There is a reversible depression of renal function observed during and after surgery in most patients, which is likely attributable to interplay between surgical procedure and duration, anesthetic techniques, and the cardiovascular and renal status of the patient. General anesthesia is associated with a transient decrease in renal function evidenced by decreases in GFR, renal blood flow (RBF), urine output, and solute excretion. The deeper the level of anesthesia, the greater the degree of depression in renal function, particularly in the presence of hypovolemia [10].

Multiple intravenous anesthetics have effects on renal function (Table 1.1). Thiopental decreases GFR and urine flow as well as renal blood flow and sodium excretion. The effect of this medication gradually reverses, and animal studies on high-dose thiopental show renal blood flow remains unchanged in spite of a decrease in myocardial contractility, cardiac preload and blood pressure, and a reflex increase in systemic vascular resistance [11]. The effects of propofol on renal injury remain controversial. Recent rat studies suggest propofol may have a protective effect in acute kidney injury [12]. Midazolam, in induction doses, decreases urine flow but does not significantly affect renal blood flow, renal vascular resistance, or sodium excretion [13]. Ketamine has been shown in dogs to increase blood pressure, renal blood flow, and renal vascular resistance though studies are conflicting [14]. At doses of 1–2 mg/kg, morphine does not decrease blood pressure or urine flow. Fentanyl may decrease GFR, urine flow, and mean arterial pressure (MAP), though with conflicting data regarding renal blood flow [3].

Inhalational anesthetics affect renal function as well. Halothane has been a fairly extensively studied volatile anesthetic. Most studies show a decrease in GFR, sodium excretion, and urine output with a variable effect on renal blood flow during halothane administration. Data suggest that halothane may not decrease renal blood flow [15]. While less information is available regarding the effects of other volatile anesthetics, enflurane decreases GFR, RBF, and urine flow in humans. Likewise, isoflurane decreases GFR and urine output in pigs with little change in renal blood flow [16]. Sevoflurane metabolism to inorganic fluoride has been implicated in experimental studies of renal toxicity; however, no human studies are available to indicate this effect [17]. Desflurane decreases renal vascular resistance as well as RBF, thus maintaining renal blood flow [8].

While multiple anesthetic drugs have direct effects on the kidneys and their function due to hemodynamic affects, they are often also dependent on the kidney for renal excretion of either the drug itself or of its metabolites. Hydrophilic and ionized drugs depend primarily on renal excretion. Mechanisms of renal excretion depend on renal blood flow. Thus renal blood flow decreases due to surgery, anesthesia, or preexisting conditions may result in decreased renal excretion by the kidneys. This knowledge becomes important in developing an anesthetic plan for patients with renal dysfunction. In addition to accumulation of drugs and their metabolites, renal failure patients may also have an altered volume of distribution, hypoalbuminemia, anemia, hyperkalemia, and metabolic acidosis.

Of the intravenous anesthetics, multiple medications are affected in patients with renal failure. Thiopental, a highly protein-bound drug, has an increased unbound fraction in the presence of hypoalbuminemia, acidemia, and uremia [18]. This increase in free drug in renal failure patients should theoretically decrease the dose required. However, renal failure patients also experience an increased volume of distribution, which counteracts the increase in unbound fraction. Thus patients with renal dysfunction usually require a normal to slightly decreased dose of thiopental. Thiopental’s elimination half-life and clearance are only slightly prolonged as the drug is primarily metabolized by the liver. Unlike the more protein-bound barbiturates, ketamine, propofol, and benzodiazepines require no alteration in induction doses in patients with renal failure [8].

Narcotics are another class of medications to be taken into consideration in patients with renal dysfunction. Morphine is metabolized primarily by hepatic glucuronidation to form morphine-6-glucuronide and morphine-3-glucuronide, both of which are excreted renally [19]. Morphine-6-glucuronide is more potent than morphine and may accumulate in renal patients causing prolonged respiratory depression. Meperidine is metabolized by the liver to normeperidine, which is eliminated both renally and hepatically. Accumulation of high levels of normeperidine can produce excitatory central nervous symptoms including seizures in extreme cases. More appropriate narcotics in renal patients include fentanyl [20], sufentanil, alfentanil, and remifentanil that do not undergo transformation to long-acting renally excreted metabolites [3].

Inhalational anesthetics including halothane, sevoflurane, isoflurane, and desflurane are all useful for patients with renal failure. Elimination of these drugs is not dependent on renal function. However, volatile anesthetics are variably metabolized by the liver to metabolites including inorganic fluoride, which is dependent on renal excretion and is nephrotoxic [21]. This metabolization is highest in halothane (12–20%) and followed by sevoflurane, enflurane, isoflurane, and desflurane (3%, 2%, 0.2%, and 0.02%, respectively). Sevoflurane has not been reported to cause renal toxicity in patients despite this laboratory data [22].

Additional medications used in general anesthesia and affected by renal failure include neuromuscular blockers and anticholinesterases. Succinylcholine increases serum potassium by 0.5 meq/l. This increase is no larger in renal patients than in nonrenal patients: however, the baseline potassium must be taken into consideration. Succinylcholine is metabolized by the hepatically produced plasma cholinesterase. This cholinesterase may be decreased in uremic renal patients, but this does not usually lead to any clinically significant effect. A metabolite of succinylcholine, succinylmonocholine, is excreted by the kidney and may be active as a nondepolarizing neuromuscular blocker. Thus continuous infusions of succinylcholine should be avoided in patients with renal failure [8].

Nondepolarizing neuromuscular blockers also include those dependent on renal excretion. Pancuronium, metocurine, gallamine, doxacurium, and pipercurium are renally excreted and will exhibit prolonged elimination half-lives in patients with renal failure. Atracurium, vecuronium, and cisatracurium are the paralytics of choice for intermediate duration as their pharmacodynamics are minimally affected. Atracurium metabolism depends on ester hydrolysis and Hoffman’s elimination, which do not require renal function. However, a metabolite of atracurium, laudanosine, is a central nervous system excitatory agent, which may accumulate in renal patients, though has not been documented to reach clinical significance [23]. Cisatracurium is metabolized by Hoffman’s elimination and is safe in renal failure [24]. Vecuronium is metabolized by the liver; however, the clinical duration of the drug may be increased in renal failure due to an increase in elimination half-life and decrease in clearance. The elimination half-life of rocuronium is increased in renal dysfunction due to the increased volume of distribution; however, there is no clinical difference noted in terms of onset, duration, and recovery of neuromuscular blockade. Mivacurium, while no longer available in the United States, is hydrolyzed by plasma cholinesterase and shows a prolonged duration of action in renal failure. This difference is only a matter of a few minutes and does not prevent usage in patients with renal failure [8].

Of the anticholinesterases, neostigmine, pyridostigmine, and edrophonium are all highly dependent on renal excretion [25–27]. As a result they have prolonged durations of action in patients with renal failure. Anticholinergics such as atropine and glycopyrrolate also have prolonged durations of actions in these patients [3].

Analgesics in addition to narcotics must be taken into consideration when administered to patients with renal disease. Acetaminophen does not inhibit renal prostaglandins and is less likely to cause renal toxicity than other nonsteroidal anti-inflammatory drugs (NSAIDs) [28]. Thus while prolonged use of acetaminophen is associated with analgesic nephropathy, occasional or moderate use is safe during the perioperative period and does not require dose adjustment. Unlike acetaminophen, the adverse effects of the nonsteroidal anti-inflammatory drugs likely outweigh any potential benefit perioperatively. They are associated with an increased risk of cardiovascular complications in this high-risk population. NSAIDs are also nephrotoxic agents that precipitate an acute decrease in GFR and may cause acute interstitial nephritis [29].

Regional anesthesia effects on renal function also involve the interplay between surgical procedure, anesthetic technique, cardiovascular, and renal status of the patient. Additionally regional anesthesia effects on renal function may involve the effects of the neural blockade on renal function. A spinal block as high as T1 produces only slight depressions in GFR and RBF in humans as long as systemic blood pressure is maintained [30]. Likewise, epidural blocks to thoracic levels with epinephrine-free local anesthetics produce minimal decreases in GFR and renal blood flow [10]. However, epidural blocks to the thoracic region with epinephrine-containing local anesthetics induce moderate reductions in GRF and RBF that parallel reductions in mean arterial pressure. Most likely the effects of neuraxial blockade on renal function depend on the hemodynamic effects induced by the sympathetic blockade. An additional mechanism of regional anesthesia’s effects on renal function may involve neuroendocrine mechanisms. Many hormones that are increased as part of the stress response to surgery (cathecholamines, aldosterone, rennin/angiotensin, ADH, cortisol) have significant effects on renal function. However, studies have not born out this theory thus far [7, 8].

Management of the renally compromised patient must first distinguish whether the patient is experiencing acute kidney injury or chronic renal failure. Acute kidney injury criteria vary but usually include increases in serum creatinine greater than two- to threefold from baseline or decreased urine output to <0.5 ml/kg/h for 12 h [31, 32]. Acute renal failure (ARF) is thought to affect between 5% and 7% of all hospitalized patients. Those at highest risk are elderly patients with a history of diabetes or underlying renal insufficiency. Risk factors for the development of ARF are multiple, including existing renal disease, age, congestive heart failure, renovascular disease, and major operative procedures such as cardiopulmonary bypass or abdominal aneurysm resections. In hospital patients iatrogenic components such as inadequate fluid replacement, sepsis, and administration of nephrotoxic drugs or contrast materials may contribute. Multiple complications are associated with acute renal failure affecting multiple organ systems. Neurologically patients can experience confusion, somnolence, and seizures. Cardiovascular complications include hypertension, congestive heart failure, and pulmonary edema. In addition patients may experience cardiac dysrhythmias and pericarditis. Gastrointestinal complications include anorexia, nausea, vomiting, and ileus [1].