INHALATIONAL ANAESTHETICS: VOLATILE

INHALATIONAL ANAESTHETICS: VOLATILE

Characteristics	DIETHYL ETHER	HALOTHANE	METHOXY FLURANE (M.F)	ENFLURANE	ISOFLURANE
Cost	CLASSICAL General anesthetic Cheaper, simple method of administration( post operative nausea and vomition)	Expensive, Complex method of  (semiclosed and closed) administration               (No post operative nausea and vomition)	Expensive	More expensive than halothane. Complex method of administration	Very expensive than others, complex method of administration
Boiling point (0C)	35	50	101	57	48.5
MAC(%)	2-3	0.75-1.1	0.23	1.5	1.5
Amount of metabolism (% of administered dose)	<20%	15-20%	50-70	2-5	0.2
Stability	Decomposes (oxidized to peroxides) on  exposure  to air, heat, light, moisture. Not to be kept in fridge. To be stored in well stoppered amber coloured bottle	Decomposes on  exposure  to light to form volatile acid. 0.01% thymol is stabilizing agent used.	Decomposes on exposure  to light. Butylated hydroxyl toluene is preservative	Very stable. No preservative required Structural analog of M.F	Very stable. No preservative required
Stability in Sodalime UV Light	Decomposes Decomposes	Decomposes Decomposes	Decomposes Decomposes	Stable Stable	Stable Stable
Stages of anesthesia induced	I,II,III,IV	I, III,IV	I, III,IV	I,II- Seizures                         ( Convulsant anaesthetic)	I,II – Dissociative anaesthesia
Effect on CNS (Anaesthesia induction)	Satisfactory Slow induction and recovery due to high solubility in blood ( HiGH Lipid water partition coefficient)	Rapid induction and recovery , Moderate degree of  solubility in blood	Slow induction and slow recovery	Rapid induction and recovery Increased CNS irritability, cortical hyper excitability	Very Rapid induction and recovery faster than halothane and others Reduced  CNS irritability and  cortical hyper excitability
Effect on CardioVascular System (CVS)	Increases epinephrine release- increased BP, heart rate, vasomotor centre depression followedby cardiac arrythmias	Initially increased heart rate, later – myocardial depressant- reduced BP, Heart rate. Sensitizes heart to catecholamines (epinephrine is to be avoided),cardiac arrhythmias during induction	Hypotension, cardiac depression, no change in heart rate.	Cardiac depression equivalent to halothane	Cardiac depression less than enflurane.
Effect on Respiratoy system	Mucous membrane irritant, increased mucous secretion, hyperventilation- results in  respiratory alkalosis, hypoventilation results in acidosis                  ( Atropine is used to prevent)	Non irritant Reduced ventilation- Co2 accumulation- result in resp.  acidosis	Non irritant Reduced ventilation- Co2 accumulation- result in resp.  acidosis	Dose dependent respiratory depression.	Respiratory depression Similar to that of halothane
Effect on body temperature	Hypothermia	Malignant hyperthermia in pig, horse, man                (Dantrolene sodium - antidote)	Hypothermia	Hypothermia	Malignant hyperthermia in pig, horse, man (Dantrolene sodium - antidote)
Effect on Kidney/Urinary system	Release ADH, oliguria/anuria	Temporary reduction in urine volume.	Temporary reduction in urine volume.	Reduced renal blood flow, GFR and urine volume	No effect
Muscle relaxation and analgesia	Satisfactory muscle relaxation and analgesia. Motor end plate/ Neuromuscular blockade – Skeletal muscle paralysis- Curariform effect	Adequate muscle relaxation and analgesia.	Excellent muscle relaxation and analgesia., preferred for abdominal surgeries	Incomplete muscle relaxation and poor to moderate analgesia. Twitching of facial, neck and limb muscles.	Adequate muscle relaxation and analgesia.
Hepatotoxicity	Reduced glycogen synthesis, Hepatotoxic	Hepatotoxic	Nontoxic	Nontoxic	Nontoxic
Renal/Nephro toxicity	Nontoxic	Nontoxic	Potent nephrotoxic	Nontoxic	Nontoxic
Effect on uterus	Relaxation of uterine smooth muscle, reduced tone and motility	reduced tone and motility (not to be used in obstetrical anesthesia) high dose- fetal respiratory depression	Do not saffect tone and motility, no untoward effect on fetus	Relaxant effect similar to that of halothane	Relaxant effect similar to that of halothane
Side/ Adverse effects	Initial excitement, cardiopulm. depression, hypoventilation , respiratory paralysis	Vasodilation, hypotension, arrhythmias, malignant hyperthermia	Nephrotoxicity. Dose dependent CV &resp. depression	Resp. & CV depression, twitching of face, neck, limb muscles; Ocassional tonic-clonic seizures	Mild hypotension, tachycardia
Drug interactions	Potentiate  any other CNS depressants actions, NMBD-	Potentiate Nondepolarising neuromuscular blocking drugs(NMBD), and ganglionic blockers action. Avoided with aminoglycosides and paracetamol	To be avoided in combination  with nephrotoxic drugs  like:aminoglycosides, NSAIDS, loop diuretics, NMBD, epinephrine(increased chance of arythmias)	Similar to that of halotahne	Not much significant interaction
Contraindications(CI) and Precautions	Acute and chronic respiratory  diseases, acidosis, shock, surgery requiring electrocautery, flammable device to  be avoided	Cardiac diseases, Congestive heart failure, liver diseases, precaution in – increased  intraocular pressure, CSF conc.(head injury), pheochromocytoma)	CI- in renal, hepatic injury and head injury	Not recommended in horses, patients with history of epilepsy, abnormalities in EEG	Cautious in respiratory  or cardiac failure patients
Clinical use in animals	Pig, dog, cat, calves, lab animals Externally used as rubefacient, cleansing agent Orally – has antispasmodic, carminative, stimulant action on heart	Maintenance anesthetic in horse, dog, cats	Maintenance anesthetic in horse, dog, cats	As alternative to halothane as maintenance  anesthetic in horse, dog, cats	Anesthetic choice for debilitated, aged,  hepatically, renally  impaired  patients
Indications and combinations used	a)with pentobarbitone  b)with morphine, pethidine(atropine –preanaesthetic) to provide balanced anesthesia	a)with nitrous oxide+oxygen(to reduce cardiopulmonary depression)  b)with  xylazine/acepromazine for both inducation and maintenanace	a)with nitrous oxide(70%)  b) with pentobarbitone  withdrawn  nowadays	a)with nitrous oxide(70%) b) diazepam  c) thiobarbitone sodium d) ethosuximide(to increase seizure threshold)	a) with barbiturates (thiopentone /pentobarb itone) b) nitrous oxide(50%)
Dose	Induction-: 10-40% Maintenance: 3-12%	Induction-: 2-4% Maintenance: Small animals: 0.5-1.5% LA: 1-2%	Induction-: 1-3% Maintenance: Small animals: 0.5-1.5% LA:  0.5%	Induction-:  4-6% Maintenance: 1-3%	Induction-: 2.5-4.5% Maintenance: 1-3%

Malignant hyperthermia (MH) or malignant hyperpyrexia

·         A rare  life-threatening condition that is usually triggered by exposure to certain drugs used for general anesthesia, specifically the volatile anesthetic agents and the neuromuscular blocking agent,succinylcholine.

·         In susceptible individuals, these drugs can induce a drastic and uncontrolled increase in skeletal muscle oxidative metabolism, which overwhelms the body's capacity to supply oxygen, remove carbon dioxide, and regulate body temperature, eventually leading to circulatory collapse and death if not treated quickly.

·          Susceptibility to MH is often inherited as an autosomal dominant disorder, for which there are at least 6 genetic loci of interest,^[2] most prominently the ryanodine receptor gene (RYR1). 

·         In the anesthetic induced malignant hyperthermia syndrome, : "triggering agents" induce a sudden rise in myoplasmic calcium either by preventing the sarcoplasmic reticulum from accumulating calcium adequately, or by accelerating its release. This rise in myoplasmic calcium activates acute catabolic processes common to the malignant hyperthermia crisis. 

·          Treatment with dantrolene sodium is usually initiated;  Dantrolene may prevent the increase in myoplasmic calcium and the acute catabolism within the muscle cell by interfering with the release of calcium from the sarcoplasmic reticulum to the myoplasm. Thus, the physiologic, metabolic and biochemical changes associated with the crisis may be reversed or attenuated.

SEVOFLURANE -  Anesthetic for  use in pigs

DESFLURANE: Fluorinated congener of isoflurane

ETHYL CHLORIDE- Volatile anesthetic used in  sprays for local anaesthetic, analgesic effect in sport injuries

CHLOROFORM

• Unpleasant odour – Powerful rapid inducer, Noninflammabla, explosive
•  Used to produce euthanasia  for killing street dogs
• Sensitizes myocardium to adrenaline → ventricular fibrillation → sudden death (20 – 30 times more potent than ether)
• Produce phosgene which is highly irritant
• Nephrotoxic and Hepatotoxic- central tubular liver  necrosis, fatty degeneration of heart and kidney
•  Discontinued nowadays

INHALATIONAL :   GASEOUS ANAESTHEICS

NITROUS OXIDE (laughing gas)

• N₂O increases pulmonary ventilation – due to direct stimulation of respiration.
• Increases  its own inhalation – (Concentration effect)  and also that of halothane or enflurane or oxygen when given together (second gas effect)
• MAC > 100% (104 in man to 255 in cat) – weak anaesthetic,   Poor muscle relaxation, But strongly analgesic
•  Used in combination with oxygen to avoid induction of hypoxia ( 30% + oxygen 70%)
• Used as an anaesthetic adjuvant- as maintenance anesthetic  in horse, pig, ruminants, dogs, cats

Other gases: ETHYLENE, CYCLOPROPANE (TRIMETHYLENE) and   XENON