1. The Art of Sedation in ICU
Yasser Zaghloul MD PhD, FCARCSI (Ireland)

2. • Sedation comes from the Latin word sedare.
• Sedare = to calm or to allay fear
Hypnosis Analgesia
± Muscle
Relaxation

3. • Sedation comes from the Latin word sedare.
• Sedare = to calm or to allay fear
Hypnosis Analgesia
± Muscle
Relaxation

4. Why sedation is necessary?
• To improve patient comfort.
• Reduce stress.
• Facilitate interventions.
• Allow effective ventilation.
• Encourage sleep.
• ?? Prevent post-ICU psychosis.

6. 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.

7. Non-pharmacological interventions
• Good nursing.
• Psychological:
- Explanation. - Reassurance.
• Physical:
- Touching & message. - Environment
- Prevent constipation - Physiotherapy.
- Tracheostomy.

8. Sedation-Analgesia Medications
• IV Anaesthetics:
- Prpofol - Thiopentone.
- Ketamine - Etomidate.
• Benzodiazepines:
- Midazolam.
- Lorazepam

9. Sedation-Analgesia Medications
• Opiodis:
- Morphine
- Fentanyl.
- Remifentanil
• α-2 receptors agonists:
– Clonidine.
– Dexmedetomidine .

10. Sedation-Analgesia Medications
• Others:
- Inhalation anaesthetics (Sevoflurane).
- Phenothiazines.
- Butyrophenones (Haloperidol).
- Local Anaesthetics.

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

14. IV Anaesthetics; Propofol
OH
(CH3)2CH CH(CH3)2
2,6 di-isopropyl phenol
Short-term sedation (< 48 h)

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 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

18. 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 3
Age 4
Wt. 100 4 4
Tc
50 2
1
0 0
0 4 8 12 16 20 24 28
l
g/m Time (hours)
t; 6µ
Star

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.

21. IV Anaesthetics - Ketamine

22. IV Anaesthetics - Ketamine
• Phencyclidine derivative.
• High lipid solubility (5–10 times > thiopental)
crosses BBB faster.
• Non-competitive antagonism at NMDA receptor

23. IV Anaesthetics - Ketamine
  HR, BP.
  CBF, ICP & CMRO2.
• Bronchial smooth muscle relaxant.
• Excellent analgesic.
• Dose: 5-30 µg/kg/min.

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.

27. Remfentnil Acid
95%
1.5%

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

30. Benzodiazepines

31. Benzodiazepines; Midazolam
• Water-soluble  lipid soluble in
the body.
• Produces sedation, anxiolysis
and amensia.
• Withdrawal agitation.

32. α2-Adrenergic agonists
Clonidine
Dexmedetomidine

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

37. Drug Elimination h1/2 (h)
Prpofol 4–7
Dexmedetomidine 2-3
Ketamine 2.5 – 2.8
Midazolam 1.7 – 2.6

38. Assessment of Sedation
• Ramsay Sedation Score.
• Motor Activity Assessment Scale
• Richmond Agitation–Sedation Scale.
• Sedation – Agitation Score.
• Modified Glasgow Coma Score.

39. Ramsay Sedation Score
Level 1 Awake, anxious, agitated, restlessness
Level 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

40. Bispectral Index

41. Is any place for neuro-
muscular Blockers in ICU?

42. Mehta S et al. Crit Care Med 2006; 34: 374

44. 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.

45. Thank You
Yasser Zaghloul