Etomidate, Ketamine and the Role of Opioids

Question 1

What is the mode of action of etomidate?

Answer 1

The mode of action of etomidate remains unclear, but it is believed to modulate inhibitory GABA (gamma-aminobutyric acid) receptors in the central nervous system.

Although etomidate is presented as a racemic mixture, only the D-isomer has pharmacological activity.

Question 2

What is the induction dose of etomidate?

Answer 2

The induction dose for an adult is 0.3 mg/kg.

Question 3

Why should etomidate be avoided in septic shock?

Answer 3

Etomidate inhibits 11- β hydroxylase and cholersterol-side-chain-cleavage enzymes in the adrenal cortex. This results in decreased cortisol and aldosterone production, even following a single bolus. Inhibition of steroidogenesis may be particularly harmful to patients with septic shock. In the patient group, avoidance of etomidate or supplementation with exogenous steroid should be considered. Etomidate should not be administered as an infusion.

Question 4

How is etomidate metabolised (pharmacokinetics)?

Answer 4

Following injection of etomidate, redistribution occurs rapidly. Metabolism occurs via ester hydrolysis in both the plasma and the liver. Metabolites are excreted via urine and bile; 2% remains unchanged.

Question 5

Prolonged infusions of etomidate may be fatal T/F

Answer 5

True. A single dose of etomidate can cause adrenal suppression for up to 24 h. Prolonged infusions, e.g. in ICU, have been associated with fatal outcomes. For this reason it is contraindicated as an infusion.

Question 6

Pain on injection is common with etomidate T/F

Answer 6

True. Etomidate does frequently cause pain on injection.

Question 7

Etomidate causes nausea and vomiting T/F

Answer 7

True. Etomidate has a high incidence of postoperative nausea and vomiting.

Question 8

Etomidate may cause bronchoconstriction T/F

Answer 8

False. Etomidate infrequently releases histamine and is safe to be given to asthmatics.

Question 9

Etomidate may cause myoclonus T/F

Answer 9

True. Etomidate frequently causes involuntary muscle movement.

Question 10

What is the mode of action of ketamine?

Answer 10

Ketamine is a NMDA (N-methyl-D-aspartate) receptor antagonist. It is a non-competitive antagonist of the calcium-ion channel in the NMDA receptor. It further inhibits the NMDA-receptor by binding to its phencyclidine binding site. Ketamine demonstrates some affinity for opioid receptors, providing potent analgesia. At higher doses, ketamine has a local anaesthetic effect, probably due to blockage of fast sodium channels. It also antagonises muscarinic acetylcholine receptors, which results in anti-cholinergeric side-effects such as bronchodilatation, delirium and a sympathomimetic action.

Question 11

What is the induction dose of ketamine?

Answer 11

The dose to induce general anaesthesia in adults is:

1-2 mg/kg IV
10 mg/kg IM

Question 12

Ketamine is an agonist at the GABA receptor T/F

Answer 12

False. Ketamine is not a traditional hypnotic agent and has no activity at the GABA receptor. It produces a state of dissociative anaesthesia.

Question 13

The R(-) enantiomer is more potent in ketamine T/F

Answer 13

False. The S(+) enantiomer is more potent.

Question 14

Ketamine causes bronchodilatation T/F

Answer 14

True. It produces bronchodilatation and can be used to treat resistant asthma.

Question 15

Ketamine is the agent of choice in patients with ischaemic heart disease T/F

Answer 15

False. It increases myocardial oxygen demand and is contraindicated in severe ischaemic heart disease.

Question 16

Ketamine may increase systolic blood pressure T/F

Answer 16

True. Ketamine increases heart rate, blood pressure and cardiac output.

Question 17

What is the mode of action of opioids?

Answer 17

Opioids are agonists at mu-, delta- and kappa-opioid receptors. These receptors are found throughout the CNS and are especially abundant supraspinally in the peri-aqueductal grey matter area and the substantia gelatinosa of the spinal cord.

Opioid receptors are also found in the gastrointestinal tract, accounting for the decreased motility which is seen with the use of opioids.

Question 18

What kind of receptors are opioid receptors?

Answer 18

Opioid recpetors are all G-protein coupled receptors. Mu and delta receptors open potassium channels, increasing potassium efflux while kappa receptors close calcium channels. This causes hyperpolarisation of cells and decreased neuronal discharge.

Question 19

Roughly how much more potent than morphine is fentanyl?

Answer 19

Fentanyl is a synthetic opioid related structurally to pethidine. It is about 100 times more potent than morphine

Question 20

How quick is the onset of alfentanil and how long does it provide analgaesia for?

Answer 20

Alfentanil is also a synthetic opioid. It has a very rapid onset of action in one arm-brain circulation time and provides intense analgesia for 5-10 minutes.

Question 21

Why is remifentanil useful for long procedures or in ICU?

Answer 21

Falls in plasma concentrations are independent of the dose and duration of infusion, hence it has a reliably short context-sensitive half-time, making it useful for lengthy operations or intensive care settings.

Question 22

A 20-year-old male, in hypovolaemic shock from a stab wound to the left ventricle. Ketamine should be considered as an induction agent T/F

Answer 22

True. Ketamine can be used as a sole anaesthetic agent in these circumstances. It produces intense analgesia, dissociative anaesthesia and does not compromise the cardiovascular system.

Question 23

An 80-year-male, in hypovolaemic shock from a ruptured aortic aneurysm. Etomidate should be considered as an induction agent T/F

Answer 23

True. Etomidate is less likely to worsen the hypotension than propofol or thiopental.

Question 24

A 40-year-old male, for an emergency appendicectomy. Etomidate is the best choice for induction T/F

Answer 24

False. In most circumstances, etomidate should not be used in this scenario due to its wide side-effect profile. Some anaesthetists may use it in severely septic and compromised patients.

Question 25

A 76-year-old male, undergoing elective coronary artery bypass grafting. Etomidate is the induction agent of choice T/F

Answer 25

False. Whilst etomidate may be used for induction due to its favourable cardiovascular profile, it is not routinely used in cardiac anaesthesia.

Question 26

Ketamine and etomidate can both safely be used in asthmatics T/F

Answer 26

True. Both agents can safely be used.

Question 27

Etomidate is a carboxylated imidazole T/F

Answer 27

True

Question 28

Ketamine is a phencyclidine derivative T/F

Answer 28

True

Question 29

A 20-year-old female with pre-eclampsia is undergoing a GA Caesarean section. Alfentanil is a useful adjunct at induction of anaesthesia T/F

Answer 29

True. Alfentanil is a potent inhibitor of the sympathetic response to intubation and would be a good choice in a patient with pre-eclampsia.

Question 30

Remifentanil is best used as a bolus dose T/F

Answer 30

False. The ultra-short half life of remifentanil makes it suitable for use only as an infusion.

Question 31

Opioids at induction result in increased dose requirements of the induction agent T/F

Answer 31

False. Opioids work synergistically with induction agents. This drug sparing effect results in fewer deleterious side-effects.

Question 32

Remifentanil is a good choice for patients undergoing an awake fibreoptic intubation T/F

Answer 32

True. Remifentanil provides excellent analgesia, blunts laryngeal reflexes and blunts sympathetic response to intubation.