TOPICAL REVIEW

Anesthesia for Patients with Renal/Hepatic Disease

Ann B. Weil, MS, DVM, DACVA
General anesthesia may be necessary for patients with signicant disease processes such as renal disease or hepatic disease. A basic understanding of the effects of general anesthetics on these organs and the anticipated problems of renal and hepatic impairment on the anesthetic process is necessary to optimize conditions for patients with renal or hepatic disease. Patient preparation, drug selection, and monitoring strategies will be discussed for patients with renal and liver disease. 2010 Elsevier Inc. All rights reserved. Keywords: general anesthesia, liver disease, renal disease, kidney

he kidneys receive approximately 25% of the bodys cardiac output and are highly dependent on adequate blood ow to function properly. Nearly every anesthetic agent decreases glomerular ltration rate (GFR) and renal blood ow, so general anesthesia should not be considered an innocuous process for patients with preexisting renal disease.1 Nevertheless, general anesthesia may be necessary for such patients, and steps should be taken to minimize any detrimental impact to remaining nephron function. It may also become necessary to anesthetize patients with acute renal failure to relieve urinary system obstruction. Regardless, as with any critical patient, the duration of general anesthesia should be minimized whenever possible. Patient preparation is crucial for animals with acute or chronic renal failure. Every effort should be made to reduce the level of azotemia before general anesthesia. Hypovolemia and dehydration should be avoided and corrected before general anesthesia. Patients that are anuric or oliguric must have their hydration status monitored very carefully because their volume decits must be managed in the face of urinary obstruction to outow. Inhalant anesthetics produce profound vasodilation and a reduction in cardiac output that can be very detrimental in the face of hypovolemia. Patients with chronic renal failure can be admitted the evening before general anesthesia and placed on intravenous uids to ensure optimal hydration. Anemia should be identied and assessed before general anesthesia. Blood products may need to be used because anemia from chronic renal failure may potentially result in a failure to deliver adequate oxygen to tissues.

General Considerations for Patients with Compensated Chronic Renal Failure

Patient evaluation for anesthetic protocol planning is critical to optimize the condition of the patient while under general anesthesia. Renal patients can present in a wide spectrum of disease states. Well-compensated, well-hydrated chronic renal failure patients can use a wide variety of anesthetic agents, whereas decompensated, critically ill uremic patients may be very limited in appropriate drug selection and must be most carefully managed. In general, anesthetic agents and adjuncts that optimize cardiac output are the best choices for patients with renal disease. Blood pressure monitoring is extremely valuable to manage renal blood ow, as is robust uid therapy. Every effort must be made to ensure adequate renal blood ow.

Pharmacologic Considerations Premedication

Premedication of renal patients with sedatives and analgesics can be very helpful to reduce stress and anxiety and provide analgesia. Stress and pain will result in sympathetic nervous system stimulation and catecholamine release, which may result in decreased blood ow to the kidney.1 General anesthetics do not provide antinociceptive activity, so the use of premedications will enhance the analgesic activity of the anesthetic plan (Table 1). The use of sedatives and analgesics will decrease the amount of induction and maintenance agents necessary for general anesthesia both of which have the potential to decrease cardiac output and reduce GFR and renal blood ow. Acepromazine is a long-lasting (6 to 8 hours) phenothiazine tranquilizer and a dopamine antagonist.2 Premedication with a low dose of acepromazine in renal patients may be advantageous because of the vasodilatory nature (via alpha blockade) of the drug. A low dose of acepromazine (0.03 mg/kg) has been shown to reduce the effectiveness of high-dose dopamine therapy at increasing systemic vascular resistance in anesthetized dogs but did not alter the dopamine-mediated peripheral vasodilation associ-

From the School of Veterinary Medicine, Purdue University, West Lafayette, IN USA. Address reprint requests to: Ann B. Weil, MS, DVM, DACVA, Department of Veterinary Clinical Sciences, School of Veterinary Medicine, Purdue University, 625 Harrison St, West Lafayette, IN 47907. E-mail: aweil@purdue.edu. 2010 Elsevier Inc. All rights reserved. 1527-3369/06/0604-0171\.00/0 doi:10.1053/j.tcam.2009.12.002

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Table 1. Sample Anesthetic Plan for Patients with Chronic Renal Disease Ensure optimal hydration status: preload with uids if necessary Premedication: Acepromazine (0.01-0.02 mg/kg) IV, IM, or SC, if dopamine not planned Opioid IV, IM, or SC Hydromorphone (0.1 mg/kg) Butorphanol (0.2-0.4 mg/kg) Buprenorphine (0.010-0.020 mg/kg) Benzodiazepine Midazolam (0.1-0.2 mg/kg) IV or IM Diazepam (0.2 mg/kg) IV Induction: Propofol 6 mg/kg IV to effect Isourane or sevourane maintenance Fluid therapy: Isotonic crystalloid: 10 mL/kg/h Monitoring: blood pressure, capnometry, pulse oximetry, urine output, body temperature, ECG
Abbreviations: IM, Intramuscularly; IV, intravenously; SC, subcutaneously; ECG, electrocardiogram.

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fol has been shown to have minimal effects on GFR. Propofol induction and maintenance with a constant-rate infusion may be helpful in patients that need chemical restraint while measuring GFR.6 Regardless of the induction agent chosen, administration of the drug to effect will help maintain hemodynamic stability.

Maintenance
Either isourane or sevourane will maintain renal blood ow better than halothane. These agents decrease GFR, so techniques that decrease the amount of inhalant needed to maintain patients are very helpful for patient care. These include the use of opioid constant-rate infusions, regional or local anesthetic techniques, and the use of premedicants.9

Monitoring
Monitoring of chronically ill patients while they are under general anesthesia is of paramount importance. Particular attention should be paid to blood pressure monitoring to help ensure that the kidneys are adequately perfused and have sufcient blood ow to support the remaining nephrons. Duration of the planned anesthesia and condition of the patient will help determine what type of blood pressure monitoring should be used. Critically ill patients who anticipate a lengthy duration of general anesthesia should be monitored via invasive or direct blood pressure monitoring if at all possible. Less compromised patients and patients who have very short-duration anesthesia may be managed with indirect monitors. Indirect, cuff-based monitors are easy to use in patients but are more prone to inaccuracy. Direct arterial pressure monitoring is more expensive but has the advantage of more accurate readings and permits easy access for blood gas analysis. Acid-base status is of particular importance in animals with renal disease, especially because animals with acute renal failure are at risk of electrolyte abnormalities such as hyperkalemia. Most point of contact blood gas analysis machines (ISTAT, IRMA) have cartridges that analyze both blood gas values and electrolytes. Mean arterial blood pressure can be considered an estimate of tissue perfusion pressure. Mean arterial blood pressure should be maintained above 60 mm Hg in small animal patients to provide sufcient blood ow to vital organs. Mean arterial pressures above 70 mm Hg are desirable if renal disease is present.1 If indirect blood pressure monitors such as Doppler or oscillometric units are used, than systolic blood pressure should be maintained above 90 mm Hg. Many patients with compensated renal disease will have secondary hypertension before anesthesia.10 As in any critical patient undergoing general anesthesia, pulse oximetry and capnography will assist in respiratory monitoring of the renal disease patient. Mucous membrane color and capillary rell time should be carefully monitored and assessed. Patients should have hematocrit or packed cell volume (PCV) assessed periodically. Patients with anemia will need to have a transfusion to ensure adequate oxygen delivery to the kidney if PCV is less than 20% (dogs) or 18%

ated with lower doses of dopamine.3 Acepromazine does not provide any analgesia, but may be helpful in reducing stress and anxiety. Opioids have many advantages when used for patients with renal disease. They provide sedation and analgesia without reducing cardiac output.4 Full mu agonists such as hydromorphone, fentanyl, morphine, or oxymorphone may be very useful before, during, and after anesthesia for pain relief. Butorphanol, a kappa agonist and mu antagonist may be used if the anticipated pain produced by the procedure is not great. Buprenorphine, a long-lasting, partial mu agonist can also be considered for patients with renal disease. Benzodiazepines (diazepam, midazolam) can be used for tranquilization and muscle relaxation in patients with renal disease. They may be used to counteract the deleterious effects of drugs such as ketamine or to reduce the dose of induction agents. They do not provide any analgesia.5 Alpha-2 agents (xylazine, dexmedetomidine) are generally avoided in patients with signicant renal disease because of the reduction in cardiac output and decrease in vital organ blood ow associated with their use.5 Medetomidine has been shown to reduce GFR in dogs.6 Alpha-2 agents inhibit antidiuretic hormone, resulting in an increase in urine volume, which is not desirable in patients with urinary tract obstruction.7

Induction
The choice of induction agent is not critical in patients with compensated renal disease. Patients who are severely depressed should have an anesthetic plan that maximizes cardiac output and stability. Ketamine is highly dependent on the kidney for excretion in the cat, so large doses of ketamine should not be administered to cats with renal disease.8 Propo-

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(cats). Every effort should be made to maintain a normal body temperature, and forced air warmers and circulating water blankets can be very helpful to stabilize body temperature during general anesthesia. Peripheral volume support is essential: 10 to 20 mL/kg/h of crystalloid isotonic uids given intravenously should be used to maintain adequate circulating volume to the kidney. Colloid therapy can be considered if blood pressure is not adequate with crystalloids alone. Hetastarch administered intravenously at rates of 2 to 10 mL/kg/h can assist in maintaining intravascular volume, not exceeding 20 mL/kg/d. Care should be taken to make sure the patient is making urine and that volume overload does not occur from overzealous crystalloid or colloid administration. Diuretic therapy may need to be instituted if pulmonary edema occurs. Urine output should be measured by aseptic catheterization of the bladder if a lengthy or complicated procedure is planned. Normal urine output is 0.5 to 2 mL/kg/h. Dopamine therapy may be considered in debilitated patients at the rate of 1 to 10 g/kg/min. Low doses (1-3 g/kg/min) of dopamine will increase renal blood ow (RBF), GFR, and urine output. Higher doses will activate beta adrenoceptors, which may dilate renal arterial beds and increase cardiac output.9 There is evidence to suggest that low-dose dopamine (3 g/ kg/min) therapy does not induce diuresis in cats.11 Ensure adequate analgesia because pain and sympathetic nervous system stimulation will cause catecholamine release, vasoconstriction, and decreased blood ow to the kidney.12 Perioperative use of nonsteroidal agents such as meloxicam or carprofen is generally not recommended in patients with renal disease.

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obstruction, and traumatic urinary tract rupture, including ruptured bladder.13 Electrolyte abnormalities like hyperkalemia, hyponatremia, and hypochloremia may occur with a ruptured bladder, as well as acidemia. An electrocardiogram should be run on patients with a ruptured bladder before general anesthesia to look for evidence of cardiac abnormalities due to hyperkalemia. Serum potassium levels greater than 5.5 to 6.0 mEq/L should be treated before general anesthesia and the serum potassium level corrected as much as possible. Intravenous uids like 0.9% NaCl should be used, as well as dextrose, insulin, or bicarbonate if necessary to reduce potassium levels. Calcium gluconate or calcium chloride may be administered to antagonize the cardiac effects of hyperkalemia if treatment is not successful.9

Hepatic Disease
Like the kidney, the liver is a major user of the bodys blood supply. About 20% of cardiac output is delivered to the liver. Seventy percent of its blood supply comes from the portal vein and 30% of the blood supply from the hepatic artery, which supplies most of its oxygen needs.14 Maintenance of adequate blood ow and oxygen delivery during general anesthesia is crucial to reduce further damage to hepatocytes. The liver is responsible for the metabolism and biotransformation of most substances in the body, both endogenous and exogenous. Anesthetics and adjuncts should be chosen to support vital organ blood ow. They should be expected to have a longer duration of effect in patients with liver disease. The liver has a central function in the formation, storage, and release of glucose. It also produces coagulation factors such as plasminogen and antithrombin and is responsible for metabolism of many activators of the coagulation and plasmin cascades. Liver failure may result in disseminated intravascular coagulation. Hemostasis [prothrombin time (PT), partial thromboplastin time (PTT), bleeding time] should be evaluated before general anesthesia in patients with liver disease, especially if surgery is planned. Patients with signicant liver disease may ooze and bleed more than anticipated. The liver is the primary site of plasma protein synthesis except for gamma globulins and factor VIII. Plasma albumin values are one of the best indicators of liver function. Albumin is very important with respect to anesthesia. Many anesthetic agents bind with plasma proteins so that the drug is divided into active versus bound (inactive) fractions. If the plasma albumin is low, this will allow a higher concentration of the active component and therefore a more profound patient response. In addition, albumin is important for producing plasma oncotic pressure, which retains uid in the intravascular space. If albumin is low ( 1.5-2.0 g/dL), uid may redistribute to the extracellular spaces with resulting edema.

General Considerations for Patients in Acute Renal Failure

Patients in acute renal failure may present in a wide spectrum of clinical statesanywhere from occult disease to profoundly ill. Every effort should be made to stabilize the patient and avoid unnecessary general anesthesia. Careful attention must be made to intravascular volume in the face of anuria. Central venous pressure can be very helpful to assess volume status and guide uid therapy in these animals. Acidbase status and electrolyte levels should be frequently assessed in these patients, so point of contact monitors such as I-stat or IRMA can be very helpful. Patients with postrenal azotemia from complete urinary obstruction are the most likely to require general anesthesia on an emergent basis. These patients present in a clinical spectrum of nearly normal to extremely obtunded and in shock. Near normal patients with acute obstruction can be treated in a similar manner as a well-compensated chronic renal failure patient. Obtunded patients will need to be managed with extreme care. Intense uid therapy will be necessary before general anesthesia, and general anesthesia should be instituted with extreme caution. The most common causes of postrenal azotemia include urethral obstruction, ureteral

General Consideration for Patients with Liver Disease

As in renal disease, patients with liver disease can present with a diverse clinical spectrum. Patients with mild liver dis-

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Table 2. Sample Anesthetic Plan for Patient with Liver Disease Premedication: opioid alone Induction Propofol 6 mg/kg IV Etomidate 1-2 mg/kg IVconsider diazepam immediately prior Mask induction with isourane or sevourane Maintenance: isourane or sevourane Fluid therapy: Crystalloid 5 mL/kg/h with 2.5% dextrose if hypoglycemic Hetastarch 5 mL/kg/h if hypoalbuminemic Monitoring: see above
Abbreviation: IV, Intravenously.

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dependent on the liver for elimination from the body, so one can expect its actions to be prolonged in a patient with liver disease. Alpha-2 agents like xylazine or dexmedetomidine compromise vital organ blood ow and oxygen delivery, so their use should be limited to animals with mild disease and an overwhelming need for profound sedation. Some clinicians consider benzodiazepines to exacerbate problems with hepatic encephalopathy in patients with liver disease and avoid their use. Others consider them a helpful and appropriate choice for patients with mild to moderate disease. Nonetheless, their sedative qualities may be exaggerated and present for a prolonged duration in a patient with signicant liver disease. Opioids, although dependent on the liver for metabolism, tend to be a good choice for patients with liver disease. Animals with signicant liver dysfunction can be expected to have an exaggerated sedative response to opioid administration. Opioids provide analgesia, a fundamental necessity for good patient care, and can be reversed by antagonists like naloxone or naltrexone if necessary. Common opioid choices for preoperative or perioperative administration include morphine, hydromorphone, oxymorphone, buprenorphine, fentanyl, and butorphanol. Opioid selection should be based on patient analgesic needs, desired duration of effect, and route of administration.

ease can be expected to have fewer problems with general anesthesia than patients with severe, fulminant disease. Patients with signs of liver dysfunction like hypoglycemia, hypoalbuminemia, high ammonia levels, and high serum bile acids should be considered at greater risk for complications associated with general anesthesia. Every effort should be made to reduce ammonia levels before general anesthesia to minimize the potential for hepatic encephalopathy post anesthesia. Lactulose administration and enemas can be performed to help reduce blood ammonia levels. To minimize further hepatic damage, techniques and drugs that support liver function, including vital organ blood ow and oxygen delivery, should be used. Anesthetic drugs that have a short half-life, depend on some mechanism other than liver metabolism for their termination, or are reversible should be considered when formulating the anesthetic plan (Table 2). Normal arterial carbon dioxide levels should be maintained, because both hypoventilation and hyperventilation can result in a decrease in hepatic blood ow. Blood glucose concentrations should be carefully monitored. If persistently low, the addition of dextrose to a balanced, crystalloid isotonic uid should be used. A nal concentration of 2.5% dextrose is helpful for many patients. If hypoalbuminemia and hypoproteinemia are present, avoid drugs with high protein binding or be aware that a higher concentration of active drug may result. Colloids such as hetastarch can be added to the uid therapy plan to avoid further dilution of blood proteins. Patients with severe hypoalbuminemia or clotting disorders may need a plasma transfusion.

Induction
In general, a minimum dose of induction agent should be used if possible to minimize the negative hemodynamic effect of the agent on hepatic blood ow. Agents that promote cardiac output are helpful in optimizing liver blood ow, but the method of elimination of the drug by the body must also be considered. Agents that are quickly eliminated by the body and not heavily dependent on the liver for this process are desirable for patients with liver disease. Choices concerning induction agents should be made depending on the degree of liver impairment and with the whole patient in mind. A single bolus dose of induction agent is redistributed to the muscle and then must be eliminated from the body. Avoidance of large cumulative doses of drugs that are dependent on the liver for ultimate removal from the body is a wise policy. Thiobarbiturates should be avoided in patients with liver disease if at all possible. Propofol, a nonbarbiturate, ultra shortacting anesthetic agent should be considered a drug of choice for animals with liver disease. Its rapid redistribution after injection is helpful in terminating its anesthetic effects. Propofol is also eliminated from the body by extrahepatic mechanisms, because clearance of the drug from the body is faster than hepatic blood ow. Etomidate, an imidazole anesthetic, can be used in patients with liver disease, because it has excellent cardiovascular support and rapid redistribution. It is metabolized by the hepatic microenzyme system and plasma esterases, but it clears the body faster than thiopental. It can produce twitching and muscle activity that can be minimized with prior

Pharmacologic Considerations Premedication

Tranquilizer and sedative selection in the patient with liver disease presents a signicant challenge to the anesthetist. Avoid acepromazine and alpha-2 adrenergic agonists in patients with moderate to severe liver disease. Acepromazine has a long duration of effect in a normal patient and is heavily

Volume 25, Number 2, May 2010

administration of a benzodiazepine. Ketamine, a dissociative anesthetic, is heavily metabolized by the liver in dogs, and prolonged recovery may occur in patients with signicant liver disease. A single, small bolus dose is appropriate for patients with mild or moderate liver disease, unless they have a seizure history.

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2. Baldessarini RJ, Tarazi FI: Drugs and the treatment of psychiatric disorders: psychosis and mania, in Hardman JG, Limbird LE (eds): Goodman & Gilmans: The Pharmacological Basis of Therapeutics (ed 10). New York, Hardman McGraw-Hill, 2001, pp 215-268 3. Monteiro ER, Teixeira Neto FJ, Castro VB, et al: Effects of acepromazine on the cardiovascular actions of dopamine in anesthetized dogs. Vet Anesth Analg 34:312-321, 2007 4. Lamont LA, Mathews KA: Opioids, nonsteroidal anti-inammatories, and analgesic adjuvants, in Tranquilli WJ, Thurmon JC, Grimm KA (eds): Lumb & Jones Veterinary Anesthesia and Analgesia (ed 4). Ames, Iowa, Blackwell, 2007, pp 241-271 5. Lemke K: Anticholinergics and sedatives, in Tranquilli WJ, Thurmon JC, Grimm KA (eds): Lumb & Jones Veterinary Anesthesia and Analgesia (ed 4). Ames, Iowa, Blackwell, 2007, pp 203-239 6. Fusellier M, Desfontis J, Madec S, et al: Inuence of three anesthetic protocols on glomerular ltration rate in dogs. Am J Vet Res 68:807-811, 2007 7. Saleh N, Aoki M, Shimada T, et al: Renal effects of medetomidine in isourane-anesthetized dogs with special reference to its diuretic action. J Vet Med Sci 67(5):461-465, 2005 8. Flecknell PA: Injectable anaesthetics, in Hall LW, Taylor PM (eds): Anaesthesia of the Cat. London, Bailliere Tindall, 1994, pp 129-156 9. Grubb TL: Anesthesia for patients with special concerns, in Carroll GL (ed): Small Animal Anesthesia and Analgesia. Ames, Iowa, Blackwell, 2008, pp 193-238 10. Brown S: The kidney as a target organ, in Egner B, Carr A, Brown S (eds): Essential Facts of Blood Pressure in Dogs and Cats. Babenhausen, Germany, Beate Egner Vet Verlag, 2003, pp 121-128 11. Wohl JS, Schwartz DD, Flournoy S, et al: Renal hemodynamic and diuretic effects of low-dosage dopamine in anesthetized cats. J Vet Emerg Crit Care 17(1):45-52, 2007 12. Otte M, Spier A: The renin-angiotensin-aldosterone system: approaches to cardiac and renal therapy. Compend Contin Educ Vets 31(1):E1-7, 2009 13. Fischer JR, Lane IF, Stokes J: Acute postrenal azotemia: etiology, clinicopathology, and pathophysiology. Compend Contin Educ Vets 31(11):520-530, 2009 14. Greene SA, Marks SL: Hepatic Disease, in Tranquilli WJ, Thurmon JC, Grimm KA (eds): Lumb & Jones Veterinary Anesthesia and Analgesia (ed 4). Ames, Iowa, Blackwell, 2007, pp 921-926

Maintenance
Inhalation anesthetics tend to be the most convenient choice to maintain general anesthesia, and they are also used to induce anesthesia if necessary. Halothane should be avoided, but either isourane or sevourane is an appropriate choice for patients with liver disease.

Monitoring
Like any other critical patient undergoing general anesthesia, patient monitoring is a vital component to excellent patient care in patients with liver disease. Particular attention should be made to maintenance of vital organ blood ow and oxygenation. Blood pressure monitoring and pulse oximetry can be very helpful in this regard. Mean arterial pressure should be maintained above 70 mm Hg and oxygen saturation above 95%. As with any anesthetized patient, body temperature should be monitored and maintained as near to normothermic as possible. Patients with severe liver disease may have ascites. If the volume of transudate in the abdominal cavity is large, removal of some of this uid should be done before general anesthesia to reduce the pressure on the diaphragm and resulting impairment of ventilation. However, ascitic uid removal must be done with extreme care and with concomitant uid therapy to support cardiovascular function.9

References
1. Greene SA, Grauer GF: Renal disease, in Tranquilli WJ, Thurmon JC, Grimm KA (eds): Lumb & Jones Veterinary Anesthesia and Analgesia (ed 4). Ames, Iowa, Blackwell, 2007, pp 915-919