Anaesthesia for Patients with Cholestatic Liver Disease

1. Anaesthesia for Patients with Cholestatic Liver Disease Dr. NitishParmar University College of Medical Science & GTB Hospital, Delhi

2. Definition Type/etiology D/D of jaundice Anaesthetic implications Anaesthetic management Cholestatic liver disease

3. Cholestasis • Cholestasis is an impairment of bile formation and/or bile flow which may clinically present with fatigue, prurutis, and in its most overt form, Jaundice. • Cholestatic liver disease may result from necro-inflammatory lesions, alteration in metabolic processes or external bile duct compression

4. Cholestasis • The two broad categories of cholestatic liver disease reflect the anatomic site of abnormal bile retention Intra-hepaticExtra hepatic (ostruction at the level of (impediment in the Hepatocytes/canalicular biliary tree) Membrane) • Distinction is important for therapeutic reasons

5. Cholestasis Intrahepatic Extrahepatic Aquired Benign Malignant Familial • Rotors syndrome • Dubin johnson syndrome • Cystic fibrosis • Common bile duct stone • Hepatoma • Acute Pancreatitis • Choledochal cyst • Pancreatic pseudocyst • Primary biliary cirrhosis/cholangitis • Drugs • Alcoholism • Pregnancy • Sepsis • TPN • Ductal carcinoma • Pancreatic carcinoma • Carcinoma of the gallbladder • Metastatic carcinoma

6. Cholestasis causing drugs • Oral contraceptives • Anabolic steroids • Chlorpromazine • Carbamazepine • Antibiotics- erythromycin, rifampicin.

7. Clinical hallmark of cholestasis

8. Contd… • Cholestatic liver disease is characterized by triad of jaundice pruritis and generalized fatigue • Jaundice is a symptom complex which is characterized by yellow discoloration of tissues and body fluids due to increase in bile pigments. • Clinical jaundice is evident when the serum bilirubin > 2.5 mg/dl

9. Jaundice

13. Cholestatic jaundice

15. Cholestatic jaundice : Benign Vs Malignant

16. Pathophysiology Cholestasis Absence of bile in the intestines Retention of bile solute in the liver Bile constituents in the serum  Hepatocyte function  Protein synthesis Clotting factor Metabolic dysfunction of cyto-450 Pruritus Hypercholesterolemias Xanthomas Systemic alterations Malabsorption syndrome  Vit A, D, E, K Escape of endotoxin in the blood

17. Anaesthetic problems in obstructive jaundice Cardiovascular effects Hyperbilirubinemia Deposition in the myocardium impaired myocardial contractility bradycardia

18. Cardiovascular Effects Circulating bile salts (cholemia) also leads to: 1. ↓ ability to mobilize blood from splanchnic circulation during hemorrhage 2. ↓ sensitivity to vasopressors  Hypotension & circulatory collapse Small blood losses are poorly tolerated: therefore replace volume losses immediately in perio-perative period.

19. Renal alterations • 8-10% association between renal failure and obstructive jaundice (related to the degree of hyperbilirubinemia) • Mortality rate – 70-80% • Causes of renal hypoperfusion

20. Coagulation abnormalities • Deficiency of plasma clotting factors due to ↓ absorption of vit K • Vit K dependent – 2, 7, 9, 10 • Non-vit K dependent- all factors except factor 8 • Platelet abnormalities, qualitative and quantitative (mainly due to re-distribution in spleen) • Low grade DIC •  production of inhibitors of coagulation such as ATIII, protein C and S • Liver is the clearance site of activated coagulation factors and fibrinolytic enzymes

21. Endotoxemia Causes 1. Bile salts are surfactants which disrupt endotoxins Absence of bile salts in intestines   clearance of endotoxins 2. Absence of bile salts in intestines   bacterial flora 3. Breakdown of GI mucosal barrier   bacterial translocation 4.  hepatic reticuloendothelial system function (in hepatic failure)   clearance of endotoxins

22. Impaired wound healing • Multiple vitamin deficiencies • Bone disease: Vit D deficiency, Hypocalcemia • Altered drug handling due to cholestasis • Long standing extrahepaticbiliary obstruction > 1yr/intrahepatic obstruction • biliary cirrhosis • problems of liver dysfunction

23. Preoperative Evaluation • Objectives • 1. Assess the type and degree of liver dysfunction • 2. Effects on other organ systems • 3. Risk stratification • History: • abdominal pain, fatigue, pruritis, weight loss, anorexia, dark urine, pale stools • Examination • Jaundice, scratch marks, xanthomas, palpable GB lump, cirrhotic stigmata in long standing cases

24. Investigations • Hemogram with platelet count • RBS • BUSE with S. creatinine, BUN may be falsely low even in presence of renal failure • LFT -  serum bilirubin (conjugated > unconjugated),  ALP, mildly elevated transaminases,  albumin, reversed A/G ratio • Coagulation profile – PT/PTTK and INR • CXR, ECG • Hepatic imaging – ERCP, liver biopsy, if required

25. Preoperative variable contributing to poor prognosis in patients undergoing surgery for Extrahepatic cholestasis • Anemia (hematocrit <30%) • Evidence of pre-existing renal disease • Malignancy • If all 3 +nt mortality >60% if none, mortality <5% • Age >60 yrs • Plasma bilirubin >12 mg/dl (204 µmol/l) • Poor preoperative quality of life

26. Type of surgery Surgery on the biliary tract Gastric surgery Colon sugrery Hepatic resection Cardiothoracic surgery Non cardiac thoracic surgery

27. Modified Child-Pugh scoring system • Class A – 5-6 pts • Class B – 7-9 pts • Class C – 10-15 pts

28. For cholestatic diseases bilirubin is disproportionate to the hepatic dysfunction

29. General considerations in anaesthetic management • Minimize the physiological insult to the liver and kidney • Maintain O2 supply-demand relationship • Adequate pulmonary ventilation and CVS function • Maintain renal perfusion & meticulous fluid balance • Choose appropriate anaesthetic agent • Metabolism of the drug and its effect on hepatic blood flow to be kept in mind

30. Preoperative optimization Prevent hypovolemia and maintain urine output • Adequate hydration is of paramount importance • IV fluids 1-2 ml/kg/hr night before surgery If bilirubin >8 mg% Mannitol to maintain a urine output of at least 1ml/hr • Maintains RBF at low perfusion pressure Prevents endothelial cell injury • Volume expansion • Diuresis/Natriuresis

31. Avoid NSAIDS, Aminoglycosides • Dopamine, mannitol, frusemide for post-op renal protection • Endothelin receptors blockers: under trial However no drug has proved effective

32. Correct coagulation defects • Vit K 10 mg IM bd × 3days prior to surgery (in severe hepatic decompensation, its use does not alter the vit K factors) • When INR >1.5 , transfuse FFP INR<1.5 • FFP 10-15 ml/kg raises the levels of most essential clotting factors by 20% • Because factor VII has a short half life (4-8 hrs) continue infusion at 6-12 hr interval may be required in persistent hepatic dysfunction • In case of thrombocytopenia, platelets should be infused just before surgery, if necessary :Goal of therapy – platelet count 1,00,000/mm3 • If fibrinogen levels are  cryoprecipitate may be used

33. Adequate nutrition • High carbohydrate diet : to build up glycogen stores • Limit fat intake to < 40g/day • Multivitamins supplemented • Antiendotoxemia measures • Intravenous antibiotics • Oral lactulose (30 ml orally, 6 hrly×3 days) • Oral ursodeoxycholic acid (10-15mg/kg/day)

34. Asymptomatic patients with abnormal LFT

35. Premedication • If neurological status is normal – oral anxiolytics • In general, there is enhancement and prolongation of action of benzodiazepines • Lorazepam and oxazepam – metabolism less affected (they undergo phase-II reaction, which is relatively spared) • H2 antagonists • Vit K 10 mg i/m 12 hrs prior • Intravenous antibiotics • Oral lactulose (30 ml orally 6 hrs prior)

36. Anaesthetic technique • Regional anaesthesia • Can be safely administered if bleeding & clotting times are normal • Guidelines • INR <1.5 • P/C >100000 • BT <12 min • Caution • To maintain hepatic blood flow by maintaining MBP (if level reaches T5 HBF  by 23%)

37. General anaesthesia: Intraoperative Monitoring • Routine monitoring – ECG, NIBP, capnography, temperature • Urine output monitoring • Neuromuscular monitoring • Cholecystectomy : consideration for laproscopic surgery • Major pancreatic surgery (e.g. Whipple’s procedure) involves major blood and third-space losses • Extensive monitoring required • Direct radial artery blood pressure monitoring • Central venous / pulmonary artery catheter • Other routine monitors

38. Cholecystectomy : consideration for laproscopic surgery • Major pancreatic surgery (e.g. Whipple’s procedure) involves major blood and third-space losses • Extensive monitoring required • Direct radial artery blood pressure monitoring • Central venous / pulmonary artery catheter • Other routine monitors

39. In contrast to the patient with hepatocellular liver disease, who may be quite sensitive to anaesthetic agents, no such contraindications hold for patients with cholestatic jaundice

40. Opioids • Opioids   in biliary tract pressure • Sphincter of oddi spasm • However this should not preclude their use to provide adequate analgesia in biliry surgery • Agonists, antagonists – butorphanol and nalbuphine may be considered • Naloxone, nitroglycerine, glucagon may be used to relieve spasm

41. Induction Agents IV induction agents

42. Neuromuscular blockers

43. Inhalational Agents

44. Inhalational agent of choice –Isoflurane

45. IPPV • Maintain eucapnia • Since liver is a low pressure tissue bed, large high airway pressure and large tidal volume should be avoided

46. Postoperative Management • In case of major surgery with severe hepatic dysfunction • IPPV to be continued in postoperative period • Fluid – electrolyte balance to be corrected • Cardiovascular stability to be achieved, • Normothermia to be aimed for • Urine output to be maintained • Analgesia • Blood to be replaced • Observe for hepatic decompensation worsening jaundice, encephalopathy, and ascites. ) • Observe for renal failure

47. Summary

48. References • Miller’s Anesthesia – 7th edition • International volume of Anaesthesia – Prys Roberts – 2nd edition • Harrison’s principles of Internal Medicine – 17th edition • Anaesthesia and coexisting disease –stoelting 5th edition • A practice of anesthesia – wylie and chulchilldavidson’s 7th edition • Anaesthesia and liver disease -Dr Robert Ginsburg – Update in Anaesthesia

50. Supportive Measures • Renal function to be maintained • Fluids + diuretics (mannitol details) • Monitor coagulation – platelet, FFP, cryoprecipitate to be given if required • Calcium supplements in case massive blood transfusion (>5 units)