Anesthesia for

H e p a t o b i l i a r y Su r g e r y
a,b, a
Chris Snowden, MBBS, FRCA, MD *, James Prentis, MBBS, FRCA

KEYWORDS
 Hepatobiliary  Anesthesia  Hepatectomy  Enhanced recovery  Intrathecal
 Opiate

KEY POINTS
 Reduced mortality after hepatobiliary surgery is related to improved patient selection,
introduction of preoperative embolization techniques, improved intraoperative surgical
techniques/equipment, and reduced operative blood loss.
 Alternative therapies (eg, radiofrequency ablation) are being introduced in patients who
are unable to tolerate extensive hepatic resections.
 Lowering the central venous pressure during hepatic resection reduces blood loss but
must be optimized to avoid hypovolemia and excessive use of vasoconstrictor
medication.
 Intrathecal opiates may provide an alternative postoperative pain control regimen to
epidural analgesia, especially where there is abnormal coagulation.

INTRODUCTION

Hepatobiliary (HPB) surgery, variably defined to include pancreatic surgery, and liver
and pancreas transplantation, has become a major surgical specialty with explicit
training opportunities, mainly as a response to poor surgical outcomes in the early
1970s. The subsequent improvement in HPB surgical outcomes (now usually <5%
mortality) has been associated with:
1. The concentration of HPB surgery to large volume centers
2. Better preoperative treatment, including radiologic venous embolization and che-
moradiotherapy regimes
3. Introduction of newer surgical techniques and equipment to minimize blood loss
(eg, Cavitron ultrasonic aspirator [CUSA] or harmonic scalpel to dissect the liver
parenchyma).

The authors have no disclosures.

a
Department of Perioperative and Critical Care Medicine, Freeman Hospital, Freeman Road,
Newcastle upon Tyne NE7 7DN, UK; b Institute of Cellular Medicine, The Medical School, Uni-
versity of Newcastle upon Tyne, Framlington Place, Newcastle upon Tyne NE1 4LP, UK
* Corresponding author. Department of Perioperative and Critical Care Medicine, Freeman
Hospital, Freeman Road, Newcastle upon Tyne NE7 7DN, UK.
E-mail address: [email protected]

Anesthesiology Clin 33 (2015) 125–141

http://dx.doi.org/10.1016/j.anclin.2014.11.008 anesthesiology.theclinics.com
1932-2275/15/$ – see front matter Ó 2015 Elsevier Inc. All rights reserved.
126 Snowden & Prentis

Alongside these surgical advances, it is recognized that advanced anesthetic man-

agement of the HPB surgery patient has significantly contributed to improved out-
comes. These advances have come predominantly through more appropriate
preoperative patient selection, intraoperative techniques to prevent and manage
blood loss, and postoperative enhanced recovery protocols with improved analgesic
regimens.
The present article relates primarily to the management of patients undergoing
hepatic resection. In this context, we address anesthetic and surgical consider-
ations, including patient selection, alternative surgical management options, the
reduction of operative blood loss, introduction of the components of postoperative
enhanced recovery, and considerations related to postoperative liver dysfunction
and failure.

HEPATIC RESECTION
Outcomes of Hepatic Resection
Hepatic resection is performed for a number of underlying pathologies, including
benign or malignant primary tumors, secondary metastases (predominantly colo-
rectal), and liver trauma. Surgical criteria for patient selection are important.1 If hepatic
malignancy is involved, operative resection is established as the only currently avail-
able modality of treatment with curative potential.
Patients with untreated but potentially resectable hepatic malignancy have been re-
ported to have a median survival time of less than 6 months,2 with virtually no 5-year
survival. Surgical treatment for hepatocellular carcinoma prolongs 10-year survival to
15%.3 Five-year survival after hepatic resection for metastases is 33%,4 compared
with 11% in those not undergoing operative resection. The aim of hepatic resection
is to effect clear tumor margins, while ensuring adequate remaining residual liver to
prevent postoperative hepatic insufficiency. The relevance of a clear resection margin
is reflected in survival. For patients with tumor-free margins greater than 1 cm, a
5-year disease-free survival rate of 35% can be expected. Survival rates are 21%
for patients for whom tumor margins are less than 1 cm, and no 5-year survivors
can be expected when the margins are involved by tumor.5

Hepatic Regeneration
Residual liver volume after surgery is important to postoperative hepatic dysfunction.6
The volume of liver that can be safely resected in humans is approximately 80%,7
assuming good function in the remaining liver, although there are early reports of sur-
vival after resections of 90%.8 The potential for these massive resections (or extensive
ablations) relies on postoperative hepatic regeneration, which has a complex mecha-
nism.9 Under normal circumstances, the human liver initiates regeneration within
3 days and has reached its original size by 6 months,10 although some studies have
shown full restoration at 3 months. Rapid regeneration may allow complete functional
recovery within 2 to 3 weeks.11

Preoperative Portal Vein Embolization

If there is a predicted risk of liver failure developing after a procedure, through need to
remove large liver components, then the preemptive maneuvers of portal embolization
of affected segments, some weeks before resection can stimulate regeneration in the
proposed liver remnant, thereby enhancing postoperative liver function.12–14 An in-
crease of 40% to 60% in the size of the nonembolized liver can be anticipated in
noncirrhotic livers.15,16 Similarly, chemoembolization can be used in potentially
 Anesthesia for Hepatobiliary Surgery 127

unresectable hepatocellular carcinoma to reduce tumor mass and increase residual

function to an extent that may permit definitive resection.

Alternatives/Adjuncts to Hepatic Resection

Because only approximately 10% to 20% of patients presenting with hepatic malig-
nancy are suitable for resection, other types of less invasive HPB surgical techniques
are used, with good success rates,17 to achieve reduction of tumor mass and symp-
tomatic control. Radiofrequency ablation,17,18 cryoablation,19,20 and the recently
applied selective internal radiation therapy techniques21,22 can be performed percuta-
neously, laparoscopically, or during open laparotomy. The percutaneous approach is
usually indicated for palliation,23 whereas laparoscopic ablation is selected for
smaller, superficially located, or easily accessible tumors with intraoperative ultra-
sound guidance. Open surgical ablation is indicated for larger or deeply located ma-
lignancy and may be combined with hepatic resection where multiple tumors are
present. Ablation probes inserted into the tumor center aim to locally destroy tumor
mass through heat (100 C–110 C) or by cooling (with liquid nitrogen). Potential com-
plications of these techniques include hemorrhage (including hepatic capsular
rupture), biliary leak, and thrombocytopenia and myoglobinuria, which have been
reported in more extensive procedures.

PREOPERATIVE CONSIDERATIONS

Perioperative management of HPB patients depends a complete understanding of the

potential benefits, limitations, and perioperative risks of major surgical procedures, in
the context of either coexisting disease states and/or preexisting liver disease.

Hepatic Resection in Patients Without Comorbidity

A significant component of metastatic (especially colorectal secondaries) HPB surgery
is undertaken in otherwise fit patients. In these situations, prolonged preoperative
assessment of anesthetic fitness is not required, even for extensive resections and
where malignant disease is present, because this will lead to unacceptable delays
in treatment. Surgery after preoperative neoadjuvant chemotherapy for colorectal me-
tastases is often delayed by up to 4 weeks to allow for patient recovery and to reduce
postoperative and surgical complications. However, there is no benefit in delaying sur-
gery for longer than 4 weeks.24

Hepatic Resection, Age, and Comorbid Disease

Improvements in anesthetic and surgical techniques, which have been successful in
improving outcomes, are already translating into more extensive HPB surgery being
undertaken in older individuals with more comorbid diseases.25,26 Advancing chrono-
logic age should not be viewed as a surgical barrier and there are multiple series sug-
gesting that resections for hepatocellular carcinoma and colorectal metastases can be
performed safely in these patients.25,27 Recent evidence suggests that cardiorespira-
tory fitness may have a more important influence on perioperative outcomes in HPB
surgery than chronologic age per se.28 Nevertheless, advancing age reduces liver
size and blood flow, decreases drug metabolism (phase I), and increases the inci-
dence of alcohol-induced cirrhosis through environmental exposure.29 Prolonged
exposure to environmental factors also leads to the development of covert forms of
liver disease, reducing hepatic reserve and increasing susceptibility to hepatic
ischemia–reperfusion injury during resection.29 Importantly, steatohepatitis consti-
tutes the third commonest liver disease in the United States and has been estimated
128 Snowden & Prentis

to be present in 20% of the US population. The etiology may be secondary to alcohol

intake or related primarily to diabetes and/or obesity in the form of nonalcoholic stea-
tohepatitis. Even so, there may be a paradoxic protective benefit of steatohepatitis af-
ter liver resection for colorectal metastases.30

Hepatic Resection and Preexisting Liver Disease

Where preexisting liver disease is present, increased perioperative risk depends on
the nature and severity of the disease and the extent of hepatic dysfunction. This con-
dition requires more specific assessment. Cirrhotics have an increased incidence of
surgical intervention for multiple reasons, including variceal bleeding and increased
hepatoma formation. Patients with cirrhosis have insufficient hepatocyte function to
meet the increased metabolic demands after partial hepatectomy,31 and have signif-
icantly reduced levels of hepatic regeneration after liver resection, making them
extremely vulnerable to posthepatectomy liver failure. Although chronic liver disease
is not an absolute contraindication to resection, morbidity and mortality increases
dramatically with worsening hepatic dysfunction. One severity scoring system is the
Child–Pugh score (Table 1), which was originally used to assess chronic liver disease
prognosis but has since been used for major surgery outcome. Child–Pugh class B or
C (scores of 7–9 and 10–15, respectively) may exclude a patient from major resection.
However, Child–Pugh class A (score of 5–6) patients should be considered for surgery
and in these patients there is significant incentive toward optimizing preoperative
medical care to improve the postoperative prognosis. However, in terms of risk pre-
diction for hepatic surgery, none of the preexisting systems relating liver disease
severity to perioperative outcome is ideal. The Child–Pugh scoring system has
demonstrated an association with perioperative risk in patients undergoing esopha-
geal transaction, nonshunt surgery, and abdominal surgery. The Model for End-
Stage Liver Disease score may be important where there is existing cirrhosis32 and
hepatocellular carcinoma,33 but should not be used in the context of elective hepatic
resection with normal liver function.34 Patients with cholangitis may also be at high risk
of postoperative complications.35 One risk prediction model suggests that renal
impairment, bleeding, ascites, American Society of Anesthesiologists grade, histolog-
ic diagnosis of cirrhosis, and intraoperative hypotension are the most important peri-
operative factors related to postoperative outcome.36 However, because newer
operative procedures have evolved and the benefits of improved diagnostic facilities,
including biochemical parameters, are absent from these predictive scoring systems,
the applicability of these systems to newer HPB surgery risk prediction is uncertain.

Table 1
Child-Pugh scoring system

Measure 1 Point 2 Points 3 Points

Total bilirubin mmol/L (mg/dL) <34 (<2) 34–50 (2–3) >50 (>3)
Serum albumin (g/dL) >3.5 2.8–3.5 <2.8
PT/INR: http://en.wikipedia.org/wiki/ <1.7 1.71–2.30 >2.30
Prothrombin_time - International_
normalized_ratio
Ascites None Mild Moderate to
severe
Hepatic encephalopathy None Grade I-II (or Grade III-IV
suppressed with (or refractory)
medication)
 Anesthesia for Hepatobiliary Surgery 129

Clinically, the relevance of each preoperative severity marker to an individual’s po-

tential risk may be more practical. Nutritional status and albumin are important factors
common to the postoperative recovery of all surgical patients and are not discussed
further herein. More specific markers of liver disease severity include jaundice, coagul-
opathy, ascites, and encephalopathy.

Jaundice
The importance of preoperative jaundice is owing to its prominent association with
perioperative renal impairment.37–39 The mean incidence of postoperative renal
impairment in surgical patients with jaundice is 8%, but may be as high 18%. Whereas
the overall postoperative mortality rate in surgical patients with jaundice ranges from
0% to 27%, the mortality for jaundiced patients who go on to develop acute renal fail-
ure is estimated at 65%. Thus, development of postoperative renal failure is a poor
prognostic sign. The etiology of postoperative renal failure in the setting of liver dis-
ease is multifactorial and includes central volume depletion, defective renal vascular
reactivity, vasoactive mediator imbalance (in which local prostaglandins play a prom-
inent role), and the effect of endotoxin. This makes the renal vasculature susceptible to
renotoxic drugs such as nonsteroidal anti-inflammatory drugs and contrast media.
Preoperative measures to prevent the onset of renal impairment have included
adequate preoperative hydration, mannitol infusion, bile salts, and lactulose. How-
ever, none have demonstrated consistent benefit in adequate clinical trials. Preoper-
ative percutaneous or endoscopic biliary drainage before major HPB surgery does not
improve perioperative outcome consistently and may increase the incidence of chol-
angitis, known to be a poor prognostic factor for outcome. However, preoperative
biliary drainage followed by portal vein embolization has been advocated as a bene-
ficial strategy for major hepatectomy in perihilar cholangiocarcinoma.40 Prolonged pe-
riods of preoperative drainage may allow for the resolution of jaundice, but does not
lead to improved perioperative outcome. Therefore, biliary drainage should be limited
to 2 weeks before surgery.41

Coagulopathy
Correction of coagulation before liver resection is essential where central neuraxial
blockade is being considered. Vitamin K, fresh frozen plasma, or cryoprecipitate
may be required to correct liver-related coagulopathy preoperatively. Reduction in
platelet counts in these patients is common, but abnormalities in platelet function
are often more relevant. Therefore, the preoperative administration of platelets is bet-
ter guided by laboratory testing (eg, thromboelastogram) results than by clinical
judgment.

Ascites
The development of ascites is a poor prognostic sign in cirrhosis and may
adversely influence perioperative respiratory mechanics. Furthermore, ascites, sec-
ondary to splanchnic arteriolar vasodilatation, develops at the expense of circu-
lating intravascular fluid. In conjunction with medical therapy, including diuresis
and paracentesis, there is a real risk of significant intravascular hypovolemia. At-
tempts should be made to correct this state preoperatively and it is important to
recognize that perioperative fluid limitation does not prevent the development of
postoperative ascites.

Encephalopathy
Subclinical hepatic encephalopathy is present in 30% to 70% of cirrhotics and can be
detected by subtle psychometric testing. Elective hepatic surgery should be deferred
130 Snowden & Prentis

until the cause of preoperative encephalopathy is ascertained and effective treatment

is provided. Preoperative lactulose may prevent encephalopathy from worsening, but
treatment of the cause, for example, infection or hemorrhage, is more important. This
is particularly relevant wherever postoperative encephalopathy develops de novo,
because it is often difficult to distinguish between encephalopathy and drug intoxica-
tion. Drug-induced intoxication has a much better prognosis than spontaneous
encephalopathy.

INTRAOPERATIVE CONSIDERATIONS

Excessive surgical blood loss is related to adverse short- and long-term postoperative
outcomes after liver resection.42 Because resting total hepatic blood flow represents
about 25% of cardiac output (1200–1400 mL/min; w100 mL/min/100 g), surgical tran-
section of liver parenchyma carries a high risk of blood loss. Reduction of blood loss is
therefore a major consideration during the intraoperative period. Advances in surgical
technique, equipment, and anesthetic measures have all been useful in reducing
blood loss and are detailed herein.

Surgical Vascular Occlusion

Hepatic vascular occlusion is used to reduce blood loss from the liver surface during
surgical dissection (Fig. 1).43,44 Although occlusion times of up to 60 minutes are
considered safe in noncirrhotic livers, postoperative hepatic insufficiency and enceph-
alopathy may occur with shorter durations.45,46 In cirrhotic livers, 30 minutes is consid-
ered safe and possibly up to 60 minutes in early disease.47
Pringle maneuver
Pringle48 first described a technique to prevent bleeding during hepatic trauma sur-
gery by clamping the hepatoduodenal ligament and interrupting blood flow in both
the hepatic artery and portal vein. The Pringle maneuver (PM) is generally well-
tolerated haemodynamically,49 even though it is associated with a 10% increase in
mean arterial pressure, a 40% increase in systemic vascular resistance, and a 10%
decrease in cardiac output. However, prolonged interruption of hepatic inflow
(>1 hour in normal liver and >30 minutes in pathologic livers)50 may cause ischemia/
reperfusion injury to the remaining liver. Recent evidence suggests that the PM should
be avoided in hepatectomy for malignancy owing to deleterious effects on tumor
recurrence.51

Fig. 1. Isolation of the portal triad before hepatic inflow occlusion. Yellow, bile duct; red 1,
right hepatic artery; red 2, left hepatic artery; blue, portal vein.
 Anesthesia for Hepatobiliary Surgery 131

Intermittent Pringle maneuver

An intermittent vascular occlusive technique (intermittent PM [IPM]) has been devel-
oped to reduce the risk of ischemia/reperfusion. This incorporates 15 to 20 minutes
of interrupted liver blood flow, followed by a 5-minute period of reperfusion and incor-
porates the mechanism of organ preconditioning.52,53 IPM reduces splanchnic
congestion and decreases hepatic ischemia/reperfusion injury. A randomized,
controlled trial concluded that a compromised liver better tolerates IPM than contin-
uous PM,52 but there is no significant benefit where normal parenchyma exists. How-
ever, disadvantages of IPM include increased blood loss from the transection surface
during the unclamped period and prolongation of the transection phase. A recent Eu-
ropean survey54 suggests that IPM is the method of choice for hepatic resection, with
a total ischemic time limited to 15 to 30 minutes.

Selective inflow occlusion

Selectively occluding the blood flow to the left or right hemiliver during resection may
further reduce theoretically the risk of hepatic ischemic/reperfusion injury seen with
IPM. However, meta-analysis has failed to show any significant improvement in
outcome when compared with either PM or IPM, except for resections on cirrhotic
livers.55,56 This technique also requires extensive hilar dissection, which can make
subsequent resection technically challenging.

Total vascular exclusion

Total vascular exclusion incorporates isolation of suprahepatic, subdiaphragmatic,
and infrahepatic vena cava combined with the PM. Total vascular exclusion reduces
bleeding, but carries with it significant per and postoperative morbidity (50%) and
mortality up to 10%57,58 and there is no evidence for benefit over the PM.56 The tech-
nique is usually restricted to cases where the tumor arises near to or involves either the
retrohepatic vena cava or the confluence of hepatic veins and vena cava. Approxi-
mately 10% of patients will not tolerate the hemodynamic effects of vena caval occlu-
sion and may require venovenous bypass.

Surgical Equipment Development

Developments in HPB surgical equipment have also assisted in reducing perioperative
blood loss. The optimal device would aim to destroy liver parenchyma while achieving
hemostasis. Unfortunately, no current equipment achieves both these goals and so
combination equipment is used.59
Cavitron ultrasonic aspirator (CUSA) uses acoustic vibrational force, produced by
saline, to promote liver parenchymal disruption (Fig. 2).60,61 A newer device, the har-
monic scalpel,62,63 is a saline-linked radiofrequency sealer that delivers energy
through saline dripping from the tip, causing coagulation via necrosis on the transec-
tion surface. The large hepatic vessels are left intact by these techniques and exposed
vascular structures are separately ligated, stapled,64 or controlled with diathermy.
There is no definitive evidence for one technique, because clinical studies tend to
include small patient numbers. Control of residual bleeding of the resected liver sur-
face may be achieved by use of argon beam coagulation or the spray application of
fibrin glue.65,66

Anesthetic Technique
Intraoperative
Anesthetic techniques during hepatic resection aim to reduce the need for vascular
occlusion techniques by minimizing the potential for blood loss through optimum fluid
132 Snowden & Prentis

Fig. 2. Hepatic resection using combined Cavitron ultrasonic aspirator (CUSA) and
diathermy techniques.

management and the avoidance of unnecessary blood transfusion through appro-

priate correction of coagulopathy.
Managing central venous pressure The reduction of hepatic venous congestion by
careful control of central venous pressure (CVP) during hepatic resection has long
been associated with a reduction in intraoperative blood loss.67–69 CVP control is
achieved by combining pharmacologic or epidural-based vasodilatation with the lim-
itation of intravenous fluid given before resection. Jones and colleagues68 found that
the volume of blood loss during liver resection correlated with CVP, regardless of us-
ing inflow occlusion. A CVP of 5 cm H2O or less resulted in a median blood loss of
200 mL and blood transfusions in only 5% of patients compared with a 1000-mL
blood loss and 48% blood transfusions in patients with a CVP greater than 5 cm
H2O (P 5 .0001 and P 5 .0008, respectively). However, this study was performed
in an era where advanced surgical dissection equipment was not available. A more
recent Cochrane review70 evidenced that a lower CVP reduced blood loss in compar-
ison to control (mean difference, 419.35 mL; 95% CI, –575.06 to –263.63), but there
was no difference in red blood cell transfusion requirements (standardized mean dif-
ference, –0.31; 95% CI, –0.65 to 0.03), intraoperative morbidity, or long-term survival
benefits.14 The avoidance of positive end-expiratory pressure (PEEP) has also been a
mainstay of liver surgery since an increase in PEEP may increase CVP. However, a
recent study71 has shown that increasing PEEP from 5 to 10 cm H20, increased he-
patic and portal venous pressure by only 1 mmHg. The requirement to reduce post-
operative pulmonary complications after major upper abdominal surgery, means that
further studies are required to define the effect of PEEP on surgical outcome.

Problems associated with reduced central venous pressure during hepatic

resection Maintaining a low CVP may lead to cardiovascular instability, the potential
for intraoperative hypovolemia, and susceptibility to reduce renal and hepatosplanch-
nic blood flow. Where there is ongoing blood loss, the risks of lowering the CVP and
maintaining a controlled but potentially hypovolemic state must be weighed against
the benefits for minimizing blood loss. More recently, the use of stroke volume varia-
tion methods has been suggested as an appropriate replacement for CVP moni-
toring.72 However, more appropriately, the two measurements may be used in a
synergistic combination to ensure reduced venous pressure (CVP), while maintaining
 Anesthesia for Hepatobiliary Surgery 133

normovolemia (stroke volume variation). Wherever low CVP practices are used in an
attempt to reduce blood loss, there may be the requirement for supplementary vaso-
constrictors (eg, phenyl ephedrine, vasopressin, or norepinephrine) to maintain sys-
temic blood pressure for perfusion of other organs. However, vasoconstrictors may
lead to splanchnic vasoconstriction and secondary hepatic ischemia. Nevertheless,
in most reported series where a low CVP technique has been used, with or without
the judicious use of vasoconstriction, there does not seem to be an increased inci-
dence of organ (especially renal) failure. Another possible complication of low CVP
techniques is air embolus.73 Diligence in monitoring sudden changes in end-tidal
CO2 and in cauterizing open hepatic vessels is vital.
Management of coagulation The coagulopathy associated with liver disease can
contribute significantly to the potential for perioperative bleeding. The liver is the
site of production of all coagulation factors (excluding von Willebrand factor) and
many coagulation inhibitors, fibrinolytic proteins, and their inhibitors. The liver is
also responsible for the breakdown of many of the activated factors of coagulation
and fibrinolysis. In addition, platelet abnormalities and thrombocytopenia secondary
to cirrhosis and hypersplenism are common in liver disease. Hence, it is clear how a
complete range of coagulation abnormalities from hypocoagulability, accelerated
fibrinolysis, through to disseminated intravascular coagulation and hypercoagulable
states associated with low protein C and S levels can be encountered perioperatively.
The complex clotting abnormalities of liver disease are succinctly reviewed by Kang.74
Preoperative assessment of coagulation is a mandatory part of the workup for major
hepatic resection. However, the complex interactions of the numerous aspects of
coagulation system often make for uncertain significance of single factor levels.
Thromboelastography provides a method for assessing clot formation, coagulation
processes, and fibrinolysis. It provides clinical information within 10 to 20 minutes
and is therefore used as a point-of-contact guide to appropriate perioperative man-
agement of coagulopathy in major hepatic resections.
The natural choice for correcting coagulopathy in liver disease is fresh frozen
plasma because it contains all the coagulation and inhibitory factors. However, its ef-
fects are relatively short lived and it has the disadvantages of a large volume load and
potential cross-infection concerns. Cryoprecipitate is a good source of fibrinogen and
tends to be administered for documented hypofibrinogenemia. Platelets transfused
during major resections often have only a transient effect, because they undergo
splenic sequestration. The antifibrinolytic agent, tranexamic acid has shown promise
in reducing transfusion requirement in liver resection and can be used in hepatic sur-
gery with anticipated high blood loss.75–77 However, a Cochrane review was less sup-
portive in their role during resection.78 Newer agents such as activated factor VII have
been used to good effect in liver failure with active hemorrhage,79 but a role in elective
liver resections remains uncertain.80
Other considerations for coagulopathy Because the liver is the site of citrate meta-
bolism, it is important to ensure adequate serum calcium levels during severe coagul-
opathy and where large volumes of citrated blood products are being transfused.
Because major liver resections are often prolonged, the infusion of large fluid volumes
and an “open” abdomen provides an efficient heat sink. Invasive temperature moni-
toring (esophageal or rectal) and scrupulous attention to active warming of the patient
and all infusions must be undertaken perioperatively. Even mild hypothermia can lead
to increased blood loss, particularly through impairment in platelet function. Labora-
tory tests of coagulation are performed at 37 C, and may remain normal requiring
adjustment where hypothermia exists.
134 Snowden & Prentis

POSTOPERATIVE CONSIDERATIONS

General postoperative complications of major abdominal surgery are also relevant to

HPB surgery. In addition, the immediate complications more specific to patients under-
going major hepatic resection include on going coagulopathy and active bleeding, onset
or exacerbation of liver failure with encephalopathy, renal impairment, and late biliary
leak. For this reason, early postoperative care (12–24 hours) after liver resection should
have the facility for the continuation of invasive hemodynamic monitoring and close
observation of renal function. In most UK hospitals, this often necessitates critical care.
Nevertheless, enhanced recovery programs developing as the accepted standard
for postoperative care in other areas of major surgery have been used in the context
of liver resection surgery and have been associated with significant reductions in hos-
pital length of stay and perioperative complications.81
Elements of the Enhanced Recovery program of specific relevance to HPB surgery
include the following.

Preoperative Carbohydrate Loading

No study has directly studied the use of carbohydrate loading in patients undergoing
liver resection. However, an enhanced recovery program in which carbohydrate
loading was used showed a reduction in both length of stay and complications.82

Surgical Drains
Surgical practice has traditionally placed a drain in the subphrenic space close to the
resection surface. The main proposed advantages are the prevention of subphrenic
fluid collection, early identification of postoperative bleeding83 and bile leak,83,84
and prevention of ascitic fluid accumulation. However, the evidence that surgical
drainage is conflicting. A Cochrane review of surgical drainage after liver resection sur-
gery85 found that bleeding and bile leakage that required emergency surgical or radio-
logic intervention was uncommon in the early postoperative period after hepatic
resection and that prophylactic drainage did not help in the identification or manage-
ment of these complications. Drainage did not influence mortality rates, and there was
an increase in both chest complications and postoperative wound infections. In
conclusion, there is no evidence to support routine drain use after liver resections.

Nasogastric Tubes/Oral Nutrition

Nasogastric tube placement and drainage of gastric contents have been routine in
liver resection surgery. However, their routine use has been questioned. A random-
ized, controlled trial of 200 patients86 concluded that nasogastric tube placement
was associated with increase risk of atelectasis and pulmonary complications. Naso-
gastric tube placement did reduce vomiting rates, but 20% of patients experienced
severe discomfort. Their routine use cannot be recommended in the majority of pa-
tients. Early oral nutrition after surgery has also been a goal for enhanced recovery
programs and has been shown to be achievable after liver resection. Early oral intake
allows for discontinuation of IV fluids and accelerated recovery. One study,87 even
though negative for its primary endpoint for the use of laxatives, showed that oral fluid
intake can be resumed on the day of surgery in 94% of patients and reintroduction of
diet was achieved in 37% on day 1 and in 78% by day 2.

Deep Venous Thrombosis Prophylaxis

Patients undergoing liver resection with prolonged surgery and with underlying meta-
static cancer are at risk of postoperative venous thromboembolism. Successful liver
 Anesthesia for Hepatobiliary Surgery 135

resection, with acceptable retained liver function, often leads to a procoagulant post-
operative state. Thromboelastogram monitoring also demonstrates a state of postop-
erative hypercoagulability after living donor hepatectomy.88 Reduction in liver function
leads to a decrease in both procoagulant and anticoagulant factors by up to 50%.89
Therefore, venous thromboembolism may occur even in the presence of elevated
standard measures of anticoagulation such as International Normalized Ratio and par-
tial thromboplastin time.90,91 In a retrospective review of 415 patients undergoing ma-
jor hepatectomy, administration of pharmacologic thromboprophylaxis lowered the
rate of venous thromboembolism but did not increase the rate of blood transfusion af-
ter hepatectomy.92 On balance, it is recommended that pharmacologic thrombopro-
phylaxis should be part of an enhanced recovery program unless there is an obvious
contraindication.

Analgesia
The risks and benefits of any mode of analgesia need to be considered for each indi-
vidual in deciding the best treatment of postoperative pain. Because this group of
patients is at risk of renal impairment and coagulation defects, nonsteroidal anti-
inflammatory agents should be avoided wherever possible. Opiates that are metabo-
lized in the liver and excreted renally have the potential disadvantage of accumulation
with cerebral depressant effects in a population with a tendency to encephalopathy.
Use of epidural techniques have been the preferred postoperative analgesic option,
given the proposed benefits on postoperative recovery after major surgery and use
of large surgical incisions during hepatic surgery. However, a major concern is the
associated prolongation of prothrombin time that may develop during surgery. It is
debatable whether this coagulopathy increases the risk of epidural hematoma, but it
often delays epidural catheter removal and increases administration of corrective
blood products.93 Several studies have suggested that intrathecal opiates are a suit-
able alternative to epidural analgesia and have a number of advantages, especially in
terms of embracing the enhanced recovery ethos.94 A recent prospective, observa-
tional study95 compared thoracic epidural with intrathecal morphine and fentanyl
patient-controlled analgesia. Although CVP and blood loss were lower in the epidural
group, in contrast, time to mobilization, fluid requirements, and length of stay were
lower in the intrathecal morphine plus fentanyl patient-controlled analgesia group.
Pain scores were not different in the first 5 postoperative days.

Postoperative Liver Dysfunction or Failure

In the event of acute liver failure arising after liver resection, attempts should be
made to support the patient to allow sufficient time for regeneration of the remaining
liver. The mainstay of this is ensuring optimal standards of intensive care manage-
ment, including airway control, adequate hydration, inotropic and renal support as
needed, control of coagulopathy and active bleeding and consideration of N-acetyl
cysteine (NAC) infusion. Beneficial effects have been seen in systemic and cerebral
hemodynamics in acute liver failure of other causes, an effect not related to stimula-
tion of liver regeneration or hepatoprotection, but initially assigned to improvements
in systemic oxygen delivery and oxygen extraction.96 A later paper97 refuted the ef-
fects of NAC on oxygen delivery and extraction in hepatic failure, suggesting instead
that the microcirculatory effects also seen when NAC is used in sepsis may be a
more important effect. A recent study,98 however, has shown that the use of NAC
does not reduce alanine aminotransferase levels, suggesting that it does not reduce
hepatocellular injury. There was also a higher level of post-hepatic liver failure.
Further studies are needed in patients at higher risk of major hepatic failure in those
136 Snowden & Prentis

undergoing more extensive resections with a background of significant preoperative

liver disease.

SUMMARY

HPB surgical outcome has improved with advancements in surgical technique,

training, and equipment. In addition, perioperative management, including improved
patient selection, preoperative venous embolization, and intraoperative maneuvers
to reduce blood loss, have played an important role in postoperative outcome. Devel-
oping enhanced recovery programs that include intrathecal opiate analgesia and
improved postoperative mobilization will undoubtedly lead to further improvements
in future outcomes.

REFERENCES

1. Van Thiel DH, Wright HI, Fagiuoli S, et al. Preoperative evaluation of a patient for
hepatic surgery. J Surg Oncol Suppl 1993;3:49–51.
2. Savage AP, Malt RA. Survival after hepatic resection for malignant tumours. Br J
Surg 1992;79(10):1095–101.
3. Franssen B, Jibara G, Tabrizian P, et al. Actual 10-year survival following hepatec-
tomy for hepatocellular carcinoma. HPB (Oxford) 2014;16(9):830–5.
4. Cummings LC, Payes JD, Cooper GS. Survival after hepatic resection in metasta-
tic colorectal cancer. Cancer 2007;109(4):718–26.
5. Dhir M, Lyden ER, Wang A, et al. Influence of margins on overall survival after he-
patic resection for colorectal metastasis: a meta-analysis. Ann Surg 2011;254(2):
234–42.
6. Schindl MJ, Redhead DN, Fearon KC, et al. The value of residual liver volume as
a predictor of hepatic dysfunction and infection after major liver resection. Gut
2005;54(2):289–96.
7. Mullin EJ, Metcalfe MS, Maddern GJ. How much liver resection is too much? Am
J Surg 2005;190(1):87–97.
8. Starzl TE, Putnam CW, Groth CG, et al. Alopecia, ascites, and incomplete regen-
eration after 85 to 90 per cent liver resection. Am J Surg 1975;129(5):587–90.
9. Kountouras J, Boura P, Lygidakis NJ. Liver regeneration after hepatectomy. Hep-
atogastroenterology 2001;48(38):556–62.
10. Gove CD, Hughes RD. Liver regeneration in relationship to acute liver failure. Gut
1991;(Suppl):S92–6.
11. Nagasue N. Liver resection for hepatocellular carcinoma: Indications, tech-
niques, complications, and prognostic factors. J Hepatobiliary Pancreat Surg
1998;5(1):7–13.
12. Farges O, Belghiti J, Kianmanesh R, et al. Portal vein embolization before right
hepatectomy: prospective clinical trial. Ann Surg 2003;237(2):208–17.
13. Ribero D, Abdalla EK, Madoff DC, et al. Portal vein embolization before major
hepatectomy and its effects on regeneration, resectability and outcome. Br J
Surg 2007;94(11):1386–94.
14. Abulkhir A, Limongelli P, Healey AJ, et al. Preoperative portal vein embolization
for major liver resection. Ann Surg 2008;247(1):49–57.
15. van Lienden KP, van den Esschert JW, de Graaf W, et al. Portal vein embolization
before liver resection: a systematic review. Cardiovasc Intervent Radiol 2013;
36(1):25–34.
16. Kawasaki S, Makuuchi M, Kakazu T, et al. Resection for multiple metastatic liver
tumors after portal embolization. Surgery 1994;115(6):674–7.
 Anesthesia for Hepatobiliary Surgery 137

17. Siperstein AE, Berber E, Ballem N, et al. Survival after radiofrequency ablation of
colorectal liver metastases. Ann Surg 2007;246(4):559–67.
18. Peng ZW, Liu FR, Ye S, et al. Radiofrequency ablation versus open hepatic resec-
tion for elderly patients (>65 years) with very early or early hepatocellular carci-
noma. Cancer 2013;119(21):3812–20.
19. Heniford BT, Arca MJ, Iannitti DA, et al. Laparoscopic cryoablation of hepatic me-
tastases. Semin Surg Oncol 1998;15(3):194–201.
20. Ravikumar TS, Kane R, Cady B, et al. 5-year study of cryosurgery in the treatment
of liver tumors. Arch Surg 1991;126(12):1520–3.
21. Pöpperl G, Helmberger T, Münzing W, et al. Selective internal radiation therapy
with SIR-spheresÒ in patients with nonresectable liver tumors. Cancer Biother
Radiopharm 2005;20(2):200–8.
22. Stubbs RS, Wickremesekera SK. Selective internal radiation therapy (SIRT): a
new modality for treating patients with colorectal liver metastases. HPB (Oxford)
2004;6(3):133–9.
23. Howard JH, Tzeng CW, Smith JK, et al. Radiofrequency ablation for unresectable
tumors of the liver. Am Surg 2008;74(7):594–600.
24. Welsh FK, Tilney HS, Tekkis PP, et al. Safe liver resection following chemotherapy
for colorectal metastases is a matter of timing. Br J Cancer 2007;96(7):1037–42.
25. Schiergens TS, Stielow C, Schreiber S, et al. Liver resection in the elderly: signif-
icance of comorbidities and blood loss. J Gastrointest Surg 2014;18(6):1161–70.
26. Mastoraki A, Tsakali A, Papanikolaou IS, et al. Outcome following major hepatic
resection in the elderly patients. Clin Res Hepatol Gastroenterol 2014;38:462–6.
http://dx.doi.org/10.1016/j.clinre.2014.01.009.
27. Taniai N, Yoshida H, Yoshioka M, et al. Surgical outcomes and prognostic factors
in elderly patients (75 years or older) with hepatocellular carcinoma who under-
went hepatectomy. J Nippon Med Sch 2013;80(6):426–32.
28. Snowden CP, Prentis J, Jacques B, et al. Cardiorespiratory fitness predicts mor-
tality and hospital length of stay after major elective surgery in older people. Ann
Surg 2013;257(6):999–1004.
29. Prentis JM, Snowden CP. Ageing and Hepatic Function: Chapter 9, p(64–70). In:
Dodds, Kumar, Veering, editors. Anaesthesia for the Elderly Patient. Oxford
(United Kingdom): Oxford University Press; 2014.
30. Parkin E, O’Reilly DA, Adam R, et al. The effect of hepatic steatosis on survival
following resection of colorectal liver metastases in patients without preoperative
chemotherapy. HPB (Oxford) 2013;15(6):463–72.
31. Wu CC, Ho WL, Yeh DC, et al. Hepatic resection of hepatocellular carcinoma in
cirrhotic livers: is it unjustified in impaired liver function? Surgery 1996;120(1):34–9.
32. Teh SH, Nagorney DM, Stevens SR, et al. Risk factors for mortality after surgery in
patients with cirrhosis. Gastroenterology 2007;132(4):1261–9.
33. Cucchetti A, Ercolani G, Vivarelli M, et al. Impact of model for end-stage liver dis-
ease (MELD) score on prognosis after hepatectomy for hepatocellular carcinoma
on cirrhosis. Liver Transpl 2006;12(6):966–71.
34. Schroeder RA, Marroquin CE, Bute BP, et al. Predictive indices of morbidity and
mortality after liver resection. Ann Surg 2006;243(3):373–9.
35. Melendez J. Extended hepatic resection: a 6-year retrospective study of risk fac-
tors for perioperative mortality. J Am Coll Surg 2001;192(1):47–53.
36. Kim DH, Kim SH, Kim KS, et al. Predictors of mortality in cirrhotic patients under-
going extrahepatic surgery: comparison of Child-Turcotte-Pugh and model for
end-stage liver disease-based indices. ANZ J Surg 2013. http://dx.doi.org/10.
1111/ans.12198.
138 Snowden & Prentis

37. Uslu A, Cayci M, Nart A, et al. Renal failure in obstructive jaundice. Hepatogas-
troenterology 2005;52(61):52–4.
38. Betjes MG, Bajema I. The pathology of jaundice-related renal insufficiency: chole-
mic nephrosis revisited. J Nephrol 2006;19(2):229–33.
39. Padillo FJ, Cruz A, Briceño J, et al. Multivariate analysis of factors associated with renal
dysfunction in patients with obstructive jaundice. Br J Surg 2005;92(11):1388–92.
40. Nimura Y. Preoperative biliary drainage before resection for cholangiocarcinoma
(Pro). HPB (Oxford) 2008;10(2):130–3.
41. Son JH, Kim J, Lee SH, et al. The optimal duration of preoperative biliary drainage
for periampullary tumors that cause severe obstructive jaundice. Am J Surg 2013;
206(1):40–6.
42. Jarnagin WR, Gonen M, Fong Y, et al. Improvement in perioperative outcome af-
ter hepatic resection: analysis of 1,803 consecutive cases over the past decade.
Ann Surg 2002;236(4):397–406.
43. Otsubo T. Control of the inflow and outflow system during liver resection.
J Hepatobiliary Pancreat Sci 2012;19(1):15–8.
44. Dixon E, Vollmer CM, Bathe OF, et al. Vascular occlusion to decrease blood loss
during hepatic resection. Am J Surg 2005;190(1):75–86.
45. Bismuth H, Dennison AR. Segmental liver resection. Adv Surg 1993;26:189–208.
46. Delva E, Camus Y, Nordlinger B, et al. Vascular occlusions for liver resections.
Operative management and tolerance to hepatic ischemia: 142 cases. Ann
Surg 1989;209(2):211–8.
47. Nagasue N, Uchida M, Kubota H, et al. Cirrhotic livers can tolerate 30 minutes
ischaemia at normal environmental temperature. Eur J Surg 1995;161(3):181–6.
48. Pringle JH. V. Notes on the arrest of hepatic hemorrhage due to trauma. Ann Surg
1908;48(4):541.
49. Lentschener C, Ozier Y. Anaesthesia for elective liver resection: some points
should be revisited. Eur J Anaesthesiol 2002;19(11):780–8.
50. Smyrniotis VE, Kostopanagiotou GG, Contis JC, et al. Selective hepatic vascular
exclusion versus Pringle maneuver in major liver resections: prospective study.
World J Surg 2003;27(7):765–9.
51. Xiaobin F, Zipei L, Shuguo Z, et al. The Pringle manoeuvre should be avoided in
hepatectomy for cancer patients due to its side effects on tumor recurrence and
worse prognosis. Med Hypotheses 2009;72(4):398–401.
52. Petrowsky H, McCormack L, Trujillo M, et al. A prospective, randomized,
controlled trial comparing intermittent portal triad clamping versus ischemic pre-
conditioning with continuous clamping for major liver resection. Ann Surg 2006;
244(6):921–8.
53. Gomez D, Homer-Vanniasinkam S, Graham AM, et al. Role of ischaemic precon-
ditioning in liver regeneration following major liver resection and transplantation.
World J Gastroenterol 2007;13(5):657–70.
54. van der Bilt JD, Livestro DP, Borren A, et al. European survey on the application of
vascular clamping in liver surgery. Dig Surg 2007;24(6):423–35. http://dx.doi.org/
10.1159/000108325.
55. Wang HQ, Yang JY, Yan LN. Hemihepatic versus total hepatic inflow occlusion
during hepatectomy: a systematic review and meta-analysis. World J Gastroen-
terol 2011;17(26):3158.
56. Gurusamy KS, Sheth H, Kumar Y, et al. Methods of vascular occlusion for elective
liver resections. Cochrane Database Syst Rev 2009;(1):CD007632.
57. Edwards MJ, Bentley FR. Major hepatic resection under total vascular exclusion
with extracorporeal venovenous bypass. Am Surg 1994;60(4):231–3.
 Anesthesia for Hepatobiliary Surgery 139

58. Emond JC, Kelley SD, Heffron TG, et al. Surgical and anesthetic management of
patients undergoing major hepatectomy using total vascular exclusion. Liver
Transpl Surg 1996;2(2):91–8.
59. Aloia TA, Zorzi D, Abdalla EK, et al. Two-surgeon technique for hepatic paren-
chymal transection of the noncirrhotic liver using saline-linked cautery and ultra-
sonic dissection. Ann Surg 2005;242(2):172–7.
60. Fasulo F, Giori A, Fissi S, et al. Cavitron ultrasonic surgical aspirator (CUSA) in
liver resection. Int Surg 1992;77(1):64–6.
61. Koo BN, Kil HK, Choi JS, et al. Hepatic resection by the Cavitron ultrasonic sur-
gical aspirator increases the incidence and severity of venous air embolism.
Anesth Analg 2005;101(4):966–70.
62. Sugo H, Mikami Y, Matsumoto F, et al. Hepatic resection using the harmonic
scalpel. Surg Today 2000;30(10):959–62.
63. Aldrighetti L, Pulitanò C, Arru M, et al. “Technological” approach versus clamp
crushing technique for hepatic parenchymal transection: a comparative study.
J Gastrointest Surg 2006;10(7):974–9.
64. Kaneko H, Otsuka Y, Takagi S, et al. Hepatic resection using stapling devices. Am
J Surg 2004;187(2):280–4.
65. de Boer MT, Klaase JM, Verhoef C, et al. Fibrin sealant for prevention of resection
surface-related complications after liver resection: a randomized controlled trial.
Ann Surg 2012;256(2):229–34.
66. Ding H, Yuan JQ, Zhou JH, et al. Systematic review and meta-analysis of appli-
cation of fibrin sealant after liver resection. Curr Med Res Opin 2013;29(4):
387–94.
67. Chen H, Merchant NB, Didolkar MS. Hepatic resection using intermittent vascular
inflow occlusion and low central venous pressure anesthesia improves morbidity
and mortality. J Gastrointest Surg 2000;4(2):162–7.
68. Jones RM, Moulton CE, Hardy KJ. Central venous pressure and its effect on
blood loss during liver resection. Br J Surg 1998;85(8):1058–60.
69. Li Z, Sun YM, Wu FX, et al. Controlled low central venous pressure reduces blood
loss and transfusion requirements in hepatectomy. World J Gastroenterol 2014;
20(1):303–9.
70. Gurusamy KS, Li J, Sharma D, et al. Cardiopulmonary interventions to decrease
blood loss and blood transfusion requirements for liver resection. Cochrane Data-
base Syst Rev 2009;(4):CD007338.
71. Sand L, Rizell M, Houltz E, et al. Effect of patient position and PEEP on hepatic,
portal and central venous pressures during liver resection. Acta Anaesthesiol
Scand 2011;55(9):1106–12.
72. Dunki-Jacobs EM, Philips P, Scoggins CR, et al. Stroke volume variation in hepat-
ic resection: a replacement for standard central venous pressure monitoring. Ann
Surg Oncol 2014;21(2):473–8.
73. Hatano Y, Murakawa M, Segawa H, et al. Venous air embolism during hepatic
resection. Anesthesiology 1990;73(6):1282–5.
74. Kang Y. Coagulopathies in hepatic disease. Liver Transpl 2000;6(4 Suppl 1):
S72–5.
75. Boylan JF, Klinck JR, Sandler AN, et al. Tranexamic acid reduces blood loss,
transfusion requirements, and coagulation factor use in primary orthotopic liver
transplantation. Anesthesiology 1996;85(5):1043–8.
76. Wu CC, Ho WM, Cheng SB, et al. Perioperative parenteral tranexamic acid in liver
tumor resection: a prospective randomized trial toward a “blood transfusion-”free
hepatectomy. Ann Surg 2006;243(2):173–80.
140 Snowden & Prentis

77. Ortmann E, Besser MW, Klein AA. Antifibrinolytic agents in current anaesthetic
practice. Br J Anaesth 2013;111(4):549–63.
78. Gurusamy KS, Li J, Sharma D, et al. Pharmacological interventions to decrease
blood loss and blood transfusion requirements for liver resection. Cochrane Data-
base Syst Rev 2009;(4):CD008085.
79. White B, McHale J, Ravi N, et al. Successful use of recombinant FVIIa (Novos-
even) in the management of intractable post-surgical intra-abdominal haemor-
rhage. Br J Haematol 1999;107(3):677–8.
80. Chavez-Tapia NC, Alfaro-Lara R, Tellez-Avila F, et al. Prophylactic activated re-
combinant factor VII in liver resection and liver transplantation: systematic review
and meta-analysis. PLoS One 2011;6(7):e22581.
81. Schultz NA, Larsen PN, Klarskov B, et al. Evaluation of a fast-track programme for
patients undergoing liver resection. Br J Surg 2013;100(1):138–43.
82. Jones C, Kelliher L, Dickinson M, et al. Randomized clinical trial on enhanced re-
covery versus standard care following open liver resection. Br J Surg 2013;
100(8):1015–24.
83. Bona S, Gavelli A, Huguet C. The role of abdominal drainage after major hepatic
resection. Am J Surg 1994;167(6):593–5.
84. Sarr MG, Parikh KJ, Minken SL, et al. Closed-suction versus Penrose drainage
after cholecystectomy. A prospective, randomized evaluation. Am J Surg 1987;
153(4):394–8.
85. Gurusamy KS, Samraj K, Davidson BR. Routine abdominal drainage for uncom-
plicated liver resection. Cochrane Database Syst Rev 2007;(3):CD006232.
86. Pessaux P, Regimbeau JM, Dondéro F, et al. Randomized clinical trial evaluating
the need for routine nasogastric decompression after elective hepatic resection.
Br J Surg 2007;94(3):297–303.
87. Hendry PO, van Dam RM, Bukkems SF, et al. Randomized clinical trial of laxatives
and oral nutritional supplements within an enhanced recovery after surgery pro-
tocol following liver resection. Br J Surg 2010;97(8):1198–206.
88. Cerutti E, Stratta C, Romagnoli R, et al. Thromboelastogram monitoring in the
perioperative period of hepatectomy for adult living liver donation. Liver Transpl
2004;10(2):289–94.
89. Bezeaud A, Denninger MH, Dondero F, et al. Hypercoagulability after partial liver
resection. Thromb Haemost 2007;98(6):1252–6.
90. Senzolo M, Sartori MT, Lisman T. Should we give thromboprophylaxis to patients
with liver cirrhosis and coagulopathy? HPB (Oxford) 2009;11(6):459–64.
91. Lesmana CR, Inggriani S, Cahyadinata L, et al. Deep vein thrombosis in pa-
tients with advanced liver cirrhosis: a rare condition? Hepatol Int 2010;4(1):
433–8.
92. Reddy SK, Turley RS, Barbas AS, et al. Post-operative pharmacologic throm-
boprophylaxis after major hepatectomy: does peripheral venous thromboem-
bolism prevention outweigh bleeding risks? J Gastrointest Surg 2011;15(9):
1602–10.
93. Tzimas P, Prout J, Papadopoulos G, et al. Epidural anaesthesia and analgesia for
liver resection. Anaesthesia 2013;68(6):628–35.
94. Sakowska M, Docherty E, Linscott D, et al. A change in practice from epidural to
intrathecal morphine analgesia for hepato-pancreato-biliary surgery. World J
Surg 2009;33(9):1802–8.
95. Kasivisvanathan R, Abbassi-Ghadi N, Prout J, et al. A prospective cohort study of
intrathecal versus epidural analgesia for patients undergoing hepatic resection.
HPB (Oxford) 2014;16(8):768–75.
 Anesthesia for Hepatobiliary Surgery 141

96. Harrison PM, Wendon JA, Gimson AE, et al. Improvement by acetylcysteine of
hemodynamics and oxygen transport in fulminant hepatic failure. N Engl J Med
1991;324(26):1852–7.
97. Walsh TS, Hopton P, Philips BJ, et al. The effect of N-acetylcysteine on oxygen
transport and uptake in patients with fulminant hepatic failure. Hepatology 1998;
27(5):1332–40.
98. Robinson SM, Saif R, Sen G, et al. N-acetylcysteine administration does not
improve patient outcome after liver resection. HPB (Oxford) 2013;15(6):457–62.