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Use of Propofol for Sedation in the ICU
Holly Covington
Crises and distress occur daily in the critical care areas of hospitals. These crises contribute to the physical
and emotional stress of patients and influence patients' ability to cope with their illness. Causes of stress can
include physiological, chemical, pharmacological, emotional, and environmental factors. Stress may lead to
physical and psychological exhaustion that interferes with patients' ability to heal. The physiological response
to stress contributes to hyperglycemia, increased metabolism, and increased oxygen demand. 1,2
Nurses in critical care areas deal on a daily basis with patients who have signs and symptoms of stress.
Stress can be manifested as defensiveness, anger, fatigue, restlessness, agitation, and anxiety. 1,2 The highly
technological world of intensive care with complicated machines and monitoring devices can be intimidating
and can add to patients' anxiety. In some instances, the anesthetic agent propofol may be used as a
sedative to treat anxiety and agitation in critically ill patients.
REASONS FOR SEDATION
Patients with acute illness often show signs or symptoms associated with anxiety or become agitated.
Sedatives are commonly used to alleviate agitation and restlessness that accompany anxiety. According to
estimates, 53% to 70% of critically ill patients receive some form of anxiolytic or sedative medication.3-7
Anxiety, a sustained state of apprehension in response to a real or perceived threat, is associated with motor
tension and increased sympathetic activity.1,7 Agitation, that is, excessive, nonpurposeful motor activity
associated with internal tension, may be accompanied by anxiety, panic, depression, delusions,
hallucination, flight of thought, and delirium.6,7
Agitation is associated with many different physiological and psychological abnormalities. A key problem with
agitation is the potential for physical or biochemical injury. Adverse effects of agitation include increases in
respiratory rate, heart rate, blood pressure, cardiac contractility, afterload, dysrhythmias, and myocardial
oxygen consumption.7,8 Agitation can also lead patients to pull out or dislodge intravenous (IV) and
hemodynamic monitoring catheters or endotracheal tubes. The expected outcomes for sedation of patients
experiencing agitation include a decrease in anxiety and agitation and freedom from injury. Use of sedation
decreases agitation and can help prevent physical injury. Sedation may also be used in critical care to
decrease a patient's activity level, thereby decreasing myocardial oxygen consumption.
CHOICES OF SEDATIVES
Intermittent sedation is a treatment based on careful nursing assessment, but its use can be subjective or
inconsistent. Administering medication on an as-needed basis has been characterized as being reactive
rather than proactive.3 In the reactive approach, administration of sedatives is based on a patient's behavior
or reaction to existing problems. Changes in staff may contribute to an inconsistent or reactive use of
sedation. In order to promote a more proactive approach, a schedule of doses can be established, and
additional as-needed doses can be used for breakthrough agitation.
For patients receiving continuous infusions of sedatives, titrating or adjusting the dose according to
anticipated responses of the patients to problems or procedures provides critical care nurses a preventionbased focus for care.
Medications and combinations of agents for sedation vary widely. Often benzodiazepines such as
midazolam or lorazepam are used.2-8 Some patients receive analgesics and sedatives concomitantly to
alleviate pain or agitation.5,6 Because of problems related to dependence, tolerance, and withdrawal,
barbiturates are not used for sedation as often as they once were. 6 Although opioids are commonly used for
pain control and sedation, benzodiazepines are used for anxiety. 7
For patients receiving mechanical ventilation, neuromuscular blocking agents may be added for paralytic
effects and to promote synchrony with the ventilator.3,5 These sedative options may contribute to risk of
untoward effects such as increased agitation, disorientation, excessive sedation, dependence, and tolerance
associated with the medication.5,7
PROPOFOL
In 1993, the Food and Drug Administration approved the use of propofol for sedation in patients receiving
mechanical ventilation in the ICU.9,10 Initially used as a general anesthetic, propofol is now being used in the
ICU when short-term sedation is required. Short-term sedation (from several hours to 5 days) may be
necessary to reduce anxiety and agitated movements that can affect hemodynamic stability. Propofol is used
to reduce anxiety during short, uncomfortable procedures; reduce restlessness in the initial hours after
surgery; decrease agitation in patients with neurological disorders or injury; and promote synchronous
breathing in patients receiving mechanical ventilation.10-16
The exact mechanism of action of propofol is unknown. Studies on the action potential and presynaptic
release of neurotransmitters show that propofol inhibits calcium influx into smooth muscle tissue, resulting in
decreased cardiac contractility and dilation of vascular smooth muscles.12-24 Propofol has no analgesic
properties but, when given at a dosage of 5 µg/kg per minute, has amnesic properties. 8,16
Pharmacokinetics
Propofol is mixed in a lipid-based diluent. One percent propofol in an oil-in-water emulsion contains 10%
soybean oil, 1.2% egg phosphatide, and 2.25% glycerol. After IV administration, propofol is rapidly
distributed to tissues because of its high solubility in lipids; redistribution back to the plasma is slow. This
high solubility enables propofol to cross the blood-brain barrier easily. Propofol is rapidly distributed from the
blood into other highly perfused areas such as heart, lung, and liver.
When tissue perfusion is poor, however, propofol is redistributed to the plasma more slowly. Plasma
concentrations decrease rapidly when infusion of the drug is stopped. With longer infusion times,
accumulation of propofol in the tissues can cause plasma levels to decrease more slowly. When IV infusions
are stopped, blood levels decrease by 50% within the first 10 to 20 minutes.25-27
The metabolism of propofol is rapid and extensive. The agent is mainly eliminated as glucuronide and sulfate
conjugates. These inactive metabolites are excreted in the kidney; 0.3% of the drug is excreted unchanged
in urine and feces.27 The primary difference between propofol and other sedatives is its rapid onset,
distribution (1.8-8.3 minutes), and metabolic elimination (30-64 minutes).28
Elimination may be prolonged in patients who receive long-term infusions.27,28 Propofol produces rapid
hypnosis, usually within 40 seconds of administration. Its mild sedating effects at doses of 5 µg/kg per
minute are useful in critical care settings for patients with cardiac, respiratory, or neurological disorders who
are receiving mechanical ventilation.12,13,29 Long-term sedation can result in tolerance and necessitate
increases in doses.19,30
The usual dosage for sedation is 5 to 50 µg/kg per minute (0.3-3.0 mg/kg per hour).11 Bolus dosing should
be avoided because it produces high peaks and low troughs that can result in inconsistent levels of propofol
in brain tissue.4,9,10,31 Doses can be increased every 5 to 10 minutes until sedation is achieved. When the
Ramsay Sedation Scale32 (see Table) is used as a guide, dosage depends on the patient's age and
condition, concomitant drug therapy, and desired level of sedation.
Table. Ramsay scale for assessing level of sedation
Level
Response
1
Patient anxious, agitated, restless, or all 3
2
Patient cooperative, accepting ventilation, oriented, and tranquil
3
Patient asleep; brisk response to light glabellar tap or loud auditory stimulus
4
Patient asleep; sluggish response to light glabellar tap or loud auditory stimulus but
does respond to painful stimulus
5
Patient does not respond to painful stimulus
Although propofol is used for short-term sedation, the medication can be given for up to 21 days in special
situations, such as severe respiratory failure or status epilepticus. 28,30 Lipid levels should be monitored in
patients receiving infusions that continue for longer than 72 hours because continued infusion can result in
marked elevations in lipids.33
Physiological
Effects
Cardiovascular. Propofol can cause hemodynamic instabilities, primarily hypotension and bradycardia.20-22
The hypotension may be related to the patient's hydration status10 or to underlying abnormalities such as
coronary artery disease or congestive heart failure. 10,20 Propofol may cause myocardial ischemia and
production of lactic acid in patients with coronary artery disease.19 Blockage by propofol of extracellular
calcium influx into the myocytes can cause decreased myocardial contractility, vasodilation, and decreased
arterial pressure.19-24
Propofol can produce an imbalance between myocardial oxygen supply and demand in patients with
coronary artery disease.24 Decreased contractility lessens myocardial workload and myocardial oxygen
demand. The decrease in oxygen demand can be a desired effect in anxious or agitated patients.
Hemodynamic instability often requires decreasing myocardial oxygen consumption in patients with adult
respiratory distress syndrome, myocardial ischemic diseases, or shock states. 29 Because of its
hemodynamic effects, propofol must be used with extreme caution in patients in shock states. Use of
alternative agents such as midazolam may be necessary when blood pressure is compromised. 28,30,33
Pulmonary. Minute ventilation, tidal volume, mean inspiratory flow rate, and functional residual capacity are
all decreased during use of propofol.10 These changes may be due to the inhibition of intracellular calcium in
the bronchioles with subsequent relaxation of bronchiolar smooth muscle. In a study4 that compared use of
midazolam with use of propofol, the mean time from discontinuation of sedation to first disconnection from
the ventilator and extubation was significantly shorter for propofol (34.8 ± 29.4 hours) than for midazolam
(97.9 ± 54.6 hours). Although the cost of propofol was $54 to $66 for a 100-mL vial, the cost of care was
$1362 less in the propofol group than in the midazolam group, because patients sedated with propofol were
extubated sooner.4
Neurological. The neurological effects of propofol occur because it easily crosses the blood-brain barrier.
Propofol can inhibit activity at both spinal and supraspinal synapses by interacting with receptors for the
neurotransmitter g-amino butyric acid, a situation that potentiates the effects of the neurotransmitter. 10,13 The
potentiation results in decreased anxiety, sedation, and muscle relaxation. Propofol can decrease elevated
intracranial pressure without causing marked decreases in cerebral perfusion pressure. 13 In addition, the
drug decreases cerebral blood flow 26% to 51%, increases cerebral vascular resistance 51% to 55%, and
decreases cerebral metabolic oxygen requirements 18% to 36%. 20 The exact mechanism of these actions is
unknown. Decreased cerebral blood flow may be related to the inhibitory effects of propofol on calcium in
vascular smooth muscles.
Awakening from sedation induced by propofol usually occurs 10 to 20 minutes after infusion of the drug is
stopped. Rapid awakening or abrupt withdrawal of propofol can cause increased anxiety, agitation, and
resistance to mechanical ventilation.10 These effects can be prevented by decreasing the dose of propofol in
small increments (5 µg/kg per minute) during a period of 5 to 10 minutes. Reorienting the patient during
awakening can also help decrease anxiety and agitation. For awakening for weaning and withdrawal of
mechanical ventilation, propofol should be titrated to maintain a level 2 sedation on the Ramsay scale.
Metabolic. The use of a lipid emulsion for propofol is associated with increased fat in the bloodstream,
leading to an increase in caloric intake and elevated triglyceride levels. Patients receiving propofol who are
also receiving enteral or parenteral nutrition must be carefully monitored to avoid overfeeding and high
triglyceride levels. Triglyceride levels in excess of 5.6 mmol/L (500 mg/dL) may require discontinuation of the
propofol infusion and use of another sedative agent. 34,35
Although long-term sedation with propofol or anesthetic doses of the drug may cause tonic-clonic activity,
this effect has not been observed with short-term sedation.10 The increased excitation at voltage-regulated
ion channels in neuronal membranes may be due to depression of inhibitory neurotransmitters in the
subcortical areas of the brain.18 Increased physiological stress associated with illness or disease triggers
hormonal responses that alter metabolism. Glucocorticoids released to aid in glucose production for energy
also alter normal immune responses. Patients experiencing anxiety are often at risk for immunosuppression
associated with stimulation of glucocorticoid production during the stress response. Malnutrition and disease
states also adversely affect the body's defenses against infection. Because propofol has no antimicrobial
activity, these factors put patients receiving this medication at high risk for infection. 1,6,10
Contraindications
Propofol is contraindicated for patients with hypersensitivity to soybean oil, eggs, lecithin, or glycerol. Use of
the drug should also be discontinued if marked hypotension or triglyceride levels greater than 5.6 mmol/L
develop.34,35 Administration of propofol can result in critically elevated lipid levels, which contribute to
elevated triglyceride levels and increase caloric intake. Use of propofol in pregnant patients is not
recommended, because pregnancy causes a physiological hyperlipidemia.34,35
The combination of catabolic states common in critically ill patients and administration of lipid emulsions may
contribute to an increase in the production of carbon dioxide. This possibility must be kept in mind when
caring for patients with chronic obstructive pulmonary disease who retain carbon dioxide. Propofol is also
contraindicated in children. Data on its use in children are limited, and adverse neurological events in this
population have been reported.36 Patients who are not intubated should not receive propofol because of the
potential for respiratory depression.10
Nursing Care
Close monitoring is required for patients receiving propofol because of the risk for hemodynamic instability,
increased agitation during awakening from propofol-induced sedation, and hyperlipidemia. Nursing
diagnoses for patients receiving propofol might include decreased cardiac output related to afterload
reduction, anxiety related to situational crisis, high risk for infection related to invasive catheters and
immunosuppression, altered nutrition related to increased lipid levels, and potential ineffective breathing
patterns related to respiratory depression. Other possible nursing diagnoses are impaired physical mobility
and self-care deficits related to sedation, and impaired verbal communication related to intubation and
sedation.
Anxiety and physiological stress stimulate release of catecholamines from the adrenal glands, resulting in
increased activity of the sympathetic nervous system. Sympathetic stimulation causes increases in heart
rate, systemic vascular resistance, and myocardial oxygen demand. Increased workload and strain on the
heart may lead to a decrease in cardiac contractility. Light sedation with propofol may reduce hemodynamic
effects of anxiety but requires close monitoring.
Blood pressure, heart rate, ECG findings, cardiac index, systemic vascular resistance, and pulmonary
capillary wedge pressures should be monitored and correlated with the patient's appearance and response
to sedation. Increases in systemic vascular resistance, heart rate, and blood pressure to more than the
patient's normal levels may indicate increased anxiety or agitation that requires additional sedation.
Patients may require opiate analgesics to manage pain, benzodiazepines for increased anxiety, and
neuromuscular blocking agents to decrease motor activity. When propofol is used concomitantly with other
medications, hypotension and respiratory depression associated with the other medications may occur.
Opioids may increase the anesthetic or sedative effects of propofol. 7,36 When analgesic and anxiolytic
medications are administered to patients who are receiving a sedative, lower doses of each drug may be
necessary.37,38
When propofol is used as a sedative, the dose should be titrated to attain the desired level of sedation. Many
tools are available to help assess the level of sedation.3,36,37 The most common instrument is the Ramsay
Sedation Scale32 (see Table). Use of the scale requires hourly assessment of sedation at levels 3 and 4.
Neurological assessment should be performed at least every 24 hours.
Because of the rapid onset of action of propofol and the rapid decrease in blood concentrations after
discontinuation of the drug, neurological assessment does not require prolonged cessation of sedation. For a
wake-up assessment, the dose is decreased to decrease the level of sedation, or administration of propofol
is stopped for a brief time and the patient's level of consciousness is assessed. After the wake-up
assessment is completed, the dose is increased until the desired level of sedation occurs.
The amount of sedation desired depends on the patient's condition. During the daytime hours, sedation
might be kept at levels 2 to 3 on the Ramsay scale to accommodate family visitations, maintain a sleep-wake
cycle, and allow daily neurological assessment. Greater sedation, level 4 or 5, might be used at night or
during painful procedures.
Because it can irritate peripheral veins, propofol must be given through a central or large peripheral IV
catheter. An infusion device is required to titrate the dose to fit the patient's response or level of sedation.
Because of the potential for microbial contamination, the IV system must be changed every 6 hours if
manufactured IV solution is not used. If manufactured solution is used and the nurse only has to access the
bag of fluid, tubing changes should be done every 12 hours.6 Nutritional support and a dietary consultation
are necessary to ensure adequate caloric needs and avoid excessively high lipid levels. Close monitoring of
laboratory results is needed to keep triglyceride levels at the patient's presedation level.
Propofol is classified as a general anesthetic.26 As with other IV anesthetics, because of the risk of
respiratory depression, patients must have mechanical ventilation while receiving propofol. A decrease in
ventilation leads to an increase in carbon dioxide tension and respiratory acidosis. Arterial blood gas levels
and oxygen saturation should be monitored to assess for hypercapnia and hypoxia associated with
respiratory depression.
Conclusion
Propofol can be used whenever continuous sedation is required to control a patient's anxiety and agitation.
Care of patients receiving propofol requires knowledge of the physiological and psychological effects of
anxiety and agitation in the critically ill. Nurses must understand the need for close assessment and
monitoring of hemodynamic parameters and neurological status of these patients. Patients' family members
and visitors must be educated about the patients' level of consciousness during sedation. Nursing care of
sedated patients is a challenge. Becoming familiar with the uses and administration of propofol as a
continuous infusion will help critical care nurses meet this challenge. 9
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