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Br. J. Anaesth.-2013-Kiamanesh-i50-61 PDF
Br. J. Anaesth.-2013-Kiamanesh-i50-61 PDF
doi:10.1093/bja/aet378
The liver metabolizes drugs, food, and toxins; synthesizes procoagulants and anticoagulants; and regulates temperature,
glucose, and metabolism. When patients with liver disease
need surgery, anaesthesiologists face several perioperative
challenges. Patients with liver disease have physiological perturbations that range from mild hyperbilirubinemia of no clinical consequence to severe coagulopathy and metabolic
disarray (Fig. 1). This article reviews the current body of knowledge of perioperative assessment, monitoring, and management of hepatic disease in patients who will undergo surgery.
(82%), and Class C patients (82%) who undergo abdominal surgeries.12 13 A newer study reports lower mortality rates after
abdominal operations: Class A2%; Class B12%; Class
C12%.14 Improvements in surgical technique, anaesthetic
management, and perioperative care might explain the difference in these findings.
The model for end-stage liver disease (MELD) score is a validated and prognostic tool that estimates disease severity and
survival in patients with liver disease. The MELD score is objective, ranges from 6 to 40 points, and is calculated from the
serum bilirubin, serum creatinine, INR, and aetiology of liver
disease.15 The MELD score has been validated across a
number of liver diseases (alcoholic hepatitis and variceal
bleeding)16 and surgeries (abdominal, orthopaedic, and cardiovascular).5 8 17 19 In patients who have undergone abdominal surgery, an elevated MELD score was a better predictor of
poor perioperative outcome than CTP classification.17 Patients
with MELD scores .15 should avoid elective surgery.20 In
2002, the United Network for Organ Sharing adopted the
MELD score as a method of allocation of organs to estimate survival. The incorporation of hyponatraemia, an important prognostic factor in patients with cirrhosis, into the MELD score
might improve risk stratification among patients awaiting
liver transplantation.21
The type of surgical procedure influences perioperative outcomes in patients with hepatic disease. During abdominal
surgery, reflexive systemic hypotension from visceral traction
and blood loss can reduce hepatic arterial blood flow.22 23
Patients with extensive liver disease who undergo abdominal
surgery have a mortality rate of 30%.12 24 Mortality rates in
cirrhotic patients who undergo open cholecystectomy are
2350%; cardiac surgery, 16 31%; laparotomy for trauma,
45%; and oesophageal surgery, 17 26%.25 33 Patients with
& The Author [2013]. Published by Oxford University Press on behalf of the British Journal of Anaesthesia. All rights reserved.
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Renal/electrolytes/glucose
Acute kidney injury
Hepatorenal syndrome
Hyponatraemia
Hypoglycaemia
Insulin resistance
Hepatic disease
Cardiovascular
Vasodilated state
Hyperdynamic cardiac function
Cirrhotic cardiomyopathy
Drug-induced hypertension
Portopulmonary hypertension
Neurologic
Hepatic encephalopathy
Cerebral oedema
Intracranial hypertension
Pulmonary
Aspiration risk
Hepatopulmonary syndrome
Compression atelectasis
Pleural effusions/hepatic hydrothorax
Acute respiratory distress syndrome
Male gender
Age .70 yr
Preoperative infection
Cirrhosis other than primary biliary cirrhosis
Elevated creatinine
Chronic obstructive pulmonary disease
Intraoperative hypotension
Upper gastrointestinal bleeding
Ascites
High-risk surgeries
Abdominal surgery
Open cholecystectomy
Cardiothoracic surgery
Trauma laparotomy
Oesophageal surgery
Emergency surgery
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Haematologic
Bleeding and thrombosis
Unreliable INR
Decreased factor synthesis
Thrombocytopenia and platelet dysfunction
Dysfibrinogenaemia
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Kiamanesh et al.
Cardiovascular response
The cardiovascular system of patients with end-stage liver
disease mimics the hyperdynamic circulatory changes in
patients with sepsis. Tachycardia, elevated cardiac output, low
arterial pressure, and low systemic vascular resistance are characteristic.81 Enhanced endogenous production or diminished
hepatic clearance of vasodilating substances (nitric oxide,
carbon monoxide, and endogenous cannabinoids, tumour necrosis factor-a, adrenomedullin, and hydrogen sulfide) and the
inflammatory response to bacterial translocation cause
splanchnic arterial vasodilation (Fig. 2).81 82 These changes
have been reversed with liver transplantation.81 83 In response
to splanchnic vasodilation and decreased systemic vascular resistance, the body retains sodium and water, which increases
plasma volume. An increase in cardiac output and heart rate
follow.81 84 Venous capacitance increases from formation of portosystemic shunts with portal hypertension to contribute to a
hyperdynamic circulation.
Management of vasodilatory hypotension focuses on
expanding the intravascular volume, administering a vasoconstricting agent such as norepinephrine or vasopressin, and determining the underlying cause of vasodilation to target.
Aggressive fluid resuscitation without assessment of fluid responsiveness should be avoided because excessive i.v. fluid administration to a non-fluid-responsive patient can increase
cardiac filling pressures, which can cause hepatic congestion,
pulmonary oedema, and resulting respiratory failure.
Systemic conditions such as haemochromatosis (ventricular
hypertrophy with increased end-diastolic and end-systolic
volumes), amyloidosis (restrictive cardiomyopathy), Wilsons
disease (supraventricular extrasytolic beats), and alcoholism
(systolic and diastolic dysfunction) can affect liver and cardiac
function.85 During the perioperative period, the circulatory
system can be challenged with shunt insertion or greater afterload from surgical stress, unmasking underlying cirrhotic cardiomyopathy. Echocardiography shows impaired myocardial
function similar to that found in sepsis.86 This condition is also
characterized by QT prolongation and systolic and diastolic dysfunction.87 Reduced b-adrenoceptor function might explain
these findings.85 Cirrhotic cardiomyopathy is often reversible
and requires inotropic and diuretic support to prevent elevation
of central venous pressure and hepatic congestion.
Patients with portal hypertension can develop portopulmonary hypertension (PPHTN) and right ventricular dysfunction.
While the exact pathogenesis of PPHTN remains unclear, histopathological findings are indistinguishable from those observed
in idiopathic pulmonary artery hypertension (medial hypertrophy, concentric intimal proliferation, plexiform lesions, in
situ thrombosis, and fibrotic changes).88 89 A hyperdynamic circulation might increase shear stress on the pulmonary vasculature to cause remodelling and pulmonary hypertension.88 90 The
mean pulmonary artery pressure .25 mm Hg at rest and pulmonary vascular resistance .240 dyn s cm25 define PPHTN.
PPHTN has been reported in 69% of patients with advanced
liver disease.91 92 In a retrospective study of patients who
underwent orthotopic liver transplantation (OLT), mortality
was 50% in patients with the mean pulmonary artery pressures
between 35 and 50 mm Hg and 100% in patients with pressures
.50 mm Hg.93 Calcium channel blockers, which can be used in
patients with pulmonary arterial hypertension, are not recommended in PPHTN because they produce mesenteric vasodilatation and worsen portal hypertension. b-Blocker therapy, which
is often used in patients with portal hypertension to reduce
the risk of variceal bleeding, is contraindicated in patients
with PPHTN because its negative inotropic effect decreases
exercise tolerance.88 90 Finally, while liver transplantation is a
tempting option to reduce PPHTN, moderate or severe uncontrolled PPHTN is associated with significant mortality risk and
is a contraindication to OLT.93 95 Intraoperative management
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Kiamanesh et al.
Liver dysfunction
Portal hypertension
Bacterial translocation and inflammation
is targeted to prevent increases in pulmonary vascular resistance by controlling hypoxia, hypercarbia, acidosis, pain, and
hypothermia.
Because of these cardiovascular changes, invasive monitors
usually are used during the perioperative period. Beat-to-beat
arterial pressure is monitored and blood is sampled frequently
via a radial artery catheter. Pulse pressure variation, calculated
from the invasive arterial tracing, assesses fluid responsiveness. Peripheral arterial pressure measurements can be unreliable in patients with severe vasoconstriction or vasodilation.
Central venous access is established to measure right atrial
pressure and to administer drugs. Monitoring central venous
pressure does not reliably measure blood volume or change
in blood volume.96 Echocardiography assesses ventricular
filling, contractility, and function. Myocardial ischaemia, pulmonary embolism, pleural effusion, and inadequate inferior
vena cava reconstruction can be observed with transoesophageal echocardiography (TOE). The risk of rupture of oesophageal varices with TOE is rare.97 98 Bladder pressures should
be measured if intra-abdominal hypertension from ascites is
suspected.
Pulmonary response
Up to 70% of patients with end-stage liver disease complain of
dyspnoea.99 100 Potential causes of preoperative hypoxaemia
and respiratory failure in patients with cirrhosis include atelectasis from the compressive effects of ascites, hepatic
hydrothorax, hepatopulmonary syndrome (HPS), underlying
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damaged livercan cause IPVD. IPVD causes hypoxaemiaviaventilation and perfusion mismatching, intrapulmonary shunt
physiology, and diffusion limitation.99 103 Patients with HPS
often complain of dyspnoea and fatigue; they can have clubbing
and spider angiomata. They may experience platypnoea (dyspnoea in the upright position relieved by recumbency) or have
orthodeoxia (arterial oxyhaemoglobin desaturation in the
upright position). Preferential perfusion of IPVDs with the
patient upright might cause these clinical manifestations.
Contrast-enhanced echocardiography or perfusion lung scanning with technetium-99m-labelled macroaggregate albumin
detects intrapulmonary shunting suggestive of IPVD.102 103
Resolution of this syndrome after transplant has been reported.
Medical therapy for HPS has, to date, been relatively ineffective.
Currently, the only known treatment option for patients with HPS
is liver transplantation.104 106
renal function is impaired rapidly and progressively with a doubling of the initial serum creatinine to .2.5 mg dl21 or a 50% reduction in the 24 h creatinine clearance to ,20 ml min21 in ,2
weeks. Patients with type II HRS have impaired renal function
and a serum creatinine .1.5 mg dl21 and do not meet the criteria for type I HRS.107 Compared with patients diagnosed with
prerenal failure, patients with HRS lack a renal response to a
1.5 litre volume challenge. Distinguishing between HRS and
acute tubular necrosis is difficult. Fractional excretion of
sodium ,1% suggests tubular function and favours a diagnosis
of HRS. The presence of renal tubular epithelial cells in urinary
sediment favours a diagnosis of acute tubular necrosis.109 112
Administration of terlipressin, a vasopressin analogue, along
with i.v. albumin has been shown to have some benefit in
patients with type 1 HRS.114 115 Medical management of HRS
is marginally effective, but liver transplantation usually reverses
HRS.116 117
Hypervolaemic hyponatraemia from accumulated secretion
of anti-diuretic hormone acts on vasopressin-2 receptors of
the renal tubular collecting duct to impair excretion of solutefree water.118 When extracellular volume expands, ascites and
oedema can result. In patients with hypovolaemic hyponatraemia via loss of extracellular fluid from the kidneys (overdiuresis)
or gastrointestinal tract, ascites or oedema is rare. These
patients can have prerenal failure from low circulating volume
or hepatic encephalopathy from rapid reduction in serum
osmolality.109 118 Distinguishing between hypervolaemic and
hypovolaemic hyponatremia guides treatment. Hypervolaemic
hyponatraemia is managed with fluid restriction (11.5 litre
day21) and withholding of diuretics. Vaptans, medications
that block the V2 receptor, increase solute-free water excretion
dose-dependently and might preclude water restriction so that
diuretics can be continued.119 Patients with hypovolaemic hyponatraemia are not given diuretics; instead, saline is administered
to increase plasma volume.118
Patients with preoperative hyponatraemia are at risk for
central pontine myelinolysis (CPM) perioperatively. CPM is a
neurological condition characterized by symmetric noninflammatory demyelinating lesions in the basis pontis. The aetiology of CPM is uncertain, but osmotic stress on central nervous
system cells has been suggested, and CPM correlates with rapid
correction of hyponatraemia.118 Rapid changes in concentration
of serum sodium cannot be predicted and a safe rate of correction of hyponatraemia has not been definitively established;
some experts recommend sodium correction at a rate ,12 mEq
litre21 day21.120 122 Preoperative correction of hyponatraemia
can prevent a rapid increase in serum sodium levels intraoperatively and after operation. Sodium bicarbonate should be administered cautiously because it has a high concentration of
sodium.
Calcineurin inhibitors, loop diuretics, and significant blood
loss can worsen hypomagnesaemia. Total serum calcium is
often low because patients commonly have low serum
albumin with reduced calcium binding. Failure to clear citrate
(metabolized by the liver) after the administration of a significant volume of packed red blood cells, malnutrition, and
vitamin D deficiency can lead to perioperative hypocalcaemia.
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Disorders of glucose metabolism are observed in patients
with chronic liver disease and cirrhosis.123 124 Multiple factors
affect glucose levels, including the inflammatory response to
surgery, steroid administration, hepatic dysfunction, altered
glycogen stores, and insulin resistance in liver failure. Episodes
of hypoglycaemia are observed in patients with end-stage liver
disease.
Haematological response
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Neurological response
Patients with liver disease can have encephalopathy before operation or after operation. Brain dysfunction manifests in acute
or chronic liver failure or after a spontaneous or surgical portosystemic shunt.151 152 Hepatic encephalopathy is a neuropsychiatric complication of acute and chronic liver disease
with features that range from mild confusion to cerebral
oedema with intracranial hypertension.101 152 Patients have
disturbances in consciousness, cognitive abilities, behaviour,
fine motor skills, concentration, reaction time, memory,
and/or electroencephalogram.152 154 The pathogenesis of
hepatic encephalopathy is not understood, but most theories
implicate elevated levels of ammonia, a gut-derived neurotoxin, which is shunted to the systemic circulation from the
portal system. Bacteria in the intestinal tract produce
ammonia, which crosses the blood brain barrier into
Kiamanesh et al.
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Conclusions
Patients with hepatic disease are at high risk for poor perioperative outcomes. Assessment of the severity of liver dysfunction
and consideration of type of surgery stratifies risk and delays
elective surgery in patients with significant hepatic disease
(CTP Class C cirrhosis). Managing surgical patients with hepatic
disease considers anaesthetic dose adjustment and monitoring
the multisystem organ responses to liver dysfunction.
Authors contributions
All authors participated in literature search, writing of first
draft, editing, and final approval.
Acknowledgement
The authors would like to thank Sally Kozlik for her invaluable
editorial assistance.
Declaration of interest
None declared.
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