This document discusses the anatomy, physiology, and functions of the liver as they relate to anesthesia. It begins with an overview of hepatic anatomy including gross and microscopic structure, blood supply, and drainage. It then covers hepatic blood flow regulation by intrinsic and extrinsic factors and how anesthesia can affect blood flow. The major sections discuss hepatic functions such as metabolism, synthesis, and detoxification. In particular, it notes the liver's roles in glucose regulation, protein and lipid metabolism, coagulation factor production, and bilirubin metabolism.

1. Anesthesia and the liver
BY
DR. MARWA A.MAHROUS
ASSISSTANT LECTURER ANESTHESIAAND ICU
SOHAG UNIVERSITY

2. Sources of this lecture:
• HEPATIC ANATOMY,PHYSIOLOGY & ANESTHETIC
EFFECTS, Dr. Mohd Saif Khan MD ,LHMC, New Delhi
• RISK OF SURGERY IN THE PATIENT WITH LIVER
DISEASE, Ajay Jain,Gastroenterology Fellow ,January
16, 2002.
• ANAESTHESIA AND LIVER DISEASES,
DR.D.KIRUBAKARAN,2011.08.08
• Dr. C.K. Pandey,new delhi, anesthetic consideration
and perioperative risks in patient with liver disease.

3. Objectives
-anatomy, physiology and function of the liver
-effect of anesthesia on liver function
-effect of liver function on anesthetic drugs
-anesthesia for a patient with liver disease:
hepatitis:acute,chronic
cirrhosis

4. • HEPATIC ANATOMY
– GROSS ANATOMY
– MICROSCOPIC ANATOMY
• HEPATIC BLOOD FLOW
• HEPATIC BLOOD FLOW REGULATION
– INTRINSIC FACTORS
– EXTRINSIC FACTORS
• EFFECTS OF ANESTHESIA ON HBF
• HEPATIC FUNCTIONS
• ANESTHETIC AGENTS & HEPATIC FUNCTIONS

5. GROSS ANATOMY
• Largest internal organ
• largest gland
• Wt. :median weight of 1.8 kg in men and 1.4 kg in
women.
• It accounts for about 2% of the total mass of healthy
adults and 5% of neonates.
• Location : Rt. Hypochondrium
• In the right midaxillary line, the liver spans from the 7th
to the 11th ribs.
• It is covered by peritoneum (Glisson's capsule), except
for the gallbladder bed, the inferior vena cava (IVC), the
bare area, and the porta hepatis.

6. LOBES vs SEGMENTS OF THE LIVER
• Customary division -
– into 4 lobes-the right, left, caudate, and quadrate lobes
– is derived from the topographic anatomy, with the
falciform ligament separating the right and left lobes.

7. The liver is separated into eight anatomic segments, each with
an independent nutrient blood supply and venous and biliary
drainage. Appreciation of this segmental anatomy is the basis of
anatomic resection of the liver.
 Functional/segmental
division-
 Divided into 8 segments
each receiving a portal
pedicle.
 Couinaud system of division
 Based on distribution of
blood flow via portal pedicles
and location of hepatic vein.

8. Biliary system
BILE CANALICULI
RT. & LT. HEPATIC DUCT
COMMON BILE DUCT
COMMON HEPATIC DUCT CYSTIC DUCT
DUODENUM
MAIN PANCREATIC DUCT

9. GALL BLADDER
• Concetration and storage of bile
• Location : inferior surface of
liver
• 7-10 cm long
• Capacity : 30-50 ml
• Blood supply: cystic artery
• Anesthetic interactions with bile
formation and storage have not
been reported.
All opioids can potentially cause spasm of
the sphincter of Oddi and increase biliary
pressure .(fenta causes max spasm).

10. Venous drainage of liver
• If thrombosis of the major hepatic veins occurs (Budd-Chiari
syndrome), the caudate veins become the key to drainage of hepatic
blood into the IVC. The caudate lobe is usually drained by its own
set of veins.
• In portal hypertension portosystemic shunts dilated.
CENTRAL VEINS INTER LOBULAR & SUBLOBULAR VEINS
3 HEPATIC VEINSIVC
HEPATIC SINUSOIDS

11. • LYMPHATIC DRAINAGE
SUPERFICIAL DEEP
CAVAL
HEPATIC
COELIAC
PARACARDIAL
NODES AROUND
IVC &
HEPATIC NODES

12. SYMPATHETIC
(T6-T11)
From celiac ganglia
PARASYMPATHETIC
(VAGUS)
HEPATIC PLEXUS
Stimulation causes
↑Hepatic vascular resistance
↓THBF & blood volume
Glycogenolysis Glucose output
NERVE SUPPLY OF LIVER
VAGAL STIMULATION DUE TO SURGERY
AROUND GALL BLADDER BED.
BRADYCARDIA

13. MICROSCOPIC ANATOMY
KIERMAN’S LOBULE
Functional unit of liver
50,000–100,000 in number.
Each lobule is composed of plates of
hepatocytes arranged cylindrically around
a centrilobular vein.
RAPPAPORT ACINUS
Parenchymal mass between 2
centrilobular veins
Centre /Axis is formed by PORTAL TRIAD
Portal Axis consists of a
terminal portal venule, a
hepatic arteriole and a bile
ductule

14.  3 zones of hepatocytes
based on Concentration
gradients of oxygen and
solutes occur along the
sinusoidal spaces.
I II III
Central vein
Portal triad
ZONES
ZONALITY(zonal relationship ) IN LIVER LOBULE
Liver lobule

15. Liver Acinus functional microvascular unit

16. ZONE I (PERIPORTAL)
• O2 TENSION=250mmHg
• LEAST SUSCEPTIBLE TO ISCHEMIA
– Zone 1- rich in Oxygen, mitochondria
Oxidative metabolism, synthesis of glycogen
Zone 2- transition
ZONE I & II BOTH
Chief producer of NH3
Contain enzymes for urea cycle
↑ No. Of mitochondria
ZONALITY(zonal relatioship ) IN LIVER LOBULE
I II III
Central vein
Portal triad
ZONES

17. 17
Hepatic Microcirculation
• Liver Acinus functional microvascular unit
– Zone 1- rich in Oxygen, mitochondria
• Oxidative metabolism, synthesis of glycogen
– Zone 2- transition
– Zone 3- lowest in Oxygen, anaerobic metabolism,
Cytochrome P-450
• Biotransformation of drugs, chemicals, and
toxins
• Most sensitive to damage due to ischemia,
hypoxia, congestion

18. ZONE III
• Last to receive blood hence O2 TENSION= 70mmHg, lowest
in Oxygen
• Most susceptible to ischemiaMost sensitive to damage due to
ischemia, hypoxia, congestion
• Anaerobic metabolism
• Detoxification & Biotransformation reactions Cytochrome P-
450
Hence with hypoxic insult to liver
Biotransformation of drugs is
Amongst the first to be affected.
ZONALITY(zonal relationship ) IN LIVER LOBULE

19. Metabolic diversity within zones
Zone 1(periportal) Zone 3(pericentral)
Rich in oxygen and the
nutrients
Relatively poor in O2 and
nutrients
Less prone to hypoxia and
drug toxicity
More prone for hypoxic &
drug induced damage
Oxidative/phaseII reaction Anaerobic/phaseI reaction
Glycogen snthesis as well
as gluconeogenesis
Glycolysis
Bile salt formation Lipolysis

20. HEPATIC ULTRASTRUCTURE
• HEPATOCYTES are arranged in plates
with intervening sinusoids.
• PITT CELLS : highly mobile lymphocytes
• KUPFFER CELLS : macrophages attached
to endothelium.
• ITO CELLS : contain fat, store vit. A.

21. • SPACE OF DISSE : Around
sinusoids. Microvilli of
hepatocytes are exposed to
this space.
• SINUSOIDS : specialized
capillary system having
fenestrated endothelium.
• ENDOTHELIAL CELLS :
fenestrated and highly
permeable Allow exchange
of molecules b/w
hepatocytes and sinusoidal
blood.
HEPATIC ULTRASTRUCTURE

23. HEPATIC BLOOD FLOW

24. Vascular supply of liver
20-30% of the cardiac output,
Average blood flow between 100 and
130 mL/minute per 100 g.
Features H.A P.V
Bl supply 25-30% 70-75%
02 supply 45-50% 50-55%
Spo2 98% 60-75%
Mean BP 40-70 5-10
THBF – 25 to 30% by hepatic artery
and 70 to 75% by portal vein.
Hepatic oxygen consumption -45 to
50% by hepatic artery and 50 to 55% by
the portal vein

25. HEPATIC BLOOD FLOW REGULATION
INTRINSIC FACTORS
(regional microvascular)
EXTRINSIC FACTORS
(neural and hormonal)
HEPATIC ARTERIAL BUFFER RESPONSE
Metabolic control
Pressure –flow autoregulation
Neural control
Humoral control

26. Intrinsic regulation
• Hepatic arterial buffer response
Decrease in portal biood flow and oxygen
tension will increase the hepatic arterial blood flow
thru increased periarteriolar adenosine whereas
increase in portal blood flow decrease the HABF thru
decrease in periarteriolar adenosine.
In portal HT – Liver depend upon
hepatic arterial blood flow as HABR reaches its
upper limit.(oxygen supply and demand should
be carefully maintained)

27. Intrinsic Regulation
Pressure FLOW AUTOREGULATION
Exist even when the SBP reaches 80mmhg.
Myogenic reflex
High TM pressure – decreases flow
Low TM pressure - increases flow
Autoregulation Doesn’t exist in portal circulation.
FOOD RELATED (metabolic control)
Postprandial hyperosmolarity increases both portal & HBF.
Hepatic arterial system undergoes flow autoregulation best when the liver is
very active metabolically(postprandial) but not during fasting state . Hence
flow autoregulation is not likely to be an important mechanism during
most anaesthetics, given that they are performed in fasted patients.

28. Extrinsic regulation
• Circulatory regulation neural
Blood flow through portal vein is indirectly regulated by vasoconstriction and
vasodilatation of splanchnic arterial bed whereas hepatic arterial flow is
directly regulated thro sympathetic system.
Hepatic artery – both alpha and beta receptors.
Portal vein - contains only alpha receptors.
• Hormonal regulation
glucagon - increases hepatic arterial blood flow.
angiotensin - decreases both portal and hepatic blood flow.
vasopressin - decreases both portal and hepatic blood flow.

29. Extrinsic regulation
Catecholamines
Portal vein - vasoconstriction.
Hepatic artery - vasoconstriction in low
dose.
vasodilatation in high
dose.

30. Decreased hepatic blood flow
• Upright posture
• Hypocarbia
• Hypoxia
• IPPV/PEEP
• Sepsis
• Haemorrhage
• Mesentric traction
• Increased IA pressure
• Alpha agonist
• Beta blockers
• Vasopressin
• Octreotide
• Volatile anaesthetics
• Intravenous induction
agents
• Regional anaesthesia

31. Increased hepatic blood flow
• Supine posture
• Postprandial state
• Hypercarbia
• Acidosis
• Acute hepatitis
• Beta agonist
• Phenobarbitone
• Glucagon
• Dopamine
• Dopeximine

32. EXTRINSIC FACTORS
↑ HEPATIC BLOOD FLOW
Feeding (hyperosmolarity)
Glucagon
β agonists
Recumbent position
Hepatocellular enzyme induction
Acute hepatitis
?hypercapnia
↓ HEPATIC BLOOD FLOW
Anesthetic agents
Surgical trauma
α agonists/β blockers
IPPV/PEEP
Vasopressin
Hepatic cirrhosis
?hypocapnia

33. EFFECTS OF ANESTHESIA ON HBF
• INHALATIONALAGENTS
• I.V.ANESTHETICAGENTS
• VENTILATION
• CENTRALNEURAXIALBLOCKADE
• HYPOXIA
• PaCO2
• TYPEOFSURGERY

34. INHALATIONAL AGENTS & HBF
• HALOTHANE-
max. vasoconstriction in hepatic arteriolar vascular bed,
reduces hepatic O2 delivery & hepatic venous O2
saturation.
Disrupts HABR.
• ENFURANE
– Same effect as halothane but with lesser intensity.
• ISOFLURANE/SEVOFLURANE
Maintains HABR
Sevoflurane is also consistently equivalent or superior to
isoflurane in maintaining HABF, hepatic O2 delivery, and
O2 delivery-to-consumption ratios.

35. Nitrous oxide on HBF
• Nitrous oxide containing anaesthetics does not
cause liver injury in the absence of impaired
hepatic oxygenation.
• Nitrous oxide may exacerbate hepatic damage
in the presence of impaired hepatic oxygenation
through sympathetic stimulant action and
methionine synthase inhibition.

36. EFFECTS OF ANESTHESIA ON HBF
• I.V.ANESTHETICAGENTS-
↓PVbloodflow
TotalHBFisunchanged.
Propofol isthebestIVinductionagentasitdoesnotdisruptHABR.
• VENTILATION-
Spontaneous-nochange
IPPV-↓↓HBF(↓C.O.)
Positive end-expiratory pressure (PEEP) further accentuates
these effects.

37. EFFECTS OF ANESTHESIA ON HBF
• Centralneuraxialblockade
– SpinalblocktoT5level→23%
• HYPOXIA
– Vasoconstrictioninsplanchnic&hepaticvasculature
– Effectofhypoxiadependsonduration,degree&
anestheticused.
↓MAP ↓ HBF↓PV BLOOD FLOW

38. EFFECTS OF ANESTHESIA ON HBF
• PaCO2
HYPOCAPNIA
HYPERCAPNIA
VASOCONSTRICTION ↓HBF
VASODIALATION
SYMPATHETIC
STIMULATION
↓HBF
↑HBF
 EFFECTOFSURGERY
 Surgical procedures near the liver can reduce hepatic blood flow up
to 60%.
 Probable mechanisms: sympathetic activation, local reflexes, and
direct compression of vessels in the portal and hepatic circulations.

39. HEPATIC FUNCTIONS

40. HEPATIC
FUNCTIONS
METABOLIC EXCRETORY SYNTHETIC
STORAGE OF BLOOD
Reservoir function
IMMUNITYDETOXIFICATION
BILIRUBIN
METABOLISM
ENDOCRINE
BLOOD
COAGULATION

41. Functions of liver
A. Albumin synthesis
B. Bilirubin secretion
C. Coagulation factor synthesis
D. Drug metabolism
E. Excretion
F. Fat metabolism
G. Glucose & Glycogen metabolism
H. Hormone metabolism
I . Immunological function

42. METABOLIC FUNCTIONS
• Carbohydrate metabolism-glucose buffer function
• Protein metabolism
• deamination
• urea cycle
• interconversions between nonessential amino acids
• Lipid metabolism
• β oxidation of FA→Acetyl CoA→ketone bodies
• FFA esterified to form TAG.
• lipoprotein synthesis
• phospholipids & cholesterol synthesis
Glycogenesis Gloconeogenesis
Glycogenolysis
EUGLYCEMIA
SURGICAL
STRESS
NH3 FORMATION

43. SYNTHETIC FUNCTIONS
• PLASMA PROTEINS-
• Albumin (10-15g/day)
• Globulins except Ig.
• CLOTTING FACTORS- all coagulation factors except factor III,IV
& VIII.
• ANTITHROMBIN III, PROTEIN C & S
• ENZYMES-ALP,SGOT,SGPT
• PSEUDOCHOLINESTERASE
• CHOLESTEROL, LIPOPROTEINS ,PHOSPHOLIPIDS
• ACUTE PHASE REACTANTS

44. BILE SYNTHESIS
• BILE EXCRETION- 600-1200 ml/day
CHOLESTEROL BILE ACIDS
BILE SALTS
ACTIVATION OF LIPASE
EMULSIFICATION OF FAT

45. BILIRUBIN
BILIVERDIN
BILIRUBIN
GLUCURONIDE
EXCRETED
IN
BILE
BILIRUBIN METABOLISM
Senescent RBCs
Hb
Heme
Non erythrocytic
hemoproteins75 % 25 %
Heme oxygenase
Biliverdin reductase
UDP Glucoronyl
tarnsferase

46. DETOXIFICATION
LIPOPHYLIC
XENOBIOTICS
HYDROPHYLIC
METABOLITES
DETOXIFICATION
PHASE I REACTIONS PHASE II REACTIONS
Oxidation,
Reduction,
Hydrolysis
N-Acetylation
Mediated by Cyt. P450
Conjugation Reaction
Addition of Glucuronic acid,Glycine
Sulphate,Methyl gp.
 INHALATIONAL AGENTS (HALOTHANE ESPECIALLY) COMPETITIVELY
INHIBIT CYT P450 & PHASE I REACTION
 Ethanol, barbiturates, ketamine, and perhaps benzodiazepines (eg,
diazepam) are capable of enzyme induction,

47. Drug metabolism
 Phase I reaction
Carried out by cyto P450 enzyme system.
Zone 3 rich in cytochrome enzyme system.
Affected early by ageing and liver disease.
Most drug hepatotoxicity is mediated by the
phase I toxic metabolite.

48. Drug metabolism
 Phase II reaction
conjugation reaction (glucuronic acid &sulfate).
Zone 1 rich in enzymes involved in conjugation.
Affected least by ageing and liver disease.
Products of phase 2 reaction are usually less
toxic when compared to phase I reaction.

49. DETOXIFICATION
• Phase III reactions
• involve specific molecular transporters—known as ATP-
binding cassette (ABC) transport proteins.
• facilitate the excretion of xenobiotics and endogenous
compounds.
• These proteins use ATP hydrolysis to drive molecular
transport.
• Examples: cystic fibrosis transmembrane conductance
regulator (CFTR), canalicular copper transporters, and
multidrug resistance protein (MDR).
• MDR-1 (formerly called P-glycoprotein) resides on the
canalicular surfaces of hepatocytes and enables biliary
excretion of cationic compounds, including anticancer
drugs.
• Dysfunction of ABC transport proteins can disrupt the flow
of bile, impair excretion of xenobiotics and endogenous
compounds, and induce cholestatic liver injury.

50. 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 = HBF X EXTRACTION RATIO
(Cl) (Q) (E)

51. Extraction ratio
 Extraction ratio is the proportion of the drug that is extracted
in single passage through the liver.
ER = intrinsic clearance/ HBF
High extraction ratio ( 0.7 )
It is affected by the hepatic blood flow but not by factors
that increase free fraction of drug.
Dose has to be reduced by as much as 50% but not the
frequency of dosing.

52. Extraction ratio
 Low extraction ratio
It is affected by intrinsic metabolic capacity But it is flow
independent.i.e increase in flow doesn’t increase extraction.
Affected by factors that increase free fraction of the drug.
Reduction in protein binding of highly protein bound drug
causes almost doubling of free fraction but with poorly
bound drug it doesn’t have much effect.
For low extraction drugs ,interval between the doses should
be increased but the drug dosage should not be altered.

53. • ER provides a measure of the relative efficiency with
which the liver extracts or eliminates a given drug.
• Amount of drug removed from blood during a single liver
transit, expressed as a fraction of 1.
CLEARANCE = HBF X EXTRACTION RATIO
(Cl) (Q) (E)

54. HIGH EXTRACTION RATIO LOW EXTRACTION RATIO
Propofol Thiopentone
Fentanyl, Morphine, Meperidine Diazepam
Lignocaine Digitoxin
Verapamil Phenytoin
Labetalol pancuronium
Propanolol
Clearance of drugs with high hepatic
extraction ratio is more markedly affected by
changes in HBF.

55. Ammonia Metabolism & Excretion
•Ammonia is toxic to the central nervous system (CNS),
and freely permeable across the blood–brain barrier
•HEPATIC ENCEPHALOPATHY

56. Liver function tests
 Quantitative - assess hepatic blood flow and
the metabolic capacity.
 Qualitative - assess hepatocellular necrosis.
assess cholestasis.
assess synthetic function.
assess excretory function.

57. Quantitative liver test
• Hepatic blood flow or perfusion
• Bromosulphothalein clearance
• Indocyanine green clearance
• Rose bengal clearance test
• Hepatic drug metabolising capacity
• Galactose elimination capacity
• Aminopyrine breath test
• Antipyrine clearance
• Monoethylglycinexylidide(MEGX) clearance
• Caffeine clearance
more expensive & time consuming

58. Aminotransferace(ALT &AST)
Alanine transaminase Aspartate transaminase
Relatively liver specific Non specific
Cytosol Cytosol and mitochondria
Zone 1>3 Zone 3>1
N.value O – 45 IU/L N.Value 0 – 35IU/L
Half life is 18hrs Half life is 36hrs

59. Examples for raised ALT &AST
 Minor < 100 IU – Chronic hepatitis B/ C
NASH
Fatty liver
 Moderate 100-300IU – Alcoholic hepatitis
Autoimmune hepatitis
Acute viral hepatitis
Exacerbation of chronic viral hepatitis
plus all the above condition

60.  Marked > 300 IU – Drugs and toxins
Acute viral hepatitis
Ischaemic hepatitis
Acute exacerbation of chronic
hepatitis
Extrahepatic cholestasis with
cholangitis.
Eventhough it is a marker of hepatocellular necrosis, the degree
of elevation does not correlate with the extent of necrosis.(no
prognostic value).
Examples for raised ALT &AST

61. Aminotransferace(ALT &AST)
 AST/ALT ratio may be of value in differential diagnosis.
>4 (wilsons hepatitis)
2-4 (alcoholic liver disease)
<1 (NASH)
 Episodic elevation of aminotransferaces is characteristics of
chronic hepatitis C.
 Suspicion of cirrhosis once AST value exceeds ALT in patient
with chronic hepatitis.
 Fall in aminotransferace level indicates recovery unless it is
accompanied by rise in bilirubin & PT.

62. Alkaline phosphatase
 Normal value – 30 to 100IU/L(liver and bone contributes more
than 80 percent of the total value).
 Value < 3fold elevation can be seen in almost any type of liver
disease i.e.elevation of liver derived ALP is not totally
specific for cholestasis.
 Degree of elevation doesn’t differentiate extrahepatic from
the intrahepatic cholestasis.
 ALP elevation in cholestasis is usually > 3fold normal value
but the level remain elevated for 7-10days even after the
obstruction resolves as the half life of ALP is 7days.

63. Alkaline phosphatase
 Value < 3 fold elevation from normal value can be seen in normal people.
Age> 60yrs – upto 1.5 times increase
Children - upto 2 times increase
Pregnancy - upto 3 times increase
B.G O & B - upto 3 times increase after a fatty meal
 Only recomended use of GGT & 5-nucleotidase (most specific) is to exclude or to
substantiate, liver is the source of raise ALP if the electrophoretic fractionation
of ALP is not available.
 Elevated ALP along with 5-nucleotidase is specific for the hepatobiliary diseases
and also helps to R/O physiological ALP elevation.
 Disproportinate elevation of ALP and bilirubin suggest the presence of infiltrative
liver disease ( tumour, sarcaidosis,tuberculosis etc).

64. Prothrombin time
 Normal prothrombin time 11-14secs.
 PT >3-4s over control value is significant.
 Increasing PT is a ominuos sign in patient with acute
hepatocellular disease (impending hepatic failure).
 Prothrombin time in contrast to s.albumin is a useful
prognostic indicator in acute hepatocellular disease.
( as half life of CF is short IC to albumin)
• CLOTTING FACTORS-
• Rapid turn over(factor VII has shortest half life : 2-6 hr)
• Hence, best measure of acute hepatic dysfunction.
• Prothrombin time is the best test
• The PT, which is normally 11–14 s, measures the activity
of fibrinogen, prothrombin, and factors V, VII, and X.

65. Prothrombin time
 Mild – moderate hepatic disease may not be detected by PT as
only 30% of CF is needed for maintaining haemostasis.
 Cholestatic jaundice -correction of PT by atleast 30%within 24
hr of vit k administration suggest hepatic synthetic function
is intact ( prolonged PT due to vit k deficiency alone).
 Prolonged PT >5sec above control not corrected by vitamin k
administration is a poor prognostic sign ( in both acute and
chronic liver disease).
 INR is a better indicator than PT because it is a standardized
value and is not subjected to lab variability as PT.

66. Albumin
 Normal value – 3.5 to 5.5gm/dl.
 Blood level depends upon rate of synthesis(10-
15gm/day),rate of degradation and plasma volume.
 Half life of serum albumin is about 21 days Slow turn over (
half life : 18-20 days)
 Not a good indicator of acute hepatic dysfunction because of
slow turnover ( long half life with 4% degredation per day).

67. Albumin
 In patients with hepatitis, albumin< 3gm/dl should
raise the possibility of chronic liver disease.
 Decreasing albumin level in patient with chronic liver
disease indicates worsening of liver function in the
absence of other causes of hypoalbuminemia.
 As long as albumin level is more than 2.5gm per dl,
free or unbound fraction of the drug wont be
altered.
Hypoalbuminemia is more common in chronic liver
disorders such as cirrhosis and usually reflects severe
liver damage

68. Bilirubin
 Normal total bilirubin value is < 1mg/dl.Out of these, upto
0.3mg is conjugated bilirubin.
 Unconjucated bilirubin is toxic for neuronal cell whereas the
conjucated bilirubin is responsible for renal dysfunction in
patient with obstructive jaundice.
 Bilirubin value rarely exceeds 6mg/dl in Haemolytic anaemia.
 Intrahepatic cholestasis to cause rise in bilirubin, drainage of
bile in >75% parenchyma should be blocked.

69. Bilirubin
 In choledocholithisis caused by CBD stone, the bilirubin value rarely
exceeds 10mg/dl.Sepsis or renal failure should be excluded if the bn
exceeds 30mg/dl in patient with CBD stone.
 In cholestatic jaundice due to malignancy, the bilirubin value is >10mg but
but less than 30mg/dl.
 Common bile duct obstruction if persist for more than 30 days will result
inliver damage and can lead to the development of cirrhosis.
 Serum bilirubin will take atleast 1-2 weeks to return to normal following
the relief of obstruction ( half life of delta bn is 2weeks).

70. Impaired liver function
Direct effects
• Hypoglycemia, Lactic acidosis , Hyper metabolism, Azotemia and
Impaired urea synthesis.
• Jaundice appears when serum bilirubin exceeds 35 µmol/l
• Defects in cholesterol metabolism together with intra-hepatic
cholestasis may lead to production of poor quality bile and
malabsorbtion of fat and fat-soluble vitamins.
• Reduced synthesis of proteins such as albumin, clotting factors,
thyroid binding globulin and pseudo-cholinesterase.
• Impaired hormone biotransformation, reduced production of
modulator proteins and reduced protein binding lead to increased
circulating levels of hormones such as insulin, thyroxine, T3,
aldosterone and oestrogen

71. Indirect effects
Cardiovascular changes
• Vasodilatation and vascular shunting are almost
invariable in ESLD.
• Low systemic vascular resistance (SVR) results in high
cardiac output and high mixed venous oxygen saturations
• Intrapulmonary & arteriovenous shunting
• Pulmonary hypertension may develop
• Tachycardia, bounding pulse ,Ejection systolic murmur

72. • Pulmonary problems are both vascular and mechanical.
• Hepato-Pulmonary syndrome – triad of end stage liver
disease, A-a gradient >2 kPa , intrapulmonary vascular dilation
• Impaired pulmonary function in absence of cardiopulmonary
disease
• Impaired hypoxic vaso-constriction and ventilation perfusion
mismatch lead to arterial desaturation and clubbing if chronic.
• Cyanosis ,dyspnoea , platypnea, orthodeoxia [desaturation
pronounced in upright position relieved by recumbency ]
• Pleural effusions together with ascites can cause considerable
mechanical embarrassment of respiration and a reduction in
functional residual lung capacity.
Pulmonary changes

73. HEPATORENAL SYNDROME
• 􀂄 Low GFR
• 􀂄 Low renal blood flow
• 􀂄 No other cause for renal failure
• 􀂄 “Functional renal failure”
• Symptoms – water retention, Azotemia,
hyponatremia, & oliguria

74. Hepatorenal failure
• Causes may be
Pre and peroperative dehydration
Hypovolaemia
Falls in renal blood flow during surgery,
Direct effect of the excess conjugated bilirubin on
the renal tubules or possibly an increased absorption
of endotoxin from the gut.
• Not a major risk in patients with Prehepatic
jaundice.

75. Management
of Hepato renal syndrome
• Avoid it developing by ensuring adequate hydration and a
urine flow of at least 50mls/hr in the average adult patient.
• In moderately elevated bilirubin - simple fluid loading for 12
hours before surgery using 0.9% NaCl and during the
operation.
If the urine output is not maintained - Mannitol 10%
• Bilirubin greatly elevated (>140 micromols/litre), -
intravenous fluids during the 24 hours before surgery and for
36 hours postoperatively.
Mannitol 10% 0.5-1g/kg - prior to surgery without
making the patient dehydrated as a result of an over-zealous
diuresis.

76. Neurological problems
• Mechanisms leading to deepening encephalopathy -
incompletely understood.
• Due to accumulation of neurotoxic compounds
penetrating an impaired blood-brain barrier.
• Symptoms can occur in chronic as well as in acute
disease, may be rapid in onset
• Precipitated by a gastrointestinal bleed, dietary
protein overload or sepsis.
• Somnolence can be exacerbated by sedative drugs
and narcotics.
• Rapid correction of hyponatraemia can lead to
osmotic demyelination and central pontine
myelinolysis and should be avoided

77. HAEMATOLOGICAL PROBLEMS
• Anaemia may be the result of nutritional deficiency,
toxic bone marrow depression or gastrointestinal
bleeding from varices or erosions.
• Coagulation defects arise from thrombocytopenia,
platelet dysfunction and decreased levels of
circulating clotting factors.
• Clotting factor levels fall because of impaired
synthesis, vitamin K malabsorbtion and intravascular
consumption.
• The short half-life of clotting factors means that INR
or Prothrombin Ratio (PTR) can reliably be used to
evaluate residual hepatic function.
• Treatment –Vit K ,FFP

78. GASTROINTESTINAL SYSTEM
• Rupture of oesophageal varices
• Vassopressin & octreotide –reduce portal
hypertension
• Susceptibility to infection - increased
Drug disposition
• Cholestasis will reduce absorption of fat-soluble
drugs after oral administration.
• Compartment changes and altered protein binding
will affect volume of distribution, clearance and re-
distribution.
• Patients with liver dysfunction may be particularly
sensitive to opiates and benzodiazepines due to
altered end-organ sensitivity

79. Effect of hepatic dysfunction on anaesthetics
• ↓ Albumin -increased free fraction
• Altered volume of distribution [Ascites &
increased total body water compartment],
• Reduced metabolism –alters drug
pharmacodynamics

80. • BENZODIAZEPINES-
• Since diazepam & midazolam is metabolized by phase I reaction,
hence recovery & elimination times ↑ in Cirrhotics.
• OXAZEPAM & LORAZEPAM are safe in mild to moderate liver
impairment.
• IV INDUCTION AGENTS-
IV agents Change in pharmacokinetics in cirrhotics
Thiopentone No change
Propofol Prolonged recovery on infusion
Etomidate Prolonged elimination

81. • MUSCLE RLAXANTS-
MUSCLE RLAXANTS Action in liver diseases
SCh Prolonged
Mivacurium Prolonged with infusion
Pancuronium/Rocuronium Prolonged
Vecuronium Slightly prolonged
Atracurium/Cisatracurium Unchanged(safe)

82. opioids
• Morphine - prolonged elimination half-life, markedly increased
bioavailability of orally administered morphine, decreased plasma
protein binding, and potentially exaggerated sedative and
respiratory-depressant effects.
• Mepridine - 50% decrease in clearance and doubling of half life.
• Fentanyl, sufentanyl, alfentanyl- highly lipid soluble, short acting
(because of rapid redistribution to storage sites), almost exclusively
metabolized in liver, hence 1st dose doesn’t affect much but
repeated top ups and continuous infusion may build up increase
levels in tissues, decrease in elimination and prolonged effect.
• Remifentanyl- Remifentanyl has an ester linkage that allows for
rapid hydrolysis by blood and tissue esterases; such hydrolysis leads
to high clearance, rapid elimination, and recovery.

83. VOLATILE ANESTHETICS
• HALOTHANE-
DIRECT EFFECT
↓HBF
IMMUNE MEDIATED INJURY
HALOTHANEASSOCIATEDHEPATITIS
Ab to
TFH
MILD, SELF LIMITING
HEPATOTOXICITY
MASSIVE HEPATIC
NECROSIS

84. Halothane Hepatitis
• The incidence is 1:7000-30,000 halothane anaesthetics
- higher in women, the middle aged and the obese
• Rarer in paediatric patients and with the newer volatile
agents.
• 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

85. • ENFLURANE
– Cross sensitivity with Halothane.
– Can cause post operative jaundice in patients
previously exposed to Halothane.

86. ANESTHETIC AGENTS & LIVER
FUNCTIONS

87. Effects of Anesthesia on the Diseased Liver
• anesthesia results in moderate reduction in hepatic
arterial blood flow and hepatic oxygen uptake
• no clinical significance of these changes seen in healthy
volunteers
• liver blood flow returns to baseline during surgery
• initial hypoperfusion and/or reperfusion injury may
contribute to postoperative liver dysfunction

88. Effects of Anesthesia on the
Diseased Liver
• Volatile Anesthetics (Halothane & Enflurane)
• reduce hepatic arterial (HA) blood flow (systemic
vasodilatation)
• small negative inotropic effect
• significant hepatic metabolism (halothane - 20%,
enflurane - 3%)
• Isoflurane
• may actually increase HA blood flow
• preferred agent in patients with liver disease
• undergo less hepatic metabolism (0.2%)
(corresponds with lower risk of drug-induced hepatitis)
(risk of halothane hepatitis quite low: 1 in 35 000)

89. Effects of Anesthesia on the
Diseased Liver
• Hypercarbia
• sympathetic stimulation of splanchnic vasculature,
thereby decreasing portal blood flow
• pCO2 should be maintained between 35-40 mmHg
during surgery

90. Effects of Anesthesia on the
Diseased Liver
• Neuromuscular Blocking Agents
• prolonged in patients with liver disease due to:
– reduced plasma pseudocholinesterase activity
– decreased biliary excretion
– increased volume of distribution
• Atracurium
• preferred agent in patients with liver disease
• metabolism independent of the liver
• Doxacurium
• long-acting muscle relaxant
• recommended for prolonged procedures including
hepatic transplantation

91. Narcotics
• morphine and meperidine
• reduces hepatic blood flow
• fentanyl
• preferred narcotic agent
Sedatives
• diazepam
• prolonged metabolism in patients with liver disease
• lorazepam
• eliminated by glucoronidation without hepatic
metabolism
• preferred agent

92. Estimating Operative Risk in Patients with Liver
Disease
• minimal data on precise estimates of operative risk
• most data from small retrospective studies of
cirrhotic patients undergoing abdominal surgery
• pre-operative risk likely dependent on type of
underlying liver disease

93. Perioperative risks

94. Risk assesment
• Child –Pugh score
• MELD score > 18 years
• PELD score < 18 years
• Garrisons score
• Dixon – Freidman score
• Knodell – Ishak score for chronic hepatitis
• ASA Classification
• POSSUM score

95. Risk scoring systems

96. The Child-turcotte-Pugh scoring system

98. CHILD SCORE AND SURGERY
• Child A - safely undergo elective surgery.
• Child B - may undergo elective surgery after
optimisation with caution.
accepted criterion for listing to OLT.
• Child C - contraindication for elective surgery.

99. Model for end stage liver disease(MELD)scoring system

103. MELD SCORE AND SURGERY
• Meld < 10 - safely undergo elective surgery.
• Meld10 -15 - may undergo elective surgery after
optimisation with caution.
accepted criterion for listing to OLT.
• Meld > 15 - contraindication for elective surgery.

106. Histological activity index
(knodell Ishak score)
• Periportal necrosis
( no necrosis to MLN)
• Intralobular necrosis
(no to marked necrosis)
• Portal inflammation
(none to marked infm)
• Fibrosis
(none to cirrhosis)
• Score 0-10
• Score 0-4
• Score 0-4
• Score 0-4 total=22

107. Garrison risk factors for
cirrhosis
• GARRISON et al –factors associated with increased
post operative mortality
S.albumin <3gm/dl
presence of infection
WBC >10.000/cu.mm
Treatment with more than two antibiotics
S.bilirubin>3mg/dl
PT>1.5sec over control
Presence of ascities
Malnutrition
Emergency surgery

108. Risk factors in obstructive jaundice
DIXON – FREIDMAN RISK FACTORS
• S.Bilirubin > 11mg/dl
• Malignant obstruction
• Haematocrit < 30%
• Renal failure
• Cholangitis
• Hypoalbuminemia
􀂄 If at least 3 of above mortality 60%
􀂄 If none of above mortality 5%

109. ASA physical status classification
• ASA I – Normal healthy patient.
• ASA II – Patient with mild systemic disease.
• ASA III – Patient with severe systemic disease.
but is not incapacitating.
• ASA IV – Patient with severe systemic disease
that is a constant threat to life.
• ASA V – Moribund patient who is not expected
to survive without the operation.
• ASA VI – Brain dead patient.

110. EXAMPLES FOR ASA CLASSES
ASA II - Cigarette smoking without COPD
More than minimal drinking
Mild obesity
Well controlled HT or DM without systemic
or end organ involvement

111. ASA III – Morbid obesity
Active hepatitis
Chronic renal failure/ ESRD
Mild COPD ( well controlled)
Poorly controlled HT or DM with systemic
involvement
Stable angina, MI, CVA, CHF, coronary
stent over 6 months ago
Ejection fraction < 40 %
EXAMPLES FOR ASA CLASSES

112. ASA IV – Hepatorenal syndrome
Unstble angina, MI,CVA,Coronary stent
of < 6 months duration
Symptomatic CHF
Ejection fraction < 25 %
Moderate to severe COPD
ASA V - MODS/Sepsis with HD instability
Poorly controlled coagulopathy
EXAMPLES FOR ASA CLASSES

113. ASA I & II - 0.3 %
ASA III - 4 to 5%
ASA IV - 25 to 30%
ASA V - > 70 %
MORTALITY IN ASA SUBCLASS

114. High risk factors for surgery
A) Type of surgery
Emergency > Elective
Intraabdominal > Extraabddominal
Upperabdomen > Intraabdomen
Nonlaproscopic > laprascopic
Emergency CT > Elective CT
Hepatic resection with MELD
score>8/CPS>6
Prior abdominal surgery

115. High risk factors for surgery(cont)
B) Characteristics of patient
Child class C>B>A.
Meld score > 15.
High ASA status.
S.bilirubin >3mg/dl(>11mg in obstructive LD).
Malignant > Benign jaundice.
S.Albumin <3gm/dl.
HCT <30%.
Acute > chronic encephalopathy.
Grade 3 or 4 encephalopathy.
Prolonged PT >3 sec above control(not corrected with vit K)
complication of cirrhosis(Ascites,GE Varices,HRS,HPS,PPHT
Hydrothorax,Cardiomyopathy).
Abnormal quantitative liver function tests.

116. Optimisation before surgery
 Ascites to be drained before surgery if possible.
 Hydrothorax should be treated before surgery.
 Encephalopathy should be corrected before surgery.
 Anemia should be corrected before surgery.
 Coagulopathy should be corrected before surgery.
 Electrolyte imbalance should be corrected before the surgery.
 Nutrional needs should be addressed by either enteral or by
parentral route before surgery.
 Alcohol abstinence for atleast 6 months is needed for elective
suregery.
 Antiendotoxin measures to reduce the renal dysfunction.
 Coexisting illness( COPD, HT & DM) should be optimised.

117. Effect of Type of Surgical Procedure on the
Diseased Liver
• important determinant of post-operative hepatic
dysfunction
• risk: laparotomy > extra-abdominal surgery
• greater reduction in HA blood flow
• cholecystectomy, gastric surgery and colectomy
associated with high mortality rates in patients
with decompensated cirrhosis
• morbidity/mortality higher for emergent than
elective surgery

118. Contraindication for elective surgery
• Acute viral hepatitis
• Acute alcoholic hepatitis
• Fulminant hepatic failure
• Severe chronic hepatitis
• Child's class C cirrhosis
• Severe coagulopathy (pl count ≤50.000/mm3 &
PT↑≥3s despite of vitamin k administration)
• Hypoxia(Po2<60mmhg)
• Cardiomyopathy/ heart failure
• Hepatorenal syndrome

119. Summary

120. Preoperative Evaluation
• 1 in 700 otherwise healthy individuals will have abnormal
liver function tests
• any patient undergoing surgery:
• careful history to identify risk factors for liver disease
• a history of jaundice or fever after anesthesia
• alcohol history and complete review of medications
• findings on physical examination suggestive of liver dz
• patients with known liver disease:
• identify presence of jaundice, ascites, or encephalopathy
• complete biochemical assessment of liver function
• correct coagulopathy, ascites and encephalopathy

121. Clinical presentation
1. Asymptomatic patient with abnormal LFT
2. Acute hepatitis/Acute liver failure
3. Chronic hepatitis
4. Cirrhosis(compensated & decompensated)
5. Obstructive jaundice(Benign & malignant)

122. Asymptmatic patient with abnormal
Liver function tests
• Biochemical screening of healthy asymptomatic
people has revealed that upto 6% have abnml
liver enzyme level but the prevalance of liver
disease in the Gen population is around 1%.
• Liver test must always interpretated along with
careful history and examination as well as to
confirm each abnormal test with another test.

123. Asymptomatic patient with
abnormal LFT
 Aminotransferace elavation < 3times the upper limit
of the normal range ULN is not a contraindication for
elective surgery if bilirubin is within normal limits.
 Liver ALP < 3times ULN is not a C/I for elective
surgery if bilirubin is within normal limits.
 Delay surgery when a patient without any risk factors
or stigmata of liver disease is having more than one
abnormal LFT.

124. Acute Hepatitis
• acute hepatitis contraindication to elective surgery
• peri-operative mortality rates: 9.5 to 13%
(in icteric patients)
• surgery also contraindicated in patients with a
histological diagnosis of alcoholic hepatitis
• mortality rates as high as 55% reported in patients
undergoing open liver biopsy or portosystemic shunt
surgery
JAMA, 1963
Br J Surg, 1982

125. Chronic Hepatitis
• surgical risk correlate with clinical, biochemical,
and histological severity of disease
• elective surgery reported to be safe in patients
with asymptomatic mild chronic hepatitis

126. Fatty Liver and Non-Alcoholic Steatohepatitis
• alcoholic or non-alcoholic fatty liver is not a
contraindication to elective surgery
• trend toward increased mortality following hepatic
resection in patients with moderate to severe
steatosis (ie. >30% of hepatocytes containing fat)
J Gastrointest Surg, 1998
• period of abstinence from alcohol before surgery
advisable

127. Other Causes of Liver Disease
• Autoimmune Hepatitis
• if in remission, elective surgery well tolerated in
patients with compensated liver disease
• perioperative administration of “stress” doses of
hydrocortisone indicated in patients taking prednisone
• Hemochromatosis
• monitoring of diabetes in perioperative period
• assess for possibility of cardiomyopathy
• Wilson’s Disease
• neuropsychiatric involvement - interferes with consent
• D-pencillamine can impair wound healing - decrease
dose in first 1-2 postoperative weeks

128. Cirrhosis
• retrospective studies have shown that perioperative
mortality and morbidity rates correlate well with the
Child-Turcotte-Pugh class of cirrhosis
• Alcoholic Cirrhosis (abdominal surgery): Mortality Rates
1984 1997
• Child’s A 10% 10%
• Child’s B 31 30
• Child’s C 76 82
• some studies have not confirmed predictive value of
Child’s classification, mainly due to few Child’s C patients
• APACHE III can predict survival in cirrhotic patients
admitted to an ICU; yet to be studied in cirrhotics
undergoing surgery

129. Drugs in Liver failure
Drugs Safe Caution
Premedication Lorazepam
Oxazepam
Midazolam
Diazepam
Induction agents Single dose all
are safe
Volatile agents Nitrous oxide
Iso/sevoflurane
Desflurane
Enflurane

130. Drugs in Liver failure
a Safe Caution
Muscle relaxants Atracurium
cisatracurim
Suxamethonium
Pancuronium
Vecuronium
Opioids Fentanyl
Sufentanil
Remifentanil
Remaining drug
Analgesics Paracetamol Other NSAID
Lidocaine
Bupivacaine

131. Resection for Hepatocellular Carcinoma (HCC)
• annual incidence of HCC 3 to 5%
• perioperative mortality rate for hepatic resection
3 to 16%
• postoperative morbidity rates as high as 60%
• 5 year recurrence rates are as high as 100%
• 5 year survival rates are no higher than 50%

132. Anaesthetic consideration for
Chronic Hepatitis
• Surgical risk correlate with clinical features,biochemical
features and histological severity of the disease.
• Elective surgery has been reported to be safe in asymptomatic
patient with mild-moderate chronic hepatitis.
• Symptomatic and histological severe CH have increased
surgical risk particularly if hepatic synthetic or excretory
function is impaired,PHT if present or bridging/MLN
necrosis is seen on liver biopsy.

133. Anaesthetic consideration for
Chronic Hepatitis
• Chronic alcoholic patient should be abstinent from alcohol
for atleast 6 mon to undergo elective procedure.
• NASH not a contraindication for elective surgery ( >30%
hepatocytes if contain fat – increased mortality)
• Hemochromatosis – Evaluate for complication such as
diabetes,hypothyrodism and cardiomyopathy.
• Wilsons disease – Antipsychiatric medication has to be
continued(surgery can ppt or aggravate neurological
symptoms).

134. IV.Complication of Decompensated
cirrhosis
• Portal HT - GE Varices
PH gastropathy
Hyperspleenism
Ascites including SBP
• Respiratory - HPS
PPHT
Hepatic hydrothorax
• Haematological - Anaemia
Thrombocytopenia (qualitative defect
also present)
Coagulopathy

135. Complication of Decompensated
cirrhosis(cont)
• Kidney - Hepatorenal syndrome
• CVS - Cardiomyopathy
• CNS - Hepatic encepalopathy
• MSK - Osteoporosis
Osteopenia
• Nutrition - Malnutrition

136. Respiratory system
• Ventilation-perfusion mismatch caused by
impaired HPV,pleural effusion,ascites
& diaphragm dysfunction.
• Decreases in diffusion capacity due to intersitial
oedema,increased ECF & pulmonary HT.
• Incidence of coexisting pulmonary abnormalities
Hepatic hydrothorax – 5 to10%
H.P.synrome - 40 to 50%
PP hypertension - 4 to 6%
ABG & PFT - 40 to 50%

137. Anaesthetic consideration(R.S)
• Ascites fluid to be drained preoperatively with simultaneous colloid
replacement to reduce the splinting effect.
• Coexistent COPD should be optimised & hydrothorax should be
treated.
• Chest tube drain is C/I in hepatic hydrothorax.
• Increased risk for aspiaration(aspiration prophylaxis & rapid
sequence induction).
• Avoid PEEP as far as possible.
• Avoid N2O in patient with COPD & PPH.
• Avoid hypoxia(High inspired 02) & hypocarbia.
• Response of OLT is poor in PPH when compared to HPS.
• Elective postoperative ventilation for major surgery.
• Extubation should be done when the patient is fully awake.
• HPS & hepatic hydrothorax if present is indication for OLT.

138. Cardiovascular system
• Decreased peripheral vascular resistance.
• Increased cardiac output.
• Increased blood volume but redistributed.
• Low- normal blood pressure with mildly elevated
heart rate.
• Decreased effective circulatorary volume.
• Diminished response to catecholamines.
• Possible cirrhotic & alcoholic cardiomyopathy.

139. Anaesthetic consideration(CVS)
• Pain and light plane of anaesthesia cause decreased HBF through
sympathetic nervous system.
• Hypotensive effect of volume depletion is exacerbated because of
impaired vasoconstrictor response to catecholamines.
• Redistribution of blood flow from splanchnic as well as Skeletal
muscle to central circulation is also impaired.
• Blunted vascular response to exogenous vasopressors and volume
expansion.
• Volume assessment and fluid management thro cvp are often misleading
as cvp are often elevated despite relative hypovolumia from increased
back pressure in the IVC from hepatic enlargement,scarring and ascites
induced increased IA pressure.

140. Anaesthetic consideration(CVS)
• PCWP/CVP guided fluid management.
• Low threshold for starting vasopressors as haemorrhage
is poorly tolerated.
• Low threshold for volume overload as well as to v.presor
induced pulmonary oedema.
• Propranolol if used for prophylaxis for GE varices may
mask the signs of haemorrhage.
• Diuretics should be used with caution in ascites patient
without oedema (protective effect from intersitial fluid
wont be there as in patient with oedema).
• Cirrhotic cardiomyopathy if present is an indication for
liver transplantation.

141. Renal system
• Decreased renal perfusion and GFR.
• Reduction in free water clearance.
• Reduction in sodium excretion.
• Hepatorenal syndrome occurs in 10% of patients with decompensated
cirrhosis(100% mortality if OLT not done).

142. Anaesthetic consideration( Kidney)
• Urea falsely low due to decrease hepatic production.
• Bilirubin lowers the measured s.creatinine(underestimation of renal
dysfunction)
• Renal function assesed by inulin ,125 I iothalamate or 51 cr- EDTA clearance.
• Avoid aggressive diuretic therapy.(Precipitate HE & HRS)
• Absence of response to spironolactone400mg/day & furosemide160mg/day
indicates ascites becomes refractory (consider LVP or TIPS).
• catheterise evening before surgery and start iv fluids while fasting @ 1- 2ml/kg/h to
maintain u.o.of atleast 1ml/kg/hr.( to prevent HRS )
• Avoid morning dose of diuretics before elective surgery.

143. Kidney(cont)
• PCWP/CVP guided I.O.fluid management.
• I.O chart in the P.O.period.
• Avoid hypotension in the P.O.period (meanB.P.10-20% 0f preop value).
• U.O.of atleast1ml/kg/hr must be achieved in the I.O.period (if not
mannitol
or furosemide infusion).
• Avoid NSAID & aminoglycosides in the I.O.period.
• Cirrhotics are also at risk for ATN in the postoperativeperiod.
• HRS if present is an indication for OLT.

144. Gastrointestinal system
 Development of GE varices & spleenomegaly signify
the development of portal hypertension.
 Development of ascites indicates the onset of
hepatic
decompensation.
 GE varices more likely to bleed if the portal vein
pressure exceeds 12mmhg.
 Prognosis after development of ascites is poor.( 50%
die within 3years from the onset of diagnosis)

145. Anaesthetic consideration regarding
gatroesophageal varices
 Blood loss in GE varices is haemodynamically sgnft
and patient should be managed in ICU.
 Propranolol used for prophylaxis will mask the signs
or haemodymamic effects of haemorrhage.
 Airway should be protected to prevent the risk from
aspiration.
 Crystalloid and colloid resuscitation along with the
pharmacological measures such as vasopressin,
somatostatin or octreotide.

146. • Alteast 8-12 units of blood should be crossmatched
during the resucscitation period.
 FFP should be given if the PT is 1.5 times more than
the control value.
 Care should be taken to prevent volume overload as
the baseline SBP of most cirrhotics is 85 to 95mmhg
(volume overload increases hge).
 Endoscopy should be done within 12hrs once the
patient is haemodynamically stable.
Anaesthetic consideration regarding
gatroesophageal varices

147.  Ascites increases the risk of aspiration by increasing intra-
abdominal pressure ( also decreased GITmotility & GERD
due to hiatal hernia in the cirrhotics).
 PICD can be prevented by concurrent administration of salt
poor albumin or other colloid.
 Ascites is said to be refractory if there is no response to the
maximum dose of furosemide and spiranolactone.
 TIPS should be considered for patient with refractory ascites
who is listed for OLT.
 Tense and refractory ascites should be drained adequately
before surgery ( significant intra and postop comp.).
Anaesthetic consideration regarding
ascites

148. Ascites Anaesthetic consideration
Preoperative Respiratory distress
Hypotension if inadeq replaced
after LVP
Hepatic hydrothorax
Risk for SBP (50% mortality)
Intraoperative Risk for aspiration
False high CVP
Haemodynamic instability
Splinting effect to diaphragm
Increased volume of distribution

149. Postoperative - Wound dehiscence
Abdominal wall herniation
Atelectasis
1 litre of ascitic fluid = 50ml of 25% albumin( i.e 1 litre
roughly contains 10gm of protein).
Albumin should be idealy used in case of LVP(>5L/day).
Half of the albumin during the procedure and the other 6 hrs
later.
Ascites Anaesthetic consideration

150. Haematological system
• Anaemia is common with chronic liver disease.
• Thrombocytopenia(qualitative as well).
• Mild thrombocytopenia is often the first manifestation of worsening of
fibrosis in patient with chronic hepatitis.
• Prothrombin time & partial thromboplastin time is prolonged (mild-
moderate prolongation).
• Fibrinogen level will be normal ( low fibrinogen level with severe
thrombocytopenia R/O DIC ).
• Drugs used to treat chronic hepatitis can cause anaemia.
Rifampin – Hemolytic anaemia
Interferon- bone marrow suppression

151. Anaes.consideration(Haematology)
• Liver biopsy can be safely performed if plateletcount>50,000/mm3 and PT as well
as APTT do not exceed 1.5 times the control value( BT not a reliable indicator).
• Avoid drugs that precipitate bleeding such as NSAID/ Warfarin.
• Avoid IM injection to prevent haematoma.
• Haematocrit should be maintained around 30% in the perioperative period.
• Anaemia should corrected preoperatively preferably with packed cell or fresh
whole blood ( Balanced against the risk of inducing HE from haemolysed RBC).
• Thrombocytopenia in hyperspleenism as a rule is mild( severe thrombocytopenia
indicates the development of DIC).

152. Haematology (Cont)
• Thrombocytopenia if present should be preoperatively corrected.
Exploratory laprotomy>50,000/mm3
Closed space surgery>1Lakh/mm3
• PT and APTT becomes abnormal only with severe deficiency of CF (abnormal
with CF < 30% of normal level).
• PT and APTT if prolonged should be corrected to be within 1.5times the control
value.(Risk of Hge increases if PT & APTT exceeds 1.5 times the control value).
• Failure of PT and APTT to respond to vitK/FFP indicates poor prognosis.
• FFP must be transfused just prior to procedure and repeated every 8-12hrs to
maintain acceptable coagulation parameters( chance of volume overload-
Exchange plasma transfusion).

153. Haematology(cont)
• Adequate blood/ blood component should be arranged prior to surgery.
• Invasive arterial BP preferable than NIBP(repeated NIBP cause bruises).
• Blood loss should be closely monitored &should be corrected immedietly
(Hematocrit maintained around 30%).
• FFP should be given when crystalloid,colloid or packed cells are given to
replace blood loss.( 1unit FFP=1unit packed cells=250ml crystalloid)
• Hypothermia should be avoided (humidified gases,warm ivf,warming
blankets,forced air warming devices & blood warmer).

154. Haematology(cont)
• Blood loss can be minimised by perioperative administration of
tranexemic
acid (prostate & ortho surgeries).
• Correct/prevent I.O. factors that increases bleeding(dilution,hpypothermia
hypocalcemia & acidosis).
• Thromboelastography for I.O. assesment of coagulation parameters.
• Universal precautions in patients with hepatitis (30% - HepB & 3% -HepC)
• Even 0.04ml blood may be enough to infect an anaesthesiologist.
• RA not contraindicated if coagulation parameters are within normal.

155. Causes of bleeding in liver disease
• Anatomical factors – gastroesophageal varices
peptic ulcer
gastritis
haemoorhoid
• Thrombocytopenia
• Hepatic function abnormalities
Decreased synthesis of procoagulant protein
Decreased synthesis of coagulation inhibitors

156. Causes of bleeding in liver disease(cont)
Failure to clear activated coagulation factors
Impaired absorbtion and metabolism of vit k
Synthesis of abnormal fibrinogen
• Intraoperative factors – Hypothermia
Dilution
Hypocalcemia
Acidosis

157. • Platelet count.
>100000/mm – safe
70,000-100000 - safe if cg scn is wnl
<70,000/mm3 - unsafe
• Prothrombin time
INR>1.5 - unsafe
• Activated partial thromboplastin time
APTT>40sec -unsafe
Coagulation parameters and neuraxial block

158. Neuraxial anaesthesia(cont)
• Epidural preferred than spinal anaesthesia.
• LA dose should be titrated.(flow limited drug)
• Hypotension more likely with high spinal( T4 level –
20% decrease in HBF) but safe for lower limb
procedures.
• Strict aseptic precautions – increased susceptiblity
for infection.
• Epidural Useful for postopanalgesia/decreases P.O
pulmonary complication.

159. Anaesthetic consideration in
obstructive jaundice
It includes
Coagulopathy
Endotoxemia
Haemodynamic instability
Renal failure
Altered drug handling due to cholestasis
Impaired wound healing.
Measures taken to to reduce the renal failure is responsive better in
benign rather than malign condition.In malignancy only way to reduce
the
incidence of renal failure is to maintain adequate iv volume and
perfusion pressure.

160. Effect of obstructive jaundice on the
cardivascular system
 Negative inotropic effect by bile salt.
 Negative chronotropic effect by bile salt.
 Altered haemodynamic response to haemorrhage.
 Blunted vascular response to vasopressor and
volume
expansion.
 Jaundiced induced cardiomyopathy.

161.  Haemodynamic instability caused by the bile salts &
endotoxin on the cardovascular function.
 Diuretic and the natriuretic effect of bile salt.
 Reduced renal perfusion because of enhanced renal
vascular reactivity to endogenous vasopressors.
 Direct nephrotoxic effect by bile salt and conjugated
bilirubin (controversial)
 Renal tubule blockade of bilirubin cast may further
potentiate the renal injury.
Effect of obstructive jaundice on the
Renal function

162. Measures to prevent perioperative
renal failure
• Maintainence of adequate iv volume( most important of all the
measures).
• Avoid NSAID & AMINOGLCOSIDES.
• Oral lactulose/ ursodeoxycholic acid.
• Endoscopic internal biliary drainage.
• Preoperative and postoperative mannitol if the Bn>8mg per dl
(controversial role).
Dopamine/ furosemide has no role.
Except for maintainence of adequate iv volume and avoidance of
NSAID, all other measures are controversial in malignant
jaundice.

163. Antiendotoxin measures
• Avoid oral antibiotics.
• Avoid percutaneous external drainage.
• Oral lactulose.
• Oral ursodeoxycholic acid.
• Endoscopic internal biliary drainage.
• Experimental drugs – Taurolidine
Rifaximin
Polymyxin.

164. Preoperative evaluation
• Complete history with clinical examination.
• Investigation.
• Risk assesment.
• Management of complication due to liver disease.
• Preoperative optimisation of modifiable risk factors
in Child B status patient and obstructive jaundice.
• Premedication and instruction before surgery(include
the informed high risk consent).

165. Preoperative investigation
• Haematological Blood grouping/typing
Haemoglobin/ HCT
WBC count
Platelet count
Bleeding Time
PT / INR
APTT
• Liver function tests.
• Serology for viral hepatitis.

166. Preoperative investigation(cont)
• Metabolic / Renal
Blood glucose
S.Electrolytes / S.Calcium
Blood urea
S.Creatinine
U.Electrolytes
• Cardiorespiratory
Chest x-ray
ECG
ECHO ( if needed)
PFT/ABG ( if needed) .

167. Ascites Treatment
• Salt restriction
• Fluid restriction
• spiranolactone
• Furosemide
• Albumin
• Not > 2 gm per day
• 800-1000ml/day if serum
sodium < 125meq/L
• Dose 100mg per day
(max dose 400mg)
• Dose 40mg per day
(max dose 160mg)
• 8-10g/L of fluid removed
(if > 5L removed)

168. Coagulopathy Treatment
• Vit K 10 mg sc or slow iv over 20 minutes for 3
days(altered PT due to vit K def if there is 30%
improvement in the first 24 hours).
• FFP in case of emergency rapid correction or in
vit K unresponsive patients.
• Platelet transfusion in case of thrombocytopenia.
• Cryoprecipitate if fibrinogen<75mg/dl.
• DDAVP if BT > 12 minutes.

169. Hepatic encephalopathy treatment
• Care of airway,haemodynamic,metabolic
and acid base status.
• Identify and correct precipitating factors.
• Restriction of protein from the diet.
• Avoid narcotics and sedatives.
• Reduction of blood ammonia by lactulose
and neomycin.

170. Premedication
• Oral premedication preffered than intramuscular.
HE absent – lora / oxazepam (small dose)
HE present - avoid sedative
• Aspiration prophylaxis.
• Vit k slow iv continue till morning of surgery.
• FFP should be given immedietly before surgery.
• Mannitol infusion if bilirubin > 8mg/dl
• Steroidal supplemenation in autoimmune hepatitis.

171. Premedication
• Antipyschotic medication to be continued in pt with wilsons disease.
• Continue other optimisation measures for ascites ,HE etc except for
morning dose of diuretics.
• Large bore iv cannulae with cvp line after excluding coagulopathy.
• Catheterise evening before surgery and start iv fluids @1-2ml/kg/hr
while fasting to maintain u.o. of atleast 1ml/kg/ hr.

172. Induction agents
All the induction agents (single dose) are safe.
Dose has to be reduced and given slowly except in
alcoholics with compensated liver disease.
Haemodynamically stable - thiopentone/propofol
Haemoynamically unstable - ketamine/etomidate

173. Inhalational agents
Halothane & Enflurane has to be avoided because of its
effect on hepatic blood fow and its metabolism.
Maintainence with Isoflurane-O2-N20 / isoflurane – O2
and fentanyl or remifentanyl if N20 has to be avoided.
PEEP may have to be given to prevent hypoxemia but
care should be taken to maintain C.O & B.P.

174. Muscle relaxants
Muscle relaxants
Suxamethonium single dose doesn’t need dose reduction.
Maintaince with Atracurium in titrated doses under neuromuscular
monitoring if available.
Loading dose larger than normal but the maintainence dose is smaller
than normal.
Reversal can be given for minor procedures but for major procedures
elective postoperative ventilation is often needed.

175. Intraoperative considerations
• Goal is to maintain the adequate blood flow and oxygen content in
the blood so as to maintain the oxygen supply – demand relation in
the liver.
• High inspired O2 to prevent hypoexemia.
• Maintainence of adequate cardiac output and B.P.(PCWP/CVP guided
fluid management)
• Avoid hepatotoxic drug / NSAID.
• Avoidance of relative overdose of anaesthetics.
• Maintainence of normocarbia and normothermia.
• Maintainence of adequate haematocrit.
• Adequate blood & volume replacement to prevent hypotension.
• Monitoring of u.o/coag parameters/glucose/calcium and electrolytes.

176. Intraoperative monitoring and equipment
• Pulse oximetry
• NIBP/INVASIVE B.P.
• Electrocardiography
• PCWP/ CVP
• ETCO2
• Temperature
• NM monitoring
• Urine output
• Blood loss(swab,suction,drape
& floor)
• Input – output
• Rapid infusion system
• Forced air warmers

177. Biochemical/Haematological
Monitoring
• Haematocrit
• Serum electrolytes / ionised calcium
• Blood glucose
• Arterial blood gas analysis
• Coagulation parameters / TEG

178. Postoperative management
 Patient with child B grade who has undergone a major surgery
should be shifted to ICU and may need to be electively
ventilated.
 Fluid , electrolyte, acid base balance, coagulation parameters
temperature, u.o and cvs stability should be maintained like
that of i.o.period.
 Sedation and pain medication should be carefully titrated.
 Chest x-ray should be immedietly taken to see the lung fields
and to check central as well as pulmonary catheter.
 Monitor the patient for features of hepatic decompensation.

179. Postoperative Period
• monitor for signs of liver decompensation
including worsening jaundice, encephalopathy
and ascites
• bilirubin and prothrombin time best measures of
hepatic function
• renal function important to monitor because of
the risk of hepatorenal syndrome
• monitoring of serum glucose levels as
hypoglycemia often accompanies postoperative
hepatic failure

180. Sources of this lecture:
• HEPATIC ANATOMY,PHYSIOLOGY & ANESTHETIC
EFFECTS, Dr. Mohd Saif Khan MD ,LHMC, New Delhi
• RISK OF SURGERY IN THE PATIENT WITH LIVER
DISEASE, Ajay Jain,Gastroenterology Fellow ,January
16, 2002.
• ANAESTHESIA AND LIVER DISEASES,
DR.D.KIRUBAKARAN,2011.08.08
• Dr. C.K. Pandey,new delhi, anesthetic consideration
and perioperative risks in patient with liver disease.