Anaesthetic management of Liver disease

Dr.K.Aditya vikram P.G. Dept of Anaesthesiology Moderator Dr. Madhavi Asst. prof Dept of Anaesthesiology Chair person Dr. Satyanarayana Prof Dept of Anaesthesiology. Speaker

Concerns of anaesthesiologist in chronic liver disease patients. Optimisation of patient .

1.coagulopathy. 2.anaemia. 3.hypoproteinaemia. 4.ascitis. 5.disturbed metabolism. 6.encephalopathy. 7.hyperbilirubinaemia.

8.altered P-K of drugs. 9.hepato-pulmonary syndrome. 10.hepatorenal syndrome. 11.hypersplenism. 12.malnutriton

Pre-operative risk factor assessment and minimizing the risk factors. Anesthetic management proper. Post operative jaundice.

Anesthetic management of patients with moderate to severe liver disease includes Pre-op optimisation of condition Modifying and minimising the risk factors of mortality

COAGULOPATHY

Decreased synthesis. Thrombocytopenia. Hypothermia.

Coagulopathy :
PT 2-3 sec control . FFP 2-6 units need to be transfused. 1FFP increases clotting factors by 2-5%. 250ml FFP increases fibrinogen by 10%. Platelets<40,000/ clinicallybleeding diathesis - Platelet transfusion required.

Bleeding and clotting abnormalities

Decrease in Vit K dependent factors.

Decreased intrinsic factors. Decreased t1/2 of clotting factors due to coagulopathy. Qualitative and quantitative platelet defects, thrombocytopenia.
Goal: PT < 2.5 sec of control

consumptive

Fresh Frozen Plasma:

is collected as the supernatant after centrifuging a donation of whole blood.

It is frozen within 8 hours to maintain the activity of factors V and VII. The main indication is deficiency of multiple coagulation factors such as that found in massive haemorrhage, DIC, liver disease, and occasionally for reversal of warfarin effect. Stored at -18 to-30 c, thawed before administeration,ABO compatibility must be done

Consider FFPs in: microvascular bleeding due to cogulopathy. after massive whole blood transfusion. APTT>1.5 times,I.N.R>2 times normal. 1 unit of FFP per 10 kg body weight will raise the fibronogen level by 100mg/ml. 1 unit of FFP to every 4units of PRBCS in actively bleeding patients guided by aPTT

Platelets: A unit of platelets is prepared from a single whole blood collection and contains at least 5.5 x 1010 platelets in 50 ml plasma. They are stored at 20-24C under agitation and have a shelf life of 5 days. Each unit can raise the platelet count by 5-10 x 109. 6 units of random donor plates or 1 unit of single donor platelets raises the count by 20000-30000 per cubic mm. Goal of platelet therapy to maintain a platelet count of 50000 to 100000per cubic mm .

Hematologic Abnormalities :
Numerous hematologic manifestations of cirrhosis are present, including anemia from a variety of causes including hypersplenism, hemolysis, iron deficiency, and perhaps folate deficiency from malnutrition.

Macrocytosis is a common abnormality in red blood cell morphology seen in patients with chronic liver disease, and neutropenia may be seen as a result of hypersplenism.

Packed Red cells: A bag of RBCs have a haematocrit of between 60-70%, and an average shelf life of 35 days if properly stored. Their function is to act as carriers of oxygen and carbon dioxide in the blood.

The main indications for transfusion is the correction of anaemia or replacement in acute haemorrhage, but there is no absolute level of Hb to trigger a transfusion.
A single unit of red blood cells will typically increase the Hb by 1g/dl, 3%haematocrit.

Management of various risk factors

Ascites indicates severe liver disease Elective surgery: carbohydrate and protein diet restrict sodium intake 2gm/day Not responding to salt restriction Use of potassium sparing diuretics alone/ loop diuretics

Tab. spironolactone 100mg/day max 400mg/d Tab. Amiloride 5-10 mg/d Frusemide 40-160 mg/d if hyponatremia (<125meq/l) restrict fluid intake 800-1000ml/d Goal: Pre-op sodium level >130mmol/L Large volume paracentesis: tense ascites - wt.loss <0.5kg/d if >1lt/d supplement with salt free albumin 10gm/d , dextran -70 8gm/d, gelatin 125ml/d.

Definition Refractory ascites is defined as fluid overload that is nonresponsive to restriction of dietary sodium to 88 mmol/day and maximal-dose diuretic therapy (furosemide + spironolactone), in the absence of ingestion of prostaglandin inhibitors, such as non-steroidal anti-inflammatory drugs. Ascites is also considered to be refractory when there is intolerance of diuretic therapy. Indications of failure of diuretic therapy include minimal or no weight loss, together with inadequate urinary sodium excretion (< 78 mmol/day). Less than 10% of patients with ascites complicating cirrhosis meet the criteria of the definition of refractory ascites.

Serum-ascites albumin gradient = serum albumin - ascitic fluid albumin o if > 1.1 g/dL portal hypertension is present; o if < 1.1 g/dL portal hypertension is not present (about 97% accurate).

A high gradient is associated with diffuse parenchymal liver disease and occlusive portal and hepatic venous disease (as well as nephrotic syndrome, liver metastasis and hypothyroidism).

Large volume paracentesis: If tense ascites is causing clinically significant symptoms, a single large volume paracentesis (46 L) can be performed safely, without adversely affecting hemodynamics, and without the necessity of concomitant colloid infusion, as an initial treatment to relieve the symptoms. If the paracentesis is > 6 L, intravenous infusion of albumin, 68 g/L removed, is recommended.

To prevent reaccumulation of fluid, dietary sodium restriction and diuretic therapy are instituted.
Large volume paracentesis is not first line therapy for all patients with tense ascites.

Solution Albumin (5%) Albumin (25%)

pH 6.4-7.4 6.4-7.4

Na

Cl

Ca

++

Lactate 0 0

Glucose 0 0

Osmolalit y 309 312

Other 50 g/L albumin 250 g/L albumin

130-160 130-160

130-160 130-160

<1 <1

0 0

Infusion rate:

25% vials: 2-3 ml/minute maximum. 5% solution: 5-10 ml/minute maximum.

Discard unused solution after 4 hours. Dilute if necessary with D5W or NS. Hypoproteinemia (Usual dose): 0.5- 1 gram/kg/dose q1-2 days as calculated to replace ongoing losses. Maximum dose/day: 250 grams/48 hours.

Albumin is a highly soluble, globular protein (MW 66,500), accounting for 70-80% of the colloid osmotic pressure of plasma. Therefore, it is important in regulating the osmotic pressure of plasma. Human Albumin 25% supplies the oncotic equivalent of approximately 5 times its volume of human plasma. It will increase the circulating plasma volume by an amount approximately 3.5 times the volume infused within 15 minutes, if the recipient is adequately hydrated.

This extra fluid reduces hemoconcentration and decreases blood viscosity.

Albumin is distributed throughout the extracellular water and more than 60% of the body albumin pool is located in the extravascular fluid compartment. The total body albumin in a 70 kg man is approximately 320 g. it has a circulating life span of 15-20 days, with a turnover of approximately 15 g per day. an albumin:electrolyte ratio of 1:3 or 1:4(it will expand the plasma volume if interstitial water is available for an inflow through the capillary walls.)

There is some evidence that a serum oncotic pressure near 20 mmHg equaling a total serum protein (TSP) concentration of 5.2 g/100 mL represents a threshold, below which the risk of complications increases.
The target organs of hypoproteinemia include the skin, the lungs, and the intestine.

Cutaneous edema lowers the oxygen tension of wounds and may thus impair the healing process.
An oncotic deficit favors the development of interstitial pulmonary edema and the intestinal accumulation of fluids, which may progress to a paralytic ileus.

In acute liver failure, Albumin solution may serve the triple purpose: of stabilizing the circulation. correcting an oncotic deficit binding excessive serum bilirubin. In the absence of active hemorrhage, the total dose should at any rate not exceed the normal circulating albumin mass, i.e. 2 g per kg body weight.

1. 2. 3.

SBP is a common and severe complication of ascites characterized by spontaneous infection of the ascitic fluid without an intraabdominal source. most common organisms are Escherichia coli and other gut bacteria; however, gram-positive bacteria, including Streptococcus viridans, Staphococcus aureus, and Enterococcus sp diagnosis of SBP : absolute neutrophil count >250/mm3 Treatment :second-generation cephalosporin, inj. cefotaxime 2gm tid x 5d

ALTERED METABOLISM

Significant impact on drug metabolism and pharmacokinetic as a result of alterations in: A.protein binding. B.altered volume of distribution. C.reduced metabolism. D.impact of chronic alcohol on enzyme induction. E.sedatives and opiods have exaggerated effects in patents with ALD ----worsen encephalopathy .

Efficacy of drug removal by the liver is determined by several factors :

A.hepatic blood flow. B.hepatic enzyme activity and efficacy. C.extent of plasma protein binding. D.cholestasis induced alteration in enterohepatic circulation. E.portosystemic shunts.

High extraction primarily dependent on hepatic blood flow ex: lidocaine,meperidine.

Low extraction ---mainly protein binding. ex: benzodiazepines.

Hepatic encephalopathy (also known as portosystemic encephalopathy) is the occurrence of confusion, altered level of consciousness, and coma as a result of liver failure. In the advanced stages it is called hepatic coma or coma hepaticum. It may ultimately lead to death.

West Haven Criteria

this is based on the level of impairment of autonomy, changes in consciousness, intellectual function, behavior, and the dependence on therapy. Grade 1 - Trivial lack of awareness; euphoria or anxiety; shortened attention span; impaired performance of addition or subtraction Grade 2 - Lethargy or apathy; minimal disorientation for time or place; subtle personality change; inappropriate behaviour Grade 3 - Somnolence to semistupor, but responsive to verbal stimuli; confusion; gross disorientation Grade 4 - Coma (unresponsive to verbal or noxious stimuli)

Hepatic Encephalopathy:
Increased Ammonia conc., increased GABA activity

Preventive measures: hydration and correction of electrolyte imbalance correcting precipitating factors vegetable protein better than animal protein
use lactulose, a nonabsorbable disaccharide acute cases- 30 40ml tid x 7d, 2-3 soft stools/d no response add Poorly absorbed antibiotics neomycin 0.5 -1gm tid x 7d metronidazole 250mg tid x 7d rifaximin - 1200mg od

Metabolic disturbances: I. Metabolic alkalosis. II. Hypokalemia. III. Hypocalcemia. IV. Hyperglycemia. V. Hypoglycemia.

EFFECTS OF HYPERBILIRUBINEMIA

Unconjugated bilirubin more toxic than conjugated. Impairs myocardial contractility, reduces vagal tone causing bradycardia (atropine double dose).

Blunts response to catecholamines, angiotensin II and isoprenaline - blunts stress response.

Therefore tolerate blood loss badly - prompt and adequate replacement of blood volume required. Binds to albumin: Relative Hypoalbuminemia results in increased free drug concentration.

Toxic to enzymes of oxidative phosphorylation, glycolysis, glycogenesis and TCA cycle, heme synthesis, amino acid and protein metabolism. Toxic to CNS - but cannot cross intact BBB. Causes kernictus in premature infants Sensitizes kidneys to hypoxia-induced injury. Bilirubin casts precipitate in renal tubules causing acute tubular necrosis. Artefactually lowers measured serum creatinine Therefore serum creatinine under estimates renal dysfunction.

Pulmonary function Hypoxemia PaO2 <70mmHg Decreased HPV response Treat associated pul. disease (smokerCOPD) Chest physiotherapy Pulmonary toileting Bronchodilators Antibiotics

Renal system:
Pre renal Azotemia- correct by fluid administration Renal failure- Gram ve septicemia, Endotoxin mediated, Bilirubin mediated Diuresis by mannitol Antibiotic coverage (non toxic)

Asses for Hepatorenal syndrome (mortality 95%) type I doubled s.creatinine (2.5mg/dl) halved creatinine clearance 20ml/min in 2wks. type II progressive , chronic, resistant to treatment

Hepatorenal failure

Pre and Peroperative dehydration. Hypovolaemia.

Fall in renal blood flow during surgery.

Direct effect of the excess conjugated bilirubin on the renal tubules . Increased absorption of endotoxin from the gut.

Rx: i.v infusion of albumin dopamine + long acting vassopressin ( ornipressin / terlipressin) octreotide midodrine, an alpha-agonist (under trail) TIPS The best therapy for HRS is liver transplantation Goal: Urine out put 50ml/hr

Obstructive jaundice Elective surgery Vit K can be given preoperatively Dose: 5-10mg/day x 7 IM 5-10mg TID x 3 IM In emergency : 5-10mg 4th hourly

Splenomegaly and Hypersplenism :

Congestive splenomegaly is common in patients with portal hypertension. Clinical features include the presence of an enlarged spleen on physical examination and the development of thrombocytopenia and leukopenia in patients who have cirrhosis. Some patients will have fairly significant left-sided and left upper quadrant abdominal pain related to an enlarged and engorged spleen.

Splenomegaly itself usually requires no specific treatment, although splenectomy can be successfully performed under very special circumstances. Hypersplenism with the development of thrombocytopenia is a common feature of patients with cirrhosis and is usually the first indication of portal hypertension.

Malnutrition :
Because the liver is principally involved in the regulation of protein and energy metabolism in the body, it is not surprising that patients with advanced liver disease are commonly malnourished.

muscle protein is metabolized.

Once patients become cirrhotic, they are more catabolic, and

multiple factors that contribute :

including poor dietary intake. alterations in gut nutrient absorption. alterations in protein metabolism. Dietary supplementation for patients with cirrhosis is helpful in preventing patients from becoming catabolic.

Bone Disease :
Osteoporosis is common in patients with chronic cholestatic liver disease because of malabsorption of vitamin D and decreased calcium ingestion. The rate of bone resorption exceeds that of new bone formation in patients with cirrhosis resulting in bone loss. Dual x-ray absorptiometry (DEXA) is a useful method for determining osteoporosis or osteopenia in patients with chronic liver disease. When a DEXA scan shows decreased bone mass, treatment should be administered with bisphosphonates that are effective at inhibiting resorption of bone and efficacious in the treatment of osteoporosis.

General measures: Acceptable sr.Albumin >3gm/dl Acceptable Sr.Bilirubin (if >8mg/dl pre-op mannitol to be given) Anemia : iron deficiency anemia ferrous sulphate 300mg tid megaloblastic folic acid 1mg/d , vit. B12 packed cell transfusion if Hct< 28% Nutrition : calories 25- 30 kcal/kg/d protein 1-1.2gm/kg/d hepatic encephalopathy restrict to 60gm/d Other factors : stop alcohol, stop smoking, correct electrolyte imbalance

Type of Anesthesia

Major intra-abdominal surgeries GA Monitoring: routine ASA monitoring spo2,ECG,NIBP,Etco2 Severe disease/major surgery Invasive: IBP, CVP Periodic ABG analysis RBS, Sr.electrolytes, Haematocrit PT,APTT, Thromboelastography

GA: Pre-med: no/minimal sedative Fentanyl (min dose) Metaclopromide (full stomach) Rapid sequence induction and intubation Induction: Propofol 2mg/kg (best agent) Thiopentone 3-5mg/kg (single dose) Intubation: Suxamethonium (duration slightly prolonged)

Opiods :
Morphine : prolonged elimination t1/2 . increased bioavailability. protein binding. Exaggerated sedative and resp depression effect .administraton interval 1.5-2 fold and oral dosage be reduced.

Fentanyl : Highly lipid soluble. Short acting synthetic. Fentanyl elimination s not appreciably altered in pt with cirrhosis. Sufentanil : Extensively metabolized by liver and more protein bound. Chronic infusion impact ill defined . Alfentanil : T1/2 doubled. High free fraction..prolong duration and enhanced effects. Remifentanil:

Intravenous inducing agents: i.v anaesthetics have modest impact on the hepatic blood flow and no meaningful adverse influence on postop liver function when arterial blood pressure is adequately maintained. TPS : small hepatic extraction . Elimination t1/2 unchanged in cirrhotic pt becoz of large Vd. KETAMINE,PROPOFOL,ETOMIDATE,METHOHEXITAL: Highly lipid soluble. High extraction ratio. Propofol has a more favourable splanchnic and hepatic oxygen delivery then halothane.

Neuromuscular blocking agents :

Succinyl choline : cholinesterase and pseudocholinesterase. Mivacurium : Longer residence time in cirrhotic then normal patients.

Maintanance : O2, N2O mixture NDMR- Atracurium/Cis-Atracurium (safe) large initial doses( inc. vd ) subsequent doses should be decreased Avoid injury/ insult to Liver Goal: maintain liver blood flow and O2 supply

Hypoxia, V/Q mismatch- increase Fio2 Prevent arterial hypotension, fall in cardiac out put Inhalational agent: Isoflurane best agent Sevoflurane Halothane better avoided in cases with liver disease. Fluid and blood products

Post-op Jaundice

Incidence in abdominal procedures <1% Manifestation: increased ALT/AST/S.bilirubin/clinical jaundice

1. 2. 3.

Only bilirubinemia:
Resorption of large haematoma, multiple blood transfusions Congenital: Gilberts, Rotors, Dubin-johnson (prognosis good), criggler-najjar syn. Intravascular haemolysis- haemolytic anaemia, G-6-PD deficiency, Sickle cell anaemia

Bilirubinemia with mild mod amino transferase increase:

post op intra hepatic cholestasis- mild fever , jaundice, upper abdominal pain <48hrs & recedes in 2-3wks Biliary tract obstruction: retained stones in biliary tract, duct injury, acute cholecystitis post op, acute pancreatitis. Circulatory failure: open heart surgery/traumatic circulatory shock, ischemic hepatic injury. Sepsis mainly obstructive type (high bilirubin levels)

Bilirubinemia with marked amino transferase increase: Shock liver- centrilobular necrosis due to hypoxia, viral hepatitis Drug induced hepatitis: alcohol AST:ALT >2:1 isoniazid,phenytoin,methyl dopa tetracycline, oc pills asprin, acetaminophin.

Halogenated inhalational agents: halothane hepatitis- type 1 type 2( severe form) Obesity: BMI >30 post op liver failure likely in 30% cases.

Time course of onset of post op jaundice

0-1wk : intra hepatic cholestasis resorption of hematoma hypotension- ischaemic hepatitis 1-2wks: above causes sepsis, biliary trauma, pancreatitis nonA,nonB hepatitis halothane hepatitis

Pre op proper history taking: h/o hepatitis(viral) familial disease,drug history, alcohol overuse, h/o jaundice past obesity, exposure to halothane Intra op: shock, retraction/major abdominal surgery, sepsis, biliary tract surgery.

S.albumin < 3 gm/dl Presence of infection WBC > 10,000 /mm3 Treatment with > 2 antibiotics Prothrombin time > 1.5 sec. over control S.bilirubin > 50 mol/L (>3 mg/dl) Presence of ascites Malnutrition Emergency surgery.

INCREASED POST-OP MORTALITY.

PREOPERATIVE MEDICATION

Phenothiazines are avoided - centrilobular necrosis. Anticholinergics - as bradycardia may be present atropine preferred. If patient is on steroids, continue till morning of surgery, supplement during induction, intraoperatively if required and post operatively.

INTRAOPERATIVE COMPLICATIONS

Hypotension . Oliguria .

Blood loss.
Hypoglycemia . Electrolyte abnormalities - hypocalcaemia may occur when citrated blood or FFP transfused.

POST OPERATIVE

Oxygen supplementation for at least 24 hrs. Postoperative chest X-ray. Continue antibiotics, H2 receptor antagonists and fluid management. Adequate analgesia should be provided using epidural CEA /PCEA, small intermittent doses of opioids, local anaesthesia Maintain urine output > 1-2 ml/kg/hr. Continue mannitol and dopamine if used intraoperatively

POST OPERATIVE

SAME MONITORING &CARE

ELECTIVE POST OPERATIVE VENTILATION

Severe liver disease Extensive surgery Associated pulmonary or cardiac disease Fluid or electrolyte imbalance Hypothermia Impaired consciousness Saturation <90% with FiO2 > 0.4.

POSTOPERATIVE COMPLICATIONS

Impaired consciousness due to over sedation . Impaired respiration due to opioid over dose. Inadequate reversal . Chest infection .

Oliguria and renal failure.

Deterioration of hepatic function. Post Operative Jaundice

Post Op Jaundice

Classification LaMont &Isselbacher. 1.Overproduction of Bilirubin

Hemolytic Anemia, Hemolysis of tranfused bld,Resorption of hematoma

2.Hepatocellular damage

Ischemic, Cholestatic, Drug induced, Preexisting hepatitis Stone, Duct injury

Gilberts, Post Op Cholecystitis

Extrahepatic Obstruction

Miscellaneous

THANK YOU

Central neuraxial blockade

The effect of regional anaesthesia on liver blood flow and hepatic function is not clearly an anaesthetic drug induced alteration in hepatic function. These changes can be reversed and hepatic blood flow may be mantained with vasopressors or fluid administration to maintain normal arterial blood pressure.

Risk stratification

Risk assessment for Anaesthesia in patients with Liver disease

Assessment of risk factors in moderate to severe liver disease CHILD-TURCOTT classification posted for major surgery
Gr-A Gr-B 2-3 Moderate Gr 1-2 Undernourished 2.8-3.5 30% Gr-C >3 Tense Gr 3-4 Poor <2.8 >40%

Factor

Sr.bilirubin(mg/dl <2 ) Ascites Encephalopathy Nutrition S. ALBUMIN(gm%) Risk(Mortality rate) NO NO Good >3.5 <10%

Child-pugh modification ( 1972 )

Factor Sr.bilirubin(mg/dl) Ascites Encephalopathy <2 NO NO 1 2-3 Moderate Gr 1-2 2 >3 Tense Gr 3-4 3

PT (Sec prolonged) INR S. ALBUMIN(gm%)

<4 <1.7 >3.5

4-6 1.7-2.3 2.8-3.5

>6 >2.3 <2.8

MELD Score Modified end stage liver disease

Sr.Bilirubin Sr.Albumin Sr.Creatinine

Meld commonly used for Transplantation and Shunt surgeries

The modified Maddrey's discriminant function) was originally described by Maddrey and Boitnott[1] to predict prognosis in alcoholic hepatitis. It is calculated by a simple formula:
(4.6 x (PT test - control))+ S.Bilirubin in mg/dl. Prospective studies have shown that, it is useful in predicting short term prognosis especially mortality within 30 days.[2] A value more than 32 implies poor outcome with one month mortality ranging between 35% to 45%.[3] To calculate Maddrey discriminant function using SI units - micromol/l (i.e. not US) divide bilirubin value by 17.

Pre op variables and peri op mortality rate in cirrhotic patients (Garrison etal)

Risk factor Mortality rate Emergency surgery 57% S.albumin <3gm/dl 58% S.bilirubin> 3mg/dl 62% PT >1.5 X control 63% Infection 64% Antibiotics >2 82% Cardiac failure 92% Pulmonary failure 100% WBC count > 10,000 cells/cumm

Causes of mortality (perioperatively)

Sepsis Renal failure Bleeding Hepatic failure Encephalopathy Pulmonary failure

PROCEDURAL ANAESTHESIA

TIPSS

Indications Complications of portal hypertension Variceal hemorrhage Refractory ascites Hepatic hydrothorax

TIPSS

Preop
Preop Considerations Altered mental status from encephalopathy Full stomach considerations due to ascites or GI bleeding Poor drug clearance due to hepatic failure Coexisting diseases: coagulopathy, renal insufficiency, anemia

Physical Findings Jaundice Ascites Asterixis Bruising Petechiae

Complications Hepatic encephalopathy, decline in liver function. Monitor for change in mental status. Keep sedatives postop to a minimum. Stents may occlude immediately or over a period of time: stents are evaluated for patency w/ ultrasound the next morning & whenever signs of portal hypertension return. Bleeding: serial hematocrits are obtained for 24 hours as well as monitoring for change in abdominal girth & blood pressure. If severe, transfusions & return to the OR are possibilities.

Pts are usually kept in the ICU overnight for monitoring. Independent predictors of short-term mortality. Need for emergent TIPS. ALT >1,000. Bilirubin >3. Encephalopathy pre-TIPS

TIPPS

ERCP

In contrast to upper gastrointestinal endoscopy, ERCP is a complex, often time consuming diagnostic and therapeutic endoscopic procedure that requires a high degree of patient cooperation in order to facilitate an intervention requiring precision from the endoscopist.

Therefore, deep sedation is preferable in ERCP. General anesthesia should be considered in patients difficult to sedate, or having difficulty in ventilation and intubation or in high risk for aspiration. Also, it should be considered in lengthy procedures.