Anesthetic Concerns for the Patient With Renal and

Hepatic Disease

R4 오 재 열

• 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 acidosisCompensated by chronic respiratory alkalosis.Buffer base is depleted.Shock, diarrhea, or hypercatabolism(sepsis, trauma, steroid therapy).Profound metabolic acidosis.

Electrolyte imbalanceExtracellular 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.

HypermagnesemiaMuscle weakness, susceptibility to muscle relaxants.

HypomagnesemiaAssociated with hypokalemia, ventricular irritability.

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

HypocalcemiaSecondary 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 syndromeIncreased susceptibility to muscle relaxants, difficult ventilatory weaning, and CNS dysfunction.

Cardiovascular problemsSystemic hypertensionLVH(concentric or asymmetric)Hyperlipidemia

a high prevalence of accelerated atherosclerosis.

Anemia and AV shuntshyperdynamic circulation with fixed low systemic vascul

ar resistance.circulatory reserve is impaired.Myocardial ischemia, sepsis 에서 hypotension 발생 .

Uremic pericarditis, hemorrhagic pericardial effusions.

Pulmonary problemsIncreased minute ventilation

to compensate chronic metabolic acidosis.

Hypoalbuminemia, decreased serum oncotic pressure, decreased muscle strength, immunosuppression.

postoperative pulmonary edema, atelectasis, pneumonia.

CAPDabdominal distensioncompromises ventilation and forced vital capacity(FVC).

Impaired hematopoiesisNormochromic, normocytic anemiaHct. 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 coagulopathyAbnormal 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 functionHyperglycemia, 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 pressureperipheral 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 ulcerup to 25% in CRF patients.

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

Neurologic dysfunctionDepend on the acuity of uremia.Personality changes, drowsiness, asterexis, myoclonus, seizures.Major surgery, gastrointestinal bleeding, infection

precipitate acute encephalopathy.Lifetime hospital dependence

passive-aggressive, depressed, manipulative, and churlish.

Uremic distal sensorimotor neuropathya 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 hypertensioninduce ascites and intravascular hypovolemia.secondary hyperaldosteronism(sodium and water retention, potassium excretion)

: hypokalemic metabolic alkalosis, generalized edema(anasarca), progressive ascites.

Asciteselevates 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 alkalosisworsens hepatic encephalopathy.Extracellular hydrogen ion concentration 감소시 , 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 dysfunctionPotential 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 syndromeAny 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 necrosisdirect nephrotoxic effect of endotoxin.Variceal bleeding with hemorrhagic shock

- ischemic tubular necrosis.

– Hyperdynamic circulationA 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 failureHepatopulmonary 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 K absorption.Prolongation of prothrombin time.

marker of hepatic synthetic dysfunction.Thrombocytopenia

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

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

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

– Nutritional-metabolic problemsLoss of glycogenesis(hepatic glycogen synthesis)

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 complicationsHepatic encephalopathy

elevated arterial ammoniamerely 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 protein-bound 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 unbound fraction in hypoalbuminemia.

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

• Drugs predominantly dependent on hepatic biotransformation.

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).

Lidocaineprimary metabolite, methylglycinexylydide.

sensitive indicator of liver function and reserve.

• Drugs that depend predominantly on renal elimination.– Gallamine, metubine, digoxin, penicillins, cephalosporins, am

inoglycosides, vancomycin, cyclosporin A.– Loading dose unaltered, maintenance dose must be drastical

ly 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 25μM : rarely associated with renal injury.greater than 150μM : ass. with severe renal failure.

EnfluraneRenal 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 Aa 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 effectsRelated 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 failurePreoperative evaluation

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

Preoperative preparationHemodialysis

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 dialysisprovides hemodynamic stability but not effective in hypermetabolic states.Abdominal distension compromise perioperative pulmonary function.

Continuous venous hemodialysisduring CPB.

Preoperative blood transfusionNot 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 erythropoietinAt 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 dysfunctionbleeding time >15minutes.A synthetic analogue of arginine vasopressin(DDAVP)

stimulates endothelial release of von Willebrand factor VIII.0.3 μg/kg, IV, over 20 minutes at least 30 minutes before anticipated bleeding.vasodilator effects – induce hypotension in hypovolemic patient.Tachyphylaxis

Cryoprecipitatecontains von Willebrand factor VIII.Critically ill patient on catecholamine inotropic agents(induce endothelial release of factor VIII) are best served than DDAVP.

Operative preparationSedative or opiod premedication

minimized or avoided.

Aspiration prophylaxisanticholinergic 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 managementRegional anesthesia

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

General anesthesiaAt 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 agentspancuronium and pipecuronium – Should be avoided.mivacurium and and cisatracurium – Metabolized independent of renal elimination.vecuronium and rocuronium – ok.

Increase mechanical minute ventilationCompensate chronic metabolic acidosis.

In anuric patients,Maintenance fluid kept in minimal, fluid losses must be fully replaced.

Postoperative careEmergence may be delayed, complicated by vomiting, aspiration, hypertension, persistent neuromuscular blockade, respiratory depression, pulmonary edema.In patient with chronic metabolic acidosis,

opioid-induced respiratory depressionCause a decrease in ph and acute hyperkalemia.

A short period of postoperative mechanical ventilationControlled emergence, avoids reversal agents, fascilitates evaluation of neurologic and ventilatory function before extubation.

• Liver disease Preoperative evaluation

Child-Pugh classificationMost widely used tool for assessment of risk in patient with cirrhosis.

Prothrombin timeProlonged > 3 seconds above control, not corrected with vitamin K.

Preoperative preparationHepatic failure

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

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

parenteral vitamin K and FFPCorrect factor VII deficiency and prolonged prothrombin time.

Treatment of encephalopathyProtein 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 shuntIn 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 managementRegional 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 handlingpharmacokinetics.

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 anestheticsDecrease hepatic blood flowOvercome by appropriate hemodynamic management.

Opioids(except remifentanil)Accumulate, delayed emergence.

PropofolA 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 careEmergence 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 problemsBleeding, oliguria, encephalopathy, acute respiratory failure, sepsis, wound dehiscence, acute hepatic failure.