http://www.aacn.org/__88256544005f0ff5.nsf/0/0232887c0ad819d588256652005b572c?OpenDocument&Highlight=0,Covington 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 prevention-based 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
Patient anxious, agitated, restless, or all 3
Patient cooperative, accepting ventilation, oriented, and tranquil
Patient asleep; brisk response to light glabellar tap or loud auditory stimulus
Patient asleep; sluggish response to light glabellar tap or loud auditory stimulus but does respond to painful stimulus
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
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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