Anaesthesia in liver disease

patient
Baharulhakim Said b Daliman
Department of Anaesthesiology & Intensive
Care
Hospital Kuala Terengganu

www.anaesthesia.co.in

anaesthesia.co.in@gmail.com

Objectives

It is an important topic?
Physiology
Pharmacology ~ Phase I & II metabolism
Perioperative Management
Discussion
Latest update

 The literature contains several good reviews on the

perioperative management of patients with liver disease,
and much of the research is based on retrospective
analyses (Conn, 1991; Patel, 1999; Friedman, 1987;
Friedman, 1999; Gholson, 1990).
Approximately 1 of every 700 patients admitted for elective
surgery has abnormal liver chemistry test results (Conn,
1991).
1991
Up to 10% of patients with end-stage liver disease may
have surgery during the last 2 years of their lives
(Jackson, 1968).

HKT experiencecholecystectomy

Year

Total no. of
patient

Laparoscopically

2001

46

2002

45

2003
(till October)

26

General
The largest organ in the body is the liver
Involved with almost all of the biochemical
pathways that allow growth, fight disease, supply
nutrients, provide energy, and aid reproduction
Dual blood supply: portal-venous (75%) and
hepatic-arterial (25%).
Surgery and anesthesia impact hepatic function
primarily due to their impact on hepatic blood flow
and not primarily as a result of the medications or
anesthetic technique utilized

Physiology
Primarily made up of hepatocytes (80% of the
cells in the liver).
Complex functions of the liver which include:
metabolism of carbohydrates
metabolism of fats
protein synthesis and metabolism
drug metabolism and the synthesis and
excretion of bilirubin.

Physiology ~ carbohydrate
metabolism
Main role ~ storage of glycogen. Normally, about
75 grams of glycogen is found in the liver
Depleted by 24-48 hours of starvation
Poor nutrition or pre-existing liver disease may
lower glycogen stores ~ prone to hypoglycemia

Physiology ~ fat & protein

metabolism
Beta oxidation of fatty acids and the formation of
lipoproteins.
Synthesis of plasma proteins ~ All proteins,
except gamma globulins and antihemophiliac
factor
Normally, 10-15 grams of albumin are produced
daily (3.5-5.5 g/dl)

Important facts
albumin can be decreased with liver disease

colloid osmotic pressure will be reduced

+
fewer binding sites for drugs and the unbound,
active portion of protein-bound drugs will be
increased example : Thiopental.

Important facts
Increased drug sensitivity is usually not clinically
relevant until the albumin drops below 2.5 g/dl
Acute liver dysfunction is unlikely to be associated
with low levels of albumin since the elimination
half-life of albumin is 14-21 days

Physiology
Clotting factors V, VII, IX, X,
prothrombin and fibrinogen are
all dependent on the liver for
synthesis ~ many of the factors
require only 20-30% of normal
levels to stop bleeding,
significant impairment of liver
function must occur before
problems begin.

Important facts:
Plasma half-lives of clotting
factors are measured in
hours. Therefore, acute liver
dysfunction can lead to
coagulopathies.
Both severe parenchymal
disease and biliary disease
may lead to coagulopathy the former due to impaired
synthesis and the second by
decreased vitamin K
absorption due to the
absence of bile salts
secondary to biliary
obstruction.

Physiology ~ drug metabolism

Microsomal enzymes convert lipid-soluble drugs to more
water-soluble and less active products.
Elimination is dependent on hepatic blood flow and the
microsomal enzyme actvity.
Drugs with high hepatic extraction ratios depend more on
blood flow as their limiting factor whereas drugs with lower
extraction ratios depend on the enzyme activity and
protein binding.

Physiology ~ drug metablism

Divided into 2 phase:
1. Phase I metabolism
Oxidation
Reduction / demethylation

2. Phase II metabolism
Conjugation

Physiology ~ drug metabolism

Factor affecting drug metabolism:
microsomal enzyme system
route of administration
liver blood flow
competitive inhibition

Physiology ~ drug metabolism

Pharmacokinetic changes cause by liver disease:
Metabolising capacity is reduced ~ liver cells sick
@ functioning normally but reduced in number
Liver cell that metabolise drugs are bypassed ~
portal-systemic shunts in cirrhosis
Liver disease cause hypoproteinaemia; drug
binding capacity , more unbound &
pharmacologically active drug may circulate

Physiology ~ drug metabolism

Pharmacodynamic changes occur because:
Cellular responses to drugs may alter. CNS
sensitivity to opioids & sedatives is increased;
effect of oral anticoagulants because synthesis
of clotting factors is impaired
Fluid & electrolyte imbalanced; Na retention may
more readily induced by NSAIDs / corticosteroids;
ascites & oedema may be more resistant to
diuretics

Important facts
Chronic liver disease can lead to decreased
metabolism due to decreased number of enzymes
or to decreased blood flow (or obviously a
combination of both).
Cirrhosis may actually be associated with
increased drug metabolism due to upregulation of
enzyme activity (due to decreased number of
hepatocytes exposed to drugs for metabolism).

Pre Operative ~ Sx
Classic symptoms are:
Poor appetite (anorexia)- a common symptom
Weight loss- poor appetite leads to loss of weight. Improper
metabolism of fat, carbohydrates, and proteins complicates the
situation.
Polyuria/polydipsia (PU/PD)- excess urinating and excess drinking
of water. This can occur in several other important diseases; kidney
disease, Cushing's disease, pyometra, and diabetes mellitus (sugar
diabetes).
Lethargy- Poor appetite and disruption in normal physiologic
processes leads to this symptom. Anemia adds to this lethargy, along
with ascites due to the discomfort it causes.

Pre Operative ~ Sx
Anemia- Improper nutrition from a poor appetite, along with disease
in the hepatocytes will cause this.
Light colored stool- If the biliary tree is prevented from secreting
normal bile pigments into the intestine the stool will lack pigmentation
and appear lighter in color.
Bleeding disorders- The normal clotting system is impaired since it
depends on a healthy liver.
Distended abdomen due to ascites or hepatomegaly. If the
distention is severe enough breathing might be labored from pain or
the pressure on the diaphragm.

Pre Operative ~ Sx
Vomiting (emesis) nausea, or diarrhea.
diarrhea Sometimes blood is present
in the vomitus (hematemesis), especially if a gastric ulcer is present.
The ulcer comes from a complex interaction of histamine, nitrogen,
bile acids, Gastrin, portal hypertension, and altered mucous
membrane lining the inside of the stomach.
Pain due to distention of a diseased liver.
Orange colored urine or mucous membranes due to jaundice.
jaundice
Behavioral changes- circling, head tilt, heap pressing, and seizures,
particularly right after a meal.

Diagnosis
A thorough approach is needed for a correct
diagnosis of any liver problem
Take full history
Do thorough physical examination
Relevant laboratory investigation eg. Complete
blood count, biochemistry panel, liver function
test, coagulation profile, ascites fluid analysis,
urinalysis, ultrasound

Clinical
Aberrations of physiology in chronic liver disease:
Increased cardiac output
Decreased systemic vascular resistance
Hepatopulmonary syndrome
Tissue hypoperfusion resulting from shunting
Pulmonary hypertension
Ascites or hepatic hydrothorax causing restrictive disease

Pre OP management
Electrolyte replacement or management of
hyperkalemia resulting from potassium-sparing
diuretics (eg, spironolactone) - Provide anemia
correction,
correction assess for ongoing gastrointestinal
blood resulting from portal gastropathy or varices,
and hydrate as needed,
needed avoiding excess sodium
load in patients with cirrhosis.

Pre OP management
Management of encephalopathy - briefly,
administer lactulose, restrict protein without
compromising nutrition, and avoid use of
sedatives that may precipitate the process

Pre OP management
Management of coagulopathy - Administer fresh
frozen plasma to correct the prothrombin time to
within 3 seconds of normal. Also, provide vitamin
K (eg, 10 mg IM), cryoprecipitate, deamino-8-Darginine vasopressin (eg, 0.3 mcg/kg IV), and
platelet transfusion (if platelet count mL) (Patel,
1999).

Childs Classification of liver disease

Group

Serum bilirubin
(mg/dl)

< 2.0

2.0 3.0

> 3.0

Serum
albumin (g/dl)

> 3.5

3.0 3.5

< 3.0

Ascites

None

Easily
controlled

Poorly
controlled

Encephalopathy

None

Minimal

Advanced

Nutrition
(PT)

Excellent
(1 4 sec)

Good
(5 6 sec)

Poor
(> 6 sec)

Mortality rate

25%

10 %

50 %

Intra operative factors

Effect of anaesthesia
Effect of surgery

Effect of anaesthesia
Most inhalation agents decrease hepatic blood flow
Fatal hepatic necrosis resulting from halothane is rare (1
case in 35,000), but severe liver dysfunction may occur in
1 case in 6000
Isoflurane is a safer choice because the effect on hepatic
blood flow and oxygenation is much less than that of
halothane. In fact, isoflurane increases hepatic arterial
blood flow.

Effect of anaesthesia
Nitrous oxide is not hepatotoxic
Hypotension resulting in "shock liver injury" is possible
Delayed clearance of drugs such as midazolam, fentanyl,
and morphine
Hypercarbia causes decreased portal blood flow and must
be avoided
# clinical pearl is to decrease the drug dosage by half and
modify as needed (Conn, 1991).

Effect of surgery
Splanchnic traction and exploratory laparotomy
can reduce blood flow to the intestines and the
liver
Upper abdominal surgery is associated with the
greatest reduction in hepatic blood flow
Elevation of liver chemistry tests is more likely to
occur after biliary tract procedures than after
nonabdominal procedures

Post operative factors

Cause of acute liver disease after surgery ~
multifactorial; drug-induced problems,
hypotension, blood loss, anesthetic-induced
hepatitis, and intraoperative hepatic hypoxia
Close monitoring of renal function is necessary,
especially if fluid shifts have occurred. Renal
failure worsens outcome, as noted in patients with
hepatorenal syndrome

Post operative factors

Monitor patients for hypoglycemia and for signs of
hepatic decompensation, such as jaundice,
ascites, and encephalopathy
Treat spontaneous bacterial peritonitis
Enteral or, rarely, parenteral nutrition may be
necessary.

Discussion

Hepatorenal syndrome
Anaesthesia for patient with cirrhosis
Anaesthesia for cholecystectomy
Anaesthesia for liver transplant

Hepatorenal syndrome
Typically occur in advanced cirrhosis with jaundice
& ascites
Low urine output with low urinary sodium
concentration
Tubular function intact & almost normal renal
histology
Renal failure ~ functional
Advanced cases progress beyond functional
stage acute tubular necrosis

Hepatorenal syndrome
Mechanism:
Extreme peripheral vasodilation extreme arterial
blood volume & hypotension

Activates homeostatic mechanism vasoconstriction of

renal vasculature

GFR & plasma renin remains high with salt & water
retention

Hepatorenal syndrome
Treatment:
Treated for prerenal failure
Stop diuretic therapy
Prognosis is poor

Anaesthesia for patient with

cirrhosis
Postoperative morbidity is increased.
Problems with wound healing, bleeding, infection,
decreased hepatic function and development of
encephalopathy
Divided into acute hepatic failure
chronic failure

Anaesthesia for patient with

cirrhosis (acute failure)
Acute hepatic failure, only truly emergency
surgery should be undertaken
Fresh frozen plasma may be necessary to correct
coagulation defects
More susceptible to sedatives - sedatives and
depressant drugs are probably not needed and
nitrous oxide may be sufficient for analgesia and
amnesia

Anaesthesia for patient with

cirrhosis (acute failure)
Use of succinylcholine is possible without risk of
prolonged effect.
Muscle relaxants are appropriate
Avoid hypotension and maintain urine output &
avoid hypoglycemia.
Patient also prone to acidosis, hypoxemia and
electrolyte abnormalities - appropriate laboratory
tests should be utilized to guide therapy

Anaesthesia for patient with

cirrhosis (chronic liver disease)
No optimal anesthetic drug or technique - perfusion (i.e.
blood pressure) and oxygenation must be maintained
Regional anesthetic techniques are acceptable as well
assuming that coagulation is normal
Plasma proteins may be decreased lead to increased
effects of protein-bound drugs ~ increased susceptibility to
cardiac depression, decreased responsiveness to
catecholamines, and alterations in anesthetic requirement

Anaesthesia for cholecystectomy

Open or laparoscopically ~ under general
anesthesia with muscle relaxation
Use of opioids ~ theoretical concern; known to
cause spasm of the sphincter of Oddi
PCA or intercostal blockade for post OP pain
(Postoperative pain can limit ventilation)

Anaesthesia for cholecystectomy

A bilirubin level of more than 3 mg/dL, elevated
creatinine level, and hypoalbuminemia are also
known to be associated with increased mortality
(Runyon, 1986).
The odds ratio for perioperative mortality in patients
with liver disease who undergo cholecystectomy is
8.47.
Open cholecystectomy in patients with cirrhosis has
been called a formidable operation, although more
recent studies have reported lower, but still
considerable, mortality rates in patients with cirrhosis
who undergo abdominal surgery

Anaesthesia for liver transplant

Preoperatively already; hypoxemia, anemia,
thrombocytopenia, coagulation defects, electrolyte
disturbances (hypokalemia and hypocalcemia),
heart failure and encephalopathy
Invasive monitoring is routinely utilized (arterial
pressure, cardiac filling pressures) and large bore
intravenous access is important

Anaesthesia for liver transplant

Avoid nitrous oxide ~ venous air embolism
Decreased venous return during cross-clamping
often requires inotropic support
Hypothermia should be avoided
Co-existing pulmonary hypertension may require
vasodilator therapy
Acid-base status, electrolytes, glucose levels, and
urine output should all be closely monitored.
Postoperative ventilation is frequently necessary

Most of us will never take part in a transplant but the

lessons learned can be applied each time we
administer anesthesia to a patient with hepatic
disease

Latest Update
1st dedicated liver unit in SEA (liver ICU) ~
Gleneagles Hospital, Singapore
Equipped with i. Monitoring devices
ii. Ventilator
iii. Liver dialysis machine
(molecular adsorbent recirculating system)

Pre-requisite; existing living donor liver transplant

(LDLT) program

Bibliography
Conn M: Preoperative evaluation of the patient
with liver disease. Mt Sinai J Med 1991 Jan; 58(1):
75-80
Sai Praveen Haranath: Perioperative
management of the patient with liver disease.
emedicine 2002
Laurence & Bennett: Clinical pharmacology 7th
edition. Churchill livingstone, pg 543

Thank you

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