GENERAL ANAESTHESIA
OVERVIEW:
- TWO MAIN TYPES of general anaesthetics (GAs):
o IV
o Inhalational (using a volatile liquid or gas)
- Anaesthesia can be INDUCED & MAINTAINED using either type (often used in combin.)
- When should the DOSE of GAs be REDUCED:
o Pt has severe hepatic impairment (less metabolism of GA)
o Pt is acutely ill (may exacerbate dyspnoea)
o Pt is debilitated
GA PHARMACOLOGY:
MOA: Cause CNS DEPRESSION through different mechanisms:
o Enhance effects of GABA (Propofol, Etomidate, Barbiturates, Fluorinated liquid)
o Inhibit effects of Glutamate on NMDA receptors (Ketamine, N2O) – illicit drugs
- This leads to THREE MAIN EFFECTS:
o Unconsciousness/Sedation
o Complete loss of sensation (Can’t feel, smell, hear, or see anything)
o Muscle Paralysis (which also disables your reflexes – no twitching during surgery)
- GAs put the pt in a MEDICALLY INDUCED, REVERSIBLE COMA
- This differs from analgesia which just treats PAIN but allows you to feel other stimuli e.g.
pressure, temperature, vibrations etc.
Intravenous GAs Inhalational GAs
- Propofol - Nitrous Oxide (N2O)
- Etomidate - Fluorinated volatile liquids
- Barbiturates (‘-Tals’) (‘-Fluranes’):
o Thiopental o Desflurane
o Phenobarbital NOT indicated for GA o Sevoflurane
- Ketamine (NMDA antagonist) o Isoflurane
GENERAL SIDE EFFECTS OF ALL GAs:
- HYPOtension: due to relaxation of vascular smooth muscle Vasodilation
- HYPOthermia: vasodilation of peripheral vessels increased HEAT LOSS (feel colder)
- Nausea & Vomiting (PONV): GAs stimulate the CTZ emesis
DRUG-SPECIFIC SIDE EFFECTS:
- Fluorinated liquids:
o Reflex Tachycardia: HR increases as a homeostatic reflex to increase BP – almost
all GAs disable this reflex EXCEPT for fluorinated liquids
o Airway irritation: these volatile liquids have a PUNGENT SMELL – induces
bronchospasm & should NOT be used for induction except for Sevoflurane
o Malignant Hyperthermia (see below)
- IV GABA enhancers: Respiratory depression - similar mechanism to benzos & opioids
- NMDA Antagonists: Hallucinations & Nightmares – rationale for abuse potential
, MALIGNANT (lethal) HYPERTHERMIA (MH):
- MH: RARE but LIFE-THREATENING reaction to TWO MAIN DRUGS:
o Fluorinated liquids (‘Fluranes’)
o Suxamethonium (Neuromuscular blocker – NOT a GA)
- SYMPTOMS (RAT): These symptoms are all caused by an INCREASE in
o Rigidity of muscles METABOLISM increased muscle activity, increased
o Acidosis CO2 production (produces carbonic acid) & increases
o Temperature temperature (heat is a by-product of metabolism)
- TREATMENT:
o Dantrolene: muscle relaxant reduces heat generated from muscle
contractions
o STOP the offending drug (e.g. fluorinated liquids or suxamethonium)
CHOICE OF GAs FOR INDUCTION (i) & MAINTENANCE (m)
- Propofol - i AND m : BEST ALL-ROUND GA (but has slight hangover effect)
- Thiopental – i ONLY: VERY SHORT ACTING barbiturate with little analgesic effect -
although it’s short-acting, it accumulates in adipose tissue sedation lasts 24 HOURS
- Etomidate – i ONLY: Like thiopental (short-acting & no analgesia) - weakest hangover
- Ketamine – i ONLY: RARELY used due to psychiatric ADRs – used mainly in PAEDIATRICS
- Nitrous oxide – m ONLY: difficult to induce sedation due to lack of potency – but has
GOOD ANALGESIC properties – often combined with other GAs to reduce their dose
PERI- & PRE-OPERATIVE DRUGS (NOT anaesthetics)
1- BENZODIAZEPINES:
- Useful for SEDATION, ANXIOLYSIS, & ANTEROGRADE AMNESIA (inability to form new
memories after taking the drug – so pt won’t remember going into the operating room)
- ORAL, SHORT-ACTING benzos often used as premedication – EXAMPLES:
o Lorazepam
o Temazepam
- ANTIDOTE for benzo OD = Flumazenil (benzo-receptor INHIBITOR on GABA receptor)
2- ANTIMUSCARINICS (AMs):
- Useful in DRYING BRONCHIAL & SALIVARY SECRETIONS which may be caused by:
o Intubation Anything that touches the RT will stimulate
o Inhalational GAs saliva/mucus secretion – this is a reflex to
o Surgery of the respiratory tract (RT) either digest/remove the foreign object
- Useful in counteracting the muscarinic ADRs of NEOSTIGMINE (acetylcholinesterase
inhibitor)
- EXAMPLES:
o Glycopyrronium
o Hyoscine hydrobromide (Scopolamine – also has ANTI-EMETIC effects)
o Atropine (ONLY FOR EMERGENCIES)
OVERVIEW:
- TWO MAIN TYPES of general anaesthetics (GAs):
o IV
o Inhalational (using a volatile liquid or gas)
- Anaesthesia can be INDUCED & MAINTAINED using either type (often used in combin.)
- When should the DOSE of GAs be REDUCED:
o Pt has severe hepatic impairment (less metabolism of GA)
o Pt is acutely ill (may exacerbate dyspnoea)
o Pt is debilitated
GA PHARMACOLOGY:
MOA: Cause CNS DEPRESSION through different mechanisms:
o Enhance effects of GABA (Propofol, Etomidate, Barbiturates, Fluorinated liquid)
o Inhibit effects of Glutamate on NMDA receptors (Ketamine, N2O) – illicit drugs
- This leads to THREE MAIN EFFECTS:
o Unconsciousness/Sedation
o Complete loss of sensation (Can’t feel, smell, hear, or see anything)
o Muscle Paralysis (which also disables your reflexes – no twitching during surgery)
- GAs put the pt in a MEDICALLY INDUCED, REVERSIBLE COMA
- This differs from analgesia which just treats PAIN but allows you to feel other stimuli e.g.
pressure, temperature, vibrations etc.
Intravenous GAs Inhalational GAs
- Propofol - Nitrous Oxide (N2O)
- Etomidate - Fluorinated volatile liquids
- Barbiturates (‘-Tals’) (‘-Fluranes’):
o Thiopental o Desflurane
o Phenobarbital NOT indicated for GA o Sevoflurane
- Ketamine (NMDA antagonist) o Isoflurane
GENERAL SIDE EFFECTS OF ALL GAs:
- HYPOtension: due to relaxation of vascular smooth muscle Vasodilation
- HYPOthermia: vasodilation of peripheral vessels increased HEAT LOSS (feel colder)
- Nausea & Vomiting (PONV): GAs stimulate the CTZ emesis
DRUG-SPECIFIC SIDE EFFECTS:
- Fluorinated liquids:
o Reflex Tachycardia: HR increases as a homeostatic reflex to increase BP – almost
all GAs disable this reflex EXCEPT for fluorinated liquids
o Airway irritation: these volatile liquids have a PUNGENT SMELL – induces
bronchospasm & should NOT be used for induction except for Sevoflurane
o Malignant Hyperthermia (see below)
- IV GABA enhancers: Respiratory depression - similar mechanism to benzos & opioids
- NMDA Antagonists: Hallucinations & Nightmares – rationale for abuse potential
, MALIGNANT (lethal) HYPERTHERMIA (MH):
- MH: RARE but LIFE-THREATENING reaction to TWO MAIN DRUGS:
o Fluorinated liquids (‘Fluranes’)
o Suxamethonium (Neuromuscular blocker – NOT a GA)
- SYMPTOMS (RAT): These symptoms are all caused by an INCREASE in
o Rigidity of muscles METABOLISM increased muscle activity, increased
o Acidosis CO2 production (produces carbonic acid) & increases
o Temperature temperature (heat is a by-product of metabolism)
- TREATMENT:
o Dantrolene: muscle relaxant reduces heat generated from muscle
contractions
o STOP the offending drug (e.g. fluorinated liquids or suxamethonium)
CHOICE OF GAs FOR INDUCTION (i) & MAINTENANCE (m)
- Propofol - i AND m : BEST ALL-ROUND GA (but has slight hangover effect)
- Thiopental – i ONLY: VERY SHORT ACTING barbiturate with little analgesic effect -
although it’s short-acting, it accumulates in adipose tissue sedation lasts 24 HOURS
- Etomidate – i ONLY: Like thiopental (short-acting & no analgesia) - weakest hangover
- Ketamine – i ONLY: RARELY used due to psychiatric ADRs – used mainly in PAEDIATRICS
- Nitrous oxide – m ONLY: difficult to induce sedation due to lack of potency – but has
GOOD ANALGESIC properties – often combined with other GAs to reduce their dose
PERI- & PRE-OPERATIVE DRUGS (NOT anaesthetics)
1- BENZODIAZEPINES:
- Useful for SEDATION, ANXIOLYSIS, & ANTEROGRADE AMNESIA (inability to form new
memories after taking the drug – so pt won’t remember going into the operating room)
- ORAL, SHORT-ACTING benzos often used as premedication – EXAMPLES:
o Lorazepam
o Temazepam
- ANTIDOTE for benzo OD = Flumazenil (benzo-receptor INHIBITOR on GABA receptor)
2- ANTIMUSCARINICS (AMs):
- Useful in DRYING BRONCHIAL & SALIVARY SECRETIONS which may be caused by:
o Intubation Anything that touches the RT will stimulate
o Inhalational GAs saliva/mucus secretion – this is a reflex to
o Surgery of the respiratory tract (RT) either digest/remove the foreign object
- Useful in counteracting the muscarinic ADRs of NEOSTIGMINE (acetylcholinesterase
inhibitor)
- EXAMPLES:
o Glycopyrronium
o Hyoscine hydrobromide (Scopolamine – also has ANTI-EMETIC effects)
o Atropine (ONLY FOR EMERGENCIES)
