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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@gmail.com. Objectives. It is an important topic? Physiology Pharmacology ~ Phase I & II metabolism

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Anaesthesia in liver disease patient

Anaesthesia in liver disease patient

Baharulhakim Said b Daliman

Department of Anaesthesiology & Intensive Care

Hospital Kuala Terengganu

www.anaesthesia.co.inanaesthesia.co.in@gmail.com


Objectives
Objectives

  • It is an important topic?

  • Physiology

  • Pharmacology ~ Phase I & II metabolism

  • Perioperative Management

  • Discussion

  • Latest update


Anaesthesia in liver disease patient

  • 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).


Hkt experience cholecystectomy
HKT experience… perioperative management of patients with liver disease, and much of the research is based on retrospective analyses cholecystectomy


General
General perioperative management of patients with liver disease, and much of the research is based on retrospective analyses

  • 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


Physiology
Physiology perioperative management of patients with liver disease, and much of the research is based on retrospective analyses

  • 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.


Physiology carbohydrate metabolism
Physiology ~ carbohydrate metabolism perioperative management of patients with liver disease, and much of the research is based on retrospective analyses

  • 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


Physiology fat protein metabolism
Physiology ~ fat & protein metabolism perioperative management of patients with liver disease, and much of the research is based on retrospective analyses

  • 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)


Important facts
Important facts perioperative management of patients with liver disease, and much of the research is based on retrospective analyses

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.


Important facts1
Important facts perioperative management of patients with liver disease, and much of the research is based on retrospective analyses

  • 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


Physiology1

Clotting factors perioperative management of patients with liver disease, and much of the research is based on retrospective analyses 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.

Physiology


Physiology drug metabolism
Physiology ~ drug metabolism perioperative management of patients with liver disease, and much of the research is based on retrospective analyses

  • 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.


Physiology drug metablism
Physiology ~ drug metablism perioperative management of patients with liver disease, and much of the research is based on retrospective analyses

Divided into 2 phase:

  • Phase I metabolism

    • Oxidation

    • Reduction / demethylation

  • Phase II metabolism

    • Conjugation


Physiology drug metabolism1
Physiology ~ drug metabolism perioperative management of patients with liver disease, and much of the research is based on retrospective analyses

Factor affecting drug metabolism:

  • microsomal enzyme system

  • route of administration

  • liver blood flow

  • competitive inhibition


Physiology drug metabolism2
Physiology ~ drug metabolism perioperative management of patients with liver disease, and much of the research is based on retrospective analyses

Pharmacokinetic changes cause by liver disease:

  • Metabolising capacity is reduced ~ liver cells sick @ 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


Physiology drug metabolism3
Physiology ~ drug metabolism perioperative management of patients with liver disease, and much of the research is based on retrospective analyses

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


Important facts2
Important facts perioperative management of patients with liver disease, and much of the research is based on retrospective analyses

  • 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).


Pre operative sx
Pre Operative ~ Sx perioperative management of patients with liver disease, and much of the research is based on retrospective analyses

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; kidneydisease, 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.


Pre operative sx1
Pre Operative ~ Sx perioperative management of patients with liver disease, and much of the research is based on retrospective analyses

  • 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.


Pre operative sx2
Pre Operative ~ Sx perioperative management of patients with liver disease, and much of the research is based on retrospective analyses

  • 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.


Diagnosis
Diagnosis perioperative management of patients with liver disease, and much of the research is based on retrospective analyses

  • 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


Clinical
Clinical perioperative management of patients with liver disease, and much of the research is based on retrospective analyses

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


Pre op management
Pre OP management perioperative management of patients with liver disease, and much of the research is based on retrospective analyses

  • 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.


Pre op management1
Pre OP management perioperative management of patients with liver disease, and much of the research is based on retrospective analyses

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


Pre op management2
Pre OP management perioperative management of patients with liver disease, and much of the research is based on retrospective analyses

  • 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).


Child s classification of liver disease
Child’s Classification of liver disease perioperative management of patients with liver disease, and much of the research is based on retrospective analyses


Intra operative factors
Intra operative factors perioperative management of patients with liver disease, and much of the research is based on retrospective analyses

  • Effect of anaesthesia

  • Effect of surgery


Effect of anaesthesia
Effect of anaesthesia perioperative management of patients with liver disease, and much of the research is based on retrospective analyses

  • 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.


Effect of anaesthesia1
Effect of anaesthesia perioperative management of patients with liver disease, and much of the research is based on retrospective analyses

  • 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).


Effect of surgery
Effect of surgery perioperative management of patients with liver disease, and much of the research is based on retrospective analyses

  • 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


Post operative factors
Post operative factors perioperative management of patients with liver disease, and much of the research is based on retrospective analyses

  • 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


Post operative factors1
Post operative factors perioperative management of patients with liver disease, and much of the research is based on retrospective analyses

  • 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.


Discussion
Discussion perioperative management of patients with liver disease, and much of the research is based on retrospective analyses

  • Hepatorenal syndrome

  • Anaesthesia for patient with cirrhosis

  • Anaesthesia for cholecystectomy

  • Anaesthesia for liver transplant


Hepatorenal syndrome
Hepatorenal syndrome perioperative management of patients with liver disease, and much of the research is based on retrospective analyses

  • 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


Hepatorenal syndrome1
Hepatorenal syndrome perioperative management of patients with liver disease, and much of the research is based on retrospective analyses

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


Hepatorenal syndrome2
Hepatorenal syndrome perioperative management of patients with liver disease, and much of the research is based on retrospective analyses

Treatment:

  • Treated for prerenal failure

  • Stop diuretic therapy

    Prognosis is poor


Anaesthesia for patient with cirrhosis
Anaesthesia for patient with cirrhosis perioperative management of patients with liver disease, and much of the research is based on retrospective analyses

  • Postoperative morbidity is increased.

  • Problems with wound healing, bleeding, infection, decreased hepatic function and development of encephalopathy

  • Divided into  acute hepatic failure

     chronic failure


Anaesthesia for patient with cirrhosis acute failure
Anaesthesia for patient with cirrhosis (acute failure) perioperative management of patients with liver disease, and much of the research is based on retrospective analyses

  • 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


Anaesthesia for patient with cirrhosis acute failure1
Anaesthesia for patient with cirrhosis (acute failure) perioperative management of patients with liver disease, and much of the research is based on retrospective analyses

  • 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


Anaesthesia for patient with cirrhosis chronic liver disease
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


Anaesthesia for cholecystectomy
Anaesthesia for cholecystectomy disease)

  • 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)


Anaesthesia for cholecystectomy1
Anaesthesia for cholecystectomy disease)

  • 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


Anaesthesia for liver transplant
Anaesthesia for liver transplant disease)

  • 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


Anaesthesia for liver transplant1
Anaesthesia for liver transplant disease)

  • 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


Anaesthesia in liver disease patient

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


Latest update
Latest Update lessons learned can be applied each time we administer anesthesia to a patient with hepatic disease

  • 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


Bibliography
Bibliography lessons learned can be applied each time we administer anesthesia to a patient with hepatic disease

  • 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


Thank you
Thank you lessons learned can be applied each time we administer anesthesia to a patient with hepatic disease

www.anaesthesia.co.inanaesthesia.co.in@gmail.com