Volatile anesthetics also raise the apneic threshold (Paco2 level below which apnea occurs through lack of CO2-driven respiratory stimulation) and decrease the ventilatory response to hypoxia. Clinically, the respiratory depressant effects of anesthetics are overcome by assisting (controlling) ventilation mechanically. The ventilatory depression produced by inhaled anesthetics may be counteracted by surgical stimulation; however, low, subanesthetic concentrations of volatile anesthetic present after surgery in the early recovery period can continue to depress the compensatory increase in ventilation normally caused by hypoxia.
Inhaled anesthetics also depress mucociliary function in the airway. During prolonged exposure to inhaled anesthetics, mucus pooling and plugging may result in atelectasis and the development of postoperative respiratory complications, including hypoxemia and respiratory infections.
D. Renal Effects
Inhaled anesthetics tend to decrease glomerular filtration rate (GFR) and urine flow. Renal blood flow may also be decreased by some agents, but filtration fraction is increased, implying that autoregulatory control of efferent arteriole tone helps compensate and limits the reduction in GFR. In general these anesthetic effects are minor compared with the stress of surgery itself and usually reversible after discontinuation of the anesthetic.
E. Hepatic Effects
Volatile anesthetics cause a concentration-dependent decrease in portal vein blood flow that parallels the decline in cardiac output produced by these agents. However, total hepatic blood flow may be relatively preserved as hepatic artery blood flow to the liver may increase or stay the same. Although transient changes in liver function tests may occur following exposure to volatile anesthetics, persistent elevation in liver enzymes is rare except following repeated exposures to halothane (see Toxicity of Anesthetic Agents).
F. Effects on Uterine Smooth Muscle
Nitrous oxide appears to have little effect on uterine musculature. However, the halogenated anesthetics are potent uterine muscle relaxants and produce this effect in a concentration-dependent fashion. This pharmacologic effect can be helpful when profound uterine relaxation is required for intrauterine fetal manipulation or manual extraction of a retained placenta during delivery. However, it can also lead to increased uterine bleeding after delivery when uterine contraction is desired.
Toxicity of Anesthetic Agents
A. Acute Toxicity 1.
Nephrotoxicity—Metabolism of enflurane and sevoflurane may generate compounds that are potentially nephrotoxic. Although their metabolism can liberate nephrotoxic fluoride ions, significant renal injury has been reported only for enflurane with prolonged exposure. The insolubility and rapid elimination of sevoflurane may prevent toxicity. This drug may be degraded by carbon dioxide absorbents in anesthesia machines to form a nephrotoxic vinyl ether compound termed “compound A,” which, in high concentrations, has caused proximal tubular necrosis in rats. Nevertheless, there have been no reports of renal injury in humans receiving sevoflurane anesthesia. Moreover, exposure to sevoflurane does not produce any change in standard markers of renal function.
2.
Hematotoxicity—Prolonged exposure to nitrous oxide decreases methionine synthase activity, which theoretically could cause megaloblastic anemia. Megaloblastic bone marrow changes have been observed in patients after 12-hour exposure to 50% nitrous oxide. Chronic exposure of dental personnel to nitrous oxide in inadequately ventilated dental operating suites is a potential occupational hazard.