TUGAS MATA KULIAH

ILMU BEDAH VETERINER

(Premedikasi dan Anestesi)

ANESTESI UMUM INHALASI PADA ANJING

Oleh:

I Made Maha Putra

1709511067

LABORATORIUM BEDAH VETERINER

FAKULTAS KEDOKTERAN HEWAN

UNIVERSITAS UDAYANA

TAHUN 2020

i
 RINGKASAN

Seiring dengan meningkatnya taraf kehidupan, minat masyarakat untuk memelihara

hewan kesayangan semakin meningkat. Anjing merupakan salah satu hewan kesayangan yang
banyak dipelihara orang. Oleh karena itu kesehatan hewan perlu diperhatikan agar senantiasa
sehat, lincah, dan dapat melanjutkan keturunan. Berbagai jenis penyakit dapat menyerang
anjing, baik yang bersifat infeksius maupun non-infeksius. Banyak diantara penyakit tersebut
yang tidak dapat ditangani dengan obat-obatan, sehingga untuk penanganannya dibutuhkan
tindakan pembedahan. Untuk keberhasilan dan kelancaran bedah, anestesi umum memegang
peranan penting. Anestesi umum dapat diberikan secara inhalasi. Anestesi umum inhalasi
merupakan salah satu metode anestesi umum yang dilakukan dengan cara memberikan agen
anestesi yang berupa gas dan atau cairan yang mudah menguap melalui alat anestesi langsung
ke udara inspirasi. Terjadi anestesi karena uap yang dihirup masuk dari alveoli mendifusi
membrane alveoli dan melarut ke dalam darah paru-paru yang selanjutnya dari paru-paru
mendifusi masuk ke jaringan tubuh terutama otak.
Anestesi umum inhalasi merupakan salah satu metode anestesi umum yang dilakukan
dengan cara memberikan agen anestesi yang berupa gas dan atau cairan yang mudah menguap
melalui alat anestesi langsung ke udara inspirasi. Adapun jenis-jenis anestesi umum inhalasi
yaitu sevoflurane, isoflurane, halothane, dan desflurane. Sevoflurane adalah agen inhalasi eter
terhalogenasi yang sekarang banyak digunakan dalam anestesi manusia dan hewan.
Sevoflurane tidak menyebabkan iritasi pada saluran pernapasan dan memiliki bau yang kurang
tajam, sehingga cocok untuk induksi anestesi inhalasi, namun memiliki nilai MAC yang relatif
tinggi. Isoflurane merupakan halogenasi eter dan secara kimia sangat mirip dengan
metoksifluran dan sevofluran. Potensi isoflurane lebih kecil dibandingkan halothane karena
mempunyai nilai MAC lebih tinggi dibandingkan halothane. Halothane adalah hidrokarbon
terhalogenasi yang tidak mudah terbakar, tidak dapat meledak, tidak berwarna, mudah
menguap pada suhu kamar, disimpan dalam botol berwarna kuning untuk mencegah degradasi
oleh cahaya. Anestesi inhalasi ini sangat popular baik di kedokteran manusia maupun
kedokteran veteriner karena lebih aman, lebih mudah mengatur kedalaman stadium
anestesinya, induksi cepat, masa pulihnya (recovery) juga cepat. Desflurane adalah eter
terhalogenasi yang memiliki nilai MAC yang relatif tinggi dibandingkan dengan agen inhalasi
lainnya. Pemberian anestesi umum inhalasi dapat dilakukan melalui beberapa cara, yakni (1)
auto inhalasi, dan (2) metode umpan balik positif yang terdiri dari beberapa metode yakni
metode terbuka, semi terbuka, semi tertutup, dan tertutup. Penggunaan anestesi inhalasi ini
juga memiliki beberapa keuntungan dan kerugian bagi pasien maupun lingkungan sekitar
pasien.

ii
 KATA PENGANTAR

Puji dan syukur kehadirat Tuhan Yang Maha Esa. Karena berkat limpahan karunia-Nya
kami dapat menyelesaikan paper “Anestesi Umum Inhalasi Pada Anjing” dengan baik.

Penyusunan paper ini untuk memenuhi tugas mata kuliah Ilmu Bedah Umum Veteriner.
Dalam paper ini menjelaskan tentang jenis anestesi inhalasi, teknik pengaplikasian, serta
keuntungan dan kerugian penggunaan anestesi inhalasi pada anjing. Materi yang disajikan
cukup terperinci agar mudah dipahami oleh pembaca. Paper ini dapat terselesaikan karena
bantuan dari berbagai pihak.

Kami telah berusaha semaksimal mungkin dalam menyelesaikan paper ini untuk
mendapatkan hasil yang sebaik-baiknya. Namun kami menyadari bahwa paper ini jauh dari
kesempurnaan. Oleh karena itu, kami mengharapkan kritik dan saran dari pembaca demi
kesempurnaan paper selanjutnya. Semoga paper ini dapat bermanfaat bagi para pembaca.

Denpasar, 14 Maret 2020

Penulis

iii
 DAFTAR ISI

HALAMAN JUDUL ............................................................................................................. i

RINGKASAN ........................................................................................................................ ii

KATA PENGANTAR .......................................................................................................... iii

DAFTAR ISI .......................................................................................................................... iv

DAFTAR GAMBAR ............................................................................................................ v

BAB I PENDAHULUAN .................................................................................................... 1

1.1 Latar Belakang .......................................................................................................... 1

1.2 Rumusan Masalah..................................................................................................... 1

BAB II TUJUAN DAN MANFAAT .................................................................................. 2

2.1 Tujuan Penulisan........................................................................................................ 2

2.2 Manfaat Penulisan ..................................................................................................... 2

BAB III TINJAUAN PUSTAKA ........................................................................................ 3

3.1 Anjing .......................................................................................................................... 3

3.2 Anestesi Umum .......................................................................................................... 3

3.3 Anestesi Umum Inhalasi ........................................................................................... 4

BAB IV PEMBAHASAN .................................................................................................... 6

4.1 Jenis-jenis Anestesi Umum Inhalasi ....................................................................... 6

4.2 Teknik Pemberian Anestesi Inhalasi ....................................................................... 10

4.3 Keunggulan dan Kerugian Pemberian Anestesi Inhalasi ..................................... 12

BAB V PENUTUP ................................................................................................................ 14

5.1 Simpulan ..................................................................................................................... 14

5.2 Saran ............................................................................................................................ 14

DAFTAR PUSTAKA ........................................................................................................... 15

LAMPIRAN ........................................................................................................................... 17

iv
 DAFTAR GAMBAR

Gambar 1. Halothane Untuk Anestesi Inhalasi .......................................................................... 7

Gambar 2. Desflurane untuk Anestesi Inhalasi .......................................................................... 8

Gambar 3. Sevoflurane Untuk Anestesi Inhalasi ....................................................................... 9

Gambar 4. Isoflurane Untuk Anestesi Inhalasi .......................................................................... 9

Gambar 5. Alat Pipa Endotracheal. ..................................................................................... 12

v
 BAB I
PENDAHULUAN

1.1 Latar Belakang

Anjing adalah salah satu hewan yang mudah bersosialisasi dengan manusia. Hubungan
anjing dan manusia sudah terjalin cukup lama sejak ratusan tahun silam. Manusia primitif
bahkan memanfaatkan anjing untuk teman berburu (Davis, 2006). Seiring dengan
meningkatnya taraf kehidupan, minat masyarakat untuk memelihara hewan kesayangan
semakin meningkat. Anjing merupakan salah satu hewan kesayangan yang banyak dipelihara
orang.

Oleh karena itu kesehatan hewan perlu diperhatikan agar senantiasa sehat, lincah, dan dapat
melanjutkan keturunan. Untuk menjaga kelestarian hewan, maka manusia perlu
memperhatikan pemeliharaan yang baik dengan cara memberikan makanan yang cukup dan
bergizi serta memberikan perhatian terhadap kesehatan hewan. Salah satu cara untuk menjaga
kesehatan hewan adalah dengan pencegahan penyakit (preventif) dan pengobatan yang sesuai
dengan penyebab penyakit (Maya, 2006).

Berbagai jenis penyakit dapat menyerang anjing, baik yang bersifat infeksius maupun non-
infeksius. Banyak diantara penyakit tersebut yang tidak dapat ditangani dengan obat-obatan,
sehingga untuk penanganannya dibutuhkan tindakan pembedahan. Untuk keberhasilan dan
kelancaran bedah, anestesi umum memegang peranan penting. Anestesi umum dapat diberikan
secara inhalasi.

1.2 Rumusan Masalah

1.2.1 Apa saja jenis-jenis dan dosis anestesi umum inhalasi?
1.2.2 Bagaimana teknik pengaplikasian anestesi inhalasi yang diberikan pada anjing
1.2.3 Apa saja keuntungan dan kerugian dari anestesi inhalasi pada anjing?

1
 BAB II

TUJUAN DAN MANFAAT TULISAN

2.1 Tujuan

Berdasarkan rumusan masalah diatas, adapun tujuan tulisan ini adalah sebagai
berikut:

1. Untuk mengetahui jenis-jenis dan dosis anestesi inhalasi

2. Untuk mengetahui teknik pengaplikasian anestesi inhalasi pada anjing
3. Untuk mengetahui keuntungan dan kerugian anestesi inhalasi pada anjing

2.2 Manfaat Tulisan

Adapun manfaat tulisan ini adalah:

1. Melalui tulisan ini diharapkan mahasiswa kedokteran hewan, khususnya Kedokteran

Hewan Universitas Udayana memiliki wawasan lebih mengenai penggunaan anestesi
inhalasi pada anjing baik itu jenis obat, teknik aplikasi serta keuntungan dan kerugian
anestesi inhalasi.
2. Memenuhi tugas Mata Kuliah Ilmu Bedah Umum Veteriner Fakultas Kedokteran
Hewan Universitas Udayana.

2
 BAB III
TINJAUAN PUSTAKA

3.1 Anjing

Anjing adalah mamalia yang telah mengalami domestikasi dari serigala abu-abu (canis
lupus) sejak 15.000 tahun yang lalu atau mungkin sudah sejak 100.000 tahun yang lalu
berdasarkan bukti genetik berupa penemuan fosil dan tes DNA. Penelitian lain mengungkap
sejarah domestikasi anjingyang belum begitu lama (Dharmawan, 2009). Anjing adalah salah
satu hewan yang mudah bersosialisasi dengan manusia. Hubungan anjing dan manusia sudah
terjalin cukup lama sejak ratusan tahun silam. Seiring dengan meningkatnya taraf kehidupan,
minat masyarakat untuk memelihara hewan kesayangan semakin meningkat. Anjing
merupakan salah satu hewan kesayangan yang banyak dipelihara orang. Selain sebagai hewan
kesayangan anjing juga berguna untuk berburu, menjaga rumah ladang dan kebun.

Klasifikasi ilmiah dari anjing menurut Dharmawan (2009) adalah:

 Kerajaan: Animalia
 Filum: Chordata
 Subfilum: Vertebrata
 Kelas: Mamalia
 Ordo: Carnidae
 Genus: Canis
 Species: Canis lupus
 Subspecies: Canis lupus familiaris

3.2 Anestesi Umum

` Anestesi berarti suatu keadaan dengan tidak ada rasa nyeri. Anestesi umum ialah suatu
keadaan yang ditandai daengan hilangnya persepso terhadap semua sensasi akibat induksi obat.
Dalam hal ini, selain hilangnya rasa nyeri, kesadaran juga hilang. Obat anestesi umum terdiri
atas golongan senyawa kimia heterogen, yang mendepresi SSP secara reversible dengan
spectrum yang hamper sama dan dapat dikontrol. Obat anestesi umum dapat diberikan secara
inhalasi dan secara intravena. Obat anestesi umum yang diberikan secara inhalasi (gas dan
cairan yang mudah menguap) yang terpenting di antaranya adalah N2O, halotan, enfluran,
metoksifluran, dan isofluran. Obat anestesi umum digunakan secara intravena, yaitu

3
tiobarbiturat, narkotik-analgesik, senyawa alkaloid lain dan molekul sejenis, dan beberapa obat
khusus seperti ketamin. (Munaf,2008).

Stadium anestesi dibagi dalam 4 yaitu; Stadium I (stadium induksi atau eksitasi
volunteer), dimulai dari pemberian agen anestesi sampai menimbulkan hilangnya kesadaran.
Rasa takut dapat meningkatkan frekuensi nafas dan pulsus, dilatasi pupil, dapat terjadi urinasi
dan defekasi. Stadium II (stadium eksitasi involunter), dimulai dari hilangnya kesadaran
sampai permulaan stadium pembedahan. Pada stadium II terjadi eksitasi dan gerakan yang
tidak menurut kehendak, pernafasan tidak teratur, inkontinensia urin, muntah, midrasis,
hipertensi, dan takikardia. Stadium III (Pembedahan/operasi), terbagi dalam 3 bagian yiatu;
Plane I yang ditandai dengan pernafasan yang teratur dan terhentinya anggota gerak. Tipe
pernafasan thoraco-abdominal, reflex pedal masih ada, bola mata bergerak-gerak, palpebra,
konjuctiva dan kornea terdepresi. Plane II, ditandai dengan respirasi thoraco-abdominal dan
bola mata ventro medial semua otot mengalami relaksasi keuali otot perut. Plane III, ditandai
dengan respirasi regular, abdominal, bola mata kembali ke tengah dan otot perut relaksasi
kecuali otot perut relaksasi. Stadium IV (paralisis medulla oblongata atau overdosis), ditandai
denga paralisis otot dada, pulsus cepat dan pupil dilatasi. Bola mata menunjukkan gambaran
seperti mata ikan karena terhentinya sekresi lakrial (Munaf,2008).

3.3 Anestesi Umum Inhalasi

Anestetika umum inhalasi yang pertama kali dikenal dan digunakan untuk membantu
pembedahan adalah N2O. Kemudian menyusul, eter, kloroform, etil klorida, halotan,
metoksifluran, enfluran, isofluran, desfluran, sevofluran, dan xenon. Anestetika umum inhalasi
yang umum digunakan saat ini adalah halotan, enfluran, isofluran, desfluran, sevofluran, dan
xenon. Obat obat anestesi yang lain ditinggalkan, karena efek sampingnya yang tidak
dikehendaki. Misalnya, eter mudah terbakar dan meledak, menyebabkan sekresi bronkus
berlebihan, mual dan muntah, kerusakan hati, dan baunya yang sangat merangsang. Kloroform
menyebabkan aritmia dan kerusakan hati. Metoksifluran menyebabkan kerusakan hati, toksik
terhadap ginjal, dan mudah terbakar.

Anestesi umum inhalasi merupakan salah satu metode anestesi umum yang dilakukan
dengan cara memberikan agen anestesi yang berupa gas dan atau cairan yang mudah menguap
melalui alat anestesi langsung ke udara inspirasi. Terjadi anestesi karena uap yang dihirup
masuk dari alveoli mendifusi membrane alveoli dan melarut ke dalam darah paru-paru yang

4
selanjutnya dari paru-paru mendifusi masuk ke jaringan tubuh terutama otak (Sudisma et al.
2016).

Kelarutan zat inhalasi dalam darah adalah faktor utama yang penting dalam
menentukan induksi dan pemulihan anestesi inhalasi. Induksi dan pemulihan akan berlangsung
cepat pada zat yang tidak larut dan lambat pada zat yang larut. Kadar alveolus minimal atau
minimum alveolar concentration (MAC) adalah kadar minimal zat anestesi dalam alveolus
pada tekanan satu atmosfir yang diperlukan untuk mencegah gerakan pada 50% pasien yang
dilakukan rangsangan insisi standar. Immobilisasi tercapai pada 95% pasien apabila kadar
anestetikum dinaikkan di atas 30% nilai MAC.

Pada subjek normal, penggunaan anestesi inhalasi sangat tinggi pada menit pertama
dan menurun dengan cepat sesudahnya; setelah 20 menit, karena jaringan dengan kapasitas
rendah dan laju aliran tinggi mencapai kesetimbangan, penyerapannya dapat dianggap konstan.
Eliminasi anestesi inhalasi dari seseorang biasanya ditentukan oleh penurunan konsentrasi
alveolar relatif terhadap konsentrasi alveolar terakhir yang ditentukan pada akhir anestesi
(FA/FAo). Semakin rendah kelarutan anestesi, semakin cepat penurunan FA/FAo dan semakin
cepat waktu pemulihan (Torri, 2010).

5
 BAB IV

PEMBAHASAN

4.1 Jenis-Jenis Anestesi Umum Inhalasi

4.1.1 Halothane
Halothane adalah hidrokarbon terhalogenasi yang tidak mudah terbakar, tidak dapat
meledak, dilisensikan untuk digunakan di semua spesies hewan domestik di Inggris. Halothane
tidak berwarna, mudah menguap pada suhu kamar, disimpan dalam botol berwarna kuning
untuk mencegah degradasi oleh cahaya. Selain itu, halotan mengandung 0,01% timol sebagai
pengawet untuk meningkatkan stabilitasnya (Welsh, 2009).
Halotan sering digunakan sebagai induksi anestesi dikombinasikan dengan N2O, karena
halotan adalah analgesik lemah tetapi sifat anestesinya kuat sehingga kombinasi keduanya
sangat ideal. Pemeliharaan anestesi dengan halotan biasanya digunakan dosis 1-2% pada napas
spontan atau dosis 0,5-1% pada nafas terkendali. Nilai MAC halotan adalah moderat,
potensinya berada diantara metoksifluran dan isofluran, yaitu 0,3 – 0,75%. Halotan mempunyai
tekanan uap yang tinggi, sehingga memerlukan ketelitian penggunaan vaporizer yang lebih
tinggi.
Anestesi inhalasi ini sangat popular baik di kedokteran manusia maupun kedokteran
veteriner karena lebih aman, lebih mudah mengatur kedalaman stadium anestesinya, induksi
cepat antara 3-5 menit, masa pulihnya (recovery) juga cepat antara 5-15 menit. Sedangkan
kekurangannya adalah merupakan cardio-respiratory depression, sehingga harus sangat hati-
hati untuk operasi caesarean yang harus juga menyelamatkan fetusnya. Kontra indikasi untuk
pasien dengan kegagalan jantung yang kronis (Sudisma et al. 2016).
Studi mengenai halothane pernah dilakukan oleh Erwin et al. (2013) dimana halothan
digunakan pada anjing lokal dan membandingkan kadar haemoglobin dengan anjing yang
diberi anestesi injeksi. Hasilnya menunjukkan bahwa terjadi perbedaan yang sangat nyata
(P<0,01) terhadap kadar hemoglobin (g/dl) antara anestesi per inhalasi (14,28+1,71) dengan
anestesi per injeksi (12,66+0,37). Hal tersebut dikarenakan adanya suplai oksigen sebagai
pelarut dari gas anestetik (halotan) pada anestesi per inhalasi sehingga kadar oksigen darah
dapat dipertahankan dan afinitas oksigen oleh hemoglobin tidak terganggu walaupun terjadinya
hipoventilasi akibat pemberian halotan. Pemasukan oksigen sebagai pelarut dalam anestesi per
inhalasi akan mengurangi tekanan karbonmonoksida dalam darah melalui alveolus. Anestesi

6
per inhalasi memberikan nilai saturasi oksigen yang lebih stabil dibandingkan anestesi per
injeksi yang disebabkan karena adanya pemasukan oksigen.

Gambar 1 Halothane Untuk Anestesi Inhalasi

4.1.2 Desflurane
Desflurane adalah eter terhalogenasi yang telah diperkenalkan relatif baru-baru ini ke
dalam praktik anestesi manusia. Agen ini memiliki kelarutan darah : gas terendah dari semua
agen inhalasi, memungkinkan perubahan cepat dalam kedalaman anestesi dan mendorong
pemulihan yang cepat. Secara teoritis, itu juga sangat berguna untuk memberikan 'masker
induksi' anestesi yang cepat, tetapi itu menyebabkan iritasi saluran pernapasan, yang
menghasilkan batuk pada pasien yang sadar dan membatasi penggunaannya dengan teknik ini
(Welsh, 2009).
Efek desflurane pada sistem kardiovaskular dan pernapasan relatif mirip dengan
isoflurane dan sevoflurane. Desflurane memiliki nilai MAC yang relatif tinggi dibandingkan
dengan agen inhalasi lainnya (8-11%), tetapi ini tidak bermasalah karena mudah diuapkan, dan
konsentrasi tinggi mudah dicapai. Titik didih desflurane mendekati suhu kamar. Akibatnya,
agen ini membutuhkan penguap khusus yang dipanaskan dan diberi tekanan listrik, untuk
memastikan output yang konstan (Welsh, 2009).
Pengeliminasian desflurane dan waktu pemulihan lebih cepat jika dibandingkan dengan
agen inhalasi lainnya. Anestesi berkepanjangan (delapan jam atau lebih) meningkatkan waktu
pemulihan dari agen yang sangat larut, dan hal tersebut merupakan efek yang terbatas untuk
anestesi dengan kelarutan rendah, terutama untuk desflurane (Torri, 2010). Sebuah studi
dilakukan oleh Altug et al. (2009) untuk meneliti efek post-anastetik recovery desflurane
terhadap karakteristik fungsi hati dan ginjal pada anjing. Penelitian ini mengungkapkan 2 hasil
penting. Pertama, desflurane memberikan induksi anestesi yang lebih cepat, pemulihan dengan

7
lebih sedikit eksitasi dan waktu pemulihan yang cepat (p <0,05) dan anjing-anjing berdiri
dalam waktu yang lebih singkat daripada isoflurane. Kedua, penelitian ini menunjukkan baik
desflurane maupun isoflurane tidak memiliki efek samping yang berbahaya pada fungsi ginjal
dan hati pada anjing.

Gambar 2. Desflurane untuk Anestesi Inhalasi

4.1.3 Sevoflurane
Sevoflurane adalah agen inhalasi eter terhalogenasi yang sekarang banyak digunakan
dalam anestesi manusia dan hewan. Kelarutan darah: gas masih jauh lebih sedikit dibandingkan
dengan isoflurane, sehingga memfasilitasi perubahan lebih cepat dari kedalaman anestesi dan
pemulihan yang lebih cepat. Selain itu, tidak seperti isoflurane, sevoflurane tidak menyebabkan
iritasi pada saluran pernapasan dan memiliki bau yang kurang tajam, sehingga cocok untuk
induksi anestesi inhalasi. Sebuah studi yang dilakukan oleh Basha et al (2018) menunjukkan
bahwa kelompok anjing yang diberikan anestesi sevoflurane untuk ovariohysterectomy
memiliki tingkat induksi dan pemulihan yang lebih cepat secara signifikan daripada kelompok
anjing yang diberikan isoflurane yang mungkin disebabkan oleh kelarutan gas darah paling
sedikit dari sevoflurane.
Nilai MAC sevoflurane relatif sama dengan kebanyakan agen inhalasi lainnya (MAC
2,36 pada anjing dan koefisien partisi gas darah 0,68), meskipun agak lebih tinggi daripada
halothane dan isoflurane. Konsekuensi utama dari potensi yang dikurangi ini adalah bahwa
pengaturan vaporiser yang lebih tinggi diperlukan dengan sevoflurane (Welsh, 2009).

8
 Gambar 3. Sevoflurane Untuk Anestesi Inhalasi

4.1.4 Isoflurane
Isoflurane merupakan halogenasi eter dan secara kimia sangat mirip dengan
metoksifluran dan sevofluran. Rentang keamanan isofluran lebih lebar dibandingkan halotan
dan metoksifluran, sehingga sangat umum digunakan pada hewan terutama anjing dan kuda
walaupun dengan harga yang lebih mahal.
Potensi isofluran lebih kecil dibandingkan halotan karena mempunyai nilai MAC lebih tinggi
dibandingkan halotan. 1 MAC pada anjing adalah 1,3%. Uap diatur pada 3-4% pada anjing
yang diinduksi dengan aliran oksigen 60 ml/ kg/menit dan berkurang antara 1,5-3% selama
pemeliharaan dengan aliran oksigen 20 ml/kg/menit (Lee, 2012).
Penggunaaan isofluran pada dosis anestesi atau subanestesi menurunkan metabolisme
otak terhadap oksigen, tetapi akan meningkatkan aliran darah di otak dan tekanan intrakranial,

Gambar 4. Isoflurane Untuk Anestesi Inhalasi

9
sehingga menjadi pilihan pada pembedahan otak. Namun, sebuah studi dilakukan oleh Caines
et al. (2014) untuk melihat perbandingan isoflurane dan propofol untuk pemeliharaan anestesi
pada anjing dengan penyakit intracranial. Anjing yang dipelihara dengan propofol selama
pencitraan MRI memiliki tekanan arteri yang lebih tinggi, penurunan dopamin, dan skor
pemulihan yang lebih baik, dibandingkan dengan anjing yang dipelihara dengan isofluran.
Pengaruh terhadap jantung dan curah jantung (cardiac output) sangat minimal, sehingga dapat
digunakan pada pasien dengan kelainan jantung.

4.2 Teknik Pemberian Anestesi Inhalasi

Cara pemberian anestesi inhalasi adalah:
1. Auto inhalasi
Udara dihirupkan melewati permukaan anestetikum atau melewati suatu bantalan yang
dibasahi dengan anestetikum.
2. Metode umpan balik positif
Udara atau oksigen dicampur dengan 5% CO2 dihembuskan diatas permukaan
anestetika. Campuran gas ini akan dibawa ke masker atau pipa endotracheal. Metode
umpan balik positif dapat diterapkan dengan empat cara, yaitu:
• Metode terbuka
Prinsip: Obat inhalasi diteteskan pada masker (sungkup) dari kawat yang
dilapisi dengan 5-7 lembar gause. Obat akan menguap setelah bercampur
dengan udara.
Keuntungan:
• Sederhana
• Mudah dilakukan
• O2 dari udara
• Tidak terjadi akumulasi CO2
Kekurangan :
• Boros
• Mudah terjadi kebakaran/ledakan
• Dapat mengiritasi kulit muka
• Level anestesi lama tercapai
• Metode Semi Terbuka

10
 Prinsip: Sama seperti metode terbuka, kecuali sungkup ditutup kain tebal
sehingga gas anestesi bisa bertahan lebih lama
Keuntungan:
• Sama seperti metode terbuka
• Konsentrasi obat lebih tinggi
• Induksi lebih cepat
Kekurangan:
• Sama open method, dan
• Bisa terjadi akumulasi CO2 dalam sungkup (mudah terjadi hipoksia)
• Metode Tertutup
Prinsip: Obat inhalasi setelah diuapkan diinhalasikan melalui suatu sistem
tertutup. Udara ekspirasi dialirkan melalui NaOH yang dapat mengikat CO2,
sehingga udara yang mengandung anestesi dapat digunakan lagi. Jadi, terjadi
100% rebreathing dari udara ekshalasi yang CO2-nya sebelumnya diikat oleh
suatu absorbed. Cara ini lebih hemat, aman, dan lebih mudah, tetapi harga
alatnya cukup mahal.

• Metode Semi Tertutup

Prinsip: Pasien diinhalasikan melalui suatu masker tertutup yang dihubungkan
dengan suatu reservoir (breathing bag) dimana gas atau obat inhalasi bercampur
dengan O2 sebelum obat inhalasi terdahulu diuapkan melalui vaporizer. Udara
ekshalasi akan terbuang keluar melalui suatu sistem klep yang dihubungkan
dengan masker.
Keuntungan:
• Lebih irit
• Tidak terjadi akumulasi O2
• Bahaya kebakaran dan ledakan kurang
Kekurangan:
• Kalau soda lime sudah tua bisa terjadi akumulasi CO2 (CO2 narcosis)
• Debu soda lime dapat mengiritasi paru pasien (soda lime ini biasanya
ditambahkan filter)

11
 Gambar 5. Pipa Endotracheal

4.3 Keuntungan dan Kerugian Pemberian Anestesi Inhalasi

Anestesi inhalan digunakan untuk induksi dan pemeliharaan anestesi umum. Adapun
keuntungan pemberian anestesi inhalasi untuk induksi yakni:
• Menawarkan keuntungan mengontrol kedalaman anestesi secara akurat selama induksi
dengan keamanan karena dapat menghentikan pemberian anestesi inhalan segera jika
masalah muncul.
• Jika timbul masalah, anestesi inhalan (sevoflurane, isoflurane atau halothane) dapat
dihilangkan dengan cepat melalui ventilasi.
• Oksigen yang diinspirasikan biasanya tinggi saat diberikan anestesi inhalan selama
induksi.

Adapun beberapa kerugian penggunaan anestesi inhalasi sebagai induksi yakni:

• Bau menyengat dari isoflurane atau halotan dapat mendorong hewan untuk menahan
napas selama induksi dan karenanya mencegah pengambilan anestesi inhalan dan
memperlambat kecepatan induksi.
• Polusi lingkungan kerja selama induksi. Limbah gas anestesi inhalan dapat
menyebabkan sakit kepala dan masalah kesehatan lainnya.
• Ini tidak cocok untuk anjing yang sehat dan tidak dipremedikasi karena kecepatan
induksi yang relatif lambat melalui anestesi inhalan.

Keuntungan penggunaan anestesi inhalasi dalam melakukan perawatan:

• Perlindungan jalan napas - karena hampir semua pasien yang dibius dengan anestesi
inhalasi diintubasi.

12
• Kedalaman anestesi selama perawatan mudah dikontrol dengan menyesuaikan output
vaporizer, pola ventilasi dan laju aliran total.
• Oksigen yang diinspirasikan tinggi biasanya diberikan anestesi inhalan selama
perawatan. Ini akan menambah kandungan oksigen dalam darah. Ini sangat membantu
pasien dengan kapasitas pembawa oksigen rendah (pasien dengan anemia atau
disfungsi pernapasan).
• Pemulihan cepat bila dibandingkan dengan sebagian besar kombinasi yang dapat
diinjeksi. (Anestesi inhalasi sebagian besar dihilangkan melalui ventilasi, sedang kan
anestesi yang diinjeksi bergantung pada hati dan ginjal untuk metabolisme/eliminasi)

13
 BAB V
PENUTUP

5.1 Simpulan
Anestesi umum inhalasi merupakan salah satu metode anestesi umum yang dilakukan
dengan cara memberikan agen anestesi yang berupa gas dan atau cairan yang mudah menguap
melalui alat anestesi langsung ke udara inspirasi. Terjadi anestesi karena uap yang dihirup
masuk dari alveoli mendifusi membrane alveoli dan melarut ke dalam darah paru-paru yang
selanjutnya dari paru-paru mendifusi masuk ke jaringan tubuh terutama otak. Beberapa zat atau
obat yang sering digunakan pada anestesi inhalasi pada anjing diantaranya isoflurane,
halothane, sevoflurane, desflurane. Tentu diantara empat jenis anestesi inhalasi ini memiliki
tingkat anestesi, daya recovery serta MAC yang berbeda-beda. Semakin rendah nilai MAC,
semakin kuat agen anestesi. Halothane, isoflurane dan sevoflurane berada di antara satu sama
lain. Sevoflurane kurang kuat daripada halotan dan isoflurane.

5.2 Saran
Anestesi inhalasi merupakan salah satu dari sekian banyak anestesi yang ada, dalam
penerapannya tentu seorang dokter hewan harus melihat resiko dari pemberian masing-masing
jenis anestesi inhalasi. Seorang dokter hewan juga harus memilih jenis anestesi inhalasi yang
tepat ketika melakukan tindakan pembedahan mulai dari tingkat anestesi, daya recovery dan
MAC karena ketika salah memilih akan menimbulkan dampak yang bisa menyebabkan
kerugian pada pasien dan owner.

14
 DAFTAR PUSTAKA

Altug, M.E. Gonenci, R. Durgut, R., Karasu, A., Abdulhayoglu. B. 2009/. Effects of
Desflurance and Isoflurance on Postanaesthetic Recovery Characteristics with Hepatic
and Renal Functions in Dogs. Journal of Animal and Veterinary Advances; 8(2): 350-
357. ISSN: 1680-5593.

Basha, K, M, A., Lingappa, R., Nagaraja, B., Kamran, C., & Swamy, M. 2018. Induction and
Recovery Characteristics of Isoflurane and Sevoflurane Anesthesia for
Ovariohysterectomy in Dogs. International Journal of Livestock Research; 8(7): 122-
130. doi: 10.5455/ijlr.20171206072401

Caines, D., Sinclair, M., Valcerde, A., Dyson, D., Galtero, L., Woodt, D. 2014. Comparison of
isoflurane and propofol for maintenance of anesthesia in dogs with intracranial disease
undergoing magnetic resonance imaging. Formerfy the Journal of Veterinary
Anaesthesia; 41: 468-479.

Dharmawan NS. 2009. Anjing Bali dan Rabies. Penerbit Buku Arti: Denpasar.

Dharmayuda, A.A.G., Gorda, I.W., Wardhita, A.A.G.J. 2012. Perbandingan Anestesi Xylazin-
Ketamin Hidroklorida dengan Anestesi Tiletamin-Zolazepam terhadap Frekuensi
Denyut Jantung dan Pulsus Anjing Lokal. Buletin Veteriner Udayana; 4(1): 9-15.

Erwin, Nuzul, A., Zuraida, Hadi, E.S. 2013. Kadar Hemoglobin Selama Induksi Anestesi Per
Inhalasi dan Anestesi Per Injeksi pada Anjing Lokal (Canis lupus familiaris). Jurnal
Medika Veterinaria; 7(2): 98-100.

Lee, L. 2012. Canine and Feline Anaesthesia. Veterinary Surgery I, VMED 7412.

Maya, E. 2006. Pengaruh Anestesi Per-injeksi dan Anestesi Per-inhalasi terhadap Nilai
Saturasi Oksigen dan Nilai Fisiologis Lainnya pada Kucing Lokal (Felis domestica)
selama Enterotomi. Skripsi. Fakultas Kedokteran Hewan, Institut Pertanian Bogor:
Bogor.

15
McKelvey D, Hollingshead KW. 2003. Veterinary Anesthesia and Analgesia 3rd Ed.
California, USA: Mosby.

Torri. G. 2010. Inhalation anesthetics: a review. Minerva Anestesiologica; 75(3): 215-228.

Welsh, L. 2009. Anaesthesia for Veterinary Nurses. Blackwell Publishing Ltd: United
Kingdom.

16
Buletin Veteriner Udayana Vol. 4 No.1. :9-15
ISSN : 2085-2495 Pebruari 2012

Perbandingan Anestesi Xylazin-Ketamin Hidroklorida dengan Anestesi Tiletamin-

Zolazepam terhadap Frekuensi Denyut Jantung dan Pulsus Anjing Lokal
(COMPARISON EFFECT OF ANESTHESIA XYLAZINE-KETAMINE
HYDROCHLORIDE WITH ANESTHESIA TILETAMINE-ZOLAZEPAM
ADMINISTRATION TO HEART PULSE FREQUENCY AND
PULSE IN LOCAL DOGS)
A. A.G. Oka Dharmayudha 1), I Wayan Gorda 2), A.A.G.Jaya Wardhita \2)
1)
Laboratorium Radiologi 2)Laboratorium Bedah
Fakultas Kedokteran Hewan -UNUD
E-mail : o_dharmayudha@yahoo.com
ABSTRAK
Penelitian dilakukan untuk mengetahui perbedaan pengaruh pemberian anestesi xylazin-
ketamin dengan anestesi tiletamin-zolazepam terhadap frekuensi denyut jantung dan pulsus
pada anjing lokal. Penelitian ini menggunakan Rancangan Acak Lengkap (RAL) pola split
in time dengan dua. perlakuan yaitu, perlakuan I : xylazin-ketamin (2 mg/kgbb xylazin,15
mg/kgbb ketamin) dan perlakuan II: tiletamin-zolazepam (20 mg/kgbb), masing-masing
perlakuan menggunakan 5 ekor anjing sebagai ulangan, sehingga secara keseluruhan
anjing yang digunakan sebanyak 10 ekor. Data yang diperoleh dianalisis dengan. Uji Sidik
Ragam. Hasil penelitian diperoleh bahwa perbedaan perlakuan tidak berpengaruh nyata
(P>0,05) terhadap frekuensi denyut jantung dan pulsus, akan tetapi waktu pengamatan
selain anjing dianastesi sangat berpengaruh terhadap frekuensi denyut jantung dan
berpengaruh nyata terhadap frekuensi pulsus.
Kata kunci : xylazin-ketamin, tiletamin-zolazepam, frekuensi denyut jantung, frekuensi
pulsus, anjing lokal.
ABSTRACT
A study to determine the effect of anesthesia xylazine- ketamine hydrochlorida with
anesthesia tiletamine-zolazepam administration to heart pulse frequency and pulse during
anesthetion. The experimental was carried duct on local dog. The experimental design use
was a splite in time with 2 treatment : treatment I xylazin-ketamin ( 2 mg/Kg Body weight
of xylazine ; 15 ing/Kg Body weight ketarnine) and treatment II tiletamine-zolazepam ( 20
mg/Kg Body weight). Each treatment use 5 dogs as refrain so we use 10 dogs for all of the
treatment. Obtain data is analized by various investigated test. Result of this study indicated
that difference of treatment there were no significance, but time of the observed during
anesthesion showed more highly significance and significant to pulse frequency.
Key words : xylazine-ketamine, tiletamine-zolazepam, heart pulse frequency, pulse
frequency, local dogs
PENDAHULUAN digemari adalah anjing. Anjing termasuk
ke dalam Ordo, carnivora, Famili :
Dengan semakin bertambahnya populasi canidae, Class : mamalia (Murray, 1986).
hewan peliharaan maka membawa Menurut Dharma, dkk., (1999) di Bali
pengaruh terhadap animo masyarakat mempunyai dua kelompok anjing yaitu
untuk memelihara hewan kesayangan. anjing kampung (anjing geladak) dan
Diantara hewan kesayangan yang banyak
9
Buletin Veteriner Udayana
ISSN : 2085-2495
anjing Kintamani yang terdapat di daerah
Kintamani,
Kecintaan masyarakat terhadap anjing
memberikan arti tersendiri bagi
pemiliknya, selain sebagai hewan
peliharaan dan penjaga rumah anjing juga
sudah memiliki nilai ekonomi yang cukup
tinggi dan mulai disenangi oleh
masyarakat kalangan ekonomi menengah
ke atas. Disamping itu pula anjing
memiliki beberapa keistimewaan antara
lain; bulunya indah, pintar, lucu, dapat
dilatih untuk membantu manusia dan juga
bisa menjadi teman bermain.
Demikian penting peranan anjing, maka
segala sesuatu yang berhubungan dengan
kesehatannya merupakan hal yang harus
diutamakan dan harus mendapatkan
perhatian. Dalam menangani kesehatan
anjing, tidak jarang para dokter hewan
memerlukan transqualizer (penenang) dan
anestetik (obat bius) yang erat kaitannya
dengan pembedahan. Sebelum melakukan
pembedahan perlu diberikan anestesi
sesuai dengan kebutuhan apakah anestesi
umum atau lokal. Cara pemberian
anestesi juga bervariasi ada yang
diberikan secara intra vena,
intramuskuler, inhalasi atau bisa juga
dikombinasikan.
Anestesi umum pada anjing dapat
diberikan secara parenteral atau inhalasi.
Salah satunya adalah kombinasi Xylazin-
Ketamin Hidroklorida. Kombinasi kedua
obat ini mempunyai beberapa keuntungan
yaitu; ekonomis, mudah dalam
pemberiannya, induksinya yang cepat,
mempunyai pengaruh relaksasi yang baik
serta jarang menimbulkan komplikasi
klinis. Kombinasi kedua obat ini sudah
pernah dilaporkan penggunaannya pada
anjing dan kucing (Benson, dkk., 1985),
burung unta (Gandini, dkk., 1986).
Menurut Walter (1985), kombinasi
xylazin-ketamin merupakan agen
10
Vol. 4 No.1. :9-15
Pebruari 2012
kombinasi yang saling melengkapi antara
etek analgesik dan relaksasi otot serta
sangat baik dan efektif untuk anjing
karena memiliki rentang keamanan yang
lebar.
Namun kendala yang ditimbulkan adalah
dosis pemberian pada anjing ras yang
memiliki keragaman yang kompleks,
kelebihan dosis pada anjing ras dapat
berakibat fatal, dan sering anjing
teranestesi dengan dosis tinggi memiliki
waktu pemulihan yang lama, sehingga
dapat menimbulkan rasa panik bagi
pemilik maupun dokter hewan yang
melakukan operasi. Disamping itu pula
kombinasi xylazin-ketamin hidroklorida
dapat mengakibatkan penurunan yang
nyata pada denyut jantung, output
jantung, volume, stroke, efektifitas
ventilasi alveolar, dan transport oksigen
(Steve dkk., 1986).
Agen anestesi lain yang dapat digunakan
selain kombinasi xylazin-ketamin
liidroklorida adalah kombinasi tiletamin
hidroklorida dengan zolazepam
(diazepinon transquilizer), kedua zat ini
dikombinasikan dengan perbandingan
yang sama dan mempunyai sirnbol CI-
774, preparat tersebut telah dievaluasi
melalui injeksi secara parenteral pada
berbagai spesies hewan di laboratorium
(Virbac., 1992), akan tetapi sejauh mana
kombinasi obat ini mampu menutupi efek
negatif dari kombinasi xylazin-ketamin
terutama terhadap denyut jantung dan
pulsus belum banyak diketahui serta
untuk mengetahui perbandingan obat
anestesi mana yang lebih. efektif dan
aman sebagai anestesi pada anjing, maka
dari itu penelitian ini dilakukan.
METODE PENELITIAN
Materi Penelitian
Buletin Veteriner Udayana Vol. 4 No.1. :9-15
ISSN : 2085-2495 Pebruari 2012

Hewan yang digunakan pada penelitian
ini adalah anjing lokal jantan dengan
berat badan 7-10 kg sebanyak 10 ekor.
Sebelum dilakukan tindakan anestesi,
dilakukan pemeriksaan fisik dan
diadaptasikan selama satu minggu.
Bahan dan obat-obatan yang dipakai
adalah ketamin hidroklorida (Ketamil 100
mg/ml diproduksi oleh Ilium, Australia),
xylazin hidroklorida (ilium xylazil
20mg/ml diproduksi oleh Ilium.
Australia), gabungan tiletamin-zolazepam
(Zoletil 50 diproduksi oleh
Virbac,Perancis), dan atropin sulfat
(0,25mg/ml).
Metode Penelitian
Dalam penelitian ini digunakan
kombinasi dosis yaitu xylazin 2 mg/kg
dan ketamin hidroklorida 15mg/kg yang
diberikan secara intramuskuler sebagai
perlakuan I. Pada perlakuan II diberikan
anestesi kombinasi tiletamin dan
zolazepam dengan dosis 20 mg/kg secara
intra muskuler. Lima belas menit sebelum
anestesi, diberikan atropin sulfat sebagai
premedikasi dengan dosis 0,04 mg/kg
secara subkutan pada kedua perlakuan.
Variabel yang diamati adalah frekuensi
denyut jantung dan pulsus 30 menit
sebelum dianestesi, saat teranestesi,
setelah 30 menit, 60 menit, dan setelah 90
menit periode teranestes. Frekuensi
denyut jantung dihitung dengan
menggunakan stetoskop dan frekuensi
pulsus dihitung dengan menekan arteri
femoralis dengan jari. Kedua variabel
dihitung frekuensinya permenit.
Penelitian ini menggunakan Rancangan
Acak Lengkap (RAL) pola split in time
Tabel 1. Hasil Rata -Rata Total Frekuensi Denyut Jantung pada Setiap Perlakuan
dan Waktu Pengamatan yang Berbeda pada Anjing Jantan Lokal
dengan. dua perlakuan yaitu XK 2:15 dan
ZZ 20, secara berturut-turut
menggunakan dosis 2 mg/kg xylazin
dengan 15 mg/kg ketamin hidroklorida
dan 20 mg/kg Zoletil (zolazepam-
tiletamin). Setiap perlakuan
menggunakan lima ekor anjing sebagai
ulangan, sehingga jumlah anjing yang
digunakan adalah 10 ekor. Data yang
diperoleh diuji dengan menggunakan
Sidik Ragam dan bila di dapatkan hasil
yang berbeda nyata dilanjutkan dengan
uji Wilayah Berganda Duncan (Stell dan
Totrie, 1989).
HAS1L DAN PEMBAHASAN
Hasil Penelitian
Total frekuensi denyut jantung
Rerata frekuensi denyut jantung disajikan
pada Tabel 1. dari pemberian anestesi
xylazin-ketamin hidroklorida dengan
tiletamin-zolazepam adalah 122,56
x/menit dan 130,0 x/menit dengan rata-
rata masing-masing perlakuan 30 menit
sebelum dianestesi (T -30) atau T kontrol,
saat mulai teranestesi T(0), saat
teranestesi 30 menit T(30), 60 menit
T(60), 90 menit T(90 ) adalah 134,4
x/menit, 140,0x/menit 126,0 x/menit,
117,0 x/menit dan 114,0 x/menit. Hasil
sidik ragam pada tabel 2 menunjukkan
bahwa perlakuan memberikan hasil yang
tidak berbeda nyata (P>0,05) terhadap
frekuensi denyut jantung, akan tetapi
waktu pengamatan menunjukan
perbedaan yang sangat nyata (P<0,01)
terhadap frekuensi denyut jantung pada
anjing jantan lokal.

Perlakuan -30 0 30 60 90 Rerata

X+K 129,6 136,8 125,2 110,8 110,4 122,56
T+Z 139,2 1-13,2 126,8 123,2 117,6 130,0

11
Buletin Veteriner Udayana Vol. 4 No.1. :9-15
ISSN : 2085-2495 Pebruari 2012

Pengaruh waktu terhadap frekuensi tidak berbeda nyata, sedangkan pada

denyut jantung perlakuan II: tiletamin-zolazepam
(20mg/kgbb) mengalami peningkatan
Pengaruh waktu pada frekuensi denyut yang sangat nyata. Pada T (0) dan
jantung ; T (0) berbeda sangat nyata mengalami penurunan pada T (30) -
terhadap T (90), T (60) dan terhadap T T(90).
(30) sedangkan dengan T (-30) tidak
berbeda nyata. T (60) tidak berbeda nyata Total frekuensi pulsus
terhadap T (90).
Rerata total frekuensi pulsus disajikan
pada Tabel 4, yakni dengan pemberian
anestesi xylazin-ketamin hidroklorida
dengan tiletamin-zolazepam adalah
116,56x/menit dan 115,60 x/menit
dengan rata-rata masing-masing
perlakuan 30 menit sebelum dianestesi
(T-30) atau T kontrol, saat mulai
teranestesi T(0), saat teranastesi 30 menit
Keterangan: FDJ (Frekuensi Denyut T(30), 60 menit T(60), 90 menit T(90)
Jantung(x/ menit)
adalah 116,8 x/menit,124,8 x/menit 115,6
Perlakuan I : Anestesi xylazin-ketamin
hidroklorida x/menit, 114,0 x/menit dan 109,2 x/menit.
Perlakuan II : Anestesi tiletamin- Hasil sidik ragam pada Tabel 5
zolazepam menunjukkan bahwa perlakuan
memberikan hasil tidak berbeda nyata,
Perlakuan 1 : xylazin (2 mg/kgbb), akan tetapi waktu pengamatan
ketamin (15 mg/kg BB) mengalami menunjukan perbedaan yang nyata
peningkatan yang sangat nyata dibanding terhadap frekuensi pulsus pada anjing
T (-30) terhadap T (0) dan mengalami jantan lokal.
penurunan pada T (30 ) dan T (60), T (90)

Tabel 2. Rerata frekuensi pulsus pada setiap perlakuan dan waktu pengamatan yang
berbeda pada anjing jantan lokal.

Perlakuan -30 0 30 60 90 Rerata

X+K 116,4 123,2 118,0 114,4 110,8 116,56
T+Z 117,2 126,4 113,2 113,6 107,6 115,6

Pengaruh waktu terhadap frekuensi tidak berbeda nyata, terhadap T (30).

pulsus Pada Lampiran 2, perlakuan I : Xylazin
(2mg/kgbb), ketamin (15mg/kgbb)
Pengaruh waktu terhadap firekuensi mengalami peningkatan nyata dibanding
pulsus : T (0) berbeda nyata terhadap T T (-30) terhadap T (0) dan menurun pada
(60) dan T (90), sedangkan dengan T (- T (30) - T (90), sedangkan pada
30) tidak berbeda nyata. T (0) dan T (-30) perlakuan II : Tiletamin-zolazepam (20
12
Buletin Veteriner Udayana
ISSN : 2085-2495
mg/kg BB) mengalami peningkatan yang
nyata pada T (0) dan mengalami
penurunan pada T (30) sampai dengan T
(90).
Ket, FP: Frekuensi Pulsus(x/menit)
Perlakuan I : Anestesi xylazin-
ketamin hidroklorida
Perlakuan II : Anestesi tiletamin-
zolazepam
Pembahasan
Hasil penelitian menunjukkan bahwa
pada kedua perlakuan mengalami
peningkatan frekuensi denyut jantung dan
frekuensi pulsus dibanding kontrol (T-30)
dan mengalami penurunan pada T (30) -
T (90) setelah pemberian. Hasil penelitian
ini menunjukkan bahwa perbedaan
perlakuan yang diberikan tidak berbeda
nyata terhadap frekuensi denyut jantung
dan pulsus pada anjing lokal jantan. Hal
ini disebabkan oleh kedua perlakuan yang
diberikan tenyata memberikan kekuatan
yang sama pada perangsangan
kardiovaskuler yaitu menaikkan tekanan
darah sistolik daa diastolik dan kecepatan
pulsus meningkat (Aitkison dan
Rushman, 1993).
Walaupun secara statistik perbedaan
perlakuan yang digunakan memberikan
pengaruh yang sama terhadap denyut
jantung dan frekuensi pulsus, tetapi rerata
denyut jantung pada tiletamin-zolazepam
jauh lebih tinggi dari pada xylazin-
ketamin hidroklorida. Perbedaan denyut
jaatung tersebut terjadi karena anestesi
tiletamin-zolazepam lebih kuat pada
13
Vol. 4 No.1. :9-15
Pebruari 2012
jantung. Hal ini sesuai dengau pendapat
Virbac, (1992) yang menyatakan bahwa
anestesi tiletamin-zolazepam pada anjing
dapat menimbulkan takikardia,
peningkatan tekanan darah yang bersifat
sementara dan induksi polipnea.
Peningkatan denyut jantung pada anjing
disebabkan efek tiletamin-zolazepam
dapat mencapai jantung dan merangsang
saraf simpatis. Cohen, (1979)
menyatakan, efek anestesi umum selain
mengenai susunan saraf pusat juga
sampai pada jantung, Denyut jantung
berada di bawah kontrol saraf otonom dan
perangsangan saraf simpatis pada jantung
dapat meningkatkan denyut jantung dan
intensitas jantung (Knight, 1989). Hasil
penelitian ini sesuai dengan Cullen dan
Reynoldson (1997), yang membuktikan
bahwa anestesi tiletamin-zolazepam dapat
menyebabkan peningkatan tekanan arteri
dan denyut jantung pada anjing.
Perbedaan waktu pengamatan
menunjukkan hasil yang berbeda sangat
nyata terhadap frekuensi denyut jantung
dan berbeda nyata terhadap frekuensi
pulsus. Meningkatnya frekuensi denyut
jantung dan pulsus pada perlakuan 1
disebabkan oleh pengaruh ketamin
sebagai perangsang kardiovaskuler,
dimana adanya efek antidysrhthymia
yang mencegah reflek adrenergik hasil
reaksi dari pembuluh darah sekelilingnya
menurun mengakibatkan terjadinya
vasodilatasi pada jaringan terutama oleh
reseptor α- adrenergik dan vasokonstriksi
oleh reseptor β (Smith dan Aitkenheard,
1996). Pada menit ke-30 sampai menit
ke-90 terjadi penurunan dimana efek dari
xylazin sudah mulai terlihat. Xylazin
menyebabkan penurunan aktivitas
simpatetik dan efek depresor pada umpan
balik baroreseptor dan inenunmkan
tekanan vagal yang dihasilkan oleh
ketamin pada penurunan denyut jantung
(Mustafa, dkk., 2000). Hasil ini sesuai
dengan penelitian Sepiawati (2002), yang
Buletin Veteriner Udayana Vol. 4 No.1. :9-15
ISSN : 2085-2495 Pebruari 2012

membuktikan bahwa kombinasi dosis Saran

xylazin (2 mg/kgbb) dan ketamin (15
mg/kgbb) dapat meningkatkan frekuensi
denyut jantung saat teranestesi pada
anjing lokal.
Meningkatnya frekuensi denyut jantung
dan frekuensi pulsus pada perlakuan II
disebabkan oleh efek tiletamin-zolazepam
dapat mencapai jantung dan merangsang
saraf simpatis. Eenstein, dkk., (1994),
menyatakan kombinasi tiletamin-
zolazepam dapat meningkatkan takikardia
dengan pengaruh sedikit pada tekanan
darah arteri dan out put jantung. Hasil
penelitian ini sesuai dengan penelitian
Cullen dan Reynoldson (1997), yang
membuktikan bahwa anestesi tiletamin-
zolazepam dapat menyebabkan
peningkatan denyut jantung dan tekanan
rerata arteri pada anjing. Sedangkan
penurunan denyut jantung saat teranestesi
pada T(30) - T(90) disebabkan oleh
anestesi tiletamin-zolazepam tidak
mengalami pcrubahan yang nyata pada
denyut jantung (Hellyer, dkk,, 1989).
SIMPULAN DAN SARAN
Simpulan
Pemberian anestesi xylazin-ketamin
hidroklorida dengan anestesi
tiletamin-zolazepam tidak menimbulkan
efek yang berbeda terhadap frekuensi
denyut jantung dan frekuensi pulsus pada
anjing jantan lokal. Sedangkan waktu
pengamatan pada pemberian anestesi
xylazin-ketamin hidroklorida dengan
anestesi tiletamin-zolazepam sangat nyata
meningkatkan frekuensi denyut jantung
dan pulsus saat induksi dan mengalami
penurunan saat pengamatan 30, 60 dan 90
menit teranestesi pada anjing lokal jantan.
Anestesi xylazin-ketamin dengan anestesi
teletamin-zolazepam aman digunakan
sebagai agen anestesi pada anjing lokal,
karena kedua anestesi ini tidak
menimbulkan efek yang berbeda pada
frekuensi denyut jantung dan pulsus.
Sedangkan anestesi xylazin-ketamin
dengan anestesi teletamin-zolazepam
dapat menstimuli sistem kardiovaskuler
dan sistem pernafasan sehingga tidak
disarankan diberikan pada anjing yang
mengalami gangguan pada sistem
kardiovaskuler maupun sistem
pernafasan. Olehkarena itu perlu
dilakukan penelitian lebih lanjut pada
kedua anestesi ini dalam dosis yang
berbeda.
DAFTAR PUSTAKA
Aitkisan, R.S dan G.B. Rushman. 1993.
f.ee 's Synopsis of Anesthesia, The
Iowa State University Press, James
Lowa, USA.
Benson, G.J, J.C. Thurmon, W.J
Tranquilli, dan C.W. Smith. 1985.
Cardiopulmonary Effects of an
Intravenous Infusion of
Ouaifenesin,Kelamine,,and
Xylazine in Dogs. Am. J. Vet. Res.
Vol. 49 : 1896-1898.
Booth, N.H., DM. Jl.Mayer, dan L.E, Me.
Donald. 1977. Velerinery
Pharmacology. The Iowa State
University Press. USA Hal: 295-
297.
Cullen, LK, dan J.A. Reynoldson. 1997.
Effects Tiletamine/Zolazepam
Premedication on Propofol
Anesthesia in Dogs. Vet.Rec. : 140 :
363-6.
Dliarma, DM, N, Hartuiingsih, M. D.
Rudyanto. 1999. Anjing Bali
Pemuliabiakan dan Pelestarian,
Penerbit Kauisius.

14
Buletin Veteriner Udayana Vol. 4 No.1. :9-15
ISSN : 2085-2495 Pebruari 2012

Gandini, G.G.M., R.H Keffen, R.E.J. Soma. L.R. 1979. Preanasthetic

Barrough, dan H. Fleedes. 1986. An Medication.Dalam Textbook of
Anesthetic Combination of Veterinary Anestesia L.R.Soma
Ketamine, Xylazine and .Macmillan Publishing Co.,
Alphaxalone-alphadalone in Oestrcl Inc.USA.: 149-150.
(Sinithiocamelus). Vet. Rec. 118:
729-730. Smith,G. dan A.R. Aitkenheard. 1996.
Text Book of Anestesia. Iowa States
HellyerJP,, W W. Muir, J.A. Hubble, dan University Press.Ameus Iowa .USA.
J, Sally. 1989. Cardi or expiratory
Effect of The Intravenous Steel, R.G.D. dan J.H Torrie. 1989.
Administration of Tiletamin- Principle and Procedures of
Zolazepam to Dogs.18(2); 160-5 Statistic.Prinsip dan Prosedur
(medline). Statistik Suatu Pendekatan
Biometrik Alih Bahasa Bambang
Hieder, H. J,H A. Prufer, P. Mischke dan Siunantri.PT.Grainedia Jakarta:
S. Oetjen. 1993. Clinical 168-229,
Experience. With an Injectable
Anesthetic Combination of Steve, C, Haskins, John, P. Far\'er, T.B.
Teletamine and Zolazepam in Cats. 1986. Xylazine and Kelamine in
Veterinary Bulletin. 63(2): 184. Dogs. Am. J. Vet. Res. : 636-640.

Knight, D.H, 1989. Heart Rate. Dalam Wulandari, N. 1998. Peruhahan

Textbook of Veterinery Internal Klinikpada Kucing Lokal selama
MedicuieJDisease of the Dogs and Pembiusan dengan Telstamin-
Cat. SJ. Ettiiiger (ed.) 3th ed. W,B. Zolazepam. Skripsi. Fakultas
savuiders Company. Philadelphia. Kedoktetan Hewan, Universitas
USA. : 901. Udayana, Denpasar,

Mustafa, Yilmaz Koc,Fahretti Alkan, Wilson, R.P., I.S. Zagon, D.R. Larach,
Zeki Ogurtan. 2000. The Effect of dan C.M Lang. 1993.
Xylazine -Ketamine and Diazepam- Cardiovascular and Respiratory
Ketamine.QJVR. Effects of rih.tamin-Zo!azepam.
Pharmacol. Biochem. Behav. : 1-8.
Murray, F.E. 1986. Zoo and Wild Animal (Medline).
Medicine.2M ed.Saunders Company
Philadelpia. Toronto London. Walter, H.H. 1985. Xylazin-Pentobarbital
Anasthesia in Dog and Its
Sepiawati, M. 2002. Pengaruh Kambinasi Antagonism Yohimbin. Am. J. Vet.
Xylazin-Ketamin Hidroklohda Ress : 852-855.
Terhadap Frekuensi Denyut Jantung
dan Nafas pada Anjing Lokal. Wilson dan Gisvold. 1982. Teks Book of
Skripsi. Fakultas Kedokteran Organic Medical and
Hewan, Universitas Udayana, Pharmaceutical Chemistry. Edisi ke-
Denpasar. 8. Diterjemahkan oleh Fatali,
Medisinal Organik. IKID. Semarang
Press

15
Jurnal Medika Veterinaria Vol. 7 No. 2, Agustus 2013
ISSN : 0853-1943

KADAR HEMOGLOBIN SELAMA INDUKSI ANESTESI PER INHALASI

DAN ANESTESI PER INJEKSI PADA ANJING LOKAL
(Canis lupus familiaris)
The Haemoglobin Concentration during Inhalation Anaesthetics and Injection
Anaesthetics on Canis lupus familiaris
Erwin1, Nuzul Asmilia1, Zuraida1, dan Ela Sesdapepi Hadi2
1
Laboratorium Klinik Fakultas Kedokteran Hewan Universitas Syiah Kuala, Banda Aceh
2
Program Studi Pendidikan Dokter Hewan Fakultas Kedokteran Hewan Universitas Syiah Kuala, Banda Aceh
E-mail: slankducati@ymail.com

ABSTRAK
Penelitian ini bertujuan mengetahui pengaruh anestesi per inhalasi dan anestesi per injeksi terhadap kadar hemoglobin anjing lokal. Hewan
coba yang digunakan adalah 6 ekor anjing jantan lokal dengan umur 4-5 bulan dengan berat badan 5-6 kg. Anjing dibagi menjadi 2 kelompok,
masing-masing kelompok terdiri atas 3 ekor anjing. Kelompok 1 (K1) diinduksi dengan halotan 3%, setelah teranestesi diturunkan menjadi 1%
untuk maintenance sedangkan kelompok 2 (K2) diinjeksi dengan ketamin 10 mg/kg bobot badan dan xylazin 1 mg/kg bobot badan. Pengambilan
darah dilakukan pada menit ke-0, 10, 20, 30, 40, dan 50 melalui vena cephalica dan dilakukan pemeriksaan kadar hemoglobin dengan metode
Sahli. Data yang diperoleh dianalisis menggunakan analisis varian pola split plot. Hasil penelitian menunjukkan bahwa terjadi perbedaan yang
sangat nyata (P<0,01) terhadap kadar hemoglobin (g/dl) antara anestesi per inhalasi (14,28+1,71) dengan anestesi per injeksi (12,66+0,37),
namun tidak terjadi perbedaan yang nyata (P>0,05) pada masing-masing periode pengamatan. Dari hasil tersebut dapat disimpulkan bahwa
pemakaian anestesi per inhalasi lebih aman dibandingkan anestesi per injeksi berdasarkan kadar hemoglobin.
___________________________________________________________________________________________________________________
Kata kunci: anestesi, per inhalasi, per injeksi, hemoglobin

ABSTRACT
This study aimed to observe the effect of per injection and inhalation anesthesia to the concentration of local dog’s haemoglobin.
Experimental animals that used in this study were 6 local dogs aged about 4-5 months and weight of 5-6 kg. Dogs were divided into 2 groups,
each group consisted of 3 dogs. First group was induced with halothane 3% and 1% for maintanance while second group was injected by
ketamine 10 mg/kg BW and xylazin 1 mg/kg BW. The blood was collected in minute 0, 10, 20, 30, 40, 50 from cephalica venous, haemoglobin
was measured using Sahli method. The obtained data were analyzed using analysis of variance with split-plot pattern. The statistical data
showed that there was significant difference (P<0.01) in the level of haemoglobin (g/dl) between the treatment group of inhalation (14.28+1.71)
and injection (12.66+0.37), but there are no significant difference (P>0.05) in observation period. In conclusion, the administration of inhalation
anesthesia saver than injection anesthesia based on haemoglobin concentration.
___________________________________________________________________________________________________________________
Key words: anesthesia, per inhalation, per injection, haemoglobin

PENDAHULUAN Banyak diantara penyakit tersebut yang tidak dapat

Anjing adalah salah satu hewan yang mudah
bersosialisasi dengan manusia. Hubungan anjing dan
manusia sudah terjalin cukup lama sejak ratusan tahun
silam. Manusia primitif bahkan memanfaatkan anjing
untuk teman berburu (Davis, 2006). Seiring dengan
meningkatnya taraf kehidupan, minat masyarakat untuk
memelihara hewan kesayangan semakin meningkat.
Anjing merupakan salah satu hewan kesayangan yang
banyak dipelihara orang. Selain sebagai hewan
kesayangan anjing juga berguna untuk berburu, menjaga
rumah ladang dan kebun. Oleh karena itu kesehatan
hewan perlu diperhatikan agar senantiasa sehat, lincah,
dan dapat melanjutkan keturunan. Untuk menjaga
kelestarian hewan, maka manusia perlu memperhatikan
pemeliharaan yang baik dengan cara memberikan
makanan yang cukup dan bergizi serta memberikan
perhatian terhadap kesehatan hewan. Salah satu cara
untuk menjaga kesehatan hewan adalah dengan
pencegahan penyakit (preventif) dan pengobatan yang
sesuai dengan penyebab penyakit (Maya, 2006).
Berbagai jenis penyakit dapat menyerang anjing,
baik yang bersifat infeksius maupun non-infeksius.
ditangani dengan obat-obatan, sehingga untuk
penanganannya dibutuhkan tindakan pembedahan.
Untuk keberhasilan dan kelancaran bedah, anestesi
umum memegang peranan penting. Anestesi umum
dapat diberikan secara parenteral dan inhalasi. Menurut
Siswandono dan Soekarjo (1995), pemberian anestesi
per injeksi akan menekan fungsi saraf sehingga
menyebabkan penurunan fungsi fisiologis, sedangkan
pada anestesi per inhalasi oksigenisasi dapat
dipertahankan karena adanya pemasukan oksigen yang
cukup walaupun terjadi penurunan fungsi fisiologis
yang lain. Kekurangan oksigen akan menyebabkan
gangguan metabolisme tubuh karena kadar oksigen
untuk reaksi oksidasi di jaringan tidak mencukupi.
Kadar oksigen dalam darah yang berikatan dengan
hemoglobin disebut dengan saturasi oksigen (SpO2).
Perubahan dari saturasi oksigen dapat juga disebabkan
adanya proses perdarahan saat dilakukan operasi yang
menyebabkan berkurangnya darah dan berakibat
penurunan pengikatan oksigen oleh darah (Schutz,
2001). Menurut Maya (2006), anestesi per inhalasi
memberikan nilai saturasi oksigen yang lebih stabil
dibandingkan dengan anestesi per injeksi.

98
Jurnal Medika Veterinaria
Hemoglobin merupakan senyawa pembawa oksigen
pada sel darah merah. Hemoglobin dapat diukur secara
kimia dan jumlah Hb/100 ml darah dapat digunakan
sebagai indeks kapasitas pembawa oksigen pada darah.
Hemoglobin di dalam darah membawa oksigen dari
paru-paru ke seluruh jaringan tubuh dan membawa
kembali karbondioksida dari seluruh sel ke paru-paru
untuk dikeluarkan dari tubuh. Kadar hemoglobin
normal pada anjing berkisar 12-18 g/dl (Smith dan
Mangkoewidjojo, 1988). Oleh karena anestesi dapat
mempengaruhi fungsi fisiologis tubuh, maka perlu
diketahui pengaruh dari anestesi per inhalasi dan
anestesi per injeksi tersebut terhadap kadar hemoglobin
anjing lokal.Penelitian ini bertujuan mengetahui
pengaruh anestesi per inhalasi dan per injeksi terhadap
kadar hemoglobin anjing lokal dan melihat perbedaan
periode waktu pengamatan terhadap kadar hemoglobin
pada masing-masing kelompok perlakuan.
MATERI DAN METODE
Penelitian ini dilaksanakan di Laboratorium Klinik
Bedah Fakultas Kedokteran Hewan Universitas Syiah
Kuala. Pelaksanaan penelitian dimulai dari bulan
Pebruari-Maret 2013. Pemeriksaan sampel dilakukan di
Laboratorium Patologi Klinik Universitas Syiah Kuala.
Dalam penelitian ini digunakan anjing jantan lokal
sebanyak 6 ekor dengan berat badan 5-6 kg dan umur
4-5 bulan. Seluruh anjing dibagi ke dalam 2 kelompok,
masing-masing terdiri atas 3 ekor anjing. Sebelum
anestesi dilaksanakan, anjing dipuasakan terhadap
makanan selama 6-12 jam dan puasa minum selama 2-6
jam. Kelompok 1 (K1) merupakan kelompok anjing
yang dianestesi secara per inhalasi dengan halotan,
dosis 3% untuk induksi awal sedangkan untuk
maintenance digunakan 1%. Pada Kelompok 2 (K2),
anjing diberi premedikasi atropin sulfat dengan dosis
0,04 mg/kg bobot badan secara subkutan. Selanjutnya
diinjeksi dengan kombinasi ketamin-xylazin secara
intramuskular dengan dosis sebagai berikut:
1. Xylazin 2% dengan dosis 1-2 mg/kg bobot badan
= bobot badan x dosis obat
konsentrasi obat
= bobot badan x 1 mg/kg bobot badan
20 mg/1 ml
2. Ketamin 10% dengan dosis 10-15 mg/kg bobot badan
= bobot badan x dosis obat
konsentrasi obat
= bobot badan x 10 mg/kg bobot badan
100 mg/1 ml
Pengambilan Darah
Pengambilan darah dilakukan pada menit ke-0, 10,
20, 30, 40, dan 50 melalui daerah vena cephalica
(terlebih dulu daerah sekitar vena cephalica
dibersihkan dengan alkohol 70%) sebanyak 1 ml.
Darah dikoleksi ke dalam vacutainer yang berisi
ethylenediaminetetraacetic acid (EDTA). Pemeriksaan
Erwin, dkk
Hb dilakukan di Laboratorium Patologi Klinik
Universitas Syiah Kuala.
Pemeriksaan Hemoglobin
Dalam penelitian ini digunakan metode Sahli.
Darah hewan coba yang telah dikoleksi diisap dengan
pipet Sahli sampai tepat angka 20. Uung pipet
dibersihkan dengan kertas saring. Kemudian darah
dalam pipet tersebut dimasukkan ke dalam tabung
hemometer Sahli yang telah diisi 2 tetes larutan HCl
0,1 N sebelumnya dan dibiarkan selama 3-5 menit.
Dilakukan pengenceran dengan akuades sambil diaduk
dengan batang pengaduk sampai warna sampel darah
sama dengan warna standar. Selanjutnya dibaca skala
yang tertera pada tabung haemometer Sahli (miniskus
bawah). Hasilnya dinyatakan dalam g/dl.
Parameter Penelitian
Parameter yang diukur selama penelitian ini adalah
kadar hemoglobin anjing lokal (Canis lupus familiaris)
selama anestesi per inhalasi dan anestesi per injeksi.
Analisis Data
Data kadar hemoglobin yang diperoleh dianalisis
dengan analisis varian pola split-splot menggunakan
statistical product and service solutions (SPSS) 18.
HASIL DAN PEMBAHASAN
Rata-rata kadar hemoglobin anjing (Canis lupus
familiaris) pada daerah tropis adalah 12-18 g/dl (Smith
dan Mangkoewidjojo, 1988). Hasil penelitian ini
menunjukkan bahwa rata-rata kadar hemoglobin anjing
lokal antara kedua kelompok perlakuan masih berada
dalam batas yang normal dan menunjukkan perbedaan
yang sangat nyata (P<0,01). Rata-rata nilai hemoglobin
(g/dl) antara kedua kelompok perlakuan disajikan pada
Tabel 1.
Tabel 1. Rata-rata (+ SD) kadar hemoglobin (g/dl) anjing
lokal setelah anestesi inhalasi dan anestesi injeksi
Kelompok perlakuan Kadar hemoglobin (g/dl)
Halotan (K1) 14,28+1,71a
Ketamin-xylazin (K2) 12,66+0,37b
a, b
Superskrip yang berbeda pada kolom yang sama menunjukkan
perbedaan yang sangat nyata (P<0,01).
Berdasarkan analisis diketahui bahwa waktu
pengamatan dan interaksi waktu pengamatan dengan
perlakuan tidak menunjukkan perbedaan yang nyata
(P>0,05). Peningkatan kadar hemoglobin pada K1
mulai terjadi pada menit ke-10 (13,60+0,69 g/dl) tidak
menunjukkan perbedaan yang nyata dengan menit ke-
20 (14,33+2,08 g/dl), sedangkan pada K2 peningkatan
yang mulai terjadi pada menit ke-10 (13,06+0,41 g/dl)
tidak berbeda nyata dengan menit ke-20 (12,80+0,34
g/dl). Peningkatan dan penurunan kadar hemoglobin
pada masing-masing waktu pengamatan disajikan pada
Tabel 2.
99
Jurnal Medika Veterinaria
Tabel 2. Rata-rata (+ SD) kadar hemoglobin (g/dl) anjing
yang diinduksi halotan dan injeksi kombinasi ketamin xylazin
Waktu Kelompok perlakuan
pengamatan Halotan (P1) Ketamin-xylazin(P2)
0 12,66 + 0,30 12,66 + 0,41
10 13,60 + 0,69 13,06 + 0,41
20 14,33 + 2,08 12,80 + 0,34
30 14,86 + 2,20 12,60 + 0,34
40 14,93 + 0,11 12,46 + 0,23
50 15,33 + 2,08 12,40 + 0,34
Hemoglobin merupakan kompleks protein globulin
(Wintrobe, 1974). Hemoglobin berikatan dengan empat
pigmen heme dan juga mampu mengikat empat
molekul O2 untuk membentuk oksihemoglobin.
Swenson (1970) menyatakan hemoglobin dalam darah
berkaitan dengan kemampuan darah membawa oksigen
dan warna merah darah. Faktor yang mempengaruhi
kadar hemoglobin adalah kondisi tubuh, jenis kelamin,
lingkungan, dan nutrisi. Satu gram hemoglobin mampu
mengikat 1,36-1,39 ml oksigen. Rata-rata kadar
hemoglobin mamalia 10-15 g/dl (Cunningham, 1992).
Jumlah oksigen dalam darah ditentukan oleh jumlah
oksigen terlarut dan jumlah hemoglobin yang ikut
dalam aliran darah (Ganong, 1995).
Kadar hemoglobin tidak menunjukkan perbedaan
yang nyata pada masing-masing waktu pengamatan.
Pada K1, kadar hemoglobin cenderung naik dan stabil.
Menurut Lumb dan Jones (1996) ini dikarenakan
adanya suplai oksigen sebagai pelarut dari gas anestetik
(halotan) pada anestesi per inhalasi sehingga kadar
oksigen darah dapat dipertahankan dan afinitas oksigen
oleh hemoglobin tidak terganggu walaupun terjadinya
hipoventilasi akibat pemberian halotan. Pemasukan
oksigen sebagai pelarut dalam anestesi per inhalasi
akan mengurangi tekanan karbonmonoksida dalam
darah melalui alveolus. Peningkatan PO2 akan
mengurangi PCO2 dan pembentukan H+ dan ion
karbonat tubuh sehingga meningkatkan afinitas oksigen
oleh hemoglobin (Soma, 1997). Noviana (2009)
menambahkan bahwa anestesi per inhalasi memberikan
nilai saturasi oksigen yang lebih stabil dibandingkan
anestesi per injeksi yang disebabkan karena adanya
pemasukan oksigen.
Peningkatan kadar hemoglobin K-2 pada menit ke-10
disebabkan oleh efek obat anestesi yang meningkatkan
frekuensi denyut jantung dan cardiac output.
Peningkatan stimulasi myocardial dalam pemompaan
jantung berhubungan dengan peningkatan kerja jantung
100
Vol. 7 No. 2, Agustus 2013
dan suplai oksigen bagi myocardial. Meningkatnya
suplai oksigen merupakan hasil dari cardiac output dan
penurunan hambatan pembuluh darah coronari, sehingga
jantung harus bekerja keras agar hemoglobin dapat
mengikat oksigen secara maksimal (Lumb dan Jones,
1996). Kadar hemoglobin pada K-2 cenderung menurun
setelah menit ke-20. Akan tetapi penurunan tersebut
masih berada dalam batas normal. Menurut Cunningham
(1992) penurunan kadar hemoglobin di bawah batas
normal dalam waktu yang lama dapat menyebabkan
hipoksia yang berakhir dengan kematian jaringan. Pada
anestesi per-injeksi jumlah oksigen yang masuk
tergantung pada kemampuan sistem respirasi untuk
menghirup oksigen. Siswandono dan Soekardjo (1995)
menambahkan bahwa pemberian ketamin-xylazin dapat
menekan kerja pons dan medulla oblongata sebagai
pusat pengatur sistem pernafasan.
KESIMPULAN
Anestesi per inhalasi lebih aman dibandingkan
anestesi per injeksi berdasarkan pemeriksaan kadar
hemoglobin.
DAFTAR PUSTAKA
Cunningham, J.G. 1992. Veterinary Physiology. WB Saunders
Company, Philadelphia.
Davis, C. 2006. Sikap-sikap Anjing yang Normal.
http://www.anjingkita.com/wmview.php? ArtID=2300
Ganong, W.F. 1995. Buku Ajar Fisiologi Kedokteran. A. Petrus
(Penterjemah). EGC, Jakarta.
Lumb, W.V. and E.W. Jones. 1996. Veterinary Anesthesia. 2nd ed.
Washington Square, Philadelphia.
Maya, E. 2006. Pengaruh Anestesi Per-injeksi dan Anestesi Per-
inhalasi terhadap Nilai Saturasi Oksigen dan Nilai Fisiologis
Lainnya pada Kucing Lokal (Felis domestica) selama
Enterotomi. Skripsi. Fakultas Kedokteran Hewan, Institut
Pertanian Bogor, Bogor.
Noviana. 2009. Pengaruh anestesi terhadap saturasi oksigen (SpO2)
selama enterotomi pada kucing lokal (Felis domestica). Hemera
zoa/ Majalah Ilmu Kehewanan Indonesia. 1(1):1-3.
Schutz, S.L. 2001. Oxygen Saturation Monitoring By Pulse
Oxymetry. In Procedur Manual of Critical Care. 4th ed. WB
Saunders Company, Philadelphia.
Siswandono dan Soekardjo. 1995. Kimia Medisinal. Airlangga
University Press, Surabaya.
Smith, S, dan S. Mangkoewidjojo. 1988. Pemeliharaan, Pembiakan
dan Penggunaan Hewan Percobaan di Daerah Tropis. UI
Press, Jakarta.
Soma, L.R. 1997. Textbook of Veterinary Anesthesia. 3rd ed. The
Williams & Wilkins Company, Baltimore.
Swenson, M.J. and G. Reece. 1970. Duke’s Physiology of Domestic
Animals. 7th ed. Cornell University Press, Ithaca USA.
Wintrobe. 1974. Clinical Haematology. 7th ed. Lea and Febiger,
Philadelphia.
See discussions, stats, and author profiles for this publication at: https://www.researchgate.net/publication/277891461

Effects of Desflurane and Isoflurane on Postanaesthetic Recovery

Characteristics with Hepatic and Renal Functions in Dogs

Article  in  Journal of Animal and Veterinary Advances · January 2009

CITATION READS

1 131

7 authors, including:

Muhammed Enes Altuğ Ramazan Gönenci

Mustafa Kemal University Mustafa Kemal University
62 PUBLICATIONS   318 CITATIONS    24 PUBLICATIONS   132 CITATIONS   

SEE PROFILE SEE PROFILE

Some of the authors of this publication are also working on these related projects:

z_yurtal@hotmail.com View project

All content following this page was uploaded by Muhammed Enes Altuğ on 08 June 2015.

The user has requested enhancement of the downloaded file.

 M E D W E L L Journal of Animal and Veterinary Advances 8 (2): 350-357, 2009
ISSN: 1680-5593
P U B L I S H I N G © Medwell Journals, 2009

Effects of Desflurane and Isoflurane on Postanaesthetic Recovery

Characteristics with Hepatic and Renal Functions in Dogs
1
M.E. Altug, 1R. Gonenci, 2R. Durgut, 3A. Karasu and 4B. Abdulhayoglu
1
Department of Surgery, 2Department of Internal Medicine,
Faculty of Veterinary Medicine, University of Mustafa Kemal, Hatay, Turkey
3
Department of Surgery, Faculty of Veterinary, University of Yuzuncu Yil, Van, Turkey
4
Antakya State Hospital, Specialist of Anaesthesiology, Hatay, Turkey

Abstract: The aim of the study, was to investigate the effects of desflurane and isoflurane on postanaesthetic
recovery characteristics with hepatic and renal functions in dogs. Sixteen adult mongrel dogs of both sexes
weighing between 16-21 kg were equally divided into 2 groups. Anaesthesia was induced with 0.3 mg kgG1
midazolam and 10 mg kgG1 thiopental intravenously. Maintenance of anaesthesia was continued with 7.2-8%
desflurane or 1.3-1.5% isoflurane. Heart and respiration rates, arterial haemoglobin oxygen saturation and rectal
temperatures were monitored before, during, 1 h and 1 day after anaesthesia periodically and postanaesthetic
recovery score times were also observed. Serum alanine aminotransferase, aspartate aminotransferase, (-
glutamyltransferase, blood urea nitrogen, total bilirubin and creatinine levels were measured in venous blood
samples. Postanaesthetic recovery scores including time to standing, time to reaching sternal recumbency, eye
opening and time to extubation were found shorter in desflurane group than isoflurane group (p<0.05). Alanine
aminotransferase, aspartate aminotransferase and (-glutamyltransferase activities were non-significantly
increased in the isoflurane group and there were no change between groups. Total bilirubin and creatinine
levels were non-significantly decreased, blood urea nitrogen levels were non-significantly increased within
normal range during and after the anaesthesia in both groups. The present study reveals 2 important results.
Firstly, desflurane provided faster anaesthetic induction, recovery with less excitation and rapid recovery times
(p<0.05) and the dogs stood up in shorter time than those of isoflurane. Secondly, this study indicates that both
volatile agents have no harmful side effects on renal and hepatic functions in dogs.

Key words: Desflurane, isoflurane, dog, postanaesthetic recovery scores, renal and hepatic functions

INTRODUCTION anaesthesia cause liver injury in man. There are several

Desflurane is a new inhalation anaesthetic agent with
rapid induction and fast recovery due to its low blood/
gas solubility ratio (0.42) (Clutton, 1998; O'Keeffe and
Healy, 1999; Go´mez-Villamandos et al., 2000;
Go´mez-Villamandos et al., 2006). Animal studies suggest
that desflurane undergoes the least metabolism
compared to all the volatile agents (Koblin et al., 1989).
Isoflurane undergoes approximately 0.2% metabolism and
desflurane metabolism is estimated to be 1-10th of that
(Koblin et al., 1989; Schmidt et al., 1999). This indicates
that tissue toxicity is unlikely (Sutton et al., 1991).
Desflurane anaesthesia has generally not been
associated with deterious effects on the liver and kidney
(O'Keeffe and Healy, 1999). However, recent studies
(Nishiyama et al., 1998; Tiainen et al., 1998; Schmidt et al.,
1999) have reported that isoflurane and desflurane
studies evaluating hepatic function during desflurane
anaesthesia in humans (Sutton et al., 1991; Zaleski et al.,
1993; Wissing and Kuhn, 2000) and isoflurane in dogs
(Topal et al., 2003). Isoflurane is also used as a common
inhalational anaesthetic agent, but its clinical application
related to desflurane is limited in the veterinary practice.
While there have been several studies (Tsai et al., 1992;
Smith et al., 1994; Dexter and Tinker, 1995; Dupont et al.,
1999; Hedenqvist et al., 2001; Ozturk and Altug, 2007)
suggesting therapid emergence of desflurane compared
with isoflurane, to date, no studies have compared
isoflurane directly with desflurane on recovery
characteristics with hepatic and renal effects in dogs.
Thus, the present study was designed to compare the
postanaesthetic recovery characteristics of desflurane
and isoflurane inhalation anaesthetics and their hepatic
and renal haemodynamic effects in dogs.

Corresponding Author: Muhammed Enes Altug, Department of Surgery, Faculty of Veterinary Medicine,
University of Mustafa Kemal, TR-31040 Hatay, Turkey
350
 J. Anim. Vet. Adv., 8 (2): 350-357, 2009
MATERIALS AND METHODS
Animals and experimental procedures: The dogs were
supplied from Antakya Municipality Dog Care House.
The experiments were conducted in accordance with the
Animal Research Ethics Committee of University of
Mustafa Kemal, Faculty of Veterinary Medicine. The
animals were vaccinated and observed for 30 days prior
to the experimental procedure. Based on a clinical
examination such as electrocardiographic and ultrasound
evaluations of the heart, liver and kidneys and complete
blood count, parasite profiles and serum biochemical
analyses, all dogs were classed as ASA (American
Society of Anaesthesiologists) class I. Sixteen healthy
mongrel dogs, 18.2±5.4 years old and weighing
(means±SD) 17.8±3.2 kg were used in this study and the
dogs were randomly divided into 2 equal groups
(for each groups; male: 4, female: 4). There were no
significant differences between groups with respect to
sex, age or body mass. Anaesthesia theatre temperature
was kept at between 18-22°C and humidity, 60-65%. Food,
but not water, was withheld for at least 12 h before the
start of the anaesthesia protocols.
Induction and inhalation anaesthesia procedures:
Anaesthetic protocols were designed as midazolam +
thiopental + desflurane (DES group) and midazolam +
thiopental + isoflurane (ISO group). Ten minutes prior to
induction of anaesthesia, the dogs received atropine
sulphate (Atropan® 2 mg mLG1; Vetas, Istanbul, Turkey)
at the dose rate of 0.04 mg kgG1 intramuscularly to control
salivation and then an intravenous catheter was placed
in the cephalic vein to infuse Lactated Ringer’s solution
(Eczacibasi-Baxter, Istanbul, Turkey) at the rate of
10 mL kgG1hG1. Anaesthesia was induced with 0.3 mg kgG1
midazolam (Dormicum® 5 mg mLG1, Roche, Istanbul,
Turkey) and 10 mg kgG1 thiopental (Pentotal Sodyum®
0, 5 g, Abbott, Istanbul, Turkey) intravenously (1/3; with
rapid infusion, its remainder; slow infusion) in all animals.
No supplement dosages were administered thereafter. The
dogs were positioned in left lateral recumbency during
anaesthesia. Following endotracheal intubation with a
cuffed tube, a semi-closed circle rebreathing anaesthesia
system was connected to the endotracheal tube and the
animals were delivered 100% oxygen. The initial vaporizer
settings were started with 1.5% isoflurane or 8.0%
desflurane in oxygen (3 L minG1) for induction of inhalant
anaesthetics and anaesthesia maintenance was continued
for 70 min with 7.2% desflurane (Suprane®, Baxter,
Munich, Germany) or 1.3% isoflurane (Aerrane®, Baxter,
Illinois, USA). Carbon dioxide was removed from the
circuit using soda lime. At the end of anaesthesia
351
procedure, the inhaled anaesthetics were discontinued
and the lungs were ventilated with 100% oxygen at a
fresh gas flow rate of 3 L minG1. The concentration of
desflurane and isoflurane were also chosen according
to previous reports in dogs. The vaporizer and the
monitoring devices were calibrated before the study
according to manufacturer’s instructions. Anaesthesia
maintenance was performed in the 2 groups with an
anaesthesia machine (AMS 200, Ankara, Turkey) and
vaporizers (Desflurane-Datex Ohmeda Tec 6 Plus
vaporizer, USA; Isoflurane-Blease Datum® vaporizer,
England). The induction times of inhalant agents
were also calculated from time to starting of the
volatile gas infusion and sings of associated with the
3rd stage (plane 2) of general anaesthesia (Thurmon et al.,
1999).
Postanaesthetic recovery characteristics: The trachea
was extubated when a regular spontaneous breathing
pattern had been reestablished and then all dogs
observed in the Post-Anaesthesia Care Unit (PACU) for
the next 3 h and the animal care unit for 1 day. Time to
reaching a Postanaesthetic Recovery Scores (PARS)
including time to extubation, time to standing, time to
reaching sternal recumbency, time to return of head
control, tongue control, eye opening and absence of anal
reflex and adverse effects during the recovery period such
as presence or absence of vomiting, coughing and
excitation were recorded. Time to extubation was
measured from time interval between the disconnection of
the volatile anaesthetic maintenance and the removal of
the endotracheal tube. Time to sternal recumbency was
recorded from time in minutes from time to extubation until
voluntary return to sternal recumbency. Time to standing
were also recorded from time in minutes from time to
extubation to stand up.
Cardiopulmonary responses: Heart Rate (HR, beats
minG1), Respiration Rate (RR, beats minG ),1 arterial
oxyhaemoglobin saturation (SpO2, %) and rectal
temperature (°C) of all animals in this experiment were
monitored at baseline, 20 (induction), 50, 70 and 90 min
(anaesthesia maintenance) and then 1 h after and one day
after, respectively. Respiration rates (RR, beats minG1)
were evaluated with auscultation of lungs and rectal
temperatures were measured using a digital thermometer.
Heat lamps were used to maintain rectal temperature at
approximately 38°C during anaesthesia. Heart Rate
(HR, beats minG1) and SpO2 (%) were monitorised using a
pulse oximeter (Criticare 504DX Pulse Oximeter,
Waukesha, USA), which was noninvasively placed
on ears.
 J. Anim. Vet. Adv., 8 (2): 350-357, 2009
Evaluating hepatic and renal functions: Venous blood
samples were taken at baseline, 20 (induction), 50 and
90 min (anaesthesia maintenance) and then 1 h after and
1 day after, respectively. Serum was separated by
centrifugation at 3000 rpm for 5 min, collected into a
microfuge tube. The obtained serum samples were
evaluated on the same day. Serum Alanine
Aminotransferase (ALT), aspartate Aminotransferase
(AST), (-Glutamyl-Transferase (GGT), Blood Urea
Nitrogen (BUN), Total bilirubin (Tbil) and Creatinine (Cr)
levels were measured using Teco diagnostic kits in an
autoanalyser (Autolab, Analyzer Medical System, Roma,
Italia) for 2 groups.
Statistical analysis: Data are reported as means±standard
deviation. Statistical evaluations were accomplished
with the standard statistical software (SPSS version 13,
Chicago, IL, USA). Continuous variables were tested for
normality with the Kolmogorov-Smirnov test. Data were
analysed with repeated measures ANOVA for the time
effect in each group; when indicated, a Bonferroni’s
correction was performed for post hoc comparisons. The
differences between groups at each time point were
evaluated with use independent t-test. Differences were
considered significant when p<0.05.
RESULTS
Induction and inhalation anaesthesia findings: The
induction of anaesthesia with midazolam and thiopental
was rapid and smooth and endotracheal tubes were
inserted without any trouble in all dogs. Induction of the
inhalation anaesthesia was generally smooth, apart from
airway irritation was observed in 2 animals in the
desflurane group. The times of the inhalation induction
were found shorter in desflurane group than isoflurane
Fig. 1: Mean times to reaching Postanaesthetic Recovery Score (PARS) and inhalation induction times in dogs. Data are
expressed as mean±SD; *p<0.05 versus the desflurane group, **p<0.01 versus the desflurane group
352
group (Fig. 1, p<0.01). In desflurane group, more coughing
(in 4 of 8 cases) was experienced immediately after
extubation when compared to isoflurane (in 1 of 8 cases).
Postanaesthetic recovery findings: Emergence from
anaesthesia was generally smooth and also vomiting was
not seen in any cases. Time to reaching a PARS such as
time to extubation, time to standing, time to reaching
sternal recumbency, time to return of head control, tongue
control, eye opening and absence of anal reflex were
presented in Fig. 1. PARS times were found shorter in
desflurane group than isoflurane group. The differences
of time to standing, time to reaching sternal recumbency,
eye opening and time to extubation between desflurane
and isoflurane group after anaesthesia were statistically
significant (Fig. 1, p<0.05). The dogs in desflurane group
stood up in shorter time with less excitation than those of
isoflurane.
Cardiopulmonary responses: The changes of heart rate,
respiration rate and arterial oxyhaemoglobin saturation
(SpO2) measurements in the groups and the statistical
differences between the groups were presented in
Table 1. The heart rate of animals in both groups
increased at induction and maintenance of anaesthesia
(p<0.005). The respiration rate significantly decreased at
induction and maintenance of anaesthesia in both groups
(p<0.05). The level of SpO2 significantly decreased at
induction of anaesthesia with thiopental (p<0.05) and
slightly non-significantly increased during anaesthesia in
each group. During and after anaesthesia, the differences
of respiration rate and SpO2 between desflurane and
isoflurane groups were not found significant, but the
increases of the heart rate in desflurane group were found
significantly higher than isoflurane group (p<0.05).
 J. Anim. Vet. Adv., 8 (2): 350-357, 2009

Table 1: Cardiopulmonary parameters before, during and after Desflurane (DES) and Isoflurane (ISO) anaesthesia in dogs
Before Induction and inhalation anaesthesia maintenance (min) After anaesthesia
anaesthesia --------------------------------------------------------------------------------------------- ---------------------------------
Parameters baseline 20th 30th 50th 70th 90th 1 h after 24 h
HR (Beats minG1)
DES 101±15 190±35§ 168±26§ 146±29*† 148±30†* 153±33†* 127±23** 102±18
ISO 88±15 160±27§ 147±32§ 122±19 116±15 112±14 94±15 92±13
RR (Beats minG1)
DES 30.8±9.8 30.1±21 19.5±7.8 14.2±7.8† 15.9±5.5 18.0±4.9 28.6±12 29.7±9.7
ISO 31.6±9.6 28.0±11 20.8±8.5 15.6±6.3† 15.8±4.7 17.6±4.7 33.8±8.1 21.4±3.1
SpO2 (%)
DES 96.8±1.6 92.1±2.1† 96.1±3.3 97.2±1.7 97.8±1.8 97.9±1.3 95.7±2.5 96.5±1.7
ISO 95.9±2.1 90.3±1.6† 97.8±3.1 97.4±1.5 98.2±1.5 97.8±1.3 95.3±2.3 95.8±2.7
HR: Heart Rate, RR: Respiration Rate; SpO2: arterial oxyhaemoglobin saturation; Data are expressed as mean±SD; †: p<0.05 compared with before anaesthesia
the measurements in the group; §: p<0.005 compared with before anaesthesia the measurements in the group; *p<0.05 versus the ISO group; **p<0.01 versus
the ISO group

Table 2: The markers of hepatic and renal functions before, during and after Desflurane (DES) and Isoflurane (ISO) anaesthesia in dogs
Before Induction and inhalation anaesthesia maintenance After anaesthesia
anaesthesia --------------------------------------------------------------------------- -------------------------------------------
baseline 20th min 50th min 90th min 1 h after 24 h
ALT U LG1
DES 41.4±23.2 35.6±22.3 32.1±29.2 24.8±12.8 41.3±23.0 34.2±25.9
ISO 37.4±12.4 34.8±12.9 35.6±10.5 32.3±12.1 46.5±22.9 46.2±18.4
AST U LG1
DES 37.7±31.1 34.0±25.6 31.5±24.5 31.2±7.2 29.5±29.8 33.7±37.2
ISO 36.5±19.9 35.4±13.7 35.8±14.6 36.1±10.7 43.4±16.6 45.8±27.4
GGT U LG1
DES 4.1±3.5 4.2±4.2 4.1±1.2 4.0±2.0 4.3±3.1 4.3±3.7
ISO 4.2±3.0 4.3±2.4 4.4±2.8 4.3±1.5 5.1±1.1 5.5±1.4
Cr mg dLG1
DES 0.89±0.3 0.83±0.3 0.77±0.1 0.77±0.1 0.78±0.2 0.81±0.1
ISO 0.95±0.3 0.78±0.1 0.76±0.1 0.71±0.1 0.74±0.1 0.77±0.06
Tbil mg dLG1
DES 0.07±0.04 0.04±0.02 0.03±0.02 0.04±0.02 0.03±0.02 0.05±0.04
ISO 0.06±0.02 0.05±0.02 0.04±0.02 0.05±0.03 0.03±0.02 0.05±0.02
1
BUN mg dLG
DES 22.2±3.7 23.4±4.0 25.7±1.9 24.6±1.3 24.9±2.0 24.3±2.2
ISO 21.2±7.7 21.1±8.0 21.3±7.7 23.0±8.0 22.8±3.8 27.1±3.8
Data are expressed as mean±SD; There were no statistically significant differences between the study groups (p<0.05)

Hepatic and renal function markers: The values of ALT,
AST, Cr, Tbil, BUN and GGT in groups and between
groups were presented in Table 2. In the isoflurane group,
ALT, AST and GGT activities non-significantly increased
1 h and one day after anaesthesia. In the desflurane
group, these enzymes retained within normal ranges.
Tbil and Cr levels were non-significantly decreased within
normal range during and after anaesthesia in both groups.
BUN levels in desflurane and isoflurane groups were non-
significantly increased during and after anaesthesia.
DISCUSSION
The Minimum Alveolar Concentration (MAC) of
desflurane and isoflurane in dogs has been reported
between 7.2 and 10.3% (Doorley et al., 1988;
Hammond et al., 1994; Go´mez-Villamandos et al., 2006)
and 1.28 and 1.30% (Steffey and Howland, 1977;
Steffey et al., 1994), respectively. In this study, the MAC
of both volatile anaesthetics were selected on the basis
of earlier reports corresponding with desflurane
(Doorley et al., 1988; Hammond et al., 1994;
Go´mez-Villamandos et al., 2006) and isoflurane
(Steffey and Howland, 1977; Steffey et al., 1994). We
initially used a vaporizer anaesthetic concentration goal
of 1.5% isoflurane and 8.0% desflurane for induction of
anaesthesia. After reaching time to surgical anaesthesia
the concentrations (%) of volatile gases were reduced to
1.3% for isoflurane and 7.2% (1 MAC) for desflurane in
maintenance of anaesthesia. These rates were seen
adequate to maintain anaesthesia in the dogs.
Desflurane has been shown to result in a more rapid
emergence and faster recovery than isoflurane in human
(Tsai et al., 1992; Smith et al., 1994; Dexter and Tinker,
1995; Dupont et al., 1999), rabbit (Hedenqvist et al., 2001)
and rats (Öztürk and Altug, 2007). Tsai et al. (1992) stated
that the quality of recovery was also felt to be better, with
less shivering and less delirium in the desflurane patients.
Martin et al. (2001) also reported that dogs anaesthesized
with desflurane stood up between 12.5-13.5 min, in
addition, Dexter and Tinker (1995) found that human
patients given desflurane were discharged a mean of

353
 J. Anim. Vet. Adv., 8 (2): 350-357, 2009
4.4 min earlier than those given isoflurane. In our study,
times of the inhalation induction and PARS times
including time to standing, time to reaching sternal
recumbency, eye opening and time to extubation were
shorter in desflurane group than isoflurane group,
respectively as presented Fig. 1 (p<0.05). Recovery scores
were also superior in the desflurane group as reported by
Martin et al. (2001). In addition, Smith et al. (1994) noticed
that eye opening and time to tracheal extubation were
shorter as found in our study. The data obtained in this
study were consistent with the studies mentioned above.
The results may be explained by the fact that desflurane
has a lower blood-gas solubility coefficient than that of
isoflurane (0.42 versus 1.4), indicating that induction and
recovery from isoflurane anaesthesia is more rapid
(Sutton et al., 1991; Clutton, 1998; Öztürk and Altug,
2007). To our knowledge, the present study is the first
report, which compared in detail the influence of
desflurane and isoflurane administration on recovery
characteristics in dogs.
The circulatory effects of desflurane are parallel to
those of isoflurane (Weiskopf et al., 1995; Clarke et al.,
1996). As with isoflurane, if the concentration of
desflurane is increased rapidly to concentrations
exceeding 1 MAC, sympathetic activity and heart rate
then increase (Clarke et al., 1996). In the study, although
both anaesthetic agents increase heart rate, the increases
of the heart rate during desflurane were significantly
higher than that of isoflurane. These findings might be an
indication for a more depressant effect on the cardiac
vagal activity of desflurane in comparison with isoflurane
as reported (Picker et al., 2001).
As the other inhaled anaesthetics, desflurane causes
dose-dependent respiratory depression. The magnitude
of respiratory depression seems to be similar that of
isoflurane and it is expressed in drastic decreases of
respiration rate (Clarke et al., 1996). Desflurane extremely
irritates to the airways with its sympathetic stimulation
effects (Clarke et al., 1996), with concentrations of 6%
or more causing coughing, breath holding and
laryngospasm, making it unsuitable to use for inhalation
induction in both children and adults (Zwass et al., 1992).
In this study, the levels of respiration rate significantly
decreased during anaesthesia in both groups (p<0.05). In
the desflurane group was experienced more coughing
immediately, after extubation than isoflurane. It shows
that isoflurane is less irritating to the airways compared
to desflurane in dogs. These findings are consistent
with other reports noting that desflurane is an airway
irritant (Zwass et al., 1992; Clarke et al., 1996). When
spontaneous respiratory inspiration and expiration were
allowed in slight anaesthesia, frequent respiration was
seen during the desflurane induction. This finding is
similar to that reported by Clarke et al. (1996).
354
Karzai et al. (1998) showed that desflurane and
isoflurane decrease arterial oxyhaemoglobin saturation
(SpO2) compared to propofol anaesthesia. Dupont et al.
(1999) found that isoflurane and desflurane provided
similar haemodynamic effects and arterial oxygenation.
Weiskopf et al. (1995) reported that desflurane maintains
myocardial, hepatic, intestinal and sceletal muscle blood
flow, although, isoflurane decreases intestinal and skeletal
muscle blood flow in a dose dependent manner and
decreases tissue perfusion at various degrees, depending
on systemic hypotension in vasculary beds in dogs.
In the present study, SpO2 levels significantly (p<0.005)
decreased immediately after receiving midozolam and
thiopental, but during desflurane and isoflurane
maintenance non-significantly increased SpO2 without
significant difference between 2 volatile anaesthetics in
regard to arterial oxygenation. This finding was contrary
to the report by Weiskopf et al. (1995) and Karzai et al.
(1998), whereas it was consistent with research by
Dupont et al. (1999). In this study, SpO2 was >95% during
desflurane and isoflurane administration in all dogs. The
occurrence that isoflurane and desflurane increased
arterial oxygenation was probably as a result of the fact
that they were delivered in oxygen.
Elevated serum levels of aminotransferase and
bilirubin activity have been regarded as the gold standard
for anaesthetic-related hepatic toxicity in humans
(Zaleski et al., 1993; Nishiyama et al., 1998; Wissing and
Kuhn, 2000) and animals (Bernard et al., 1990;
Topal et al., 2003). Sutton et al. (1991) and Zaleski et al.
(1993) reported that desflurane affected liver function
minimally or not at all in adults. In addition, Wissing and
Kuhn (2000) expressed that there was no any observed
toxic effect on liver of desflurane exposure. This may
be related to its minimal biodegradation and the rapid
elimination after anaesthesia. Nishiyama et al. (1998)
states that isoflurane increases the levels of AST, ALT
and Tbil and leads to hepatic damage. Topal et al. (2003)
reported that isoflurane significantly increased ALT and
AST activities 2 days after anaesthesia and GGT activities
significantly increased seven days after anaesthesia.
In the present study, ALT, AST and GGT levels
non-significantly increased without resulting in hepatic
damage in isoflurane group 1 h and one day after
anaesthesia. These findings were inconsistent with those
of Nishiyama et al. (1998) and Topal et al. (2003) results.
On the other hand, these enzymes retained in the normal
reference limits in desflurane group. These findings
confirm that isoflurane and desflurane affect liver
functions minimally and not cause hepatotoxicity in dogs.
The levels of ALT and AST in desflurane group were
consistent with previous human reports (Sutton et al.,
1991; Zaleski et al., 1993; Wissing and Kuhn, 2000).
Conversely, the findings of the present study were
 J. Anim. Vet. Adv., 8 (2): 350-357, 2009
inconsistent with those of Steffey et al. (2000) results,
indicating AST activity increased by desflurane in horses.
Nephrotoxicity, directly attributable to halothane and
isoflurane, or their metabolites has not been reported in
dogs (Clutton, 1998). In addition, there is no evidence of
about renal toxicity of desflurane, even after prolonged
exposure. Eger et al. (1997) examined markers of renal
function (urinary albumin, glucose, "-glutathione-S-
transferase and serum creatinine and blood urea nitrogen)
before and for up to 7 days after exposure to 8 h of 1.25
times MAC desflurane and they found no evidence of
renal injury. As for hepatic function, desflurane only
minimally affects renal function in human patients
(Sutton et al., 1991; Weiskopf et al., 1995), dogs
(Merin et al., 1991) and horses (Steffey et al., 2000).
Zaleski et al. (1993) noticed that desflurane and isoflurane
seemed to be unaffected both renal function and blood
flow. In addition, Wissing and Kuhn (2000) reported that
Tbil and Cr remained unchanced or decreased. In our
study, it was seen that Tbil and Cr levels non-significantly
decreased and also BUN levels were non-significantly
increased during and after anaesthesia in both groups
(p>0.05, Table 2). The levels of Cr and Tbil obtained are
consistent with Wissing and Kuhn’s results (2000).
Therefore, it may be suggested that these agents not
attributed nephrotoxicity and occured similar renal effects.
CONCLUSION
The present study reveals 2 important results. Firstly,
desflurane provided faster anaesthetic induction, time
to standing, time to reaching sternal recumbency, eye
opening and tracheal extubation in a shorter time and
more rapid recovery than isoflurane. Secondly, this study
suggests that both volatile agents have similar effects on
kidney and liver functions without lead to renal and
hepatic damage in dogs.
ACKNOWLEDGEMENT
The authors wish to acknowledge Mustafa Kemal
University Scientific Projects Support Foundation for
supporting this research (Project number: 02 G 0203).
REFERENCES
Bernard, J.M., P.F. Wouters, M.F. Doursout, B. Florence,
J.E. Chelly and R.G. Merin, 1990. Effects of
sevoflurane and isoflurane on cardiac and coronary
dynamics in chronically instrumented dogs.
Anesthesiology, 72: 659-662. PMID: 2321783.
http://www.anesthesiology.org/pt/re/anes/pdfhand
ler.00000542-199004000-00014.pdf.
355
Clarke, K.W., D.Y. Song, H.I. Alibhai and Y.H. Lee, 1996.
Cardiopulmonary effects of desflurane in ponies,
after induction of anaesthesia with xylazine and
ketamine. Vet. Rec., 24: 180-185. PMID: 8873398.
http://veterinaryrecord.bvapublications.com/cgi/re
print/139/8/180.
Clutton, R.E., 1998. New drugs in companion animal
anaesthesia. Waltham Focus, 8: 9-16. http://www.
bearscampnewfs.com/health/Waltham%20Center/N
ew%20Drugs%20in%20Companion%20Animal%20
Anesthesia.pdf.
Dexter, F. and J.H. Tinker, 1995. Comparisons between
desflurane and isoflurane or propofol on time to
following commands and time to discharge. A
metaanalysis. Anesthesiol., 83: 77-82. PMID:7605021.
http://www.anesthesiology.org/pt/re/anes/fulltext.0
0000542-199507000-00009.htm.
Doorley, B.M., S.J. Waters, R.C. Terrell and J.L.
Robeinson, 1988. MAC of I-653 in Beagle dogs
and New Zealand White rabbits. Anesthesiology,
69: 89-91. PMID: 3389568. http://www.anesthesio-
logy.org/pt/re/anes/pdfhandler.00000542-198807000-
00013.pdf.
Dupont, J., B. Tavernier, Y. Ghosez, L. Durinck, A.
Thevenot, N. Moktadir-Chalons, L. Ruyffelaere-
Moises, N. Declerck and P. Scherpereel, 1999.
Recovery after anaesthesia for pulmonary surgery:
Desflurane, sevoflurane and isoflurane. Br. J.
Anaesth., 82: 355-359. DOI: 10.1093/bja/82.3.355.
PMID: 10434815. http://bja.oxfordjournals.org/cgi/
reprint/82/3/355.
Eger, E.I., D.D. Koblin, T. Bowland, P. Ionescu,
M.J. Laster, Z. Fang, D. Gong, J. Sonner and
R.B. Weiskopf, 1997. Nephrotoxicity of sevoflurane
versus desflurane anaesthesia in volunteers. Anesth.
Analg., 84: 160-168. PMID: 8989018. http://www.
anesthesia-analgesia.org/cgi/reprint/84/1/160.
Go´mez-Villamandos, R.J., A.E. Sa´nchez, J.M.
Domi´nguez, J.I. Redondo, E.M. Marti´n, I. Ruiz and
J.M. Santisteban, 2000. Desflurane in dogs. A clinical
trial. Proceedings of the 7th International Congress of
Veterinary Anaesthesiology. Association of
Veterinary Anaesthetists, Berne, pp: 98.
Go´mez-Villamandos, R.J., C. Palacios, A. Beni´tez,
M.M. Granados, J.M. Domý´nguez, I. Lo´pez, I. Ruiz,
E. Aguilera and J.M. Santisteban, 2006.
Dexmedetomidine or medetomidine premedication
before propofol-desflurane anaesthesia in dogs J.
Vet. Pharmacol. Therapy, 29: 157-163. DOI: 10.1111/j.
1365-2885.2006.00732. PMID:16669859. http://www3.
interscience.wiley.com/cgi-bin/fulltext/118571336/
PDFSTART.
 J. Anim. Vet. Adv., 8 (2): 350-357, 2009
Hammond, R.A., H.I.K. Alibhai, K.P. Walsh and
K.W. Clarke, 1994. Desflurane in the dog: Minimal
alveolar concentration alone and in combination
with nitrous oxide. J. Vet. Anaesth., 21: 21-26.
Hedenqvist, P., J.V. Roughan, L. Antunes, H. Orr,
P.A. Flecknell, 2001. Induction of anaesthesia
with desflurane and isoflurane in the rabbit. Lab.
Anim., 35: 172-179. DOI: 10.1258/0023677011911561.
PMID: 11315168. http://la.rsmjournals.com/cgi/
reprint/35/2/172.
Karzai, W., J. Haberstroh and H.J. Priebe, 1998. Effects of
desflurane and propofol on arterial oxygenation
during one-lung ventilation in the pig. Acta
Anaesthesiol. Scand., 42: 648-652. PMID: 9689269.
http://www.ncbi.nlm.nih.gov/sites/entrez.
Koblin, D.D., R.B. Weiskopf, M.A. Holmes, K. Konopka,
I.J. Rampil, E.I. Eger and L. Waskell, 1989. Metabolism
of I-653 and isoflurane in swine. Anesth. Analg.,
68: 147-149. PMID: 2913848. http://www.anesthesia-
analgesia.org/content/vol68/issue2S/.
Martin, M.F., J.R. Lima, L.J. Ezquerra, M.S. Carrasco and
J. Uson-Gargallo, 2001. Prolonged anaesthesia with
desflurane and fentanyl in dogs during conventional
and laparoscopic surgery. J. Am. Vet. Med. Assoc.,
219: 941-945. DOI: 10.2460/javma.2001.219.941.
PMID: 11601789. http://avmajournals.avma.org/doi/
abs/10.2460/javma.2001.219.941.
Merin, R.G., J.M. Bernard, M.F. Doursout, M. Cohen and
J.E. Chelly, 1991. Comparison of the effects of
isoflurane and desflurane on cardiovascular
dynamics and regional blood flow in the chronically
instrumented dog. Anesthesiology, 74: 568-574.
PMID: 2001036. http://www.anesthesiology.org/pt/
re/anes/pdfhandler.00000542-199103000-00027.pdf.
Nishiyama, T., T. Yokoyama and K. Hanaoka, 1998. Liver
function after sevoflurane or isoflurane anaesthesia
in neurosurgical patients. Can. J. Anaesth., 45: 753-
756. PMID: 9793665. http://www.cja-jca.org/cgi/
reprint/45/8/753?view=long&pmid=9793665.
O'Keeffe, N.J. and T.E. Healy, 1999. The role of new
anaesthetic agents. Pharmacol. Ther., 84: 233-248.
DOI:10.1016/S0163-7258(99)00034-0.PMID:10665829.
http://www.sciencedirect.com/science/journal/0163
7258.
Öztürk, A. and M.E. Altug, 2007. Effects of repeated
application of isoflurane and desflurane on
electrocardiogram, anaesthesia induction and
recovery characteristics in rats. Bull. Vet. Inst.
Pulawy, 51: 635-640. http://bulletin.piwet.pulawy.pl/
51_04.htm.
356
Picker, O., T.W. Scheeren and J.O. Arndt, 2001. Inhalation
anaesthetics increase heart rate by decreasing
cardiac vagal activity in dogs. Br. J. Anaesth.,
87: 748-54. DOI: 10.1093/bja/87.5.748. PMID:
11878527. http://bja.oxfordjournals.org/cgi/reprint/
87/5/748.
Schmidt, C.C., S.W. Suttner, S.M. Piper, D. Nagel and
J. Boldt, 1999. Comparison of the effects of
desflurane and isoflurane anaesthesia on
hepatocelluler function assessed by alpha
glutathione S-transferase. Anaesthesia, 54: 1204-
1219. DOI: 10.1046/j.1365-2044.1999.01105.x. PMID:
10594421. http://www3. interscience.wiley.com/cgi-
bin/fulltext/119060113/ PDFSTART.
Smith, I., E. Taylor and P.F. White, 1994. Comparison
of tracheal extubation in patients deeply
anesthetized with desflurane or isoflurane. Anesth.
Analg., 79: 642-645. PMID:7943769. http://www.
anesthesia-analgesia.org/cgi/reprint/79/4/642.
Steffey, E.P. and D. Howland, 1977. Isoflurane potency in
the dog and cat. Am. J. Vet. Res., 38: 1833-1836.
PMID: 931167.
Steffey, E.P., J.D. Baggot, J.H. Eisele, N. Willits,
M.J. Woliner, K.A. Jarvis, A.R. Elliott and
M. Tagawa, 1994. Morphine-isoflurane interaction
in dogs, swine and rhesus monkeys. J. Vet.
Pharmacol. Ther., 17: 202-210. DOI: 10.1111/j.1365-
2885.1994. tb00234.x. PMID:7933058. http://www3.
interscience.wiley.com/journal/119274273.
Steffey, E.P., F. Galey, K.R. Mama and B. Puschner, 2000.
Influence of sevoflurane and desflurane anaesthesia
on blood biochemical values in horses. Vet. Anesth.
Analg., 27: 54-62. DOI: 10.1046/j.1467-2995.2000.
00008-3.x. http://www3.interscience.wiley.com/cgi-
bin/fulltext/120192236/HTMLSTART.
Sutton, T.S., D.D. Koblin, L.D. Gruenke, R.B. Weiskopf,
I.J. Rampil, L. Waskell and E.I. Eger, 1991. Fluoride
metabolites following prolonged exposure of
volunteers and patients to desflurane. Anesth.
Analg., 73: 180-185. PMID: 1854033. http://www.
anesthesia-analgesia.org/cgi/reprint/73/2/180.
Tiainen, P., L. Lindgren and P.H. Rosenberg, 1998.
Changes in hepatocellular integrity during and after
desflurane or isoflurane anaesthesia in patients
undergoing breast surgery. Br. J. Anaesth., 80: 87-89.
DOI: 10.1093/bja/80.1.87. PMID: 9505785. http://bja.
oxfordjournals.org/cgi/reprint/80/1/87.
Thurmon, J.C., W.J. Tranquilli and G.J. Benson, 1999.
Essentials of Small Animal Anaesthesia and
Analgesia. 1st Edn. Baltimore, Maryland. USA.,
pp: 23-25. ISBN: 0683301071.
 J. Anim. Vet. Adv., 8 (2): 350-357, 2009
Topal, A., N. Gul, Y. Icol and O.S. Gorgul, 2003. Hepatic
Effects of Halothane, Isoflurane or Sevoflurane
Anaesthesia in Dogs. J. Vet. Med. A., 50: 530-533.
DOI: 10.1111/j.1439-0442.2004.00589.x. PMID: 1515
7022. http://www3.interscience.wiley.com/cgi-bin/
fulltext/118844628/PDFSTART.
Tsai, S.K., C. Lee, W.F. Kwan and B.J. Chen, 1992.
Recovery of cognitive functions after anaesthesia
with desflurane or isoflurane and nitrous oxide. Br.
J. Anaesth., 69: 255-258. DOI: 10.1093/bja/69.3.255.
PMID: 1389842. http://bja.oxfordjournals.org/cgi/
reprint/69/3/255.
Weiskopf, R.B., E.I. Eger, M. Daniel and M. Noorani,
1995. Cardiovascular stimulation induced by rapid
increases in desflurane concentration in humans
results from activation of tracheopulmonary and
systemic receptors. Anesthesiology, 83: 1173-1178.
PMID:8533909. http://www.anesthesiology.org/pt/re/
anes/fulltext.00000542-199512000-00007.htm.
357
View publication stats
Wissing, H. and I. Kuhn, 2000. The effect of desflurane on
liver function markers in infants and children. Report
of a study and a pertinent case report. Acta
Anaesthesiol. Scand., 44: 1149-1153. DOI: 10.1034/j.
1399-6576.2000.440920.x. PMID: 11028739.
http://www3.interscience.wiley.com/cgi-bin/fulltext/
119179781/PDFSTART.
Zaleski, L., D. Abello and M. Gold, 1993. Desflurane
versus isoflurane in patients with chronic hepatic
and renal disease. Anesth. Analg., 76: 353-356.
PMID: 8424515. http://www.anesthesia-analgesia.
org/contents-by-date.1993.shtml.
Zwass, M.S., D.M. Fisher, L.G. Welborn, C.J. Cote,
P.J. Davis, M. Dinner, R.S. Hannallah, L.M. Liu,
J. Sarner and W.A. McGill, 1992. Induction and
maintenance characteristics of anaesthesia with
desflurane and nitrous oxide in infants and children.
Anesthesiology, 76: 373-378. PMID: 1539848.
http://www.anesthesiology.org/pt/re/anes/pdfhand
ler.00000542-199203000-00009.pdf.
See discussions, stats, and author profiles for this publication at: https://www.researchgate.net/publication/326741116

Induction and recovery Characteristics of Isoflurane and Sevoflurane anesthesia

for ovariohysterectomy in dogs

Research · July 2018

DOI: 10.13140/RG.2.2.19876.17287

CITATIONS READS

0 108

5 authors, including:

Mohammed Arif Basha

Department of Animal Husbandary
32 PUBLICATIONS   7 CITATIONS   

SEE PROFILE

Some of the authors of this publication are also working on these related projects:

Studies on internal fixation of femoral fractures in Canines View project

Small Animal Orthopedics View project

All content following this page was uploaded by Mohammed Arif Basha on 01 August 2018.

The user has requested enhancement of the downloaded file.

 Vol 8 (07) Jul ’18
International Journal of Livestock Research eISSN : 2277-1964 NAAS Score -5.36

Original Research

Induction and Recovery Characteristics of Isoflurane and Sevoflurane

Anaesthesia for Ovariohysterectomy in Dogs

Mohammed Arif Basha K1*, Ranganath Lingappa2, B. N. Nagaraja3, C. Ansar Kamran4

and M. Narayana Swamy5
Veterinary College, Hebbal, Bangalore-560024, Karnataka Veterinary, Animal and Fisheries
Sciences University (KVAFSU), Bidar, Karnataka, INDIA
1
Department of Veterinary Surgery and Radiology
2
Dean, Veterinary College, Hassan
3
Department of Veterinary Surgery and Radiology
4
Department of Veterinary Medicine
5
Department of Veterinary Physiology

*Corresponding author: vetarif@gmail.com

Rec. Date: Dec 06, 2017 07:24

Accept Date: Feb 20, 2018 15:41
DOI 10.5455/ijlr.20171206072401

Abstract
A study was carried out to evaluate induction and recovery characteristics of isoflurane and sevoflurane
inhalant anaesthesia for ovariohysterectomy in young and healthy female dogs. All the animals were
premedicated with Atropine sulphate and Diazepam. Induction of anaesthesia was achieved by using
Isoflurane (5%) in group A and Sevoflurane (5%) in group B along with oxygen (1.5L/min) using close
fitting face mask with rubber diaphragm. Anaesthesia was maintained in group A and B by using
Isoflurane and Sevoflurane respectively by endotracheal intubation till effect using small animal
anaesthesia machines of rebreathing or circle system with vaporizer outside the circuit. Quantitative
parameters like average induction time, average dose volume of maintenance and average time of
reappearance of various reflexes during recovery were recorded. Quality of induction was compared by
assessing subjective parameters like degree of various reflexes and scored accordingly during surgical
plane. Also qualitative parameters during recovery phase were assessed based on video recordings
obtained during the recovery phase and were scored using simple descriptive scale (SDS) and visual
analog scale (VAS). Results indicated that Sevoflurane (group B) animals were having significantly faster
induction and recovery rates than Isoflurane (group A) which may be attributed to its least blood gas
solubility of Sevoflurane. Mean ± SE values for average maintenance dose volume (Vol %) were 3.16 ±
0.16 for group A and 2.04 ± 0.16 for group B. There was no significant difference in quality of induction
and qualitative parameters of recovery between the groups. There was no significant difference in SDS
122

and VAS scales between the groups and the values were within acceptable levels. Thus the quality of
recovery and analgesia in both the groups was satisfactory. We do not conclude both the agents have
significant analgesic effects though best results can be achieved with opiod analgesic pre medication. It
Page

was concluded though induction and recovery characteristics of sevoflurane anaesthesia are faster than

Hosted@www.ijlr.org DOI 10.5455/ijlr.20171206072401

 Vol 8 (07) Jul ’18
International Journal of Livestock Research eISSN : 2277-1964 NAAS Score -5.36

isoflurane, both isoflurane and sevoflurane are advantageous inhalant anaesthetics in terms of ease of
administration, excellent maintenance quality and rapid and smooth recovery with minimal adverse
effects on healthy female dogs subjected for ovariohysterectomy procedure. Although sevoflurane is
associated with faster induction and recovery there is no clinical significance in usage with this finding
except sevoflurane having low pungency and airway irritation.

Key words: Anaesthesia, Dogs, Isoflurane, Induction and Recovery, Sevoflurane

How to cite: Basha, K, M, A., Lingappa, R., Nagaraja, B., Kamran, C., & Swamy, M. (2018). Induction
and Recovery Characteristics of Isoflurane and Sevoflurane Anesthesia for Ovariohysterectomy in
Dogs. International Journal of Livestock Research, 8(7), 122-130. doi: 10.5455/ijlr.20171206072401

Introduction
Isoflurane is a highly stable, non-explosive, potent volatile inhalation anaesthetic. Isoflurane is more
potent with the MAC value of 1.31 in dogs but low blood gas solubility of 1.40 at 37oC (Mutoh et al.,
1995). Similar to other anaesthetics isoflurane causes hypothermia, dose dependent respiratory and
cardiovascular depression (Meyer et al., 1984). Isoflurane is a popular anaesthetic agent in veterinary
practice because of its cardiovascular stability, low blood solubility, resistance to hepatic metabolism and
more of patient safety (Mutoh et al., 2001).
Sevoflurane is a non-inflammable halogenated inhalant anaesthetic with a MAC of 2.36 in dogs and
blood gas partition coefficient of 0.68, since it has fluorine atoms only, it is more stable and less soluble
in blood than isoflurane and hence sevoflurane possesses chemical properties that should produce more
rapid induction of anaesthesia in comparison to halothane or isoflurane. Sevoflurane appears to have
some advantages over isoflurane, including faster and smoother mask induction (Johnson et al., 1998).
Similar to isoflurane, sevoflurane also causes similar dose related cardiovascular depression, but less at
higher exponent anaesthetic doses and also much safer on hepatic function than halothane anaesthesia in
dogs (Galloway et al., 2004). Sevoflurane produces anaesthesia of excellent quality, undergo limited
biotransformation and has little or no systemic toxicity (Holaday et al., 1981). Concentrations of
compound A, a degradation product of sevoflurane with sodalime in anaesthetic circuits was less than
reported values to produce renal toxicosis in rats (Muir and Gadawski, 1998). In the view of above facts,
a comparative study on isoflurane and sevoflurane anaesthesia in dogs was carried out to study the
efficacy of isoflurane and sevoflurane as inhalant anaesthetics in dogs and to evaluate and compare two
anesthetics in terms of induction, duration of surgical anaesthesia and recovery patterns.

Materials and Methods

123

The study was conducted on 12 clinical cases of young female dogs, which were presented for
Page

ovariohysterectomy to Department of Surgery and Radiology, Veterinary College Hospital, Bangalore.

Hosted@www.ijlr.org DOI 10.5455/ijlr.20171206072401

 Vol 8 (07) Jul ’18
International Journal of Livestock Research eISSN : 2277-1964 NAAS Score -5.36

Dogs were randomly divided into two groups viz., Group A (Isoflurane) and Group B (Sevoflurane)
comprising six dogs each. The animals were administered with atropine sulphate 0.04 mg/kg i/m and
diazepam 1mg/kg i/v, at 30 minutes and 20 minutes, respectively prior to induction with inhalant
anaesthesia and animals were not disturbed for at least 15 minutes from the point of administration of
atropine sulphate. Twenty minutes after premedication with diazepam, anaesthesia was induced with
isoflurane (for Group A) and sevoflurane (Group B) using close fitting face mask with rubber diaphragm
with maximum vaporizer settings available for both i.e. 5%. Dogs were pre oxygenated for 2 minutes
before induction using close fitting face mask.
Isoflurane (SOSRANE, Metrex Pharmaceuticals Pvt. Ltd., Mumbai) in group A and Sevoflurane
(SEVORANE, Abbott India Ltd., Mumbai) in group B were administered in combination with oxygen
(1.5 L/min) during induction as well as maintenance of anaesthesia. Surgivet small animal anaesthesia
machines (Smith Medical PM. Inc., Veterinary Division, Wisconsin, USA) of rebreathing or circle system
with vaporizer outside the circuit for isoflurane and sevoflurane were used for the study. The dose for
induction of anaesthesia was calculated on the basis of total time required by an animal to attain the plane
of surgical anaesthesia, which was marked by absence of pedal reflex, ventromedial deviation of eyeball
and deep abdominal breathing with decrease in respiratory rate. The time required for induction, average
maintenance dose volume of inhalant anaesthesia, duration of surgery and recovery parameters were
recorded. Ovariohysterectomy procedure was carried out in all the female dogs for an average time of
(Mean ± SE minutes) in both the groups. Average maintenance dose volume of anaesthesia (Vol %) of
inhalant anaesthetic required to maintain surgical plane of anaesthesia was calculated by monitoring the
reappearance of pedal reflex and central upward movement of eyeball from state of ventromedial
deviation and finally through mathematical formula as summation of time in minutes multiplied by
respective vaporizer setting of maintenance divided by total time of maintenance in minutes. Surgical
plane of anaesthesia was marked as the duration of anaesthesia between abolition of pedal reflex and
completion of surgical procedure. Completion of surgery was marked as point of completion of last skin
suture.
Assessment of subjective parameters for various reflexes during surgical plane for quality of induction
was done and graded as following. Salivation was graded on 0 to 2 scale, with score 0 (present), score 1
(sluggish) and score 2 (absent). Vomition was graded on 0 to 2 scale, with score 0 (present), score 1
(sluggish) and score 2 (absent). Skeletal muscle relaxation was graded from scale of 1 to 2, with score 1
(good) and score 2 (moderate). Jaw relaxation was graded from scale of 1 to 2, with score 1 (moderate)
124

and score 2 (good). Anal relaxation was graded from scale of 1 to 2, with score 1 (moderate) and score 2
(good). Palpebral reflex was graded on 0 to 2 scale, with score 0 (present), score 1 (sluggish) and score 2
Page

(absent). Pupillary reflex was graded on 0 to 2 scale, with score 0 (present), score 1 (sluggish) and score 2

Hosted@www.ijlr.org DOI 10.5455/ijlr.20171206072401

 Vol 8 (07) Jul ’18
International Journal of Livestock Research eISSN : 2277-1964 NAAS Score -5.36

(absent). Pain pick reflex (flank region) was graded on 0 to 2 scale, with score 0 (present), score 1
(sluggish) and score 2 (absent). Tail prick reflex was graded on 0 to 2 scale, with score 0 (present), score
1 (sluggish) and score 2 (absent). Pinna reflex was graded on 0 to 2 scale, with score 0 (present), score 1
(sluggish) and score 2 (absent). Position of eyeball was graded from scale of 1 to 2, with score 1 (centre)
and score 2 (ventromedial). Cutaneous analgesia was graded on 0 to 2 scale, with score 0 (present), score
1 (sluggish) and score 2 (absent).
At the end of the surgery, marked by placing of the last skin suture, the vaporizer was set off and the
animals were allowed to breathe fresh oxygen for three additional minutes. Animals were shifted to
recovery room and video recording was performed to study the qualitative (non-interactive) and
quantitative recovery parameters. During recovery period, dogs were left undisturbed until they were able
to stand up and walk on their own. The point at which the animal stood up was the last piece of data
recorded for qualitative parameters for recovery phase of inhalation anaesthesia. Quantitative parameters
like the average time for return of swallowing reflex, pedal reflex, head righting reflex, time taken for
voluntary leg movement, time taken for sternal recumbency and time taken for animal to ambulate after
cessation of anaesthesia during recovery period were recorded. Qualitative parameters during recovery
phase were assessed directly on observations and later based on video recordings obtained during
recovery phase by three different observers starting directly after extubation till the time animal walked
unassisted. Recovery was scored based on simple descriptive scale (SDS) of 0-4 and visual analogue
scale (VAS) defined one extreme at 0 mm as perfect recovery whilst the other end 100 mm was defined
as worst recovery imaginable as described in Table 1.

Table 1: Comparative mean ± SE values of different parameters recorded during study period in Group A
(Isoflurane) and Group B (Sevoflurane) dogs
S. No. Parameters (minutes) Group A Group B
1 Time taken for induction (min) 7.16 ± 0.21 6.01 ± 0.11*
2 Duration of anaesthesia for surgical procedure (min) 35.33 ± 1.58 32.00 ±0.66
3 Average maintenance volume of anaesthesia for group (Volume %) 3.16 ± 0.16 2.04 ± 0.16*
4 Time taken for regain of swallowing reflex from the point of termination of anaesthesia (min) 3.33 ± 0.05 1.98 ± 0.09*
5 Time of return of pedal reflex from the point of termination of anaesthesia (min) 6.04 ± 0.10 3.19 ± 0.04*
6 Time of head righting reflex from the point of termination of anaesthesia (min) 7.33 ± 0.04 3.94 ± 0.12*
7 Time taken for voluntary leg movement from the point of termination of anaesthesia (min) 7.88 ± 0.13 4.38 ± 0.05*
8 Time taken for sternal recumbency from the point of termination of anaesthesia (min) 11.83 ± 0.50 5.54 ± 0.10*
9 Time taken for attempt to stand from the point of termination of anaesthesia (min) 17.87 ± 0.13 8.69 ± 0.12*
*Significant (p<0.05)

The quality of recovery was considered unacceptable (SDS score 4 and VAS > 70 mm). Medication for
125

post operative analgesia as butorphanol 0.2 mg/kg IV was administered in all cases immediately after
Page

animal walked unassisted. Recovery parameters as start position (starting position of the body), position

Hosted@www.ijlr.org DOI 10.5455/ijlr.20171206072401

 Vol 8 (07) Jul ’18
International Journal of Livestock Research eISSN : 2277-1964 NAAS Score -5.36

change (change of body position), end position (last position of body before attaining a recumbency or
standing procedure), head position, ear position, eyeball position, tail carriage, vocalizations and others
(arched back, stretching, rigid back, licking of snout and drawing legs up) were observed.
Statistical Analysis
The data was analyzed for statistical significance using computer based statistical program Graph pad
prism and interpreted as per the procedure described by Snedecor and Cochran (1996) to arrive at a
conclusion. The mean and standard error for all the data were computed. The variations during and after
anaesthesia at different time intervals for both within and between treatments were analyzed by single
tailed unpaired ‘t’ test. The test of significance was fixed at five per cent for all the comparisons (p≤0.05).
The subjective data generated from the scoring were analyzed using Kruskal-Wallis test (Snedecor and
Cochran, 1996). In each analysis, the differences were considered significant at a value of p<0.05 and
very significant at a value of p<0.01.

Results
Quantitative parameters observed during recovery phase are as indicated in (Table 1, Fig.1).

126

Induction Time of Inhalation Anaesthesia

The mean duration to attain optimal level of induction for isoflurane anaesthesia (Group A) was 7.16 ±
Page

0.21 minutes and for sevoflurane anaesthesia (Group B) was 6.01 ± 0.11 minutes. In group A dogs, time

Hosted@www.ijlr.org DOI 10.5455/ijlr.20171206072401

 Vol 8 (07) Jul ’18
International Journal of Livestock Research eISSN : 2277-1964 NAAS Score -5.36

taken for induction was significantly longer compared to group B however, animals in group A showed
resistance during initial uptake of mask induction of isoflurane.

Average Maintenance Dose Volume (Vol%)

Average maintenance dose volume of isoflurane Group A (Isoflurane) and Group B (Sevoflurane)
anaesthesia required during ovariohysterectomy were 3.16 ± 0.16 and 2.04 ± 0.16 (Vol %), respectively.
The values were significantly higher in Group A animals.

Assessment of Subjective Parameters for Various Reflexes during Surgical Plane for Quality of
Induction
There was no significant difference with the scoring system in monitoring of various reflexes during
surgical plane of anaesthesia between groups.

Quantitative Values of Regaining of Reflexes during Recovery

In Group A animals the duration of return of swallowing reflex, head righting reflex, voluntary leg
movement attainment of sternal recumbency and duration of animals to ambulate were significantly faster
in group B animals compared to Group A animals (Table 1).

Qualitative Parameters Recorded During Recovery

In group A animals, recovery phase was relatively a smooth transition from anaesthesia to the state of full
consciousness. No struggling, tremors or other unconscious movements were found except for one
instance of slight pedaling. Vocalization was observed in one case. Moderate attempts of licking of snout,
licking of floor, legs and bandage were evident but at lesser frequency. In group B animals, also recovery
was relatively much smoother and rapid than the group A. No struggling, pedaling, tremors or other
unconscious movements were observed. Very few attempts of licking of snout, licking of floor, legs and
bandage were seen. Three observers each (P, Q and R) were assigned to score SDS and VAS scales for
the evaluation of quality of recovery. There were no significant differences between groups for SDS and
VAS scores for quality of recovery for any of the observers (Table 2).

Discussion
Time of induction of inhalation anaesthesia: During mask induction, average time taken for mask
induction in group B animals was significantly faster than that of group A animals. Similar findings were
observed by Johnson et al. (1998) and Jadon et al. (2008) while Mutoh et al. (1995) and Pottie et al.
(2008) found no significant difference in speed of induction between these two inhalant agents. This
127

could be due to the special chemical properties of sevoflurane viz., low blood gas partition coefficient that
produces rapid increase in alveolar anaesthestic concentration (Kubota, 1992). Faster mask induction of
Page

anaesthesia is advantageous in point of view of minimal struggling, minimizing likelihood of aspiration of

Hosted@www.ijlr.org DOI 10.5455/ijlr.20171206072401

 Vol 8 (07) Jul ’18
International Journal of Livestock Research eISSN : 2277-1964 NAAS Score -5.36

stomach contents and rapid access to intubation and airway maintenance. Resistance to initial uptake of
isoflurane in Group A may be due to its pungent odour. Sloan et al. (1999) found similar induction times
in human patients receiving isoflurane and sevoflurane in single-breath induction. However, coughing
occurred more frequently in patients receiving isoflurane and patients receiving sevoflurane had fewer
complications. The maximal vaporizer settings used in this study of 5% in both the groups corresponds to
3.8 MAC and 2.1 times MAC for isoflurane and sevoflurane respectively (Steffy and Mama, 2007).

Table 2: Quality of recovery as assessed with SDS (Simple descriptive scale) and VAS (Visual analog
Scale) by observers P, Q and R in Group A (Isoflurane) and Group B (Sevoflurane) dogs
Group A Group B P value
SDS
Observer P 2.333 1.5 0.06
Observer Q 2 1.5 0.17
Observer R 2.167 1.667 0.29
VAS in mm
Observer P 34.67 32 0.55
Observer Q 32.67 27.67 0.21
Observer R 39.83 34.67 0.17
*Significant (p<0.05)

Average Maintenance Dose Volume (Vol%)

The average maintenance volume of anaesthesia for group A (isoflurane) and group B (sevoflurane)
animals were 3.16 ± 0.16 and 2.04 ± 0.16 (Vol%), respectively. Surgical anaesthesia is normally achieved
at 1.5 times of MAC. With sevoflurane having higher MAC value, group B dogs should have consumed
more anaesthetic agent with higher vaporizer settings theoretically when fresh gas flow rate being the
same in both the groups. This significant difference in average maintenance dose volume between group
A and B animals may be attributed to resistance offered by group A animals during mask induction and
partial loss of anaesthetic gas at face mask junction, thus consuming higher maintenance dose via
endotracheal intubation during maintenance than group B animals. Values obtained during present study
were lower in overall may be because of usage of rebreathing or circle system in this study. Jadon et al.
(2008) used 3 % isoflurane and 2.5 % sevoflurane for maintenance.

Assessment of Subjective Parameters for Various Reflexes during Surgical Plane for Quality of
Induction
Animals in both the groups had rapid transition from consciousness to anaesthesia with minimal
resistance in terms of movement, sufficient muscle relaxation, good jaw relaxation, sufficient cutaneous
128

analgesia and negative tail clamp reflex with no significant difference between groups in scoring system.
Similarly Pottie et al. (2008) did not find any significant difference in quality of induction in both the
Page

Hosted@www.ijlr.org DOI 10.5455/ijlr.20171206072401

 Vol 8 (07) Jul ’18
International Journal of Livestock Research eISSN : 2277-1964 NAAS Score -5.36

agents. Johnson et al. (1998) reported sevoflurane was associated significantly better quality of induction
compared to isoflurane.
Quantitative Parameters Observed During Recovery Phase (Table 1, Fig.1)
In group B animals the regaining of reflexes was significantly faster than group A animals. Quick
recovery from anaesthesia in Isoflurane can be attributed to the low solubility of the isoflurane which
facilitated fast elimination from the body. Significantly faster recovery in Group B could be due to least
blood gas solubility of sevoflurane. Johnson et al. (1998) did not find any significant difference in
recovery parameters using isoflurane and sevoflurane in adult dogs.

Qualitative Parameters Recorded During Recovery (Table 2)

In terms of qualitative characteristics there was no significant difference in SDS and VAS scales between
groups. Thus the quality of recovery and analgesia in both the groups was satisfactory and within
acceptable levels. We do not conclude both the agents have significant analgesic effects though best
results can be achieved with opiod analgesic pre medication. Group B animals had non significantly
lower values in SDS and VAS with smoother recovery and limited movements. Hence group B animals
seem to have slightly better recovery quality. Love et al. (2007) found subjectively better quality of
recovery in dogs that received sevoflurane than in those that received isoflurane, also did not found any
much difference in time to recover. Johnson et al. (1998) opined recovery quality in usage of isoflurane
and sevoflurane in adult dogs is comparable. Sloan et al. (1996) used isoflurane and sevoflurane for
human patients for single-breath induction with nitrous oxide and oxygen mixture and found patients
receiving sevoflurane were less clumsy and less confused but had higher pain scores. Further they also
opined sevoflurane is more suitable than isoflurane in single breath-induction, because it produces
smoother induction and lower incidence of complications and better patient acceptance.
Speed of anaesthesia induction with inhalant anaesthetics is determined by the agent’s blood solubility,
airway irritation, alveolar concentration and rate of which the concentration is achieved (a function of
cardiac output, alveolar ventilation, regional distribution and inspired anaesthestic concentration).
Anaesthesia recovery depends not only on blood:gas solubility, but on alveolar ventilation, cardiac output
and venous-to-alveolar anaesthestic partial pressure differences (Eger, 1974). However speed of recovery
and quality of recovery must be considered as separate criteria for assessment of recovery. Further rapid
recovery may not be always indicative of better quality of recovery. But considering limited movements,
number of attempts made to stand, degree of ataxia and limited vocalizations during recovery period
129

sevoflurane may be having slight advantage. Although sevoflurane is associated with faster induction and
recovery there is no clinical significance in usage with this finding except sevoflurane having low
Page

pungency and airway irritation.

Hosted@www.ijlr.org DOI 10.5455/ijlr.20171206072401

 Vol 8 (07) Jul ’18
International Journal of Livestock Research eISSN : 2277-1964 NAAS Score -5.36

Conclusion
In conclusion, though induction and recovery characteristics of sevoflurane anaesthesia are faster than
isoflurane, both isoflurane and sevoflurane are advantageous inhalant anaesthetics in terms of ease of
administration during induction, excellent maintenance quality with rapid and smooth recovery without
any significant adverse effects on healthy female dogs subjected for ovariohysterectomy procedure.

References
1. Eger E I. 1974. Recovery from anesthesia. In: Anesthetic uptake and action. Baltimore: The Williams
and Wilkins Co.pp. 228-247.
2. Galloway S D, Ko J C H, Reaugh H F, Mandsager R E, Payton AE, Inoue T, Portillo E. 2004.
Anaesthetic indices of sevoflurane and isoflurane in unpremedicated dogs. Journal of American
Veterinary Medical Association. 225: 700-704.
3. Holaday DA and Smith FR. 1981. Clinical characteristics and biotransformation of sevoflurane in
healthy human volunteers. Anesthesiology. 54: 100-106.
4. Jadon NS, Kumar S, Kandpal M, Sharma VK, Thathoo AK. 2008. Comparative evaluation of
isoflurane and sevoflurane anaesthesia in puppies. Indian Journal of Veterinary Surgery. 29: 110-111.
5. Johnson RA, Striler E, Sawyer DC, Brunson DB. 1998. Comparison of isoflurane with sevoflurane for
anaesthesia induction and recovery in adult dogs. American Journal Veterinary Research. 59: 478-481.
6. Kubota Y. 1992. Comparative study of sevoflurane with other inhalation agents. Anesthesia Progress.
39: 118-124.
7. Love E J, Holt P E, Murison P J. 2007. Recovery characteristics following maintenance of anaesthesia
with sevoflurane or isoflurane in dogs premedicated with acepromazine. Veterinary Record. 161: 217-
221.
8. Meyer R E, Gleed R D, Harvey H J. 1984 Isoflurane anaesthesia as an adjunct to hypothermia for
surgery in a dog. Journal of American Veterinary Medical Association. 184: 1387-1389.
9. Muir W W and Gadawski J, 1998. Cardiorespiratory effects of low-flow and closed circuit inhalation
anaesthesia, using sevoflurane delivered with an in-circuit vaporizer and concentrations of compound
A. American Journal of Veterinary Research. 59: 603-608.
10. Mutoh T, Nishimura R, Kim H, Matsunaga S, Kadosawa T, Mochizuki M, Sasaki, N.1995. Rapid
inhalation induction of anaesthesia by halothane, enflurane, isoflurane and sevoflurane and their
cardiopulmonary effects in dogs. Journal of Veterinary Medical Science. 57:1007-1013.
11. Mutoh T, Kanamaru A, Suzuki H, Tsubone H, Nishimura R, Sasaki N. 2001. Respiratory reflexes in
spontaneously breathing anesthetized dogs in response to nasal administration of sevoflurane,
isoflurane, or halothane. American Journal of Veterinary Research. 62: 311-319.
12. Pottie R G, Dart C M and Perkins N R. 2008. Speed of induction of anesthesia in dogs administered
halothane, isoflurane, sevoflurane or propofol in a clinical setting. Australian Veterinary Journal. 86:
26-31.
13. Sloan M H, Conard P F, Karsunky P K, Gross JB. 1996. Sevoflurane vs isoflurane: induction recovery
characteristics with single breath inhaled inductions of anaesthesia. Anesthesia and Analgesia. 82:
528-532.
14. Snedecor C W and Cochran W G. 1996. In: Statistical Analysis. 8th Edn. Oxford and IBH publishing
Co. New Delhi, pp. 335-345.
15. Steffy E P and Mama K R. 2007. Inhalation anaesthetics. In: Lumb and Jones’ Veterinary Anesthesia
130

and Analgesia, 4th Edn. Tranquilli W J, Thurmon J C and Grimm K A (Eds), Blackwell Publishing,
Iowa 50014, USA, pp. 297-329.
Page

Hosted@www.ijlr.org DOI 10.5455/ijlr.20171206072401

View publication stats

 MINERVA MEDICA COPYRIGHT®

REVIEW

Inhalation anesthetics: a review

G. TORRI
Department of Anesthesiology, S. Raffaele University, Milan, Italy

ABSTRACT
Inhalation agents represent a basic drug used in modern balanced anesthesia. In the present review, the pharmacoki-
netics, effectiveness and clinical effects of inhalation agents on different systems are discussed. Data concerning the metab-
olism and related toxicity of halogenated agents is reviewed, with particular regard to the problem of chronic exposure
to traces of anesthetic gases in the operating room. The cardioprotective effect of halogenated agents and the actual role
of nitrous oxide and xenon are discussed. The different mechanisms of action of the inhalation agents and the evolu-
tion from a unitary theory of inhaled anesthetics to a multiple mechanism concept are presented.
(Minerva Anestesiol 2010;76:215-28)
Key words: Anesthetics, inhalation - Pharmacokinetics - Anesthetics.

T he demonstration of the anesthetic proper-

ties of diethyl ether by William Morton in
1846 was one of the most significant discoveries in
medical science. Thereafter, many other anesthet-
ics, including nitrous oxide, chloroform, ethyl-
ene, cyclopropane, trichloroethylene and divinyl
ether were introduced into clinical practice.
Unfortunately, some of these anesthetics were
explosive or toxic and have since been discontin-
ued for clinical use.
In the 1950s, fluroxene, the first fluorinated
agent, was tested in clinical trials; however, the
drug was withdrawn in 1974 when toxic effects
were observed.1
In 1957, halothane, a halogenated hydrocar-
bon, was tested in clinical practice and successful-
ly applied for surgical anesthesia.2 In 1960, a new
halogenated ether, methoxyflurane, was discov-
ered, but its clinical application lasted a very short
time. Prolonged methoxyflurane anesthesia was
frequently associated with nephrotoxicity due to
inorganic fluoride production from its biodegra-
dation. Simultaneously, rare cases of fatal hepati-
tis caused by halothane focused the search on a
safer inhalation anesthetic. Enflurane was synthe-
sized in 1963, while its isomer isoflurane was syn-
thesized in 1965. The clinical introduction of
isoflurane was delayed due to its very difficult
chemical synthesis. Enflurane was introduced in
clinical practice; however, several years later, when
isoflurane was approved for clinical use, this agent
was preferred given its lower solubility and high-
er potency.
Sevoflurane and desflurane were developed in
the late 1960s and tested in clinical practice much
later. Sevoflurane was not immediately introduced
to the USA because of its fluorine release and its
reaction with absorbed carbon dioxide. A large
clinical trial of sevoflurane was performed in Japan,
where this agent was approved for clinical use only
in the 1990s.3 In 1995, sevoflurane was approved
in the USA for clinical use. After several years of
clinical application, no renal failure was observed,
and appropriate studies on compound A did not
show any renal effects in humans.
Desflurane is largely appreciated for its high
stability. Less than 0.02% of desflurane is metab-
olized, thus, plasma fluorine levels are very low.

Vol. 75 - No. 3 MINERVA ANESTESIOLOGICA 215

 MINERVA MEDICA COPYRIGHT®
TORRI INHALATION ANESTHETICS

TABLE I.— Preoperative status and risk factors of 132 patients undergoing reoperative CABG off pump (OP) or with cardiopul-
monary bypass (CPB).
Halothane Enflurane Isoflurane Desflurane Sevoflurane Nitrous
oxide

Formula C2HCIBrF3 CF2H-O-CF2CClFH CF2H-O-CClH-CF3 CF2H-O-CFH-CF3 (CF3)2CHF-O-CH2F N2O

Molecular 197.54 184.54 184.5 168.04 200.05 44.02
weight
Boiling 49-51 56.54 48.5 22.84 58.64 -88.54-
point
°C (at 760
mmHg)

Liquid 1.86 1.52 1.50 1.50 1.53

density
(g/mL)
(25 °C/4 °C)

Vapor
pressure
(mmHg at 2884,3 2184,3 295,3 79844 197,3 44.84
24/25 °C)
(mmHg at 2434,3 1754,3 238,3 66944 157,3 39.84
20 °C)

Blood/gas 2.35 1.91 1.44 0.42 0.63 0.47

partition
coefficient

The very low solubility of desflurane allows for a
surprisingly rapid emergence from anesthesia.
Today, nitrous oxide has a controversial role in
anesthesia, and its contribution to modern bal-
anced anesthesia will be discussed later on.
All halogenated anesthetics are very powerful.
Their therapeutic index ranges from two to four,
and their use requires knowledge of their physi-
co-chemical properties, pharmacokinetics and
pharmacological effects on different system to pre-
vent side effects.
Chemical and physical properties
The structure of inhalation anesthetics and their
physico-chemical properties are shown in Table I.
With the exception of desflurane, the partial
pressure of isoflurane and sevoflurane at ambient
temperatures is sufficient to obtain an adequate
concentration for clinical use with conventional
by-pass vaporizers. The high partial pressure of
desflurane (700 mmHg at ambient temperature)
requires the development of a particular vaporiz-
er. In this vaporizer, desflurane is heated in the
sump to obtain a vapor pressure of 1400 mmHg.
Desflurane vapor flows from the heated sump in
parallel to the fresh gas line through two variable
resistances. One resistance is controlled by the dial
setting, while the second resistance is controlled
by a differential transducer that regulates the pres-
sures of both desflurane and fresh gas flow.
Nitrous oxide at ambient pressures and tem-
peratures exists in a gaseous phase and can be deliv-
ered through a flow meter.
In Table I, the solubility of inhalation anes-
thetics is represented by the blood/gas partition
coefficient (λ), i.e., the ratio of the concentra-
tions of two phases (blood and gas) when their
partial pressures are in equilibrium. At the same
alveolar concentration, the higher the blood/gas
partition coefficient, the higher the anesthetic
concentration in the blood. The solubility of an
anesthetic in tissue differs from its solubility in the
blood, which is due to their lipid affinity. All
inhalation anesthetics are very soluble in fatty
tissues and less soluble in other tissues. Solubility
in the blood increases as body temperature
decreases, while hemodilution reduces blood sol-
ubility.4 Solubility plays a fundamental role in
the kinetics of the agents.

216 MINERVA ANESTESIOLOGICA March 2010

 MINERVA MEDICA COPYRIGHT®
INHALATION ANESTHETICS
N2O
1 1
Desflurane
0.8 Sevoflurane
Isoflurane
0.6
FA/FI
Halothane
0.4
0.2
Mean±SD
0 0.001
0 10 20 30
Minutes of administration
Figure 1.—Uptake and elimination of inhaled anesthetics. From Yasuda et al.6 Courtesy of the Editor.
Uptake, distribution and elimination
Factors contributing to the uptake, distribu-
tion and elimination of inhaled anesthetics have
been extensively studied and described by Eger.5
This complex process has been investigated using
mathematical, electrical analogues or by comput-
er simulation. The different models of uptake and
distribution include tissues with different capac-
ity (volume x λ tissue/blood) and with different region-
al blood flow.
These models, although not perfect, allow cli-
nicians to predict the effects of changes in physi-
ological parameters or the physico-chemical prop-
erties of the anesthetic on uptake, distribution and
elimination of these drugs.
In humans, the ratio between the alveolar and
inspired concentration (FA/FI) is used to repre-
sent the equilibrium between body tissues and
inspired concentration. The rate of rise of FA/FI
depends on many factors: the blood and tissue sol-
ubility of the anesthetic, the functional residual
capacity, alveolar ventilation, cardiac output,
regional blood flows and tissue capacity. When all
Vol. 76 - No. 3 MINERVA ANESTESIOLOGICA
TORRI
N2O
Halothane
0.1 Isoflurane
FA/FA0
0.01
Sevoflurane
Desflurane
0 60 120
Minutes of elimination
physiological parameters are constant the increase
in FA/FI depends on the solubility of the anes-
thetic. The lower the anesthetic solubility the faster
the equilibration between FA and FI.
Figure 1 shows the wash-in and wash-out curves
of different anesthetics.6 Nitrous oxide, with a
greater solubility than desflurane, has more rapid
kinetics than desflurane. This effect depends on
the inspired concentration of nitrous oxide (70%)
versus 2% of desflurane. A high inspired concen-
tration determines a faster increase in alveolar con-
centration, which is defined as a “concentration
effect”.7 FA/FI increases more rapidly when ven-
tilation is increased with the most soluble anes-
thetics, while this effect is limited for low solubil-
ity agents. An increase in cardiac output reduces the
rate of rise of FA/FI of high solubility agents.5
In obese patients, the wash-in and wash-out
curves are faster with sevoflurane than with isoflu-
rane.8 However, in obese patients, these kinetics are
slightly affected by low solubility agents, such as
desflurane or sevoflurane, when compared to nor-
mal patients.9 On the contrary, in obese patients,
anesthetic uptake is increased. Consequently, to
217
 MINERVA MEDICA COPYRIGHT®
TORRI
maintain a constant end-tidal concentration of
anesthetic, the inspired concentration must be
increased.9
In normal subjects, the uptake of inhaled anes-
thetics is very high in the first minutes and declines
rapidly afterwards; after 20 minutes, as tissues with
low capacity and high flow rate reach the equilib-
rium, the uptake may be considered constant.10
Elimination of inhaled anesthetics from the
body is usually defined by the decrease in alveolar
concentration relative to the last alveolar concen-
tration determined at the end of anesthesia
(FA/FAo) (Figure 1). The lower the anesthetic sol-
ubility, the faster the decrease in FA/FAo and the
shorter the recovery time. Desflurane elimination
and recovery time are more rapid when compared
to other inhalation agents. Prolonged anesthesia
(eight hours or more) increases the recovery time
from very soluble agents, an effect that is limited
for low solubility anesthetics, particularly for des-
flurane.11
The elimination of inhalation anesthetics may
also be expressed by their pulmonary clearance.12
This parameter represents the amount of mixed-
venous blood cleared by the anesthetic in one
minute. The pulmonary clearance depends on
alveolar ventilation, cardiac output and blood
solubility. At normal values of alveolar ventila-
tion and cardiac output, the pulmonary clear-
ance of desflurane, nitrous oxide, sevoflurane and
isoflurane are 3.5, 3.1, 2.8 and 1.8 L/min, respec-
tively.
During clinical anesthesia, the rate at which the
inspired anesthetic concentration rises towards the
concentration delivered by the vaporizer is depend-
ent on the breathing system and on the amount of
fresh gas flowing into the system. When the patient
breathes in a non-rebreathing system, the inspired
concentration is constant, and the rate of rise of the
anesthetic alveolar concentration is more rapid
than it would be in a circular system. During anes-
thetic uptake in a circular system, the inspired
concentration of anesthetic is less than that deliv-
ered from the vaporizer. In the first phase of anes-
thesia, when the anesthetic uptake is very high,
the slow increase in FA/FI should be compensat-
ed for by an increase in the delivered anesthetic
concentration and fresh gas flow, as proposed by
Hendrickx 13, with simple methods.
218 MINERVA ANESTESIOLOGICA
INHALATION ANESTHETICS
Anesthetic potency
In 1965, Eger et al.14 introduced the concept of
anesthetic equipotency, which was defined as the
minimum alveolar concentration of anesthetic
(MAC) preventing movement to surgical stimula-
tion in 50% of subjects. In all studies concerning the
determination of MAC, the alveolar concentration
was held constant for at least 15 minutes before sur-
gical stimulation to obtain an equilibrium between
alveolar and brain partial pressure. The MAC val-
ues are shown in Table II. MAC for nitrous oxide is
104%, a value which was determined in hyperbar-
ic conditions.15 Since its introduction from the
experimental arena, MAC has been used in many
clinical studies to compare the effects of different
inhaled agents on physiological parameters.
Of the factors that may affect the value of MAC
(e.g., hypothermia, extreme hypoxia, acidosis,
hypotension and pregnancy), opioids and patient
age play a relevant role.18, 31, 32 Benzodiazepines
and barbiturates result in a limited reduction of
MAC. Acute alcohol intoxication reduces MAC,
whereas chronic intake of alcohol or sedatives
increases MAC.33 For a large number of inhala-
tion agents, their association with nitrous oxide
is additive,34, 35 i.e., the reduction of halogenated
MAC approximately corresponds to the inspired
fraction of nitrous oxide.
From the clinical introduction of neuromuscu-
lar blocking agents and intravenous opioids, the
clinical signs of general anesthesia were unreliable
in assessing the level of anesthesia. For this reason,
MAC was regarded as a possible approach for deter-
mining the level of surgical anesthesia. Consequently,
different types of MAC were proposed.
Because MAC represents the end tidal concen-
tration of anesthetic determining immobility to
surgical stimulation in only 50% of patients, de
Jong and Eger 36 proposed an Extended MAC (i.e.,
MAC 95%) that approximately corresponds to
1.3 MAC (Table II).
MAC awake (MACaw) 37 represents the mini-
mum alveolar concentration of inhalation agent
that inhibits responses to verbal command in 50%
of patients.
MAC-BAR, which was proposed by Roizen et
al.,28 represents the minimum alveolar concentra-
tion of anesthetic required to block the autonom-
ic response to surgical stimulation in 50% or 95%
March 2010
 MINERVA MEDICA COPYRIGHT®
INHALATION ANESTHETICS
TABLE II.—Different MAC values determined in oxygen. The MAC BAR values have been determined in oxygen/nitrous oxide
mixture.
Nitrous oxide Halothane
MAC50 104 15 0.78 16
MAC awake 64 21 0.41 20
MAC95 0.90 24
MACEI (50) 1.46 25
MAC-BAR(50) 1.45 28
of patients. Its value is higher than the MACaw
and MAC, allowing for control of memory, move-
ments and autonomic responses.
The alveolar concentration corresponding to
MAC-BAR50 and particularly MAC BAR95 may
determine severe cardiovascular depression in
patients. For this reason, anesthesia is usually
obtained by combining halogenated agents with
opioids or nitrous oxide in clinical practice.
In 1999, Katoh et al.18 studied the effects of
nitrous oxide and fentanyl on different values of
MAC, and the results are shown in Figure 2. The
results of this study can be summarized as follows:
1. all points of each relationship shown in Figure
2 are equivalent in terms of anesthetic potency,
and values of MAC or MAC-BAR may be
obtained by different combinations of end-tidal
anesthetic and plasma fentanyl concentrations;
2. both nitrous oxide and fentanyl may reduce
the values of MAC and MAC-BAR; consequent-
ly, both drugs may reduce the halogenated agent
requirement. A similar effect has been obtained
with remifentanil in humans;38
3. fentanyl has limited effects in reducing the
MACaw; consequently, when high opioids con-
centrations are associated with a low halogenated
agent concentration, awareness may occur.
This study suggests that anesthesia may be
obtained by combining halogenated agents and
opioids (with or without nitrous oxide) in differ-
ent proportions to minimize side effects of each
drug. However, the alveolar concentration of
inhaled agents must be higher than MACaw to
suppress recall of emotionally-laden information
during anesthesia.39
Effect on central nervous system
Inhaled anesthetics modify electrical activity of
the central nervous system, as measured by an
Vol. 76 - No. 3 MINERVA ANESTESIOLOGICA
TORRI
Enflurane Isoflurane Sevoflurane Desflurane
1.68 17 1.14 30 2.05 18 6.0 19
0.49 21 0.62 22 2.42 23
1.88 24 1.63 24
3.23 26 3.35 27
1.60 28 , 391.48 29, 39 2.52 18 7.8 29
EEG. During light anesthesia, the voltage of the
EEG increases, and its frequency decreases. As the
anesthetic concentration increases and anesthesia
level becomes deeper, the EEG activity decreases.
Desflurane and isoflurane do not produce epilep-
tic activity, while enflurane may increase epileptic
waves.40 Data concerning sevoflurane remain con-
troversial. Convulsions in patients with intractable
epilepsy may be suppressed by isoflurane and
sevoflurane.41
In normal subjects, cerebral flow is auto-regu-
lated and coupled to cerebral metabolic rate. All
inhalation agents decrease cerebral metabolic rate
and oxygen consumption. The extent to which
flow and metabolism are altered depends on the
specific properties of the selected agent. In fact,
the resulting cerebral blood flow depends on two
factors, the vasoconstriction determined by meta-
bolic suppression and the direct vasodilation deter-
mined by the anesthetic.
The inhalation agents also partially uncouple
the reactivity of cerebral blood flow to CO2. At
clinical concentrations, desflurane and isoflurane
preserve the reactivity of cerebral circulation to
changes in CO2 and flow-metabolism coupling.42
Summors et al.43 showed that sevoflurane preserves
the auto-regulation of cerebral blood flow when the
anesthetic concentration does not exceed 1.5
MAC.
The vasodilation of cerebral vessels caused by
these anesthetic agents has the potential to raise
intracranial pressure. Fraga et al.44 reported that
there was no increase in intracranial pressure for
isoflurane or desflurane in normocapnic patients.
A similar result was obtained by Artru et al.45 for
sevoflurane.
A particular effect of some inhalation agents is
the presence of excitatory effects at emergence. In
preschool children, during emergence from anes-
thesia, agitation has been reported to occur at high-
219
 MINERVA MEDICA COPYRIGHT®
TORRI
4.5
Sevofluraneconcentration (%)
4 MAC-BAR
3.5
MAC
MAC-awake
3 MAC-BAR in N2O
2.5
2 reduce the mean arterial pressure and cardiac out-
1.5
1 in mean arterial pressure determined by desflurane,
0.5
0 by the reduction in systemic vascular resistances.
0 2 4 6 8 10
Fenantyl concentration (ng/mL)
Figure 2.—Reduction of MAC, MACawake and MAC BAR by
increasing plasma concentrations of fentanyl. From Katoh et
al.18 Courtesy of the Editor.
er frequencies after sevoflurane or desflurane anes-
thesia when compared to halothane.46
At present, the role of inhalation agents in neu-
roprotection represents a new area for further inves-
tigations.
Effects on respiratory system
All potent halogenated agents depress ventila-
tion by reducing tidal volume. The concomitant
increase in the respiratory rate does not compen-
sate for the reduced alveolar ventilation, as it pri-
marily determines increased dead space ventila-
tion. Consequently, PaCO2 increases. All inhala-
tion agents raise the threshold of the respiratory
centers to CO2, while simultaneously decreasing
ventilatory responses to CO2.47, 48
Conflicting data from different animal experi-
ments do not allow for the determination of the
clinical relevance of the effects of inhaled anes-
thetic on hypoxic pulmonary vasoconstriction.
The decrease in this reflex has a minimal effect on
oxygenation during one lung anesthesia.49
Halothane, isoflurane and particularly sevoflu-
rane decrease airway resistance, while desflurane
does not produce any change in bronchial tone.50
Halothane and sevoflurane have a minimally irri-
tating effect on airways at clinical concentrations
and may be used for induction of anesthesia both
in children and adults.
Desflurane may act as an irritant during induc-
tion at high inspired concentrations, but has little
effect during the maintenance of anesthesia.
220 MINERVA ANESTESIOLOGICA
INHALATION ANESTHETICS
Cardiovascular effects
From experimental studies in healthy subjects,51, 52
the cardiovascular effects of inhaled anesthetics may
be summarized as follows. All halogenated agents
put index in a dose-related manner. The reduction
sevoflurane and isoflurane is primarily determined
On the contrary, halothane reduces the mean arte-
rial pressure by reducing cardiac output without
reducing systemic vascular resistance. As anesthet-
ic concentrations of desflurane and isoflurane
increase, heart rate increases; with increasing
halothane concentrations, heart rate remains near-
ly constant. An increase in heart rate is observed
with sevoflurane at alveolar concentrations above
1 MAC. All inhalation agents produce a dose-
dependent reduction in the cardiac index that may
be partially compensated by an increase in heart
rate during desflurane and sevoflurane anesthesia.
The anesthesiologist must be aware of the effects
of these particular agents on cardiovascular param-
eters. Patients’ responses to inhalation agents may
be modified by cardiac diseases, surgical stimula-
tion and many drugs. In some studies, desflurane
and sevoflurane showed high cardiovascular sta-
bility both in young and old patients.53, 54
The myocardial depression and reduction in
mean arterial pressure produced by halogenated
agents is slightly increased when these agents are
combined with nitrous oxide.
The mechanism of arrhythmia induction during
administration of potent halogenated anesthetics is
not completely understood. Sevoflurane may prolong
the QT interval and should be administered with
caution in patients with idiopathic or acquired long
QT intervals.55 Sevoflurane and isoflurane may sup-
press arrhythmias caused by local anesthetics.56.
The threshold of epinephrine for ventricular
arrhythmia is higher for desflurane and sevoflu-
rane when compared to halothane or isoflurane,
and the arrhythmogenic effects are very low with
these two agents.57, 58
Regional blood flows
Coronary blood flow is auto-regulated and
depends primarily on myocardial demand. Some
March 2010
 MINERVA MEDICA COPYRIGHT®
INHALATION ANESTHETICS
studies in animals have demonstrated that auto-reg-
ulation is preserved during exposure to clinical
concentrations of halogenated anesthetics. In an
animal model, isoflurane may result in “coronary
steal”, a diversion of blood flow arising from a
fixed stenosis.59 This effect has not been confirmed
in humans. Sevoflurane and desflurane do not
cause coronary steal.
The effects of inhalation agents on cerebral
blood flow have been previously discussed.
Many inhalation anesthetics decrease portal
venous flow, while halothane decreases hepatic
artery blood flow and oxygen delivery to the liv-
er.60 All halogenated agents decrease renal blood
flow, glomerular filtration and urine output,
although auto-regulation of renal blood flow is
preserved.61 The decrease in renal blood flow dur-
ing maintenance of anesthesia is often related to a
reduction in circulating volume caused by increased
vascular capacity.
Cardiac protection by inhaled anesthetics
Halogenated agents mimic the cardioprotec-
tive effect of ischemia first described in 1986 by
Murry,62 which represents an adaptive response
to brief sublethal episodes of ischemia leading to
protection against subsequent lethal ischemia.
Two windows of cardioprotection have been
described: an early phase lasting two hours and a
late preconditioning phase reappearing 24 hours
in the postoperative period and lasting 72 hours.63
The mechanism of cardioprotection is very com-
plex. It includes intracellular reactions involving
membrane Gi protein-coupled receptors, phos-
pholipase β, diglycerol and protein kinase C, caus-
ing activation of the KATP channels of both the
mitochondria and sarcolemma. Reactive oxygen
species (ROS) also appear to play an important
role.64, 65 Moderate ROS production induced by
inhaled anesthetics is required to induce precon-
ditioning, which in turn, allows for a reduction
in the ROS excess seen during reperfusion.
Inhaled anesthetics also reduce platelet adhe-
sion to the vascular wall, while not impacting
endothelial cell activation.66
Many clinical studies have confirmed the cardiac
preconditioning effects of inhaled anesthetics in
patients undergoing cardiac surgery,67-71 and a
recent meta-analysis pooling data from studies
Vol. 76 - No. 3 MINERVA ANESTESIOLOGICA
TORRI
exploring the effects of desflurane and sevoflurane
found a significant reduction in myocardial infarc-
tion, ICU stay, time on mechanical ventilation in
the ICU, hospital stay, in-hospital mortality and
incidence of long term events.72
The cardioprotective effect of halogenated agents
in patients with coronary artery disease who are
undergoing non-cardiac surgery has not yet been
supported by clinical trials.
Effects on muscle-relaxation
Inhaled anesthetics cause an enhancement of
the effects of neuromuscular blocking drugs and,
consequently, reduce the muscle relaxants require-
ment.
All halogenated agents may trigger malignant
hyperthermia (MH), a very rare adverse event of
general anesthesia. Nevertheless, cases of MH or
delayed MH have been reported both for desflu-
rane and sevoflurane.73-75 However, the incidence
of MH seems to be much lower with desflurane
and sevoflurane than with halothane, particular-
ly when it is administered in association with suc-
cinylcholine.
Metabolism and toxicity related to inhalation
agents
Recently, interest around the metabolism of
inhaled agents has been focused on the toxicity of
its metabolites, which may be harmful for patients.
Halothane is largely metabolized to fluoride,
80% of which is found in the urine as hexafluo-
roiodopropanol; this compound does not under-
go further biodegradation but is instead conjugat-
ed to glucoronide. In patients who develop
halothane hepatitis, a reactive metabolite of
halothane is thought to acetylate liver proteins,
which can modify these proteins, making them
neoantigens. It is the antibodies that are formed
against neoantigens that result in liver injury.76
Fatal halothane hepatitis is estimated to occur in
1 every 100,000 anesthesia procedures.
The extent of enflurane metabolism is approx-
imately 2%, and the majority of the anesthetic is
eliminated through the lungs. Enflurane is metab-
olized in the liver by the cytochrome P450
enzymes. The final products of its metabolism
221
 MINERVA MEDICA COPYRIGHT®
TORRI
include difluoromethoxydifluoroacetic acid and
fluoride. The possible nephrotoxicity of enflurane
is a concern only when high inspired concentra-
tions of the drug are used or after prolonged anes-
thetic procedures.
Isoflurane undergoes minimal oxidative metab-
olism to inorganic trifluoroacetic acid and fluo-
ride and involves the cytochrome P450 2EI
enzyme.
Desflurane is very resistant to metabolism, as
only 0.02% of the drug is metabolized. Its bio-
transformation is very similar to isoflurane.
Desflurane is unlikely to result in formation of
neoantigens from oxidative metabolism. Serum
fluoride has not been observed in humans after
exposure to high desflurane concentrations or pro-
longed anesthesia.77
Sevoflurane is subjected to cytochrome P450
2EI oxidative degradation, and the final metabol-
ic products are carbon dioxide, inorganic fluoride
and hexafluoroisopropanol. Fluoride-induced
nephrotoxicity after sevoflurane administration
has been extensively investigated. The relative
paucity of renal sevoflurane defluorination may
explain the absence of the clinical nephrotoxicity
of this agent, despite the fact that plasma fluoride
concentrations may in some cases approach 50
µmol/L.78 Kharasch et al. found that there is no
significant difference in renal tubular function and
cell integrity between the renal effect of sevoflurane
and isoflurane in surgical patients undergoing low-
flow anesthesia for as long as seven hours.79
Prolonged anesthesia with sevoflurane does not
impair renal concentrating functions, as demon-
strated by a study based on the desmopressin test.80
Degradation in CO2 absorbents
All halogenated agents degrade in the presence
of dry alkaline CO2 absorbents. The degradation
of sevoflurane to compound A depends on the
temperature and water content in the absorber.81
Compound A has been shown to cause renal
injuries in rats when inhaled at high inspired con-
centrations. Compound A is less toxic in humans
because the activity of the β-liase enzyme is much
lower in humans than in rats.82 When a fresh gas
flow of 2 L/min is given, compound A concen-
tration in the circuit is very low, and renal toxici-
ty has never been reported.
222 MINERVA ANESTESIOLOGICA
INHALATION ANESTHETICS
In dry CO2 soda lime or Baralyme, desflurane,
enflurane and isoflurane degrade to carbon monox-
ide (CO).83 Carbon monoxide may result from
the biodegradation of these anesthetics because a
particular moiety (CF2H-) is present in their mol-
ecules. Sevoflurane and halothane do not possess
this moiety and do not degrade to CO.
In new absorbents, the elimination of mono-
valent bases prevents both compound A and CO
production; this is also the case when these new
absorbents are dry.84
Long term exposure to trace of anesthetic.
At the beginning of the 1960s, some studies
demonstrated that in the operating room, with-
out adequate climate control and without a waste
gas scavenging system, occupational exposure to
anesthetic gases exceeded the threshold limits. A
study by Veisman 85 suggested that long term expo-
sure to traces of nitrous oxide could contribute to
the increased incidence of abortion and congeni-
tal abnormalities in female anesthesiologists.
Consequently, exposures to trace inhaled anes-
thetics have been thought by many anesthesiolo-
gists to cause adverse effects on operating room
personnel.
The majority of the following epidemiological
studies on occupational hazard have been focused
on miscarriage, birth defects, teratogenicity, car-
cinogenicity and neurobehavioral functioning.
These studies have been used in a meta-analysis
by Buring et al.86 that showed somewhat of an
increase in the relative risk for liver or kidney dis-
eases and for cervical cancer in woman. In a sec-
ond meta-analysis, Bovin 87 found a borderline
increase in the relative risk of spontaneous abortion
in female anesthesiologists, while in the subgroup
exposed to nitrous oxide, the relative risk of abor-
tion was not increased.
However, the studies used in the two meta-
analyses have been heavily criticized for loading
of the questionnaires, lack of information on expo-
sure time and anesthetic levels, poor response rates
to questionnaires and selection bias.88 Further
studies failed to demonstrate an increased rate of
cervical cancer or other diseases.89
Two studies by Ericson and Kallen,90, 91 based on
the registered data of operating room personnel
showed no association between occupational expo-
March 2010
 MINERVA MEDICA COPYRIGHT®
INHALATION ANESTHETICS
sure and reproductive effects. A prospective study
among female anesthesiologists and other doctors
was conducted by Spence.92, 93 This study con-
cluded that there is no evidence to suggest that
exposure to traces of waste anesthetic gases results
in adverse health consequences. The results also
indicated that female anesthesiologists did not
have a greater incidence of infertility than other
physicians.
Given the fact that many of the studies that
have been conducted have been retrospective stud-
ies and have had many methodological errors, the
evidence for an association between anesthetic
exposure and congenital abnormality seems to be
inconsistent and unrelated to hours of exposure
to trace of anesthetics.
Because the possible effects of health hazards
from long-term exposure to traces of inhalation
agents cannot yet be excluded, many authorities in
different countries have established limits for expo-
sure to inhalation anesthetics. These limits range
from two to ten ppm as a time-weighted average
concentration over the time of exposure for halo-
genated agents and 50-100 ppm for nitrous oxide.
The reduction in operating room pollution
should be a high priority. For this reason, the ASA
Committee on the Occupational Health of
Operating Room Personnel has offered recom-
mendations to minimize exposure levels. These
recommendations include an efficient climate sys-
tem, a waste gas scavenging system, the use of low
flow ventilation technique and correct technique
of anesthesiologist.
Should we continue to use nitrous oxide ?
For one and a half centuries, nitrous oxide has
played a relevant role in general anesthesia; how-
ever, in the last decade, some critical reports on
nitrous oxide have been published.94-99
Many of the side effects of nitrous oxide corre-
late with its physical properties. Its ability to dif-
fuse into air filled cavities increases the likelihood
of pneumothorax, air emboli and pressure in the
cuff of the endotracheal tube. Nitrous oxide diffu-
sion causes an increase in middle ear pressure and
distension of the bowel, possibly resulting in
increases in postoperative nausea and vomiting
According to Neuman,100 during laparoscopic
Vol. 76 - No. 3 MINERVA ANESTESIOLOGICA
TORRI
abdominal surgery, nitrous oxide in combination
with methane or hydrogen contained in the bow-
el could cause combustion.
The biological effects of nitrous oxide have been
recently reviewed by Sanders et al.101
Nitrous oxide inactivates vitamin B12 by an
irreversible oxidation of the central cobalt and
depresses methionine synthetase activity in both
animals and humans.102 Recent data show that in
patients with a homozygous mutation, nitrous
oxide anesthesia results an increase in plasma
homocysteine levels. The increase in plasma homo-
cysteine level could increase perioperative myocar-
dial complications 103, however, no clinical data
are available to support this hypothesis. An inter-
national study involving a large number of patients
at risk of coronary artery disease (Enigma II) will
probably ascertain the benefits and risks of remov-
ing nitrous oxide from the anesthetic technique.104
The results from a questionnaire proposed by
the Association of Anesthetists of Great Britain
and Ireland indicate that 49% of anesthetists had
reduced their use of nitrous oxide. This was due to
medical considerations rather than concerns over
health and pollution.105
According to Baum,106 nitrous oxide should not
be used routinely as a carrier gas, and the safer
mixture of oxygen/medical air is able to replace
this old anesthetic with some economical advan-
tages.
The combination of halogenated agents with
short acting opioids results in the possibility of
limiting the clinical application of nitrous oxide.
The advantages of nitrous oxide include its anal-
gesic properties, which allow for the reduction of
halogenated agents and may limit their cardiores-
piratory effects in critically ill patients. A recent
paper suggests that nitrous oxide prevents the
enhancement of pain sensitivity induced by noci-
ceptive inputs and by acute fentanyl and mor-
phine tolerance.107 Consequently, whether the side
effects of nitrous oxide support its exclusion from
clinical practice remains controversial.
The interest in the continued use of nitrous
oxide can be found in intravenous sedation to
reduce the risk of awareness and recall or in some
critical situations when administration of halo-
genated agents must be rapidly interrupted.
Attempts to replace nitrous oxide with other
223
 MINERVA MEDICA COPYRIGHT®
TORRI
gases had led to an increase in studies on xenon.
This inert gas does not undergo metabolic bio-
transformation and has no direct negative envi-
ronmental effects. Xenon has a very low solubili-
ty in the blood (λ=0.15), and its potency is high-
er when compared to nitrous oxide blood solubil-
ity (MAC 63% vs. 105%).108
Xenon cannot be synthesized, and the available
amount is very low. Consequently, at present, the
cost of the compound may be a limiting factor for
clinical use. All methods proposed for the use of
xenon in a totally closed system, with recycling of
the waste gas, are very sophisticated and require a
high technology anesthesia workstation. Therefore,
this gas should be of great interest in our field as
a possible alternative to nitrous oxide for particu-
lar surgical procedures.
Where and how inhalation agents act?
The mechanism of general anesthesia has been
presented in two excellent reviews and is here sum-
marized.109, 110
Over the last decades, our understanding of the
mechanism of general anesthesia has rapidly
evolved. Overton and Mayer 111, 112 independent-
ly observed a strong correlation between inhala-
tion anesthetic potency and their solubility in olive
oil. This correlation suggested that the site of action
of these agents could be the lipids of the cell mem-
brane. The “lipid theory” proposed in the 19th
century persisted until the late 1970s when new
research introduced the hypothesis that proteins
could be directly involved in the mechanism of
general anesthesia. Franks and Lieb 113, 114 demon-
strated that protein may be a site of action for
inhalation agents; in these studies, inhalation agents
inhibited a lipid-free preparation of the enzyme
firefly luciferase.
In the last year, particular attention has been
given to ion channels. Ion channels are specific
proteins that regulate the flow of ions across the cell
membrane and act as mediators of neural activity.
Binding sites for anesthetics have been identi-
fied in different ion channels, including serotonin
receptors, nicotinic acetylcholine receptors, γ-
aminobutyric acid type A (GABAA) receptors,
glycine receptors and glutamate receptors activat-
ed by N-methyl-D-aspartate (NMDA) or alpha-
224 MINERVA ANESTESIOLOGICA
INHALATION ANESTHETICS
amino-3-hydroxy-methyl-4-isoxazolepropionic
acid (AMPA).115, 116 Inhalation agents prolong
inhibitory postsynaptic channel activity of GABAA
and glycine receptors and inhibit excitatory synap-
tic channel activity (nicotinic acetylcholine, sero-
tonin and glutamate receptors). Although there is
strong evidence that anesthetics may act on GABAA
receptors, xenon and nitrous oxide only minimal-
ly enhance the activity of these receptors.117
Inhalation agents prevent movements in
response to surgical noxious stimulation by depress-
ing spinal cord function. The evidence for this
comes from experiments in decerebrate rats and
goats by Rampil et al.118 and Antognini and
Schwartz.119 This study demonstrated that MAC
measures the effect of inhalation agents on the
spinal cord rather than in the brain.
At the level of spinal motor-neurons, inhala-
tion agents increase the activity of inhibitory
glycine receptors and inhibit post-synaptic AMPA
and NMDA receptors independent of their action
on GABAA receptors.120 Sonner et al. hypothe-
sized that GABAA receptors are not involved in
mediating immobility.121 According to other
sources, inhalation agents determine a contribution
of GABAA receptors to immobility.122
Inhalation agents decrease the transmission of
noxious stimulation ascending from the spinal
cord to the brain and affect their action in the
brain.123
The amnesic effect of anesthetic agents is medi-
ated within particular regions of the brain. At low
concentrations, inhalation agents inhibit nicotinic
acetylcholine receptors and impair memory and
learning, but not immobility.124 The susceptibil-
ity of neurocortical neurons to inhalation anes-
thetics at concentration equivalent to MACawake
significantly increases the GABAAergic synaptic
inhibition.125
These data suggest that anesthetics induce amne-
sia and immobility by affecting different sites.
Using brain imaging (positron emission tomog-
raphy and functional magnetic resonance imag-
ing) Alkire et al. found a decrease in glucose meta-
bolic activity produced by inhalation agents, which
reflects a reduction in synaptic activity.126, 127 The
thalamus and midbrain reticular formation are
more depressed by inhalation agents than other
regions of the brain. Some regions of the brain dif-
March 2010
 MINERVA MEDICA COPYRIGHT®
INHALATION ANESTHETICS
fered in their activity between the awake state and
the anesthetic state.
Another study of Alkire et al. shows a signifi-
cant correlation between the regional metabolic
reductions that occur during isoflurane anesthesia
in humans and the regional distribution of mus-
carinic (acetylcholine) receptors.128
In conclusion, after the identification of many
sites of action for inhalation agents our knowl-
edge on the mechanism of general anesthesia have
evolved from a “unitary hypothesis” to the more
recent concept of “complex effects and multiple
mechanisms”. Despite the development of new
techniques and the increased interest in under-
standing this area, the exact mechanism of anes-
thetic action remains a complex and unresolved
problem.
Conclusions
The pharmacokinetic advantages of inhalation
anesthetics are unique. By increasing or decreasing
their inspired concentration, it is possible to
increase or decrease their concentration in the
blood and tissues, allowing for rapid changes in
anesthesia depth and providing a simple method
for inducing, maintaining and reversing general
anesthesia. The early pioneers of anesthesia were
aware of these advantages, and today, the moni-
tors included in modern anesthesia workstations
allow us to directly control the inspired and the
end-tidal concentrations of these agents. The flex-
ibility of inhalation anesthesia cannot be repro-
duced with modern intravenous hypnotics or opi-
oids, even when they are delivered by sophisticat-
ed infusion pumps. Furthermore, it is important
to underline the protective effects of inhalation
agents on several different organs, as similar effects
cannot be obtained with clinical concentrations
of hypnotics or opioids.
References
1. Calverley RK. Fluorinated anesthetics. II. Fluroxene. Surv
Anesth 1987;30:126-30.
2. Suckling CW. Some chemical and physical factors in the
development of fluothane. Br J Anaesth 1957;29:466-72.
3. Jones RM. Desflurane and sevoflurane: inhalation anaesthet-
ics for this decade? Br J Anaesth 1990;65:527-36.
4. Lockwood GG, Sapsed-Byrne SM, Smith MA. Effect of tem-
perature on the solubility of desflurane, sevoflurane, enflu-
rane and halothane in blood. Br J Anaesth 1977;79:517-20.
Vol. 76 - No. 3 MINERVA ANESTESIOLOGICA
TORRI
5. Eger EI. Anesthetic uptake and action. Baltimore, MD: The
Williams and Wilkins Co.; 1974.
6. Yasuda N, Lockhart SH, Eger EI II, Weiskopf RB, Lin J.
Comparison of kinetics of desflurane and halothane in
humans. Anesthesiology 1991;72:316-24.
7. Epstein RM, Rackow H, Salanitre E, Wolf GL. Influence of
the concentration effect on the uptake of gas mixtures: the
second gas effect. Anesthesiology 1964;25:364-71.
8. Torri G, Casati A, Comotti L, Bignami E, Santorsola R,
Scarioni M. Wash-in and wash-out curves of sevoflurane and
isoflurane in morbidity obese patients. Minerva Anestesiol
2002;68:523-7.
9. Lemmens HJM, Saidman LJ, Eger EI II, Laster MJ. Obesity
modestly affects inhaled anesthetic kinetics in humans. Anesth
Analg 2008;107:1864-70.
10. Eger EI II. Desflurane: A compendium and reference.
Rutherford, NJ: Heolthpress Publishing Group; 1993. p. 80-9.
11. Eger EI II, Gong D, Koblin DD, Bowland T, Ionescu P, Laster
MG et al. Effect of anesthetic duration of kinetic and recov-
ery characteristics of desflurane vs desflurane in volunteers.
Anesth Analg 1998;86:414-21.
12. Torri G, Damia G. Pulmonary clearance of anaesthetic agents.
A theoretical study. Br J Anaesth 1968;40:757-66.
13. Hendrickx JF, Dewulf BB, De Mey N, Carette R, Deloof T,
De Cooman S et al. Development and performance of a two-
step desflurane –o(2)/N(2)O fresh gas flow sequence. J Clin
Anesth 2008;20:501-7.
14. Eger EI II, Saidman LJ, Brandstater B. Minimum alveolar
anesthetic concentration: a standard of anesthetic potency.
Anesthesiology 1965;26:756-63.
15. Hornbein TF, Eger EI II, Winter PM, Smith G, Wetstone
D, Smith KH. The minimum alveolar concentration of nitrous
oxide in men. Anesth Analg 1982;61:553-6.
16. Saidman LJ, Eger EI II, Munson ES, Babad AA, Muallem
M. Minimum alveolar concentrations of methoxyflurane,
halothane, ether and cyclopropane in man: correlation with
theories of anesthesia. Anesthesiology 1967;28:994-1002.
17. Gion H, Saidman LJ. The minimum alveolar concentration
of enflurane in man. Anesthesiology 1971;35:361-4.
18. Katoh T, Kobayashi S, Suzuki A, Iwamoto T, Bito H, Ikeda
K. The effect of on sevoflurane requirements for somatic and
sympathetic responses to surgical incision. Anesthesiology
1999;90:398-405.
19. Rampil I, Lockhart S, Zwass M, Peterson N, Yasuda N, Eger
EI II et al. Clinical characteristics of desflurane in surgical
patients: Minimum Alveolar Concentration. Anesthesiology
1991;74:429-33.
20. Stoelting RK, Longnecker DE, Eger EI. Minimum alveolar
concentrations in man on awakening from methoxyflurane,
halothane, ether and fluroxene anesthesia: MAC awake.
Anesthesiology 1970;33:5-9.
21. Dwyer R, Bennett HL, Eger EI. Effect of isoflurane and
nitrous oxide in subanesthetic concentrations on memory
and responsiveness in volunteers. Anesthesiology 1992;77:888-
98.
22. Katoh T, Uchiyama T, Ikeda K. Effect of fentanyl on awak-
ening concentration of sevoflurane. Br J Anaesth 1994;73:322-
5.
23. Chortkoff BS, Eger EI II, Crankshaw DP, Gonsowski CT,
Dutton RC, Ionescu P. Concentrations of desflurane and
propofol that suppress response to command in humans.
Anesth Analg 1995;81:737-43.
24. De Jong RH, Eger EI II. Mac expanded: AD50 and AD95 val-
ues of common inhalation anesthetics in man. Anesthesiology
1975;42:384-9.
25. Yakaitis RW, Blitt CD, Angiulo JP. End-tidal halothane con-
centration for endotracheal intubation. Anesthesiology
1977;47:386-8.
26. Yakaitis RW, Blitt CD, Angiulo JP. End-tidal enflurane con-
centration for endotracheal intubation. Anesthesiology
1979;50:59-61.
225
 MINERVA MEDICA COPYRIGHT®
TORRI
27. Katoh T, Nakajima Y, Moriwaki G, Kobayashi S, Suzuki A,
Iwamoto T et al. Sevoflurane requirements for tracheal intu-
bation with and without fentanyl. Br J Anaesth 1999;82:561- 47.
5.
28. Roizen MF, Horrigan RW, Frazer BM. Anesthetic doses block- 48.
ing adrenergic (stress) and cardiovascular responses to inci-
sion – MAC-BAR. Anesthesiology 1981;54:390-8.
29. Daniel M, Weiskopf RB, Noorani M, Eger EI II. Fentanyl 49.
augments the blockade of the sympathetic response to inci-
sion (MAC BAR) produced by desflurane and isoflurane:
desflurane and isoflurane MAC BAR without and with fen-
tanyl. Anesthesiology 1998;88:43. 50.
30. Stevens WC, Dolan WM, Gibbons RT, White A, Eger EI II.
Minimum alveolar concentration (MAC) of isoflurane with
and without nitrous oxide in patients of various age.
Anesthesiology 1975;42:197-200. 51.
31. Gregory GA, Eger EI II, Munson ES. The relationship between
age and halothane requirement in man. Anesthesiology
1969;30:488-91. 52.
32. Melvin MA, Johnson BH, Quasha AI, Eger EI II. Induction
of anesthesia with midazolam decreases halothane MAC.
Anesthesiology 1982;57:238-41.
33. Firestone LL, Korpi ER, Niemi L, Rosenberg PH, Homanics 53.
GE, Quinlan JJ. Halothane and desflurane requirements in
alcohol-tolerant and nontolerant rats. Br J Anaesth
2000;85:757-62. 54.
34. Di Fazio CA, Brown RE, Ball CG, Heckel CG, Kennedy SS.
Additive effects of anesthetics and theories of anesthesia.
Anesthesiology 1972;36:57-63.
35. Torri G, Damia G, Fabiani ML. Effect of nitrous oxide on 55.
the anaesthetic requirement of enflurane. Br J Anaesth
1974;46:468-72.
36. de Jong RH, Eger EI II. MAC expanded: AD50 and AD95 56.
values of common inhalation anesthetics in man.
Anesthesiology 1975;42:384-9.
37. Stoelting RK, Longnecker DE, Eger EI II. Minimal alveolar
concentrations on awakening from methoxyflurane, halothane, 57.
ether and fluroxene in man: MACawake. Anesthesiology
1970;33:5-9.
38. Albertin A, Casati A, Bergonzi PC, Fano G, Torri G. Effect 58.
of two target-controlled concentrations of remifentanil on
MAC-BAR of sevoflurane. Anesthesiology 2004;100:255-9.
39. Chortkoff BS, Gosowski CT, Bennet HL, Levinson B,
Crankshaw DP, Dutton RC et al. Subanesthetic concentrations 59.
of desflurane and propofol suppress recall of emotionally
charged information. Anesth Analg 1995;81:728-36.
40. Neigh JL, Garman JK, Harp JR. The electroencephalograph-
ic pattern during anesthesia with ethrane: effects of depth of 60.
anesthesia, PaCO2 and nitrous oxide. Anesthesiology
1971;35:482-7.
41. Endo T, Sato K, Shamato H, Yoshimoto T. Effect of sevoflu- 61.
rane on electrocorticography in patient with intractable tem-
poral lobe epilepsy. J Neurosurg Anesthesiol 2002;14:59-62.
42. Mielck F, Stefan H, Buhre W. Effect of 1 Mac desflurane on 62.
cerebral metabolism, blood flow and carbon dioxide reactiv-
ity in humans. Br J Anaesth 1998;81:155-60.
43. Summors AC, Gupta AK, Matta BF. Dynamic cerebral 63.
autoregulation during sevoflurane anesthesia: a comparison
with isoflurane. Anesth Analg 1999;88:341-5.
44. Fraga M, Rama Marceira P, Rodino S, Aymerich H, Pose P, 64.
Belda J. The effect of isoflurane and desflurane on intracra-
nial pressure, cerebral perfusion pressure, and cerebral arterove-
nous oxygen content difference in normocapnic patients with 65.
supratentorial brain tumors. Anesthesiology 2003;98:1085-
90.
45. Artru AA, Lam AM, Johnson JO, Sperry RJ. Intracranial 66.
pressure, middle cerebral artery flow velocity, and plasma
inorganic fluoride concentrations in neurosurgical patients 67.
receiving sevoflurane or isoflurane. Anesth Analg 1997;85:587-
92.
46. Aono J, Ueda W, Mamiya K, Takimoto E, Manabe M. Greater
226 MINERVA ANESTESIOLOGICA
INHALATION ANESTHETICS
incidence of delirium during recovery from sevoflurane anes-
thesia in preschool boys. Anesthesiology 1997;87:1298-300.
Doi M, Ikeda K. Respiratory effects of sevoflurane. Anesth
Analg 1987;66:241-4.
Lockhart SH, Rampil IJ, Yasuda N, Eger EI II, Weiskopf RB.
Depression of ventilation by desflurane in humans.
Anesthesiology 1991;74:484-8.
Wang JY, Russell GN, Page RD, Oo A, Pennefather SH. A
comparison of the effects of desflurane and isoflurane on arte-
rial oxygenation during one-lung ventilation. Anaesthesia
2000;55:167-73.
Goff MJ, Arain SR, Ficke DJ, Uhrich TD, Ebert TJ. Absence
of bronchodilation during desflurane anesthesia: a compari-
son to sevoflurane and thiopental. Anesthesiology
2000;93:404-8.
Weiskopf RB, Cahalan MK, Ionescu P, Eger EI II, Yasuda N,
Lockhart SH et al. Cardiovascular action of desflurane in nor-
mocapnic volunteers. Anesth Analg 1991;73:143-56.
Malan TP, Di Nardo JA, Isner RJ, Frink EJ Jr, Goldberg M,
Fenster PE et al. Cardiovascular effects of sevoflurane compared
with those of isoflurane involunteers. Anesthesiology
1995;83:918-28.
Bartkowski RR, Azad SS, Witkowski TA, Seltzer JL, Marr A,
Lessin J. Hemodynamic responses to desflurane anesthesia: a
comparison with isoflurane. Anesth Analg 1991;72:S13.
Torri G, Casati A. Cardiovascular homeostasis during inhala-
tional general anesthesia. A clinical comparison between
sevoflurane and isoflurane. On behalf of the Italian Research
Group on Sevoflurane. J Clin Anesth 2000;12:117-22.
Gallagher JD, Weindling SN, Anderson G, Fillinger MP. Effects
of sevoflurane on QT interval in a patient with congenital long
QT syndrome. Anesthesiology 1998;89:1569-73.
Fukuda H, Hirabayashi Y, Shimizu R, Saitoh K, Mitsuhata H.
Sevoflurane is equivalent to isoflurane for attenuating bupi-
vacaine-induced arrhythmias and seizures in rats. Anesth
Analg 1996;83:570-3.
Moore M, Weiskopf RB, Eger EI II. Arrhythmogenic doses
of epinephrine are similar during desflurane or isoflurane
anesthesia in humans. Anesthesiology 1993;79:943-7.
Navarro R, Weiskopf RB, Moore MA, Wilson C. Humans
anesthetized with sevoflurane or isoflurane have similar
arrhythmic responses to epinephrine. Anesthesiology
1994;80:545-9.
Reiz S, Balfors E, Sorensen MB, Ariola S Jr, Friedman A,
Truedsson H. Isoflurane – a powerful coronary vasodilator
in patients with coronary artery disease. Anesthesiology
1983;59:91-7.
Frink EJ, Morgan SE, Coetzee A, Conzen PF, Brown BR Jr.
The effects of sevoflurane, halothane, enflurane and isoflurane
on hepatic blood flow. Anesthesiology 1992;76:85-90.
Bastron RD, Perkins RM, Pyne JL. Autoregulation of renal
blood flow during halothane anesthesia. Anesthesiology
1977;46:142-4.
Murry CE, Jennings RB, Reimer KA. Preconditioning with
ischemia: a delay of lethal cell injury in ischemic myocardium.
Circulation 1986;74:1124-36.
Yellon DM, Baxter GF. A “second window of protection” or
delayed preconditioning phenomenon: future horizons for
myocardial protection? J Mol Cell Cardiol 1995;27:1023-4.
Okubo S, Xi L, Bernardo NL, Yoshida K, Kukreja RC.
Myocardial preconditioning: basic concepts and potential
mechanisms. Mol Cell Biochem 1999;196:3.
De Hert SG, Turani F, Mathur S, Stowe DF. Cardioprotection
with volatile anesthetics. Mechanism and clinical implica-
tion. Anesth Analg 2005;93,1584-93.
Zweier JL, Talukder MA. The role of oxidants and free radi-
cals in reperfusion injury. Cardiovasc Res 2006;70:181-90.
Kowalski C, Zahler S, Becker BF, Flaucher A, Conzen PF,
Gerlach E et al. Halothane, isoflurane and sevoflurane reduce
postischemic adhesion of neutrophils in the coronary system.
Anesthesiology 1997;81:188-95.
March 2010
 MINERVA MEDICA COPYRIGHT®
INHALATION ANESTHETICS
68. Belhomme D, Peynet J, Louzy M, Launay JM, Kitakaze M,
Menasché P. Evidence for preconditioning by isoflurane in
coronary artery bypass graft surgery. Circulation
1999;100(Suppl. 2):340-4.
69. Julier K, da Silva R, Garcia C, Bestmann L, Frascarolo P,
Zollinger A et al. Preconditioning by sevoflurane decreases
biochemical markers for myocardial and renal dysfunction
in coronary artery bypass graft surgery: a double-blinded,
placebo-controlled, multicenter study. Anesthesiology
2003;98:1315-27.
70. De Hert SG, Cromheecke S, ten Broecke PW, Mertens E,
De Blier IG, Stockman BA et al. Effect of propofol, desflurane
and sevoflurane on recovery on myocardial function after
coronary surgery in elderly high-risk patients. Anesthesiology
2003;99:314-23.
71. De Hert SG, Van der Linden PJ, Cromheecke S, Meeus R, ten
Broecke PW, De Blier IG et al. Choice of primary regimen can
influence intensive care unit length of stay after coronary sur-
gery with cardiopulmonary bypass. Anesthesiology
2004b;101:9-20.
72. Landoni G, Biondi-Zoccai GL, Zangrillo A, Bignami E,
Calabrò MG. Desflurane and sevoflurane in cardiac surgery:
a meta-analysis of randomized clinical trials. J Cardiothor
and Vasc Anesth 2007;14:502-11.
73. Lane JE, Brooks AG, Logan MS, Newman WH, Castresana
MR. An unusual case of malignant hyperthermia during des-
flurane anesthesia in an Africa-American patient. Anesth
Analg 2000;91:1032-4.
74. Hsu SC, Huang WT, Yeh HM, Hsieh AY. Suspected malig-
nant hyperthermia during sevoflurane anesthesia. J Clin Med
Assoc 2007;70:507-10.
75. Nakamura N, Ueda T, Ishikawa R, Tasaka Y, Fukuuchi K,
Sato N. Malignant hyperthermia developing during esophageal
resection in an 82-year-old man. J Anesth 2008;22:464-6.
76. Lind R, Gandolf A, Hall P. The role of oxidative biotransfor-
mation of halothane in the guinea pig model of halothane –
associated hepatotoxicity. Anesthesiology 1999;70:649-59.
77. Sutton TS, Koblin DP, Gruenke LD. Fluoride metabolites
after prolonged exposure of volunteers and patients to des-
flurane. Anesth Analg 1991;73:180-5.
78. Frink EJ Jr, Malan TP Jr, Isner RJ, Brown EA, Morgan SE,
Brown BR Jr. Renal concentrating function with prolonged
sevoflurane or enflurane anesthesia in volunteers.
Anesthesiology 1994;80:1019-25.
79. Kharasch ED, Howkins DC, Thummel KE. Human kidney
methoxyflurane and sevoflurane metabolism : intrarenal flu-
oride production as a possible mechanism of methoxyflurane
nephrotoxicity. Anesthesiology 1995;82:689-99.
80. Kharasch ED, Frink EJ Jr, Zager R, Bowdle TA, Artro A,
Nogami WM. Assessment of low-flow sevoflurane and isoflu-
rane effects on renal function using sensitive markers of tubu-
lar toxicity. Anesthesiology 1997;86:123-58.
81. Fang ZX, Eger EI II, Laster MJ, Chottkoff BS, Ionescu P.
Carbon monoxide production from degradation of desflu-
rane, enflurane, isoflurane, halothane and sevoflurane by dry
soda lime and baralyme. Anesth Analg 1995,80,1187-93.
82. Iyer RA, Ander MW. Cysteine congregate beta-lyase-depend-
ent biotransformation of the cysteine-s-conjugate of the
sevoflurane degradation product compound A in human,
non-human primate and rat kidney cytosol and mitochondria.
Anesthesiology 1996;85:1454-61.
83. Fang ZX, Eger EI II. Source of toxic CO expanded – CHF2
anesthetic + dry absorbent. APSF Newsletter 1995;1187.
84. Neumann MA, Laster MJ, Weiskopff RB, Gong DH, Dudziak
R, Forster H, Eger EI II. The elimination of sodium and
potassium hydroxides from dissicated soda lime diminishes
degradation of desflurane to carbon monoxide and sevoflurane
to compound A but does not compromise carbom dioxide
absorption. Anesth Analg 1999:89;768-73.
85. Veisman AI. Working conditions in the operating rooms and
their effect on the health of anesthetists. Eksperimentalnaia
Kirurgiia i Anestesiologiia 1967;12:44-54.
Vol. 76 - No. 3 MINERVA ANESTESIOLOGICA
TORRI
86. Buring JE, Hennekens CH, Mayrent SS. Health experiences
of operating room personnel. Anesthesiology 1985;62:325-
30.
87. Bovin JF. Risk of spontaneous abortion in women occupa-
tionally exposed to anesthetic gases: a meta-analyzer. Occup
Environ Med 1997;54:541-8.
88. Ferstanding LL. Trace concentrations of anesthetic gas: a
critical review of their disease potential. Anesth Analg
1978;33:430-8.
89. Lauweys R, Siddons M, Misson CB. Anesthetic hazards
among Belgian nurses and physicians. Int Arch Occup
Environ Health 1981;48:195-203.
90. Ericson A, Kallen B. Survey of infants born in 1973 or 1975
to Swedish women working in operating rooms during their
pregnancies. Anesth Analg 1979;58:302-5.
91. Ericson HA, Kallen AJB. Hospitalization for miscarriage
and delivery outcome among Swedish nurses working in
operating rooms, 1973-1978. Anesth Analg 1985;64:981-8.
92. Spence AA. Environmental pollution by inhalation anes-
thetics. Br J Anaesth 1987;5:96-103.
93. Spence AA. How safe is anesthesia for you and your patient?
Data from U.K. Ten years prospective study. Bulletin of the
New York State. Postgraduate Assembly 1985;12:140-9.
94. Shaw ADS, Morgan M. Nitrous oxide: time to stop laugh-
ing? (Editorial) Anaesthesia 1998;53:213-5.
95. James MF. Nitrous oxide: still useful in the year 2000? Curr
Opin Anaesthesiol 1999;12:461-6.
96. Myles PS, Leslie K, Chan MTV, Forbes A, Paech MJ, Peyton
P et al. Avoidance of nitrous oxide for patients undergoing
major surgery. A randomized controlled trial. Anesthesiology
2007;107:221-31.
97. Moseley H, Kumar AY, Bhavani Shankar K, Rao PS, Homi
J. Should air-oxygen replace nitrous oxide-oxygen in gener-
al anaesthesia? Anaesthesia 1987;42:609-12.
98. Baum VC. When nitrous oxide is no laughing matter: nitrous
oxide and pediatric anesthesia. Paediatr Anaesth 2007;17:824-
30.
99. Schmitt EL, Baum VC. Nitrous oxide in pediatric anesthe-
sia: friend or foe? Curr Opin Anaesthesiol 2008;21:356-9.
100. Neuman GG, Sidebotham G, Negoianu E, Bernstein J,
Kopman AF, Hicks RG et al. Laparoscopy explosion hazards
with nitrous oxide. Anesthesiology 1993;78:875-9.
101. Sanders RD, Weimann J, Maze M. Biologic effects of nitrous
oxide. A mechanistic and toxicologic review. Anesthesiology
2008;109:707-22.
102. Koblin DD, Waskel L,Watson JE. Nitrous oxide inactivates
methyonine synthetase in human liver, Anesth Analg
1982;61:75-8.
103. Myles PS, Chan MT, Kaye DM, McIlroy DR, Lau CW,
Symons JA et al. Effect of nitrous oxide anesthesia on plas-
ma homocysteine and endothelial function. Anesthesiology
2008;109:657-63.
104. Myles PS, Leslie K, Peyton P, Paech M, Forbes A, Chan MT
et al. Nitrous oxide and perioperative cardiac morbidity
(ENIGMA II) trial: rationale and design. Am Heart J
2009;157:488-94.
105. Henderson KA, Raj N, Hall JE. The use of nitrous oxide in
anaesthetic practice: a questionnaire survey. Anaesthesia
2002;57:1155-8.
106. Baum JA. The carrier gas in anaesthesia: nitrous oxide/oxy-
gen, medical air/oxygen and pure oxygen. Curr Opin
Anaesthesiol 2004;17:513-6.
107. Richebé P, Rivat C, Creton C, Laulin JP, Maurette P, Lemaire
M, Simonnet G. Nitrous oxide revisited. Anesthesiology
2005;103:845-54.
108. Hecker K, Baumert JH, Horn N, Roissant R. Xenon, a mod-
ern anesthesia gas. Minerva Anesthesiol 2004;70:255-60.
109. Campagna JA, Miller KW, Forman SA. Mechanism of action
of inhaled anesthetics. N Engl J Med 2003;348:2110-24.
110. Grasshoff C, Uwe R, Bernd A. Molecular and systemic mech-
anisms of generale anesthesia: the “multi-site and multiple
227
 MINERVA MEDICA COPYRIGHT®
TORRI
mechanism’ concept. Curr Opin Anesthesiol 2005;18:386-
91.
111. Overton E. Studien ueber die Narkose Zugleich ein Beitrag
zur Allgemeinen Pharmakologie. Jena: Verlag F Ed; 1901.
112. Meyer KH. Contributions to theory of anesthesia. Trans
Faraday Soc 1937;18;33-9.
113. Franks NP, Lieb WR. Where do general anesthetics act ?
Nature 1978;74:39-42.
114. Franks NP, Lieb WR. Do general anesthetics act by compet-
itive binding to specific receptors? Nature 1984;310:99-601.
115. Franks NP, Lieb WR. Molecular and cellular mechanism of
general anesthesia. Nature 1994;367:607-14.
116. Macdonald RI, Olsen RW. GABAA receptors channels. Ann
Rev Neurosci 1994;17:569-602.
117. Yamakura T, Harris RA. Effects of gasesous anesthetics nitrous
oxide and xenon on ligand-gated ion channels. Comparison
with isoflurane and ethanol. Anestesiology 2000;93:1095-
101.
118. Rampil I, Mason P, Singh H. Anesthetic potency (MAC) is
independent of forebrain structures in rat. Anesthesiology
1993;78:707-12.
119. Antognini JF, Schwartz K. Exagerated anesthetic require-
ment in the preferentially anesthetised brain. Anesthesiology
1993;79:1244-49.
120. Cheng G, Kending JJ. Enflurane directly depresses gluta-
mate AMPA and NMDA currents in mouse spinal cord
motor neurons independent of action on GABAA or glycine
receptors. Anesthesiology 2000;93:1075-84.
121. Sonner JM, Antognini JF, Dutton RC, Flood P, Gray AT,
Harris RA et al. Inhaled anesthetics and immobility: mech-
Received on March 20, 2009 - Accepted for publication on October 27, 2009.
Corresponding author: G. Torri, Department of Anesthesiology, S. Raffaele University, via Olgettina 60, 20132 Milan, Italy.
E-mail: torri.giorgio@hsr.it
228 MINERVA ANESTESIOLOGICA
INHALATION ANESTHETICS
anisms, mysteries, and minimum alveolar concentration.
Anesth Analg 2003;97:718-40.
122. Jurd R, Arras M, Lambert S, Drexler B, Siegwart R, Crestani
F et al. General anesthetic action in vivo strongly attenuat-
ed by a point mutation in the GABA(A) receptor beta 3 sub-
unit. FASEB J 2003;17:250-2.
123. Collins JG, Kendig JJ, Mason P. Anesthetic actions within the
spinal cord: contributions to the state of general anesthesia.
Trends Neurosci 1995;18:549-53.
124. Hentschke H, Schwarz C, Antkowiak B. Neocortex is the major
target of sedative concentrations of volatile anaesthetics: strong
depression of firing rates and increase GABAA receptor-medi-
ated inhibition. Eur J Neurosci 2005;21:93-102.
125. Flood P, Ramirez-Latorre J, Role L. Alpha-4 beta2 neuronal
nicotinic acetylcholine receptors in the central nervous sys-
tem are inhibited by isoflurane and propofol, but alpha-7-type
nicotinic acetylcholine receptors are unaffected.
Anesthesiology 1997;86:859-65.
126. Alkire MT, Haier RJ, Shah NK, Anderson CT. Positron
emission tomography study of regional cerebral metabolism
in humans during isoflurane anesthesia. Anesthesiology
1997;86:549-57.
127. Alkire MT, Haier RJ, Fallon JH. Toward a unified theory of
narcosis: brain imaging evidence for thalamocortical switch
as the neurophysiologic basis of anesthetic-induced uncon-
sciousness. Conscious Cogn 2000;9:370-86.
128. Alkire MT, Haier RJ. Correlating in vivo anaesthetic effects
with ex vivo receptor density data supports a GABAergic
mechanism of action for propofol, but not for isoflurane.
Br J Anaesth 2001;86:618-26.
March 2010