the art of sedation in icu yasser zaghloul md phd, fcarcsi (ireland)
TRANSCRIPT
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