2002A11 Briefly outline the effects of thiopentone and ketamine not mediated by the central nervous system.

 

List:

For each:

·     CVS

·     Resp

·     Other

 

Thiopentone:

 

Cardiovascular:

Mechanisms

·  ↑Nitric oxide release

(↓SNS output from medulla)

Effects

·  ↓Venous tone, ↓MSFP, ↓preload

·  ↓contractility, ↓myocardial O2 consumption

·  ↓SVR

·  ↓mAP

·  Relatively preserved baroreceptor response; reflex ↑HR common

·  Pronounced CVS depression if unwell (acidaemia -> ↑↑ % unionised

 

Respiratory:

Mechanisms

·  Mostly central; ↑GABA -> suppression of respiratory centre

Effects

·  ↓RR, ↓TV

·  ↓Response to ↓PaO2 and ↑PaCO2

·  ↓Pharyngeal dilator tone

·  Relatively preserved airway reflexes; risk of laryngospasm, bronchospasm

·  Relatively preserved HPV

 

Other:

Pharmaceutic

·  Extravasation -> necrosis

·  Intra-arterial injection -> crystallization -> microvascular occlusion

·  Histamine release

·  Anaphylaxis 1 in 20,000

Pharmacokinetic

·  Can precipitate acute intermittent porphyria

·  ↑Activity D-aminolaevulinic acid synthetase

·  Induction of hepatic CYP450

 

Ketamine:

 

Cardiovascular:

Mechanisms

·  R-ketamine: direct negative inotropy, vascular smooth muscle relaxation
 (↓L-Ca2+ activity, ? other)

·  (Indirect ↑SNS)

Direct effects

·  ↓HR, ↓contractility

·  Venodilatation -> ↓preload

·  Vasodilatation -> ↓SVR

·  Baroreceptor reflex preserved

·  Direct effects balance indirect effects in health

·  Direct effects can be unmasked if maximal SNS activity or high dose vasoactives

 

Respiratory:

Mechanisms

·  Direct: ↓L-Ca2+, ? other

·  (Indirect: ↑SNS output)

Effects

·  Preserved RR, TV

·  Preserved airway reflexes -> ↓risk aspiration

·  ↑Airway secretion (often need antisialogogue)

·  R-ketamine causes bronchodilation (preferred induction agent in status asthmaticus)

 

Other:

Neurotoxicity

·  Benzethonium chloride (theoretical risk)

Emetogenesis

·  ? Peripheral 5-HT3

·  ? Central effect

Hepatotoxicity

·  If prolonged infusion