Transcript ICU Sedation & Analgesia

The Art of Sedation in ICU
Yasser 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?
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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.
- Prevent constipation
- Tracheostomy.
- Environment
- Physiotherapy.
Sedation-Analgesia Medications
• IV Anaesthetics:
- Prpofol
- Ketamine
• Benzodiazepines:
- Midazolam.
- Lorazepam
- Thiopentone.
- Etomidate.
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?
90
80
70
60
50
Midazolam
Propofol
40
30
20
10
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
is loaded correctly
Finger grip Tag = PMR
(Programmaable Magnetic Resonance*)
Aerial
‘Diprifusor’ TCI Subsystem
Recognition software/electronics
‘Diprifusor’ TCI Software/
2 microprocessors
Pump hardware
Pump
software
Target concentrations with ‘Diprifusor’ TCI
1200
8
Calculated concentration
(automatic calculation and display by system)
Infusion rate (ml/h)
Age
Wt.
Tc
2
3
5
6
6
4
4
100
50
4
2
1
0
0
0
4
8
12
Time (hours)
16
20
24
28
Blood concentration (µg/ml)
Target concentration
(selected by anaesthetist, displayed)
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
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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%
Plasma concentration after long term infusion
After 240 min
Context –sensitive half-time
Fentanyl 262 min
Time to 50% drop in
concentration at effect site (minutes)
100
75
Alfentanil 59 min
50
Sufentanil 34 min
25
Remifentanil 3.7 min
0
0
100
200
300
400
Duration of infusion (minutes)
500
600
Unwanted side-effects of opioids
Opioids
Vasodilation
Respiratory
depression
Confusion
Gut motility
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/extubation
2-agonists
Benzodiazepines
Hypotension
Respiratory depression
Agitation/Confusion
Hypotension
Bradycardia
Propofol
Hypertriglyceridemia
CVS depression
Hypotension
Ketamine
Hypertension
Secretions
Dysphoria
Drug
Elimination h1/2 (h)
Prpofol
4–7
Dexmedetomidine
2-3
Ketamine
2.5 – 2.8
Midazolam
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 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
Bispectral Index
Is any place for neuromuscular Blockers in ICU?
Mehta S et al. Crit Care Med 2006; 34: 374
The Art of Sedation
* Under sedation:
* Over sedation:
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Fighting the ventilator.
V/Q mismatch.
Accidental extubation.
Catheter displacement.
CV stress  ischemia.
Anxiety, awareness.
Post-traumatic stress
disorder.
Tolerance, tachyphylaxis.
Withdrawal syndrome.
Delirium.
Prolonged ventilation.
CV depression.
 neuro testing.
Sleep disturbance.
Thank You
Yasser Zaghloul