ANAESTHETIC IMPLICATIONS IN ACUTE PARENCHYMAL LIVER DISEASE

1
ANAESTHETIC IMPLICATIONS IN ACUTE PARENCHYMAL
LIVER DISEASE

• Dr. Mansi Arora

University College of Medical Science GTB
Hospital, Delhi
2
Modified Child-Pugh Score
Parameters 1 2 3
Albumin(g/dl) gt3.5 2.8 - 3.5 lt2.8
INR lt1.7 1.7 - 2.3 gt2.3
Bilirubin(mg/dl) lt2 2 - 3 gt3
Ascites Absent Moderate Tense
Encephalopathy None Grade I-II Grade III-IV
Class Mortality A 5 to 6 10 B 7 to 9 31 C10 to 15 76
3
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.

4
MELD SCORE

• 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
• 3.78Ln serum bilirubin (mg/dL) 11.2Ln INR
  9.57Ln
• serum creatinine (mg/dL) 6.43 (x 0 for
  alcoholics/cholestasis)
• (x
  1 for remainder)

5
MELD SCORE AND SURGERY

• Meld lt 10 - safely undergo elective surgery.
• Meld10 -15 - may undergo elective surgery after
• optimisation with
  caution.
• accepted criterion
  for listing to
• OLT
• Meld gt 15 - contraindication for elective
• surgery

6
ANAESTHETIC IMPLICATIONSIN ACUTE
PARENCHYMALLIVER DISEASE

• By-Mansi Arora
• Moderator-Dr. Sharmila Ahuja

7
SPECIAL CONCERNS

• 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
  (Millers,7ed)

8
ANAESTHETIC GOALS

• 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

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ANAESTHETIC GOALS(cont)

• Maintain renal perfusion
• Avoid-
• Hypotension (adequate fluid balance)
• Hypoxia
• Hypocarbia/Hypercarbia
• Hypothermia/Hyperthermia
• Hypoglycaemia/ Hyperglycaemia

• .

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• 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.

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• EFFECT OF VARIOUS ANAESTHETIC
• DRUGS ON LIVER

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Volatile Anaesthetics

• 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

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Volatile Anaesthetics(cont.)

• 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 O2 delivery hepatic
  venous O2 saturation.
  

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Volatile Anaesthetics(cont)

• ISOFLURANE - Increase flow velocity in hepatic
  sinusoids
• Preserve microvascular blood flow
• DESFLURANE, SEVOFLURANE
• Preserve total hepatic blood flow

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EFFECT OF VOLATILE AGENTS ON HBF
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
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INTRAVENOUS AGENTS

• 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

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INTRAVENOUS AGENTS(cont..)

• 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.

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INTRAVENOUS AGENTS(cont..)

• 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.

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Effect of Hepatic Dysfunction on the Drug
Pharmacokinetics
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)
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MUSCLE RELAXANTS

• 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 (lt0.15mg/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.

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MUSCLE RELAXANTS(cont..)

• 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.

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• To prevent residual muscle weakness in the post
  op. period because of altered pharmacokinetics,
  careful monitoring of the neuromuscular function
  is needed.

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OPIOIDS

• 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.

25
OPIOIDS

• 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.

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NITROUS OXIDE

• 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.

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Drugs in Liver Dysfunction
Drugs Safe Caution
Premedication Lorazepam Oxazepam Midazolam Diazepam
Induction agents Single dose all are safe
Volatile agents Nitrous oxide Iso/Sevoflurane Desflurane Enflurane Halothane
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Drugs in Liver Dysfunction
Drugs Safe Caution
Muscle relaxants Atracurium cisatracurim Suxamethonium Pancuronium Vecuronium
Opioids Fentanyl Sufentanil Remifentanil Remaining drugs
Analgesics Paracetamol Other NSAIDs
Local Anaesthetics Amino esters Lidocaine Bupivacaine
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ANAESTHESIA-RELATED FACTORS

• 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.

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Factors Affecting HBF

• Supine posture Postprandial
  state
• Acidosis Acute
  hepatitis
• Beta agonist
  Phenobarbitone
• Glucagon Dopamine
• Wylie and
  churchill-Davidson

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Factors Affecting HBF

• Upright posture
  Hypocarbia
• Hypoxia
  IPPV/PEEP
• Sepsis
  Haemorrhage
• Mesentric traction Alpha
  agonist
• Beta blockers Volatile
  anaesthetics
• I/V induction agents Regional anaesthesia

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SURGERY RELATED FACTORS

• 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.

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SURGERY RELATED FACTORS

• 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.

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AIMS OF INTRAOP. MANAGEMENT

• 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_at_1-2ml/kg/hr
• Fluids
• Mannitol
• Dopamine

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AIMS OF INTRAOP. MANAGEMENT(cont..)

• 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.

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INTRAOPERATIVE MONITORING

• 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

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INDUCTION OF ANAESTHESIA

• 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

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MAITENANCE OF ANAESTHESIA

• 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.

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EMERGENCE FROM ANAESTHESIA

• 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)

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POSTOPERATIVE MANAGEMENT

• 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

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POSTOPERATIVE MANAGEMENT(cont..)

• 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

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POSTOPERATIVE COMPLICATIONS

• Impaired Consciousness - over sedation.
• Impaired Respiration - opioid overdose.
• Inadequate reversal.
• Chest infection.
• Oliguria renal failure.
• Deterioration of hepatic function/ postop.
  Jaundice.

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REGIONAL ANAESTHESIA

• Coagulation profile should be within normal
  limits.
• If there is marked hypotension (gt20 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.

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REGIONAL ANAESTHESIA(cont)

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

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SUMMARY

• 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.

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REFERENCES

• Miller RD. Millers Anaesthesia.7th ed.
  Anaesthesia and the hepatobiliary system66.
• Wylie and Churchill-Davidsons-A Practice of
  Anaesthesia 7th ed.The physiology of
  liver17297-307.
• Roberts-Prys. International Practice of
  anaesthesia. Volume170-73.
• 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 Anaesthesia34773-801

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THANK YOU
48
ANAESTHETIC GOALS(cont..)

• Choose an appropriate anaesthetic agent-
• Effect on HBF
• Metabolism

49
Modified Child-Pugh Score
Parameters 1 2 3
Albumin(g/dl) gt3.5 2.8 - 3.5 lt2.8
INR lt1.7 1.7 - 2.3 gt2.3
Bilirubin(mg/dl) lt2 2 - 3 gt3
Ascites Absent Moderate Tense
Encephalopathy None Grade I-II Grade III-IV
Class Mortality A 5 to 6 10 B 7 to 9 31 C10 to 15 76
50
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.

51
MELD SCORE

• 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)

52
MELD SCORE AND SURGERY

• Meld lt 10 - safely undergo elective surgery.
• Meld10 -15 - may undergo elective surgery after
• optimisation with
  caution.
• accepted criterion
  for listing to
• OLT
• Meld gt 15 - contraindication for elective
• surgery

53
EFFECT OF HEPATIC DYSFUNCTION ON DRUG
PHARMACODYNAMICS

• 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.

54

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