Simplified review of the most commonly used drugs for sedation in ICU

1. SEDATION IN ICU
YASSER ABDELMAQSOUD HASSAN ALZAINY
MBBCH-NEUROLOGY RESIDENT

2.  Anxiety and related disorders (agitation and delirium) are observed in as many
as 85% of patients in the
ICU (20). The common denominator in these disorders is the absence of a
sense of well-being. These
disorders can be defined as follows:
1. Anxiety is characterized by exaggerated fear sustained by internal
mechanisms more than external events.
2. Agitation is a state of anxiety that is accompanied by increased motor
activity.
3. Delirium is an acute confusional state that may, or may not, have agitation
as a component.

3. ASSESSMENT OF SEDATION
 Sedation-Agitation Scale (SAS)
 Richmond Agitation-Sedation Scale (RASS)

4. SEDATIVE DRUGS
 Benzodiazepines
 Propofol
 Dexmedetomidine
 Haloperidol

5. BENZODIAZEPINES (MIDAZOLAM)
 Rapid-acting drug (high lipid solubility)
 Sedative effects are apparent within 1–2 minutes
 Short-lived effect (1–2 hrs)
 Given as a continuous IV infusion for more prolonged
sedation.
 Avid drug uptake into tissues (rather than drug
elimination from the body)
 A continuous infusion of midazolam will result in
progressive drug accumulation in tissues. (infusion
should be limited to ≤48 hours)
 Cytochrome P450 enzyme system
 Drugs that interfere with this enzyme system (e.g.,
diltiazem, erythromycin) can inhibit midazolam
metabolism and potentiate its effects.
 Kidney clearance
 Need modification of dosing if renal functions are
impaired

6. ADVANTAGES
 Dose-dependent amnestic effect that extends beyond the sedation period
(antegrade amnesia).
 Anticonvulsant effects
 Sedatives of choice for drug withdrawal syndromes, including alcohol, opiate,
and (surprise) benzodiazepine withdrawal.

7. DISADVANTAGES
 Prolonged sedation: due to its accumulation in tissues
 Daily interruption
 Titration according to a sedation scale
 Delirium
 As it acts through activation of GABA receptors
 Withdrawal syndrome
 Abrupt termination of prolonged benzodiazepine infusions can produce a withdrawal
syndrome, characterized by agitation, disorientation, hallucinations, and seizures

8. PROPOFOL
 Rapidly-acting general anesthetic that acts through an interaction with the
inhibitory neurotransmitter γ-aminobutyric acid (GABA).
 Sedative and amnestic effect, no analgesic effect
 short duration of action, propofol is given as a continuous infusion. When the
infusion is stopped, awakening occurs within 10–15 minutes, even with
prolonged infusions allowing frequent evaluations of mental status.

9. ADVERSE EFFECTS
 Respiratory depressant
 Used only on MV
 Propofol-induced hypotension
 Systemic vasodilation
 Propofol infusion syndrome
 Abrupt onset of bradycardic heart failure, lactic acidosis, rhabdomyolysis, and acute renal failure
 Avoid propofol infusion rates above 5 mg/kg/hr for longer than 48 hrs to reduce the risk of this
condition

10. DEXMEDETOMIDINE
 Selective alpha-2 adrenergic agonist that has sedative, amnestic, and mild
analgesic effects, yet does not depress ventilation
 Unique because arousal is maintained, despite deep levels of sedation
 Patients can be aroused from sedation without discontinuing the drug infusion, and when
awake, patients are able to communicate and follow commands.
 Lower prevalence of delirium

12. ADVERSE EFFECTS
 Hypotension and bradycardia
 central α-2a receptor activation (promote vasodilation)
 Hypertension
 peripheral α-2b receptors (promote vasoconstriction)

13. HALOPERIDOL
 First-generation antipsychotic
 Blocks dopamine receptors in the central
nervous system.
 Following an IV bolus dose of
haloperidol:
 Sedation is evident in 10–20 minutes
 Effect lasts 3–4 hours
 Not appropriate when rapid sedation is
required
 No respiratory depression
 Suited for sedation during weaning from
mechanical ventilation

14. ADVERSE EFFECTS
 Extrapyramidal reactions
 Rigidity and spasmodic movement
 Dose related: Oral preparation > IV preparation
 Neuroleptic Malignant syndrome
 Hyperpyrexia, severe muscle rigidity, and rhabdomyolysis
 IV preparation
 Prolongation of the QT interval
 Can trigger polymorphic ventricular tachycardia
 IV preparation (3.5% of patients)

15. Thank you