In order to reduce burning and stinging
associated with administration, propofol should be administered through large-bore
intravenous lines whenever possible. Although propofol is formulated with a
preservative to prevent bacterial growth, product labeling suggests the bottles and
tubing should be changed every 12 hours, and line integrity should be assessed to
prevent bacterial contamination. The caloric load of the lipid vehicle should be
considered when evaluating nutritional needs in patients receiving propofol.
Propofol may cause a life-threatening syndrome called propofol infusion syndrome
(PRIS) in about 1% of patients. PRIS is characterized by metabolic acidosis,
hypertriglyceridemia, progressive hypotension, bradyarrythmias, and cardiovascular
collapse. Other complications of PRIS may include AKI, hyperkalemia,
rhabdomyolysis, and liver failure.
59,60 PRIS has been observed most commonly at
doses exceeding 70 mcg/kg/minute and with use beyond 48 hours, but it has been
reported at lower infusion rates and with shorter infusions.
difficult to distinguish from other conditions in critically ill patients and because of
its high mortality rate, members of the health care team should diligently monitor
patients in order to rapidly identify PRIS. When PRIS is suspected, propofol should
be discontinued and patients should receive appropriate supportive care.
Dexmedetomidine is a centrally acting α-receptor agonist that is similar to
clonidine. It demonstrates greater anxiolytic and fewer symptholytic properties as
compared to clonidine. In addition to anxiolysis, dexmedtomidine also has sedative
and opioid-sparing effects. It does not have anticonvulsive characteristics, induce
amnesia, or cause respiratory depression.
37 Dexmedetomidine often allows patients
to awaken more easily and better interact with caregivers as compared to propofol
and benzodiazepines, but it is not appropriate for patients requiring deeper levels of
sedation and those paralyzed with neuromuscular receptor antagonists.
Dexmedetomidine starts working within approximately 15 minutes after the initiation
of an infusion and reaches its peak effect at 1 hour.
64,65 Clinicians may administer a
bolus to achieve faster onset, but bolus administration is associated with increased
risk of hemodynamic instability, which can manifest as either hypertension or
66 Additional adverse effects include nausea, atrial
fibrillation, and, rarely, cardiogenic shock.
In the United States, dexmedetomidine
is approved for use as a continuous infusion at doses up to 0.7 mcg/kg/hour for a
maximum of 24 hours, but clinical trials have demonstrated safety and effectiveness
at doses up to 1.5 mcg/kg/hour for as much as 28 days.
every 30 minutes. Patients with severe hepatic disease may require lower doses of
dexmedetomidine to avoid prolonged offset of effect and excessive hemodynamic
effects. Dexmedetomidine-induced hypotension and bradycardia may occur more
commonly in patients who are hypovolemic or those who have cardiovascular
Importantly, because dexmedetomidine does not cause respiratory
depression, it can be continued during and after extubation, unlike propofol.
continuing dexmedetomidine in this fashion, clinicians should be aware that it may
cause loss of oropharyngeal muscle tone, resulting in airway obstruction.
Consequently, patients getting dexmedetomidine without mechanical ventilation must
receive continuous respiratory monitoring.
Clinical Considerations with Sedative Agents
Midazolam GABAA 2–5 Effect prolonged
Lorazepam GABAA 15–20 Accumulation of
Propofol 1–2 No clinically significant No clinically significant
Dexmedetomidine Central α-2 5–10 No clinically significant
Benzodiazepines are GABA receptor agonists that demonstrate anxiolytic,
sedative, hypnotic, and anticonvulsant effects.
73 Current guidelines no longer
recommend use of benzodiazepines as first-line sedatives in most critically ill
patients, although they remain the mainstay of therapy for management of alcohol
37 Benzodiazepines can potentiate respiratory failure and hypotension,
especially when coadministered with opioids.
35 They can also cause mental status
changes and are risk factors for development of delirium.
occasionally experience a paradoxical reaction involving agitation and restlessness.
Elderly patients are more likely to experience adverse effects, while patients taking
benzodiazepines prior to hospitalization and those on them for long periods of time
may demonstrate decreased sensitivity. Usually, benzodiazepines are administered
parenterally in the critical care setting and the most commonly used agents are
lorazepam and midazolam. Either lorazepam or midazolam may be given via
intermittent or by continuous intravenous infusion, but the two drugs have key
differences relative to their pharmacokinetic, pharmacodynamic, and adverse effect
profiles. Because it is more lipophilic, midazolam has a faster onset and shorter
duration of action than lorazepam. However, because midazolam deposits in the
adipose tissue, it can lead to variable and prolonged awakening when it is
administered continuously over the course of several days.
hepatic metabolism to an active metabolite, which is eliminated renally, while
lorazepam is inactivated in the liver. Both agents should be used cautiously in renal
accumulate at doses as low as 1 mg/kg/day and cause metabolic acidosis and
77,78 When benzodiazepines must be used clinicians should carefully manage the
dosing regimen to target the desired level of sedation at the lowest dose possible.
Avoiding continuous infusions of benzodiazepines in favor of as needed bolus doses
based on symptoms of agitation may result in decreased total benzodiazepine
exposure and a lower chance of benzodiazepine-related complications.
After thoroughly assessing J.A. and addressing reversible causes of agitation such
as metabolic disorders and withdrawal syndromes, sedation with propofol should be
considered if he remains agitated and his hemodynamics are adequate. Propofol and
dexmedetomidine are both suggested first-line sedatives according to current
guidelines. However, because J.A. may require frequent awakenings for neurologic
examinations, the faster offset of effect with propofol may make it more appropriate.
J.A.’s blood pressure and heart rate should be monitored when propofol is started,
and it should be titrated to a light level of sedation based on the RASS or SAS. His
triglyceride concentrations should be evaluated periodically if propofol is
administered for several days, and clinicians should be aware of the symptoms of
PRIS in order to identify any potential episodes as soon as possible.
Delirium is a symptom of acute brain dysfunction that involves the following
combination of symptoms: acute change or fluctuation from baseline mental status,
inattention, and disorganized thinking or altered level of consciousness.
who are delirious may experience hallucinations, delusions, or hyperactivity, but
these symptoms are not present in all delirious patients. In fact, three different forms
of delirium have been described based on the symptoms that patients demonstrate. In
hyperactive delirium, patients are agitated, while in hypoactive delirium they are
calm or lethargic. Patients with mixed delirium fluctuate between these two
Delirium occurs at least once during the ICU stay in up to 80% of critically ill
patients and is associated with negative patient outcomes, including increased
mortality, ICU and hospital-length of stay, long-term cognitive impairment, and health
81–84 Clinicians are more likely to fail to identify delirium if patients
manifest hypoactive delirium rather than hyperactive delirium.
patients who have delirium, current guidelines recommend that clinicians routinely
assess patients several times each day using a validated delirium assessment tool.
The two recommended tools for assessing delirium are called the Confusion
Assessment Method for the ICU (CAM-ICU) and the Intensive Care Delirium
Based on his symptoms, J.A. is likely experiencing delirium. It is clear that his
mental status has changed from baseline as “he does not seem to be himself.” In
addition, the fluctuation between unresponsiveness and agitation combined with the
inattention and disorganized thinking he is exhibiting by not being able to answer
simple questions fulfill the other criteria of delirium. Clinicians should formally
evaluate J.A. for delirium using a validated tool such as the CAM-ICU or the ICDSC.
There are a variety of modifiable and non-modifiable risk factors associated with
the development of delirium in critically ill patients.
37 Non-modifiable risk factors
include baseline dementia, hypertension, alcoholism, and greater severity of
37,75,86 Current evidence suggests that benzodiazepine exposure, very deep
sedation, and anticholinergic medications may increase the risk that patients develop
delirium. Any association between opioids and propofol and delirium is unclear
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