General Anaesthetics Flashcards
Uses of GA:
- Produce unconsciousness and lack of responsiveness to all painful stimuli – inhibit sensory and autonomic reflexes
- causes hypnosis, amnesia and analgesia
- allow for skeletal muscle relaxation
GA stages:
- Pre-assessment/premed
- Induction of anaesthesia
- Airway management
- Maintenance of anaesthesia
- Reversal/emergency
- Post-operative care
Traits of ideal GA:
- Unconsciousness
- Analgesia
- Muscle relaxation
- Amnesia
- Brief and pleasant
- Depth of anesthesia can be increased or decreased with ease
- Minimal adverse effects
- Large margin of safety
Drugs commonly used in combination in GA:
- inhalation and intravenous anaesthetics
- Short-acting barbiturates (induction)
- NM blocking agents (muscle relaxation)
- Opioids and nitrous oxide (analgesia)
What is MAC:
index of inhalation anaesthetic potency (the lower the MAC, the more potent it is)
- Defined as minimum concentration of drug in alveolar air that will produce immobility in 50% of patients exposed to painful stimulus
- Values alter with age, condition, concommitant administration of other drugs etc.
Examples of inhalation anaesthetics:
volatile liquids: halothane, enflurane, desflurane, isoflurane, sevoflurane
Gases: nitrous oxide
Possible MoA of Inhaled GA:
- enhance neurotransmission at inhibitory synapses via allosterically increasing GABA receptor sensitivity to action by GABA itself (positive allosteric modulator)
- Depress neurotrransmission at excitatory synapses via blocking glutamate neurotransmitter acting on NMDA receptor – prevent activation (negative allosteric modulator)
Factors affecting absorption of Inhaled GA:
- Concentration of anaesthetic in inspired air
- Solubility of GA in blood
- Blood flow through lungs
Factor affecting distribution of inhaled GA:
Regional blood flow – determines which tissues receive GA – highly perfused tissues will have the anaesthetic levels equilibrating with those in blood quickly after administration
mechanism of elimination of inhalation anaesthetics:
exported in expired breath
eliminated almost entirely via lungs
minimal hepatic metabolism
Metabolites of inhalation anaesthetics
- Inorganic fluorides(isoflurane and enflurane) – nephrotoxic
- Halothane – hepatotoxic
Adverse effects of halothane:
- Respiratory depression (dose-dependent)
- decreased BP due to depression of cardiac output
- Arrhythmia
- halothane-associated hepatitis
- (May be a use as well) relaxes skeletal muscle and potentiates skeletal muscle relaxants
Adverse effects of isoflurane:
- dose-dependent respiratory depression
- decreased BP due to decrease in systemic/vascular resistance
- less hypotension and arrhythmia compared to halothane
MAC of inhaled anaesthetics:
Halothane: 0.75%
Isoflurane: 1.4%
Sevoflurane: 2%
Nitrous oxide: 105-110%
mechanism of nephrotoxicity in sevoflurane:
metabolised in liver to release inorganic fluoride
Rank the time needed for onset and recovery of inahled anaesthetics:
- Isoflurane
- Halthane
- Nitrous Oxide
- Sevoflurane
nitrous oxide < sevoflurane < isoflurane and halothane
limitations of use of nitrous oxide in GA: :
give analgesia and amnesia but not complete unconsciousness/surgical anaesthesia
- used to supplement analgesic effects of primary anaesthetic
Major concern in use of nitrous oxide
post-operative nausea and vomiting
Things to take note of in the use of sevoflurane:
degrade to compound that is potentially nephrotoxic when exposed to carbon dioxide absorbants in anaesthetic machines
Types of intravenous anaesthetics
thiopentane, etomidate, propofol, ketamine, midazolam
Purpose of IV anaesthetics. Comment on its duration of action
- induce unconsciousness
- does not keep you asleep for very long – effects on its own is not very long
Advantages of using a combination of inh and iv anaesthetics:
- permit dosage of inhalation agent to be decreased
2. produce effects that cannot be achieved with an inhalation GA alone
advantage of thiopentone:
extremely high lipid solubility – enters brain easily and rapidly for rapid onset of action – unconsciousness occurs 10-20 sec after IV
pk of thiopentone:
- Large Volume of Distribution
- Active metabolite Pentobarbital – liver cirrhosis can result in prolongation of clinical action
- Extensively bound to plasma proteins – small amount of free drug excreted by glomerular filtration + reabsorption in tubules
- Less than 1% excreted unchanged
MoA of thiopentone:
Cause CNS depression by potentiating action of GABA on GABA-A receptor-gated chloride ion channels
- Does not replace neurotransmitter but allow for more effective binding
- lead to greater entry of chloride ions as channel is open, making it difficult to depolarise
What is Propofol used for in patients who require anaesthesia?
For both induction and maintenance (by infusion)
Onset and duration of propofol:
rapid onset ( unconsciousness develops within ~60 sec) short duration of action (~3-5 min following single injection) rapid distribution from brain to other tissues
use of propofol:
extensively used in day surgeries, need continuous, low dose infusion for extended effects
benefits of using propofol over using other anaesthetic agents
- reduced postoperative vomiting (anti-emetic action)
side effects of propofol:
significant CV effects during induction: lowered BP and negative inotropic –> hypotension
caution for use of propofol:
used with caution in elderly patients, patients with compromised cardiac function, hypovolemic patients
what makes ketamine different from other IV anaesthetic
- only IV anaesthetic possessing analgesic property
- produce state of dissociative anaesthesia – patient dissociated from environment, commonly used in vet practice/antidepressant with fast onset
Effects of ketamine:
Sedation, immobility, analgesia, amnesia
PK of ketamine:
- metabolised in liver to less active metabolite, excreted in bile
- Large volume of distribution, rapid clearance – suitable for continuous infusion without lengthening duration of action
benefits of using ketamine:
rapid induction, responsiveness to pain is lost – good analgesic effects
Adverse effects of ketamine:
unpleasant psychologic reactions (hallucination, disturbing dreams, delirium) may occur during recovery
Methods to reduce adverse effects of ketamine:
premedication of diazepam/midazolam
Types of anaesthetic adjuncts:
- Benzodiazepines (IV midazolam)
- a2 adrenergic agonists (IV dexmedetomidine)
- Analgesics (NSAIDs/Opioids)
- Neuromuscular blockers (succinylcholine, vecuronium)
use of BZDs as anaesthetic adjuncts:
used for sedation during procedures not requiring GA
as anxiolytics, for amnesia and sedation prior to induction of anaesthesia
benefits of using BZDs as anaesthetic adjuncts:
- rapid onset when used for induction (unconsciousness develops in 80 seconds)
- High therapeutic index
metabolism of IV midazolam:
metabolised in liver – people with liver issues will be more sensitive
adverse effects of IV midazolam:
CV and respiratory depressing effect (less compared to other IV anaesthetics) – compounded by use with other agents
how to mitigate adverse effects of IV midazolam:
inject midazolam slowly (2 or more mins) and wait another 2 more mins for full effects before dosing again – side effects minimised by dragging out administration duration
how is IV dexmedetomidine used in GA:
- sedation prior to and/or during procedures in non-intubated patients
- short-term sedation (<24 hours)
benefits in use of IV dexmedetomidine:
- little respiratory depression
- has sedative and analgesic effects
- Tolerable decrease in bp and HR
Side effects of IV dexmedetomidine:
nausea, dry mouth, hypotension, bradycardia
list of possible analgesics that can be used during/post operation:
fentanyl morphine sufentanil remifentanil alfentanil
Why and when are analgesics used with GA:
- to decrease anaesthetic requirement
- for minor surgical procedures (cox-2 inhibitors, paracetamol and opioids for perioperative period)
Metabolism and excretion of analgesics:
metabolised in liver (remifentanil hydrolysed by tissue and plasma esterases)
excretion in urine and bile
Use of NM blockers in GA:
used during induction of anaesthesia to relax muscles to facilitate laryngoscopy and endotracheal intubation
- aids many surgical procedures and provide additional insurance of immobility
two NM blockers commonly used:
depolarising: succinylcholine
non-depolarising: vecuronium
caution when using IV NM blockers:
barbiturates will precipitate when mixed with muscle relaxants – should be allowed to clear from IV line
Reason for ultra-short duration of action of thiopentone
redistributes to less vascularised tissues
