Anaesthesia in liver disease patient

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Anaesthesia in liver disease patient

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

www.anaesthesia.co.in anaesthesia.co.in_at_gmail.c
om
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Objectives

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

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

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HKT experiencecholecystectomy
Year Total no. of patient Laparoscopically
2001 46 6
2002 45 3
2003 (till October) 26 2
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General

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

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Physiology

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

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Physiology carbohydrate metabolism

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

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Physiology fat protein metabolism

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

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Important facts

• albumin can be decreased with liver disease
• ?
• colloid osmotic pressure will be reduced
• fewer binding sites for drugs and the unbound,
  active portion of protein-bound drugs will be
  increased example Thiopental.

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Important facts

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

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Physiology

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

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

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Physiology drug metabolism

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

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Physiology drug metablism

• Divided into 2 phase
• Phase I metabolism
• Oxidation
• Reduction / demethylation
• Phase II metabolism
• Conjugation

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Physiology drug metabolism

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

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Physiology drug metabolism

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

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Physiology drug metabolism

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

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Important facts

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

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Pre Operative Sx

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

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Pre Operative Sx

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

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Pre Operative Sx

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

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Diagnosis

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

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Clinical

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

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Pre OP management

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

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Pre OP management

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

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Pre OP management

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

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Childs Classification of liver disease
Group A B C
Serum bilirubin (mg/dl) lt 2.0 2.0 3.0 gt 3.0
Serum albumin (g/dl) gt 3.5 3.0 3.5 lt 3.0
Ascites None Easily controlled Poorly controlled
Encephalopathy None Minimal Advanced
Nutrition (PT) Excellent (1 4 sec) Good (5 6 sec) Poor (gt 6 sec)
Mortality rate 2 5 10 50
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Intra operative factors

• Effect of anaesthesia
• Effect of surgery

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Effect of anaesthesia

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

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Effect of anaesthesia

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

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Effect of surgery

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

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Post operative factors

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

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Post operative factors

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

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Discussion

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

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Hepatorenal syndrome

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

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Hepatorenal syndrome

• Mechanism
• Extreme peripheral vasodilation ? extreme ?
  arterial blood volume hypotension
• ?
• Activates homeostatic mechanism ?
  vasoconstriction of renal vasculature
• ?
• ? GFR plasma renin remains high with salt
  water retention

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Hepatorenal syndrome

• Treatment
• Treated for prerenal failure
• Stop diuretic therapy
• Prognosis is poor

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Anaesthesia for patient with cirrhosis

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

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Anaesthesia for patient with cirrhosis (acute
failure)

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

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Anaesthesia for patient with cirrhosis (acute
failure)

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

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Anaesthesia for patient with cirrhosis (chronic
liver disease)

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

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Anaesthesia for cholecystectomy

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

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Anaesthesia for cholecystectomy

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

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Anaesthesia for liver transplant

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

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Anaesthesia for liver transplant

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

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• Most of us will never take part in a transplant
  but the lessons learned can be applied each time
  we administer anesthesia to a patient with
  hepatic disease

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Latest Update

• 1st dedicated liver unit in SEA (liver ICU)
  Gleneagles Hospital, Singapore
• Equipped with i. Monitoring devices
• ii. Ventilator
• iii. Liver dialysis machine
• (molecular adsorbent recirculating system)
• Pre-requisite existing living donor liver
  transplant (LDLT) program

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Bibliography

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

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Thank you
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om