Anesthesia and

Liver disease

Dr JM Dippenaar

Physiology

• Glucose homeostasis

– Glucose metabolism

– Glycogenesis, Glycogenolysis

– Gluconeogenesis

• Fat metabolism

– B oxidation

– Lipoprotein production

Physiology

• Protein metabolism

– Deamination of amino acids

– Urea formation

• Plasma protein synthesis

– All except gamma globulins, FVIII and vWF

– Transferrin, haptoglobin

– Ceruloplasmin

– Hemoglobin synthesis

Physiology

• Vascular function

– Reservoir for venous return

• Immunological function

– Kupffer cells = reticuloendothelial system

– Prevent bacterial translocation

– Dispose of cell debris, endotoxin etc.

Physiology

• Drug metabolism

– Albumin

– Cytochrome P-450 (Phase I)

– Conjugation = glucuronide ( Phase II)

• Hormone metabolism

– T4 to T3 conversion

– Degradation of Thyroxin, insulin, steroid hormone,

glucagon ADH.

Physiology

• Storage

– Glycogen

– Vit A, B12, D, E

• Bilirubin formation and excretion

– Bilirubin from break down of haem

– Conjugated and excreted into gut

– Enterohepatic circulation

Physiology: hepatic blood flow

• Dual supply

• Arterial

– 25% of blood flow

– 50% of oxygen supply

• Portal vein

– 75% of blood flow

– 50% oxygen supply

• ↓BP = disproportionate ↓ O2 supply

Evaluation of liver function• Hepatocellular damage

– ↑AST & ALT, ↑conjugated bilirubin

– ↓ Synthesis (↓albumin, clotting factors)

• Bile duct obstruction

– ↑ GGT & ALP , ↑conjugated bilirubin

• Non specific

• Large reserve

Liver disease

• Acute/chronic hepatitis

– Viral, toxins, sepsis, heart failure

• Cirrhosis

– Alcohol, Primary biliary cirrhosis,

hemochromatosis, Wilson's disease, a-1-

antitripsin deficiency, Chronic hepatitis, auto

immune hepatitis

• Idiopathic hyper bilirubinemia

– Gilbert syndrome, Crigler-Najiar, Dubin Johnson,

intrahepatic cholestasis

Clinical presentation• Nonspecific

– malaise, weight loss, pruritis

• Palmar erythema

– disturbed vasomotor tone

• Spider nevi

– SVC drainage distribution

• Gynecomasty

• Testicular atrophy

Clinical presentation• Hepatomegaly

– Later small, firm, nodular

• Signs of portal hypertension

– – ascitis, splenomegaly, caput medusa

• Osteoporosis

– deranged Vit D metabolism

• Anemia

• Striae

Clinical presentation• Dupuytren contracture

• Parotid hypertrophy

• Leukonechia

• Clubbing

• Muscle atrophy

• Hair loss

Clinical presentation• Hepatic encephalopathy

– Confabulation, apraxia

– Asterixis

– Fetor hepatis

– Coma

Complications and pathophysiological

changes

• Portal hypertension

• >10mmHg

• Progressive scarring → resistance to blood flow

• Extensive collaterals

- gastro-esophageal

- Hemorrhiodal

- peri-umbilical

- retro peritoneal

Complications and pathophysiological

changes

• Gastro esophageal varices

– Massive bleeding : major cause of m+m

– Treatment: IVI fluid, blood, platelets, FFP’s,

tracheal intubation

– Vasopressin and nitroglycerin

– Propranolol (? Prophylactic)

– Somatostatin

Complications and pathophysiological

changes

• Gastro esophageal varices

– Sengstaken-Blakemore tube

– Sclerotherapy

– Porto systemic shunts

– Distal splenorenal preferred

• Careful with NG tubes, TEE

Complications and pathophysiological

changes

• Spontaneous bacterial peritonitis

– Bacteria enter through Porto systemic collaterals ,

avoids RES

– Low protein ascitis = ↓ opsonic activity

– Mortality >50%

Complications and pathophysiological

changes

• ↑ risk of aspiration

– N+V

– delayed gastric emptying

– abdominal distention

• ↑ Gall stones

– chronically increased bilirubin load (

splenomegaly and hemolytic anemia)

• ↑ Duodenal ulcers

– anemia and increased ammonia load

Fluid and electrolyte balance

complications• ASCITIS: Causes

– portal hypertension

– low albumin levels

– leakage of protein rich lymphatic fluid

– renal sodium retention

Fluid and electrolyte balance

complications

• ASCITIS: Renal mechanisms

– Relative hypovolemia → ↑aldosteronism +

increased ADH.

– Abnormal Na+ retention

– ↑cathecholamines

– Relative insensitivity to circulating ANP

• Sign of decompensation

Fluid and electrolyte balance

complications

• ASCITIS: Treatment

– Restriction of Na to < 90mEkw/d

– Spironolactone and Furosemide

– Paracenthesis ±IVI albumin (6-8g/l ascitis)

– LeVeen shunt for refractory ascitis

Renal complications

• Hepatorenal syndrome

– Renal failure ass. with cirrhosis

– Pre renal that does not respond to fluid

resuscitation

• 2 groups.

– Fast vs. slower progress

Hematological and immune

complications• Anemia

– Multifactorial

– Chronic / acute blood loss

– Malnutrition

– Megaloblastic

– increased erythrocyte breakdown

• Thrombocytopenia, leucopenia– Congestive splenomegaly

Haemostatic failure

• ↓ clotting factors

– except VIII and VWf

• ↓ Vit K stores depleted in 10 days

• Prot C+S deficiency

• DIC ( ↑ FDP, not metabolized)

• ↑PT +INR = severe disease,

– 20 – 30 % fx needed for n clotting

Circulatory complications• Hyper dynamic circulation

• CO increased

– AV shunts in GIT +lungs

– decreased blood viscosity

– increased cathecholamines

– peripheral vasodilatation

– ↑ NO = iNOS by bact endotoxins

– role of VIP, glucagon, substance P

Circulatory complications• CO increased

– Splanchnic vasodilatation

– ↑portal blood flow and pressure

• Can end in cardiac failure

Respiratory complications• Hyperventilate

– ↑ammonia → respiratory alkalosis

• Hypoxemic → ortodeoxia– R to L shunts (≤ 40% of CO)

– intrapulmonary, portopulm and pleural vasc shunts → V/Q mismatch

– vasoconstrictive and vasodilatory substances →not metabolized

– decreased HPV

Respiratory complications• Diaphragm displaced

– ↓ lung volumes, ↓ FRC

– Atelectasis

• Pleural effusions

– restrict ventilation

Metabolic complications• Hypoglycemia

– Glycogen depletion

– Alcohol → glycogenolysis

– ↓ lactate clearance → metabolic acidosis

• Hyponatremia, Hypokaleamia,

• Hypo-albuminemia

CNS complications• HEPATIC ENCEPHALOPATHY

– Initially reversible

– Asterixis

– Degree of cerebral involvement extremely variable

– Degree of encephalopathy relates to amount of

hepatocellular damage and degree of shunting of

portal blood away from the liver

CNS complications• Proposed pathogenesis

– elevated ammonia levels

– abnormal thryptophan metabolism

– over activity of GABA

– increased permeability of BBB

– substrate deficiency ( glucose, O2)

CNS complications:

Treatment

• Dietary protein restriction

• Avoid precipitating factors

• Oral lactulose

• Neomycin or Metronidazole

• Flumazanil

• Liver transplant

Preoperative anesthetic management

• Peri-operative deterioration

• Multi-system involvement

• Careful evaluation

– of cardioresp fx. Renal fx, coagulation status, nutritional status and intravascular volume is necessary

• Hepatic reserve = Child-Pugh classification

Preoperative anesthetic management

• FBC

• Clotting profile

• U&E, glucose

• LFT’s,

• Bloodgas,

• ECG and CXR

Preoperative anesthetic management

• Correct coagulopathy

– IVI Vit K

• Hct >30%

• Intravascular fluid deficiencies

– corrected with colloids

• Paracenthesis

– tense ascitis

• Hypoglycemia

Premedication• Sedative medication avoided

• Aspiration prophylaxis is indicated

Intra–op management• Aseptic technique

• Routine monitors

• Invasive monitoring

– Fluid status in oedema

– Rapid fluid shifts expected.

• Prevent hypothermia

• Avoid unnecessary esophageal manipulation

Regional techniques• Safe if there is no coagulopathy

• Hypotension should be prevented

Intra–op management• Response to anesthetic drugs variable

– Pharmacodynamics & -kinetics changes

– Increased volume of distribution

– metabolism and elimination disturbed

– ↓ protein binding

– ↓ hepatic enzyme function

Intra–op management• ↓ liver bloodflow < O2 consumption

• More depended on hepatic artery perfusion

• Aim to maintain hepatic bloodflow

– Isoflurane increases blood flow

Intra–op management• Induction agents

– Rely on redistribution for emergence

– Decreased protein binding = lower dose

• Rapid sequence induction

– Modified with atracurium

– ↓ Pseudocholine esterase

– Avoid steroid muscle relaxants

Intra–op management• Narcotics

– All will accumulate = decrease dose

• Vapours

– Isoflurane ↑ arterial blood flow

– Isoflurane & Desflurane < 0.2% metabolized

– Halothane hepatitis

Intra–op management• Low urine output

– Mannitol

– Low dose dopamine

• Blood transfusion

– citrate toxicity

– calcium replacement

Post op management• Prolonged emergence

• Extubate only when awake

– reduce the risk of aspiration

Post operative care

• ↑ hepatic dysfunction common

– detrimental nonspecific effects of anesthetic agents

• ↑ morbidity

– sepsis, bleeding, poor wound healing, renal failure and encephalopathy may develop.

• ↑ risk

– to develop post-operative pulmonary oedema, atelectasis and pneumonia

Conclusion• Multi system disease

• 5-10% will need surgery in the last 2 years

• Increased risk of peri-operative morbidity and

mortality

• Handle with care!