INTRODUCTION

Diseases of liver are increasing in incidence and

these patients are presenting themselves to
increasing number of diagnostic and therapeutic
procedures which need anesthesia.
Liver disease apart from causing primary
problems
due to hepatic dysfunction also causes
multisystem dysfunction secondary to progressive
liver failure.
It is necessary to understand the normal
physiology and anatomy of liver, pathophysiology
of disease process that involves the liver and
biliary tract, to deliver safe and suitable
anaesthesia.

ANATOMY

MICROSCOPIC ANATOMY
KIERMANS LOBULE

RAPPAPORT ACINUS

Parenchymal mass between 2

Functional unit of liver
centrilobular veins
50,000100,000 in number.
Centre
/Axis is formed
by
Each lobule is composed of platesof
hepatocytes
arranged
cylindrically around a centrilobular PORTAL
vein. TRIAD

Liver
acinu
s

Vascular supply of liver (DUAL BLOOD SUPPLY)

25% of the cardiac

output, 1.5 lit / min
Average blood flow
between 100 and 130
mL/minute per 100
g.

25 %
1
22
75 %
1 2

PORTAL VEIN
75%
NUTRIENT RICH
5055% OXYGEN

HEPATIC ARTERY
25%
OXYGEN RICH
4550% OXYGEN

MEAN PRESSURE
5-10 mmHg

MEAN PRESSURE
40-90 mmHg

CONTROL OF LIVER BLOOD FLOW

A.INTRINSIC REGULATION
1) 1) HEPATIC ARTERIAL BUFFER
RESPONSE
- most important intrinsic mechanism
- changes in portal venous flow cause reciprocal
changes in hepatic arterial flow
- mechanism involves the synthesis and washout of
adenosine (i.e., a vasodilator) from periportal
regions

2) AUTOREGULATION
- Only in postprandial
-Mechanism
state
involves myogenic responses of
vascular smooth muscle to stretch

3) METABOLIC CONTROL
-Decrease oxygen tension or ph of portal
venous blood increase hepatic arterial flow
whereas postprandial hyperosmolarity
increase both hepatic and portal flow

 B.EXTRINSIC REGULATION
1.NEURAL CONTROL
-Fibers of the vagus, phrenic, and splanchnic nerves (postganglionic
sympathetic fibers from T6 through T11)
-When sympathetic tone : splanchnic reservoir volume increases.
-Vagal stimulation : alters the tone of the presinusoidal sphincters
-the net effect is a redistribution of intrahepatic blood flow
without
changing total hepatic
blood flow.
2.HUMORAL
CONTROL
- hepatic arterial bed has 1-, D-1, and 2-adrenergic receptors
- portal vein has -1 & D-1 receptors
Glucagon induces relaxation of hepatic arterial smooth muscle.
angiotensin II constricts the hepatic arterial and portal venous beds.
Vasopressin elevates splanchnic arterial resistance, but it lowers
portal venous resistance.

EXTRINSIC FACTORS
HEPATIC BLOOD
FLOW

HEPATIC BLOOD
FLOW

Supine position

Upright position

Feeding (hyperosmolarity)

Anesthetic agents

Hypercapnia

Surgical trauma

Glucagon
agonists
Hepatocellular enzyme
induction

agonists/ blockers
IPPV/PEEP
Vasopressin

Acute hepatitis

Hepatic cirrhosis

?Hypercapnia

?hypocapnia , hypoxia

HEPATIC DRUG CLEARANCE

GOVERNED BY Rate of HBF.
Plasma protein binding of drug
Hepatic intrinsic clearance.

CLEARANCE :
Volume of blood from which the drug is completely
removed per unit TIME .

CLEARANCE
(Cl)

HBF
X
(Q)

EXTRACTION RATIO
(E)

HIGH EXTRACTION
RATIO

LOW EXTRACTION
RATIO

Propofol

Thiopentone

Fentanyl, Morphine,
Meperidine

Diazepam

Lignocaine

Digitoxin

Verapamil

Phenytoin

Labetalol

pancuronium

Propanolol

Theophylline,

Clearance of drugs with high hepatic

extraction ratio is more markedly affected
by changes in HBF.

EXCRETORY
METABOLIC

DETOXIFICATIO
N

SYNTHETIC

HEPATIC
FUNCTION
S

IMMUNITY

BLOOD
COAGULATIO
N
BILIRUBIN
METABOLISM

ENDOCRINE

STORAGE OF
BLOOD
Reservoir function

Liver Function Tests

Uses
To detect the presence of
liver disease
To distinguish among
different type of liver
disorders
To guage the extent of
known liver damage
To follow the response to
treatment

 Classification of LFTs
Tests based on detoxification and excretory functions
Serum bilirubin
Breakdown product of porphyrin ring of heme containing proteins
2 fractions -

conjugated (direct 30%)

unconjugated (indirect 70%)

Normal total serum bilirubin 1 mg/dl
in unconjugated fraction is rarely due to liver disease

 Urine bilirubin
Any bilirubin found in urine is conjugated, therefore bilrubinuria implies
presence of liver disease

Blood ammonia
Detection of encephalopathy, monitoring hepatic synthetic function

Serum enzymes
No known function in serum
ed level- rate of entrance into serum from damaged liver cells

 Enzymes that reflect damage to hepatocytes

Aminotransferases
Aspartate aminotransferase (AST or SGOT): Liver, cardiac muscle, skeletal
muscle, kidneys, brain, pancreas, etc.
Alanine aminotransferase (ALT or SGPT): 1 in liver
Sensitive indicators of liver cell injury
Normal levels <35-45 IU/L

AST/ALT ratio DERITIS QUOTIENT

Normal - 1 or slightly > 1
<1 non-alcoholic steatosis or hepatitis without cirrhosis
2-4 ALD
>4 Wilsonian hepatitis

 Glutathione S transferase
Relatively sensitive and specific test for detecting drug-induced
hepatocellular injury

Enzymes reflecting cholestasis

Alkaline phosphatase-Normal levels- 42-122 IU/L
Pathological cause of -1 biliary cirrhosis ,Choledocholithiasis,Hepatic
malignancy1 & 2,Pagets disease

-Non-pathological - Age >60 yrs,Bld group O & B,Growing

children & adolescent,Late in normal pregnancy

 5' NT
Sensitive and specific for hepatobiliary disorders (HBD)
Normal pregnancy, bone growth and bone diseases do not affect 5' NT
In pts with HBD, changes in ALP are usually followed by similar
changes in 5' NT

GGT
Inducible microsomal enzyme. N levels 5- 40 IU/L.
Less specific than 5' NT as a marker for HBD
Unlike 5' NT, GGT may be released from many sites beside the
hepatobiliary tree
Bone important source of ALP, has little GGT thus GGT useful for
differentiating hepatic & osseous sources of ALP

 Tests for bio-synthetic function of the liver

Estimation of plasma proteins
Tests for reversal of A:G ratio
Tests for coagulability of blood
Plasma protein
Total

Normal levels
6.4 8.3 g%

S. Albumin

3 5 g%

Serum globulin

2 3 g%

Serum fibrinogen

0.3 g%

Serum prothrombin

40 mg%

A:G ratio

1.7 : 1

 Serum albumin
S. albumin <3 g/dl suspect chronic liver disease
Hypoalbuminemia not specific for liver disease
Protein malnutrition of any cause
Protein losing enteropathies
Nephrotic syndrome
Chronic infections
Burns

Reversal of A : G ratio chronic liver dysfunction.

 Serum globulin

in gamma globulin chronic liver disease

Ig M - Primary billiary cirrhosis.
Ig A Alcoholic liver disease.
Ig G - Auto immune hepatitis.

Thymol turbidity test

Test for reversal of A:G ratio
Marked turbidity liver insufficiency

 Coagulation factors
Factor I, II, V, VI, VII
Short t1/2 single best measure of acute hepatic synthetic function
Tests PT- N 11-16 sec
- PTTK N 30- 40 sec

Prognostic value PT > 5 sec above control indicative of poor prognostic sign in acute
viral hepatitis.
in hepatitis, cirrhosis, disorders leading to vit K deficiency such as
obstructive jaundice or fat malabsorption

 Immunological tests
Antibodies to specific etiologic agents

HBV- HBsAg , HBcAg, HBeAg

Antibody to Entamoeba histolytica
Antibody to CMV, HCV, EBV

Non specific antibodies

Antimitochondrial antibody- PBC

Antismooth muscle antibody- Auto immune hepatitis
pANCA- Primary sclerosing cholangitis

 Serum tumor markers

feto-protein - in HCC.

Hepatobiliary imaging

USG, CT scan - 1st line investigation

ERCP, PTC- visualization of biliary tract
Doppler USG& MRI- hepatic vasculature & heamodynamics
CT & MRI- hepatic masses & tumours

Manifestations of Liver
Disease

Jaundice
Portal hypertension
Ascites
Hepatic encephalopathy
Splenomegaly
Blood abnormalities
Light stools/Dark urine
Peripheral edema
Pruritus (itching)
Abdominal pain

pathway of bilirubin formation and excretion

Preoperative assessment in liver

dysfunction

Type and extent of liver disease

Extra hepatic effects
Risk assessment
Patients general condition- hydration
,nutrition
Associated co-morbid conditions
LFT
Consent

Modified Child- Turcotte -Pugh Scoring System

1

S. Bilirubin

< 2 gm%

2 - 3 gm%

> 3 gm%

S. albumin

> 35 gm%

2.8 -35 g%

< 2.8 gm%

Ascites
Encephalopathy

None

slight-moderate tense

None

Grade I & II

Grade III & IV

Prothrombin time
Sec prolonged
INR

<4

4-6

<1.7

1.7- 2.3

>6

>2.3

Modified Child- Turcotte -Pugh Scoring System

CLASSES

SCORE

MORTALITY

5-6

10%

7-9

31%

10-15

76%

MELD
Objective assessment in predicting 3-month mortality
Primarily used to select patients for liver transplant
0. 38 X ln (bilirubin mg/dl) + 1.12 X ln (INR) + 0.96
ln (creatinine mg/dl) + 0.64
Best outcomes : MELD score < 14.
For patients with a MELD score of 15-24
Clinical judgment
Further discussion with the family and the patient

Preoperative approach: Patient with Known/

Suspected liver disease

 PREOPERATIVE INVESTIGATION IN A
CASE OF LIVER DISEASE
CBC
BT.PT.APTT
Urine analysis
S.protein,s.albumin
Blood glucose,blood urea
S.electrolyte
S.urea,s.creatinine
Viral markers-HBV,HCV
CHEST X-RAY
ECG

 PREOPERATIVE PREPARATION

Short acting anxiolytic

Oral H-2 antagonist.
Vit-k 10mg OD for 3 days
Oral bile salt
Maintain adequate urination-1ml/kg/hr
IV fluid-1-2ml/kg/hr

ANAESTHETIC GOALS Maintain hepatic blood flow

Avoid sympathetic
stimulation,hypotension,hypocapnia,hypoxemia
Avoid pressure effects caused by surgical
traction,tumors,laparoscopy.

 Avoid hepatic venous congestion caused

by head down position,ippv with PEEP,
Avoid hepatotoxic drugs like
halothane,acetaminophen
MAINTAIN RENAL FUNCTION PREOPERATIVELY
Avoid NSAIDS,aminoglycoside
Prophylactic antibiotic
Oral bile salt to maintain gut flora.
INTRAOPERATIVELY
Avoid hypotension and hypoxemia
Avoid dehydration.
Mannitiol/furosemide/low dose dopamine.

Regional Anaesthesia
Contraindicated if PT >2.5 s above control,
platelet count < 50,000 /cu.mm, bleeding
time >12 mts
Spinal and epidural anaesthesia carries the
risk of epidural haematoma and paralysis if
there is abnormal clotting but there are
otherwise no special precautions.
liver function affect the rate of metabolism of amide
local anesthetics & significant liver dysfunction is a
relative contraindication to the use of amide local

GENERAL
ANAESTHESIA

Opioids -Fentanyl (DOC)- maintains hepatic o2supply demand.

Remifentanyl Ideal

opioids can cause spasm of sphincter of Oddi (incidence < 3%)

fentanyl> morphine> meperidine> butorphenol

T/T naloxone, glucagon, atropine, nitroglycerine.
Benzodiazepines
Diazepam - prolonged half life
Oxazepam and lorazepam preferrred metabolised by glucuronidation
without liver requirement
Volatile anaesthetic- Isoflurane ,sevoflurane& desflurane
maintains hepatic blood flow & oxygen supply
IPPV - Maintain eucapnia, Avoid high airway pressures

Induction agent - Thiopentone/Propofol

slow titrated dose avoid hypotension
gentle intubation avoid sympathetic stimulation
Depolarising Muscle relaxant
Reduced plasma pseudo cholinesterase activity
Suxamethonium Rapid sequence Induction
Nondepolarising Muscle relaxant
Increased volume of distribution larger initial doses
Prolonged action due to reduced metabolismlower maintanance doses
Atracurium /cisatracurium- Hoffmans elimination

 Intra Operative Monitoring

Routine
Pulse oximetry, ECG, NIBP
EtCO2
Urine output
Core temperature
NMJ monitoring
Longer & extensive surgeries
Intra arterial and CVP monitoring.
Insertion of Intra arterial line care to
prevent haematoma
Biochemical Blood Sugar, ABGs.
Electrolytes.
Haematology -Hb, PT

Postoperative management
Conscious, adequate neuromuscular recovery, vitals
stable extubate oxygen enriched air
Else- Continue IPPV

Correct Fluid & Electrolyte imbalance

Correct hypothermia

Achieve CVS stability

Adequate analgesia & chest physiotherapy

Antibiotics andH2 receptor antagonist
Maintain urine output
Replace blood and blood products

Mgt of postoperative pain

If coagulation profile normal lower thoracic

or upper lumbar epidural 0.0625%
bupivacainewith fentanyl 2 mcg/ml.
Small doses of acetaminophen 325mg in 34
doses/day can be added.
If abnormal IV PCA.
The catheter should be removed once the INR
normalizes, which usually takes 46 days.

Causes Of Postoperative Liver Dysfunction

Cirrhosis of liver

Cirrhosis is a pathological condition where normal

architecture of liver is distorted due to development of
fibrous tissue and formation of regenerative nodules
Causes of cirrhosis?
. Alcoholism
. Chronic viral hepatitis (Hepatitis B, Hepatitis C)
. Inherited metabolic liver diseases
Hemochromatosis, Wilsons disease
Autoimmune hepatitis
. Nonalcoholic steatohepatitis
. Primary biliary cirrhosis
Primary sclerosing cholangitis
Cardiac cirrhosis
. Miscellaneous
Cystic fibrosis,cryptogenic cirrhosis,-1 antitrypsin def.

Hemodynamic changes in the typical

cirrhotic

patient.

Renal effect of liver

dysfunction

Increased reabsorption of sodium.

Impaired free water clearance.
Decreased renal perfusion.
Hepatorenal syndrome
Hyperkalaemia.
circulatory decompensation.
oedema and ascites

 Gastrointestinal effect of liver

dysfunction Portal hypertension
Ascites
Esophageal varices
Hemorrhoids
Gastrointestinal bleeding
Metabolic effect of liver dysfunction
Hyponatremia and hypernatremia
Hypokalemia and hypocalcemia
Hypomagnesemia
Hypoalbuminemia
Hypoglycemia

 Hematological effect of liver

dysfunction
Anemia
Coagulopathy
Hypersplenism
Thrombocytopenia
Leukopenia
Vit k def
factor ,V, X,X
PT
Due to prolonged biliary obstruction-

 effects of liver dysfunction on

respiratory system
Increased intrapulmonary shunting;
hepatopulmonary syndrome
Decreased functional residual capacity
Pleural effusions
Restrictive ventilatory defect
Respiratory alkalosis
Complications of cirrhosis ;
Portal hypertension
Variceal bleeding, ascites, splenomegaly and
hypersplenism
Hepatic encephalopathy
Hepatorenal syndrome.
Spontaneous bacterial peritonitis.

Portal hypertension
defined as an increase in the hepatic venous
pressure gradient to > 5 mm Hg.
Presinusoidal causes: splenic AV fistula,
splenic or portal vein thrombosis, massive
splenomegaly. Sarcoidosis, schistosomiasis.
Sinusoidal causes: Established cirrhosis,
alcoholic hepatitis.
Postsinusoidal causes: Budd-Chiari
syndrome, right heart failure, constrictive
pericarditis
complications of portal hypertension
Variceal bleeding, splenomegaly,
hypersplenism and ascites

Management of portal
hypertension in
cirrhosis
Removal of offending agents
Non-selective b-blockers (such as propranolol) to
reduce portal venous pressure.
Low salt diet.
Diuretics for ascites: Spironolactone to
counteract sodium retention; loop diuretics can
also be added.
Vasoactive drugs
Portosystemic shunt procedures:
TIPS/ Surgically created portosystemic shunts.

 Management of acute variceal

bleeding
1. General resuscitation (fluid resuscitation
and replacement blood and blood products
hemodynamic and respiratory support).
2.vasoconstrictor drugs to stop bleeding like
vasopressin ,terlipressin, glypressin,
somatostatin and octreotide.
Mechanical measures inflatable balloons for
tamponade by direct pressure. Eg.Sengstaken-Blakemore tube ,Linton-Nachlas
tube .

ASCITIS

Ascitis is accumulation of excess of fluid

within the peritoneal cavity.
Pathogenesis:Liver failure and portal
hypertension results in ascitis.
. Complication of ascitis Refractory ascites
spontaneous bacterial peritonitis.
Increases risk of abdominal wound
dehiscence,abdominal wall herniation,
respiratory compromise.

Management of ascites
Salt restricted diet (water restriction only if
patient is hyponatremic).
Spironlactone 100200 mg/d (can be
increased to 400600 mg/d) and frusemide
4080 mg/d (can be increased to 120160
mg/d) might be added in patients with
peripheral edema.
. If ascites persists despite above
measures refractory ascites:
1- Repeated large volume abdominal
paracentesis with albumin replacement as
needed.
2-TIPS.

Hepatic encephalopathy

Hepatic
encephalopathy (HE)
is an alteration in
mental status and
cognitive function
occurring in the
presence of liver
failure.

Grading of hepatic
encephalopathy(West Haven criteria)

MANAGEMENT OF HEPATIC

Dietary
protein withheld or limited to 60-80 g/d; vegetable protein
ENCEPHALOPATHY
better

Control GI bleed and purge blood out. 120 mL of magnesium citrate

orally or NG tube 3-4hrly until the stool is free of gross blood, or by
administration of lactulose (two or three soft stools per day )

Oral antibiotic ;nonabsorbable agent rifaximin, 400 mg orally three

times daily, is preferred. Other agents metroinidazole or neomycin
Flumazenil is effective in about 30% of patients with severe hepatic
encephalopathy
Treatment with acarbose (an alpha glucosidase
carnitine
inhibitor)
and L- factor in the mitochrondrial transport of long. (an essential
chain fatty acids) is under study

Hepatopulmonary syndrome (HPS)

Hepatopulmonary syndrome (HPS) is defined by the presence

of liver disease, an increase alveolar-arterial gradient on room
air, and evidence of intrapulmonary vascular dilations.
A room-air Pao2 less than 60 mm Hg is highly suggestive of
HPS.
A contrast-enhanced echocardiogram will detect intrapulmonary
shunting. Peripheral pulmonary vasculature (precapillary and
capillary) has characteristic vascular dilations, thought to
increase the distance between red blood cells and the alveoli
which impairs oxygenation.

Portopulmonary hypertension (POPH

Pulmonary hypertension syndrome with vascular obstructio

and increased resistance to pulmonary arterial flow
It occurs due to pulmonary endothelial/smooth muscle
proliferation, vasoconstriction and in-situ thrombosis.
The development of POPH has not been demonstrated to
correlate with the severity of liver disease

he diagnostic criteria for POPH include a mean pulmonary

rtery pressure(mPAP) greater than 25 mmHg at rest and
ulmonary vascular resistance (PVR) of > 240 dynes.s.(cm
better measure is a transpulmonary gradient > 12 mm
PAP-PAOP) as this reflects the obstruction to flow (PVR)

Special precaution in alocoholic pts

A patient with acute alcohol intoxication Sedative drugs are less likely to be needed.
They are to be treated as having full
stomach, due to delayed gastric emptying,
thus rapid sequence induction is needed.
Alcohol induced depression means hypotension
is likely after induction.(induction agents
dose requirement will be lower).
Metabolic conditions like hypoglycemia,
alcoholic ketoacidosis may be found.
Excessive dextrose may precipitate Wernickes
encephalopathy.

 A chronic alcoholic Volatile anesthetics and induction agents

dose requirement will be higher.
The initial dose requirement of most
drugs will be higher (increased volume of
distribution) but their effect is prolonged.
Thrombocytopenia, leukopenia, anemia,
coagulopathy and electrolyte
derangements (hypomagnesemia,
hypophosphatemia, and hypocalcemia) are
common.
Postoperative course may be complicated by
alcohol withdrawal syndrome (AWS).

Halothane Hepatitis
The incidence is 1:7000-30,000
halothane anaesthetics - higher in
women, the middle aged and the obese
Rarer in paediatric patients
Commonest iatrogenic cause of fulminant
hepatic failure
Unexplained liver damage within 28 days
of halothane exposure in previously
normal patient idiosyncratic reaction
Clinical features : malaise,
anorexia,fever within 7 days ,jaundice
within days to 4 weeks

Halothane Hepatitis
DIAGNOSIS

Serum antibodies that react with specific liver

microsomal proteins that are altered by
trifluroacetyl chloride metabolite of
halothane
Gross rise of Transaminases [500 -2000 u/l]
Risk factors
High - recent previous exposure [ 78 %]
previous adverse reaction
Uncertain - obesity
Female [1.6 :1 ]
Drug allergy [ 15 %]
Family history
Lymphocyte sensitivity to phenytoin

ACUTE LIVER FAILURE

ANESTHETIC MANAGEMENT AND

PREPARATION OF PATIENTS WITH
ACUTE LIVER FAILURE

SUMMERY

Surgery is contraindicated-child pugh C,acute

hepatitis,sever coagulopathy,acute renal failure
Optimise medical therapy for pt with cirrhosis
Carefully titrate the drug doses
Minimise ascites to decrease risk of abdominal wall
herniation,wound dehicence,ventilation problems
Correct coagulopathy with vit-K and FFP to achive PT
within 3secs.
Monitor renal function
Monitor and correct electrolyte abnormality
Monitor for signs of acute liver failure.