2017B14 Describe the pharmacodynamic properties of propofol excluding its
effects on the central nervous system. Describe how these influence clinical use.

· CVS

· Resp

· Other

Mechanisms	· ↓L-Ca²⁺ activity in vascular smooth muscle · ↑NO release from endothelium · ↑GABA/glycine -> ↓SNS output from medulla
Haemodynamics	· ↓Venous tone, ↓MSFP, ↓preload · ↓Heart rate, ↓contractility · ↓Baroreceptor reflex (cf. volatiles · ↓SVR (most important cause of ↓mAP) · ↓Cardiac output · ↓mAP
Regional flow	· ↓Coronary blood flow -> risk ischaemia · ↓Cerebral blood flow (due to preserved metabolic autoregulation) · ↓Hepatic blood flow -> risk ischaemia · ↓Renal blood flow -> oliguria · ↓Uterine blood flow (cf. volatiles)
Implications	· Vasopressor, inotrope, chronotrope often needed o Especially at induction o Especially for high risk groups (unwell, shocked, elderly, LV failure) · Rapid effective treatment of intra-op hypertension · ↓Risk PPH if Caesarean section under GA

Mechanisms

· ↑GABA/glycine -> depression of respiratory centre, chemoreceptors

· ↓Spinal cord a-motor neuron activity

· ↓Presynaptic L-Ca²⁺ activity

· ↓Post-synaptic nnAChR activity

Clinical effects

· ↓RR, ↓TV

· ↓Response to ↑PaCO₂ and ↓PaO₂

· ↓Pharyngeal dilator tone

· ↓Airway reflexes

· Bronchodilation

· Relative preservation of HPV (cf. volatiles)

Implications

· Apnoea common after induction; risk hypoxia if not ventilated

· Airway obstruction common if no airway device, especially if OSA

· Allows airway instrumentation without paralysis

· Risk of aspiration

· Improved oxygenation during one lung ventilation

Change	Cause	Implication
Anti-emetic	· 5-HT3 antagonist in CTZ	· Propofol TIVA preferred if PHx PONV++
Pain on injection	· ?Activation of endothelial TRPA1 receptors ? other	· Mix with small dose lignocaine · Use fast, free flowing IV
Lipotoxicity	· Lipid load: 20mg/mL soybean oil	· Avoid prolonged high dose infusion
Propofol infusion syndrome	· ? Lipid load	· Avoid prolonged use in unwell children