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

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

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

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

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

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)

Neurotoxicity

·   Benzethonium chloride (theoretical risk)

Emetogenesis

·   ? Peripheral 5-HT₃

·   ? Central effect

Hepatotoxicity

·   If prolonged infusion