8/12/2019 Wita

1/86

Sevoflurane

1) Deskripsi

Adalah obat anestesi inhalasi berbentuk cairan yang mudah menguap,berbau

harum, dan tidak mudah terbakar.

Sevofluran adalah suatu obat anestesi umum inhalasi derivat eter dengan

kelarutan dalam darah yang lebih rendah dari halotan, enfluran dan isofluran.

Rendahnya kelarutan serta tidak adanya bau yang menyengat

menyebabkan induksi inhalasi berjalan dengan cepat dan mulus, juga kelarutan

dalam darah yang rendah menyebabkan pemulihan berjalan dengan cepat.

Dibandingkan dengan Desfluran, Sevofluran mempunyai A! yang lebih

rendah "#,$%).

Desfluran mempunyai kelarutan yang lebih rendah, akan tetapi, iritasi jalan nafas

lebih besar dengan Desfluran, maka obat anestesi inhalasi yang paling cocokuntuk teknik &'A adalah Sevofluran.

(idak ada iritasi saluran nafas, sehingga induksi berjalan lancar. ejadian

iritasi saluran nafas serta kelarutan lebih rendah daripada halotan, sehingga

induksi inhalasi "baik untuk pediatrik atau de*asa) akan lebih cepat dengan

sevofluran daripada dengan halotan.

+ada induksi inhalasi kejadian batuk, menahan nafas, spasme laring,

eksitasi lebih rendah daripada halotan, sehingga &'A dengan Sevofluran akan

lebih menyenangkan daripada dengan halotan.

angun dari anestesi, pemulihan fungsi psikomotor, kognitif, orientasi

lebih cepat dengan sevofluran dari pada dengan halotan. Sevofluran mendepresi

SS+, kardiovaskuler dan respirasi paralel dengan isofluran.

Sevofluran didegradasi oleh soda lime membentuk suatu haloalken yang

bersifat toksik pada ginjal tikus, tetapi efek tersebut tidak terlihat pada manusia.

Aman digunakan untuk operasi bedah saraf, pasien dengan kelainan serebral,

bedah !aesar, pasien dengan risiko miokardial iskhemia, penyakit hepar,

penyakit ginjal.#) 'ndikasi

Digunakan untuk induksi dan maintenance pada anestesi umum.

-) ontra 'ndikasi

a. pasien yang diketahui sensitive terhadap sevoflurane

b. pasien yang diketahui atau dicurigai secara genetik mudah menderita demam yang

hebat " malignant hipertrofi )

8/12/2019 Wita

2/86

c. pasien dengan hipovolemia yang berat

d. pasien dengan hipertensi intracranial

) /armakologi

Sevoflurane merupakan suatu eter isopropil berflourinasi yang tidak menyala.empunyai tekanan uap sekitar 10# mm g pada #$ 2! dan mendidih pada %0,% 2

!, dalam hal ini sevofluran serupa dengan anestertik volatil lainnya dan diberikan

melaui vaporisator standar.kurang poten dibanding isofluran dengan A! dalam

oksigen sebesar $,00 3.

oefisian partisi darah 4 gas pada -5 2 ! adalah $,%6, kelarutan yang menengah

dalam darah ini menimbulkan induksi anestesia yang cepat. Sevoflurane kurang

bersifat iritan terhadap saluran pernafasan bagian atas dibanding desfluran, pada

induksi menyebabkan lebih sedikit batuk dan laringospasme. Setelah pemberian -$

menit, ratio konsentrasi alveolar terhadap konsentrasi yang diinspirasi adalah $,7%

dibandingkan dengan $,66 untuk oksida nitrosa dan $,5- untuk isoflurane.

%) Dosis

Sevoflurane harus diberikan dengan menggunakan vapori8er yang khusus

dikalibrasi untuk sevoflurane agar konsentrasi yang dihasilkan itu akurat dan mudah

dikendalikan.

a. Dosis untuk premedikasi

+remedikasi harus dipilih dan dipertimbangkan sesuai dengan kebutuhan pasien.

b. Dosis untuk induksi

Sevoflurane dapat diberikan pada anak atau orang de*asa dengan dosis

disesuakan dengan individu pasien aik dari segi umur maupun status fisik

pasien,alternatif lain bisa dengan pemberian obat barbiturat yang bekerja cepat atau

obat intravena lain kemudian dilanjutkan dengan inhalasi sevoflurane,jika induksi

langsung diberikan dengan sevoflurane maka dapat dilakukan dengan campuran

o9ygen saja atau dengan campuran o9ygen dan :#;, pada pasien de*asa yang

diberi sevoflurane sampai %3 akan masuk pada stadium bedah dalam *aktu #

menit, sedang pada anak anak sevoflurane dengan konsentrasi 53 akan masuk ke

stadium bedah dalam *aktu kurang dari # menit sedangkan pasien yang tidak

mendapat premedikasi dapat diberikan sevoflurane untuk induksi sampai 7 3.

c. Dosis untuk maintenanceSetelah dicapai stadium bedah konsentrasi sevoflurane diturunkan untuk

mempertahankan stadium anestesi,dengan konsentrasi antara $,% < -,$$ 3 dalam

o9ygen dan :#;.

8/12/2019 Wita

3/86

0) =fek samping

Dapat menimbulkan depresi system cardiovaskuler dan respirasi seperti obat>

obatan anestesi halogen yang lain.

enimbulkan rasa mual dan muntah pada masa pasca bedah4anestesi sama

seperti obat anestesi inhalasi lain. +ada anak>anak sering terjadi hypotensi.

+ada orang tua dapat terjadi hypotensi dan bradikardi.

Dapat terjadi tetapi jarang? somnolen, menggigil, rasa pusing, bradikardi, salivasi

meningkat, gangguan respirasi, hypertensi tachycardia, laringismus, demam, sakit

kepala, hypothermia.

(erjadi kadang>kadang ? arrhythmia, peningkatan @D, peningkatan S+(,

hypo9ia, apnoe, leukositosis, ventriculer e9trasystole, supraventricular e9trasystole,

asthma, retensio urinae, peningkatan creatinin, glycosuria, atrial fibrilasi, A& lock,

begeminus, leukopeni.

Dapat terjadi tetapi sangat jarang ? kejang>kejang terutama pada anak>anak. Buga

terjadinya melignant hyperthermia dan kegagalan fungsi ginjal akut.

5) +enatalaksanaan

edalaman anestesi berubah dengan cepat , segera setelah ditingkatkanya

konsentrasi uap yang dihirup oleh pasien.hilangnya kesadaran dapat dicapai dalam

% kali tarikan nafas tunggal dengan induksi sevoflurane sebanyak #3, kelarutan

darah 4 gas yang rendah "$,07) menghasilkan induksi dan recovery yang cepat,

karena bau yang enak maka jadi pilihan induksi untuk pasien anak dan de*asa.

http://ether.stanford.edu/library/pediatric_anesthesia/Anatomy,%20Physiology%20and

%20Pharmacology%20in%20Pedaitric%20anesthesia/ClinicalPharmocoinetics!f"e#oflurane.pdf

Current Drugs|Archives| Search

13

Sevoflurane Baxter

Admin Kalbe Medicalposted on August 13, 2013 0!00SEVOFLURANE BAXTER

http://ether.stanford.edu/library/pediatric_anesthesia/Anatomy,%20Physiology%20and%20Pharmacology%20in%20Pedaitric%20anesthesia/ClinicalPharmocokineticsOfSevoflurane.pdfhttp://ether.stanford.edu/library/pediatric_anesthesia/Anatomy,%20Physiology%20and%20Pharmacology%20in%20Pedaitric%20anesthesia/ClinicalPharmocokineticsOfSevoflurane.pdfhttp://ether.stanford.edu/library/pediatric_anesthesia/Anatomy,%20Physiology%20and%20Pharmacology%20in%20Pedaitric%20anesthesia/ClinicalPharmocokineticsOfSevoflurane.pdfhttp://www.kalbemed.com/Products/Drugs/Branded.aspxhttp://www.kalbemed.com/Products/Drugs/Branded.aspxhttp://www.kalbemed.com/Products/Drugs/Branded/tabid/245/articleType/Archives/Default.aspxhttp://www.kalbemed.com/Products/Drugs/Branded/tabid/245/articleType/Archives/Default.aspxhttp://www.kalbemed.com/Products/Drugs/Branded/tabid/245/articleType/Search/Default.aspxhttp://www.kalbemed.com/Products/Drugs/Branded/tabid/245/ID/4554/Sevoflurane-Baxter.aspxhttp://www.kalbemed.com/Products/Drugs/Branded/tabid/245/articleType/AuthorView/authorID/12/UserAdmin.aspxhttp://ether.stanford.edu/library/pediatric_anesthesia/Anatomy,%20Physiology%20and%20Pharmacology%20in%20Pedaitric%20anesthesia/ClinicalPharmocokineticsOfSevoflurane.pdfhttp://ether.stanford.edu/library/pediatric_anesthesia/Anatomy,%20Physiology%20and%20Pharmacology%20in%20Pedaitric%20anesthesia/ClinicalPharmocokineticsOfSevoflurane.pdfhttp://ether.stanford.edu/library/pediatric_anesthesia/Anatomy,%20Physiology%20and%20Pharmacology%20in%20Pedaitric%20anesthesia/ClinicalPharmocokineticsOfSevoflurane.pdfhttp://www.kalbemed.com/Products/Drugs/Branded.aspxhttp://www.kalbemed.com/Products/Drugs/Branded/tabid/245/articleType/Archives/Default.aspxhttp://www.kalbemed.com/Products/Drugs/Branded/tabid/245/articleType/Search/Default.aspxhttp://www.kalbemed.com/Products/Drugs/Branded/tabid/245/ID/4554/Sevoflurane-Baxter.aspxhttp://www.kalbemed.com/Products/Drugs/Branded/tabid/245/articleType/AuthorView/authorID/12/UserAdmin.aspx

8/12/2019 Wita

4/86

Komposisi:Sevoflurane 1$$3.

Bentuk Sediaan:!airan inhalasi dalam botol aluminium #%$ m@.

Farmakologi:erupakan anestetik inhalasi berhalogen dengan onset dan pulih sadar yang cepat, bau tidak tajam, A!

#,13, metabolisme di hati %3, dan tidak stabil terhadap CO2absorbent.

ndikasi:'nduksi dan pemeliharaan anestesi umum pada de*asa dan anak>anak.

!osis:" 'nduksi anestesi? 'ndividual> +emeliharaan anestesi? $,%>-3 dengan atau tanpa :#;> (idak dianjurkan diberikan dengan // C 1 @ 4 menit selama lebih dari # A!>jam.

Kontraindikasi:ipersensitif terhadap anestetik berhalogen, pasien yang diketahui atau mempunyai kerentanan genetikterhadap hipertermia maligna.

#eringatan dan #er$atian:" Diberikan dengan vapori8er khusus sevoflurane.> Sevofluranedapat mempengaruhi pernapasan dan meningkatkan tekanan intrakranial.> (idak dianjurkan menggunakan CO2absorbent yang mengandung ;.> CO2absorbent harus sering diganti.> angguan fungsi hati atau ginjal berat.> ;perasi obstetri.> 'bu hamil.

E%ek Samping:ipotensi, depresi napas, batuk, laringospasme dan apnu pada induksi, mual, muntah, hipertermia maligna.

8/12/2019 Wita

5/86

"osted in! Anesthetics

Sevoflurane (Inhalation-Systemic)

VA CLASSIFICATIONPrimary:CN201

Commonly used brand name(s): Sevorane; Ultane.

Note:For a listing of dosage forms and brand names by country availability, see DosageFormssection(s).

Category:

Anesthetic (general)

Indications

Accepted

Anesthesia, generalSevoflurane is indicated for the induction and maintenance of generalanesthesia in adult and pediatric patients during inpatient or outpatient surgery. Often,sevoflurane is used with other medications to induce or supplement anesthesia{01}{65}.

UnacceptedSevoflurane does not have analgesic activity at subanesthetic concentrations and is notrecommended as an analgesic {02}.

Pharmacology/Pharmacokinetics

Note:Concentration-response relationships for inhalation anesthetics are described in termsof the minimum alveolar concentration (MAC), which is defined as the alveolar concentrationthat prevents movement in 50% of patients after surgical skin incision. The MAC decreaseswith pregnancy, hypothermia, hypotension, increasing age, and concurrent use of othercentral nervous system (CNS) depressants, including other inhalation anesthetics. AverageMAC values for sevoflurane (vaporized in oxygen) are 3.3%, 3%, 2.6%, 1.7%, and 1.4% for

neonates, and patients 1 to 6 months, 25 years, 60 years, and 80 years of age,respectively{01}. While MAC is commonly used to compare the concentration-response

relationships for inhalation anesthetics, the AD 95(the dose preventing 95% of patients frommoving in response to skin incision) is more clinically relevant in dosing patients withinhalation anesthetics, if the inhalation anesthetic is used alone {03}. Often, inhalationanesthetics are used in combination with other agents to supplement anesthesia.

Physicochemical characteristics:

http://www.kalbemed.com/Products/Drugs/Branded/tabid/245/articleType/CategoryView/categoryId/131/Anesthetics.aspxhttp://www.drugs.com/mmx/sevoflurane.html#citec00198701http://www.drugs.com/mmx/sevoflurane.html#citec00198701http://www.drugs.com/mmx/sevoflurane.html#citec00198701http://www.drugs.com/mmx/sevoflurane.html#citec00198765http://www.drugs.com/mmx/sevoflurane.html#citec00198702http://www.drugs.com/mmx/sevoflurane.html#citec00198701http://www.drugs.com/mmx/sevoflurane.html#citec00198701http://www.drugs.com/mmx/sevoflurane.html#citec00198703http://www.kalbemed.com/Products/Drugs/Branded/tabid/245/articleType/CategoryView/categoryId/131/Anesthetics.aspxhttp://www.drugs.com/mmx/sevoflurane.html#citec00198701http://www.drugs.com/mmx/sevoflurane.html#citec00198765http://www.drugs.com/mmx/sevoflurane.html#citec00198702http://www.drugs.com/mmx/sevoflurane.html#citec00198701http://www.drugs.com/mmx/sevoflurane.html#citec00198703

8/12/2019 Wita

6/86

Chemical group A halogenated hydrocarbon (methyl ethyl ether) anesthetic.Molecular weight 200.06 {04}

Other characteristics MAC in oxygen for adults 40 years of age: 2.1% {01}. Blood-to-gas partition coefficient (37 C [98.6 F]): 0.63 to 0.69 {01}. Brain-to-gas partition coefficient (37 C [98.6 F]): 1.15{01}. Oil-to-gas partition coefficient (37 C [98.6 F]): 47 to 54{01}.

Mechanism of action/Effect:

The precise mechanism by which inhalation anesthetics produce loss of perception ofsensations and unconsciousness is not known. Inhaled anesthetics act at many areas in theCNS. The Meyer-Overton theory suggests that the site of action of inhalation anestheticsmay be the lipid matrix of neuronal membranes or other lipophilic sites. Anesthetics may

cause changes in membrane thickness, which in turn affect the gating properties of ionchannels in neurons. Interference with the hydrophobic portion of neuronal ion channelmembrane proteins may be an important mechanism {05}{06}.

Other actions/effects:

Cardiovascular system effects:

Sevoflurane has several effects that serve to lower blood pressure. It depresses cardiacfunction, decreases cardiac contractility, and decreases peripheral vascular

resistance{01}

{07}

{08}

{66}

in a manner similar to that of isoflurane{66}

. These effects are dose-related; increasing the concentration of sevoflurane during maintenance of anesthesiaresults in a dose-dependent decrease in blood pressure {01}{07}. The effect of sevoflurane onthe coronary arteries and the potential for coronary steal has been investigated in dogs.Sevoflurane administration to chronically instrumented dogs resulted in a reduced ratio ofoccluded/normal and stenotic/normal coronary artery flows. However, the ratios returned tonormal when the arterial blood pressure and heart rate were restored to conscious values {67}.

Sevoflurane has little effect on heart rate or rhythm. At clinically useful doses, sevofluranedoes not increase heart rate or myocardial oxygen consumption {07}{10}{11}{63}. At higherconcentrations, sevoflurane may increase heart rate{66}.A study on the effects of sevofluraneon the arrhythmic response to epinephrine suggests that sevoflurane does not greatlysensitize the myocardium to the arrhythmogenic effect of catecholamines {09}.

CNS:

Electroencephalogram (EEG): Sevoflurane causes a dose-dependent decrease in EEGactivity. In dogs and rabbits, EEG burst suppression occurs at doses of 1 MAC orhigher {12}{13}{63}. Although sevoflurane is not believed to be epileptogenic, case reportsdescribe clonic and tonic seizure-like movements and clinically silent electrical seizures

http://www.drugs.com/mmx/sevoflurane.html#citec00198704http://www.drugs.com/mmx/sevoflurane.html#citec00198701http://www.drugs.com/mmx/sevoflurane.html#citec00198701http://www.drugs.com/mmx/sevoflurane.html#citec00198701http://www.drugs.com/mmx/sevoflurane.html#citec00198701http://www.drugs.com/mmx/sevoflurane.html#citec00198701http://www.drugs.com/mmx/sevoflurane.html#citec00198701http://www.drugs.com/mmx/sevoflurane.html#citec00198701http://www.drugs.com/mmx/sevoflurane.html#citec00198705http://www.drugs.com/mmx/sevoflurane.html#citec00198705http://www.drugs.com/mmx/sevoflurane.html#citec00198706http://www.drugs.com/mmx/sevoflurane.html#citec00198701http://www.drugs.com/mmx/sevoflurane.html#citec00198707http://www.drugs.com/mmx/sevoflurane.html#citec00198707http://www.drugs.com/mmx/sevoflurane.html#citec00198708http://www.drugs.com/mmx/sevoflurane.html#citec00198766http://www.drugs.com/mmx/sevoflurane.html#citec00198766http://www.drugs.com/mmx/sevoflurane.html#citec00198701http://www.drugs.com/mmx/sevoflurane.html#citec00198707http://www.drugs.com/mmx/sevoflurane.html#citec00198767http://www.drugs.com/mmx/sevoflurane.html#citec00198707http://www.drugs.com/mmx/sevoflurane.html#citec00198710http://www.drugs.com/mmx/sevoflurane.html#citec00198710http://www.drugs.com/mmx/sevoflurane.html#citec00198710http://www.drugs.com/mmx/sevoflurane.html#citec00198711http://www.drugs.com/mmx/sevoflurane.html#citec00198763http://www.drugs.com/mmx/sevoflurane.html#citec00198766http://www.drugs.com/mmx/sevoflurane.html#citec00198766http://www.drugs.com/mmx/sevoflurane.html#citec00198766http://www.drugs.com/mmx/sevoflurane.html#citec00198709http://www.drugs.com/mmx/sevoflurane.html#citec00198712http://www.drugs.com/mmx/sevoflurane.html#citec00198713http://www.drugs.com/mmx/sevoflurane.html#citec00198763http://www.drugs.com/mmx/sevoflurane.html#citec00198763http://www.drugs.com/mmx/sevoflurane.html#citec00198704http://www.drugs.com/mmx/sevoflurane.html#citec00198701http://www.drugs.com/mmx/sevoflurane.html#citec00198701http://www.drugs.com/mmx/sevoflurane.html#citec00198701http://www.drugs.com/mmx/sevoflurane.html#citec00198701http://www.drugs.com/mmx/sevoflurane.html#citec00198705http://www.drugs.com/mmx/sevoflurane.html#citec00198706http://www.drugs.com/mmx/sevoflurane.html#citec00198701http://www.drugs.com/mmx/sevoflurane.html#citec00198707http://www.drugs.com/mmx/sevoflurane.html#citec00198708http://www.drugs.com/mmx/sevoflurane.html#citec00198766http://www.drugs.com/mmx/sevoflurane.html#citec00198766http://www.drugs.com/mmx/sevoflurane.html#citec00198701http://www.drugs.com/mmx/sevoflurane.html#citec00198707http://www.drugs.com/mmx/sevoflurane.html#citec00198767http://www.drugs.com/mmx/sevoflurane.html#citec00198707http://www.drugs.com/mmx/sevoflurane.html#citec00198710http://www.drugs.com/mmx/sevoflurane.html#citec00198711http://www.drugs.com/mmx/sevoflurane.html#citec00198763http://www.drugs.com/mmx/sevoflurane.html#citec00198766http://www.drugs.com/mmx/sevoflurane.html#citec00198709http://www.drugs.com/mmx/sevoflurane.html#citec00198712http://www.drugs.com/mmx/sevoflurane.html#citec00198713http://www.drugs.com/mmx/sevoflurane.html#citec00198763

8/12/2019 Wita

7/86

during induction of anesthesia{14}{15}{73}.

Effect on intracranial pressure: Sevoflurane did not impair cerebral autoregulation of bloodflow when studied in patients with ischemic cerebrovascular disease {16}. However,sevoflurane has the potential to increase intracranial pressure{12}.

Neuromuscular effects:

Sevoflurane impairs neuromuscular conduction and decreases muscle contractility.Sevoflurane may produce sufficient muscle relaxation to allow some types of surgery to beperformed without a neuromuscular blocker {17}{63}.

Respiratory system effects:

Respiration: Sevoflurane depresses ventilation in a dose-dependent manner, with apnea

occurring between 1.5 and 2 MAC. Surgical stimulation changes the threshold at whichapnea occurs {18}. Sevoflurane increases carbon dioxide tension and decreases ventilatoryresponse to increased carbon dioxide concentrations {19}{63}.

Effects on the airway: Sevoflurane results in a low incidence of respiratory irritation asevidenced by a low incidence of breath-holding, coughing, increased salivation, andlaryngospasm during induction{01}{20}{21}{22}.

Absorption:

Sevoflurane is rapidly absorbed into the circulation via the lungs. Its solubility in the blood is

low; for a given concentration of sevoflurane in the gas phase, only a small amount dissolvedin the blood is necessary to achieve equilibrium between the alveolar partial pressure andthe arterial partial pressure {01}{23}.

Biotransformation:

Approximately 5% of the sevoflurane dose is metabolized, primarily by cytochrome P4502E1, with release of inorganic fluoride and carbon dioxide {24}{25}{26}. The plasma inorganicfluoride concentration is increased to > 95 mcg per dL (mcg/dL) (50 micromoles per L[micromoles/L]) following surgery of long duration {27}{28}.

Time to peak concentration:

The alveolar concentration of sevoflurane increases rapidly toward the inspiredconcentration. The ratio of alveolar concentration to inspired concentration increases morerapidly with nitrous oxide and desflurane than with sevoflurane but more rapidly withsevoflurane than with isoflurane and halothane {23}.

Time to peak effect:

Onset of anesthesiaSevoflurane has a favorable rate of increase of the ratio of alveolarconcentration to inspired concentration. When sevoflurane is used alone and is administered

http://www.drugs.com/mmx/sevoflurane.html#citec00198714http://www.drugs.com/mmx/sevoflurane.html#citec00198714http://www.drugs.com/mmx/sevoflurane.html#citec00198714http://www.drugs.com/mmx/sevoflurane.html#citec00198715http://www.drugs.com/mmx/sevoflurane.html#citec00198773http://www.drugs.com/mmx/sevoflurane.html#citec00198716http://www.drugs.com/mmx/sevoflurane.html#citec00198712http://www.drugs.com/mmx/sevoflurane.html#citec00198712http://www.drugs.com/mmx/sevoflurane.html#citec00198712http://www.drugs.com/mmx/sevoflurane.html#citec00198717http://www.drugs.com/mmx/sevoflurane.html#citec00198763http://www.drugs.com/mmx/sevoflurane.html#citec00198763http://www.drugs.com/mmx/sevoflurane.html#citec00198763http://www.drugs.com/mmx/sevoflurane.html#citec00198718http://www.drugs.com/mmx/sevoflurane.html#citec00198719http://www.drugs.com/mmx/sevoflurane.html#citec00198763http://www.drugs.com/mmx/sevoflurane.html#citec00198763http://www.drugs.com/mmx/sevoflurane.html#citec00198701http://www.drugs.com/mmx/sevoflurane.html#citec00198701http://www.drugs.com/mmx/sevoflurane.html#citec00198720http://www.drugs.com/mmx/sevoflurane.html#citec00198721http://www.drugs.com/mmx/sevoflurane.html#citec00198721http://www.drugs.com/mmx/sevoflurane.html#citec00198722http://www.drugs.com/mmx/sevoflurane.html#citec00198701http://www.drugs.com/mmx/sevoflurane.html#citec00198723http://www.drugs.com/mmx/sevoflurane.html#citec00198723http://www.drugs.com/mmx/sevoflurane.html#citec00198723http://www.drugs.com/mmx/sevoflurane.html#citec00198724http://www.drugs.com/mmx/sevoflurane.html#citec00198725http://www.drugs.com/mmx/sevoflurane.html#citec00198725http://www.drugs.com/mmx/sevoflurane.html#citec00198726http://www.drugs.com/mmx/sevoflurane.html#citec00198727http://www.drugs.com/mmx/sevoflurane.html#citec00198728http://www.drugs.com/mmx/sevoflurane.html#citec00198728http://www.drugs.com/mmx/sevoflurane.html#citec00198723http://www.drugs.com/mmx/sevoflurane.html#citec00198714http://www.drugs.com/mmx/sevoflurane.html#citec00198715http://www.drugs.com/mmx/sevoflurane.html#citec00198773http://www.drugs.com/mmx/sevoflurane.html#citec00198716http://www.drugs.com/mmx/sevoflurane.html#citec00198712http://www.drugs.com/mmx/sevoflurane.html#citec00198717http://www.drugs.com/mmx/sevoflurane.html#citec00198763http://www.drugs.com/mmx/sevoflurane.html#citec00198718http://www.drugs.com/mmx/sevoflurane.html#citec00198719http://www.drugs.com/mmx/sevoflurane.html#citec00198763http://www.drugs.com/mmx/sevoflurane.html#citec00198701http://www.drugs.com/mmx/sevoflurane.html#citec00198720http://www.drugs.com/mmx/sevoflurane.html#citec00198721http://www.drugs.com/mmx/sevoflurane.html#citec00198722http://www.drugs.com/mmx/sevoflurane.html#citec00198701http://www.drugs.com/mmx/sevoflurane.html#citec00198723http://www.drugs.com/mmx/sevoflurane.html#citec00198724http://www.drugs.com/mmx/sevoflurane.html#citec00198725http://www.drugs.com/mmx/sevoflurane.html#citec00198726http://www.drugs.com/mmx/sevoflurane.html#citec00198727http://www.drugs.com/mmx/sevoflurane.html#citec00198728http://www.drugs.com/mmx/sevoflurane.html#citec00198723

8/12/2019 Wita

8/86

by conventional technique, induction is accomplished in 2 minutes. This time can be reducedby the addition of nitrous oxide or the use of a vital capacity breath technique. With the useof a vital capacity breath technique, induction can be accomplished in about 1 minute{29}{30}.

Duration of action:

Time to recoveryRecovery after discontinuation is rapid but is subject to interpatientvariability. Recovery time is affected by the administered concentration and other CNSdepressants used concurrently. Emergence from sevoflurane is more rapid than emergencefrom isoflurane, but less rapid than from desflurane {68}. Spontaneous eye opening, responseto simple commands, extubation, and orientation are more quickly achieved with sevofluranethan with isoflurane{68}. However, time to later recovery events (walking, tolerating oral fluids,voiding, and home readiness) does not differ between isoflurane and sevoflurane ordesflurane and sevoflurane{20}{31}{68}.

Elimination: Rapidly eliminated via exhalation. The metabolite is conjugated with glucuronic acid andeliminated via the urine. Up to 3.5% of the sevoflurane dose appears in the urine asinorganic fluoride. Up to 50% of fluoride is taken up into the bone. As compared to the half-

life in healthy individuals, the fluoride ion half-life is prolonged in patients with renal functionimpairment (33 hours versus 21 hours) and slightly prolonged in patients with hepaticfunction impairment{01}.

Precautions to Consider

Cross-sensitivity and/or related problems

Patients sensitive to other halogenated ether hydrocarbons may be sensitive to sevofluranealso{01}.

Carcinogenicity

Studies have not been done {01}.

Mutagenicity

No mutagenic effect was observed in the Ames test. No chromosomal aberrations wereinduced in cultured mammalian cells. Problems in humans have not been documented {01}.

Pregnancy/ReproductionFertilityReproduction studies performed in rats and rabbits at doses of up to 1 minimum alveolarconcentration (MAC) revealed no evidence of impaired fertility.

PregnancySevoflurane crosses the placenta. Adequate and well-controlled studies have not been donein humans{01}.

Studies in pregnant rabbits and rats at doses of 0.3 MAC, the highest nontoxic dose,revealed no fetal damage{01}.

FDA Pregnancy Category B{01}.

http://www.drugs.com/mmx/sevoflurane.html#citec00198729http://www.drugs.com/mmx/sevoflurane.html#citec00198729http://www.drugs.com/mmx/sevoflurane.html#citec00198729http://www.drugs.com/mmx/sevoflurane.html#citec00198730http://www.drugs.com/mmx/sevoflurane.html#citec00198768http://www.drugs.com/mmx/sevoflurane.html#citec00198768http://www.drugs.com/mmx/sevoflurane.html#citec00198768http://www.drugs.com/mmx/sevoflurane.html#citec00198720http://www.drugs.com/mmx/sevoflurane.html#citec00198720http://www.drugs.com/mmx/sevoflurane.html#citec00198720http://www.drugs.com/mmx/sevoflurane.html#citec00198731http://www.drugs.com/mmx/sevoflurane.html#citec00198768http://www.drugs.com/mmx/sevoflurane.html#citec00198701http://www.drugs.com/mmx/sevoflurane.html#citec00198701http://www.drugs.com/mmx/sevoflurane.html#citec00198701http://www.drugs.com/mmx/sevoflurane.html#citec00198701http://www.drugs.com/mmx/sevoflurane.html#citec00198701http://www.drugs.com/mmx/sevoflurane.html#citec00198701http://www.drugs.com/mmx/sevoflurane.html#citec00198701http://www.drugs.com/mmx/sevoflurane.html#citec00198701http://www.drugs.com/mmx/sevoflurane.html#citec00198701http://www.drugs.com/mmx/sevoflurane.html#citec00198701http://www.drugs.com/mmx/sevoflurane.html#citec00198701http://www.drugs.com/mmx/sevoflurane.html#citec00198701http://www.drugs.com/mmx/sevoflurane.html#citec00198701http://www.drugs.com/mmx/sevoflurane.html#citec00198701http://www.drugs.com/mmx/sevoflurane.html#citec00198729http://www.drugs.com/mmx/sevoflurane.html#citec00198730http://www.drugs.com/mmx/sevoflurane.html#citec00198768http://www.drugs.com/mmx/sevoflurane.html#citec00198768http://www.drugs.com/mmx/sevoflurane.html#citec00198720http://www.drugs.com/mmx/sevoflurane.html#citec00198731http://www.drugs.com/mmx/sevoflurane.html#citec00198768http://www.drugs.com/mmx/sevoflurane.html#citec00198701http://www.drugs.com/mmx/sevoflurane.html#citec00198701http://www.drugs.com/mmx/sevoflurane.html#citec00198701http://www.drugs.com/mmx/sevoflurane.html#citec00198701http://www.drugs.com/mmx/sevoflurane.html#citec00198701http://www.drugs.com/mmx/sevoflurane.html#citec00198701http://www.drugs.com/mmx/sevoflurane.html#citec00198701

8/12/2019 Wita

9/86

Labor and delivery

The safety of sevoflurane in labor and vaginal delivery has not been established.Sevoflurane was used as part of general anesthesia in 61 women undergoing elective

cesarean section{01}{32}

{69}

{70}

{71}

. There was no harmful effect in any mother or neonate.There was no difference between sevoflurane and isoflurane in recovery characteristics,Apgar score, or Neurological and Adaptive Capacity Score{32}. In one study two of sixteenpatients had poor spontaneous uterine contractions after receiving sevoflurane {69}.

Breast-feeding

It is not known if sevoflurane is distributed into breast milk. However, because of rapidwashout, sevoflurane concentrations in milk are predicted to be below those found with otheranesthetics. The concentrations of sevoflurane in milk are thought to be of no clinicalimportance 24 hours after anesthesia {01}.

Pediatrics

Due to its lack of pungency, sevoflurane is widely used in Japan for induction of anesthesiain pediatric patients. As compared to halothane, sevoflurane for induction is associated witha higher incidence of excitation {33}. In one study, this led to a longer time to intubation withsevoflurane {33}. The longer time to intubation was not seen in two other studies, perhaps dueto differences in the speed with which maximum concentrations of anesthetic werereached {34}{35}.

Pediatric patients require a higher concentration of sevoflurane for maintenance of generalanesthesia than that required by adults {01}.

Sevoflurane is associated with a higher incidence of emergence excitation in children than is

halothane, perhaps due to earlier emergence and the resultant earlier experience of pain inchildren receiving sevoflurane {33}{36}{63}.

Geriatrics

MAC decreases with increasing age. The average concentration of sevoflurane to achieveMAC in a patient 80 years of age is approximately 50% of that required in a patient 20 yearsof age{01}{03}.

Older adults may be slower than younger adults in achieving full cognitive recovery fromgeneral anesthesia with sevoflurane{78}.

Drug interactions and/or related problemsThe following drug interactions and/or related problems have been selected on the basis oftheir potential clinical significance (possible mechanism in parentheses where appropriate)not necessarily inclusive (= major clinical significance):

Note:Combinations containing any of the following medications, depending on the amountpresent, may also interact with this medication.

http://www.drugs.com/mmx/sevoflurane.html#citec00198701http://www.drugs.com/mmx/sevoflurane.html#citec00198732http://www.drugs.com/mmx/sevoflurane.html#citec00198769http://www.drugs.com/mmx/sevoflurane.html#citec00198770http://www.drugs.com/mmx/sevoflurane.html#citec00198770http://www.drugs.com/mmx/sevoflurane.html#citec00198771http://www.drugs.com/mmx/sevoflurane.html#citec00198732http://www.drugs.com/mmx/sevoflurane.html#citec00198732http://www.drugs.com/mmx/sevoflurane.html#citec00198769http://www.drugs.com/mmx/sevoflurane.html#citec00198701http://www.drugs.com/mmx/sevoflurane.html#citec00198733http://www.drugs.com/mmx/sevoflurane.html#citec00198733http://www.drugs.com/mmx/sevoflurane.html#citec00198734http://www.drugs.com/mmx/sevoflurane.html#citec00198735http://www.drugs.com/mmx/sevoflurane.html#citec00198735http://www.drugs.com/mmx/sevoflurane.html#citec00198735http://www.drugs.com/mmx/sevoflurane.html#citec00198701http://www.drugs.com/mmx/sevoflurane.html#citec00198733http://www.drugs.com/mmx/sevoflurane.html#citec00198736http://www.drugs.com/mmx/sevoflurane.html#citec00198736http://www.drugs.com/mmx/sevoflurane.html#citec00198736http://www.drugs.com/mmx/sevoflurane.html#citec00198763http://www.drugs.com/mmx/sevoflurane.html#citec00198701http://www.drugs.com/mmx/sevoflurane.html#citec00198703http://www.drugs.com/mmx/sevoflurane.html#citec00198778http://www.drugs.com/mmx/sevoflurane.html#citec00198778http://www.drugs.com/mmx/sevoflurane.html#citec00198778http://www.drugs.com/mmx/sevoflurane.html#citec00198701http://www.drugs.com/mmx/sevoflurane.html#citec00198732http://www.drugs.com/mmx/sevoflurane.html#citec00198769http://www.drugs.com/mmx/sevoflurane.html#citec00198770http://www.drugs.com/mmx/sevoflurane.html#citec00198771http://www.drugs.com/mmx/sevoflurane.html#citec00198732http://www.drugs.com/mmx/sevoflurane.html#citec00198769http://www.drugs.com/mmx/sevoflurane.html#citec00198701http://www.drugs.com/mmx/sevoflurane.html#citec00198733http://www.drugs.com/mmx/sevoflurane.html#citec00198733http://www.drugs.com/mmx/sevoflurane.html#citec00198734http://www.drugs.com/mmx/sevoflurane.html#citec00198735http://www.drugs.com/mmx/sevoflurane.html#citec00198701http://www.drugs.com/mmx/sevoflurane.html#citec00198733http://www.drugs.com/mmx/sevoflurane.html#citec00198736http://www.drugs.com/mmx/sevoflurane.html#citec00198763http://www.drugs.com/mmx/sevoflurane.html#citec00198701http://www.drugs.com/mmx/sevoflurane.html#citec00198703http://www.drugs.com/mmx/sevoflurane.html#citec00198778

8/12/2019 Wita

10/86

Many of the following interactions have not been reported with sevoflurane. However,because they have been reported with other halogenated hydrocarbon anesthetics, thepossibility of a significant interaction with sevoflurane must be considered.

Alcohol, chronic use (anesthetic requirement may be increased; induction of cytochromeP450 2E1 hepatic enzymes increases the extent of metabolism of sevoflurane, increasing

the production of inorganic fluoride{25}

)

Aminoglycosides, systemic orAnesthetics, parenteral-local orBacitracin orCapreomycin orCitrate-anticoagulated blood, massive transfusions of orClindamycin orColistimethate sodium orColistin orLidocaine, systemic orLincomycin, systemic or

Neuromuscular blocking agents orPolymyxins, systemic orProcaine, systemic orTetracyclines orTrimethaphan (large doses) (neuromuscular blocking activities of these medications maybe additive to that of sevoflurane, with the degree of potentiation increasing as theconcentration of sevoflurane is increased {37})

Amiodarone (concurrent use with inhalation anesthetics may potentiate hypotension andincrease the risk of atropine-resistant bradycardia {50}{82})

Antimyasthenics (antimyasthenics may decrease the neuromuscular blocking activity ofhalogenated hydrocarbon anesthetics; also, the neuromuscular blocking activity of theanesthetic may interfere with the efficacy of antimyasthenics; neuromuscular blockade withvecuronium during sevoflurane anesthesia may be more difficult to reverse with neostigminethan when similar blockade is produced during isoflurane anesthesia {38})

Beta-adrenergic blocking agents, including ophthalmics (severe hypotension may resultbecause beta-blockade reduces the ability of the heart to respond to beta-adrenergicallymediated sympathetic reflex stimuli{60})

Catecholamines, such as dopamine, epinephrine, or norepinephrine (sevoflurane maycause some sensitization of the myocardium to the effects of catecholamines, increasing therisk of arrhythmias; this is similar to isoflurane's effect on the myocardium; sevofluranesensitizes the myocardium much less than does halothane {09}{73})

CNS depressionproducing medications, other, including those commonly used forpreanesthetic medications, or induction or supplementation of anesthesia (see AppendixII) (may cause increased CNS depression, respiratory depression, and/or hypotension,

http://www.drugs.com/mmx/sevoflurane.html#citec00198725http://www.drugs.com/mmx/sevoflurane.html#citec00198737http://www.drugs.com/mmx/sevoflurane.html#citec00198750http://www.drugs.com/mmx/sevoflurane.html#citec00198782http://www.drugs.com/mmx/sevoflurane.html#citec00198782http://www.drugs.com/mmx/sevoflurane.html#citec00198738http://www.drugs.com/mmx/sevoflurane.html#citec00198760http://www.drugs.com/mmx/sevoflurane.html#citec00198760http://www.drugs.com/mmx/sevoflurane.html#citec00198709http://www.drugs.com/mmx/sevoflurane.html#citec00198773http://www.drugs.com/mmx/sevoflurane.html#citec00198773http://www.drugs.com/mmx/drugeff.html#00204http://www.drugs.com/mmx/drugeff.html#00204http://www.drugs.com/mmx/sevoflurane.html#citec00198725http://www.drugs.com/mmx/sevoflurane.html#citec00198737http://www.drugs.com/mmx/sevoflurane.html#citec00198750http://www.drugs.com/mmx/sevoflurane.html#citec00198782http://www.drugs.com/mmx/sevoflurane.html#citec00198738http://www.drugs.com/mmx/sevoflurane.html#citec00198760http://www.drugs.com/mmx/sevoflurane.html#citec00198709http://www.drugs.com/mmx/sevoflurane.html#citec00198773http://www.drugs.com/mmx/drugeff.html#00204http://www.drugs.com/mmx/drugeff.html#00204

8/12/2019 Wita

11/86

decrease the anesthetic requirement, and prolong the recovery from anesthesia {01})

Hypotension-producing medications (see Appendix II) (hypotensive effects may bepotentiated when these medications are used concurrently with an inhalation anesthetic)

Isoniazid and other cytochrome P450 2E1 hepatic enzyme inducers (enzyme inductionincreases the extent of metabolism of sevoflurane, increasing the production of inorganicfluoride{41}{42}; increased plasma fluoride concentrations have been associated with renalfunction impairment with other volatile inhalation anesthetics)

Laboratory value alterationsThe following have been selected on the basis of their potential clinical significance (possibleeffect in parentheses where appropriate)not necessarily inclusive (= major clinicalsignificance):

With physiology/laboratory test valuesAlanine aminotransferase (ALT [SGPT]), serum andAspartate aminotransferase (AST [SGOT]), serum andBilirubin, serum, indirect andLactate dehydrogenase, serum (values may be transiently increased; the increases aredose-related {27}{43}{44})

Blood urea nitrogen (BUN) andCreatinine, serum andFluoride, serum (concentration may be increased {01}{27}{28}{43}{45}{46})

Glucose, serum (concentration may be increased{01})

Leukocytes (counts may be increased {01})

Medical considerations/ContraindicationsThe medical considerations/contraindications included have been selected on the basis oftheir potential clinical significance (reasons given in parentheses where appropriate) notnecessarily inclusive (= major clinical significance).

Except under special circumstances, this medication should not be used when thefollowing medical problems exist:Malignant hyperthermia, history of (possible increased risk of malignant hyperthermiawith sevoflurane {01}; malignant hyperthermia has been associated with the use ofsevoflurane in both children and adults {47}{48}{49})

Sensitivity to halogenated ether anesthetic agents (possible increased risk of sensitivityto sevoflurane {01}; although not yet reported with sevoflurane, cases of immune-mediated

http://www.drugs.com/mmx/sevoflurane.html#citec00198701http://www.drugs.com/mmx/drugeff.html#00214http://www.drugs.com/mmx/sevoflurane.html#citec00198741http://www.drugs.com/mmx/sevoflurane.html#citec00198741http://www.drugs.com/mmx/sevoflurane.html#citec00198742http://www.drugs.com/mmx/sevoflurane.html#citec00198727http://www.drugs.com/mmx/sevoflurane.html#citec00198743http://www.drugs.com/mmx/sevoflurane.html#citec00198744http://www.drugs.com/mmx/sevoflurane.html#citec00198744http://www.drugs.com/mmx/sevoflurane.html#citec00198701http://www.drugs.com/mmx/sevoflurane.html#citec00198727http://www.drugs.com/mmx/sevoflurane.html#citec00198727http://www.drugs.com/mmx/sevoflurane.html#citec00198727http://www.drugs.com/mmx/sevoflurane.html#citec00198728http://www.drugs.com/mmx/sevoflurane.html#citec00198743http://www.drugs.com/mmx/sevoflurane.html#citec00198745http://www.drugs.com/mmx/sevoflurane.html#citec00198745http://www.drugs.com/mmx/sevoflurane.html#citec00198745http://www.drugs.com/mmx/sevoflurane.html#citec00198746http://www.drugs.com/mmx/sevoflurane.html#citec00198701http://www.drugs.com/mmx/sevoflurane.html#citec00198701http://www.drugs.com/mmx/sevoflurane.html#citec00198701http://www.drugs.com/mmx/sevoflurane.html#citec00198701http://www.drugs.com/mmx/sevoflurane.html#citec00198747http://www.drugs.com/mmx/sevoflurane.html#citec00198748http://www.drugs.com/mmx/sevoflurane.html#citec00198748http://www.drugs.com/mmx/sevoflurane.html#citec00198749http://www.drugs.com/mmx/sevoflurane.html#citec00198701http://www.drugs.com/mmx/sevoflurane.html#citec00198701http://www.drugs.com/mmx/drugeff.html#00214http://www.drugs.com/mmx/sevoflurane.html#citec00198741http://www.drugs.com/mmx/sevoflurane.html#citec00198742http://www.drugs.com/mmx/sevoflurane.html#citec00198727http://www.drugs.com/mmx/sevoflurane.html#citec00198743http://www.drugs.com/mmx/sevoflurane.html#citec00198744http://www.drugs.com/mmx/sevoflurane.html#citec00198701http://www.drugs.com/mmx/sevoflurane.html#citec00198727http://www.drugs.com/mmx/sevoflurane.html#citec00198728http://www.drugs.com/mmx/sevoflurane.html#citec00198743http://www.drugs.com/mmx/sevoflurane.html#citec00198745http://www.drugs.com/mmx/sevoflurane.html#citec00198746http://www.drugs.com/mmx/sevoflurane.html#citec00198701http://www.drugs.com/mmx/sevoflurane.html#citec00198701http://www.drugs.com/mmx/sevoflurane.html#citec00198701http://www.drugs.com/mmx/sevoflurane.html#citec00198747http://www.drugs.com/mmx/sevoflurane.html#citec00198748http://www.drugs.com/mmx/sevoflurane.html#citec00198749http://www.drugs.com/mmx/sevoflurane.html#citec00198701

8/12/2019 Wita

12/86

hepatitis have been reported with similar inhalation anesthetics {79})

Risk-benefit should be considered when the following medical problems existFamilial periodic paralysis orMuscular dystrophy or

Myasthenia gravis orMyasthenic syndrome orOther neuromuscular disease leading to muscle weakness (the neuromuscular blockingactivity of sevoflurane may increase the risk of severe muscle weakness in patients withthese conditions; although use of an inhalation anesthetic with substantial neuromuscularblocking activity may be safer than [and eliminate the need for] a neuromuscular blockingagent in these patients, caution is recommended {61})

Head injury orIncreased intracranial pressure orIntracranial lesions, space-occupying (sevoflurane may increase intracranial pressure tothe same extent that isoflurane may {01}{12}; in a study on ten patients with ischemic

cerebrovascular disease, carbon dioxide response and cerebral autoregulation weremaintained under 0.88 MAC anesthesia{16})

Hepatic function impairment (in patients with mild to moderate hepatic function impairment,administration of sevoflurane resulted in prolonged terminal disposition of fluoride, asevidenced by longer inorganic fluoride half-life than that observed in patients with normalhepatic function; there is no published clinical experience with use of sevoflurane in patientswith severe hepatic function impairment{01})

Pulsed dye laser therapy for portwine stain (sevoflurane anesthesia is associated with

portwine stain fading and subsequent early termination of pulsed dye laser treatment,resulting in inadequate treatment of the stain; the incidence of portwine stain fade withsevoflurane is significantly higher than the incidence of fade with halothane, enflurane, orisoflurane{51})

Renal function impairment (extended anesthesia with sevoflurane is associated withhyperfluorinemia; with methoxyflurane, hyperfluorinemia in excess of 95 mcg per dL [mcg/dL][50 micromoles per L (micromoles/L)] has been associated with renal function impairment; atendency toward decreased urine concentrating ability and increased urinary excretion of N-acetyl-beta-glucosaminidase [NAG] has been associated with the use of sevoflurane{40}{72};serum fluoride concentrations in excess of 95 mcg/dL [50 micromoles/L] achieved with theuse of sevoflurane have not been associated with frank renal failure {27}{28}{33}{45}{52}{53}{74};

reaction of sevoflurane with carbon dioxide [CO 2] absorbents is associated with theformation of compound A, a nephrotoxin in rats {54}{64}; the toxicity of compound A has notbeen established in humans {55}; although causality could not be established, transientnonoliguric renal failure was reported after a 25-year-old burn patient with previously normalrenal function received sevoflurane three times within 2 weeks for debridement of burnedtissue{39}; caution is recommended in patients with renal function impairment because oflimited studies done in this patient population {80}{81})

http://www.drugs.com/mmx/sevoflurane.html#citec00198779http://www.drugs.com/mmx/sevoflurane.html#citec00198761http://www.drugs.com/mmx/sevoflurane.html#citec00198701http://www.drugs.com/mmx/sevoflurane.html#citec00198712http://www.drugs.com/mmx/sevoflurane.html#citec00198716http://www.drugs.com/mmx/sevoflurane.html#citec00198716http://www.drugs.com/mmx/sevoflurane.html#citec00198701http://www.drugs.com/mmx/sevoflurane.html#citec00198701http://www.drugs.com/mmx/sevoflurane.html#citec00198751http://www.drugs.com/mmx/sevoflurane.html#citec00198751http://www.drugs.com/mmx/sevoflurane.html#citec00198740http://www.drugs.com/mmx/sevoflurane.html#citec00198740http://www.drugs.com/mmx/sevoflurane.html#citec00198740http://www.drugs.com/mmx/sevoflurane.html#citec00198772http://www.drugs.com/mmx/sevoflurane.html#citec00198727http://www.drugs.com/mmx/sevoflurane.html#citec00198728http://www.drugs.com/mmx/sevoflurane.html#citec00198728http://www.drugs.com/mmx/sevoflurane.html#citec00198733http://www.drugs.com/mmx/sevoflurane.html#citec00198745http://www.drugs.com/mmx/sevoflurane.html#citec00198752http://www.drugs.com/mmx/sevoflurane.html#citec00198752http://www.drugs.com/mmx/sevoflurane.html#citec00198752http://www.drugs.com/mmx/sevoflurane.html#citec00198753http://www.drugs.com/mmx/sevoflurane.html#citec00198774http://www.drugs.com/mmx/sevoflurane.html#citec00198754http://www.drugs.com/mmx/sevoflurane.html#citec00198764http://www.drugs.com/mmx/sevoflurane.html#citec00198755http://www.drugs.com/mmx/sevoflurane.html#citec00198739http://www.drugs.com/mmx/sevoflurane.html#citec00198739http://www.drugs.com/mmx/sevoflurane.html#citec00198780http://www.drugs.com/mmx/sevoflurane.html#citec00198781http://www.drugs.com/mmx/sevoflurane.html#citec00198781http://www.drugs.com/mmx/sevoflurane.html#citec00198779http://www.drugs.com/mmx/sevoflurane.html#citec00198761http://www.drugs.com/mmx/sevoflurane.html#citec00198701http://www.drugs.com/mmx/sevoflurane.html#citec00198712http://www.drugs.com/mmx/sevoflurane.html#citec00198716http://www.drugs.com/mmx/sevoflurane.html#citec00198701http://www.drugs.com/mmx/sevoflurane.html#citec00198751http://www.drugs.com/mmx/sevoflurane.html#citec00198740http://www.drugs.com/mmx/sevoflurane.html#citec00198772http://www.drugs.com/mmx/sevoflurane.html#citec00198727http://www.drugs.com/mmx/sevoflurane.html#citec00198728http://www.drugs.com/mmx/sevoflurane.html#citec00198733http://www.drugs.com/mmx/sevoflurane.html#citec00198745http://www.drugs.com/mmx/sevoflurane.html#citec00198752http://www.drugs.com/mmx/sevoflurane.html#citec00198753http://www.drugs.com/mmx/sevoflurane.html#citec00198774http://www.drugs.com/mmx/sevoflurane.html#citec00198754http://www.drugs.com/mmx/sevoflurane.html#citec00198764http://www.drugs.com/mmx/sevoflurane.html#citec00198755http://www.drugs.com/mmx/sevoflurane.html#citec00198739http://www.drugs.com/mmx/sevoflurane.html#citec00198780http://www.drugs.com/mmx/sevoflurane.html#citec00198781

8/12/2019 Wita

13/86

Patient monitoringThe following may be especially important in patient monitoring (other tests may bewarranted in some patients, depending on condition; = major clinical significance):

Note:Various organizations, including medical specialty societies, and institutions haveestablished standards for the preprocedural, intraprocedural, and postprocedural care,evaluation, and monitoring of patients receiving various forms of anesthesia. The followingrecommendations represent the minimum standards established by the American Society ofAnesthesiologists for monitoring the status of patients receiving general anesthesia.Individual patients may require additional monitoring. {62}

Blood pressure andBody temperature andCardiac/pulse rate andCardiac rhythm andPulse oximetry andRespiratory and ventilatory status (continuous monitoring is advisable during anesthetic

administration; respiratory depression and excessive decreases in blood pressure may berelated to the depth of anesthesia and may be corrected by decreasing the inspiredconcentration of sevoflurane {62})

Side/Adverse EffectsThe following side/adverse effects have been selected on the basis of their potential clinicalsignificance (possible signs and symptoms in parentheses where appropriate)notnecessarily inclusive:

Those indicating need for medical attentionIncidence more frequent (greater than 3%)During induction by mask (adult patients)Airway obstruction{01}

bradycardia{01}

breath-holding{01}

cough, increased{01}

hypotension{01}

laryngospasm{01}

During induction by mask (pediatric patients)Breath-holding{01}

cough, increased{01}

http://www.drugs.com/mmx/sevoflurane.html#citec00198762http://www.drugs.com/mmx/sevoflurane.html#citec00198762http://www.drugs.com/mmx/sevoflurane.html#citec00198701http://www.drugs.com/mmx/sevoflurane.html#citec00198701http://www.drugs.com/mmx/sevoflurane.html#citec00198701http://www.drugs.com/mmx/sevoflurane.html#citec00198701http://www.drugs.com/mmx/sevoflurane.html#citec00198701http://www.drugs.com/mmx/sevoflurane.html#citec00198701http://www.drugs.com/mmx/sevoflurane.html#citec00198701http://www.drugs.com/mmx/sevoflurane.html#citec00198701http://www.drugs.com/mmx/sevoflurane.html#citec00198762http://www.drugs.com/mmx/sevoflurane.html#citec00198762http://www.drugs.com/mmx/sevoflurane.html#citec00198701http://www.drugs.com/mmx/sevoflurane.html#citec00198701http://www.drugs.com/mmx/sevoflurane.html#citec00198701http://www.drugs.com/mmx/sevoflurane.html#citec00198701http://www.drugs.com/mmx/sevoflurane.html#citec00198701http://www.drugs.com/mmx/sevoflurane.html#citec00198701http://www.drugs.com/mmx/sevoflurane.html#citec00198701http://www.drugs.com/mmx/sevoflurane.html#citec00198701

8/12/2019 Wita

14/86

hypotension{01}

tachycardia{01}

During induction by mask (adult and pediatric patients)

Agitation{01}

During maintenance and recovery (adult and pediatric patients)Bradycardia{01}

excitement{33}{74}{83}

hypotension{01}

Incidence less frequent (1 to 3%)During induction by mask (adult patients)

Tachycardia{01}

During induction by mask (pediatric patients)Apnea{01}

laryngospasm{01}

During maintenance and recovery (adult and pediatric patients)Breath-holding{01}

fever{01}

hypertension{01}

hypothermia{01}

laryngospasm{01}

tachycardia{01}

Incidence rare (less than 1%)

Acidosis{01}

arrhythmias{01}

bronchospasm{01}

hypoxia{01}

http://www.drugs.com/mmx/sevoflurane.html#citec00198701http://www.drugs.com/mmx/sevoflurane.html#citec00198701http://www.drugs.com/mmx/sevoflurane.html#citec00198701http://www.drugs.com/mmx/sevoflurane.html#citec00198701http://www.drugs.com/mmx/sevoflurane.html#citec00198733http://www.drugs.com/mmx/sevoflurane.html#citec00198733http://www.drugs.com/mmx/sevoflurane.html#citec00198774http://www.drugs.com/mmx/sevoflurane.html#citec00198783http://www.drugs.com/mmx/sevoflurane.html#citec00198701http://www.drugs.com/mmx/sevoflurane.html#citec00198701http://www.drugs.com/mmx/sevoflurane.html#citec00198701http://www.drugs.com/mmx/sevoflurane.html#citec00198701http://www.drugs.com/mmx/sevoflurane.html#citec00198701http://www.drugs.com/mmx/sevoflurane.html#citec00198701http://www.drugs.com/mmx/sevoflurane.html#citec00198701http://www.drugs.com/mmx/sevoflurane.html#citec00198701http://www.drugs.com/mmx/sevoflurane.html#citec00198701http://www.drugs.com/mmx/sevoflurane.html#citec00198701http://www.drugs.com/mmx/sevoflurane.html#citec00198701http://www.drugs.com/mmx/sevoflurane.html#citec00198701http://www.drugs.com/mmx/sevoflurane.html#citec00198701http://www.drugs.com/mmx/sevoflurane.html#citec00198701http://www.drugs.com/mmx/sevoflurane.html#citec00198701http://www.drugs.com/mmx/sevoflurane.html#citec00198701http://www.drugs.com/mmx/sevoflurane.html#citec00198701http://www.drugs.com/mmx/sevoflurane.html#citec00198701http://www.drugs.com/mmx/sevoflurane.html#citec00198733http://www.drugs.com/mmx/sevoflurane.html#citec00198774http://www.drugs.com/mmx/sevoflurane.html#citec00198783http://www.drugs.com/mmx/sevoflurane.html#citec00198701http://www.drugs.com/mmx/sevoflurane.html#citec00198701http://www.drugs.com/mmx/sevoflurane.html#citec00198701http://www.drugs.com/mmx/sevoflurane.html#citec00198701http://www.drugs.com/mmx/sevoflurane.html#citec00198701http://www.drugs.com/mmx/sevoflurane.html#citec00198701http://www.drugs.com/mmx/sevoflurane.html#citec00198701http://www.drugs.com/mmx/sevoflurane.html#citec00198701http://www.drugs.com/mmx/sevoflurane.html#citec00198701http://www.drugs.com/mmx/sevoflurane.html#citec00198701http://www.drugs.com/mmx/sevoflurane.html#citec00198701http://www.drugs.com/mmx/sevoflurane.html#citec00198701http://www.drugs.com/mmx/sevoflurane.html#citec00198701http://www.drugs.com/mmx/sevoflurane.html#citec00198701

8/12/2019 Wita

15/86

malignant hyperthermia{01}

seizures{14}{15}

syncope{01}

wheezing{01}

Those indicating need for medical attention only if they continue or are bothersomeIncidence more frequent (greater than 3%)During maintenance and recovery (adult and pediatric patients)Cough{01}

dizziness{01}

drowsiness{01}

nausea{01}

salivation, increased{01}

shivering{01}

vomiting{01}

Incidence less frequent (1 to 3%)During maintenance and recovery (adult and pediatric patients)

Headache{01}

OverdoseFor more information on the management of overdose or unintentional ingestion, contact aPoison Control Center(see Poison Control Center Listing).

Clinical effects of overdose

The clinical effects of an overdose of sevoflurane represent an extension of its therapeuticeffects. Some respiratory effects of increased depth of anesthesia (for example, respiratorydepression and apnea) do not present difficulties if assisted or controlled ventilation is beingused during the procedure. The following effects have been selected on the basis of theirpotential clinical significance (possible signs and symptoms in parentheses whereappropriate)not necessarily inclusive:Acute effectsApnea{18}{19}

http://www.drugs.com/mmx/sevoflurane.html#citec00198701http://www.drugs.com/mmx/sevoflurane.html#citec00198714http://www.drugs.com/mmx/sevoflurane.html#citec00198714http://www.drugs.com/mmx/sevoflurane.html#citec00198715http://www.drugs.com/mmx/sevoflurane.html#citec00198701http://www.drugs.com/mmx/sevoflurane.html#citec00198701http://www.drugs.com/mmx/sevoflurane.html#citec00198701http://www.drugs.com/mmx/sevoflurane.html#citec00198701http://www.drugs.com/mmx/sevoflurane.html#citec00198701http://www.drugs.com/mmx/sevoflurane.html#citec00198701http://www.drugs.com/mmx/sevoflurane.html#citec00198701http://www.drugs.com/mmx/sevoflurane.html#citec00198701http://www.drugs.com/mmx/sevoflurane.html#citec00198701http://www.drugs.com/mmx/sevoflurane.html#citec00198701http://www.drugs.com/mmx/poison.htmlhttp://www.drugs.com/mmx/poison.htmlhttp://www.drugs.com/mmx/sevoflurane.html#citec00198718http://www.drugs.com/mmx/sevoflurane.html#citec00198718http://www.drugs.com/mmx/sevoflurane.html#citec00198719http://www.drugs.com/mmx/sevoflurane.html#citec00198701http://www.drugs.com/mmx/sevoflurane.html#citec00198714http://www.drugs.com/mmx/sevoflurane.html#citec00198715http://www.drugs.com/mmx/sevoflurane.html#citec00198701http://www.drugs.com/mmx/sevoflurane.html#citec00198701http://www.drugs.com/mmx/sevoflurane.html#citec00198701http://www.drugs.com/mmx/sevoflurane.html#citec00198701http://www.drugs.com/mmx/sevoflurane.html#citec00198701http://www.drugs.com/mmx/sevoflurane.html#citec00198701http://www.drugs.com/mmx/sevoflurane.html#citec00198701http://www.drugs.com/mmx/sevoflurane.html#citec00198701http://www.drugs.com/mmx/sevoflurane.html#citec00198701http://www.drugs.com/mmx/sevoflurane.html#citec00198701http://www.drugs.com/mmx/poison.htmlhttp://www.drugs.com/mmx/sevoflurane.html#citec00198718http://www.drugs.com/mmx/sevoflurane.html#citec00198719

8/12/2019 Wita

16/86

bradycardia{07}{10}

cardiac arrest{01}{07}

circulatory collapse{01}{07}

circulatory depression{01}{07}

decreased cardiac contractility{08}

decreased peripheral vascular resistance{01}{07}

hypotension{01}{07}

respiratory depression{18}{19}

Treatment of overdose

Discontinuing sevoflurane, maintaining a patent airway, initiating assisted or controlledventilation with oxygen, and maintaining adequate cardiovascular function with generalmeasures of circulatory support{01}.

Patient ConsultationAs an aid to patient consultation, refer to Advice for the Patient, Sevoflurane (Inhalation-Systemic).

In providing consultation, consider emphasizing the following selected information (= majorclinical significance):

Before using this medication Conditions affecting use, especially:Sensitivity to sevoflurane or other halogenated ether anesthetics

PregnancySevoflurane crosses the placentaOther medications, especially aminoglycosides (systemic), capreomycin, citrate-anticoagulated blood (massive transfusions of), clindamycin, lincomycin, neuromuscularblocking agents, or polymyxins (systemic)Other medical problems, especially a history of or genetic susceptibility to malignanthyperthermia

Proper use of this medication

Proper dosing

Precautions after receiving this medicationPossibility of psychomotor impairment following anesthesia; for 24 hours followinganesthesia, avoiding driving or performing other tasks requiring alertness and coordination

Avoiding use of alcohol or other CNS depressants within 24 hours following anesthesia,unless specifically prescribed or otherwise authorized by physician or dentist

http://www.drugs.com/mmx/sevoflurane.html#citec00198707http://www.drugs.com/mmx/sevoflurane.html#citec00198707http://www.drugs.com/mmx/sevoflurane.html#citec00198707http://www.drugs.com/mmx/sevoflurane.html#citec00198710http://www.drugs.com/mmx/sevoflurane.html#citec00198701http://www.drugs.com/mmx/sevoflurane.html#citec00198701http://www.drugs.com/mmx/sevoflurane.html#citec00198707http://www.drugs.com/mmx/sevoflurane.html#citec00198701http://www.drugs.com/mmx/sevoflurane.html#citec00198707http://www.drugs.com/mmx/sevoflurane.html#citec00198701http://www.drugs.com/mmx/sevoflurane.html#citec00198701http://www.drugs.com/mmx/sevoflurane.html#citec00198701http://www.drugs.com/mmx/sevoflurane.html#citec00198707http://www.drugs.com/mmx/sevoflurane.html#citec00198708http://www.drugs.com/mmx/sevoflurane.html#citec00198701http://www.drugs.com/mmx/sevoflurane.html#citec00198701http://www.drugs.com/mmx/sevoflurane.html#citec00198707http://www.drugs.com/mmx/sevoflurane.html#citec00198701http://www.drugs.com/mmx/sevoflurane.html#citec00198707http://www.drugs.com/mmx/sevoflurane.html#citec00198718http://www.drugs.com/mmx/sevoflurane.html#citec00198718http://www.drugs.com/mmx/sevoflurane.html#citec00198719http://www.drugs.com/mmx/sevoflurane.html#citec00198701http://www.drugs.com/mmx/sevoflurane.html#citec00198701http://www.drugs.com/mmx/sevoflurane.html#citec00198707http://www.drugs.com/mmx/sevoflurane.html#citec00198710http://www.drugs.com/mmx/sevoflurane.html#citec00198701http://www.drugs.com/mmx/sevoflurane.html#citec00198707http://www.drugs.com/mmx/sevoflurane.html#citec00198701http://www.drugs.com/mmx/sevoflurane.html#citec00198707http://www.drugs.com/mmx/sevoflurane.html#citec00198701http://www.drugs.com/mmx/sevoflurane.html#citec00198707http://www.drugs.com/mmx/sevoflurane.html#citec00198708http://www.drugs.com/mmx/sevoflurane.html#citec00198701http://www.drugs.com/mmx/sevoflurane.html#citec00198707http://www.drugs.com/mmx/sevoflurane.html#citec00198701http://www.drugs.com/mmx/sevoflurane.html#citec00198707http://www.drugs.com/mmx/sevoflurane.html#citec00198718http://www.drugs.com/mmx/sevoflurane.html#citec00198719http://www.drugs.com/mmx/sevoflurane.html#citec00198701

8/12/2019 Wita

17/86

Side/adverse effectsNotifying physician if cough, dizziness, drowsiness, nausea, increased salivation, shivering,vomiting, or headache occurs or persists after discharge

General Dosing InformationSevoflurane is to be administered only by trained anesthesiologists or nurse anesthetists {83}.Equipment and personnel for support of ventilation must be immediately available {01}.

The dosage of sevoflurane must be individualized according to surgical requirements;concurrent use of adjuvant medications and/or nitrous oxide; and patient variables,especially age. Anesthetic requirements are increased in young children and decreased ingeriatric patients {03}{33}{35}{36}.

The dosage requirement for neuromuscular blockers may change with sevofluraneanesthesia. The dose of neuromuscular blocker administered for endotracheal intubationshould not be decreased, because delayed intubation may result {01}. During maintenance ofanesthesia with sevoflurane, the dose of neuromuscular blocker is likely to be lower than that

required during anesthesia maintained with nitrous oxide and opioid agents{01}.Neuromuscular blockade with vecuronium during sevoflurane anesthesia may be moredifficult to reverse with neostigmine than when similar blockade is produced during isofluraneanesthesia {38}.

Sevoflurane has a nonpungent odor and is associated with a low incidence of respiratoryirritability, making it suitable for mask induction{01}{33}{35}{36}{63}.

Sevoflurane may be vaporized in a flow of oxygen or a nitrous oxideoxygen mixture {01}. Theconcentration of sevoflurane being delivered from a vaporizer during anesthesia should beknown. This may be accomplished by using a vaporizer calibrated specifically forsevoflurane. Fresh gas flow rates below 2 L per minute (L/min) are not recommended {01}. A

concern in low-flow systems is accumulation of compound A, a substance produced whensevoflurane interacts with carbon dioxide absorbents (e.g., soda lime or bariumhydroxide) {56}{64}.Compound A has been found to be a dose-dependent nephrotoxin inrats{54}{75}{77}. The toxicity of compound A in humans has not been established.

During the maintenance of anesthesia, increasing the concentration of sevoflurane producesdose-dependent decreases in blood pressure. These hemodynamic changes may occurrapidly with sevoflurane due to its relative insolubility in blood. Excessive respiratorydepression or decreases in blood pressure may be related to the depth of anesthesia andmay be corrected by decreasing the inspired concentration of sevoflurane{01}.

No specific premedication is indicated or contraindicated with the use of sevoflurane. Thedecisions regarding premedication should be based on the judgment of the health care

professional{01}.

Safety considerations for handling this medicationAcute overexposure of operating room personnel to sevoflurane may cause headache,dizziness, and, in extreme cases, unconsciousness.

The results of some epidemiological studies suggest a link between chronic exposure ofoperating room personnel to low concentrations of inhalation anesthetics (waste anestheticgases [WAGs]) and increased health problems, including reproductive problems (increases

http://www.drugs.com/mmx/sevoflurane.html#citec00198783http://www.drugs.com/mmx/sevoflurane.html#citec00198701http://www.drugs.com/mmx/sevoflurane.html#citec00198703http://www.drugs.com/mmx/sevoflurane.html#citec00198703http://www.drugs.com/mmx/sevoflurane.html#citec00198733http://www.drugs.com/mmx/sevoflurane.html#citec00198735http://www.drugs.com/mmx/sevoflurane.html#citec00198735http://www.drugs.com/mmx/sevoflurane.html#citec00198736http://www.drugs.com/mmx/sevoflurane.html#citec00198701http://www.drugs.com/mmx/sevoflurane.html#citec00198701http://www.drugs.com/mmx/sevoflurane.html#citec00198701http://www.drugs.com/mmx/sevoflurane.html#citec00198701http://www.drugs.com/mmx/sevoflurane.html#citec00198738http://www.drugs.com/mmx/sevoflurane.html#citec00198701http://www.drugs.com/mmx/sevoflurane.html#citec00198701http://www.drugs.com/mmx/sevoflurane.html#citec00198701http://www.drugs.com/mmx/sevoflurane.html#citec00198733http://www.drugs.com/mmx/sevoflurane.html#citec00198735http://www.drugs.com/mmx/sevoflurane.html#citec00198736http://www.drugs.com/mmx/sevoflurane.html#citec00198736http://www.drugs.com/mmx/sevoflurane.html#citec00198763http://www.drugs.com/mmx/sevoflurane.html#citec00198701http://www.drugs.com/mmx/sevoflurane.html#citec00198701http://www.drugs.com/mmx/sevoflurane.html#citec00198756http://www.drugs.com/mmx/sevoflurane.html#citec00198764http://www.drugs.com/mmx/sevoflurane.html#citec00198764http://www.drugs.com/mmx/sevoflurane.html#citec00198764http://www.drugs.com/mmx/sevoflurane.html#citec00198754http://www.drugs.com/mmx/sevoflurane.html#citec00198754http://www.drugs.com/mmx/sevoflurane.html#citec00198775http://www.drugs.com/mmx/sevoflurane.html#citec00198777http://www.drugs.com/mmx/sevoflurane.html#citec00198701http://www.drugs.com/mmx/sevoflurane.html#citec00198701http://www.drugs.com/mmx/sevoflurane.html#citec00198701http://www.drugs.com/mmx/sevoflurane.html#citec00198701http://www.drugs.com/mmx/sevoflurane.html#citec00198701http://www.drugs.com/mmx/sevoflurane.html#citec00198701http://www.drugs.com/mmx/sevoflurane.html#citec00198783http://www.drugs.com/mmx/sevoflurane.html#citec00198701http://www.drugs.com/mmx/sevoflurane.html#citec00198703http://www.drugs.com/mmx/sevoflurane.html#citec00198733http://www.drugs.com/mmx/sevoflurane.html#citec00198735http://www.drugs.com/mmx/sevoflurane.html#citec00198736http://www.drugs.com/mmx/sevoflurane.html#citec00198701http://www.drugs.com/mmx/sevoflurane.html#citec00198701http://www.drugs.com/mmx/sevoflurane.html#citec00198738http://www.drugs.com/mmx/sevoflurane.html#citec00198701http://www.drugs.com/mmx/sevoflurane.html#citec00198733http://www.drugs.com/mmx/sevoflurane.html#citec00198735http://www.drugs.com/mmx/sevoflurane.html#citec00198736http://www.drugs.com/mmx/sevoflurane.html#citec00198763http://www.drugs.com/mmx/sevoflurane.html#citec00198701http://www.drugs.com/mmx/sevoflurane.html#citec00198701http://www.drugs.com/mmx/sevoflurane.html#citec00198756http://www.drugs.com/mmx/sevoflurane.html#citec00198764http://www.drugs.com/mmx/sevoflurane.html#citec00198754http://www.drugs.com/mmx/sevoflurane.html#citec00198775http://www.drugs.com/mmx/sevoflurane.html#citec00198777http://www.drugs.com/mmx/sevoflurane.html#citec00198701http://www.drugs.com/mmx/sevoflurane.html#citec00198701

8/12/2019 Wita

18/86

in spontaneous abortions, stillbirths, and possibly birth defects) {57}{58}.Although a causalrelationship has not been established, measures to minimize exposure are recommended{57}{58}. Such measures include maintaining adequate general ventilation in the operating room,using a well-designed and well-maintained scavenging system, and, by employment ofcareful work procedures and routine equipment maintenance, minimizing leaks and spillswhile the anesthetic is in use{57}{58}.

Although no specific work exposure limit has been established for sevoflurane, the NationalInstitute for Occupational Safety and Health Administration has recommended an 8-hour,time-weighted average limit of 2 parts per million (ppm) for halogenated anesthetic agents ingeneral. The limit for halogenated anesthetics coupled with nitrous oxide is 0.5 ppm{01}.

For treatment of adverse effectsRecommended treatment consists of the following

For malignant hyperthermic crisisDiscontinuation of possible triggering agents (such asinhalation anesthetics or succinylcholine), managing increased oxygen requirement, coolingthe patient, and correcting fluid and electrolyte imbalances and metabolic acidosis.Dantrolene can be administered by rapid intravenous injection (see Dantrolene

[Systemic]monograph) {01}.

Inhalation Dosage Forms

SEVOFLURANE

Usual adult doseAnesthetic (general)

Inhalation, vaporized in a flow of oxygen or nitrous oxide and oxygen:

InductionDosage must be individualized according to patient response{01}

.

MaintenanceDosage must be individualized according to patient response. Surgical levelsof anesthesia usually can be achieved with concentrations of 0.5 to 3% sevoflurane with orwithout concomitant use of nitrous oxide {01}.

Note:Anesthetic requirements decrease with increasing age. Minimum alveolarconcentration (MAC) values for sevoflurane in oxygen are 2.6% for patients 25 years of age,2.1% for patients 40 years of age, 1.7% for patients 60 years of age, and 1.4% for patients80 years of age. Geriatric patients require lower doses of sevoflurane for induction andmaintenance of anesthesia{01}{03}.

Usual pediatric doseAnesthetic (general)

Inhalation, vaporized in a flow of oxygen or nitrous oxide and oxygen:InductionDosage must be individualized according to patient response {01}.

http://www.drugs.com/mmx/sevoflurane.html#citec00198757http://www.drugs.com/mmx/sevoflurane.html#citec00198758http://www.drugs.com/mmx/sevoflurane.html#citec00198758http://www.drugs.com/mmx/sevoflurane.html#citec00198758http://www.drugs.com/mmx/sevoflurane.html#citec00198757http://www.drugs.com/mmx/sevoflurane.html#citec00198757http://www.drugs.com/mmx/sevoflurane.html#citec00198758http://www.drugs.com/mmx/sevoflurane.html#citec00198757http://www.drugs.com/mmx/sevoflurane.html#citec00198757http://www.drugs.com/mmx/sevoflurane.html#citec00198757http://www.drugs.com/mmx/sevoflurane.html#citec00198758http://www.drugs.com/mmx/sevoflurane.html#citec00198701http://www.drugs.com/mmx/sevoflurane.html#citec00198701http://www.drugs.com/mmx/sevoflurane.html#citec00198701http://www.drugs.com/mmx/dantrolene-sodium.htmlhttp://www.drugs.com/mmx/dantrolene-sodium.htmlhttp://www.drugs.com/mmx/sevoflurane.html#citec00198701http://www.drugs.com/mmx/sevoflurane.html#citec00198701http://www.drugs.com/mmx/sevoflurane.html#citec00198701http://www.drugs.com/mmx/sevoflurane.html#citec00198701http://www.drugs.com/mmx/sevoflurane.html#citec00198701http://www.drugs.com/mmx/sevoflurane.html#citec00198701http://www.drugs.com/mmx/sevoflurane.html#citec00198703http://www.drugs.com/mmx/sevoflurane.html#citec00198701http://www.drugs.com/mmx/sevoflurane.html#citec00198757http://www.drugs.com/mmx/sevoflurane.html#citec00198758http://www.drugs.com/mmx/sevoflurane.html#citec00198757http://www.drugs.com/mmx/sevoflurane.html#citec00198758http://www.drugs.com/mmx/sevoflurane.html#citec00198757http://www.drugs.com/mmx/sevoflurane.html#citec00198758http://www.drugs.com/mmx/sevoflurane.html#citec00198701http://www.drugs.com/mmx/dantrolene-sodium.htmlhttp://www.drugs.com/mmx/dantrolene-sodium.htmlhttp://www.drugs.com/mmx/sevoflurane.html#citec00198701http://www.drugs.com/mmx/sevoflurane.html#citec00198701http://www.drugs.com/mmx/sevoflurane.html#citec00198701http://www.drugs.com/mmx/sevoflurane.html#citec00198701http://www.drugs.com/mmx/sevoflurane.html#citec00198703http://www.drugs.com/mmx/sevoflurane.html#citec00198701

8/12/2019 Wita

19/86

MaintenanceDosage must be individualized according to patient response. Surgical levelsof anesthesia usually can be achieved with concentrations of 0.5 to 3% sevoflurane with orwithout concomitant use of nitrous oxide {01}{33}{36}.

Note:Anesthetic requirements decrease with increasing age. MAC values for sevoflurane in

oxygen are 3.3% for neonates, 3% for infants less than 6 months of age, 2.8% for infantsand children 6 months to 3 years of age, and 2.5% for children 3 to 12 years of age. MAC inpremature neonates has not been determined {01}.MAC in adolescents has not been determined. The adolescent dose for other inhalationanesthetics is slightly higher than the dose for adult patients {73}{81}.

Usual geriatric doseAnesthetic (general)Geriatric patients require lower doses of sevoflurane for induction and maintenance ofanesthesia {01}{03}. SeeUsual adult dose.

Product(s) usually available:U.S.

[Ultane{01}]

Canada

[Sevorane{65}]

Packaging and storage:Store between 15 and 30 C (59 and 86 F) {01}.

Stability:Stable at room temperature {01}. No discernible degradation occurs in the presence of acid orheat{01}. The only known degradation reaction in the clinical setting is through direct contactwith carbon dioxide absorbents such as soda lime {01}.This reaction producespentafluoroisopropenyl fluoromethyl ether, also known as compound A, and trace amountsof pentafluoromethoxy isopropyl fluoromethyl ether, also known as compound B {01}. Theconcentration of the degradants is inversely correlated with fresh gas flow rate{01}{56}.

With sevoflurane, unlike with desflurane, enflurane, and isoflurane, degradation of theanesthetic during use does not result in significant production of carbon monoxide{59}.

Revised: 12/11/1998

http://www.drugs.com/mmx/sevoflurane.html#citec00198701http://www.drugs.com/mmx/sevoflurane.html#citec00198733http://www.drugs.com/mmx/sevoflurane.html#citec00198733http://www.drugs.com/mmx/sevoflurane.html#citec00198736http://www.drugs.com/mmx/sevoflurane.html#citec00198701http://www.drugs.com/mmx/sevoflurane.html#citec00198773http://www.drugs.com/mmx/sevoflurane.html#citec00198781http://www.drugs.com/mmx/sevoflurane.html#citec00198781http://www.drugs.com/mmx/sevoflurane.html#citec00198781http://www.drugs.com/mmx/sevoflurane.html#citec00198701http://www.drugs.com/mmx/sevoflurane.html#citec00198703http://www.drugs.com/mmx/sevoflurane.html#citec00198703http://www.drugs.com/mmx/sevoflurane.html#s001987113http://www.drugs.com/mmx/sevoflurane.html#s001987113http://www.drugs.com/mmx/sevoflurane.html#citec00198701http://www.drugs.com/mmx/sevoflurane.html#citec00198765http://www.drugs.com/mmx/sevoflurane.html#citec00198701http://www.drugs.com/mmx/sevoflurane.html#citec00198701http://www.drugs.com/mmx/sevoflurane.html#citec00198701http://www.drugs.com/mmx/sevoflurane.html#citec00198701http://www.drugs.com/mmx/sevoflurane.html#citec00198701http://www.drugs.com/mmx/sevoflurane.html#citec00198701http://www.drugs.com/mmx/sevoflurane.html#citec00198701http://www.drugs.com/mmx/sevoflurane.html#citec00198701http://www.drugs.com/mmx/sevoflurane.html#citec00198701http://www.drugs.com/mmx/sevoflurane.html#citec00198701http://www.drugs.com/mmx/sevoflurane.html#citec00198756http://www.drugs.com/mmx/sevoflurane.html#citec00198759http://www.drugs.com/mmx/sevoflurane.html#citec00198759http://www.drugs.com/mmx/sevoflurane.html#citec00198701http://www.drugs.com/mmx/sevoflurane.html#citec00198733http://www.drugs.com/mmx/sevoflurane.html#citec00198736http://www.drugs.com/mmx/sevoflurane.html#citec00198701http://www.drugs.com/mmx/sevoflurane.html#citec00198773http://www.drugs.com/mmx/sevoflurane.html#citec00198781http://www.drugs.com/mmx/sevoflurane.html#citec00198701http://www.drugs.com/mmx/sevoflurane.html#citec00198703http://www.drugs.com/mmx/sevoflurane.html#s001987113http://www.drugs.com/mmx/sevoflurane.html#citec00198701http://www.drugs.com/mmx/sevoflurane.html#citec00198765http://www.drugs.com/mmx/sevoflurane.html#citec00198701http://www.drugs.com/mmx/sevoflurane.html#citec00198701http://www.drugs.com/mmx/sevoflurane.html#citec00198701http://www.drugs.com/mmx/sevoflurane.html#citec00198701http://www.drugs.com/mmx/sevoflurane.html#citec00198701http://www.drugs.com/mmx/sevoflurane.html#citec00198701http://www.drugs.com/mmx/sevoflurane.html#citec00198756http://www.drugs.com/mmx/sevoflurane.html#citec00198759

8/12/2019 Wita

20/86

References

1. Ultane package insert (AbbottUS), Rev 9/97, Rec 10/98.

2. Tomi K, Mashimo T, Yagi M, et al. Alterations in pain threshold and psychomotorresponse associated with subanesthetic concentrations of inhalation anaesthetics inhumans. Br J Anaesth 1993; 70: 684-6.

3. Nakajima R, Nakajima Y, Ikeda K. Minimum alveolar concentration of sevoflurane inelderly patients. Br J Anaesth 1993; 70: 273-5.

4. Canada JR, editor. USP dictionary of USAN and international drug names 1998.Rockville, MD: The United States Pharmacopeial Convention Inc; 1997. p. 665.

5. Urban BW. Differential effects of gaseous and volatile anaesthetics on sodium andpotassium channels. Br J Anaesth 1993; 71: 25-38.

6. Elliott JR, Elliott AA, Harper AA, et al. Effects of general anaesthetics on neuronalsodium and potassium channels. Gen Pharmacol 1992; 23: 1005-11.

7. Holaday D, Smith F. Clinical characteristics and biotransformation of sevoflurane in

healthy human volunteers. Anesthesiology 1981; 54: 100-6.8. Kikura M, Ikeda K. Comparison of effects of sevoflurane/nitrous oxide and

enflurane/nitrous oxide on myocardial contractility in humans. Anesthesiology 1993; 79:235-43.

9. Navarro R, Weiskopf RB, Moore MA, et al. Humans anesthetized with sevoflurane orisoflurane have similar arrhythmic response to epinephrine. Anesthesiology 1994; 80:545-9.

10. Frink EJ, Malan TP, Atlas M, et al. Clinical comparison of sevoflurane and isoflurane inhealthy patients. Anesth Analg 1992; 74: 241-5.

11. Manabe M, Ookawa I, Nonaka A, et al. Effects of sevoflurane with or without nitrous

oxide on cardiac contractility and sinoatrial node rate. J Anesth 1989; 3: 145-8.12. Scheller M, Tateishe A, Drummond J, et al. The effects of sevoflurane on cerebral blood

flow, cerebral metabolic rate for oxygen, intracranial pressure, and theelectroencephalogram are similar to isoflurane in the rabbit. Anesthesiology 1988; 68:548-51.

13. Scheller M, Nakakimura K, Fleischer J. Cerebral effects of sevoflurane in the dog:comparison with isoflurane and enflurane. Br J Anaesth 1990; 65: 388-92.

14. Adachi M, Ikemoto Y, Kubo K, et al. Seizure-like movements during induction ofanaesthesia with sevoflurane. Br J Anaesth 1992; 68: 214-5.

15. Komatsu H, Taie S, Endo S, et al. Electrical seizures during sevoflurane anesthesia intwo pediatric patients with epilepsy. Anesthesiology 1994; 81: 1535-7.

16. Kitaguchi K, Ohsumi H, Kuro M, et al. Effects of sevoflurane on cerebral circulation andmetabolism in patients with ischemic cerebrovascular disease. Anesthesiology 1993; 79:704-9.

17. Saitoh Y, Toyoka H, Amaha K. Recoveries of post-tetanic twitch and train-of-fourresponses after administration of vecuronium with different inhalation anaesthetics andneuroleptanaesthesia. Br J Anaesth 1993; 70: 402-4.

8/12/2019 Wita

21/86

18. Nishino T, Kochi T. Effects of surgical stimulation on the apnoeic thresholds for carbondioxide during anaesthesia with sevoflurane. Br J Anaesth 1994; 73: 583-6.

19. Doi M, Ikeda K. Respiratory effects of sevoflurane. Anesth Analg 1987; 66: 241-4.

20. Smith I, Ding Y, White P. Comparison of induction, maintenance, and recoverycharacteristics of sevoflurane-N 2O and propofol-sevoflurane-N 2O with propofol-

isoflurane-N 2O anesthesia. Anesth Analg 1992; 74: 253-9.

21. Yurino M, Kimura H. Comparison of induction time and characteristics betweensevoflurane and sevoflurane/nitrous oxide. Acta Anaesthesiol Scand 1995; 39: 356-8.

22. Doi M, Ikeda K. Airway irritation produced by volatile anaesthetics during brief inhalation:comparison of halothane, enflurane, isoflurane, and sevoflurane. Can J Anaesth 1993;40: 122-6.

23. Yasuda N, Lockhart S, Eger E, et al. Comparison of kinetics of sevoflurane andisoflurane in humans. Anesth Analg 1991; 72: 316-24.

24. Kharasch ED, Karol MD, Lanni C, et al. Clinical sevoflurane metabolism and disposition;sevoflurane and metabolite pharmacokinetics. Anesthesiology 1995; 82: 1369-78.

25. Kharasch ED, Armstrong AS, Gunn K, et al. Clinical sevoflurane metabolism anddisposition: the role of cytochrome P450 2E1 in fluoride and hexafluoroisopropanolformation. Anesthesiology 1995; 82: 1379-88.

26. Kharasch ED, Thummel KE. Identification of cytochrome P450 2E1 as the predominantenzyme catalyzing human liver microsomal defluorination of sevoflurane, isoflurane, andmethoxyflurane. Anesthesiology 1993; 79: 795-807.

27. Bito H, Ikeda K. Plasma inorganic fluoride and intracircuit degradation productconcentrations in long-duration, low-flow sevoflurane anesthesia. Anesth Analg 1994;79: 946-51.

28. Frink E, Malan T, Isner R, et al. Renal concentrating function with prolonged sevoflurane

or enflurane anesthesia in volunteers. Anesthesiology 1994; 80: 1019-25.29. Yurino M, Kimura H. Vital capacity rapid inhalation induction technique: comparison of

sevoflurane and halothane. Can J Anaesth 1993; 40: 440-3.

30. Yurino M, Kimura H. Induction of anesthesia with sevoflurane, nitrous oxide, and oxygen:a comparison of spontaneous ventilation and vital capacity rapid inhalation induction(VCRII) techniques. Anesth Analg 1993; 76: 598-601.

31. Eriksson H, Haasio J, Korttila K. Recovery from sevoflurane and isoflurane anaesthesiaafter outpatient gynaecological laparoscopy. Acta Anaesthesiol Scand 1995; 39: 377-80.

32. Gambling DR, Sharma SK, White PF, et al. Use of sevoflurane during elective cesareanbirth: a comparison with isoflurane and spinal anesthesia. Anesth Analg 1995; 81: 90-5.

33. Sarner JB, Levine M, Davis P, et al. Clinical characteristics of sevoflurane in children: acomparison with halothane. Anesthesiology 1995; 82: 38-46.

34. Taivainen T, Tianen P, Meretoja OA, et al. Comparison of the effects of sevoflurane andhalothane on the quality of anaesthesia and serum glutathione transferase alpha andfluoride in paediatric patients. Br J Anaesth 1994; 73: 590-5.

35. Piat V, Dubois M, Johanet S, et al. Induction and recovery characteristics andhemodynamic responses to sevoflurane and halothane in children. Anesth Analg 1994;79: 840-4.

8/12/2019 Wita

22/86

36. Naito Y, Tamai S, Shingu K, et al. Comparison between sevoflurane and halothane forpaediatric ambulatory anesthesia. Br J Anaesth 1991; 67: 387-9.

37. Morita T, Tsukagoshi H, Sugaya T, et al. The effects of sevoflurane are similar to thoseof isoflurane on the neuromuscular block produced by vecuronium. Br J Anaesth 1994;72: 465-7.

38. Morita T, Tsukagoshi H, Sugaya T, et al. Inadequate antagonism of vecuronium-inducedneuromuscular block by neostigmine during sevoflurane or isoflurane anesthesia. AnesthAnalg 1995; 80: 1175-80.

39. Tung A, Jacobsohn E. A case of nonoliguric renal failure after general anesthesia withsevoflurane and desflurane. Anesth Analg 1997; 85: 1407-9.

40. Higuchi H, Sumita S, Wada H, et al. Effects of sevoflurane and isoflurane on renalfunction and on possible markers of nephrotoxicity. Anesthesiology 1998; 89: 307-22.

41. Martis L, Synch S, Napoli M, et al. Biotransformation of sevoflurane in dogs and rats.Anesth Analg 1981; 60: 186-91.

42. Cook T, Beppu W, Hitt B, et al. A comparison of renal effects and metabolism of

sevoflurane and methoxyflurane in enzyme-induced rats. Anesth Analg 1975; 54: 829-35.

43. Soma LR, Tierney WJ, Hogan GK, et al. The effects of multiple administrations ofsevoflurane to cynomolgus monkeys: clinical pathologic, hematologic, and pathologicstudy. Anesth Analg 1995; 81: 347-52.

44. Tinker JH, Baker MT. Sevoflurane, fluoride ion, and renal toxicity [letter]. Anesthesiology1995; 83: 232-3.

45. Frink EJ, Ghantous H, Malan P, et al. Plasma inorganic fluoride with sevofluraneanesthesia: correlation with indices of hepatic and renal function. Anesth Analg 1992; 74:231-5.

46. Conzen PF, Nuscheler M, Melotte A, et al. Renal function and serum fluorideconcentrations in patients with stable renal insufficiency after anesthesia withsevoflurane or enflurane. Anesth Analg 1995; 81: 569-75.

47. Ducart A, Adnet P, Renaud B, et al. Malignant hyperthermia during sevofluraneadministration. Anesth Analg 1995; 80: 609-11.

48. Ochiai R, Toyoda Y, Nishio I, et al. Possible association of malignant hyperthermia withsevoflurane anesthesia. Anesth Analg 1992; 74: 616-8.

49. Otsuka H, Komura Y, Mayumi T. Malignant hyperthermia during sevoflurane anesthesiain a child with central core disease. Anesthesiology 1991; 75: 699-701.

50. Liberman BA, Teasdale SJ. Anesthesia and amiodarone. Can Anaesth Soc J 1985; 32:629-38.

51. Tanaka K, Nakamura M, Domen M, et al. The influence of volatile anesthetics onportwine stain. Clin Ther 1993; 15: 567-9.

52. Newman PJ, Quinn AC, Hall GM, et al. Circulating fluoride changes and hepatorenalfunction following sevoflurane anaesthesia. Anaesthesia 1994; 49: 936-9.

53. Kharasch ED, Hankins DC, Thummel KE. Human kidney methoxyflurane andsevoflurane metabolism. Anesthesiology 1995; 82: 689-99.

8/12/2019 Wita

23/86

54. Kandel L, Laster MJ, Eger EI, et al. Nephrotoxicity in rats undergoing a one-hourexposure to compound A. Anesth Analg 1995; 81: 559-63.

55. Bito H, Ikeda K. Closed-circuit anesthesia with sevoflurane in humans. Anesthesiology1994; 80: 71-6.

56. Fang ZX, Eger EI. Factors affecting the concentration of compound A resulting from the

degradation of sevoflurane by soda lime and Baralyme in a standard anesthetic circuit.Anesth Analg 1995; 81: 564-8.

57. Rosenberg P, Kirves A. Miscarriages among operating theatre staff. Acta AnaesthesiolScand 1973; 53: 37-42.

58. Holmberg K, Lambert B, Lindstein J, et al. DNA and chromosomal alterations inlymphocytes of operating room personnel and inpatients before and after inhalationalanaesthesia. Acta Anaesthesiol Scand 1982; 26: 531-9.

59. Fang ZX, Eger EI, Laster MJ, et al. Carbon monoxide production from degradation ofdesflurane, enflurane, isoflurane, halothane, and sevoflurane by soda lime andBaralyme. Anesth Analg 1995; 80: 1187-93.

60. Mishra P, Calvey TN, Williams NE, et al. Intraoperative bradycardia and hypotensionassociated with timolol and pilocarpine eye drops. Br J Anaesth 1983; 55: 897-9.

61. Nishi M, Nakagawa H, Komotsu R, et al. Neuromuscular effects of sevoflurane in apatient with myasthenia gravis. J Anesth 1993; 7: 237-9.

62. Standards for Basic Intraoperative Monitoring, American Society of Anesthesiologists. In:Miller RD, editor. Anesthesia. 3rd ed. New York: Churchill Livingstone Inc; 1990. p.2392-4.

63. Eger EI. New inhaled anesthetics. Anesthesiology 1994; 80: 906-22.

64. Frink EJ. Toxicologic potential of desflurane and sevoflurane. Acta Anaesthesiol Scand1995; 39(suppl 105): 120-2.

65. Sevorane package insert (AbbottCanada), Rev 10/95, Rec 2/96.

66. Malan T, DiNardo J, Isner R, et al. Cardiovascular effects of sevoflurane compared withthose of isoflurane in volunteers. Anesthesiology 1995; 83: 918-28.

67. Kersten J, Brayer A, Pagel P, et al. Perfusion of ischemic myocardium during anesthesiawith sevoflurane. Anesthesiology 1994, 81: 995-1004.

68. Nathanson M, Fredman B, Smith I, et al. Sevoflurane versus desflurane for outpatientanesthesiaa comparison of maintenance and recovery profiles. Anesth Analg 1995;81: 1186-90.

69. Asada A, Fujimori M, Tomoda S, et al. Sevoflurane for elective cesarean section. JAnesth 1990, 4: 67-72.

70. Taktekawa S, Asada A, Nishikawa K, et al. Comparison of sevoflurane with isofluraneanesthesia for use in elective cesarean section. Anesthesiology 1993; 79(3A): A1018.

71. Hatano M, Asada A, Nishi S, et al. Maternal and fetal serum inorganic fluoride levelsfollowing isoflurane and sevoflurane anesthesia for cesarean section. Hiroshima JAnesth 1993; 29: 49-51.

8/12/2019 Wita

24/86

72. Higuchi H, Sumikura H, Sumita S, et al. Renal function in patients with high serumfluoride concentrations after prolonged sevoflurane anesthesia. Anesthesiology 1995;83; 449-58.

73. Panel consensus on monograph revision of 10/95.

74. Lerman J, Sikich N, Kleinman S, et al. The pharmacology of sevoflurane in infants and

children. Anesthesiology 1995; 82: 38-46.

75. Gonsowski C, Laster M, Eger E, et al. Toxicity of compound A in rats: effect of a 3-houradministration. Anesthesiology 1994; 80: 556-65.

76. Gonsowski C, Laster M, Eger E, et al. Toxicity of