General Anaesthesia

General Anaesthesia:

It is the state of unconsciousness with lowered sensory and motor stimuli by controlled, reversible intoxication of CNS.

Stages of general anaesthesia :

Divided into 4 stages:

Stage I : Stage of voluntary excitement (Stage of induction)

In this stage ,the animal is fully conscious, excited with increased pulse and respiratory rate and in apprehension it may pass urine and faeces.

Stage II : Stage of involuntary excitement

In this stage animal has lost consciousness with regular respirations and some time holding its breath, there will be exaggerated response to stimuli with voluntary limb movements like cycling of legs with muscular rigidity.

Stage III : Satge of surgical anaesthesia

This stage is divided into 3 planes.

First plane: Plane of light anaesthesia

In this breath is  regular, limb movements stopped, eye balls move from side to side, sluggish palpebral, conjuctival and corneal reflexes with pedal reflex present. Minor surgeries like opening of an abscess is done in this stage.

Second plane: Plane of medium anaesthesia

In this stage breath is regular, with sluggish pedal reflex and pronounced muscle relaxation, eye balls are fixed in cattle,horse,pigs and sheep but in dogs and cats eye balls roll down. Most operations except thoracotomy and laprotomy can be performed.

Third plane: Plane of deep anaesthesia

In this shallow respirations are seen with pause between inspiration and expiration, pedal reflexes are abolished, eye balls are centered again in dogs and cats, with generalized muscle relaxation.

Stage IV : Stage of medullary depression or Anaesthetic over dosage stage

In this stage, pulse is rapid with dry and dialated pupils , thoracic muscles are paralysed diaphragmatic movements are jerky with gasping respirations.

If proper counter measures are not taken, respiration ceases with dry and cyanotic mucous membrane and when heart fails mucous membrane turns ash-grey.

 

General anaesthetic agents

INTRODUCTION

· Injectable anaesthetics can be administered through various routes.

· The equipment required for administration of injectable anaesthetics is minimal.

· Following are the commonly used equipments

oSyringes

oNeedles

oButterfly needles

oIntravenous catheters.

oInfusion controllers and Syringe devises.

ROUTES OF ADMINISTRATION

· Intravenous e.g. thiopentone in horses

· Intramuscular e.g. ketamine in dogs

· Intraperitonial e.g. thiopentone in cats

· Intrathoracic e.g. thiopentone in cats

· Intratesticular e.g. pentobarbitone in pigs for castration

· Subcutaneous e.g. droperidol – fentanyl in cats

ADVANTAGE AND DISADVANTAGE

Advantages

· Simple to administer

· Have rapid onset of action

· Useful as induction agents

· Does not irritate the airways

· Non explosive and inflammable

· Does not pollute the theatre

· Controls convulsions

Disadvantages

· May induce tissue damage if not injected through appropriate route.

· Excess dose administered without calculating the dose or patient evaluation may cause toxicity. It may not be possible to recover the patient without the use of specific reversal/antagonistic agents, oxygen supplementation, intermittent positive pressure ventilation and other life saving supports.

 

 

 

CLASSIFICATION OF INJECTABLE ANAESTHETICS

 

Main category	Examples
Barbiturates	Thiobarbiturate e.g. thiopentone sodium, thiamylal sodium Methylated oxybarbiturate e.g. methohexitone sodium Oxybarbiturate e.g. phentobarbital sodium
Dissociative anaesthetics	Ketamine hydrochloride Tilatamine Phencyclidine
Steroid anaesthetics	Combination of Alphaxalone and alphadolone e.g. Saffan, Althesin
Imidazole derivatives	Etomidate Metomidate
Alkylphenols	Propofol
Opioid synthetic analgesics	Fentanyl citrate Alfentanil Sufentanil Lofentanil Etorphine
Neuroleptanaesthetic mixture	Droperidol and Fentanyl Fluanisone and Fentanyl Etorphine combinations
Centrally acting muscle relaxants	Glyceryl Quaiacolate
Chloral hydrate	-

 

 

 

 

ULTRA SHORT ACTING

· The commonly used ultra short acting barbiturates are thiopentone sodium , thiamylol sodium and methohexitone sodium.

oThiopentone and thiamylal - thiobarbiturates

oMethohexitone - oxybarbiturate.

· These agents are strong alkalies, converted into acid form, which bind with the plasma protein particularly with albumin fraction.

·  The narcotic and anaesthetic action is induced by the unbound fraction.

o Unbound fractions will be more and may cause profound depression.

oThese agents produce unconsciousness in 30 to 90 seconds, the duration of anaesthesia varies from 5 to 15 minutes.

oThe recovery from anaesthesia is not due to the detoxification, biotransformation and elimination, it is due to distribution. A small quantity injected rapidly as a bolus will produce high plasma and brain concentration resulting in narcosis and the recovery will be faster.

oThe amount of thiopentone and thiamylal required to produce anaesthesia vary from 10 to 18 mg/kg in small animals and 6 to 10 mg/kg in large animals.

oMethohexitone is administered as 1% solution in small animals and as 6% in large animals. The dose is 3 to 5 mg/kg intravenously.

CARDIOVASCULAR AND RESPIRATORY EFFECTS

· Cardiovascular effects 

oBarbiturates are potent cardiovascular depressants.

oBy  stimulation of baroreceptors and chemoreceptors and myocardial hypoxia.

oAdministration of oxygen will prevent further manifestations.

oLidocaine can be administered to control ventricular arrhythmia.

oIt prevents and corrects ventricular arrhythmia and reduce the requirement of barbiturates.

· Respiratory effects

oUltrashort acting barbiturates induce severe respiratory.

oIf respiratory arrest is noticed it must be managed with oxygen supplementation and mechnical ventilation.

oThese agents are metabolized in the liver and to a less extend in kidney, brain and in other tissues.

oThese agents do not cause prolonged decrease in gastrointestinal motility. They produce sufficient muscle relaxation required for minor surgery.

oBarbiturates readily cross the placental barrier and depress fetus.

 

 

CONCURRENT USE OF OTHER DRUGS AND BENEFITS

· Antichlolinergics

oAnticholinergics are administered to reduce salivation and prevent bradycardia.

o Atropine sulphate - Dogs & Cats = 0.044 mg/kg S.C/I.M, 0.022 mg/kg I.V

oGlycopyrorolate - Dogs & Cats = 0.011 mg/kg I.M.

· Tranquilizers

oTranquilizers are administered to reduce the anxiety and the dose of the anaesthetic drugs

oTriflupromazine - Dogs & Cats  = 1.0 mg/kg I.V

oAcepromazine - Dogs & Cats  = 0.1 - 0.2 mg/kg I.M., Horses  = 0.06 - 0.1 mg/kg I.V/I.M.

oChlorpromazine - Dogs & Cats  = 1.1 - 2.2 mg/kg I.V/I.M.

oXylazine

§ Dogs = 1.0 mg/kg I.V.

§ Cats =  1.0 mg/kg I.M.

§ Horses = 1.1 mg/kg I.V

§ Cattle   0.1 – 0.2 mg/kg I.V

oDiazepam - Dogs & Cats 0.04 mg/kg I.V

·  Neuraleptanalgesics

oNot safe to combine with barbiturates as the combined effects will be extreme bradycardia, hypotension and cardiac arrest.

· Narcotics

oNarcotics markedly reduce the dose of barbiturates.

oMorphine - Dogs  0.11 – 0.66 mg/kg S.C, Cats not recommended

oMethadone - Dogs  0.11 – 0.55 mg/kg I.M/I.V, Cats not recommended

oOxymorphine - Dogs  0.22 mg/kg I.V/I.M/S.C, Cats  0.88 --- 3.3 mg total dose I.V/I.M/S.C

oPentozocaine - Dogs & Cats 2.2 – 3.3 mg/kg I.M./S.C

oInnovar vet - Dogs  1 ml/7 to 9 kg I.M. , Cats not recommended

·  Muscle relaxants

oIn large animals centrally acting muscle relaxant glyceryl guaiacolate (Guaifenisin) is combined with barbiturates.

•  In dogs succinyl choline, pancuronium, gallamine and other products can be combined with barbiturates.

· Procaine and lidocaine

oProcaine hydrochloride and lidocaine hydrochloride can be given for ventricular arrythmia with  thiopentone and thiamylol.

 

 

 

LONG ACTING BARBITURATES

· Pentobarbital sodium is the long acting barbiturate presented  in  50 mg/ml and 65 mg/ml  for  small animal and swine by intravenously.

· Dose - Dogs & cats 20 - 30 mg/kg without premedication 10 - 20 mg/kg with premedication.

· A special preparation containing 240 mg/ml of pentobarbital is available and is used for euthanasia of animals at the rate of 1 ml/5kg.

· This solution is often used to castrate large boars at a dose  24 mg/kg.

 

DISSOCIATIVE ANAESTHETICS

· Ketamine hydrochloride and tilatamine are the common.

· Phencyclidine is another cyclohexamine product withdrawn from use because of drug abuse.

· The dissociative anaesthesia is characterized by

oProfound amnesia, superficial analgesia and catalepsy

oInvoluntary spontaneous movements

oPersistence of reflexes like swallowing, pharyngeal palpebral and corneal

oLarge dose may induce convulsions

oLack of muscle relaxation

KETAMINE

· Ketamine is a popular by its wide margin.

· It was first synthezied in 1963 and introduced in human anaesthesia in 1965 and in veterinary anaesthesia in 1970.

· Ketamine alters the central nervous system activity to sensory impulses without blocking it at spinal cord or brain stem levels.

· It allows the impulses to reach the cortical receiving areas but not perceived because of the depression and dissociation of limbic system and other cortical association areas.

· It can cause seizures even in patients not known to be epileptic and may occur even after 24 hours administrations.

· Cardiovascular effects - Ketamine increases heart rate, cardiac out put, peripheral vascular resistance, systemic and pulmonary blood pressure, cardiac contractility and myocardial oxygen consumption.

· Respiratory effects - The effect of ketamine on respiratory functions are increase in respiratory rate.

· Muscle relaxation.

·  It induces copious salivation and lacrimation.

·  Ketamine is metabolized in the liver.

· Decreases total RBC counts.

·  Leukocytosis following ketamine administration.

· Induces hyperglycaemia

· It increases the cerebrospinal fluid flow and pressure.

· It increases the blood pressure and intraocular pressure.

· The aims of combining ketamine with other agents are to achieve

oMuscle relaxation

oEliminate side effects like salivation and recovery delirium.

oImprove visceral analgesia and

oProlong the period of anaesthesia

DOSE RATE OF KETAMINE

· Cats

oIn cats the dose of ketamine is 10 - 30 mg/kg I.M.

oThe standard protocols are

§ Xylazine 1.0 mg/kg I.M. and Ketamine 20-25 mg/kg I.M.

§ Acepromazine 0.1 mg/kg I.M. and Ketamine 20 --- 25 mg/kg I.M.

§ Midazolam 0.2 mg/kg I.M. and Ketamine 10 mg/kg I.M

§ Meditomidine 80 µg/kg I.M. and Ketamine 2.5 – 7.5 mg/kg I.M.

§ Butorphenol 0.1 mg/kg I.V. Meditomidine 40 µg/kg I.M. and
Ketamine 1.25 mg/kg I.V

· Dogs

oXylazine 1 - 2 mg/kg I.M and Ketamine 10 mg/kg IM/IV

oDiazepam  5 mg/kg I.V and Ketamine 5 mg/kg I.V

oMeditomidine 40 µg/kg I.M. and Ketamine 5- 7.5 mg/kg I.M.

oButorphenol 0.1 mg/kg I.M, Meditomidine 25 µg/kg I.M. and Ketamine 5 mg/kg I.M. 15 minutes later.

· Horses

§ Xylazine 1.1 mg/kg I.V and Ketamine 2.2 mg/kg I.V.

§ Diazepam at the rate of 0.22 mg/kg I.V, glyceryl quaiacolate at 50 mg/kg I.V for good muscle relaxation. 

· Cattle

oXylazine 0.1 mg/kg and Ketamine 2 - 5 mg/kg I.V

· Sheep and Goats

oXylazine 0.04 - 0.06 mg/kg and Ketamine 2.2 - 4.4 mg/hg I.V

· Pigs

oXylazine 2 mg/kg, Oxymorphone 0.075 mg/kg and Ketamine 2 mg/kg I.V

 

TILATAMINE

· Tilatamine is closely related to ketamine and is two to three times potent than ketamine.

· It induces muscle rigidity and tonic-clonic convulsions if administered alone hence it is marketed in combination with a benzodiazepine Zolazepam.

·  This combination provides muscle relaxation and a dissociative state of anaesthesia in dogs, cats and wild animals.

· Animals anaesthetized with telozol – zolazepam will respond to palpebral, laryngeal, pharyngeal, pedal and pinnal reflexes. Salivation is more marked and can be controlled by the use of anticholinergic premedication. Anticolinergic premedicationis very important while using this combination

· Dossage

oCat   @ 7 - 15 mg/kg I.M; 5 - 10 mg/kg I.V

oDog  @ 10 - 15mg/kg I.M; 5 - 7 mg/kg I.V

 

STEROID ANAESTHETIC

· Combination of alphaxalone and alphadolone is presented as saffan.

· Low solubility of these steroids in water made them less popular.

· Saffan is used in cats.

· In dogs  not recommended.

· It selectively decreases cerebral oxygen consumption to a greater extend by reducing the blood flow.

·  Retching, vomiting and twitching of facial muscles may occur during induction.

· It induces respiratory depression.

· It poduces good muscle relaxation.

· It can be used in cats for caesarian section.

· It may cause oedema of ear pinnae and paws in cats due to histamine release.

· Not recommended in horses.

· Dose

oCats 4 - 6 mg/kg I.M/I.V

oPigs 4 - 6 mg/kg I.V

IMIDAZOLE DERIVATIVES

Metomidate

· Metomidate is a non-barbiturate belonging to imidazole group.

· Metomidate has hypnotic and central muscle relaxant property, but does not have analgesic property hence often combined with fentanyl or azaperone premedication.

· It is mainly used in pigs and birds.

· Birds dose 3 - 20 mg/kg I.M

Etomidate

· Etomidate is a white crystalline power available as 20 mg dissolved in 10 ml.

· Intravenous injection is associated with high incidence of spontaneous movements, involuntary muscle tremors and hypertonus.

· Premedication with fentanyl or diazepam reduces the side effects.

· It is used in dogs for caesarian section at the dose of 1.5 - 3.0 mg/kg I.V along with diazepam (0.2 mg/kg I.V total dose not exceeding 5 mg).

· Etomidate is recommended in high risk allergic patients as it does not release histamine.

· In hyperadrenocortism,  safe induction agent.

ALKYLPHENOLS

· Propofol is a lipophilic alkylphenol (2-6 diisoprophylphenol).

· It is an oil at room temperature and can not be injected hence was formulated with Intralipid which contains soybean oil, glycerol and purified egg phosphatide.

· Propofol induce rapid loss of unconsciousness in 20 to 40 seconds after I.V. administration due to its lipophilic nature.

·  It crosses the blood-brain barrier and redistributed from plasma, brain and well-perfused tissues to less perfused tissues as thiopentone.

· Recovery periods are shorter without any undesirable side effects in propofol anaesthesia half of the calculated dose in infused as a bolus and the remaining half is administered in a slow phase.

· Propofol can be administered in continuous infusion to maintain anaesthesia.

· It is metabolized in liver and excreted in urine.

· Cardiovascular effects – Propofol induce 20 to 40% reduction in arterial blood pressure. Its use is cautioned in dehydrated dogs.

· Respiratory effects - Propofol induce apnea and greater respiratory depression.

· Propofol does not affect hepatic and renal functions

· It can be used for long term sedation and anaesthesia in intensive care patients, as it does not alter adrenocortical function.

· It reduces the intraocular pressure hence can be used in patients undergoing intraocular procedures

· Propofol is a good induction agent for caesarian section in dogs and cats. It reported that the puppies were bright and the mother was alert enough to care the puppies immediately following recovery.

· It is a safe anaesthetic in branchycephalic breeds of dogs.

· Dose

oDogs

§ 3 - 4 mg/kg I.V. in premedicated,

§ 5 - 6.5 mg/kg I.V. in Unpremedicated (continuous infusion 0.4 – 0.6 mg/kg/minute)

oCats

§ 8 mg/kg I.V. in unpremedicated (continuous infusion 0.51 mg/kg/minute)

oHorses

§ 2.0 mg/kg with xylazine 0.5 mg/kg I.V.(continuous infusion 0.2 mg/kg/minute)

oSheep and goats  = 3 - 4 mg/kg I.V

oRabbit = 7.5 - 15 mg/kg I.V

oMouse = 26 mg/kg I.V

oBirds = 1-15 mg/kg I.V

oReptiles = 10 mg/kg

PURE AGONISTS - MORPHINE

· Morphine is derived from the dried milky exudates of the unripe seed capsules of the opium poppy (Papaver somniferum).

· The exudates contains 3-25% of morphine, 5% noscapine and 0.8% papaverine.

· The laboratory synthetic agents are codeine, heroin (dimorphine = diacetylmorphine) and oxymorphine.

· Morphine produces

oAnalgesia

oDrowsiness

oNausea and vomiting by stimulating  vomiting centre.

oInduce respiratory depression

oDepress cough

oProduces increase in vagal tone and slowing of heart.

oMorphine is used as a postoperative analgesic.

oIt decreases motility of stomach.

oIt is absorbed from the gut and oral mucosa.

oIt is used in the treatment of congestive heart failure to relieve pain.

· Dose

oHorses: Morphine gives good results in horses if administered after xylazine sedation. Xylazine 1.0 mg/kg I.V and morphine 0.6 mg/kg I.V

oDogs: 0.2 – 0.5 mg/kg (total dose not exceeding 10 mg) I.M/I.V

oIn cats induces CNS stimulation, hence notused.

 

PATHADINE, MEPERIDINE AND OXYMORPHONE

· Pathadine

oPathadine is a vagolytic  at clinical doses.

oIt reduces salivation and respiratory secretion without inducing vomiting and defecation.

oPathadine induces histamine release if administered through intravenous route.

oDose

§ Dogs = 2 - 6.5 mg/kg S.C/I.M

§ Catls = 2 - 4.4 mg/kg S.C/I.M

· Meperidine

oIt is a synthetic product, less potent (one tenth of morphine) and used in dogs and cats.

oDose: Dogs and Cats 2-5 mg/kg I.M

 

· Oxymorphone

oOxymorphone is a synthetic derivative having 10 times greater potency than morphine.

oIt is widely used in dogs and cats for its analgesic property. Analgesia lasts for 4 hours.

oIt does not cause histamine release as meperidine.

oIt is used popularly in small animal anaesthesia due to its analgesic and lack of release of histamine.

oThe only limitation with drug is stimulation of vagus leading to bradyarrhythmias and it can be reduced or prevented with the use of antichlinergic agents in the protocol.

oDose

§ Dogs 0.05 - 0.2 mg/kg I.V/I.M/S.C (total dose not exceeding 4.5 mg)

§ Cats 0.05 - 0.4 mg/kg I.V/I.M/S.C

§ Horses 0.02 - 0.03 mg/kg I.V/I.M.

FENTANYL CITRATE AND ETORPHINE

Fentanyl citrate

· Fentanyl is a synthetic opioid product related to phenylpiperidines.

· Its analgesic property is 80 times greater than morphine.

· Cardiac out put, heart rate, respiratory rate and arterial oxygen tension (PaO2) are reduced following administration of fentanyl.

· Fentanyl citrate is available alone, or in combination with droperidol (Innovar vet contains 0.4 mg of fentanyl and 20 mg of droperidol per milliliter) or fluanisone. Fentanyl combinations provides good intra operative analgesia.

· It is not recommended in cats.

· Dose - Dogs 0.01 - 0.02 mg/kg I.M/I.V.

Etorphine

· Etorphine is a potent synthetic morphine derivative.  

· The dose of etorphine is 0.5 mg/500 g B.W

· Etorphine is an extremely long acting agent whose effects are maintained by enterohepatic recycling.

· The action of this drug can only be terminated by the administration of the specific antagonist Diprenorphine.

· Each pack of the marketed drug will be having two components. 1-Immobilon and 2-Revivon.

· This mixture is popularly used to capture elephants and giraffes

· Etorphine is extremely potent in human and any accidental injection may cause death if not treated with naloxone or diprenorphine.

PENTAZOCAINE, BUTORPHENOL TARTRATE AND BUPRENORPHINE

· Pentazocaine

oIt is analgesic.

oIn human it causes  hallucination and pentazocaine is developed to prevent drug abuse.

oIn horses it is used in the treatment of colic and administered at the rate of 0.33 mg/kg I.V.

oPenlog -Duration of analgesia 3-4 hour .Onset 1 min – one hour

· Butorphenol tartrate

oButorphenol is used in horses, cats and dogs.

oIt produces sedation, analgesia.

oDose

§ Horse = 0.1 mg/kg I.V

§ Dogs = 0.2 – 0.8 mg/kg I.M/S.C

§ Cats = 0.2 – 0.4 mg/kg I.V/I.M/S.C

§ Onset 1 mint – 15 mint I.V. rapid

· Buprenorphine

oRespiratory depression is more and often treated with intermittent positive pressure ventilation.

oDose

§ Horses = 6 - 10 µg/kg

§ Dogs = 0.01 - 0.02 mg/kg S.C/I.M/I.V

§ Cats = 0.005 - 0.02 mg/kg S.C/I.M

PURE ANTAGONISTS

· Naloxone hydrochloride, nalorphine hydrochloride and diprenoorphine are the opioid pure antagonists used for the reversal of the effects of pure agonists and partial agonists.

· In horses naloxone is used in the control of crib biting.

· Dose

oNaloxone

§ Dogs and cats = 0.04 - 0.1 mg/kg I.V/I.M/S.C

§ Horses 0.005 = 0.2 mg/kg I.V

oDiprenorphine

§ Dogs & Cats = 0.0272 mg/kg I.V

§ Horse = 0.02 - 0.03 mg/kg I.V

 

 

 

CENTRALLY ACTING MUSCLE RELAXANTS (guaifenisin)

· Glyceryl guaiacolate ether (Guaifenisin) is the centrally acting muscle relaxant and it acts on the internuncial neurons of the spinal cord.

· It does not influence the respiratory centers in brain.

· It also induces sedation and hypnosis.

· It has got bactericidal action.

· The maximum dose of GGE is 90 to 100 mg/kg and if this dose is exceeded it will cause spasm, hypertonicity of muscles and cardiac arrest.

· GGE does not cross the placental barrier.

Horses

· GGE 50 mg/ml (5% solution) in 5% dextrose mixed with xylazine 0.5 mg/ml and ketamine 1.0 mg/ml is the routinely used mixture in horses.

Cattle

· GGE 50 mg/ml (5% solution) in 5% dextrose mixed with xylazine 0.05 mg/ml and ketamine 1.0 mg/ml is the mixture used in cattle.

CHLORAL HYDRATE

· Chloral hydrate is used as a sedative hypnotic in cattle and horses.

· It is less expensive. It has deep  aromatic odour and is bitter in taste.

· The CNS depression is due to its metabolic product namely 2,2,2 trichloro ethanol.

· It has no analgesic property.

· Chloral hydrate depresses the motor and sensory responses at sedative dose and produces cerebral and medullary center depression at anaesthetic dose resulting in muscle relaxation and depression of cardiac and respiratory system.

· In cattle it can be drenched preferably through stomach tube, at the dose of 30 to 120 grams dissolved as 1 in 20 solution in water.

· Chloral hydrate is administered as 10% solution intravenously in cattle at the dose of 80 to 90 mg/kg.

· It is combined with magnesium sulphate and pentobarbital and administered to horses (Equithesin mixture).

· Intravenous dose of chloral hydrate in horses

oChloral hydrate alone 5 to 10 mg/kg for mild sedation and hypnosis, 20 to 40 mg/kg for moderate sedation and hypnosis, 50 to 75 mg/kg for profound sedation and hypnosis and 150 to 250 mg/kg for anaesthesia.

· Disadvantages of chloral hydrate

oProlonged hangover with ataxia and stupor

oPerivascular administration causes pain, swelling and necrosis

oInduces abortion in mares.