Peri-Anaesthesia Pharmacology

By
Hyder Gulam,FRCNA
 OVERVIEW:

Introduction
Overview of General Anaesthesia
Inhalational Agents
Neuromuscular Blockade
Intravenous Agents – Benzodiazepines
Intravenous Agents – Hypnotics
Summary
 Overview of General Anaesthesia
Anaesthesia first used by Plato in 400 BC to
describe “absence of emotions”.
Other terms commonly used in association with
anaesthesia include:
-Analgesia: without pain
-Hypnosis: sleep
-Narcosis: dulling of consciousness
-Paralysis: without movement
A typical GA now includes a premedication, an
analgesic agent, iv induction, and the combination
of a volatile and gaseous agent (with or without a
muscle relaxant) as a maintenance anaesthesia.
 Overview of General Anaesthesia

There are 4 clinical stages of anaesthesia, which

recognise a progressive loss of cortical, sensory
and motor function.
The stages predict progressively decreasing
responses to surgical stimuli with increasing
anaesthesia. Depth of anaesthesia can therefore be
gauged by progressive loss of respiratory
response, reflexes such as coughing and
hiccuping, eyelid and gag reflexes, and finally
loss of cardiovascular responses such as
tachycardia, hypertension and diaphoresis.
 Clinical Stages of Anaesthesia
Stage 1 – Begins with the initiation of anaesthesia and
ends with loss of consciousness. Protective reflexes remain
intact. NURSING ACTION: Close OR doors, keep room
quiet, stand by patient to assist, rest and reassure.
Stage 2 – Starts with loss of consciousness with the onset
of regular pattern of breathing and disappearance of the lid
reflex. Patient may appear agitated and excited reactions to
stimuli (noise, being touched suddenly). NURSING
ACTION: Be ready to restrain patient.
Stage 3 – equated to the ‘surgical stage of anaesthesia’ as
at this level of anaesthesia there is depression of nervous
system function so that there is absence of cardiovascular
or respiratory responses to surgical stimulation. Eyelash
response, blink and swallowing reflex are absent. PREP
Stage 4 (over dosage) – extends from diaphragmatic
paralysis, apnoea, and loss of all reflex activity.Circulatory
collapse
 Triad of Anaesthesia

Hypnosis/Amnesia (Unconsciousness)

Reflex Suppression
(Analgesia) Paralysis (Muscle Relaxation)
 Inhalational Agents
MAC – Minimum Alveolar Concentration, the term used
to compare concentrations of inhalational agents. Refers to
the lowest concentration of the inhalational agents that
prevents movement in 50% of the patients when subjected
to a painful stimulus.
All inhalational agents depress the myocardium and
depress ventilation.
Either gases or liquids that evaporate at room temp to form
vapours that may be inhaled
These agents use the respiratory system for their uptake,
and to a large extent, their elimination form the body.
Nitrous Oxide (gaseous inhalation agent)

Relatively weak anaesthetic agent used in

conjunction with other volatile agents to lower
concentrations and decrease negative effects of
volatile agents.
Non-irritating to the respiratory tract
Analgesic properties
Depresses CNS. CO, SV, HR & BP remain
relatively constant
May increase cerebral blood flow and ICP
Always administered with approx.30% oxygen to
prevent hypoxia
 Halothane (Fluothane)

Primarily used in paediatric population

Non-irritating to respiratory tract, causes bronchodilation
Dilates cerebral blood vessels, increases ICP
Diminishes hepatic function, may cause ‘halothane
hepatitis’- 1:100,000 anesthetics.
Marked shivering related to decrease in body temperature,
may cause 3-4 fold increase in the persons oxygen
consumption.
Decreases glomerular filtration rate by 50%, possibly
resulting in nephrotoxicity.
May cause arrhythmias due to sensitisation of the
myocardium to catecholamines.
Isoflurane (Forane)(Forane)
Isoflurane
Stabilising effects on CV system
Does not increase sensitivity to catecholamines –
less incidence of arrhythmias
Reduces cerebral metabolic requirements,
maintains carbon dioxide responsiveness, and
causes a lesser degree of cerebral vasodilation –
agent of choice for neurosurgical procedures due
to degree of cerebral protection.
May be irritative to the respiratory system
Rapid recovery and emergence.
 Sevoflurance

More rapid induction and emergence that

isoflurane
No predisposition to arrhythmias
Less airway irritation
Increased ICP
Emerging as the agent of choice for ambulatory
and paediatric surgery.
Expensive $300-$400 per bottle.
 Neuromuscular Blockade

Used as an adjunct to inhalational agents to facilitate

intubation, provide relaxation of skeletal muscles
(abolishes laryngeal spasm), and enhance optimal surgical
conditions.
Normal Neuromuscular Transmission – Action potential
travels along the axon of a motor neuron. Motor nerve
releases an enzyme Acetylcholine (ACh). ACh acts on the
receptor site at the muscle surface resulting in polarization
(contraction). ACh is then metabolised by the enzyme
acetylcholinesterase and the muscle repolarises (relaxes).
Suxamethonium (Depolarizing muscle relaxant)

Onset: Rapid (30-60secs)

Duration: Short 3-5min
Causes muscular fasciculation– keeps muscle in a
depolarised state until metabolised by
pseudocholinesterase (found in the plasma). No
reversal required. Stored in fridge.
Side Effects: Bradycardia, myalgia, hyperkalemia
(fatal in burns, spinal injuries or massive trauma),
Sux apnoea, increased ICP. Hypothermia
increases duration.
Triggering agent for Malignant Hyperthermia,
 Non-Depolarizing Block

Compete with ACh for receptor sites, thereby

blocking the action of ACh resulting in
neuromuscular blockade.
Mivacurium (short acting 6-10min, minimal CV
effects, dose related histamine release),
Atracurium (intermediate acting 45min CV stable,
slight histamine release, used in ICU settings),
Vecuronium (power form, intermediate acting 20-
40min, no histamine release), Rocuronium (rapid
onset 60-90secs – alternative to SUX for rapid
sequence induction, Pancuronium (long acting 60-
80min, tachycardia).
 Non-Depolarizing Block-cont

Do not cause muscular fasciculation.

Reversed by Neostigmine – anticholinesterase drug),
restore neuromuscular transmission by displacing the
neuromuscular blocking agent from the receptor site.
Anticholinesterase drug bind with Acetylcholinesterase
preventing the hydrolysis of ACh. This increases the
concentration of ACh and allows the ACh to reclaim the
receptor site, thus preventing the blockade.
NEOSTIGMINE Onset: 6-8mins, Duration 60min,
Usual Dose 0.5-2.5mg IV. Causes muscarinic effects ie
bradycardia, bronchoconstriction, hypotension, nausea,
vomiting, salivation, lacrimation and urinal urgency.
 Non-Depolarizing Block-cont

Anticholinergic drugs are given concurrently with

anticholinesterase drugs to counteract these
muscarinic side effects.
ATROPINE Duration: 40mins, Dose: 2mg IV.
Tachydysrhythmias common.
GLYCOPYRROLATE Duration 80min, Dose:
1mg IV. More expensive, lower incidence of
dysrhythmias, slow change in heart rate – better
for the elderly and cardiac compromised.
Factors that may contribute to prolonged
neuromuscular blockade

Hypothermia
Hypercarbia
Acidosis
Hypokalemia
Renal disease, hepatic disease
Mycin antibiotics - tetracycline
Clinical Assessment for adequate reversal

Opens eyes
Sustain hand grasps
Sustains head lift for 5 secs
Adequate respirations and depth
Tidal Volume 5ml/kg
Monitor vital signs, assess secretions
Intravenous Agents – Benzodiazepines

Wide variety of uses including premedication

before surgery, induction and anaesthetic iv
sedation for hypnosis, amnesia and suppression of
seizure activity.
DIAZEPAM(Valium) – produces calming effect,
and skeletal muscle relaxation. Minimal
depressant effects on ventilation and circulation.
Dosage: 2-10mg IV; 0.4 mg/kg IM
Onset 1-3min IV, IM 20min - Duration 1 hour
Burns when given IV – note Dizac (Diazepam in
Emulsion) does not burn (decreased
thrombophlebitis)
Intravenous Agents – Benzodiazepines

MIDAZOLAM (Versed): Short acting CNS Depressant.

Possesses antianxiety, sedative, (retrograde) amnesic,
anticonvulsant and skeletal muscle relaxant effects. 3x
potent that diazepam
Dosage: 0.5-5mg IV titrated to effect
Onset: 1-5min - Duration 2-6 hours
Water Soluble – does not burn on injection.
FLUMAZENIL – Benzodiazepine antagonist
Dosage 0.2mg IV (Max dose 1mg/15min or 3mg/hour)
Onset 1-2min – Duration 1-3 hours
May cause nausea/vomiting.
 Intravenous Agents – Hypnotics
Used for anaesthetic, induction, sedation and maintenance

THIOPENTONE 4-6mg/kg IV PROPROFOL –Diprivan

Action: CNE Depressant, short
acting IV barbiturate. No
analgesic properties.
Onset: Rapid 15-40secs
Duration: 3-8mins, initial
hypnotic action is intense,
followed by mild sedation for
up to 24hrs
Uses: IV induction, brief
surgical procedures
Side Effects: Resp depression
(apnoea), hypotension,
laryngospasm, anaphylaxis,
arrhythmias, tissue necrosis
2mg/kg
Action: CNS Depressant. Short
acting anaesthetic agent
Onset: Rapid 15-40secs
Duration: 5-10min, with
minimal residual sedation
Uses: IV Induction,
Maintenance via infusion, brief
surgical procedures. Reduces
ICP and cerebral metabolic rate
Side Effects:
Minimal, pain upon injection,
hypotension, Resp depression
(apnoea), anaphylaxis, hiccup.
 References:

Aitkinson, R.S., Rushman, G.B. and Lee, J.A. 1987, A

Synopsis of Anaesthesia, Wright, Bristol.
Drain, C.B. 1994, The Post Anesthesia Care Unit (3rd edn),
W.B. Saunders,Philadelphia, P.A.
Litwack, K. 1995, Post Anesthesia Care Nursing (2nd
edn.), M.O. Mosby, St Louis.
Morgan, E.G. & Mikhail, M.S. 1996, Clinical
Anesthesiology, Appleton & Lange, California.
Rosewarne, F., Harley, I. And Hore, P. (eds) 1994,
Introductory Notes on Anaesthesia Australia (3rd Edn),
Royal Melbourne Hospital Anaesthetic Department.