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  • 8/11/2019 Liver Resection 2

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    The Safety

    of

    Continuous Hepatic

    nflow

    Occlusion During Major liver Resection

    Douglas Quan

    and

    WilliamJ.

    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 and44 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 ~ t c o m e . ~ - ~

    t

    has also been suggested that there is an

    association between the risk of cancer recurrence and

    the amount of perioperative blood t r an s f~ si on . ~ . ~n

    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.8-10This 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, we retrospec-

    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, 283 227 IU/L; mean alanine aminotransfer-

    ase [ALT] level, 269 238 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 2.6 U of packed red blood

    cells, and 0.94

    -c

    2.13 U of fresh frozen plasma.

    We conclude hat 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 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 noncir rhotic livers between 198 4 and 1993 were remewed.

    There were 44 females and 2 7 males ranging in age from 25 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

    5

    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 1 9 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: William J. Wall, MD, FRCS C),

    Department

    of

    Surgery, University Hospital, London, Ontano, N6A

    SA.5

    Canada.

    Copyright

    996

    by the American Association for the Study of

    Liver Diseases

    1074-3022/96/0202-000I

    3.00/0

    Liver

    Transplantation an d Surgery,

    Vol2,N o

    2 March), 1996:

    pp

    991

    04

    99

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    100

    Quan nd 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

    aneurysm clip 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 ~ m y . ~or 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 cm to the right

    of the falciform ligament. 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 from the raw edge of the liver after restoration

    of blood flow was controlled with chromic catgut sutures or

    topical hemostatic agents (gelfoam soaked 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-

    tive management to give

    1

    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

    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 2lo/, xperienced 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

    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 eak

    Urinary retention

    Total

    3

    1

    1

    1

    1

    15

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    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

    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. It

    was slightly prolonged on the first and second

    400

    PF ? E O P I 2 3 4 5 7

    DAY

    Figure 1. Mean +SD) AST levels in 71 patients

    who underwent major liver resection norm al, 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

    PREOP

    I

    2 3

    4

    5

    DAY

    Figure 3. Mean (+ SD) alkaline phosphatase lev-

    els normal, 18t o 113 IU/L).

  • 8/11/2019 Liver Resection 2

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    102

    Quan and Wall

    o o r

    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 a18 reported

    9

    patients who

    had both portal and caval occlusion for an average of

    38 minutes without mortality. Stimulated by that

    report, we studied 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.20~21ur results suggest that this approach is

    unnecessary. Indeed, there is evidence suggesting

    that intermittent reperfusion may be harmful.22Reper-

    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

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    Liver Ischem ia

    During

    Partial Hepatectomy

    103

    occlusion, Bismuth et a124 eported 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 n d e ~ , ~ ~ , ~ 'hanges 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.2yThis 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-

    t a t i ~ n . ~ 'atty livers do not tolerate cold preservation

    well, and there is recent experimental evidence

    showing that livers laden with fat do not tolerate

    warm i~chern ia.~'W elso 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.

    s

    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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