evidence suggesting
that intermittent reperfusion may be harmful.22 Reper-
fusion injury has been shown to be an important
component of tissue damage from ischemia, and it
may be that subjecting the liver to several reperfusion
episodes could cause more harm than a single,
prolonged period of continuous ischemia. Complete
hepatic vascular exclusion was described as early as
1966 by Heaney et al.23 for the resection of difficult
tumors. In a series of 51 patients (38 had major liver
resections) who underwent total hepatic vascular
Liver Ischemia During Partial Hepatectomy
103
occlusion, Bismuth et a124 reported a low transfusion
rate of 1.4 U of packed red blood cells and mortality
and morbidity rates that are similar to our results.
Recently Habib et aI2* reported good results with
total hepatic vascular exclusion for a mean period of
37 minutes in 47 patients. There was no 30-day
mortality, and the average transfusion was 930 mL of
blood. Total vascular exclusion achieves the best
possible vascular control, because the vena cava is
isolated above and below the liver in addition to
occlusion of the portal vein and hepatic artery. That
approach may be most suited to the unusually large
tumors that lie in close proximity to the vena cava,
during which there is the risk of producing a tear or
hole in the vena cava. Total hepatic vascular exclu-
sion may cause significant hemodynamic effects with
a decrease in the mean arterial blood pressure and a
reduced cardiac i nde~, ~~, ~' changes that do not occur
with portal triad occlusion alone. The most extreme
approach is that of cooling the liver as part of vascular
exclusion, as described by Fortner et aL2* That
technique would only seem necessary if several hours
of liver ischemia were required.
The increase in liver enzymes during in the first
few days after the resections in our series was
moderate and it may be explained by local tissue
injury at the line of the liver transection plus the
effect of the transient ischemia on the nonresected
lobe of the liver. The brief increase and subsequent
decrease of the aminotransferases observed in the
patients in our study are similar to what has been
documented after major liver resection without in-
flow occlusion.2y This suggests that tissue trauma at
the line of resection is primarily responsible for the
acute change in the liver enzymes. One study by
Makuuchi et aI3O showed no significant difference in
the aminotransferase level between two groups of
patients with and without intermittent inflow occlu-
sion during liver resection with a mean occlusion
time of 30 minutes.
We have been reluctant to apply continuous
inflow occlusion to patients in whom the liver was
found to be grossly fatty at the time of surgery
because of the experience with fatty livers in transplan-
tati ~n.~' Fatty livers do not tolerate cold preservation
well, and there is recent experimental evidence
showing that livers laden with fat do not tolerate
warm i~chernia.~'We also did not use this technique
in patients who had cirrhotic livers. Nonetheless, two
clinical reports have shown that inflow occlusion
appears to be safe even in cirrhotic livers for periods
of 30 to 57 minute^.^^,^^In those studies, most of the
patients were Child's class A which may be relevant
to the results.
We doubt that absolute hepatic ischemia was
created by the technique that we have used. Some
collateral arterial supply to the nonresected lobe of
liver exists in the undivided ligamentous attachments
of that lobe, and there is likely some supply via small
collateral channels within the connective tissue of the
porta hepatis. As opposed to methods in which a
clamp is applied across the entire portal triad, we
isolated and occluded the hepatic artery proper and
the portal vein leaving other vascular tributaries in
the hepatoduodenal ligament undisturbed. When
this technique was used in pigs, we found there was a
residual flow of approximately 10% of the preocclu-
sion flow as measured by Xenon washout.'* Whether
that residual flow has any clinical significance in
preventing ischemic injury to the remainder of the
liver is unknown.
In conclusion, continuous hepatic inflow occlu-
sion is a safe technique and was not harmful to the
liver for periods of 1 hour. It offers technical advan-
tages without compromise to the liver in the immedi-
ate postoperative period.
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