Anesthetic Concerns for the Patient With Renal and Hepatic Disease

R4

 Advanced renal or hepatic disease

Systemic disease processes, affecting multiple organ systems. Fundamental defect in protein metabolism
hyperammonemia or elevated BUN(markers for other circulating byproducts of protein metabolism). Defective ion transport across cell membranes, resulting in intracellular sodium and water accumulation.

Imply abnormal handling of anesthetic drugs, multiorgan dysfunction, general debility, and specific problem associated with replacement therapy and transplantation.
- A challenge to anesthegiologists.

Systemic Manifestations of Renal and Hepatic Disease

 Chronic renal failure(1)

Fluid and acid-base imbalance
Dialysis : control metabolic acidosis, hyperkalemia, and CHF. In anuric patients, Only fluid loss is insensible(500ml/day) Excessive sodium intake - edema, hypertension. Excessive water intake - hyponatremia. In polyuric CRF, Urine output is normal, but concentrating ability is absent. Acute fluid loss - hypovolemia. A moderate anion gap acidosis Compensated by chronic respiratory alkalosis. Buffer base is depleted. Shock, diarrhea, or hypercatabolism(sepsis, trauma, steroid therapy). Profound metabolic acidosis.

Electrolyte imbalance
Extracellular potassium
Maintained in narrow range(3.5 to 5.0 mEq/l). Active intracellular transport by a sodium ATP pump at the cell membrane. Clinical and ECG manifestations of hyperkalemia(or hypokalemia) depend on potassium flux rather than the serum concentration. Catabolic stress, acidosis, potassium-sparing diuretics, erythrocyte transfusion Rapid, life-threatening hyperkalemia.

Hypermagnesemia
Muscle weakness, susceptibility to muscle relaxants.

Hypomagnesemia
Associated with hypokalemia, ventricular irritability.

Hyperphosphatemia
Increased bone deposition of calcium hypocalcemia. Decreased renal synthesis of vitamin D. and

Hypocalcemia
Secondary hyperparathyroidism and bone resorption. The syndrome of renal osteodystrophy. Treatment : vitamin D, calcium salts, phosphate binders(aluminium hydroxide), dietary phosphate restriction.

Hypophosphatemia(< 2.5 mg/dl)

Aggressive dialysis, aluminum hydroxide therapy, or TPN. The phosphate depletion syndrome Increased susceptibility to muscle relaxants, difficult ventilatory weaning, and CNS dysfunction.

Cardiovascular problems
Systemic hypertension LVH(concentric or asymmetric) Hyperlipidemia
a high prevalence of accelerated atherosclerosis.

Anemia and AV shunts

hyperdynamic circulation with fixed low systemic vascular resistance. circulatory reserve is impaired. Myocardial ischemia, sepsis hypotension .

Uremic pericarditis, hemorrhagic pericardial effusions.

Pulmonary problems
Increased minute ventilation
to compensate chronic metabolic acidosis.

Hypoalbuminemia, decreased oncotic pressure, decreased strength, immunosuppression.

postoperative pneumonia. pulmonary edema,

serum muscle
atelectasis,

CAPD
abdominal distension compromises ventilation capacity(FVC). and forced vital

Impaired hematopoiesis
Normochromic, normocytic anemia Hct. between 25 and 28%. Decreased erythrpoietin production by the kidney. Bone marrow depression(uremia, aluminum toxicity), decreased RBC survival, chronic blood loss from GI tract or laboratory studies.

Uremic coagulopathy
Abnormal platelet function(thrombocytopathy) occurs when BUN exceeds 60 to 80 mg/dl. Bleeding time prolonged(> 15 minutes). Impaired platelet aggregation.
d/t defective endothelial release of von Willebrand factor-factor VIII complex.

Impaired metabolic and immune function

Hyperglycemia, hypertriglyceridemia
peripheral insulin resistance and decreased lipoprotein lipase activity in uremia. protein malnutrition(kwashiorkor, hypoalbuminemic malnutrition) dietary protein restriction, chronic albuminuria. Protein loss via CAPD(10 to 20 g/dl, 30 to 40 g/dl with peritonitis). Hypoalbuminemia, lowered colloid oncotic pressure peripheral edema, pulmonary edema. Impaired leukocyte chemotaxis and immunoglobulin responses nosocomial or oppportunistic infection. Depleted lean body mass and catabolic effects of uremia. wound dehiscence, fistulas, bed sores.

Gastrointestinal dysfunction (Uremic enteropathy)

Anorexia, hiccups, nausea, vomiting.
Autonomic neuropathy
delays gastric emptying. Regurgitation and aspiration during anesthetic induction.

Peptic ulcer
up to 25% in CRF patients.

Hepatitis B and C
high incidence in patients hemodialysis. often anicteric or in a carrier state. on chronic

Neurologic dysfunction
Depend on the acuity of uremia. Personality changes, drowsiness, asterexis, myoclonus, seizures. Major surgery, gastrointestinal bleeding, infection
precipitate acute encephalopathy.

Lifetime hospital dependence

passive-aggressive, and churlish. depressed, manipulative,

Uremic distal sensorimotor neuropathy

a marker for autonomic neuropathy. orthostatic hypotension, impaired circulatory response to anesthesia, delayed gastric emptying. silent myocardial ischemia(without angina).

 Chronic liver disease

Ascites, fluid, and electrolyte imbalance
Hypoalbuminemia, portal hypertension
induce ascites and intravascular hypovolemia. secondary hyperaldosteronism(sodium and water retention, potassium excretion) : hypokalemic metabolic alkalosis, generalized edema(anasarca), progressive ascites.

Ascites
elevates diaphragm, decreases FRC. increase intraabdominal pressure, decreases venous return and renal blood flow. Spontaneous bacterial peritonitis(10% of patients). resistance to loop diuretics. exacervate intravascular hypovolemia and hypokalemia, worsen hepatic perfusion. spironolactone(specific aldosteron antagonist): choice.

Metabolic alkalosis
worsens hepatic encephalopathy. Extracellular hydrogen ion concentration , ammonium(NH4+) is converted to ammonia(NH3), crosses lipid membrane(nonionic diffusion trapping). Treatment potassium chloride with careful volume repletion. Refractory alkalosis corrected by central venous infusion of dilute(0.1N) hydrochloric acid.

Gastrointestinal dysfunction
Potential for active viral hepatitis(A,C,D). Delayed gastric emptying
risk of regurgitation and aspiration during induction.

Patients with portal hypertension

risk of massive bleeding from esophageal or gastric varices.

Risk of peptic ulcer disease(bleeding source).

 Hepatorenal syndrome
Any degree of renal insufficiency that occurs in the presence of liver failure. A specific form of vasomotor nephropathy
severe prerenal oliguria, low urine sodium(10mEq/l), progressive azotemia.

Severe obstructive jaundice(total bilirubin>8mg/dl) or liver failure

bile salts bind to endotoxin in the gut, access into the portal circulation. Endotoxin enters into the systemic circulation and induces renal vasoconstriction. Renal tubular water and sodium retention.

Acute tubular necrosis

direct nephrotoxic effect of endotoxin. Variceal bleeding with hemorrhagic shock - ischemic tubular necrosis.

 Hyperdynamic circulation
A fixed low systemic vascular resistance.
countless tiny arteriovenous shunts in the skin(spider nevi, palmar erythema), GI tract and lung.

Chronic low systemic arterial pressure. Impaired circulatory reserve

hypovolemia, sepsis, myocardial ischemia decompensation and shock.

Respiratory failure
Hepatopulmonary syndrome
hypoxemia refractory to increased inspired oxygen fraction in patients with advanced liver disease. By intrapulmonary shunting through the arteriovenous anstomoses. Reactive or fixed pulmonary hypertension.

Aspiration risk(in hepatic encephalopathy). High risk for perioperative pulmonary complications.

 Hematologic abnormalities.
Factor VII deficiency
Impaired hepatic synthesis, impaired vitamin absorption. Prolongation of prothrombin time. marker of hepatic synthetic dysfunction. K

Thrombocytopenia
platelet count 50,000 to 75,000/mm3. Hypersplenism in portal hypertension, bleeding or DIC. acute GI

Factor V deficiency
a sensitive marker of acute liver dysfunction. used after liver transplantation. Dysfibrinogenemia(in advanced liver disease).

Anemia
acute or chronic blood loss, malnutrition, bone marrow suppression. Chronic alcoholism : macrocytic anemia.

 Nutritional-metabolic problems
Loss of glycogenesis(hepatic synthesis) glycogen
Poikiloglycemic(regulated by exogenous administration) Hypoglycemia(blood glucose<100mg/dl) acute liver failure or end stage liver disease.

Depleted lean body mass, hypoalbuminemia, low colloid oncotic pressure.

loss of hepatic malnutrition, protein malnutrition, catabolic effects. Ascites, anasarca, pulmonary edema. Impairs normal immune and healing mechanisms. - infection, wound dehiscence, fistulas, bedsores.

 Neurologic complications
Hepatic encephalopathy
elevated arterial ammonia merely a marker of disordered protein mechanism. caused by various peptides, mercaptans, and false or depressive neurotransmitters(octopamine, tryptophan). grade 1 = confabulation, construction apraxia; grade 2 = drowsiness, asterexis, confusion; grade 3 = stupor; grade 4 = coma. Breakdown of the blood-brain barrier result in acute cerebral edema. precipitating factors hypovolemia, GI bleeding, surgery, infection, hypokalemic metabolic alkalosis. alcohol-induced encephalopathy(thiamine deficiency), Wernicke encephalopathy(oculomotor palsy, cerebellar ataxia), Korsakoff psychosis(amnesia, confabulation).

Pharmacologic Effects of Renal and Hepatic Failure

Lipid soluble and nonionized drugs.

undergo hepatic biotransformation to water-soluble metabolites, excreted in the bile or urine.

Lipid insoluble, highly ionized drugs.

directly excreted by the kidney.

Renal and hepatic disease alter drug clearance by several mechanism.

decreased organ blood flow(decreased drug delivery) Increased unbound free fraction of highly proteinbound drugs(hypoalbuminemia, acidosis). Decreased enzymes and transport process.

Both diseases alter drug pharmacodynamics.

debilitated patients, with lean body mass. reduce all drug dosages by 25% to 50%.

 Drugs independent of liver and renal function for elimination.

Undergo enzymatic or spontaneous breakdown in the blood.

 Drugs

with increased hypoalbuminemia.

unbound

fraction

in

Thiopental, methohexital, and diazepam. Should be decreased 20% to 50%.

Drugs

predominantly biotransformation.

dependent

on

hepatic

Lidocaine, all benzodiazepines, all opioids, many nondepolarizing muscle relaxants(except atracurium, cisacurium). Drugs with metabolism that depends on the cytochrome oxidase(CP450) system(diazepam, midazolam). - more sensitive to liver dysfunction than simple glucuronide conjugation(lorazepam, propofol). Lidocaine primary metabolite, methylglycinexylydide. sensitive indicator of liver function and reserve.

 Drugs that depend predominantly on renal

elimination.
Gallamine, metubine, digoxin, penicillins, cephalosporins, aminoglycosides, vancomycin, cyclosporin A. Loading dose unaltered, maintenance dose must be drastically decreased.

Drugs that depend in part on renal elimination.

Anticholinergic and cholinergic agents, pancuronium, pipecuronium, vecuronium, rocuronium, doxacurium, milrinone, amrinone, phenobarbital, aprotinin, aminocaproic acid, tranexamic acid. Maitenance dose must be decreased by 30% to 50%.

 Drugs with active metabolites that are eliminated by the kidneys.

Exert a prolonged effect in CRF. The parent drugs should be avoided or maintenance doses must be decreased by 30% to 50%.

 Volatile anesthetic drugs.

Nephrotoxic effects
Polyuric renal failure after prolonged methoxyflurane anesthesia.
related to nephrotoxicity of the fluoride metabolite. directly related to the peak plasma fluoride concentration and duration. less than 25M : rarely associated with renal injury. greater than 150M : ass. with severe renal failure.

Enflurane
Renal injury only in the presence of nephrotoxins, hepatotoxins, or enzyme inducers.

Substantial amount of the fluoride causing nephrotoxicity stems from local production(in the kidney), not correlate with serum concentrations.

Compound A
a metabolite produced by the interaction of sevoflurane with outdated sodalime when fresh gas flows are less than 2 L/min. use sevoflurane with fresh gas flow greater than 2 L/min, avoid in patients at risk for perioperative renal injury.

Hepatotoxic effects
Related to the extent of hepatic metabolism. Mild hepatotoxicity
1 in 700 cases. related to injury caused by reductive metabolites, formed in an hypoxic milieu.

Fulminant hepatic necrosis (halothane hepatitis)

induced by immune sensitization to the trifluoroacetylated products of oxidative metabolism(CP450 2E1). Occurred in 1:35,000 exposure to halothane. Risk factors. genetically predisposed patients, concomitant use of agents that induce mixed function oxidases, reexposure to halothane within 2 weeks(most important). cross-reactivity with other agents.

Perioperative Management

 Chronic renal failure

Preoperative evaluation
The cause of CRF, complicated systemic disease, the other manifestations of the disease. Daily urine output, type of dialysis, recent treatment.

Preoperative preparation
Hemodialysis
controls the manifestations of ARF(fluid overload, acidosis, hyperkalemia, acute uremia). Does not completely correct thrombocytopathy or not reverse osteodystrophy and neuropathy. Adverse effects hypovolemia, hypotension, MI, electrolyte imbalance. best scheduled the day before surgery.

Peritoneal dialysis
provides hemodynamic stability but not effective in hypermetabolic states. Abdominal distension compromise perioperative pulmonary function.

Continuous venous hemodialysis

during CPB.

Preoperative blood transfusion

Not indicated for patients with a stable hematocrit(> 26%). Only to treat acute blood loss, for patients with cardiopulmonary disease undergoing major surgery. Transfusion shoud be administered during dialysis only(risk of hypervolemia and hyperkalemia). Causes immunosuppression, increase the infection risk.

Human recombinant erythropoietin

At a dose of 50 to 75 IU/kg subcutaneously three times weekly. Normalizes the hematocrit concentration. Decrease the requirement for erythrocyte transfusion, decrease hospitalization, cardiovascular mortality(30%), improve the quality of life. Adverse effects. Hypertension, increase the risk for arteriovenous graft thrombosis.

Treatment of platelet dysfunction

bleeding time >15minutes. A synthetic analogue of arginine vasopressin (DDAVP) stimulates endothelial release of von Willebrand factor VIII. 0.3 g/kg, IV, over 20 minutes at least 30 minutes before anticipated bleeding. vasodilator effects induce hypotension in hypovolemic patient. Tachyphylaxis Cryoprecipitate contains von Willebrand factor VIII. Critically ill patient on catecholamine inotropic agents(induce endothelial release of factor VIII) are best served than DDAVP.

Operative preparation
Sedative or opiod premedication
minimized or avoided.

Aspiration prophylaxis
anticholinergic agents, H2 blockers, metoclopramide, sodium bicitrate.

BP cuffs or arterial catheters should be avoided on the arm with an AV fistula or shunt. Do not place a urinary catheter in anuric or oliguric patients(ascending infection). Fracture and joint injury in patient with renal osteodystrophy. Active warming devices(prevent hypothermia).

Anesthetic planning and management

Regional anesthesia
Not contraindicated if coagulopathy is corrected. Increase risk of hypotension(autonomic neuropathy), and site infection.

General anesthesia
At induction : aspiration precautions, preoxygenation, preinduction fluid load(250 to 1000 ml). Succinylcholine Not contraindicated if serum potassium < 5.0 mEq/l, had dialysis within 24 hours. nondepolarizing agents pancuronium and pipecuronium Should be avoided. mivacurium and and cisatracurium Metabolized independent of renal elimination. vecuronium and rocuronium ok.

Increase mechanical minute ventilation Compensate chronic metabolic acidosis. In anuric patients, Maintenance fluid kept in minimal, fluid losses must be fully replaced.

Postoperative care
Emergence may be delayed, complicated by vomiting, aspiration, hypertension, persistent neuromuscular blockade, respiratory depression, pulmonary edema. In patient with chronic metabolic acidosis,
opioid-induced respiratory depression Cause a decrease in ph and acute hyperkalemia. A short period of postoperative mechanical ventilation Controlled emergence, avoids reversal agents, fascilitates evaluation of neurologic and ventilatory function before extubation.

 Liver disease
Preoperative evaluation
Child-Pugh classification Most widely used tool for assessment of risk in patient with cirrhosis. Prothrombin time Prolonged > 3 seconds above control, not corrected with vitamin K.

Preoperative preparation
Hepatic failure
Drain tense ascites before surgery. Performed with caution because of the hypovolemia, hypotension, and liver injury. risk of

spironolactone(aldosterone antagonist)
Exacerbate hyperkalemia in the presence of ARF. Should be discontinued 3 to 4 days before surgery.

parenteral vitamin K and FFP

Correct factor VII prothrombin time. deficiency and prolonged

Treatment of encephalopathy
Protein restriction, lactulose, neomycin.

Protection of hepatorenal syndrome(in patients with end stage liver disease)

Ensure adequate preoperative hydration. Pharmacological renal protection(low dose dopamine, furosemide, fenoldopam).

Transjugular intrahepatic portosystemic shunt

In patients for orthotopic liver transplantation. Decompresses portal system, relieves severe ascites, decrease the risk of variceal bleeding, improves renal perfusion and hepatorenal syndrome. Risks : bleeding, acute heart failure d/t sudden increase in right atrial filling, endotoxemia, encephalopathy.

Anesthetic planning and management

Regional anesthesia
Help to preserve hepatic blood flow if bp and cardiac output is maintained. Should not use in the presence of coagulopathy, ascites, encephalopathy.

Drug handling
pharmacokinetics. Large volume of distribution and impaired hepatic elimination. Loading dose requirement may be high, but emergence is delayed. Doses of all sedative drugs should be decreased. Cisatracurium Metabolism is independent of liver function. Neuromuscular blocker of choice

Volatile anesthetics Decrease hepatic blood flow Overcome by appropriate hemodynamic management. Opioids(except remifentanil) Accumulate, delayed emergence. Propofol A relatively short-acting drug in patients with cirrhosis. Myocardial depression, inhibition of reflex tachycardia, vasodilation. Intraoperative hypoxemia(ascites, intrapulmonary shunting), bleeding(coagulopathy), oliguria(vasomotor nephropathy).

Management of partial hepatectomy or liver transplantation.

The avoidance of excessive volume loading. Hepatic venous congestion Increase venous oozing and intraoperative bleeding. Most important determinant of outcome after hepatic resection. Keep CVP 10 mmHg in patient with normal cardiac function.

Postoperative care
Emergence may be delayed, complicated by vomiting, aspiration, hypotension, respiratory depression, acute respiratory failure.
extubate only when the patient is fully awake. A short period of postoperative mechanical ventilation.

Potential postoperative problems

Bleeding, oliguria, encephalopathy, acute respiratory failure, sepsis, wound dehiscence, acute hepatic failure.