General anesthesia for patients with renal or hepatic disease (Proceedings)

General considerations for patients with liver disease

Liver disease patients can present with a diverse clinical spectrum.  Patients with mild liver disease 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 prior to general anesthesia in order to minimize the potential for hepatic encephalopathy post anesthesia.  Lactulose and enemas can be performed to help reduce blood ammonia levels.

In order to minimize further hepatic damage, techniques and drugs that support liver function, including vital organ blood flow and oxygen delivery, should be utilized. Anesthetic drugs that have a short half-life, depend upon some mechanism other that liver metabolism for their termination, or are reversible should be considered when formulating the anesthetic plan. Normal arterial carbon dioxide levels should be maintained, as both hypo and hyperventilation can result in a decrease in hepatic blood flow.

Blood glucose concentrations should be carefully monitored.  If persistently low, the addition of dextrose to a balanced, crystalloid isotonic fluid should be utilized.  A final 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 be result.  Colloids such as Hetastarch or Dextran 70 can be added to the fluid therapy plan to avoid further dilution of blood proteins.  Patients with severe hypoalbuminemia or clotting disorders may need a plasma transfusion.

Premedication

Tranquilizer and sedative selection in the liver disease patient presents a significant 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 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 flow 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 liver disease patients 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 significant liver disease.

Opioids, although dependent on the liver for metabolism, tend to be a good choice for patients with liver disease.  Animals with significant 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.

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 flow.  Agents that promote cardiac output are helpful in optimizing liver blood flow, 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.

Propofol, a nonbarbiturate, ultrashort acting 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, as clearance of the drug from the body is faster than hepatic blood flow.

Etomidate, an imidazole anesthetic, can be used in liver disease patients, as 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 myotonic-clonic activity that can be minimized with prior administration of a benzodiazepine.  Ketamine, a dissociative anesthetic, is heavily metabolized by the liver in dogs and prolonged recovery may occur in patients with significant liver disease.  A single, small bolus dose is appropriate for patients with mild or moderate liver disease, unless they have a seizure history.

Maintenance

Inhalation anesthetics tend to be the most convenient choice to maintain general anesthesia, and they are also used to induce anesthesia if necessary.  Either isoflurane or sevoflurane is an appropriate choice for liver disease patients.

Monitoring

Like any other critical patient undergoing general anesthesia, patient monitoring is a vital component to excellent patient care in liver disease patients.  Particular attention should be made to maintenance of vital organ blood flow and oxygenation.  Blood pressure monitoring and pulse oximetry can be very helpful in this regard.

Renal disease

The kidneys receive approximately 25% of the body's cardiac output, and are highly dependent on adequate blood flow in order to function properly.  Nearly every anesthetic agent decreases glomerular filtration rate and renal blood flow, so general anesthesia should never be considered an innocuous process for patients with preexisting renal disease.  Nevertheless, general anesthesia may be necessary for such patients and steps taken to minimize any detrimental impact to remaining nephron function.  It may also become necessary to anesthetize patients with acute renal failure in order 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 prior to 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 as their volume deficits must be managed in the face of urinary obstruction to outflow.  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 prior to general anesthesia and placed on intravenously fluids to ensure optimal hydration.  Anemia should be identified and assessed prior to general anesthesia.  Blood products may need to be utilized as anemia from chronic renal failure may potentially result in a failure to deliver adequate oxygen to tissues.

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 utilize 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 renal disease patients.  Blood pressure monitoring is extremely valuable to manage renal blood flow, as is robust fluid therapy.

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 flow to the kidney.  General anesthetics do not provide antinociceptive activity, so the use of premeds will enhance the analgesic activity of the anesthetic plan.  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 flow.  Acepromazine is a long lasting (6 to 8 hours) phenothiazine tranquilizer and a dopamine antagonist.  Premedication with a low dose of acepromazine in renal patients may be advantageous due to the vasodilatory nature (via alpha blockade) of the drug.  Do not use acepromazine if dopamine administration is planned to improve renal blood flow.  Acepromazine does not provide any analgesia, but may be helpful in reducing stress and anxiety.  Opioids have many advantages when used for renal diseased patients.  They provide sedation and analgesia without reducing cardiac output.   Full mu agonists such as hydromorphone, fentanyl, morphine, or oxymorphone may be very useful before, during and after the 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.  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.  Alpha-2 agents (xylazine, dexmedetomidine) are generally avoided in patients with significant renal disease due to the reduction in cardiac output and decrease in vital organ blood flow associated with their use.  Alpha-2 agents inhibit antidiuretic hormone, resulting in an increase in urine volume which is not desirable in patients with urinary tract obstruction.

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

Maintenance

 Either isoflurane or sevoflurane will maintain renal blood flow better than halothane.  These agents decrease glomerular filtration rate, 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.

Monitoring

Monitoring of chronically ill patients 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 sufficient blood flow 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 utilized.  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 as 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 is considered to be an estimate of tissue perfusion pressure. Mean arterial blood pressure should be maintained above 60 mm Hg in small animal patients in order to provide sufficient blood flow to vital organs.  Mean arterial pressures above 70 mm Hg are desirable if renal disease is present.  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 prior to anesthesia.

Peripheral volume support is essential: 10-20 mls/kg/hr of crystalloid isotonic fluids 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 given intravenously at rates of 2-10 mls/kg/hr can assist in maintaining intravascular volume.  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 0.5-2 mls/kg/hr.  Dopamine therapy may be considered in debilitated patients at the rate of 1-10 µg/kg/min.  Low doses (1-3 µg/kg/min) of dopamine will increase RBF, GFR, and urine output.  Higher doses will activate beta adrenoceptors which may dilate renal arterial beds and increase cardiac output.

Ensure adequate analgesia since pain and sympathetic nervous system stimulation will cause catecholamine release, vasoconstriction and decreased blood flow to the kidney.  Perioperative use of non steroidal agents such as meloxicam or carprofen is generally not generally recommended in patients with renal disease.

Suggested readings

Weil AB. Anesthesia for patients with renal/hepatic disease. Topics Comp Anim Med. 2010;25:87-91.