Lecture 29: Inhalation and Intravenous Anasesthetic agents

Question 1

What is aim of anaesthesia achieved by IV or Volatile agent (inhaled)

Answer 1

To produce hypnosis/ amnesia:

Question 2

What is the mechanism of action and uptake for inhalation anaesthetic agents

Answer 2

• Likely through GABA modulation in the brain and glycine in the spinal cord: hyperpolarise the neurons more.
• There is an equilibrium formed because concentration inhaled, then alveolar, arterial and then brain concentration. As it isn’t metabolised, when the conc inhaled decreases, the equilibrium moves out from the brain.
• The more lipid soluble, the lower the dose required.- but not all lipophilic agents produce anaesthesia

Question 3

What is the MAC and how does this relate to potency of an inhaled anaesthetic

Answer 3

Minimum alveolar concentration (%) that producing immobility on standard surgical stimulus in 50% of patients.

• Way to compare dosing to clinical effect.
  More potent agents have a lower MAC.

Question 4

Describe the MAC dose response curve and what factors shift this: needing higher MAC for same effect and needing lower MAC for same effect

Answer 4

• Curve is S shaped and steep so that effect increases rapidly with small increase of alveolar conc.
• Need a higher MAC For people that are younger, hyperthermia, hyperthyroid, on drugs (amphetamine), and heavy alcohol as curve shifts to the left
• Need a lower MAC for people that are older, hypothermia,hypothyroid, opioids, depressants, Pregnancy and low O2, high CO2

Question 5

How does blood flow and minute volume affect the measured alveolar concentration of the dose (end tidal agent) for inhaled anaesthetics

Answer 5

Increasing minute volume will increase the conc : introducing more gaseous anaesthetic whereas increasing the blood flow will decrease the conc because inspired gas is taken to other parts of the body

Question 6

What are the CNS, CVS and RS pharmacodynamic effects produced by inhaled anaesthetics

Answer 6

CNS:
Decreases Cerebral Metabolic rate of oxygen
Hypnosis, amnesia, immobility
Dose dependent increase in Cerebral blood flow and ICP.

CVS: Periphovasodilation= lower BP, but unchanged HR. SV not affected too greatly

RS: impair ventilatory response to hypoxia and hypercapnia. bronchodilation

Question 7

Give examples of modern inhaled anaesthetics 3 types and their special benefit

Answer 7

1. Isoflurane: CVS stability, wears off fast
2. Sevoflurane: good for gas inductions with kids
3. Desflurane: Rapid on and offset. Good for long cases: obese patients

Question 8

What are the 4 types of IV anaesthetic agents and their mechanisms of action

Answer 8

1. Barbituates: thiopentone
2. Phenols: propofol
3. Imadazole: Etomidate
   All enhance GABA- prolonging Cl- current hyperpolarisation
4. Phencyclidine derivatives: Ketamine
   Bind to PCP receptor (NMDA receptor) to antagonise glutamate and suppress excitation: also has analgesic effects

Question 9

Describe the pharmacokinetics of IV anaesthetics after entering the body

Answer 9

1. Drug from IV bolus taken up by vessel rich group - brain=20%. It is highly lipid soluble and can cross the BBB via diffusion.
2. As slower perfused tissues (fat) take up the drug, it leaves the VRG and concentration in blood falls. due to this redistribution the patient may wake up after a single IV dose even though the amount of drug in the body hasn’t changed much = offset
3. Actual metabolism is slower.

Question 10

Compare Thiopentone and Propofol- which is better but what is the failing of both

Answer 10

Propofol is the standard IV anaesthetic compared to Thiopenton

• Has 10x faster clearance, with cleaner offset so good for day stay surgery
• It only has minor accumulation in multi-dosing or infusion so can be used for maintenance
• Decreases CBF and ICP so good for neurosurgery compared to volatile agents
• Both metabolised in liver but has less induction of liver enzymes

However both agents cause CVS instability: reduction in Pulmonary vascular resistance and BP + resp depression and loss of reflexes

Question 11

What are the good and bad things about Etomidate

Answer 11

Good CVS stability, less respiratory depression.
Rapid clearance and good recovery

Bad: myoclonus + epileptogenic. Impairs adrenocorticoid release especially in rpt dose or infusion so can impair wound healing and patient recovery

Question 12

What are the good and bad things about Ketamine

Answer 12

Good for shocked patient: CVS stimulant
Preserves respiratory reflexes and drive to keep breathing

Bad: not good for neurosurgery: increases Cerebral metabolic rate of O2, CBF and ICF.
Slow induction and lasts longer in dissociative state, dysphoria

Question 13

What are the good and bad things using Total IV anaesthesia instead of both inhale and IV

Answer 13

• avoid inhalation anaesthetics which aren’t good for neurosurgery
  -Avoid complications of vapours: malignant hyperthermia, Nausea and Vomiting, Intracranial hypertension
  But Bad:
  -Cannot monitor the agent during surgery like inhalation (alveolar end tidal agent)
  -expensive