The Art of Sedation in ICU Yasser ZaghloulMD 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? 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
OH (CH3)2CH CH(CH3)2 IV Anaesthetics; Propofol 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’ PFSis loaded correctly Finger grip Tag = PMR(Programmaable Magnetic Resonance*) Aerial ‘Diprifusor’ TCI SubsystemRecognition software/electronics‘Diprifusor’ TCI Software/2 microprocessors Pumpsoftware Pump hardware
Calculated concentration (automatic calculation and display by system) Target concentration (selected by anaesthetist, displayed) 5 2 3 4 1 Target concentrations with ‘Diprifusor’ TCI 1200 8 End ↑ Tc Titration 6 6 Age Wt. Tc 4 Infusion rate (ml/h) Blood concentration (µg/ml) 100 4 50 2 0 0 16 0 4 8 12 20 24 28 Start; 6µg/ml Time (hours)
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 Acid 95% 1.5%
Fentanyl 262 min Alfentanil 59 min Sufentanil 34 min Remifentanil 3.7 min Plasma concentration after long term infusion After 240 min Context –sensitive half-time 100 75 Time to 50% drop in concentration at effect site (minutes) 50 25 0 0 100 200 300 400 500 600 Duration of infusion (minutes)
Unwanted side-effects of opioids Opioids Confusion Vasodilation Respiratorydepression Gut motilitydepression
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/extubation • 2-agonists • Hypotension • Bradycardia Benzodiazepines Hypotension Respiratory depression Agitation/Confusion Propofol Hypertriglyceridemia CVS depression Hypotension • Ketamine • Hypertension • Secretions • Dysphoria
Assessment of Sedation • Ramsay Sedation Score. • Motor Activity Assessment Scale • Richmond Agitation–Sedation Scale. • Sedation – Agitation Score. • Modified Glasgow Coma Score.
Ramsay Sedation Score
Bispectral Index
Is any place for neuro-muscular Blockers in ICU?
Mehta S et al. Crit Care Med 2006; 34: 374
* Under 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. The Art of Sedation
Thank You Yasser Zaghloul
