Anaesthetic Agents

Anaesthetic Agents

Dose Calculations of Anaesthetic Drugs

·        Concentrations.  Four most common methods of specifying concentration are:

o   Mg/ml: weight of drug per volume of dilutent 

o   % - number of grams of drug per 100ml. E.g. 50% = 50 grams per 100 ml or 500 mg/ml. 1% = 10 mg/ml. Multiplying by 10 gives mg/ml. Often used for lignocaine (Xylocaine)

o   1:1000 is the same as 0.1% (1 mg/ml).  Used for adrenaline and isoprenaline

o   mmol/l: used for electrolytes

·        Infusions:

o   Use for drugs with very short T½ where fluctuations in dose of drug are dangerous

o   Common for adrenaline, dopamine, dobutamine & lignocaine

·        E.g. post arrest infusion of lignocaine at 2 mg/min with 2% xylocaine. This is 20 mg/ml, so want 0.1 ml per minute. Using a burette system can deliver 6 drops a minute (60 drops = 1 ml) or dilute 10 fold and run at 60 drops per minute (easier)

Inhalational Anaesthetics

·        Gases = compounds in the gaseous state at a temperature above their critical temperature.

·        Vapours = compounds in gaseous phase but can be returned to liquid by ­ in pressure. Ambient temperature must be below the critical temperature for the compound

·        The partial pressure in the brain necessary to achieve anaesthesia will depend on its potency

·        Poorly soluble gases will have higher partial pressure at a given concentration and will have a fast onset.

·        Lipid soluble drugs are more potent

·        So more soluble drugs have slower uptake in blood and require lower partial pressure to achieve their effect

·        Factors affecting uptake:

o  Inspired partial pressure

o  Alveolar ventilation

o  Circulation

o  Properties of the anaesthetic agent (e.g. blood solubility)

·        Nitrous Oxide (N2O):

o  Pleasant, non-irritating, non-flammable (but supports combustion)

o  Stored in blue cylinders 

o  Poorly soluble in tissues ® rapid uptake and elimination

o  Good analgesic but low potency

o  Always given with at least 30% O2 to avoid hypoxia 

o  Expands in enclosed air spaces: so avoided for middle ear operations and where air embolism may occur 

o  Give 100% O2 at end of N2O anaesthesia to avoid diffusion hypoxia – N2O rapidly leaves pulmonary capillaries ® ¯alveolar O2 concentration

·        Halothane: 

o  High potency (Minimum Alveolar Concentration, MAC = 0.7% - level that produces immobility in 50% of people, NO2 is 105% Þ not so good) 

o  No irritation and moderately rapid induction and recovery

o  Poor relaxant and analgesic properties

o  Requires accurate vaporisers

o  High concentrations produce profound respiratory and cardiac depression

o  Rare complication is hepatic necrosis

·        Isoflurane:

o  Similar to halothane, but more irritant so difficult to use for induction

o  More potent vasodilator ® hypotension and tachycardia

o  Also sevoflurane: not so irritant, quicker onset, but more expensive.  Use in kids if can‟t cannulate

Intravenous Anaesthetics

·        Can be given as bolus for induction or infusion for maintenance

·        All have similar characteristics:

o  All are lipid soluble

o  Unionised fraction crosses the blood brain barrier

o  Loss of consciousness usually occurs in one arm to brain circulation time (approx. 30 secs)

o  Rapidly redistributed to tissues with high blood flow so rapid fall in peak plasma concentration

·        Thiopentone:

o  Barbiturate derivative containing sulphur (® yellow)

o  Highly alkaline in solution ® thrombophlebitis 

o  Blood level results from distribution (seconds), redistribution (e.g. from muscle to fat – minutes/hours) and metabolism (15%/hour by liver) 

o  CNS depression - ¯cerebral O2 consumption, potent anticonvulsant

o  Respiratory depression: especially initially – may be apnoeic for short period 

o  Circulatory effects - ¯cardiac outputs, ¯vasomotor depression ® peripheral vasodilation ® ¯BP

o  Poor analgesia and prolonged hangover

o  Dose: 4 mg/kg – less for elderly, more for robust male

o  Complications: acute intermittent porphyria and IgE mediated hypersensitivity

·        Propofol:

o  White, oil in water emulsions, 20 ml ampoules, 1% solution = 10 mg/ml

o   Structurally different to barbiturates 

o   Highly lipid soluble: so rapid onset – and short duration due to rapid distribution, metabolism (T ½ = 35 – 50 minutes) and delayed return from poorly perfused tissues (e.g. fat)

o   Smooth induction, rapid recovery

o   Poor analgesic

o   Apnoea for about 30 seconds common 

o   More ¯BP but less nausea/vomiting than thiopentone

o   Induction dose: 2 mg/kg in young and 1.5 mg in elderly

·        Midazolam:

o   H2O soluble benzodiazepine

o   Muscle relaxant, amnesic, anxiolytic, anticonvulsant

o   Rapid onset and rapid elimination (T½ = 2 hours) cf. other benzodiazepines

o   Unlike other iv anaesthetics can be reversed, with flumazenil

o   Used for minor procedures, ICU sedation 

o   Slower, more variable induction cf. thiopentone.  Small dose may ® deep anaesthesia

o   Dose for sedation: 1 – 5 mg titrated

o   Dose of induction: 10 – 15 mg (highly variable)

·        Ketamine:

o   Related to angel dust

o   Dissociative anaesthesia

o   BP and respiration well supported, bronchodilator

o   Dose for induction: IV 1 – 2 mg/kg, IM 5 – 12 mg/kg 

o   Smaller doses ® potent analgesia

o   A sympathetic stimulant, can have bad dreams

Neuromuscular Blockade

·        Muscle relaxants are used to:

o   Facilitate intubation and artificial ventilation

o   To facilitate abdominal access during abdominal surgery

o   To allow lighter levels of anaesthetic to be used ® rapid recovery and less cardiovascular depression

·        Block neuromuscular transmission from motor nerve to voluntary muscle (ACh transmission across synaptic cleft, broken down by cholinesterase)

·        Non-depolarising blocking agents:

o   Competitive antagonists of the nicotinic cholinergic motor end plate receptors. E.g. rocuronium, pancuronium, atracurium, vecuronium

o   Degree of block determined by train of four stimuli. Each successive twitch is a lower amplitude – trails off. No interference with twitch response until 75 – 80% receptors blocked. 90 – 95% block required for surgery

o   Reversed by anticholinesterase drugs: neostigmine (onset in 2 minutes, lasts 20 minutes), pyridostigmine, edrophonium. Inhibit acetylcholinesterase ® ­ACh, but also effects muscarinic sites in parasympathetic nervous system. Side effects include salivation, bronchospasm, ­gut motility and bradycardia. These effects blocked by atropine – which blocks the parasympathetic system

o   Analgesia ended with anticholinesterase (commonly neostigmine 2.5 mg) and atropine 1.2 mg

·        Depolarising Neuromuscular Blocking Agents:

o   Faster onset and shorter duration (4 – 6 mins) than non-depolarising. Used for short procedures (quick intubation), supplemented with non-depolarising for long procedures or given by constant infusion

o   Suxamethonium: reacts with ACh receptors to produce depolarisation (® fasciculation), but because it is not so rapidly eliminated as ACh, depolarisation persists ® inexcitability of membrane around endplate. Repolarisation happens when suxamethonium is hydrolysed by pseudocholinesterase (unless atypical genetic variant ® prolonged effect). If overdose or poor elimination ® drug-receptor complex forms, unavailable for ACh ® dual or phase II block. No antagonist to suxamethonium except fresh frozen plasma (contains pseudocholinesterase)

o   Train of four different to competitive antagonists: each twitch the same height (although reduced over normal)

o   Has other muscarinic side effects due to similarity to ACh: ­BP, ­intra-ocular pressure, ­bronchial secretions, ¯heart rate, post operative muscle pain

·         Suxamethonium is contraindicated in major burns, neurological injuries, hyperkalaemia, myasthenia and myotonic diseases, ¯pseudocholinesterase and history of malignant hyperthermia