ABCs of Anaesthesia Basic Anaesthesia Drugs

Question 1

Name common induction agents

Answer 1

Propofol
Ketamine
Thiopentone
Midazolam 
Etomidate
Opioids

Question 2

Propofol

Mechanism
Dose
Onset
Offset
Adverse Effects
Special features
Metabolites

Answer 2

Mechanism - unclear. potentiates inhibitory transmitters GABA and glycine, may reduce Na channel opening times

Dose - induction 1-3mg/kg, maintenance 4-12mg/kg/hr (elderly induction 0.5-1.5mg/kg, maintenance 3-6mg/kg/hr

Onset - ~30seconds, peak 1-2min

Offset- 5-10minutes after single dose

Effects
CVS - decreased SVR, decreased CO, vasodilation secondary to propofol-induced production and release of NO, profound bradycardia possibly due to resetting barorecptor reflex
RS- Apnoea, bronchodilation
CNS- ICP, CPP and cerebral O2 consumption all decrease, vivid dreams
GI- antiemetic ?dopamine D2 receptor antagonist
Adverse
- pain on injection
- propofol infusion syndrome (metabolic acidosis, rhabdomyolysis, multiorgan failure)
- quinol metabolites turning urine/hair green

Special features
- fast onset, smooth wake up

Metabolites - Hepatic and extrahepatic metabolism - inactive glucuronide and quinol. renal and hepatic impairment do not effect use

Question 3

Thiopentone

Mechanism
Dose
Onset
Offset
Adverse Effects
Special features
Metabolites

Answer 3

yellow powder
Mechanism - Barbiturate- depress post-synaptic sensitivity to neurotransmitters and pre-synaptic release of neurotransmitters. multisynaptic pathways are depressed preferentially (RAS)

Dose - 3-5mg/kg

Onset - faster onset than propofol (no blinking eyes)

Offset- 5-10mins

Adverse Effects

• CVS: more significant CVS effects than propofol. negative inotrope and decreased SVR
• Resp: apnoea, less depression of upper airway reflexes, potentially bronchoconstriction
• Neuro: decreased cerebral blood flow, ICP, intraocular pressure. anticonvulsant.

Special features
- Faster more predictable onset

Metabolites
- metabolized in the liver: oxidation to pentobarbitol (active) then further broken down to urea + other. renal excretion

Question 4

Ketamine

Mechanism
Dose
Onset
Offset
Adverse Effects
Special features
Metabolites

Answer 4

Mechanism - non-competetive antagonist of NMDA receptor, complex interactions with opioid receptors. antagonist at monoaminergic, muscarinic and nicotinic receptors. dissociative anaesthesia
(S and R isomers)

Dose

• Induction: IV 1-2mg/kg (0.5 if unstable), IM 4-10mg/kg
• maintenance: 10-50mcg/kg/min
• analgesia IM 2-4mg/kg, IV 0.05-0.25mg/kg/hr

Onset
IV 30sec
IM 2-8min

Offset
IV 5 - 15min
IM 10-20min

Adverse Effects

• CVS: direct negative inotrope, indirect sympathomimetic
• Resp: preserves airway reflexes, mild stimulant of respiration, bronchial smooth muscle relaxant
• Neuro: hallucinations, mydriasis, CBF, CMR, ICP and IOP all increase
• increased secretions
• increases uterine tone

Metabolites
cyp450>Norketamine(30% as potent)>inactiver glucuronide, excreted in urine (mild accum in renal failure)

Question 5

Midazolam

Mechanism
Dose
Onset
Offset
Adverse Effects
Special features
Metabolites

Answer 5

Mechanism
- Benzodiazepine receptors throughout CNS (mainly cortex+midbrain) which facilitate activation of GABA receptors and open Cl channels to hyperpolarize synaptic memberane. some kappa-opioid activity in vitro

Dose

• 0.05-0.1mg/kg
• IT 0.3-2mg, Epidurally 0.1-0.2mg/kg

Onset
-1-2min onset

Offset
~ 30min

Adverse Effects

• CVS: mild decrease in SVR
• Resp: decrease TV, increase RR (MV unchanged), apnoea. impairs ventilatory response to hypercapnia
• CNS: sedation, hypnosis and amnesia, CMR and CBF are decreased, antinociceptive effects IT/epidurally

Metabolites
- metabolized in liver to active metabolites such as oxazepam then conjugated and excreted in urine - renal impairment has little effect

Question 6

Etomidate

Mechanism
Dose
Onset
Offset
Adverse Effects
Special features
Metabolites

Answer 6

Mechanism
- acts on GABAa to modulated inhibitory synaptic transmission within the CNS

Dose -
0.2-0.3mg/kg

Onset
- 10-65s

Offset
-6-10min

Adverse Effects

• CVS: known for cardiac stability
• Resp: dose related decrease in RR and TV, transient apnoea
• CNS: involuntary muscle movements. decreases ICP, IOP, CBF, CMR
• increased rate of PONV
• inhibits 11Bhydroxylase and 17ahydroxylase causing decreased cortisol and aldosterone synthesis for 24-48hrs
• antiplatelet activity
• porphyrinogenic
• prepared in propylene glycol (hurts on injection)

Metabolites
- plasma and hepatic esterases produce inactive metabolites. mostly excreted in urine, some in bile

Question 7

40yo 70kg hypovolaemic shock post trauma induction

Answer 7

- homeopathic dose of propofol 10-30mg
or 
- Ketamine 0.5 - 1 mg/kg, combine with some midaz
or
- just midaz

Question 8

70kg heart failure induction

Answer 8

• unlike shock patients need to aim for normal preload/afterload/contractility/rate
• midaz +/- low dose propofol infusion
• 2mg of midaz with lines, 1mg with preox then 10mg propofol, give fluids for preload, high dose 200-400mcg fent to depress htn/tachy with laryngoscopy