This document discusses sedation in the intensive care unit (ICU). It begins by defining sedation and explaining why it is necessary in the ICU, such as to improve patient comfort and reduce stress. It then discusses various pharmacological and non-pharmacological interventions for sedation. The main sedation-analgesia medications discussed are IV anesthetics like propofol and ketamine, benzodiazepines like midazolam, opioids like morphine and remifentanil, and alpha-2 agonists like dexmedetomidine. It also covers factors to consider when choosing a sedative drug and describes scales used to assess sedation levels. Unwanted side effects of different sedative agents are also outlined

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