PREANAESTHETIC
MEDICATION & I/V
ANAESTHETIC AGENTS
Dr. Shashi Bhushan
Professor
Dept. of Anaesthesiology
KGMU, Lucknow
Overview
Pre-anaesthetic Medication
Drugs used in pre-anaesthetic medication
General Anaesthetics
History
Stages of anaesthesia
Pharmacokinetics
Mechanism of action
Complications of general anaesthesia
Summary
Preanaesthetic medication
It is the term applied to the
administration of drugs prior to
general anaesthesia so as to make
anaesthesia safer for the patient
Ensures comfort to the patient & to
minimize adverse effects of
anaesthesia
Aims
Relief of anxiety & apprehension
preoperatively & facilitate smooth induction
Amnesia for pre- & post-operative events
Potentiate action of anaesthetics, so less
dose is needed
Aims(contd.)
Antiemetic effect extending to post-
operative period
Decrease secretions & vagal stimulation
caused by anaesthetics
Decrease acidity & volume of gastric juice to
prevent reflux & aspiration pneumonia
Drugs used for preanesthetic
medication
Anti-anxiety drugs-
- Provide relief from apprehension &
anxiety
- Post-operative amnesia
e.g. Diazepam (5-10mg oral), Lorazepam
(2mg i.m.) (avoided co-administration with
morphine, pethidine)
Sedatives-hypnotics-
e.g. Promethazine (25mg i.m.) has
sedative, antiemetic & anticholinergic
action
Causes negligible respiratory depression
& suitable for children
Opioid analgesics
Morphine (8-12mg i.m.) or Pethidine (50-
100mg i.m.) used one hour before surgery
Provide sedation, pre-& post-operative
analgesia, reduction in anaesthetic dose
Fentanyl (50-100g i.m. or i.v.) preferred
nowadays (just before induction of
anaesthesia)
Anticholinergics-
Atropine (0.5mg i.m.) or Hyoscine (0.5mg
i.m.) or Glycopyrrolate (0.1-0.3mg i.m.) one
hour before surgery(not used nowadays)
Reduces salivary & bronchial secretions,
vagal bradycardia, hypotension
Glycopyrrolate(selective peripheral action)
acts rapidly, longer acting, potent
antisecretory agent, prevents vagal
bradycardia effectively
Antiemetics-
Metoclopramide (10mg i.m.) used as
antiemetic & as prokinetic gastric emptying
agent prior to emergency surgery
Domperidone (10mg oral) more preferred
(does not produce extrapyramidal side effects)
Ondansetron (4-8mg i.v.), a 5HT3 receptor
antagonist, found effective in preventing post-
anaesthetic nausea & vomiting
Drugs reducing acid secretion
Ranitidine (150-300mg oral) or Famotidine
(20-40mg oral) given night before & in
morning along with Metoclopramide reduces
risk of gastric regurgitation & aspiration
pneumonia
Proton pump inhibitors like Omeprazole
(20mg) with Domperidone (10mg) is
preferred nowadays
GENERAL ANAESTHETICS
GeneralAnaesthetics (GA) are drugs which
produce reversible loss of all sensation &
consciousness
Neurophysiologicstate produced by general
anaesthetics characterized by five primary
effects:
Unconsciousness
Amnesia
Analgesia
Inhibition of autonomic reflexes
Skeletal muscle relaxation .
Ideal anaesthetic-
- Rapid induction
- Smooth loss of consciousness
- Rapidly reversible upon
discontinuation
- Possess a wide margin of safety
The cardinal features of general anaesthesia are:
Loss of all sensation, especially pain
Sleep (unconsciousness) & amnesia
Immobility & muscle relaxation
Abolition of somatic & autonomic reflexes
Development of intravenous anaesthetic
agents such as Propofol
Combined with Midazolam,
Dexmedetomidine & Remifentanyl
Led to the use of total intravenous
anaesthesia (TIVA) as clinically useful tool
in modern anaesthetic practice.
Intravenous Anaesthetics
a. Fast inducers
i.) Thiopental, Methohexital
ii.) Propofol, Etomidate
b. Slow inducers
i.) Benzodiazepines Diazepam,
Lorazepam & Midazolam
c. Dissociative anaesthesia Ketamine
d. Opioid analgesia Fentanyl
Pharmacokinetics
Procedure for producing anaesthesia
involves smooth & rapid induction
Maintenance
Prompt recovery after discontinuation
Induction
Time interval between the administration of
anaesthetic drug & development of stage of
surgical anaesthesia
Fast& smooth induction desired to avoid
dangerous excitatory phase
Thiopental or Propofol often used for
rapid induction
Unconsciousness results in few minutes
after injection
Muscle relaxants(Pancuronium or
Atracurium) co-administered to facilitate
intubation
Lipophilicity
is key factor governing
pharmacokinetics of inducing agents
Maintenance
Patient remains in sustained stage of
surgical anaesthesia(stage 3 plane 2)
Depth of anaesthesia depends on
concentration of anaesthetic in CNS
Usually maintained by administration of
gases or volatile liquid anaesthetics (offer
good control over depth of anaesthesia)
Recovery
Recovery phase starts as anaesthetic drug is
discontinued (reverse of induction)
In this phase, nitrous oxide moves out of
blood into alveoli at faster rate (causes
diffusion hypoxia)
Oxygen given in last few minutes of
anaesthesia & early post-anaesthetic period
More common with gases relatively insoluble
in blood
Mechanism of Anaesthesia
Non-selective in action
At molecular level, anaesthetics interact with
hydrophobic regions of neuronal membrane proteins
Inhaled anaesthetics, Barbiturates, Benzodiazepines,
Etomidate & propofol facilitate GABA-mediated
inhibition at GABAA receptor sites & increase Cl- flux
Ketamine blocks action of glutamate on NMDA
receptor
General anaesthetics disrupt neuronal
firing & sensory processing in thalamus,
by affecting neuronal membrane
proteins
Motor activity also reduced GA inhibit
neuronal output from internal pyramidal
layer of cerebral cortex
Intravenous anaesthetics
Thiopentone sodium
Ultrashort acting thiobarbiturate, smooth
induction within one circulation time
Crosses BBB rapidly
Diffuses rapidly out of brain, redistributed
to body fats, muscles & other tissues
Typical induction dose is 3-5mg/kg
Metabolised in liver
Cerebral vasoconstriction, reducing
cerebral blood flow & intracranial
pressure(suitable for patients with cerebral
oedema & brain tumours)
Laryngospasm on intubation
No muscle relaxant action
Barbiturates in general may precipitate
Acute intermittent porphyria (hepatic ALA
synthetase)
Propofol
Available as 1% or 2% emulsion in oil
Inductionof anaesthesia with 1.5-2.5mg/kg within 30 sec
& is smooth & pleasant
Low incidence of excitatory voluntary movements
Rapid recovery with low incidence of nausea &
vomiting(antiemetic action)
Non-irritant to respiratory airways
No analgesic or muscle relaxant action
Anticonvulsant action
Preferred agent for day care surgery
Apnoea & pain at site of injection are common after
bolus injection
Produces marked decrease in systemic blood
pressure during induction(decreases peripheral
resistance)
Bradycardia is frequent
Ketamine
Phencyclidine derivative
Dissociative anaesthesia: a state characterized by
immobility, amnesia and analgesia with light sleep
and feeling of dissociation from surroundings
Primary site of action cortex and limbic system
acts by blocking glutamate at NMDA receptors
Highly lipophilic drug
Dose: 1-2mg/kg i.v.
Only i.v. anaesthetic possessing significant
analgesic properties & produces CNS stimulation
Increases heart rate, blood pressure & cardiac
output
Markedly increases cerebral blood flow & ICP
Suitable for patients of hypovolaemic shock
Recovery associated with emergence delirium,
more in adults than children
Use of diazepam or midazolam i.v. prior to
Fentanyl
Potent, short acting (30-50min), opioid
analgesic
Generally given i.v.
Reflex effects of painful stimuli are
abolished
Respiratory depression is marked but
predictable
Decrease in heart rate, slight fall in BP
Nausea, vomiting & itching often occurs
during recovery
Also employed as adjunct to spinal & nerve
block anaesthesia & to relieve postoperative
pain
Complications of Anaesthesia
During anaesthesia: After anaesthesia:
Respiratory depression Nausea and vomiting
Salivation, respiratory Persisting sedation
secretions Pneumonia
Cardiac arrhythmias Organ damage liver,
Fall in BP kidney
Aspiration Nerve palsies
Laryngospasm and Emergence delirium
asphyxia Cognitive defects
Awareness
Delirium and convulsion
Fire and explosion
Balanced anaesthesia
General anaesthetics rarely given as sole agents
Anaesthetics adjuvants used to augment specific components
of surgical anaesthesia, permitting lesser doses of GA
General anaesthetic drug regimen for balanced anaesthesia:
Thiopental + Opioid analgesic(pethidine or fentanyl/
benzodiazepine) + Skeletal muscle relaxant
(pancuronium) & Nitrous oxide along with inhalation
anaesthetic(Halothane/other newer agents )
Summary
Anaesthetics Characteristics
Nitrous oxide Highest MAC, Second gas effect, Diffusion
hypoxia
Halothane Used in bronchial asthma, Malignant
Hyperthermia
Ether Safest in unskilled hands, highly inflammable
Sevoflurane Agent of choice for induction in children
Isoflurane Neurosurgery
Ketamine Dissociative anaesthesia, used in CHF & shock
Thiopentone Epilepsy, thyrotoxicosis
Propofol Day care anaesthesia, i.v. Anaesthetic of choice
in patients with Malignant Hyperthermia
Etomidate Aneurysm surgeries & cardiac diseases
References
Pharmacological Basis of Therapeutics, 12th
Edition, Goodman & Gilman's
Medical Pharmacology, S.K. Srivastava
Principles of Pharmacology, 2nd edition K.K. Sharma
Review of Pharmacology, 8th edition Gobind Rai
Garg
Thank You
