The Art of Sedation in ICU Yasser Zaghloul MD PhD, FCARCSI (Ireland)
Transcript of The Art of Sedation in ICU Yasser Zaghloul MD PhD, FCARCSI (Ireland)
The Art of Sedation in ICU
Yasser Zaghloul MD PhD, FCARCSI (Ireland)
Hypnosis
± MuscleRelaxation
Analgesia
• Sedation comes from the Latin word sedare.• Sedare = to calm or to allay fear
Hypnosis
± MuscleRelaxation
Analgesia
• Sedation comes from the Latin word sedare.• Sedare = to calm or to allay fear
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?
0
10
20
30
40
50
60
70
80
90
France Norway Finland Belgium Italy
Midazolam
Propofol
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; PropofolIV Anaesthetics; Propofol
(CH3)2CH CH(CH3)2
OH
2,6 di-isopropyl phenol2,6 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.
‘Diprifusor’ TCI SubsystemRecognition software/electronics
‘Diprifusor’ TCI Software/2 microprocessors
Pumpsoftware
Pump hardware
Finger grip Tag = PMR(Programmaable Magnetic Resonance*)
Full ‘Diprivan’ PFSis loaded correctly
Aerial
Target concentrations with ‘Diprifusor’ TCI
Target concentrations with ‘Diprifusor’ TCI
0
50
100
1200
0 4 8 12 16 20 24 28
4
6
8
0
2
Time (hours)
Infu
sio
n r
ate
(ml/h
)
Blo
od
con
centratio
n (µ
g/m
l)
Calculated concentration(automatic calculation and display by system)
Target concentration(selected by anaesthetist, displayed)
432
1
5
Start; 6µg/m
l
TitrationEnd
4
6
AgeWt.Tc
↑ T
c
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%
Sufentanil 34 minSufentanil 34 min
Alfentanil 59 minAlfentanil 59 min
00
100 200 300 400 500 600
25
50
75
100
Duration of infusion (minutes)
Tim
e to
50%
dro
p in
co
ncen
trat
ion
at e
ffec
t si
te (
min
utes
)
Fentanyl 262 min
Remifentanil 3.7 minRemifentanil 3.7 min
Plasma concentration after long term infusion
After 240 minContext –sensitive half-time
Unwanted side-effects of opioids
Respiratorydepression
ConfusionVasodilation
Gut motilitydepression
Opioids
Benzodiazepines
Benzodiazepines; Midazolam
• Water-soluble lipid soluble in the body.
• Produces sedation, anxiolysis and amensia.
• Withdrawal agitation.
α2-Adrenergic agonistsClonidine
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
PropofolHypertriglyceridemia
CVS depression
Hypotension
2-agonists
Hypotension
Bradycardia
BenzodiazepinesHypotension
Respiratory depression
Agitation/Confusion
KetamineHypertension
Secretions
Dysphoria
GeneralOver sedation
Delayed awakening/extubation
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 neuro-muscular Blockers in
ICU?
Mehta S et al. Crit Care Med 2006; 34: 374
The Art of Sedation
* 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.
Thank You
Yasser Zaghloul