Effects on CNS
- Sevoflurane raises intracranial pressure
- Sevoflurane had minimal effect on intracranial pressure (ICP) and preserved CO2, responsiveness in patients with normal ICP.
- Rare cases of seizures have been reported in association with sevoflurane use.
- Sevoflurane suppresses the background central nervous system electrical activities in a dose dependent manner, leaving the reactive capabilities facilitated at deep anesthesia. (1)
Effects on circulation
- During the maintenance of anaesthesia, increasing the concentration of sevoflurane produces dose-dependent decreases in blood pressure.
- Excessive decrease in blood pressure may be related to depth of anaesthesia and in such instances may be corrected by decreasing the inspired concentration of sevoflurane.
- Sevoflurane has not been associated with untoward cardiovascular changes in volunteers and patients undergoing elective surgery and may have less potent effects on the vascular smooth muscle. (2)
- Autonomic nerve activity is attenuated by sevoflurane. Parasympathetic input to the heart by respiration is suppressed following apperance of isoelectric EEG. (3)
- Sevoflurane uptake is higher in patients with higher cardiac output. (4)
Effects on respiration
- Sevoflurane causes respiratory depression which increase as anesthesia is deepened
- Sevoflurane is a suitable agent for induction under spontaneous respiration with higher concentrations in pediatric anesthesia. (5)
- Sevoflurane produce more profound respiratory depression at high MAC. (6)
Effects on GI function
- Deep sedatioj with inhaled sevoflurane for pediatric outpatient gastrointestinal endoscopy is as safe as conventional sedation technique, potentially less expensive, increases endoscopy unit productivity and eliminates the inconvenience associated with obtaining intravenous access in children. (7)
Effects on neuromuscular function
- Use of sevoflurane can cause malignant hyperthermia.
- The syndrome may include non-specific features such as muscle rigidity, tachycardia, tachypnoea, cyanosis, arrhythmias and unstable blood pressure.
- Treatment includes discontinuation of triggering agents (e.g. Sevoflurane), administration of intravenous dantrolene sodium, and application of supportive therapy.
- Renal failure may appear later, and urine flow should be monitored and sustained if possible.
- Use of sevoflurane has been associated with very rare increases in serum potassium levels that have resulted in cardiac arrhythmias and death in children during the postoperative period.
- The condition has been described in patients with latent as well as overt neuromuscular disease, particularly Duchenne muscular dystrophy.
Effects on renal function
- Sevoflurane should be used with caution in patients with renal insufficiency
- No significant renal effects are seen with low flow or high flow sevoflurane. (8)
Effects on hepatic function
- Sevoflurane can be administered to patients with normal or mild-to-moderately impaired hepatic function.
- Use of sevoflurane in patients with severe hepatic dysfunction has not been investigated.
- Very rare cases of mild, moderate and severe post-operative hepatic dysfunction or hepatitis with or without jaundice have been reported from post marketing experiences. 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.
- Sevoflurane at concentrations less than 2.0 MAC preserves hepatic arterial blood flow, total hepatic O2 delivery and the O2 delivery to consumption ratio. (9)
Effects on hematologic and immune systems
- Transient increases in serum inorganic fluoride levels may occur during and alter Sevoflurane anaesthesia.
- Generally, concentrations of inorganic fluoride peak within 2 hours of the end of sevoflurane anaesthesia and return within 48 hours to pro-operative levels.
Biotransformation; reaction with CO2 absorbants; toxicity
- Sevoflurane produces low levels of Compound A (pentafluoroisopropenyl fluoromethyl ether (PIFE)) and trace amounts of Compound B (pentafluoromethoxy isopropyl fluoromethyl ether (PMFE)), when in direct contact with CO2 absorbents. Levels of Compound A Increase with:- increase in canister temperature; increase in anaesthetic concentration; decrease in gas flow rate and increase more with the use of Baralyme rather than Soda lime.
- 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.
- Rare cases of extreme heat, smoke and/or spontaneous fire in the anesthesia machine have been reported during sevoflurane use in conjunction with the use of desiccated CO2 absorbent.
- 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 canister.
Minimum alveolar concentration and pressures
MAC = 2.1 vol %
MAC of sevoflurane decrease with age and with the addition of nitrous oxide
157 mm Hg 22.9 kPa (at 20 deg C)
197 mm Hg 26.3 kPa (at 25 deg C)
317 mm Hg 42.3 kPa (at 36 deg C)
Blood gas partition coefficient = 0.68
Oil: gas partition coefficient = 47
Trace concentrations, O.R. pollution, personnel hazards
- Frequent adverse effects of sevoflurane are nausea and vomiting
- Other adverse effects are:
in adults, hypotension; in elderly, hypotension and bradycardia; in children, agitation and increased cough.
- Less frequent adverse events associated with sevoflurane administration were; agitation, somnolence, chills, bradycardia, dizziness, increased salivation, respiratory disorder, hypertension, tachycardia, laryngismus, fever, headache, hypothermia, increased SGOT.
- Occasionally reported adverse effects associated with the administration of sevoflurane administration include : arrhythmias, increased LDH, increased SGPT, hypoxia, apnoea, leukocytosis, ventricular extrasystoles, supraventricular extrasystoles, asthma, confusion, increased creatinine, urinary retention, glycosuria, atrial fibrillation, complete AV block, bigeminy, leucopenia. Allergic reactions, such as rash, urticaria, pruritus, bronchospasm, anaphylactic or anaphylactoid reactions have also been reported. As with all potent inhaled anaesthetics, sevoflurane may cause dose-dependent cardiorespiratory depression.
- Convulsions may occur extremely rarely following sevoflurane administration, particularly in children. There have been very rare reports of pulmonary oedema.
- Fast induction/ recovery
- High potency (least soluble)
- Non irritating vapor
- Osawa M, Shingu K, Murakawa M, Adachi T, Kurata J, Seo N, Murayama T, Nakao S, Mori K. Effects of sevoflurane on central nervous system electrical activity in cats. Anesth Analg. 1994 Jul;79(1):52-7.
- Ebert TJ. Cardiovascular and autonomic effects of sevoflurane. Acta Anaesthesiol Belg. 1996;47(1):15-21.
- Itsuo Nakatsuka, Ryoichi Ochai, Junzo Takeda. Changes in heart rate variability in sevoflurane and nitrous oxide anesthesia: effects of respiration and depth of anesthesia. Journal of Clinical Anesthesia. May 2002;14(3):196-200.
- JFA Hendrickx, AAJ Van Zundert, AM De Wulf. Sevoflurane pharmacokinetics: effect of cardiac output. British Journal of Anesthesia. 1998;81:495-501
- Mori N, Suzuki M. Sevoflurane in pediatric anesthesia: effects on respiration and circulation during induction and recovery. Pediatr Anaesth. 1996;6(2):95-102.
- M Yamakage,K Tamiyamd, Dai Horikawa, K Sato, A Namikimd. Effects of halothane and sevoflurane on the pediatric respiratory pattern. Pediatric Anesthesia. January 1994;4(1):53-56.
- Montes RG, Bohn RA. Deep sedation with inhaled sevoflurane for pediatric outpatient gastrointestinal endoscopy. J Pediatr Gastroenterol Nutr. 2000 Jul;31(1):41-6.
- Bito Hiromichi, Ikeuchi Yukako, Ikeda Kazuyuki. Effects of low flow sevoflurane anesthesia on renal function: comparison with high flow sevoflurane anesthesia and low flow isoflurane anesthesia. Anesthesiology 1997;86(6):1231-1237.
- Frink Edward J, Morgan Scott EBS, Coetzee Andre, Conzen Peter F, Brown Burnell R. The effects of sevoflurane, halothane, enflurane and isoflurane on hepatic blood flow and oxygenation in chronically instrumented greyhound dogs. Anesthesiology January 1992;76(1).