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Chapter: Clinical Anesthesiology: Anesthetic Management: Anesthesia for Patients with Kidney Disease

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Altered Renal Function the Effects of Anesthetic Agents

Most drugs commonly employed during anesthesia (other than volatile anesthetics) are at leat partly dependent on renal excretion for elimination.

Altered Renal Function the Effects of Anesthetic Agents

Most drugs commonly employed during anesthesia (other than volatile anesthetics) are at leat partly dependent on renal excretion for elimination. In the presence of renal impairment, dosage modifi-cations may be required to prevent accumulation of the drug or its active metabolites. Moreover, the systemic effects of AKI can potentiate the phar-macological actions of many of these agents. This latter observation may be the result of decreased protein binding of the drug, greater brain penetra-tion due to some breach of the blood–brain barrier, or a synergistic effect with the toxins retained in kidney failure.

INTRAVENOUS AGENTS

Propofol & Etomidate

The pharmacokinetics of both propofol and etomi-date are minimally affected by impaired renal func-tion. Decreased protein binding of etomidate in patients with hypoalbuminemia may enhance its pharmacological effects.

Barbiturates

Patients with kidney disease often exhibit increased sensitivity to barbiturates during induction, even though pharmacokinetic profiles appear to be unchanged. The mechanism appears to be an increase in free circulating barbiturate as a result of decreased protein binding. Acidosis may also favor a more rapid entry of these agents into the brain by increasing the nonionized fraction of the drug.

Ketamine

Ketamine pharmacokinetics are minimally altered by kidney disease. Some active hepatic metabolites are dependent on renal excretion and can potentially accumulate in kidney failure.

Benzodiazepines

Benzodiazepines undergo hepatic metabolism and conjugation prior to elimination in urine. Because most are highly protein bound, increased sensitiv-ity may be seen in patients with hypoalbuminemia. Diazepam and midazolam should be administered cautiously in the presence of renal impairment because of a potential for the accumulation of active metabolites.

Opioids

Most opioids currently in use in anesthetic man-agement (morphine, meperidine, fentanyl, sufent-anil, and alfentanil) are inactivated by the liver; some of these metabolites are then excreted in urine. Remifentanil pharmacokinetics are unaf-fected by renal function due to rapid ester hydro-lysis in blood. With the exception of morphine and meperidine, significant accumulation of active metabolites generally does not occur with these agents. The accumulation of morphine (morphine-6-glucuronide) and meperidine(normeperidine) metabolites has been reported to prolong respiratory depression in patients with kidney failure, and increased levels of normeperi-dine has been associated with seizures. The phar-macokinetics of the most commonly used opioid agonist–antagonists (butorphanol, nalbuphine, and buprenorphine) are unaffected by kidney failure.

Anticholinergic Agents

In doses used for premedication, atropine and glyco-pyrrolate can generally be used safely in patients with renal impairment. Because up to 50% of these drugs and their active metabolites are normally excreted in urine, however, the potential for accumulation exists following repeated doses. Scopolamine is less dependent on renal excretion, but its central ner-vous system effects can be enhanced by the physi-ological alterations of renal insufficiency.

Phenothiazines, H2 Blockers, & Related Agents

Most phenothiazines, such as promethazine, are metabolized to inactive compounds by the liver. Droperidol may be partly dependent on the kidneys for excretion. Although their pharmacokinetic pro-files are not appreciably altered by renal impairment, potentiation of the central depressant effects of phe-nothiazines by the physiological milieu of renal insufficiency can occur.

All H2-receptor blockers are dependent on renal excretion, and their dose must be reduced for patients with renal insufficiency. Proton pump inhibitor dosage does not need to be reduced for patients with renal insufficiency. Metoclopramide is partly excreted unchanged in urine and will accu-mulate in kidney failure. Although up to 50% of dol-asetron is excreted in urine, no dosage adjustments are recommended for any of the 5-HT3 blockers in patients with renal insufficiency.

INHALATION AGENTS

Volatile Agents

Volatile anesthetic agents are ideal for patients with kidney disease because of lack of dependence on the kidneys for elimination, ability to control blood pressure, and minimal direct effects on renal blood flow. Although patients with mild to moderate renal impairment do not exhibit altered uptake or distri-bution, accelerated induction and emergence may be seen in severely anemic patients (hemoglobin <5 g/dL) with chronic kidney failure; this observa-tion may be explained by a decrease in the blood:gas partition coefficient or by a decrease in minimum alveolar concentration. Some clinicians avoid sevo-flurane (with <2 L/min gas flows) for patients with kidney disease who undergo lengthy procedures.

Nitrous Oxide

Some clinicians omit entirely or limit the use of nitrous oxide to 50% concentration in severely anemic patients with end-stage renal disease in an attempt to increase arterial oxygen content. This may be justified in patients with hemoglobin below 7 g/dL, in whom even a small increase in the dissolved oxygen content may represent a significant percentage of the arterial to venous oxygen difference .

MUSCLE RELAXANTS

Succinylcholine

Succinylcholine can be safely used in patients with kidney failure, in the absence of hyper-kalemia at the time of induction. When the serum potassium is known to be increased or is in doubt, a nondepolarizing muscle relaxant should be sub-stituted. Although decreased plasma cholinesterase levels have been reported in uremic patients follow-ing dialysis, significant prolongation of neuromus-cular blockade is rarely seen.

Cisatracurium & Atracurium

Cisatracurium and atracurium are degraded by plasma ester hydrolysis and nonenzymatic Hofmann elimination. These agents are often the drugs of choice for muscle relaxation in patients with kid-ney failure, especially in clinical situations where neuromuscular function monitoring is difficult or impossible.

Vecuronium & Rocuronium

The elimination of vecuronium is primarily hepatic, but up to 20% of the drug is eliminated in urine. The effects of large doses of vecuronium (>0.1 mg/kg) are only modestly prolonged in patients with renal insufficiency. Rocuronium primarily undergoes hepatic elimination, but prolongation in patients with severe kidney disease has been reported. In general, with appropriate neuromuscular monitor-ing, these two agents can be used with few problems in patients with severe kidney disease.

Curare (d-Tubocurarine)

Elimination of d-tubocurarine is dependent on both renal and biliary excretion; 40–60% of a dose of curare is normally excreted in urine. Increasingly prolonged effects are observed following repeated doses in patients with renal insufficiency. Smallerdoses and longer dosing intervals are therefore required for maintenance of optimal muscle relax-ation. In the days before intermediate acting neuro-muscular blockers, curare was the nondepolarizing paralytic of choice for patients with kidney disease.

Pancuronium

Pancuronium is primarily dependent on renal excre-tion (60–90%). Although pancuronium is metabo-lized by the liver into less active intermediates, its elimination half-life is still primarily dependent on renal excretion (60–80%). Neuromuscular function should be closely monitored if these agents are used in patients with abnormal renal function.

Reversal Agents

Renal excretion is the principal route of elimina-tion for edrophonium, neostigmine, and pyridostig-mine. The half-lives of these agents in patients with renal impairment are therefore prolonged at least as much as any of the above relaxants, and problems with inadequate reversal of neuromuscular blockade are usually related to other factors . In other words, “recurarization” due to inadequate duration of reversal agents is unlikely.

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