11. Choice of the sedative drug
• Short-term Vs long-term sedation.
• Pain & painful Procedures.
• Organ problems (Renal, hepatic, brain, CVS).
• Drug withdrawal (Alcohol, heroin, .....)
• Prescriber & Prescription.
12. Which Medication?
90
80
70
60
50
Midazolam
40 Propofol
30
20
10
0
France Norway Finland Belgium Italy
Soliman et al, Brit J Anaesth 2001;87:186-92
13. IV Anaesthetics; Thiopentone
• Acts on the GABAA.
• Zero order kinetics (accumulation).
• Provides a cerebral protection effect.
• Main uses in ICU:
- High ICP.
- Status epilepticus
24. Opioids; Morphine
• Isolated in 1803 by the German pharmacist Friedrich Adam.
• Named it 'morphium' after Morpheus, the Greek god of dreams.
25. Opioids - Morphine
• Plasma levels do not correlate with clinical
effect.
• Low lipid solubility causes slow equilibration
across BBB.
• Metabolized in the liver by conjugation.
• Morphine-6-glucuronide (active).
26. Remifentanil
• Piperidine derivative.
• Selective mu-receptor agonist.
• Potency similar to fentanyl.
• Terminal half-life < 10 min.
• Rapid blood-brain equilibrium.
• Metabolised by non-specific esterases.
28. Plasma concentration after long term infusion
Context –sensitive half-time After 240 min
100 Fentanyl 262 min
concentration at effect site (minutes)
75
Time to 50% drop in
Alfentanil 59 min
50 Sufentanil 34 min
25
Remifentanil 3.7 min
0
0 100 200 300 400 500 600
Duration of infusion (minutes)
29. Unwanted side-effects of opioids
Opioids
Vasodilation Confusion
Gut motility
Respiratory depression
depression
33. α2 – agonists
• Sedation-hypnosis:
by an action on α2-receptors in
the locus ceruleus.
• Analgesia:
by an action on α2-receptors
within the locus ceruleus and
the spinal cord
34. α2 – agonists; Dexmedetomidine
• 94% protein bound.
• Narrow therapeutic range (0.5 - 1.0 ng/mL)
• It undergoes conjugation & N-methylation.
• Approved only for sedation ≤ 24 h.
35. α2 – agonists
• Haemodynamics Effects:
- heart rate.
- Initial then BP.
- SVR.
- CO
• No respiratory depression
36. Unwanted side-effects of sedative agents
General
Over sedation
Delayed awakening/extubation
Benzodiazepines α 2-agonists
Hypotension Hypotension
Respiratory depression
Bradycardia
Agitation/Confusion
Ketamine
Propofol Hypertension
Hypertriglyceridemia
Secretions
CVS depression
Hypotension Dysphoria
38 1 Start ‘Diprifusor’ TCI with initial target concentration of 6 g/ml Rapid bolus (1,200 ml/h) to reach target 2 Variable-rate infusion to maintain initial target 3 10 minutes, select lower target of 4 g/ml (titrate downwards) Infusion stops until blood concentration falls to lower target Resumption of infusion at decreased rate to maintain new target 4 20 minutes, select higher target of 6 g/ml (titrate upwards) Another bolus to reach new target Resumption of infusion at increased rate to maintain higher target 5 30 minutes, end of ‘Diprifusor’ TCI Blood concentration falls ... What happens when an initial target concentration has been set? A ‘Diprifusor’ System can be considered as a “smart pump”. ‘Diprifusor’ TCI Software “commands” the syringe pump to deliver a rapid infusion at a rate of 1,200 ml/h until the pharmacokinetic model calculates that the selected target concentration has been reached. Variable-rate infusions are then provided automatically to maintain the selected target concentration. The target concentration can be changed at any time by the anaesthetist — and is displayed. Selection of a higher target concentration results in administration of a bolus followed by infusion at an increased rate. Selection of a lower target concentration results in a temporary discontinuation of infusion followed by resumption at a lower rate. The calculated concentration is displayed continuously both during and after stopping drug infusion. The display of both the selected target concentration and the calculated concentration provides feedback to the anaesthetist. These principles apply to the commercially-available pumps that incorporate ‘Diprifusor’ as well as to the ‘Diprifusor’ System used for clinical trials.