Renal Effects of the Inhalation Agents

Published on 07/02/2015 by admin

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Renal Effects of the Inhalation Agents

Richard L. Applegate, II, MD

Inhalation anesthetic agents can alter renal function through physiologic effects or through toxic effects of the agents or their breakdown products. Physiologic effects of inhalation anesthetics are typically transient. The risk for renal toxicity with modern inhalation agents is low.

Physiologic Effects

Autoregulation of renal blood flow appears to be maintained during administration of modern inhalation anesthetic agents, though the use of these agents associated with changes in cardiovascular function that may include decreases in cardiac output and arterial pressure. If prolonged, these decreases may adversely affect renal function. However, perioperative renal dysfunction is most commonly caused by intravascular volume depletion and anemia, leading to hypoperfusion of the kidney, with intracellular hypoxia. The impact of surgical stress may add to renal ischemia, as the kidney has few β2-adrenergic receptors; therefore, catecholamine stimulation leads to unopposed renal vasoconstriction. Additionally, positive-pressure ventilation during anesthesia is associated with reversible decreases in renal perfusion pressure, creatinine clearance, and sodium excretion, as is abdominal insufflation during laparoscopic procedures.

Toxicity

Metabolic Products

The halogenated anesthetic agents undergo varying degrees of metabolic degradation. The metabolic pathways differ depending on the agent, with the production of a number of intermediate metabolites and the release of fluoride (F−). Inhaled anesthetic gases may also undergo chemical degradation in CO2 absorbers to produce a number of compounds, including fluoromethyl-2, 2-difluoro-1-(trifluoromethyl) vinyl ether (FDVE), known as compound A, from sevoflurane. CO may also be produced from the breakdown of desflurane and, to a lesser degree, from other halogenated anesthetic agents currently in use. These products of metabolism and degradation may contribute to postoperative renal dysfunction.

When methoxyflurane was clinically available and used, its metabolism led to release of F−; a F− concentration above 50 μmol/L was identified as a risk factor for anesthesia-related renal dysfunction and raised concern about the renal safety of all halogenated anesthetic agents that release F− as a product of metabolism. Elevated F− concentrations after prolonged exposure to enflurane (which is also no longer available in the United States) may be associated with transient renal dysfunction, but following exposure to other halogenated agents (isoflurane and sevoflurane), these levels are not associated with clinical renal damage in humans. Investigation into long administration (>10 h) of inhaled anesthetic agents at a fresh-gas flow of 1 L/min or less has shown no association with significant renal dysfunction, although transient elevation of sensitive markers of renal damage may occur.

Published evidence indicates that the renal damage associated with methoxyflurane administration is caused by O-demethylation to produce F− and DCAA (dichloroacetic acid), which is nephrotoxic, especially in the presence of F−. It is also possible that intrarenal metabolism is responsible for renal dysfunction following methoxyflurane administration. Other currently available halogenated anesthetic agents (isoflurane, sevoflurane, desflurane) are not metabolized in renal cells, nor are they metabolized to DCAA, and their use is not associated with clinically significant renal dysfunction.

Breakdown Products

Sevoflurane can degrade in some CO2 absorbers to produce compound A (FDVE) and other products. This degradation is more likely to occur at low fresh-gas flow rates. Compound A is nephrotoxic in rats. The amount of compound A that is generated varies with the type of absorbent, with newer absorbent materials producing little to no compound A, compared with absorbents, such as soda lime, that have larger amounts of strong bases (KOH, NaOH). Current U.S. Food and Drug Administration labeling suggests limiting sevoflurane exposure to 2 minimum alveolar concentration hours at fresh-gas flow rates of 1 to 2 L/min and discourages the administration at fresh-gas flow rates under 1 L/min because this will minimize exposure to compound A. However, numerous reports of longer administration have been published showing no difference in renal function or sensitive markers of renal damage following the administration of sevoflurane, when compared with other inhaled anesthetic agents.

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Renal Effects of the Inhalation Agents

Richard L. Applegate, II, MD

Inhalation anesthetic agents can alter renal function through physiologic effects or through toxic effects of the agents or their breakdown products. Physiologic effects of inhalation anesthetics are typically transient. The risk for renal toxicity with modern inhalation agents is low.

Physiologic Effects

Autoregulation of renal blood flow appears to be maintained during administration of modern inhalation anesthetic agents, though the use of these agents associated with changes in cardiovascular function that may include decreases in cardiac output and arterial pressure. If prolonged, these decreases may adversely affect renal function. However, perioperative renal dysfunction is most commonly caused by intravascular volume depletion and anemia, leading to hypoperfusion of the kidney, with intracellular hypoxia. The impact of surgical stress may add to renal ischemia, as the kidney has few β2-adrenergic receptors; therefore, catecholamine stimulation leads to unopposed renal vasoconstriction. Additionally, positive-pressure ventilation during anesthesia is associated with reversible decreases in renal perfusion pressure, creatinine clearance, and sodium excretion, as is abdominal insufflation during laparoscopic procedures.