SEDATIVES
USE IN ICU
Definitions
Agitation in ICU
An emotional state of anxiety, nervous
excitement and restlessness.
Agitation can precipitate accidental removal of endotracheal tubes
or of IV catheters used for administration of life-sustaining
medications.
Consequently, sedatives are among the most commonly
administered drugs in ICUs
Pain and discomfort are primary causes of agitation; therefore, treat
pain first and add a sedative if needed.
Definitions
Sedation
Common causes of agitation in the ICU include
Pain….. Not an indication for sedative
use
delirium,
hypoxia,
hypoglycemia,
dehydration,
drug or alcohol withdrawal.
Definitions
Sedation
Sedation is:
the depression of a patient's awareness to the
environment and reduction of his or her
responsiveness to external stimulation.
Prior to the administration of medications, clinicians
must know the level of sedation required and the
appropriate dose of the pharmacologic agent or agents
chosen.
Assessment Scales
Level of sedation
Richmond Agitation-Sedation Scale (RASS)
Sedation-Agitation Scale (SAS)
Assessment Scales
Richmond Agitation-Sedation Scale (RASS)
Assessment Scales
Sedation-Agitation Scale (SAS)
Lighter vs deeper sedation…?
• The use of light sedation resulted in
more ventilator-free and ICU-free
days.√√√
• In comparison with deep sedation, the
use of light sedation did not increase
the rate of short-term adverse events,
and long-term psychiatric outcomes
were either unaffected or improved.
Thus, the overall benefits of maintaining a light sedation
level in ICU patients appear to outweigh the risks.
Assessment of Sedation
- Goal sedation scores should be individualized for each patient, but
generally an SAS score of 3 to 4 or a RASS score of 0 to –1 is
recommended
• Level of sedation should be assessed every 2–4 hours throughout
the day and evening.
• Consider assessing every 4 hours during nighttime sleeping
hours to minimize sleep interruption.
Levels of Sedation
A minority of ICU patients have
an indication for continuous
deep sedation, for reasons such
as:
➢ treatment of intracranial hypertension
➢ severe respiratory failure
➢ refractory status epilepticus
➢ prevention of awareness in patients treated with
neuromuscular blocking agents.
➢ ventilator dyssynchrony
Management
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Types of Sedatives
Primary medications for the treatment of agitation include
propofol, dexmedetomidine, and benzodiazepines
(usually lorazepam and midazolam)
Mild sedation
Types of Sedatives
using either propofol or dexmedetomidine over
benzodiazepines [midazolam or lorazepam] for
sedation in critically ill, mechanically ventilated adults”
Benzodiazepines are first-line agents for:
✓ status epilepticus,
✓ alcohol withdrawal,
✓ benzodiazepine dependence or withdrawal,
✓ need for deep sedation or amnesia,
✓ Intermittent sedation
Types of Sedatives
1. Benzodiazepines
• They have anxiolytic, amnestic, sedating, hypnotic, and
anticonvulsant effects, but no analgesic activity.
• Lorazepam is long-acting benzodiazepine, can be used as
PO or IV boluses to produce mild to moderate sedation.
✓ Not recommended to be given as continuous infusion due
to risk of prolonged sedation and propylene glycol
toxicity.
• Midazolam is a Short acting benzodiazepine produce
deep sedation and amnesia.
✓ Highest risk of delirium (especially with elderly > 70 yrs),
long-term cognitive impairment & withdrawal symptoms.
✓ Associated with longer duration on MV.
Types of Sedatives
1. Benzodiazepines
Side Effects:
Higher risk of delirium and tolerance than sedatives.
Dose dependent CNS depression.
Respiratory depression.
Benzodiazepine clearance is reduced in patients with hepatic dysfunction and
other disease states, in elderly patients.
Types of Sedatives
2. Propofol
Preferred over midazolam as it is less likely cause prolonged
sedation and/or delirium.
Decreases ICP.
Drug of choice in pregnancy.
Available as lipid emulsion 1%.
Monitor: Calories provided from 10% lipid emulsion (1 kcal/mL).
May cause hypotension and bradycardia (higher risk in patients
with cardiac dysfunction)
May cause hypertriglyceridemia (most institutions use a threshold
of 800–1000 as a cut off of when to stop propofol).
Types of Sedatives
2. Propofol
PRIS = propofol-related infusion syndrome:
➢ lactic acidosis,
➢ arrhythmia, and cardiac arrest.
➢ AKI, hypertriglyceridemia, rhabdomyolysis
• usually occurring at doses greater than 50 mcg/kg/minute for
48 hours or more.
• The mechanism of PRIS may include alterations in hepatic
metabolism of the lipid emulsion, leading to an accumulation of
ketone bodies and lactate
Risk factors for PRIS or other adverse effects of propofol:
Neurologic injury, sepsis, use of vasoactive medications,
high-dose propofol, acute liver failure
Types of Sedatives
3. Dexmedetomidine
Has analgesic sparing properties
Lower risk of delirium.
Less likely to produce respiratory depression. (could be used
safely with NIV)
A very deep level of sedation is not possible with
dexmedetomidine alone.
Monitoring: bradycardia….CI
Lower ↓↓ duration of mechanical ventilation than
midazolam.
Does not cause drug dependency, but withdrawal symptoms
(e.g., nausea, vomiting, agitation) after prolonged use (1 week).
Types of Sedatives
4. Ketamine
Lower ↓↓ duration of mechanical ventilation than
midazolam.
Has analgesic sparing properties
Relieves bronchospasm…… asthma???
For deep sedation
• May increase ICP…. Use with caution
• Delirium, nightmares, and hallucinations
• May cause cardiovascular stimulation (inappropriate in patients
with ischemic heart disease)
Anxiety/agitation
• For patients with anxiety who do not need a continuous infusion,
intermittent dosing with benzodiazepines is appropriate.
• Low dose, intermittent, IV boluses, of long-acting benzodiazepines
(lorazepam, diazepam) might be needed to treat anxiety and produce
mild to moderate sedation in patients with agitation, lack of self control
(pulling out lines), sleep deprivation,…etc.
• For severe agitation due to anxiety requiring a continuous infusion, we
use propofol or dexmedetomidine rather than a benzodiazepine.
• BNZ infusion is associated with increased risk of delirium, mechanical
ventilation days, and ICU length
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Anxiety/agitation
• For patients in whom rapid sedation is required (eg, immediately
following intubation) or rapid awakening is desirable (eg, patients who
require frequent neurologic examinations)….. Propofol is useful
because it has a rapid onset and short duration of effect.
• Deeper sedation may be required in some patients …..Propofol is the
agent of choice for deep sedation because it allows relatively rapid
emergence from deep levels of sedation. Recovery from deep sedation
with benzodiazepines may be prolonged, and deep sedation may not
be easily attained in many patients with dexmedetomidine alone.
• For deep sedation: Propofol plus an opioid is appropriate. For patients
who are intubated and mechanically ventilated.
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Anxiety/agitation
• For patients with bradycardia…. Dexmedetomidine and propofol is
generally avoided since bradycardia is a common side effect of this
agent.
• For patients with obesity, prolonged and high-dose benzodiazepines
are often avoided ….. metabolites accumulation in adipose tissue,
prolonging sedation and increasing length of stay and mechanical
ventilation.
• For patients with significant hypotension, Propofol is often avoided or
dosing limited since hypotension is a common adverse effect.
• For patients with severe hypertriglyceridemia, propofol is
contraindicated. 22
Delirium
Antipsychotics can be used intermittently as supplements to other sedatives
for the treatment of hyperactive (agitated) delirium. ….. use intravenous
(IV) Haloperidol for acute management of delirium.
When chronic control is delirium limiting the ability of the patient to wean
off sedative infusions in preparation for extubation)….. Enteral quetiapine
is used
For patients with prolonged QTc interval or on agents that prolong the QTc
interval, antipsychotics are avoided to decrease the risk of ventricular
arrythmias
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Discontinuation:
• If the sedative-analgesic agent has been administered for a short
duration (≤7 days), discontinuation over a short period of time is
acceptable (eg, over hours).
• If the sedative-analgesic agent has been administered for >7 days a
gradual reduction may be necessary (eg, approximately 10 to 25
percent per day).
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Sedation Holiday
• Daily awakening (sedation holiday) involves an
interruption of continuous infusion opioid or sedatives until
the patient is awake (SAS at least 4 or RASS at least 0) or
shows discomfort or pain .
Sedation Holiday
Benefits:
(a) Assess the patient’s neurologic function.
(b) Reevaluate lowest effective opioid or sedative dose.
(c) Prevent drug accumulation and overdose
(d) Reduce time on the ventilator (although one randomized
study contradicts this by finding no reduction in the duration of
mechanical ventilation or ICU stay with sedation interruption
(e) Reduce mortality and ICU length of stay when combined
with a spontaneous breathing trial.
(f) Reduce symptoms of posttraumatic stress disorder.
Analgosedation
Analgosedation Method in the ICU:
This method of sedation advocates the use of opiate medications
before prescribing an anxiolytic/hypnotic medication to provide
patient comfort in the ICU unless anxiolytics are otherwise
indicated.
Providing pain relief early in the ICU stay may decrease the
agitation associated with pain and/or general discomfort while
minimizing the use of alternative medications commonly used for
agitation (e.g., benzodiazepines)
