1840– DISCOVERY OF NITROUS OXIDE , DIETHYL ETEHR AND CHLOROFORM
1951– First halogenated hydro carbon anaesthetic , fluroxene introduced – inflammable and had organ toxicity
1956 – halothane clinically used
1960 – methyl flurane , methyl ether was first derivative – in clinical use devoid of dysrhythmogenic effect with epinephrine , prolonged induction and slow recovery, nephrotoxicity.
1973– enflurane methyl ethyl ether derivative.
1992– desflurane fluorinated methyl ethyl ether.
1994– sevoflurane fluorated methyl iso propyl ether.
Low molecular weight odourless to sweet smelling, non-flammable gas of low potency and poor blood solubility . So rapid achievement of an alveolar and brain partial pressure of dreug.
Has analgesic effect and mild skeletal muscle relaxation
Gas at room temperature and ambient pressure
Kept as a liquid under pressure because its critical temperature lies above room temperature
- CVS: Sympathetic stimulation so blood pressure, cardiac output unchanged or slighltly increases.
Depresses myocardial contractility.
Constriction of pulmonary vascularsmooth muscles and increase peripheral vascular resistanace.
Increase endogenous catecholamine which can be dysrythmogenic.
Stable in sodalime at 40 degree celscius.
Blood gas coefficient is 0.46.
- RS: stimulate Central nervous system / increase respitratory rate and decrease tidal volume.
Minimal change in minute ventilation and resting arterial CO2 level.
Hypoxic drive depressed by N2O.
- CNS: increase cerebral blood flow.
Increase cerebral blood volume – increase Intracranial tention.
Levels below MAC – analgesia , dental surgeries.
- Neuro Muscular: No signisicant muscle relaxation.
High concentration in hyper baric chamber cause skeletal muscle injury.
- Renal: Decrease renal blood flow by increasing renal vascular resistance , decrease GFR and decrease Urine output.
- Hepatic: decrease but less than volatile agents.
- GIT:Post op nausea and vomiting by activating chemoreceptor trigger zone and positive vomiting center in medulla.
- Biotransformation: 0.01% Reductive metabolism in GIT by anaerobic bacteria . Irreversibly oxidizing cobalt atom in vitamin B12 , nitrous oxide inhibits enzymes that are
vitamin B12 dependent.
Inhibit methionine synthetase – myelin formation and
Thymidylate synthetase – DNA synthetase.
- Bone marrow depression:
- Neurologic deficiencies : Peripheral neuropathies and Pernicious anaemia
- Alters immunologic response to chemostaxis.
It has 35times solubility than N2 so hazardous in
☛ Air embolism
☛ Acute intestinal obstruction
☛ Intracranial air (pneumo cephaly)
☛ Pulmonary air cysts
☛ Intra ocular air bubbles
☛ Tympanic membrane grafting
☛ Pulmonbary hypertension.
☛ Addition of 65% N2O to volatile Anaesthetic decreases MAC by 50%.
☛ Potentiate neuro muscular blockade.
☛ Halogenated alkane
☛ Carbon fluoride bands are responsible fprous non flammable and non explosive nature
☛ Thymol preservative and amber coloured bottles (retard special oxidative decomposition)
☛ Molecular weight 197
☛ Boiling point 50.2
☛ Vapourisation pressure: 244
☛ Stability in soda lime 40 degree celscius- less.
☛ Blood gas partition coefficient: 2.54
☛ MAC- 0.75
Odour : organic
Preservative: Thymol necessary
☛ Decrease myocardial contractility by interfening Na-K exchange.
☛ Decrease BP.
☛ Though coronary vaso dilator – coronary flow decreases by decrease in BP.
☛ Halothane blunts aortic and carotid body reflex and cause bradycardia and junctional rhythm.
☛ Dysrhythmogenic effect above dose of epinephrine 0.15mcg/kg.
RS: Rapid and shallow breathing alveolar ventilation and PaCO2 is elevated.
Apneic threshhold is highest.
Ventilation effects : due to central and intercostals muscle dysfunction mechanism.
Attenuates airway reflexes and relaxes bronchial smooth muscles by inhibiting intracellular Ca mobilization.
Alters mucociliary function.
Decrease cerebral vascular resistance.
Increase cerebral blood flow.
Autoregulation is blunted.
Neuromuscular: Relaxes smooth muscle and potentiates non depolarizing neuro muscular blocking drug.
Triggers malignant hyperthermia
RENAL: Decrease renal blood flow.
Decerase urine output.
HEPATIC: Decrease hepatic blood flow.
Biotransformation and Toxicity: Metabolixed in liver by cytochrome P450 in flueroacetic acid (disulfarum Ca inhibits).
Post op hepatic dysfunction.
☛ Liver dysfunction
☛ Increase ICT[intracranial tention]
☛ Patients with AS , hypovolemic patients.
Molecular weight : 184
Stability in Na saline – present.
Blood gas partition coefficient:1.9
CVS :decrease myocardial contractility.
Decrease vardiac output.
Deceraase systemic vascular resistance.
Dysrhythmogenic above doses upto 4.5 mcg/kg.
RS: same as halothane.
CNS: increase cerebral blood flow , increase ICT[intracranial tension]
Neuro muscular: Relaxes skeletal muscles.
Metabolism in liver.
CONTRA INDICATIONS: Renal diseases.
Vapor pressure: 160.
Non pungent so preferable inhalation induction agent in paediatric patients.
Potent preconditioning effect.
Less sympathetic activation than desflurane.
Both decreases SVR , BP and Cardiac ouput in dependent fashion.
Sevoflurane has favourable cardio protective properties intra op and postoperatively.
Prolongation of QT interval.
- Production of plasma fluoride.
- Production of compound A with low flow technique.
- Increase serum creatinine.
☛ Unique hemodynamic effects
☛ Decreases SVR, BP , and CO than sevoflurane in dose dependent fashion
☛ Increase in HR and PAP and PCWP
☛ Increase sympathetic activity occurs when desflurane concentration rapidly and with higher absolute concentrations
☛ Increase in HR may cause myocardial ischemia
☛ Direct airway mucosal irritation and sites within the lung that responds because of increase sympathetic activation in response to desflurane.
☛ Administration of fentanyl , beta blocker and clonidine partially blunts sympathetic activation of desflurane.
☛ MAC: 1.2
☛ Vapor pressue: 240 mmhg at 20 degrre celcius.
☛ Non inflammable volatile anaesthetic pungent ethereal odor.
☛ Less LV depression.
☛ CO is maintained , decrease in SVR , Decrease in BP.
☛ Contraversial issue regarding coronary steal phenomenon.
☛ Decrease in MV , Decrease in RR , Blunts nnormal ventillatory response to hypoxia and hypercapnea
☛ Has brocnho dilator effect less than halothane
☛ Increases CBF and ICT less than halothane
☛ It decreases cerebral metabolic oxygen requirement at 2 MAC
RENAL: Decrease bloof flow , GFR and urinary output
Hepatic: Hepatic artery perfusion i9s preserved with isoflurane as anaesthesia
METABOLISM: Metabolized to tri fluoro acetic acid and may increase fluoride levels during prolonged anaesthesia.
CONTARINDIACATIONS: No unique contra indications to use.