15 IV Anaesthetics; Propofol Mechanisms of actions:- Acts on GABAA receptors in the hippocampus.- Inhibits of NMDA. IOP, ICP & CMRO2.
16 IV Anaesthetics; Propofol Decreases (10 – 30%):- HR.- SBP, DBP & MAP.- SVR.- CI.- SV.
17 Target concentrations with ‘Diprifusor’ TCI Full ‘Diprivan’ PFS is loaded correctlyFinger grip Tag = PMR (Programmaable Magnetic Resonance*)Aerial‘Diprifusor’ TCI Subsystem Recognition software/electronics ‘Diprifusor’ TCI Software/ 2 microprocessorsPump softwarePump hardware
18 Target concentrations with ‘Diprifusor’ TCI 38Target concentrations with ‘Diprifusor’ TCI1200↑ TcEnd8Calculated concentration(automatic calculation and display by system)Target concentration(selected by anaesthetist, displayed)Titration56623AgeWt.Tc44Infusion rate (ml/h)100Blood concentration (µg/ml)41 Start ‘Diprifusor’ TCI with initial target concentration of 6 mg/mlRapid bolus (1,200 ml/h) to reach target2 Variable-rate infusion to maintain initial target3 10 minutes, select lower target of 4 mg/ml (titrate downwards)Infusion stops until blood concentration falls to lower targetResumption of infusion at decreased rate to maintain new target4 20 minutes, select higher target of 6 mg/ml (titrate upwards)Another bolus to reach new targetResumption of infusion at increased rate to maintain higher target5 30 minutes, end of ‘Diprifusor’ TCIBlood 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.5021481216202428Start; 6µg/mlTime (hours)
19 IV Anaesthetics; Propofol Propofol infusion syndrome:- Rare but fatal.- 1st described in children.- Infusion ≥ 5 mg/kg/hr or ≥ 48 hours.
20 Propofol Infusion Syndrome Clinical features:- Cardiomyopathy with acute cardiac failure.- Myopathy.- Metabolic acidosis, K+- Hepatomegaly.Inhibition of FFA entry into mitochondria failure of its metabolism.
24 Opioids; MorphineIsolated in 1803 by the German pharmacist Friedrich Adam.Named it 'morphium' after Morpheus, the Greek god of dreams.
25 Opioids - MorphinePlasma 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 After 240 minContext –sensitive half-timeFentanyl 262 min10075Alfentanil 59 minTime to 50% drop in concentration at effect site (minutes)Sufentanil 34 min5025Remifentanil 3.7 min100200300400500600Duration of infusion (minutes)
29 Unwanted side-effects of opioids VasodilationConfusionRespiratory depressionGut motility depression
44 The Art of Sedation * Under sedation: * Over sedation: Fighting the ventilator.V/Q mismatch.Accidental extubation.Catheter displacement.CV stress ischemia.Anxiety, awareness.Post-traumatic stress disorder.* Over sedation:Tolerance, tachyphylaxis.Withdrawal syndrome.Delirium.Prolonged ventilation.CV depression. neuro testing.Sleep disturbance.