SEVOFLURANE BAXTER 100 % INHALATION VAPOUR LIQUID

/ Baxter

Since level of anesthesia may be altered rapidly, only vaporizers producing predictable concentrations of sevoflurane should be used.
The concentration of sevoflurane being delivered from a vaporizer should be known. This may be accomplished by using a vaporizer calibrated specifically for sevoflurane. The administration of general anesthesia must be individualized based on the patient’s response.
Replacement of Desiccated CO2 Absorbents When a clinician suspects that the CO2 absorbent may be desiccated, it should be replaced. The exothermic reaction that occurs with sevoflurane and CO2 absorbents is increased when the CO2 absorbent becomes desiccated, such as after an extended period of dry gas flow through the CO2
absorbent canisters.
Maintenance
Surgical levels of anesthesia can usually be achieved with concentrations of 0.5 – 3% sevoflurane with or without the concomitant use of nitrous oxide. Sevoflurane can be administered with any type of anesthesia circuit.
See prescribing information for full details.

Indicated for induction and maintenance of general anesthesia in adult and pediatric patients for inpatient and outpatient surgery.

* Known or suspected genetic susceptibility to malignant hyperthermia
* Sensitivity to sevoflurane or to other halogenated inhalational
anesthetics.

Renal Injury
Because clinical experience in administering sevoflurane to patients with renal insufficiency (creatinine > 1.5 mg/dL) is limited, its safety in these patients has not been established.
Sevoflurane may be associated with glycosuria and proteinuria when used for long procedures at low flow rates. The safety of low flow sevoflurane on renal function was evaluated in patients with normal preoperative renal function. One study compared sevoflurane to an active control administered for ≥ 2 hours at a fresh gas flow rate of ≤ 1 Liter/minute. One patient in the sevoflurane group developed elevations of creatinine, in addition to glycosuria and proteinuria. There were no patients in the active control group who developed treatment emergent elevations in serum creatinine.
Sevoflurane may present an increased risk in patients with known sensitivity to volatile halogenated anesthetic agents. KOH containing CO2 absorbents are not recommended for use with sevoflurane.
Respiratory Depression
Sevoflurane may cause respiratory depression, which may be augmented by opioid premedication or other agents causing respiratory depression. Monitor respiration and, if necessary, assist with ventilation.
QT Prolongation
Reports of QT prolongation, associated with torsade de pointes (in exceptional cases, fatal), have been received. Caution should be exercised when administering sevoflurane to susceptible patients (e.g. patients with congenital Long QT Syndrome or patients taking drugs that can prolong the QT interval).
Malignant Hyperthermia
In susceptible individuals, volatile anesthetic agents, including sevoflurane, may trigger malignant hyperthermia, a skeletal muscle hypermetabolic state leading to high oxygen demand. Fatal outcomes of malignant hyperthermia have been reported. In clinical studies of sevoflurane, 1 case of malignant hyperthermia was reported.
The risk of developing malignant hyperthermia increases with the concomitant administration of succinylcholine and volatile anesthetic agents. Sevoflurane can induce malignant hyperthermia in patients with known or suspected susceptibility based on genetic factors or family history, including those with certain inherited ryanodine receptor (RYR1) or dihydropyridine receptor (CACNA1S) variants.
Signs consistent with malignant hyperthermia may include hyperthermia, hypoxia, hypercapnia, muscle rigidity (e.g., jaw muscle spasm), tachycardia (e.g., particularly that unresponsive to deepening anesthesia or analgesic medication administration), tachypnea, cyanosis, arrhythmias, hypovolemia, and hemodynamic instability. Skin mottling, coagulopathies, and renal failure may occur later in the course of the hypermetabolic process.
Successful treatment of malignant hyperthermia depends on early recognition of the clinical signs.
If malignant hyperthermia is suspected, discontinue all triggering agents (i.e., volatile anesthetic agents and succinylcholine), administer intravenous dantrolene sodium, and initiate supportive therapies.
Driving and Operating Machinery
Performance of activities requiring mental alertness, such as driving or operating machinery, may be impaired after sevoflurane anesthesia.
Pediatric Neurotoxicity
Some studies in children suggest that repeated or prolonged anesthetic exposure in early life (up to ~3 years of age) may lead to cognitive or behavioral deficits, though findings are inconclusive and may reflect the underlying condition or surgery rather than the drug itself. For elective procedures in young children, weigh the benefits against potential risks and consider delaying when possible.
Bradycardia in Down Syndrome
Episodes of severe bradycardia and cardiac arrest, not related to underlying congenital heart disease, have been reported during anesthesia induction with sevoflurane in pediatric patients with Down syndrome. In most cases, bradycardia improved with decreasing the concentration of sevoflurane, manipulating the airway, or administering an anticholinergic or epinephrine.
During induction, closely monitor heart rate, and consider incrementally increasing the inspired sevoflurane concentration until a suitable level of anesthesia is achieved. Consider having an anticholinergic and epinephrine available when administering sevoflurane for induction in this patient population.
Hepatic Function
Occasional cases of transient changes in postoperative hepatic function tests were reported with both sevoflurane and reference agents. Cases of mild, moderate, and severe hepatic dysfunction or hepatitis (e.g., jaundice associated with fever and/or eosinophilia) after anesthesia with sevoflurane have been reported. Clinical judgement should be exercised when sevoflurane is used in patients with underlying hepatic conditions or under treatment with drugs known to cause hepatic dysfunction. It has been reported that previous exposure to halogenated hydrocarbon anesthetics may increase the potential for hepatic injury.
See prescribing information for full details.

Adverse events are derived from controlled clinical trials conducted in the United States, Canada and Europe. The reference drugs were isoflurane, enflurane and propofol in adults, and halothane in pediatric patients. The studies were conducted using a variety of premedications, other anesthetics and surgical procedures of varying length. Most adverse events reported were mild and transient, and may reflect the surgical procedures, patient characteristics (including disease) and/or medications administered. Of the 5,182 patients enrolled in the clinical trials, 2906 were exposed to sevoflurane, including 118 adults and 507 pediatric patients who underwent mask induction. Each patient was counted once for each type of adverse event. Adverse events reported in patients in clinical trials and considered to be possibly or probably related to sevoflurane are presented within each body system in order of decreasing frequency in the following listings. One case of malignant hyperthermia was reported in pre-registration clinical trials.
For full details see prescribing information.

In clinical studies, no significant adverse reactions occurred with other drugs commonly used in the perioperative period, including: central nervous system depressants, autonomic drugs, skeletal muscle relaxants, anti-infective agents, hormones and synthetic substitutes, blood derivatives, and cardiovascular drugs.
Epinephrine- Epinephrine administered with sevoflurane may increase the risk of ventricular arrhythmias. Monitor the electrocardiogram and blood pressure and ensure emergency medications to treat ventricular arrhythmias are readily available.
Calcium antagonists
Sevoflurane may lead to marked hypotension in patients treated with calcium antagonists. Blood pressure should be closely monitored and emergency medications to treat hypotension should be readily available when calcium antagonists are used concomitantly with sevoflurane.
Non-selective MAO-inhibitors
Concomitant use of MAO inhibitors and inhalational anesthetics may increase the risk of hemodynamic instability during surgery or medical procedures.
Benzodiazepines and Opioids
Benzodiazepines and opioids would be expected to decrease the MAC (Minimum Alveolar Concentration) of sevoflurane in the same manner as with other inhalational anesthetics. Sevoflurane administration is compatible with benzodiazepines and opioids as commonly used in surgical practice.
Nitrous Oxide
As with other halogenated volatile anesthetics, the anesthetic requirement for sevoflurane is decreased when administered in combination with nitrous oxide. Using 50% N2O, the MAC equivalent dose requirement is reduced approximately 50% in adults, and approximately 25% in pediatric patients.
Neuromuscular Blocking Agents
As with other volatile anesthetics, sevoflurane increases both the intensity and duration of neuromuscular blockade induced by nondepolarizing muscle relaxants. When used as an adjunct to alfentanil-N2O anesthesia, sevoflurane and isoflurane increase the neuromuscular blockade induced by pancuronium, and curonium or atrecurium to a similar extent. Therefore, during anesthesia with sevoflurane, dose adjustments for muscle relaxants are required.
The potentiation of neuromuscular blocking agents requires balancing the muscle with the delivered partial pressure of sevoflurane. Reduced doses of neuromuscular blocking agents during induction of anesthesia may result in a delay in conditions suitable for endotracheal intubation or inadequate muscle relaxation.
Of the available non-depolarizing agents, only vecuronium, pancuronium, and atracorium have been studied for interactions during sevoflurane anesthesia. In the absence of specific guidelines:
1. For endotracheal intubation, the dose of non-depolarizing muscle relaxants should not be reduced.
2. During maintenance of anesthesia, the required dose of non-depolarizing muscle relaxants is likely to be reduced compared to that during N2O/opioid anesthesia. The administration of
supplementary doses of muscle relaxants should be guided by the response to nerve stimulation.
Desiccated CO2 Absorbents
An exothermic reaction occurs when sevoflurane is exposed to CO2 absorbents. This reaction is increased when the CO2 absorbent becomes desiccated, such as after an extended period of dry gas flow through the CO2 absorbent canisters. Rare cases of extreme heat, smoke, and/or spontaneous fire in the anesthesia breathing circuit have been reported during sevoflurane use in conjunction with the use of desiccated CO2 absorbent, specifically those containing potassium hydroxide (e.g. Baralyme). KOH containing CO2 absorbents are not recommended for use with sevoflurane. An unusually delayed rise or unexpected decline of inspired sevoflurane concentration compared to the vaporizer setting may be associated with excessive heating of the
CO2 absorbent and chemical breakdown of sevoflurane.
As with other inhalational anesthetics, degradation and production of degradation products can occur when sevoflurane is exposed to desiccated absorbents.

Pregnancy: There are no adequate and well-controlled studies in pregnant women. Sevoflurane has been used in clinical studies, as part of general anesthesia for elective
cesarean section, in 29 women. There were no untoward effects in mother or neonate. The safety of sevoflurane in labor and delivery has not been demonstrated.
Sevoflurane can cause uterine smooth muscle relaxation and may contribute to uterine atony.
Lactation: It is not known whether sevoflurane or its metabolites are present in human milk. To minimize infant exposure to sevoflurane or its metabolites, a nursing mother may temporarily pump, and discard breast milk produced during the first 24 hours after administration of sevoflurane.
See prescribing information for full details.

In the event of overdosage, or what may appear to be overdosage, the following action should be taken: discontinue administration of sevoflurane, maintain a patent airway, initiate assisted or controlled ventilation with oxygen, and maintain adequate cardiovascular function.