CVS effects of inhalational anaesthetic agents

[SH4:p51]

Mean arterial pressure (MAP)

• Halothane, isoflurane, desflurane, and sevoflurane all produce similar and dose-dependent decreases in MAP.
• N2O produces either no change or modest increase in MAP

Mechanism

• Halothane reduce MAP by decreases in myocardial contractility (and cardiac output)
  * No effect on SVR
• Isoflurane, desflurane, and sevoflurane reduce MAP by decrease in systemic vascular resistance

Heart rate (HR)

• Isoflurane, desflurane, and sevoflurane increase HR
  * Sevoflurane increase HR only at >1.5 MAC
  * Isoflurane and desflurane increase HR at lower concentration
• Halothane does not cause reflex HR (secondary to decreased BP)
  * Due to depressed carotid sinus reflex and depressed sinus node depolarisation

This increase in HR is prevented by a small dose of opioid

Isoflurane vs desflurane

• At 0.5 MAC, isoflurane and desflurane produce similar decrease in MAP
• At 0.5 MAC, isoflurane increase HR, but desflurane does not
• With isoflurane, the increase in HR is:
  * Blunted in elderly
  * More likely to occur in younger patients

Cardiac output and stroke volume

• All inhalational anaesthetic agents (except N2O) decrease cardiac output by 15-30%
• Increase in HR tend to compensate for the decrease in cardiac output
• N2O causes mild increase in cardiac output
  * Possibly due to mild sympathomimetic effect of N2O

Right atrial pressure (RAP)

--> Indicator of central venous pressure

• Halothane, isoflurane, and desflurane all increase RAP
  * Due to myocardial depression
  * Peripheral vasodilating effect may minimise the increase in RAP
• N2O increases RAP
  * Possibly due to increased pulmonary vascular resistance due to sympathomimetic effect

Systemic vascular resistance (SVR)

• Isoflurane, desflurane, and sevoflurane decrease SVR
• Halothane and N2O does not affect SVR

Blood flow distribution with isoflurane

• Isoflurane increases blood flow in skeletal muscle and skin
  * beta agonist effect
• Implications include:
  * Excess perfusion relative to O2 requirement
  * Loss of body heat
  * Enhanced drug delivery to neuromuscular junctions

Cutaneous blood flow

• Halothane does not increase overall SVR
  * But increase blood flow to brain and skin
• All inhalational anaesthetic agents (except for N2O) increase cutaneous blood flow 
  * Most likely due to inhibition on temperature regulating mechanisms
• N2O may produce cutaneous vasoconstriction

Clinical relevance

Peripheral vasodilation:

• Undesirable in aortic stenosis
• Beneficial in mitral or aortic regurgitation

Pulmonary vascular resistance (PVR)

• All inhalational anaesthetic agents (except for N2O) exert little effect on PVR
• N2O causes pulmonary vasoconstriction
  * Exaggerate pulmonary hypertension
  * Increase magnitude of right-to-left intracardiac shunting of blood

Duration of administration

• After 5 hours, cardiac output recovers from the cardiac depressant effects of inhalational anaesthetic agents
• HR is increased and SVR is decreased
  --> BP unchanged

This recovery is

• Most pronouced in halothane
• Least in isoflurane
  * Isoflurane caused minimal drop in cardiac output anyway

Cardiac dysrhythmias

• Alkane derivative (e.g. halothane)
  --> Decreases the dose of epinephrine necessary to evoke ventricular cardiac arrhythmia
• Ether derivatives (e.g. ENF, isoflurane, desflurane, sevoflurane)
  --> Minimal effect
• Both halothane and isoflurane
  * Slow the rate of SA node discharge
  * Prolong His bundle and ventricular conduction time

NB:

[James] [???]

• Both halothane and isoflurane prolong QTc

Accessory pathway and ablation procedures

• Isoflurane increases refractory of accessory pathways
  --> Interfer with postablation studies
• Sevoflurane has almost no effect on AV or accessory pathways
  --> Acceptable for ablation procedures

Spontaneous breathing

Spontaneous breathing during anaesthesia has 2 effects relevant to CVS

• Accumulation of CO2
  * Sympathetic stimulation
  * Direct relaxing effect on peripheral vascular smooth muscles
• Better venous return 
  * Due to less pressure on pulmonary vessels

Thus,

During spontaneous breathing

• Cardiac output is higher
• HR is higher
• MAP is higher
• Total peripheral resistance is lower

Coronary blood flow

• Inhalational anaesthetic agents causes coronary vasodilation
  * Preferentially dilates vessels with diameters from 20 microm to 50 microm

However,

• Coronary steal syndrome is not clinically significant
  * All inhalational anaesthetic agents (including isoflurane) are cardioprotective
  * [SH4:56]

Neurocirculatory response

• Abrupt increase in isoflurane and desflurane (from 0.55 to 1.66 MAC)
  --> Sympathetic stimulation and increase renin-angiotensin activity
  --> Increased HR and MAP
  * Greater increase with desflurane
  * Blunted by fentanyl, esmolol, and clonidine
• Abrupt increase in sevoflurane
  --> No neurocirculatory response

Effect of pre-existing disease

• In patients with coronary artery disease,
  * N2O produce myocardial depression which doesn't occur in patients without cardiac disease
• Calcium channel blockers
  --> Myocardial depression
  --> More vulnerable to direct depressant effect of inhalational anaesthetic agents

Cardiac protection

Ischaemic preconditioning

• Brief episodes on myocardial ischaemia
  --> Offers protection against subsequent longer periods of ischaemia and infarct

Two phases

• First phase last for 1-2 hours
• Second phase occurs after 24 hours, lasting up to 3 days

Mechanism of ischaemic preconditioning

Release of adenosine
--> Binds to adenosine receptors
--> Increase protein kinase C activity
--> Phosphorylation of ATP-sensitive K+ channel (K_ATP)
--> Less sensitive to inhibition by ATP
--> More K+ current
--> Less Ca2+ accumulation and more hyperpolarization
--> More relaxation and mild negative inotropic effect

Anaesthetic preconditioning

• Brief exposure to isoflurane, sevoflurane, and desflurane
  --> Activate K_ATP channel
  --> Cardioprotection identical to ischaemic preconditioning
• Cardiac surgical patients receiving sevoflurane has less troponin I release in the first 24 hours than patients receiving propofol