Anesthesia for Patients with Renal Disease

Renal Blood Flow and Perfusion Pressure

Most renal functions take place in the nephron. The vascular tone of the afferent and efferent arterioles within each nephron contributes to renal vascular resistance and subsequent renal perfusion pressure. The kidney alters the resistance in the afferent arterioles to protect the delicate glomerular capillaries during hypertension and to conserve their functioning during hypotension. Renal blood flow and glomerular filtration rate tend to remain constant in the face of variations in mean arterial pressures between 80 and 180 mm Hg. This basic essential feature of the kidney is an intrinsic property referred to as autoregulation. Autoregulation allows the renal arterioles and arteries to adjust their resistance rapidly and accurately during fluctuations in arterial pressure. Maintenance of adequate systemic blood pressure is significant in any patient, especially those with renal disease, because autoregulation fails when confronted with hypo- and hypertension (Greene and Grauer 2007). Because the kidneys possess inherently unique vasculature, local tissue ischemia and hypoxia may occur regardless of normal organ blood flow. The thick ascending loop of Henle is especially vulnerable to hypoxic injury due to its high metabolic rate and active transport of electrolytes (Merin et al. 1991).

The Renin-Angiotensin System

Renal blood flow and glomerular filtration rate are controlled by a microscopic structure called the juxtaglomerular apparatus (JGA). The JGA is situated where the distal convoluted tubule and the afferent arteriole come into direct contact with each other. This apparatus’ function is to control renal blood flow and glomerular filtration rate through the release of renin and the initiation of the renin-angiotensin system. If renal perfusion decreases, the JGA releases the enzyme renin. Renin then splits the inactive peptide angiotensinogen to form angiotensin I. Angiotensin I has little to no biological activity, and it exits solely as a precursor for angiotensin II. Angiotensin I is converted to angiotensin II by the angiotensin converting enzyme (ACE), which is primarily found in the capillaries of the lungs, but is also present in the kidney. Angiotensin II is a potent systemic vasoconstrictor. It increases renal vascular resistance in both the afferent and efferent arterioles, increases systemic arterial pressure, and decreases renal blood flow, and it may affect the glomerular filtration rate, depending on the physiological state of the animal (Fig. 24.3). Angiotensin II is the major bioactive product of the renin-angiotensin system (DiBartola 2006). Drugs called ACE inhibitors (enalapril, benazapril, etc.) are used to treat hypertension by decreasing the rate of angiotension II production through inhibition of the ACE enzyme.

Figure 24.2. The nephron. Each nephron originates with a Bowman’s capsule and continues as the proximal convoluted tubule, the loop of Henle, and the distal convoluted tubule. The distal convoluted tubule terminates into the renal calyces and renal pelvis where fluids collect and eventually flow out as urine. The blood supply to the nephron begins at the renal artery, enters the hilus of the kidney, and diverges to form the afferent arterioles. The afferent arterioles enter the Bowman’s capsule and divide to form the capillaries that make up the glomerulus. The vessels then form the slightly larger efferent arterioles that exit the Bowman’s capsule and become the capillaries and arterioles that surround and encircle the entire nephron. These vessels eventually reunite to ultimately form the renal vein upon exiting the kidney (Bone 1988).


Figure 24.3. The renin-angiotensin system. When the JGA senses decreased blood flow to the kidney, it releases renin and initiates the renin-angiotensin system. Renin splits the inactive peptide angiotensinogen to form angiotensin I. Angiotensin I exists solely as a precursor to angiotensin II and is converted to angiotensin II by the angiotensin converting enzyme (ACE). Angiotensin II is a potent vasoconstrictor that acts to increase renal vascular resistance and increase systemic arterial pressure (DiBartola 2006).


Antidiuretic Hormone (ADH)

The kidney helps to maintain the volume and composition of the blood through the utilization of antidiuretic hormone (ADH). The body’s water content remains very stable despite wide variations in the amount of fluids taken in and lost each day. This stability can be attributed to ADH. ADH prevents the production of dilute urine by reducing the amount of water lost as urine and by promoting the reabsorption of water back into the circulation. In the absence of ADH the kidney’s collecting ducts are virtually impermeable to water, allowing much of it to flow out as urine (no reabsorption). The release of ADH is triggered by the osmolarity of the blood. Osmolarity refers to the concentration of solutes such as nondiffusible particles, ions, or molecules that are dissolved in a solution such as blood or urine. When the osmolarity of the blood is low (containing few solutes, dilute), ADH is suppressed and less water is reabsorbed into the blood. When osmolarity is high (containing many solutes, concentrated), ADH is stimulated and more water is reabsorbed into the blood, “diluting” out the high solute concentration. Secretion of ADH can also be stimulated by a decrease in blood pressure or blood volume. This is sensed by baro-receptors located in the heart and large arteries. Changes in blood pressure and volume are not as sensitive as changes in osmolarity. For example, the loss of 15–20% of blood volume is necessary before massive amounts of ADH are excreted.

Acid-Base Balance

The kidney is an important organ in the body’s buffer system; however, it is not the most significant organ involved. In this capacity, the renal system operates at a relatively slow rate by eliciting change in blood pH over hours to days (Trim 1979). In contrast, the lungs are able to adjust blood pH in a matter of minutes, and the body’s chemical buffering system takes only seconds (Moss and Glick 2005). The renal system functions to maintain acid-base balance in the body by tubular excretion of hydrogen ions and the formation of NaPO4 and ammonium salts. Acids, with the exception of carbon dioxide removed via the lungs, are ultimately eliminated through the kidney by way of metabolic processes. Impaired renal function may mean impaired drug metabolism and excretion as well as acid-base disturbances, making proper drug dosing a challenge.

Tests of Renal Function

There is no single test that is an ideal way of determining renal function. A 70–75% decrease in renal function must be present before abnormalities are noticed on blood chemistry (Kellen et al. 1994). Even a mild increase in blood urea nitrogen (BUN) and serum creatinine (SCr) may indicate severe disease. It is a good rule of thumb to thoroughly evaluate all middle-aged and older patients and those with suspected renal disease (Paddleford 1988c). Even if renal enzymes are not increased, older patients should be treated with care since there probably exists a degree of renal compromise.

On presentation, renal patients may be dehydrated, anemic, azotemic, and/or anorexic, or they might present with electrolyte abnormalities or acid-base imbalances. An evaluation of the suspected renal patient should include a comprehensive history; a thorough physical exam; a complete blood count (CBC) to assess hematocrit (kidneys produce erythropoietin, a precursor to red blood cells); and a chemistry profile (emphasizing BUN, creatinine, and electrolytes). Ideally, acid/base status, urinalysis with specific gravity, and a urine protein: creatinine ratio (a damaged glomerulus will allow more protein through) should be evaluated prior to anesthesia. Usually, trends are more useful than singular measurements. Plasma creatinine, creatinine clearance, and BUN all look at glomerular filtration rate (GFR). GFR is analogous to the assorted function of the nephrons (Kellen et al. 1994). GFR can be assessed through the use of radio-isotopes and nuclear scintigraphy, but it is not readily available and can be technically challenging. In the clinic, we often rely on the results of plasma creatinine, BUN, and urinalysis when evaluating the renal patient.

BUN concentration is influenced by a number of factors. This makes it a potentially misleading test of renal function. Some factors that can elevate BUN in a patient with normal GFR include diet (high protein intake), hepatic insufficiency (decreases BUN), steroid administration, gastrointestinal hemorrhage, and intravascular fluid volume. Serum creatinine (sCr) is similar in that respect because increases in the face of a normal GFR can be seen with protein ingestion, strenuous exercise, and muscle injury.

The above-mentioned blood tests of renal function cannot distinguish between the types or causes of renal disease or determine the magnitude of azotemia (azotemia refers to increased concentration of circulating BUN, creatinine, and other nonprotein nitrogenous compounds in the blood). Renal dysfunction can be broken down into three categories of azotemia prerenal, primary renal, and postrenal (Table 24.1).

Table 24.1 Categories of azotemia.

Source: Paddleford 1988.

Category Causes Disease/Condition
Caused by factors
that diminish
renal function—
kidney is
normal prior to
Decreased renal
perfusion Heart disease
Addison’s disease
Diseases affecting
the parenchyma:
cortex, medulla, nephrons, etc.
Polycystic kidney
Disease due to
with excretion
of urine from
the kidney
Kidneys may be
normal initially.
Ureter, bladder,
or urethral

Hyperkalemia is a potentially life-threatening sequela of renal failure, urethral obstruction, or acidemia. Elevated levels of circulating potassium (above 6.5 mmol/L) can lead to decreased myocardial contractility and bradycardia, and may initiate cardiac arrest. The patient with a plasma potassium concentration above 6.5 mmol/L should not be anesthetized unless other processes are concurrently threatening life and must be addressed first. Suspected hyperkalemic patients should have ECG monitoring for the presence of peaked T waves but also for bradycardia, flattening or absence of P waves, and prolongation of QT interval. If left untreated, asystole or ventricular fibrillation often ensues.

Once the physical status of the renal patient has been determined, dosage adjustments may be necessary to prevent cumulative effects of anesthetic drugs. Many anesthetic drugs are excreted by the kidney, making a normal GFR important when choosing an anesthetic protocol (Greene and Grauer 2007). It is essential to correct underlying metabolic disturbances and electrolyte abnormalities prior to anesthesia. For example, severe azotemia can reduce the minimal alveolar concentration (MAC) of inhalant anesthetics (Steffey and Mama 2007), hyperkalemia can initiate ventricular fibrillation, and anemia implies a decrease in the blood’s oxygen-carrying capacity.

Anesthesia and the Renal Patient

Moderate to severe renal dysfunction poses an increased risk to the patient needing anesthesia. These patients are often debilitated and may present with dehydration, anemia, hypovolemia, or hyperkalemia. Azotemia increases sensitivity and decreases tolerance to all preanesthetic and anesthetic agents and can lessen the liver’s ability to metabolize drugs. Animals with chronic renal failure (CRF) often present with subsequent congestive heart failure and/or a decrease in the body’s ability to concentrate urine. These disease-states can cause a fluctuation in blood volume, seesawing between hypervolemia and hypovolemia. Metabolic acidosis is also seen with CRF due to the chronic retention of hydrogen ions, sulfates, and phosphates. Regardless of the anesthetic protocol used, adequate renal per-fusion cannot always be predicted, and proper monitoring is vital.

Many anesthetic monitors analyze more than one body system. The most complete picture of the anesthetized patient’s physiologic status is gained through the utilization of a combination of body system measurements, including cardiovascular, pulmonary, and central nervous system observation. Urinary output (normal 1–2 mL/kg/hr in the dog) can be monitored as an indirect measure of renal blood flow (RBF). It is possible to increase renal or organ blood flow by optimizing circulating blood volume through delivery of intravenous fluids such as crystalloids and/or with positive inotropes such as dobutamine or dopamine. Fluid administration minimizes hypovolemia, hypotension, and hypoxia.

Specific Drug Classes and Their Effect on Renal Function


Anticholinergics such as atropine and glycopyrrolate do not significantly affect renal function at therapeutic doses.


Acepromazine is a widely used phenothiazine sedative. Administration of acepromazine may cause intraoperative hypotension because it decreases cardiac output, stroke volume, and mean arterial blood pressure on a dose-dependent basis. Phenothiazines produce hypotension through peripheral vasodilation. This vasodilation may actually improve renal blood flow and increase renal output with normal blood volume and blood pressure. It is also thought that GFR is maintained in dogs given acepromazine and anesthetized with isoflurane (Bostrom et al. 2003). The effects of phenothiazines may be prolonged in the azotemic patient because they are highly protein-bound, and conjugated and uncon-jugated metabolites are excreted in the urine.

Alpha-2 adrenergic agonists

Alpha-2 adrenergic agonists are the most widely used class of sedatives in veterinary medicine (Lemke 2007). These drugs cause dose-dependent changes in cardiovascular function. After administration, there is an initial peripheral effect that causes vasoconstriction, an increase in arterial blood pressure and a reflex bradycardia. Subsequently, central effects arise with a decrease in sympathetic tone, blood pressure, and heart rate. Despite these decreases in cardiovascular function, blood flow to the heart, brain, and kidney is maintained by way of redistribution of flow from less vital organs and tissues (Lawrence et al. 1996). In dogs, medetomidine administered at 10–20 μ g/kg IV decreases urine specific gravity and increases urine production for approximately 4 hours. Alpha-2 adrenergic agonists interfere with the action of ADH on the renal tubules and collecting ducts. This increases the production of dilute urine and promotes diuresis (Rouch et al. 1997).


This highly protein-bound class of sedatives has minimal effect on renal function at therapeutic doses.


The opioids are effective analgesics and are considered to be the foundation of pain management in veterinary medicine. The use of opioids during anesthesia causes minimal effects on cardiovascular function and subsequent renal blood flow at clinically appropriate doses. Morphine is eliminated via glomerular filtration, and very little of it is excreted unchanged in the urine. Persistent clinical effects and an accumulation of morphine’s metabolites may be seen with administration of morphine to an animal in renal failure (Mercadante 2004). Administration of pure mu agonist opioids can cause transient oliguria through an increase in the release of ADH (Stoelting 1997). The release of ADH leads to alterations in renal tubular function and decreases urine volume. Kappa agonists have the opposite diuretic effect through the inhibition of ADH secretion.

Epidural opioid administration provides effective analgesia in a variety of cases. This route decreases the negative systemic side effects of opioids, but although controversial, urine retention following epidural administration has been reported. This may occur by way of a dose-dependent suppression of the detrusor muscle (muscle of the bladder wall) contractility as well as a decrease in the sensation of urge (Herpenger 1998). Manual expression of the bladder or urinary catheterization may be necessary until these functions return to normal.


This class of drugs can have profound effects on cardiovascular function at high doses. Barbiturates decrease renal blood flow and GFR; pheno-barbitol and pentobarbitol inhibit water diuresis by stimulating the release of ADH. Azotemia can cause an increase in the amount of circulating active barbiturate and a decreased amount of circulating protein-bound barbiturate.

Dissociative a nesthetics

Dissociative anesthetic agents do not have a direct effect on renal function but should be given cautiously in the renal patient. The majority of the drug ketamine is metabolized by the liver in both dogs and horses, and its metabolites are excreted in the urine. In the cat, ketamine is eliminated virtually unchanged by the kidney and is contraindicated for use in cats with primary renal disease (Paddleford 1988b).

Recovery from dissociative anesthesia is achieved through rapid redistribution of the drug from the central nervous system to other tissues in the body such as the fat, lungs, liver, and kidney. Prolonged sleep times after dissociative anesthetic administration are seen in animals with renal disease and those given large doses of ketamine (Short 1987).


Propofol administration causes a transitory decrease in renal function secondary to hypotension. The hypotension is a result of vasodilation that depresses arterial blood pressure and cardiac contractility. Quick redistribution of the drug restores these functions to preadministration levels.

Inhalant a nesthetics

Commonly used inhalant anesthetics such as isoflurane and sevoflurane are not considered to be nephrotoxic. They provide mild, reversible dose-related changes in renal blood flow and GFR and a release of ADH. The decrease in renal blood flow mirrors the anesthetic-induced decreases in cardiac output commonly seen with vasodilation secondary to inhalant anesthesia (Stoelting 1999). A reduction in GFR is often seen in patients anesthetized with inhalants, leading to reduced volumes of concentrated urine being produced compared to the awake animal. A reduction in renal function is influenced by an animal’s hydration level and subsequent intraoperative hemodynamics. Intravenous fluid administration will lessen or counteract anesthesia-induced reductions in renal function. Prolonged inhalant anesthesia can also cause an increase in BUN, creatinine, and phosphorus (Steffey 1993). In most cases, effects of inhalants on renal function are rapidly reversed after anesthesia.

When sevoflurane is degraded by carbon dioxide absorbants like sodalime and baralyme; a nephrotoxic breakdown product called compound A is produced. Compound A can cause renal injury and death in rats (Morio et al. 1992). The ultimate importance of this in veterinary patients remains to be established (Driessen et al. 2002). Until such information is available, avoid sevoflurane for prolonged anesthesia utilizing low fresh gas flow rates (promotes compound A accumulation) and in patients with known kidney disease or marginal kidney function.

Nitrous oxide

This adjunctive inhalant anesthetic potentiates the release of ADH produced by other inhalants but is not known to cause renal dysfunction.

Nonsteroidal antiinflammatory drugs

Nonsteroidal antiinflammatory drugs (NSAIDs) should not be given to patients with acute renal insufficiency, dehydration, hypotension, hepatic insufficiency, low circulating blood volume (as seen with congestive heart failure), coagulopathies, and gastric ulceration (Tables 24.2, 24.3). They should also not be used concurrently with steroids. Patient selection should be made carefully because NSAIDs may elicit potentially harmful side effects.

Table 24.2 Quick reference drug chart for the renal patient.

Sources: Bostrom et al. 2003; Lemke 2007; Lawrence et al. 1996; Rouch et al. 1997; Mercadante and Arcuri 2004 ; Herpenger 1998; Paddleford 1988; Short 1987; Stoelting 1999; Steffey et al. 1993; Morio et al. 1992; Driessen et al. 2002; Lobetti and Joubert 2000; Lamont and Matthews 2007; Vane and Botting 1995.


Only gold members can continue reading. Log In or Register to continue

Stay updated, free articles. Join our Telegram channel

Aug 12, 2017 | Posted by in SUGERY, ORTHOPEDICS & ANESTHESIA | Comments Off on Anesthesia for Patients with Renal Disease

Full access? Get Clinical Tree

Get Clinical Tree app for offline access