SEVO-SWISS

Indications

• Induction of general anesthesia
• Maintenance of general anesthesia

Dosage

Children: Refer to the BNF for Children for specific dosing guidelines.

Adults: For induction of anesthesia: Initially 0.5–1%, increased to a maximum of 8% based on patient response. For maintenance of anesthesia: Up to 50%, adjusted according to response.

Mechanism of action

Sevoflurane induces anesthesia by binding to ligand-gated ion channels and blocking central nervous system (CNS) neurotransmission. It enhances inhibitory postsynaptic channel activity through GABA_A and glycine receptors, while inhibiting excitatory synaptic activities via nicotinic acetylcholine, serotonin, and glutamate receptors. Sevoflurane modulates various ionic currents, impacting cardiac excitability and contractility.

Pharmacodynamics

Sevoflurane induces muscle relaxation and reduces tissue excitability, leading to a fast onset of action. It lowers the extent of gap junction-mediated cell-cell coupling, affecting the channels responsible for action potentials. Compared to other agents like halothane and isoflurane, it offers shorter emergence times and quicker onset of analgesia. However, it may increase risks of renal injury, respiratory depression, and QT prolongation, with notable adverse effects in pediatric populations.

Pharmacokinetics

Sevoflurane is rapidly absorbed and distributed due to its low blood solubility, allowing for swift equilibration between alveolar and arterial partial pressures. The drug is metabolized mainly in the liver, with minimal hepatic metabolism compared to other halogenated anesthetics. Its pharmacokinetic profile contributes to its rapid onset and recovery, making it suitable for outpatient procedures.

Contra-indications

• Known hypersensitivity to sevoflurane or any of its components
• Personal or family history of malignant hyperthermia
• Severe hepatic impairment

Adverse effects

• Drowsiness
• Fever
• Hypothermia
• Confusion
• Increased muscle rigidity
• Nephritis tubulointerstitial
• Abdominal distension
• Cardiac arrest
• Severe bradycardia
• Malignant hyperthermia
• Respiratory depression
• QT interval prolongation

Interactions

• Amfetamines (unknown additive effect)
• Sympathomimetics (unknown additive effect)

Precautions

• Use with caution in patients with a history of QT interval prolongation
• Monitor for respiratory depression and renal injury
• Assess plasma vitamin B12 concentration in at-risk patients
• Patients with Down Syndrome may have increased risk of severe bradycardia

Pregnancy

May depress neonatal respiration if used during delivery.

Breast-feeding

Breastfeeding can be resumed as soon as the mother has recovered sufficiently from anaesthesia.

Storage

Store at room temperature. Protect from light and moisture.

Formulations

• Sevoflurane volatile liquid 250 ml

Mechanism of action

The precise mechanism of action of sevoflurane has not been fully elucidated. Like other halogenated inhalational anesthetics, sevoflurane induces anesthesia by binding to ligand-gated ion channels and blocking CNS neurotransmission. It has been suggested that inhaled anesthetics enhance inhibitory postsynaptic channel activity by binding GABA_A and glycine receptors, and inhibit excitatory synaptic channel activity by binding nicotinic acetylcholine, serotonin, and glutamate receptors. Sevoflurane has an effect on several ionic currents, including the hyperpolarisation-activated cation current (I_f), the T-type and L-type Ca²⁺ currents (I_{Ca, T} and I_{Ca, L}), the slowly activating delayed rectifier K⁺ currents (I_Ks), and the Na⁺/Ca²⁺ exchange current (I_NCX). This ability to modulate ion channel activity can also regulate cardiac excitability and contractility. Sevoflurane is widely used as a volatile anesthetic in clinical practice. However, its mechanism is still unclear. ...It has been reported that voltage-gated sodium channels have important roles in anesthetic mechanisms. Much attention has been paid to the effects of sevoflurane on voltage-dependent sodium channels. To elucidate this, /investigators/ examined the effects of sevoflurane on Na(v) 1.8, Na(v) 1.4, and Na(v) 1.7 expressed in Xenopus oocytes. The effects of sevoflurane on Na(v) 1.8, Na(v) 1.4, and Na(v) 1.7 sodium channels were studied by an electrophysiology method using whole-cell, two-electrode voltage-clamp techniques in Xenopus oocytes. Sevoflurane at 1.0 mM inhibited the voltage-gated sodium channels Na(v)1.8, Na(v)1.4, and Na(v)1.7, but sevoflurane (0.5 mM) had little effect. This inhibitory effect of 1 mM sevoflurane was completely abolished by pretreatment with protein kinase C (PKC) inhibitor, bisindolylmaleimide I. Sevoflurane appears to have inhibitory effects on Na(v)1.8, Na(v)1.4, and Na(v) 1.7 by PKC pathways. However, these sodium channels might not be related to the clinical anesthetic effects of sevoflurane. Sevoflurane has been demonstrated to vasodilate the feto-placental vasculature. /Investigators/ aimed to determine the contribution of modulation of potassium and calcium channel function to the vasodilatory effect of sevoflurane in isolated human chorionic plate arterial rings. Quadruplicate ex vivo human chorionic plate arterial rings were used in all studies. Series 1 and 2 examined the role of the K+ channel in sevoflurane-mediated vasodilation. Separate experiments examined whether tetraethylammonium, which blocks large conductance calcium activated K+ (KCa++) channels (Series 1A+B) or glibenclamide, which blocks the ATP sensitive K+ (KATP) channel (Series 2), modulated sevoflurane-mediated vasodilation. Series 3 - 5 examined the role of the Ca++ channel in sevoflurane induced vasodilation. Separate experiments examined whether verapamil, which blocks the sarcolemmal voltage-operated Ca++ channel (Series 3), SK&F 96365 an inhibitor of sarcolemmal voltage-independent Ca++ channels (Series 4A+B), or ryanodine an inhibitor of the sarcoplasmic reticulum Ca++ channel (Series 5A+B), modulated sevoflurane-mediated vasodilation. Sevoflurane produced dose dependent vasodilatation of chorionic plate arterial rings in all studies. Prior blockade of the KCa++ and KATP channels augmented the vasodilator effects of sevoflurane. Furthermore, exposure of rings to sevoflurane in advance of TEA occluded the effects of TEA. Taken together, these findings suggest that sevoflurane blocks K+ channels. Blockade of the voltage-operated Ca++channels inhibited the vasodilator effects of sevoflurane. In contrast, blockade of the voltage-independent and sarcoplasmic reticulum Ca++channels did not alter sevoflurane vasodilation. Sevoflurane appears to block chorionic arterial KCa++ and KATP channels. Sevoflurane also blocks voltage-operated calcium channels,

Pharmacodynamics

Sevoflurane induces muscle relaxation and reduces sensitivity by altering tissue excitability with a fast onset of action. It does so by decreasing the extent of gap junction-mediated cell-cell coupling and altering the activity of the channels that underlie the action potential. Compared to [halothane] and [isoflurane], sevoflurane has a shorter emergence time, as well as a shorter time to first analgesia. To reach an equilibrium between alveolar and arterial partial pressure, only a minimal amount of sevoflurane needs to be dissolved in blood. The use of sevoflurane can increase the risk of renal injury, respiratory depression, and QT prolongation. Also, it can lead to malignant hyperthermia, perioperative hyperkalemia, and pediatric neurotoxicity. Episodes of severe bradycardia and cardiac arrest have been reported in pediatric patients with Down Syndrome given sevoflurane. Sevoflurane anesthesia may impair the performance of activities requiring mental alertness, such as driving or operating machinery.