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