Art of sedation in icu
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  • 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.

Art of sedation in icu Art of sedation in icu Presentation Transcript

  • The Art of Sedation in ICUYasser Zaghloul MD PhD, FCARCSI (Ireland)
  • • Sedation comes from the Latin word sedare.• Sedare = to calm or to allay fear Hypnosis Analgesia ± Muscle Relaxation
  • • Sedation comes from the Latin word sedare.• Sedare = to calm or to allay fear Hypnosis Analgesia ± Muscle Relaxation
  • Why sedation is necessary?• To improve patient comfort.• Reduce stress.• Facilitate interventions.• Allow effective ventilation.• Encourage sleep.• ?? Prevent post-ICU psychosis.
  • Inadequate Sedation• All ICU patients suffer from severe sleep deprivation.• REM sleep is 6% ( Normal 25 %).• Stress  neuroendocrine response ( ACTH, GH, Aldosterone, Adrenaline, .....)• Release of cytokines  inflammatory response.
  • Non-pharmacological interventions• Good nursing.• Psychological: - Explanation. - Reassurance.• Physical: - Touching & message. - Environment - Prevent constipation - Physiotherapy. - Tracheostomy.
  • Sedation-Analgesia Medications• IV Anaesthetics: - Prpofol - Thiopentone. - Ketamine - Etomidate.• Benzodiazepines: - Midazolam. - Lorazepam
  • Sedation-Analgesia Medications• Opiodis: - Morphine - Fentanyl. - Remifentanil• α-2 receptors agonists: – Clonidine. – Dexmedetomidine .
  • Sedation-Analgesia Medications• Others: - Inhalation anaesthetics (Sevoflurane). - Phenothiazines. - Butyrophenones (Haloperidol). - Local Anaesthetics.
  • 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.
  • Which Medication?9080706050 Midazolam40 Propofol302010 0 France Norway Finland Belgium Italy Soliman et al, Brit J Anaesth 2001;87:186-92
  • IV Anaesthetics; Thiopentone• Acts on the GABAA.• Zero order kinetics (accumulation).• Provides a cerebral protection effect.• Main uses in ICU: - High ICP. - Status epilepticus
  • IV Anaesthetics; Propofol OH(CH3)2CH CH(CH3)2 2,6 di-isopropyl phenol Short-term sedation (< 48 h)
  • IV Anaesthetics; Propofol• Mechanisms of actions: - Acts on GABAA receptors in the hippocampus. - Inhibits of NMDA.  IOP, ICP & CMRO2.
  • IV Anaesthetics; Propofol• Decreases (10 – 30%): - HR. - SBP, DBP & MAP. - SVR. - CI. - SV.
  • Target concentrations with ‘Diprifusor’ TCI Full ‘Diprivan’ PFS Finger grip Tag = PMR is loaded correctly (Programmaable Magnetic Resonance*) Aerial ‘Diprifusor’ TCI Subsystem Recognition software/electronics Pump ‘Diprifusor’ TCI Software/ software 2 microprocessors Pump hardware
  • Target concentrations with ‘Diprifusor’ TCI 1200 8 c Tit Calculated concentration d En ↑T (automatic calculation and display by system) rat ion Blood concentration (µg/ml) Target concentration (selected by anaesthetist, displayed) 5 6 Infusion rate (ml/h) 6 2 3Age 4Wt. 100 4 4Tc 50 2 1 0 0 0 4 8 12 16 20 24 28 l g/m Time (hours) t; 6µ Star
  • IV Anaesthetics; Propofol• Propofol infusion syndrome: - Rare but fatal. - 1st described in children. - Infusion ≥ 5 mg/kg/hr or ≥ 48 hours.
  • 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.
  • IV Anaesthetics - Ketamine
  • IV Anaesthetics - Ketamine• Phencyclidine derivative.• High lipid solubility (5–10 times > thiopental) crosses BBB faster.• Non-competitive antagonism at NMDA receptor
  • IV Anaesthetics - Ketamine  HR, BP.  CBF, ICP & CMRO2.• Bronchial smooth muscle relaxant.• Excellent analgesic.• Dose: 5-30 µg/kg/min.
  • Opioids; Morphine• Isolated in 1803 by the German pharmacist Friedrich Adam.• Named it morphium after Morpheus, the Greek god of dreams.
  • 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).
  • 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.
  • Remfentnil Acid95% 1.5%
  • Plasma concentration after long term infusionContext –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)
  • Unwanted side-effects of opioids OpioidsVasodilation Confusion Gut motility Respiratory depression depression
  • Benzodiazepines
  • Benzodiazepines; Midazolam• Water-soluble  lipid soluble in the body.• Produces sedation, anxiolysis and amensia.• Withdrawal agitation.
  • α2-Adrenergic agonists Clonidine Dexmedetomidine
  • 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
  • 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.
  • α2 – agonists• Haemodynamics Effects: -  heart rate. - Initial  then  BP. -  SVR. -  CO• No respiratory depression
  • Unwanted side-effects of sedative agents General Over sedation Delayed awakening/extubationBenzodiazepines α 2-agonists Hypotension HypotensionRespiratory depression Bradycardia Agitation/Confusion Ketamine Propofol Hypertension Hypertriglyceridemia Secretions CVS depression Hypotension Dysphoria
  • Drug Elimination h1/2 (h)Prpofol 4–7Dexmedetomidine 2-3Ketamine 2.5 – 2.8Midazolam 1.7 – 2.6
  • Assessment of Sedation• Ramsay Sedation Score.• Motor Activity Assessment Scale• Richmond Agitation–Sedation Scale.• Sedation – Agitation Score.• Modified Glasgow Coma Score.
  • Ramsay Sedation ScoreLevel 1 Awake, anxious, agitated, restlessnessLevel 2 Awake, cooperative, tranquil.Level 3 Respond to commands.Level 4 Asleep, brisk response to stimuli.Level 5 Asleep, sluggish response to stimuli.Level 6 Asleep, no response
  • Bispectral Index
  • Is any place for neuro-muscular Blockers in ICU?
  • Mehta S et al. Crit Care Med 2006; 34: 374
  • The Art of Sedation* Under sedation: * Over sedation:• Fighting the ventilator. • Tolerance, tachyphylaxis.• V/Q mismatch. • Withdrawal syndrome.• Accidental extubation. • Delirium.• Catheter displacement. • Prolonged ventilation.• CV stress  ischemia. • CV depression.• Anxiety, awareness.   neuro testing.• Post-traumatic stress • Sleep disturbance. disorder.
  • Thank YouYasser Zaghloul