Dr. Mansi Arora

University College of Medical Science & GTB Hospital, Delhi

Parameters 1 2 3

Albumin(g/dl)

>3.5 2.8 - 3.5 <2.8

INR <1.7 1.7 - 2.3 >2.3

Bilirubin(mg/d

l)

<2 2 - 3 >3

Ascites Absent Moderate Tense

Encephalopat

hy

None Grade I-II Grade III-IV

Class Mortality

A =5 to 6 10%

B= 7 to 9 31%

C=10 to 15 76%

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.

Objective score ( no interindividual variation in contrast to child –pugh score that has 2 subjective component).

Designed to predict survival after TIPS 2 control bleeding varices but now used for prioritizing patients for OLT.

MELD = 3.78[Ln serum bilirubin (mg/dL)] + 11.2[Ln INR] + 9.57[Lnserum creatinine (mg/dL)] + 6.43 (x 0 for alcoholics/cholestasis) (x 1 for remainder)

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

By-Mansi Arora

Moderator-Dr. Sharmila Ahuja

Advanced liver disease may impair the elimination, prolong the half life & potentiate the effects of several drugs.

So drugs with their adjusted dosages should be used cautiously

Data suggests that patient with acute hepatitis are at increased risk for hepatic failure and death after elective surgery.

Post op. jaundice may occur as a result of intraop. Hepatobilliary injury, anaesthetic induced hepatotoxicity, severe hepatic hypoperfusion and medications (Miller’s,7ed)

In a patient with acute parenchymal liver disease - main objective is to

Minimize physiological insult to liver and kidney.

Achieved by-

Maintain HBF Maintain O2 supply-demand relationship in liver.

Adequate pulmonary ventilation and CVS function

Maintain renal perfusion Avoid-

Hypotension (adequate fluid balance)

Hypoxia

Hypocarbia/Hypercarbia

Hypothermia/Hyperthermia

Hypoglycaemia/ Hyperglycaemia

.

Various anaesthetic drugs & techniques affect the hepatic function by alteration in HBF(mainly) or directly causing hepatocellular injury.

AND

Hepatic dysfunction also alters the pharmacokinetic

-s of the drug. So altering their dosages , clearance and metabolism.

EFFECT OF VARIOUS ANAESTHETIC DRUGS ON LIVER

All volatile anaesthetics decrease total hepatic blood flow.

THBF= PBF + HABF

Techniques of measuring PBF/HABF :-

• Plasma clearance of Indocynine green dye

• TEE

• Doppler

Most profound decrease in hepatic blood flow :-

Halothane

Mechanism of decrease in THBF -

◦ Decrease in MAP.

◦ Decrease in CO

HALOTHANE - more effect on HABF : Hepatic artery

vasoconstriction.

Disrupt compensatory mech.- Hepatic arterial buffer

response.

Also decreases hepatic O22 delivery & hepatic venous

O2 2 saturation.

ISOFLURANE - Increase flow velocity in hepatic sinusoids

Preserve microvascular blood flow

DESFLURANE, SEVOFLURANE

Preserve total hepatic blood flow

V. Agent

Metabolism HABF HABR

O2 delivery

Halothane 20 – 46 - - - - Lost Decrease

Enflurane 2.5- 8.5 - - - Lost Decrease

Desflurane 0.02 - - Lost Decrease

Isoflurane 0.2 – 2 preserved preserved preserved

Sevoflurane 2 - 5 preserved preserved preserved

THIOPENTONE – capacity limited drug. Dose has to

be reduced for induction because of decreased protein

binding & reduction in enzyme activity.

Thiopentone- Higher dose is needed in alcoholic with

compensated liver disease because of CYP-450

enzyme induction by alcohol.

Duration of action of single dose will not be prolonged

as the major determinant of a single dose is

redistribution

KETAMINE-Flow limited drug having high extraction ratio & high hepatic clearance.

Maintains the CO by sympathomimetic action. So maintains the HBF

ETOMIDATE-Highly protein bound drug with high vd & clearance.

Maintains the CO & MAP-so minimal effect on HBF. Metabolism by-hepatic microsomal enzymes and

esterases-so dosages should be decreased in hepatic dysfunction.

Metabolism of PROPOFOL is dependent on Hepatic

blood flow as it is primarily metabolized in liver .

Propofol cause the maximum decrease in HBF among

the induction agents. Thus resulting in prolongation of

action even after single dose.

Propofol in contrast to other iv induction agents has

extrahepatic metabolism.

Slow titrated dose of induction agents with smooth

intubation will have little impact on the HBF.

Liver dysfunction Effect on the drug

Decreased PBF & fraction

of shunt increased

First pass metabolism for the

oral drug decreased (e.g. BZD)

Hypoalbuminemia Increased unbound fraction

(e.g. propofol)

Obstructive jaundice Decreased biliary excretion of drugs (e.g.morphine)

Change in enzyme function Metabolism either can be

increased or decreased

Ascites Increased Vd (e.g. NM Blocking agents)

Succinylcholine– Duration of action rarely gets prolonged

despite reduced pseudocholinesterase level.

Duration of action of Pancuronium and Rocuronium gets

prolonged because of increased Vd and impaired hepatic

metabolism (altered pharmacokinetics).

Duration of action of Vecuronium (<0.15mg/kg) may be

slightly prolonged or unaffected as it is excreted in bile

(30%).

Duration of action of Mivacurium gets prolonged because of

the reduced plasma cholinesterase level.

Atracurium and cis-atracurium – Duration of

action not affected as both the drugs undergo

organ independent elimination – Ester hydrolysis

and Hoffmans degradation.

Duration of action of above drugs are infact

reduced because of increased Vd & increased

binding to globulins.

To prevent residual muscle weakness in the post op.

period because of altered pharmacokinetics, careful

monitoring of the neuromuscular function is needed.

Morphine- Hepatic metabolism Extrahepatic metabolism

Decreased plasma protein binding- increased bioavailability.

Interval of dosages-should be increased to 1.5-2

fold. Spasm of sphincter of Oddi.

Should be used cautiously in pts. with liver disease.

Fentanyl and Sufentanil- Duration of action of single

dose is not altered in compensated liver disease.

Alfentanil- Duration of action is prolonged because of

the increased free fraction of the drug.

Remifentanil- Duration of action is unaffected as it is

metabolised by nonspecific esterase.

Meperidine- 50% decrease in clearance leading to

doubling of half life.

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.

Drugs Safe Caution

Premedication Lorazepam

Oxazepam

Midazolam

Diazepam

Induction agents Single dose all

are safe

Volatile agents Nitrous oxide

Iso/Sevoflurane

Desflurane

Enflurane

Halothane

Drugs Safe Caution

Muscle relaxants Atracuriumcisatracurim

SuxamethoniumPancuroniumVecuronium

Opioids Fentanyl Sufentanil Remifentanil

Remaining drugs

Analgesics Paracetamol Other NSAID’s

Local Anaesthetics Amino esters LidocaineBupivacaine

ARTIFICIAL VENTILATION-◦ Decreases hepatic blood flow◦ Significant decrease with addition of PEEP.

HYPOXIA-◦ Arteriolar constriction & decrease in flow.

HYPOCAPNIA & HYPERCAPNIA-◦ Both causes decrease in HBF.

Supine posture Postprandial state

Acidosis Acute hepatitis

Beta agonist Phenobarbitone

Glucagon Dopamine

Wylie and churchill-Davidson

Upright posture Hypocarbia

Hypoxia IPPV/PEEP

Sepsis Haemorrhage

Mesentric traction Alpha agonist

Beta blockers Volatile anaesthetics

I/V induction agents Regional anaesthesia

Nature and extent of surgery - Most important determinant of hepatic blood flow & postop. Hepatic dysfunction.

Risk greatest with-◦ Abdominal surgery◦ Billiary surgery◦ Cardiac surgery

Increased risk of morbidity & mortality of any type of surgery in presence of acute parenchymal liver disease.

In case of acute parenchymal liver disease-postpone elective surgery until liver dysfunction is investigated & managed.

In emergency cases- optimize the patient in whatever time available before surgery.

Avoid & minimize physiological insults to the liver. Avoid renal insults. Preserve cardiac output with fluid loading. Maintain- Normovolemia Normocapnia (PaCO2 around 40mmHg) Monitor acid base disturbances & electrolyte

abnormalities. Preservation of urine output@1-2ml/kg/hr Fluids Mannitol Dopamine

Accurate replacement of blood loss - crystalloids/ colloids/packed cells

Maintain normoglycemia- (prone to hypoglycemia).

Maintain normothermia (hypothermia worsens coagulopathy) - warm fluids, humidification, space blankets etc.

Avoid nephrotoxic antibiotics & NSAIDS.

Invasive monitoring may be considered.

ECG (H.R.), B.P, SpO2

ETCO2

CVP Urine Output Core body temperature NM monitoring ABG with S.E. Blood Sugar Blood Loss If needed- Hb, PT, PTTK

Preoxygenation◦ 3-5 min. with 100% O2

Choice of Agents◦ Induction Agents

Thiopentone Etomidate Propofol

◦ Muscle Relaxants Atracurium Vecuronium Succinylcholine

◦ Volatile Anaesthetics Isoflurane Sevoflurane Desflurane

O2 + N2O + Inhalational agent + Muscle relaxant.

Controlled ventilation:-

◦ Avoid large tidal volumes.◦ Resp. rate of 10-12 breaths/min.◦ Add PEEP if necessary.◦ Avoid high airway pressure.

Reversal of NM blockade should be guided by NM monitoring.

Done only when patient completely out of muscle relaxants effects.

Extubate the trachea when patient completely awake.

Reverse with Neostigmine(0.03-0.05mg/kg)and Atropine(0.01mg/kg)

Achieve cardiovascular stability- fluids, dopamine..

Maintain oxygenation◦ Supplement O2 up to 12-16 hrs post op.

Continue Mannitol if used intraop. (till 36 hrs postoperatively)◦ Maintain Urine Output(0.5 ml/kg/hr)

Replace urine losses

◦ Avoid Dyselectrolytemia

Adequate analgesia :- Intravenous agents ( tailored doses) Regional anaesthesia (if coagulation profile is

normal) Epidural Intercostal nerve block

Avoid Hypothermia / Hyperthermia

Replace blood/ blood products.

Proper antibiotics in post op. period

Impaired Consciousness - over sedation.

Impaired Respiration - opioid overdose.

Inadequate reversal.

Chest infection.

Oliguria & renal failure.

Deterioration of hepatic function/ postop. Jaundice.

Coagulation profile should be within normal limits.

If there is marked hypotension (>20% baseline)- Decreased HBF Increased chances of renal failure

Dosages of Lignocaine & Bupivacaine should be

reduced upto 50%.

Epidural anaesthesia has an added advantage of CVS stability.

Key Points- Avoid hypotension. Maintain adequate fluid balance. Maintain urine output ≥ 1ml/kg. Avoid vasopressors (If Warranted Dopamine may be used.)

Patients with acute parenchymal liver injury have increased morbidity & mortality after elective surgery.

Choice of anaesthetic agents & techniques should aim at minimizing physiological insult to liver and kidney.

Dosages of drugs should be altered in accordance with degree of hepatic dysfunction present.

Meticulous post.op monitoring is required with maintenance of oxygenation &circulation.

Miller RD. Miller’s Anaesthesia.7th ed. Anaesthesia and the hepatobiliary system;66.

Wylie and Churchill-Davidson’s-A Practice of Anaesthesia; 7th ed.The physiology of liver;17:297-307.

Roberts-Prys. International Practice of anaesthesia. Volume1;70-73.

Friedman LS, Maddrey WC: Surgery in the patient with liver disease. Med Clin North Am 1987 May; 71(3): 453-76.

MorganGE. Clinical Anaesthesiology.4 ed.Hepatic physiology& Anaesthesia;34:773-801

Choose an appropriate anaesthetic agent-

Effect on HBF

Metabolism

ParametersParameters 11 22 33

Albumin(g/dl) Albumin(g/dl) >3.5>3.5 2.8 - 3.52.8 - 3.5 <2.8<2.8

INRINR <1.7<1.7 1.7 - 2.31.7 - 2.3 >2.3>2.3

Bilirubin(mg/dl)Bilirubin(mg/dl) <2<2 2 - 32 - 3 >3>3

AscitesAscites AbsentAbsent ModerateModerate TenseTense

EncephalopathyEncephalopathy NoneNone Grade I-IIGrade I-II Grade III-IVGrade III-IV

ClassClass

MortalityMortality

A =5 to 6A =5 to 6

10%10%

B= 7 to 9B= 7 to 9

31%31%

C=10 to 15C=10 to 15

76%76%

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.

Objective score ( no interindividual variation in contrast to child –pugh score that has 2 subjective component).

Designed to predict survival after TIPS 2 control bleeding varices but now used for prioritizing patients for OLT.

Meld score = 3.78 x Log (BN) + 11.2 x Log (INR) +

9.57x Log(cr) +6.43 (x 0 for alcoholic and cholestatic condition , x 1 for remainder)

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

Increased sensitivity to CNS depressants.

Decreased sensitivity to vasopressors.

Enhanced effect to anticoagulation.

Enhanced Na retention – NSAIDs/ Steroid.

Ascites /oedema may be resistant to diuretics.

Friedman LS, Maddrey WC: Surgery in the patient with liver disease. Med Clin North Am 1987 May; 71(3): 453-76[Medline].