Approach to Jaundice

Dr.Ashok.K.

Jaundice factfile

Approximately 1 out of 80 healthy patients who undergo cardiac surgery and anaesthesia may have clinically significant post operative liver dysfunction that is totally unrelated to surgery or anaesthesia

Key Learning Objectives

What is jaundice? Bilirubin metabolism Implications of hyperbilirubinemia D/D of post operative jaundice Appropriate workup. Management

Definition of Jaundice

Jaundice from French word “jaune” for yellow. Yellow discoloration of skin, M/M and sclera -

secondary to hyperbilirubinemia. Bilirubin is yellow tetrapyrrole. Clinical Jaundice when total bilirubin is > 2.0-

3.0 mg.

Bilirubin metabolism

PREHEPATIC - HAEMOLYTIC

HEPATOCELLULAR POST HEPATIC-OBSTRUCTIVE

Cardiovascular implications of hyperbilirubinemia

Cholemia can impair myocardial contractility

Direct depressant effect on the SA node. Blunts response to vasopressors Hyperdynamic circulation More susceptible to hypotension from

blood loss.

HYPERBILIRUBINEMIA

Production Clearance

Increased Bilirubin production

Hemolysis Massive blood transfusion Incompatible transfusions Ineffective erythropoiesis Large hematoma absorption

Hemolytic Jaundice

Unconjugated hyperbilirubinemia due - hemolysis,

- resorption of hematoma,

- minor/ major incompatibility

- massive transfusion 10% of transfused RBCs hemolyse within the

first 24 hours following transfusion. Each unit of blood provides a bilirubin load of

250 mgs/100 cc of blood

Hemolytic Jaundice

Seen in caged ball valves, multiple prosthetic valves, periprosthetic leaks, prosthetic valve endocarditis.

Diagnosis is by elevated LDH, reticulocyte count, unconjugated bilirubin, and urinary haptoglobin.

ECHO- abnormal rocking of prosthesis, regurgitant jets.

Hemolytic Jaundice

Medical therapy: Blood transfusion.

Iron and folate supplements.

Avoid hepatotoxic drugs. Surgical therapy: Repair of perivalvular leaks

or valve replacement in patients with severe hemolysis in patients requiring repeated blood transfusions or those with CCF.

Decreased clearance of Bilirubin

Decreased uptake by hepatocytes - Gilberts Syndrome

- Criggler Najjar Type I,II

Impaired excretion of conjugated Bile from Hepatocytes

- Dubin Johnson Syndrome

- Rotor Syndrome

Acute Liver Diseases

Viral infections

Parasitic infections- Malaria, Leptospirosis

Reye’s Syndrome

Alcoholism

Chronic Liver Diseases

Viral ( Hep B & C ) Alcohol Vinyl chloride, CCl 4 Metabolic Liver Diseases

- Wilson’s, - Hemochromatosis,

- Alpha-1antitrypsin deficiency.

Viral hepatitis

Hepatitis A-E They can elude peri op detection during

their incubation periods. Diagnosis made by clinical symptoms,

signs, and serology Mainstay of therapy is supportive Appropriate preventive measures to be

taken to prevent cross infection

Benign postoperative cholestasis

Mild self - limiting conjugated hyperbilirubinemia

Reactive hepatitis - multifactorial origin

- reduced HBF

- hypoxia, hypercarbia

- breakdown of transfused cells

- temporary hepatocellular dysfunction

Benign postoperative cholestasis

Warrants assessment of the patient’s condition and sequential biochemical profiles.

Coagulopathy corrected with Vit K. Usually subside within 3-4 weeks. Failure of Vit K to correct a prolonged

PT typically indicates the presence of hepatic parenchymal dysfunction

Progressive severe jaundice

Primary biliary tract problem Significant liver disease Severe sepsis

Sepsis

Early - Increased splanchnic blood flow as a consequence of increased hepatic oxygen extraction to support phagocytosis of sudden overload of bacterial endotoxins.

Late - Constricted splanchnic vasculature due to septic shock.

Dysregulation of physiologic hepatic arterial buffer response.

Right heart failure

Passive hepatic congestion due to CCF causes little if any damage to liver.

Prognosis depends on the severity of underlying cardiac illness.

Reversible after the cardiac function is improved.

Anaesthetic Agents

N20 – Higher prevalence of jaundice in personnel chronically exposed to N2O.

Propofol, midazolam, fentanyl have not been shown to significantly alter hepatic function.

Very large doses (>750 mgs) of thiopentone may cause hepatic dysfunction.

Halothane hepatitis

Incidence 1:7000-30,000 It is even rarer in paediatric patients and

with the newer volatile agents. The risk is thought to be higher in - women, - middle aged, - obese, - repeated exposure within 4 weeks

Halothane hepatitis

Possible immunological mechanism.. Hepatic blood flow is decreased by

halothane in parallel with an overall decrease in cardiac output.

Avoid repeat exposure within 3 months. History of unexplained jaundice following

Halothane use is an absolute contraindication for its further usage

Common Hepatotoxic drugs

Isoniazid Oral contraceptives Androgens Chlorpromazine Erythromycin Acetaminophen Hydralazine Methyl dopa

Halothane Alcohol Valproic acid Phenytoin Carbamazepine Statins Allopurinol Amiodarone

Drug induced liver damage

ANTIBIOTICS

Tetracyclines - fatty infiltration Penicillins,Cephalosporins – hepatitis Sulphonamides - hypersensitivity focal hepatocellular

necrosis

Drug induced liver damage

ANALGESICS

Paracetamol - centrilobular necrosis Salicylates - focal hepatic necrosis Carbamazepine - cholestasis

Drug induced liver damage

STEROIDS - cholestasis. HALOTHANE - hepatitis ,massive liver

cirrhosis. PHENYTOIN - hepatocellular necrosis

Statins

HMG - CoA reductase inhibitors. Statins reduce cholesterol by blocking

an enzyme in the liver (HMG-CoA reductase) that produces cholesterol.

Statins cause abnormalities of liver tests, and cause transient elevations in liver enzymes.

Statins

Therapy should be discontinued if > 3- fold elevation in AST,ALT occurs.

Enzyme levels return to normal within 2 weeks. Levels should be measured 6 weeks and 3

months after initiation of therapy and every 6 months thereafter.

Contraindicated in the presence of pre existing hepatic dysfunction.

Aspirin

Well documented cause of dose-related, reversible form of hepatotoxicity.

Within days to weeks after initiating therapy.

Increased aminotransferases. Hyperbilirubinemia uncommon. Resolves with discontinuation of therapy.

Paracetamol

Commonly used drug for post op pain. Large doses (3-8 gm/day) results in

chronic liver injury. In patients with poor nutritional status

even 2 gm/day may produce serious liver injury.

Whenever suspected , N-acetylcysteine should be given without delay,

Post Pump Jaundice

Hypotension Hypoxia Haemolysis Heart failure. Hypothermia ???

Post Cardiopulmonary bypass

Neurohumoral response Non pulsatile perfusion High dose vasopressors

History

H/O Blood transfusion H/O IV drug abuse Alcohol Hepatotoxic drugs, toxins,infections Family History Past Medical History Any Abdominal Surgery

Physical Examination

Icterus Fever Abdominal mass/ tenderness Stigmata of Chronic Liver Disease Kayser-Fleischer ring Hyperpigmentation, Xanthomas

Lab investigations

Liver function tests Blood culture USG/ CT ERCP/ PTC Liver biopsy

Aminotransferases

Indicators of hepatocellular injury Normal levels:

AST- 5-35 IU/L

ALT- 5-35 IU/L

Aminotransferases

Small increase (<3-fold) – steatosis, chronic viral hepatitis

Larger increases (3-20 fold) – suggest acute hepatitis or exacerbation of chronic hepatitis

Largest increases (>20-fold) – indicates massive hepatocellular necrosis (severe viral hepatitis, septic shock, drug toxicity)

Alkaline Phosaphatase

Sensitive test for assessing the integrity of the biliary system.

Also elevated in hepatocellular jaundice, Pajet’s disease, pregnancy.

Normal level: 30-300 IU/L.

Bilirubin

Assessment is central to the evaluation of hepatobiliary disorders.

Normal level- 0.25-1.0 mg/dl Estimation of direct, indirect and

total bilirubin.

Albumin

Constitutes 60% of total protein Major determinant of C.O.P Best indicator of hepatic synthetic function. Normal value: 3.5-5.0 gm/dl May be decreased in nutritional deficiency Long half life -20 days- may not reflect

acute injury .

Glutathione -S- transferase Sensitive and specific marker for drug induced

liver damage. Aminotransferases are highly located in zone 1

periportal region. GST is predominantly located in zone 2

centrilobular hepatocytes. Centrilobular hepatocytes are more susceptible

to injury from hypoxia, hypotension and toxic products of drug metabolism

Gamma glutamyl transpeptidase

Specific marker for alcoholic liver disease.

Normal values:

Males: 11-51 IU/L.

Females: 7-33 IU/L.

5’ Nucleotidase

Highly specific for hepatobiliary injury Also increased in cholestatic jaundice

LDH

Serves as a marker for hepatic injury. Markedly increased in hepatocellular

necrosis, shock liver, hemolysis, myocardial infarction.

Normal level: 70-250 IU/L.

Serological Markers

Hepatitis A, B, C

Ferritin

Alpha-1 antitrypsin level

Ceruloplasmin

AMA

ANA & antismooth muscle antibody

CLINICAL APPROACH

Management of post op jaundice

Determine the nature of jaundice by LFTs and urine testing for bilirubin

When suspected- screening tests for hemolysis

R/o sepsis – blood culture If jaundice is cholestatic, - withdraw any offending drug - USG,ERCP,PTC - Percutaneous liver biopsy

Hemolytic jaundice

Unconjugated hyperbilirubinemia Increased urobilinogen and urobilin in

urine. Increased LDH Increased reticulocyte count History S/O hemolysis.

Hepatocellular jaundice

Grossly elevated serum transaminases. Conjugated hyperbilirubinemia. Increased GGT,5’ Nucleotidase Increased alkaline phosphatase History S/O hepatocellular injury.

Cholestatic jaundice

Conjugated hyperbilirubinemia Increased GGT Increased 5’ Nucleotidase Increased Alkaline phosphatase Minimal or no elevation of transaminases Presence of bilirubin in urine. USG,CT,PTC.

Interpretation of LFTs

TESTS HEMOLYSIS PARENCHYMA CHOLESTASIS

AST,ALT N INCREASED N

ALP N N INCREASED

Sr.protein N DECREASED N

PT / INR N INCREASED N

Bilirubin UNCONJUGATED CONJUGATED CONJUGATED

Patients with active liver disease, such as hepatitis, are at high risk of deterioration during surgery and this should be avoided or delayed where possible.

Hypoperfusion, haemodilution and other factors that reduce the delivery of oxygen to the liver or increase the bilirubin load are thought to cause postoperative hyperbilirubinaemia and should be avoided.

Longer the operative time and the larger the volume of blood transfused, the higher the incidence of postoperative hyperbilirubinaemia

Summary

Distinguish whether jaundice is prehepatic, hepatic or post hepatic.

Identify reversible causes. Mainstay of treatment - supportive. Discontinue possible hepatotoxic drugs. Sepsis mandates aggressive therapy. Extrahepatic biliary obstruction may

prompt surgical treatment.

THANK YOU