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To learn more about sedation assessment, read "Consensus Conference on Sedation Assessment: A Collaborative Venture by Abbott Laboratories, American Association of Critical-Care Nurses, and Saint Thomas Health System" in Critical Care Nurse, 2004; 24(2):33-41. Available at www.ccnonline.org.
Now that you’ve read the article, create or contribute to an online discussion about this topic using eLetters. Just visit www.ccnonline.org and click "Respond to This Article" in either the full-text or PDF view of the article.
None reported.
Corresponding author: Jenni Short, RN, MSN, ARNP-BC, 400 S Santa Fe Ave, Salina, KS 67401 (e-mail: jeshort{at}srhc.com).
Continuous chemical sedation in the intensive care unit (ICU) is commonly used to control respiratory rate and anxiety and thus promote sleep and ultimately optimize care. The sedatives used most often include propofol, midazolam, and lorazepam.4 All 3 of these medications provide adequate sedation but also can cause oversedation. Oversedation can lead to prolonged duration of mechanical ventilation, longer ICU and hospital stays, increased incidence of ventilator-associated pneumonia, and inability of patients to communicate with health care providers or family members.5 Undersedation is also harmful and can lead to anxiety, ventilator dysynchrony, dislodged equipment, delirium, increased oxygen consumption, and hyperactivity.6 Making the distinction between too much sedation and not enough sedation can sometimes be difficult when propofol, midazolam, or lorazepam is used.
Achieving adequate sedation can also be a financial burden. Costs associated with undersedation include increased nursing and respiratory care staffing, discomfort and dissatisfaction of patients and their families, decreased staff satisfaction, adverse physiological consequences, and potential to progress to oversedation. Costs associated with oversedation include inadequate examinations of patients, increased costs of diagnostic imaging and other tests, possible delay in the diagnosis of treatable problems, prolonged duration of mechanical ventilation, prolonged stay in the acute care setting, and prolonged hospital stay.
The purpose of this article is to increase nurses’ awareness of the pros and cons of chemical sedation in the ICU and of newer, alternative options. Dexmedetomidine has been available for more than 10 years, but information on its use and effectiveness is just now being published. In this article, I compare the profile of dexmedetomidine with the profiles of other common sedative agents used in the ICU. As more studies on dexmedetomidine are being performed, and positive results are being reported, the drug is becoming more popular. I describe the results of one hospital’s experience with dexmedetomidine and the usefulness and benefit of this sedative in the ICU.
Profile of Dexmedetomidine
Dexmedetomidine was approved for use in the United States in 1999. It is a short-acting 
2-agonist with anxiolytic, anesthetic, hypnotic, and analgesic properties.7 -Agonists promote sedation by stimulating the locus caeruleus, a part of the brain stem involved in the sleep-wake cycle. Sedation is caused by inhibition of the sympathetic vasomotor center of the brain. Table 1
lists presynaptic and postsynaptic activation of 2-adrenoceptors.8,9 Unlike propofol and midazolam, which act on the 
-aminobutyric acid system and produce a clouding of consciousness, dexmedetomidine produces sedation by reducing sympathetic activity and the level of arousal.7
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The relatively short distribution half-life of about 6 minutes of dexmedetomidine results in rapid onset of sedation, and an elimination half-life of approximately 2 hours facilitates clearance of the drug.10 Dexmedetomidine is highly bound to protein and albumin. The drug is extensively metabolized in the liver, and its metabolites are excreted by the kidneys.10 Patients with severe liver disease may require a lower dose of dexmedetomidine than do other patients because the disease can increase the elimination half-life of the drug and decrease clearance.10
Delirium is a common psychiatric problem in ICU patients. Up to 85% of ICU patients may experience some degree of delirium,4 leading to increased morbidity and mortality, prolonged hospital stays, prolonged duration of mechanical ventilation, patient injury or self-extubation, and respiratory complications.10 Table 2 lists the most commonly documented side effects associated with infusion of dexmedetomidine. Delirium has not been identified as a potential side effect of dexmedetomidine. In the MENDS randomized controlled trial10 in patients receiving mechanical ventilation who were managed with individualized targeted sedation, a dexmedetomidine infusion resulted in more days alive without delirium or coma and more time at the targeted level of sedation than did a lorazepam infusion. The use of lorazepam and other agents that stimulate -aminobutyric acid receptors is a risk factor for delirium. Therefore, medications, such as dexmedetomidine, that do not stimulate these receptors may minimize the development of delirium.7
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In the Safety and Efficacy of Dexmedetomidine Compared With Midazolam study,4 the efficacy, safety, and pharmacokinetics of prolonged sedation with dexmedetomidine and midazolam in ICU patients receiving mechanical ventilation were examined. Compared with patients treated with midazolam, patients treated with dexmedetomidine had a significantly lower cumulative incidence of delirium. Nurses thought that the patients treated with dexmedetomidine were more cooperative, better able to communicate, and easier to treat overall than were patients sedated with midazolam. Patients given dexmedetomidine required 44.6 fewer hours of mechanical ventilation and 1.8 fewer days in the ICU than did patients given midazolam.4 Tables 3 and 4 compare the clinical effects and pharmacokinetics of dexmedetomidine with those of other commonly used sedatives.
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Research on the use of dexmedetomidine during pregnancy, labor, delivery, and lactation is limited. The Food and Drug Administration has classified dexmedetomidine as a category C pregnancy risk, so the drug should be used with extreme caution in women who are pregnant. Dexmedetomidine should not be used in patients with advanced heart block or severe ventricular dysfunction.7 Studies have indicated the safety of dexmedetomidine infusions in intubated children and its benefit in providing sedation for procedures, such as magnetic resonance imaging.8
Methods
Salina Regional Health Center, Kansas, is a 200-bed regional medical center with a 12-bed general medical-surgical ICU. Dexmedetomidine was first used in the center in September 2007, with prompting and support from the pulmonary/critical care specialist. Previously, propofol was the primary drug for sedation. Midazolam was used occasionally if a patient had an allergy to propofol or another medical reason the drug could not be used. The types of patients who commonly received propofol included postoperative patients and patients who had respiratory failure or sepsis. The ICU had a routine order set for patients receiving propofol (Table 5). A nurse would start the infusion at 5 µg/kg per minute and titrate the dose by 5 to 10 µg/kg per minute every 5 to 10 minutes to reach the desired level of sedation. The patient’s level of sedation was assessed by using the Ramsay Sedation Scale (RSS; Table 6). Typically, the target score was 3 (responds to commands only). At 5 AM each day, the nurse would decrease the propofol infusion by 5 to 10 µg/kg per minute every 5 to 10 minutes until the patient reached light levels of sedation. Once the nurse was confident the patient would awaken and move all extremities, an evaluation was performed to determine if the patient was ready for weaning from mechanical ventilation. If the patient was ready for weaning, the propofol infusion would be left at a low level so the patient could participate in weaning. If the patient was not ready for weaning, the propofol dose would be increased to provide a level of adequate sedation (according to the RSS).
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A daily assessment of neurological status must be performed on patients receiving sedative agents. Prolonged immobility paired with critical illness places patients at high risk for central nervous system events, such as strokes. A daily decrease in sedation and assessment of neurological status will alert health care providers to any changes in a patient’s function. Propofol is a lipid-soluble agent that provides 1.1 kcal/mL as fat.15 High doses of propofol in addition to enteral or parenteral feeding can lead to a high caloric load. All of these issues can lead to prolonged duration of mechanical ventilation, prolonged stay in the ICU, and a prolonged hospital stay.15
I worked with a pharmacist to develop a protocol for initiation of the dexmedetomidine infusion. Dexmedetomidine is supplied in a single 2-mL clear-glass vial at a concentration of 100 µg/mL. It must be diluted to a final concentration of 4 µg/mL.10 The infusion is prepared with 200 µg of dexmedetomidine in 50 mL of normal saline (concentration=4 µg/mL). The decision was made to omit the loading dose because patients in the ICU commonly experience hypotension, and the loading dose is associated with a high risk for hypotension. After obtaining a physician’s order, the nurse would start the infusion at 0.2 µg/kg per hour and titrate up to a maximum of 0.8 µg/kg per hour to the desired level of sedation, typically a score of 2 or 3 on the RSS. According to the protocol (Table 7), if a patient requires the maximum dose of dexmedetomidine and agitation persists, a fentanyl infusion could be started at 50 µg/h. The protocol also allows the nurse to administer midazolam 1 to 5 mg intravenously as needed for procedures. Zolpidem is available on the physician’s routine orders if it is needed for sleep at night.
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Results
During the study period (September 2006 through May 2007), a dexmedetomidine infusion was started in 42 patients. A data tool (Table 8) was developed to keep track of the patients receiving dexmedetomidine. This tool was used to track diagnosis, date of intubation, dose of dexmedetomidine, use of other sedatives, mean blood pressure, mean heart rate, score on the RSS, ventilator settings, and any weaning from mechanical ventilation that was started. Of the 42 patients, only 4 continued to be agitated when given the maximum dose (dexmedetomidine 0.8 µg/kg per hour plus fentanyl 50 µg/h) and had to be given propofol. Table 9 gives the study results. None of the 42 patients experienced hypotension or bradycardia sufficient to require discontinuation of the dexmedetomidine infusion.
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gives the data on days of mechanical ventilation (ventilator days) before dexmedetomidine was used (September 2006 through May 2007) and during use of the drug (September 2007 through May 2008). Total ventilator days were 1003 for September 2006 through May 2007 and 928 for September 2007 through May 2008, an 8% decrease (75 fewer days) in total days of mechanical ventilation (P = .05). Table 11 gives data on ICU length of stay before dexmedetomidine was used (October 2006 through May 2007) and during use of the drug (October 2007 through May 2008). Total ICU days were 1686 for October 2006 through May 2007 and 1414 for October 2007 through May 2008, a 19% decrease (272 fewer days) in total ICU days (P = .05). Mean length of stay decreased from 2.34 days to 2.31 days (1.5% reduction; P = .05). All of these results are statistically significant.
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Decreasing the duration of mechanical ventilation and length of stay in the ICU can have a significant effect not only on the recovery period of a patient but also financially. Studies4–6 have confirmed that agitation can have a deleterious effect on patients by contributing to ventilator dysynchrony and an increase in oxygen consumption, situations that can lengthen the duration of mechanical ventilation.4–6 The use of sedatives is essential in the ICU.15 This study showed that dexmedetomidine can help reduce duration of mechanical ventilation and number of days in the ICU. Because dexmedetomidine facilitates a cooperative sedation, weaning from mechanical ventilation can be started sooner, and patients are able to cooperate with physical therapy while communicating their needs. Both of these factors are important in recovery, which can be hastened when a patient is alert. Dexmedetomidine is as effective as propofol and midazolam for sedation of critically ill patients.4,6,10 In this study, patients receiving dexmedetomidine were calm, in stable hemodynamic status, and able to participate in the weaning process more quicker than were patients given midazolam or propofol.
An incidental discovery was that the rate of ventilator-associated pneumonia was 0% during the time dexmedetomidine was used. Previously the center had 5 cases February through May 2007 and 1 case June through September 2007. This finding supports the well- established fact that less time receiving mechanical ventilation helps prevent pneumonia.
Because patients in the ICU account for nearly one-third of total inpatient costs, efforts to reduce duration of mechanical ventilation, time in the ICU, and complications associated with being in the ICU have a significant effect on hospital costs.16 In the experience at Salina Regional Medical Center, dexmedetomidine is a safe, effective sedative for use in the ICU.
PRIME POINTS
References
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