General Anaesthesia Morton successfully demonstrated ether general anaesthesia on 16.10.1846 at Boston, Massachusetts and his epitaph by the surgeon Henry Bigelow reads : "Thomas Green Morton : By whom pain in surgery was annulled, Before whom, in all time surgery was agony, Since whom, science has control over pain " Stages of Anaesthesia Guedel's classic description of the four stages of anaesthesia in 1937, in un-pre-medicated patients breathing diethyl ether in air was based on : • Progressive reduction of catecholamine induced autonomic responses • Progressive muscle paralysis (eye muscles first and intercostals and diaphragm last) • Progressive abolition of reflexes (eyelash, conjunctiva), corneal, cough, carinal) Stage I : Stage of analgesia (conscious and pain free as in Entonox for labour) Stage II : Stage of excitement due to catecholamines (increased BP, pulse, restless) Deep, irregular respiration, eye movements, divergent and dilated pupils, Lacrimation, vomiting, coughing, laryngospasm. Eyelash reflex lost. Stage III : Stage of surgical anaesthesia progressing through four planes : Plane I : Signs seen in stage II reduce. Movements cease. Conjunctiva! reflex lost. Plane II : Light GA. BP,pulse,respiration, pupils, tone normal. Corneal reflex lost Plane III : Deep GA. BP, pulse, respiration, muscle tone, reduced. Cough reflex Jost. Plane IV : Overdose. BP very low, only diaphragmatic breathing. Carina! reflex Jost. Stage IV : Cardio-respiratory failure and arrest with dilated pupils Since the early days anaesthetists have relied on clinical signs to judge the onset and depth of anaesthesia, and titrated anaesthetic agents accordingly. The use of muscle relaxants has abolished the signs of progressive muscle paralysis and loss of reflexes. Thus detection of autonomic signs of light anaesthesia are now more important as clues to recognize the occurrence of "awareness". With modem intravenous and inhalational induction the progression is too rapid for the stages to be recognized, but they are more clearly seen in the reverse on emergence from general anaesthesia. 6

General anaesthesia has traditionally consisted of a classical triad, and each component is varied without affecting the other two by using selective drugs. 1. Hypnosis with i. v. induction agents and inhalational anaesthetics 2. Analgesia with strong opiates 3. Muscle relaxation and reflex suppression with neuro-muscular blocking agents 4. Attenuation of the stress response is a fourth component, added recently. • Intubation response is abolished by high dose opiates, lignocaine or MgSO 4. • Surgical stress is attenuated by regional blockade with local anaesthetics. Intravenous Anaesthetic Agents THIOPENTAL : Short acting thiobarbiturate, slows GABA receptor dissociation Dose : 3-6 mg/kg as a 2.5% solution. Advantages Disadvantages Lower dose in hypovolaemia, elderly, cardiac compromised : Unconscious in 30 sec, peak in 3 min, redistributed in 5 min. Anti-convulsant, cerebral protective Less hypotension than propofol at induction : Hypotension due to vasodilatation and myocardial depression Danger of intra arterial injection (see page 19.17) Laryngospasm and apnoea at peak blood levels Slow metabolism and excretion (12h) causing hangover Contraindications : Airway obstruction, porphyria PROPOFOL Dose Advantages : 2,6, di-isopropyl phenol, slows GABA receptor dissociation : 2-3mg/kg bolus (dose adjusted as for thiopentone) 6-lOmg/kg/h infusion. Sedative in low dose (0-3mg/kg/h) : Recovery and metabolism in the liver are rapid with no hangover. Best agent for day surgery and total intravenous anaesthesia Depresses airway reflexes and allows easy insertion of LMA Reduces the sympathetic response to intubation Anti-emetic Disadvantages : Hypotension, apnoea, similar to thiopentone (more in the elderly) Pain on injection (use a large vein, with lml of2% lignocaine) Myoclonus. A void if allergic to soya bean oil and in epilepsy TIV A : Total Intra-Venous Anaesthesia and Target Controlled Infusion (TCI) A micro-processor controlled syringe pump automatically adjusts the rate of infusion, to attain the target plasma concentration programmed by the anaesthetist e.g. 5µg/ml propofol (according to age, weight, and height). Depth is adjusted by setting a new target (similar to adjusting the vapouriser).

ETOMIDATE Dose Advantages Disadvantages Contraindications : lmidazole derivative 0.2-0.4mg/kg Cardiovascular stability Adrenocortical suppression Pain on injection, myoclonus, nausea, vomiting Excitatory and emergence phenomena Porphyria, airway obstruction MIDAZOLAM : Short acting benzodiazepine, increases GABA recepor coupling Dose : 0.02-0.l mg/kg Advantages : Anxiolytic, amnesic, sedative, hypnotic, anticonvulsant, relaxant Disadvantages KETAMINE Dose Advantages Disadvantages Useful to avoid awareness and for co-induction Short duration (1-2 hours). Antagonized by flumazenil 200µg. CVS and RS depression if given in high dose in the elderly Phencyclidine; dissociative anaesthesia at NMDA receptor. 2mg/kg loading dose, lmg/kg maintenance, i.v.; 4mg/kg i.m. Provides somatic analgesia Maintains BP unless sympathetic activity is maximal as in shock Bronchodilator (useful in asthma) Maintains tone of airway muscles (useful in difficult airways) Emergence delirium and nightmares (reduced with midazolam) Excess salivation (reduced with atropine) Nausea, vomiting (reduced with anti-emetics) Increased intra-ocular and intra-cranial pressures Increased sympathetic activity (increases HR and BP) Analgesic Agents GA exacerbates the stress response and requires adequate, potent, opiate analgesics. Morphine : loading dose 0.15mg/kg and 1A dose hourly Pethidine : loading dose 1 mg/kg and 14 dose hourly Fentanyl : loading dose 1 µg/kg and 1A dose hourly Alfentanil : loading dose IOµg/kg and repeated hourly Remifentanil : loading dose 1 µg/kg with 0.4µg/kg/min infusion Reduce dose and frequency in extremes of age, respiratory, hepatic and renal disease. 

Inhalational Anaesthetic Agents Inhalational anaesthetics are used for induction as well as maintenance. The ability to titrate the dose and withdraw if in excess is useful in children and airway compromised patients. The minimal alveolar concentration (MAC) required (indicating potency) depends on lipid solubility, and the rapidity of induction depends on low blood I gas solubility. HALOTHANE Advantages Disadvantages ISOFLURANE Advantages MAC 0.75, blood I gas solubility 2.4 Non irritant, easy induction, bronchodilator Sensitises the myocardium to catecholamines, arrhythmias Hypotension is due to myocardial depression. Increases cerebral blood flow and intra cranial pressure Halothane hepatitis may occur in susceptible patients. MAC 1.15, blood I gas solubility 1.4 More rapid induction and recovery allows easier titration Does not sensitise the myocardium to catecholamines Hypotension is due to vasodilatation and not cardiac depression. Disadvantages : Pungent odour makes it unsuitable for gaseous induction. SEVOFLURANE MAC 1.7, blood/ gas solubility 0.6 Advantages : Very quick induction and recovery Disadvantages DESFLURANE Advantages Disadvantages Useful for induction especially in children and for neurosurgery. Degrades with heat and should not use low flows with soda lime MAC 6, blood I gas solubility 0.42 Least metabolism and solubility in fat Pungent, irritant, CO production NITROUS OXIDE MAC 105, blood I gas solubility 0.46 Advantages Disadvantages 6.4 Carrier gas, 200 gas effect hastens induction with halothane. Potential for hypoxia, diffusion hypoxia, reduced safe period Increases volume of air embolus, pneumothorax, intestines Increases pressure in sinuses, ears, eyes, tube cuffs Cardiac depression, sympathetic stimulation, PONV Increases cerebral blood flow Prolonged use and in the critically ill interferes with methionine synthase, B 12, folate, DNA, and bone marrow function Nausea and vomiting (reduced with anti-emetics) Increased intra-ocular and intra-cranial pressures Increased sympathetic activity (increases HR and BP).

 Muscle Relaxants CHOICE OF MUSCLE RELAXANT The choice depends on the requirements. • Speed of onset Full stomach: suxamethonium (30-60sec), rocuronium (60-90sec) • Duration of action Difficult intubation Long surgery : short acting for safety eg. suxamethonium (5min) : long acting (bolus) e.g. rocuronium or short acting relaxant as bolus or an infusion • Mode of metabolism and excretion Kidney failure Liver dysfunction : avoid pancuronium, reduce vecuronium : avoid vecuronium Elderly, organ dysfunction : use atracurium • Side effects o Hypertension and tachycardia by pancuronium (vagolytic) o Bradycardia by vecuronium I fentanyl combination ("clean drugs") o Histamine release and hypotension by mivacurium, atracurium (large doses) SUXAMEIBONIUM (DEPOLARISING MUSCLE RELAXANT) Dose lmg/k:g has a half life of 3 min. (duration of action is dose dependent) Drug of choice in "full stomachs" due to rapid onset (30sec) and in difficult intubation due to its short duration of action. Disadvantages • Muscle pains are common in ambulant patients . • Increases intra-ocular, intra-cranial and intra-gastric pressures • Increases serum K (normal increase 0.5mmol/L, in muscle injury 2mmol/L) e.g. bums ( 1-60 days), crush injury, myopathies, immobilization • Bradycardia occurs with the second dose specially in children. • Malignant hyperpyrexia and suxamethonium apnoea (see page 19.22 NON-DEPOLARISING MUSCLE RELAXANTS Drug ED95 Intubating Maintenance Recovery (min.) dose( mg/kg) dose( mg/kg) dose (mg) 25% 95% Atracurium 0.25 05 5-10 mg 3045 60-90 Vecuronium 0.05 0.1 !mg 30-60 60-120 Rocuronium 0.30 0.6 6-lOmg 3045 60-120 Pancuronium 0.06 0.1 lmg 3045 60-120 Mivacurium 0.08 0.1 6mg 10-20 20-40 6

INTUBATION (see page 4.7) • Use 2-3 times ED 95 and wait 2 mins before intubation. Priming ( 1/lQth of intubating dose 2 min. prior) accelerates onset by 30 seconds. • Ensure best possible ventilation with 2 persons, triple maneuvre and oral airway if necessary to prevent gastric distension due to insufflation. • Ensure best possible oxygenation with volatile agent in 02 __ Avoid nitrous oxide. • Intubation is possible at TOF count of 1 or even before, as muscles of the jaw and larynx relax before the peripheral muscles. Facial nerve stimulation correlates better with the larynx than ulnar nerve stimulation. MAINTENANCE The degree of block required depends on the type of surgery. • For immobility e.g. vitrectomy and neurosurgery, a TOF count of 0 with PTC <20 • For abdominal relaxation and IPPV, a TOF count of 1-2 Indication for top up doses : "curare cleft" on capnography or TOF count as required. Airway pressure changes are relatively insensitive. REVERSAL 1. Confirm onset of recovery from bag movement, curare cleft, or TOF 3-4. 2. Give atropine 0.5-lmg and neostigmine 1.25-2.5mg depending on the degree of recovery. (For children neostigmine 0.04mg/kg and atropine 0.02mg/kg). Sugammadex : a new, unique, selective relaxant binding agent (SRBA) which rapidly reverses amino-steroid relaxants (vecuronium, rocuronium). Dose depends on the intensity of block 2-16mg/kg (see page 19.8). 3. Continue oxygen and volatile agent until ventilation is adequate via a circle or Bain breathing system (volatile agent could be tailed off if surgery lasted> lhr.) 4. Ventilation should be adequate in 6 minutes (peak effect ofneostigmine). 5. Withdraw ventilatory support when: • Normal ventilatory pattern is restored (chest expansion) • Excursion of the reservoir bag is adequate or ETCO 2 <40mm • PNS shows TOF 4 with no fade. 6. Extubation (see page 4.12) RECOVERY Patient should not be returned to the ward unless recovery from relaxants is complete. The following should be tested after recovery of consciousness. 1. Sustained head or arm lift for 5 seconds (most useful). 2. Effective cough (indicates respiratory reserve and airway protection) 3. Tongue protrusion (indicates ability to maintain the airway) 4. Hand grip (indicates muscle power) 5. Eye opening without wrinkling the forehead (small muscles recover last)  

Awareness "Not only must we not give too much anaesthesia, we must not give too little." Awareness occurs when muscle relaxants are used with light GA. Incidence 0.2%. It is the ability to feel discomfort, pain, paralysis or hear sounds during GA. It maybe explicit when the memory is recalled or implicit if not. It may cause psychological stress disorders, insomnia, depression, flashbacks etc. High risk : Endoscopies, caesarean section, trauma, the critically ill, C-P bypass Clinical signs: Movements, wrinkling of eye brows (abolished with relaxants) sweating, lacrimation, dilatation of pupil, hypertension, tachycardia and dysrhythmias PREVENTION OF AWARENESS 1. Check the machine, vaporizer and ventilator for leaks to ensure delivery of volatile agent as nitrous oxide does not prevent awareness. 2. Premedicate with midazolam. 3. Induction and intubation • Use an adequate induction dose or if there is a need to reduce as in a moribund patient, use co-induction with midazolam or ketamine. • Ventilate with oxygen and a volatile agent prior to intubation when using non-depolarising relaxants. • Check whether the patient is losing consciousness before injecting suxamethonium as otherwise it may act before the induction agent. • Add the inhalational agent soon after intubation . 4. Maintenance • Use a volatile agent throughout, and increase the dose if >50% 02 is given. • Do not give >50% oxygen for hypotension unless there is desaturation. • Give adequate opiates with "top up" doses hourly. • When using the circle circuit, give 6L FGF with volatile agent for 10 min to establish the depth of anaesthesia, before reducing FGF. When reducing FGF, increase the vaporizer setting accordingly. Monitor pulse, BP, end-tidal gases (ensure lMAC if possible), BIS index • A void adverse comments regarding the patient or the surgery. • Ventilate with a volatile agent until spontaneous ventilation is adequate. POST-OPERATIVE VISIT: Communicate, explain, empathise, counsel