Isoflurane nervous system

A hydrogen bond, involving an acidic hydrogen atom borne by a fluorine-substituted or halogen-substituted carbon, seems to contribute to the activity and selectivity of volatile fluorinated anesthetics (Table 3.2). These molecules, although nonfunctional, can bind stereoselectively with protein targets of the central nervous system. Different biological behaviors have been reported for both enantiomers of isoflurane (cf. Chapter 8). ... 

Unlike isoflurane, desflurane may stimulate the sympathetic nervous system at concentrations above 1 MAC. Sudden and unexpected increases in arterial blood pressure and heart rate have been reported in some patients, accompanied by increases in plasma catecholamine and vasopressin concentrations and increased plasma renin activity. These pressor effects may increase morbidity or mortality in susceptible patients. The mechanism of sympathetic activation is unclear but does not appear to be baroreceptor-mediated. Clonidine, esmolol, fentanyl and propofol partially block the response but lignocaine (lignocaine) is ineffective. 

Inhaled anesthetics change heart rate either directly by altering the rate of sinus node depolarization or indirectly by shifting the balance of autonomic nervous system activity. Bradycardia can be seen with halothane, probably because of direct vagal stimulation. In contrast, enflurane, and sevoflurane have little effect, and both desflurane and isoflurane increase heart rate. In the case of desflurane, transient sympathetic activation with elevations in catecholamine levels can lead to marked increases in heart rate and blood pressure when high inspired gas concentrations are administered. 

Inhaled (volatile) anesthetics potentiate the neuromuscular blockade produced by nondepolarizing muscle relaxants in a dose-dependent fashion. Of the general anesthetics that have been studied, inhaled anesthetics augment the effects of muscle relaxants in the following order isoflurane (most) sevoflurane, desflurane, enflurane, and halothane and nitrous oxide (least) (Figure 27-9). The most important factors involved in this interaction are the following (1) nervous system depression at sites proximal to the neuromuscular junction (ie, central nervous system) (2) increased muscle blood flow (ie, due to peripheral vasodilation produced by volatile anesthetics), which allows a larger fraction of the injected muscle relaxant to reach the neuromuscular junction and (3) decreased sensitivity of the postjunctional membrane to depolarization. 

CRITICAL ASSESSEMENT OF THE METHOD In general pharmacological studies during anesthesia should be assessed appropriately due to the possible interaction between the test compound and the used anesthetic as well as due to the reduced tone of the autonomic nervous system. Enteral administration of the candidate compound should be avoided, because enteral absorption of the test compound might be reduced due to the impaired intestinal motility during anesthesia. With respect to the effect of the aesthetic compound itself on intermediary metabolism the barbiturate pentobarbital sodium is the most inert anesthetic and does not cause alterations of metabolic blood and tissue parameters. In contrast, e.g. urethane as well as isoflurane (inhalation aesthetic) influences by itself substantially metabolic parameters over time (hours). 

Nervous System Isoflurane reduces cerebral metabolic consumption and causes less cerebral vasodilation than do either enflurane or halothane, making it a preferred agent for neurosurgical procedures. The modest effects of isoflurane on cerebral blood flow can be reversed readily by hyperventilation. 

Nervous System Sevoflurane produces effects on cerebral vascular resistance, cerebral metabolic consumption, and cerebral blood flow similar to those produced by isoflurane and desflurane. Sevoflurane can increase ICP in patients with poor intracranial compliance. The response to hypocapnia is preserved during sevoflurane anesthesia, and increases in ICP can be prevented by hyperventilation. 

The (-I-) enantiomer of isofiurane appears to be more potent as an anesthetic agent than is its antipode [192,193]. It appears that the (-I-) enantiomer causes a greater inhibition of neuronal activity by stimulation of GABAa receptors in the central nervous system [194]. Compared to isoflurane, halothane enantiomers do not appear to differ as much in their effects on GABAa responses [195]. 

Nervous system Two patients developed signal abnormalities on MRI brain scans after prolonged use of isoflurane for refractory status epilepticus [3 ]. 

---