TY - JOUR
AU - Szumita, Paul, M.
AB - Abstract Purpose The role of dexmedetomidine for the management of pain, agitation, and delirium in adult patients in the intensive care unit (ICU) is reviewed and updated. Summary Searches of MEDLINE (July 2006–March 2012) and an extensive manual review of journals were performed. Relevant literature with a focus on data published since our last review in 2007 was evaluated for topic relevance and clinical applicability. Optimal management of pain, agitation, and delirium in ICUs requires a systematic and multimodal approach aimed at providing comfort while maximizing outcomes. Dexmedetomidine is among multiple agents, including opioids, propofol, benzodiazepines, and antipsychotics, used to facilitate and increase patients’ tolerability of mechanical ventilation. This article reviews the newest evidence available for dexmedetomidine use for sedation and analgesia in medical–surgical ICUs. Adverse effects associated with dexmedetomidine were similar among the studies examined herein. The most common adverse effects with dexmedetomidine were bradycardia and hypotension, in some cases severe enough to warrant the use of vasoactive support. Due to the adverse events associated with rapid dosage adjustment and bolus therapy, dexmedetomidine may not be the best agent for treating acute agitation. Conclusion In medical–surgical ICUs, dexmedetomidine may be a viable non-benzodiazepine option for patients with a need for light sedation. In cardiac surgery patients, dexmedetomidine appears to offer no advantage over propofol as the initial sedative. The role of dexmedetomidine in unique patient populations such as neurosurgical, trauma, and obstetrics is yet to be established. Pain, agitation, and delirium (PAD) management in mechanically ventilated patients is a cornerstone of therapy in the intensive care unit (ICU) and requires experienced clinicians to optimize patient outcomes.1 ICU clinicians seek to tailor PAD management, within the larger scope of awakening and breathing trial coordination, frequent delirium monitoring, and early mobility, to the needs of the individual patient instead of a one-size-fits-all approach.2,3 Failure to appropriately manage pain and agitation has been linked to prolonged mechanical ventilation, poor mental health outcomes, increased incidence of delirium, increased length of stay, and self-extubation.4,5 Clinicians should select a regimen based on the individual patient and the goals of care.6 All sedative and analgesic regimens should aim to maximize survival, reduce ICU and hospital lengths of stay, and facilitate mechanical ventilation while reducing the total time on the ventilator. Patient-specific regimens should also minimize adverse events.7,8 All of these objectives can be achieved through the use of protocol-driven, goal-oriented care that incorporates evidence-based drug selection and requires clinical familiarity with such agents.9 The number of sedatives and analgesics available to the bedside clinician is limited. Agent selection should take into consideration the primary mechanism of action as well as potential adverse effects.10 Evaluation of pharmacokinetic properties should also play a role in the initiation and maintenance of sedation to optimize fast onset of action with quick abandonment of effect once therapy is discontinued.11,–13 Benzodiazepines and propofol have become a standard of care for sedation, as evidence exists to guide their appropriate use.14,15 As newer sedative agents become available, it is this standard against which they will be compared for safety and efficacy or with which they will be used concomitantly to optimize therapy.16 The purposes of this review are to evaluate the medical literature published since 2007, when an earlier review of dexmedetomidine appeared,1 and to use this literature to help establish dexmedetomidine’s role in clinical practice. Searches of MEDLINE (July 2006–March 2012) and an extensive manual review of the medical literature were performed using the key search terms dexmedetomidine, intensive care unit, sedation, analgesia, and delirium. Relevant clinical trials resulting from the search were evaluated for topic relevance and clinical applicability. Pharmacology and administration Dexmedetomidine, the pharmacologically active isomer of medetomidine, is a potent, centrally acting α2-adrenergic agonist available for sedation in mechanically ventilated patients.17 Its mechanism of action is distinct from other sedatives targeting γ-aminobutyric acid (GABA) or opioid receptors. It provides sedation and, as some evidence suggests, anxiolysis, analgesia, and possible organ protection through its unique mechanism of action primarily within the locus coeruleus.18,19 An evaluation of electroencephalogram (EEG) sleep spindles in healthy, young volunteers found that the sedative effects of dexmedetomidine mimic S2 sleep in humans.20 The level of sedation can reproducibly be measured using EEG-based spectral entropy and is dose dependent.21 Labeling approved by the Food and Drug Administration (FDA) for dexmedetomidine limits its use to 24 hours of sedation at a maximum dose of 0.7 μg/kg/hr i.v., as studies have found conflicting data at higher doses and for longer durations.22,23 Therapeutic efficacy: PAD management Studies published in recent years have evaluated new indications for, higher doses of, and longer durations of dexmedetomidine, as well as its use in expanded critically ill patient populations. New studies examining dexmedetomidine have helped to define methodology that reflects clinical practice and advance clinical trial design of PAD management in the ICU. Wunsch et al.24 completed a retrospective cohort study of 58,391 patients who received i.v. infusion sedation in 174 ICUs. The authors concluded that dexmedetomidine use, as well as doses and durations in excess of those included in approved labeling, has increased in the clinical practice setting. The randomized trials (select studies summarized in Table 1), retrospective analyses, and case series discussed in this review further define the role of dexmedetomidine in the ICU setting. The studies are presented based on the patient populations studied and the interventions included. Table 1. Select Prospective, Randomized Trials of Dexmedetomidinea Ref. Patient Population Intervention Select Outcomes in Dexmedetomidine Group 25 Medical–surgical ICU requiring MV for at least 24 hr and up to 120 hr (n = 106) Dexmedetomidine 0.15–1.5 μg/kg/hr i.v. or lorazepam 1–10 mg/hr i.v.; rescue sedation with propofol; sedation or analgesia with fentanyl Reduction in coma-free days (p <0.001); more time in goal sedation per nurse (p = 0.04) and physician (p = 0.008); difference observed in length of MV or ICU stay (p = NS); neuropsychological testing or mortality at 28 days and 12-mo survival (p = NS) 27 Medical–surgical ICU within 96 hr of MV and requiring MV plus sedation for at least 3 additional days (n = 375) Dexmedetomidine 0.2–1.4 μg/kg/hr i.v. or midazolam 0.02–0.1 mg/kg/hr i.v.; rescue sedation with midazolam and fentanyl as needed Reduction in frequency of delirium (p <0.001); reduction in time to extubation (p = 0.01); increased incidence of bradycardia (p <0.001) 29b Medical–surgical ICU on invasive MV requiring light-to-moderate sedation (RASS score, 0 to −3) for at least 24 hr after randomization (n = 251 for midazolam, n = 249 for dexmedetomidine) Dexmedetomidine 0.2–1.4 μg/kg/hr i.v. or midazolam 0.03–0.2 mg/kg/hr i.v.; fentanyl boluses for pain; rescue sedation determined by clinician Higher RASS scores (p <0.001); reduction in median duration of MV (p <0.05); ICU LOS or hospital LOS (p = NS); more arousable, cooperative, and better able to communicate pain per nurse assessment (p <0.001); increased rates of hypotension and bradycardia (p <0.007) 29c Medical–surgical ICU on invasive MV requiring light-to-moderate sedation (RASS score, 0 to −3) for at least 24 hr after randomization (n = 247 for propofol, n = 251 for dexmedetomidine) Dexmedetomidine 0.2–1.4 μg/kg/hr i.v. or propofol 0.3–4.0 mg/kg/hr i.v.; fentanyl boluses for pain; rescue sedation determined by clinician Higher RASS scores (p <0.001); median duration of MV (p = NS); ICU LOS or hospital LOS (p = NS); more arousable, cooperative, and better able to communicate pain per nurse assessment (p <0.001); increased frequency of first-degree atrioventricular block (p = 0.04) 35 Age ≥ 60 years and undergoing pump cardiac surgery including CABG, valve surgery, or both (n = 299) Dexmedetomidine 0.1–0.7 μg/kg/hr i.v. or morphine 10–70 μg/kg/hr i.v.; rescue sedation with propofol; dexmedetomidine group allowed morphine as needed Reduced time to extubation (p = 0.036); reduced number of days in delirium (p = 0.031); increased rates of systolic hypotension and bradycardia (p = 0.006); overall amounts of rescue propofol and morphine in each group (p = NS) 37 Postoperative cardiac-valve repair and CPB requiring MV and sedation (n = 118) Dexmedetomidine 0.4 μg/kg i.v. after weaning from CPB and 0.2–0.7 μg/kg/hr i.v. maintenance; propofol 25–50 μg/kg/min i.v.; midazolam 0.5–2 mg/hr; rescue sedation with increased doses ICU LOS and hospital LOS or intubation time (p = NS); reduced overall opioid use (p <0.001); reduced opioid use when directly compared with propofol (p = NS) Ref. Patient Population Intervention Select Outcomes in Dexmedetomidine Group 25 Medical–surgical ICU requiring MV for at least 24 hr and up to 120 hr (n = 106) Dexmedetomidine 0.15–1.5 μg/kg/hr i.v. or lorazepam 1–10 mg/hr i.v.; rescue sedation with propofol; sedation or analgesia with fentanyl Reduction in coma-free days (p <0.001); more time in goal sedation per nurse (p = 0.04) and physician (p = 0.008); difference observed in length of MV or ICU stay (p = NS); neuropsychological testing or mortality at 28 days and 12-mo survival (p = NS) 27 Medical–surgical ICU within 96 hr of MV and requiring MV plus sedation for at least 3 additional days (n = 375) Dexmedetomidine 0.2–1.4 μg/kg/hr i.v. or midazolam 0.02–0.1 mg/kg/hr i.v.; rescue sedation with midazolam and fentanyl as needed Reduction in frequency of delirium (p <0.001); reduction in time to extubation (p = 0.01); increased incidence of bradycardia (p <0.001) 29b Medical–surgical ICU on invasive MV requiring light-to-moderate sedation (RASS score, 0 to −3) for at least 24 hr after randomization (n = 251 for midazolam, n = 249 for dexmedetomidine) Dexmedetomidine 0.2–1.4 μg/kg/hr i.v. or midazolam 0.03–0.2 mg/kg/hr i.v.; fentanyl boluses for pain; rescue sedation determined by clinician Higher RASS scores (p <0.001); reduction in median duration of MV (p <0.05); ICU LOS or hospital LOS (p = NS); more arousable, cooperative, and better able to communicate pain per nurse assessment (p <0.001); increased rates of hypotension and bradycardia (p <0.007) 29c Medical–surgical ICU on invasive MV requiring light-to-moderate sedation (RASS score, 0 to −3) for at least 24 hr after randomization (n = 247 for propofol, n = 251 for dexmedetomidine) Dexmedetomidine 0.2–1.4 μg/kg/hr i.v. or propofol 0.3–4.0 mg/kg/hr i.v.; fentanyl boluses for pain; rescue sedation determined by clinician Higher RASS scores (p <0.001); median duration of MV (p = NS); ICU LOS or hospital LOS (p = NS); more arousable, cooperative, and better able to communicate pain per nurse assessment (p <0.001); increased frequency of first-degree atrioventricular block (p = 0.04) 35 Age ≥ 60 years and undergoing pump cardiac surgery including CABG, valve surgery, or both (n = 299) Dexmedetomidine 0.1–0.7 μg/kg/hr i.v. or morphine 10–70 μg/kg/hr i.v.; rescue sedation with propofol; dexmedetomidine group allowed morphine as needed Reduced time to extubation (p = 0.036); reduced number of days in delirium (p = 0.031); increased rates of systolic hypotension and bradycardia (p = 0.006); overall amounts of rescue propofol and morphine in each group (p = NS) 37 Postoperative cardiac-valve repair and CPB requiring MV and sedation (n = 118) Dexmedetomidine 0.4 μg/kg i.v. after weaning from CPB and 0.2–0.7 μg/kg/hr i.v. maintenance; propofol 25–50 μg/kg/min i.v.; midazolam 0.5–2 mg/hr; rescue sedation with increased doses ICU LOS and hospital LOS or intubation time (p = NS); reduced overall opioid use (p <0.001); reduced opioid use when directly compared with propofol (p = NS) a All trials were prospective, randomized, double-blind, multicenter trials except for reference 37, which was a prospective, randomized, open-label trial. ICU = intensive care unit, MV = mechanical ventilation, RASS = Richmond Agitation and Sedation Scale, CABG = coronary artery bypass graft, CPB = cardiopulmonary bypass, LOS = length of stay, NS = nonsignificant. b MIDEX trial. c PRODEX trial. Open in new tab Table 1. Select Prospective, Randomized Trials of Dexmedetomidinea Ref. Patient Population Intervention Select Outcomes in Dexmedetomidine Group 25 Medical–surgical ICU requiring MV for at least 24 hr and up to 120 hr (n = 106) Dexmedetomidine 0.15–1.5 μg/kg/hr i.v. or lorazepam 1–10 mg/hr i.v.; rescue sedation with propofol; sedation or analgesia with fentanyl Reduction in coma-free days (p <0.001); more time in goal sedation per nurse (p = 0.04) and physician (p = 0.008); difference observed in length of MV or ICU stay (p = NS); neuropsychological testing or mortality at 28 days and 12-mo survival (p = NS) 27 Medical–surgical ICU within 96 hr of MV and requiring MV plus sedation for at least 3 additional days (n = 375) Dexmedetomidine 0.2–1.4 μg/kg/hr i.v. or midazolam 0.02–0.1 mg/kg/hr i.v.; rescue sedation with midazolam and fentanyl as needed Reduction in frequency of delirium (p <0.001); reduction in time to extubation (p = 0.01); increased incidence of bradycardia (p <0.001) 29b Medical–surgical ICU on invasive MV requiring light-to-moderate sedation (RASS score, 0 to −3) for at least 24 hr after randomization (n = 251 for midazolam, n = 249 for dexmedetomidine) Dexmedetomidine 0.2–1.4 μg/kg/hr i.v. or midazolam 0.03–0.2 mg/kg/hr i.v.; fentanyl boluses for pain; rescue sedation determined by clinician Higher RASS scores (p <0.001); reduction in median duration of MV (p <0.05); ICU LOS or hospital LOS (p = NS); more arousable, cooperative, and better able to communicate pain per nurse assessment (p <0.001); increased rates of hypotension and bradycardia (p <0.007) 29c Medical–surgical ICU on invasive MV requiring light-to-moderate sedation (RASS score, 0 to −3) for at least 24 hr after randomization (n = 247 for propofol, n = 251 for dexmedetomidine) Dexmedetomidine 0.2–1.4 μg/kg/hr i.v. or propofol 0.3–4.0 mg/kg/hr i.v.; fentanyl boluses for pain; rescue sedation determined by clinician Higher RASS scores (p <0.001); median duration of MV (p = NS); ICU LOS or hospital LOS (p = NS); more arousable, cooperative, and better able to communicate pain per nurse assessment (p <0.001); increased frequency of first-degree atrioventricular block (p = 0.04) 35 Age ≥ 60 years and undergoing pump cardiac surgery including CABG, valve surgery, or both (n = 299) Dexmedetomidine 0.1–0.7 μg/kg/hr i.v. or morphine 10–70 μg/kg/hr i.v.; rescue sedation with propofol; dexmedetomidine group allowed morphine as needed Reduced time to extubation (p = 0.036); reduced number of days in delirium (p = 0.031); increased rates of systolic hypotension and bradycardia (p = 0.006); overall amounts of rescue propofol and morphine in each group (p = NS) 37 Postoperative cardiac-valve repair and CPB requiring MV and sedation (n = 118) Dexmedetomidine 0.4 μg/kg i.v. after weaning from CPB and 0.2–0.7 μg/kg/hr i.v. maintenance; propofol 25–50 μg/kg/min i.v.; midazolam 0.5–2 mg/hr; rescue sedation with increased doses ICU LOS and hospital LOS or intubation time (p = NS); reduced overall opioid use (p <0.001); reduced opioid use when directly compared with propofol (p = NS) Ref. Patient Population Intervention Select Outcomes in Dexmedetomidine Group 25 Medical–surgical ICU requiring MV for at least 24 hr and up to 120 hr (n = 106) Dexmedetomidine 0.15–1.5 μg/kg/hr i.v. or lorazepam 1–10 mg/hr i.v.; rescue sedation with propofol; sedation or analgesia with fentanyl Reduction in coma-free days (p <0.001); more time in goal sedation per nurse (p = 0.04) and physician (p = 0.008); difference observed in length of MV or ICU stay (p = NS); neuropsychological testing or mortality at 28 days and 12-mo survival (p = NS) 27 Medical–surgical ICU within 96 hr of MV and requiring MV plus sedation for at least 3 additional days (n = 375) Dexmedetomidine 0.2–1.4 μg/kg/hr i.v. or midazolam 0.02–0.1 mg/kg/hr i.v.; rescue sedation with midazolam and fentanyl as needed Reduction in frequency of delirium (p <0.001); reduction in time to extubation (p = 0.01); increased incidence of bradycardia (p <0.001) 29b Medical–surgical ICU on invasive MV requiring light-to-moderate sedation (RASS score, 0 to −3) for at least 24 hr after randomization (n = 251 for midazolam, n = 249 for dexmedetomidine) Dexmedetomidine 0.2–1.4 μg/kg/hr i.v. or midazolam 0.03–0.2 mg/kg/hr i.v.; fentanyl boluses for pain; rescue sedation determined by clinician Higher RASS scores (p <0.001); reduction in median duration of MV (p <0.05); ICU LOS or hospital LOS (p = NS); more arousable, cooperative, and better able to communicate pain per nurse assessment (p <0.001); increased rates of hypotension and bradycardia (p <0.007) 29c Medical–surgical ICU on invasive MV requiring light-to-moderate sedation (RASS score, 0 to −3) for at least 24 hr after randomization (n = 247 for propofol, n = 251 for dexmedetomidine) Dexmedetomidine 0.2–1.4 μg/kg/hr i.v. or propofol 0.3–4.0 mg/kg/hr i.v.; fentanyl boluses for pain; rescue sedation determined by clinician Higher RASS scores (p <0.001); median duration of MV (p = NS); ICU LOS or hospital LOS (p = NS); more arousable, cooperative, and better able to communicate pain per nurse assessment (p <0.001); increased frequency of first-degree atrioventricular block (p = 0.04) 35 Age ≥ 60 years and undergoing pump cardiac surgery including CABG, valve surgery, or both (n = 299) Dexmedetomidine 0.1–0.7 μg/kg/hr i.v. or morphine 10–70 μg/kg/hr i.v.; rescue sedation with propofol; dexmedetomidine group allowed morphine as needed Reduced time to extubation (p = 0.036); reduced number of days in delirium (p = 0.031); increased rates of systolic hypotension and bradycardia (p = 0.006); overall amounts of rescue propofol and morphine in each group (p = NS) 37 Postoperative cardiac-valve repair and CPB requiring MV and sedation (n = 118) Dexmedetomidine 0.4 μg/kg i.v. after weaning from CPB and 0.2–0.7 μg/kg/hr i.v. maintenance; propofol 25–50 μg/kg/min i.v.; midazolam 0.5–2 mg/hr; rescue sedation with increased doses ICU LOS and hospital LOS or intubation time (p = NS); reduced overall opioid use (p <0.001); reduced opioid use when directly compared with propofol (p = NS) a All trials were prospective, randomized, double-blind, multicenter trials except for reference 37, which was a prospective, randomized, open-label trial. ICU = intensive care unit, MV = mechanical ventilation, RASS = Richmond Agitation and Sedation Scale, CABG = coronary artery bypass graft, CPB = cardiopulmonary bypass, LOS = length of stay, NS = nonsignificant. b MIDEX trial. c PRODEX trial. Open in new tab Mixed medical–surgical ICUs Dexmedetomidine versus GABA agonists The MENDS randomized trial compared dexmedetomidine and lorazepam infusions for the outcomes of delirium- and coma-free days and percentage of days spent within one point of the sedation goal.25 Patients randomized to the dexmedetomidine group had over twice as many delirium- and coma-free days when compared with the lorazepam group. Coma was defined as a Richmond Agitation and Sedation Scale (RASS) score of −4 to −5. When looking specifically at coma-free days, the dexmedetomidine group had significantly more days than the lorazepam group. When assessing delirium-free days alone, no significant difference was found between therapies. Dexmedetomidine-treated patients were more frequently found to be within one point of their individualized goal RASS score, as reported by nurses and physicians, and lorazepam-treated patients experienced more oversedation. Concomitant analgesic use was higher in the dexmedetomidine group, an observation that the study authors attributed to differences in levels of sedation. In a subgroup analysis of patients with sepsis, therapy with dexmedetomidine was shown to decrease days with brain dysfunction (delirium and coma) and mechanical ventilation and decrease mortality.26 The SEDCOM randomized trial compared dexmedetomidine infusion with midazolam infusion, either with optional loading doses, and assessed the efficacy and safety of prolonged sedation.27 This study targeted a RASS score of −2 to +1, with allowance of open-label bolus doses of fentanyl for analgesia, of midazolam for additional sedation, and of haloperidol for agitation or delirium as defined by the Confusion Assessment Method for the Intensive Care Unit (CAM-ICU) algorithm. Evaluation of the primary endpoint showed no difference in time within the target RASS score range, though a large percentage of each intervention required study drug interruption to maintain the target RASS score, and there was no disparity in the percentage of successful daily sedation holidays between groups. The frequency of delirium at baseline for both groups was similar; however, the daily incidence of delirium after study drug initiation decreased with dexmedetomidine therapy and increased with midazolam therapy. For patients who did not have delirium and agitation (as defined by the CAM-ICU) at the initiation of the study drug, a higher percentage in the midazolam group went on to develop delirium. The dexmedetomidine group had more delirium-free days with a decreased number of days on the study drug. Open-label midazolam use was higher in the dexmedetomidine group, though the total rescue midazolam dose used was similar between groups. There was also a trend toward a higher percentage of dexmedetomidine-treated patients requiring fentanyl, though the total dose administered was comparable. Ruokonen et al.28 conducted a randomized trial to compare dexmedetomidine with institutional-specific standard care (i.e., midazolam boluses, midazolam infusions, or propofol infusions) to assess ability to maintain target sedation and impact on ICU length of stay. Once randomized, patients either continued their current standard care therapy or received dexmedetomidine. Both treatments included daily sedation interruptions, and sedation was assessed with the RASS algorithm, with target scores dependent on study-center-specific goals. Due to statistical limitations, noninferiority of dexmedetomidine could not be proven, though primary endpoints of time within target sedation range and length of ICU stay were analogous between the study groups. Dexmedetomidine tended to be less effective than standard care when trying to achieve deep sedation (RASS score of −4) than when the goal sedation level was lighter. Secondary outcomes showed a higher rate of delirium in the dexmedetomidine group when combining adverse events and CAM-ICU results. Patients in the dexmedetomidine group did, however, undergo more assessments for delirium than did patients in the standard care group; when proportionalized to CAM-ICU findings, the frequency of delirium was similar between groups. The PRODEX and MIDEX randomized trials compared dexmedetomidine with propofol and midazolam, respectively.29 Patients were randomized to either continue their current standard of care (i.e., propofol 0.3–4.0 mg/kg/hr i.v. or midazolam 0.03–0.2 mg/kg/hr i.v.) or switch sedative therapy to dexmedetomidine 0.2–1.4 μg/kg/hr i.v. to assess the drugs’ ability to maintain sedation and impact on mechanical ventilation and patients’ ability to interact with nursing staff. These trials were sufficiently powered and showed the noninferiority of dexmedetomidine in achieving mild-to-moderate sedation, defined as an RASS score of 0 to −3. The duration of mechanical ventilation was significantly shorter with dexmedetomidine versus midazolam, with patients being more arousable and communicative per nursing-conducted visual analog scale. Significantly fewer patients treated with midazolam therapy experienced hypotension (p < 0.007) and bradycardia (p < 0.001) compared with the dexmedetomidine group, though no significant difference in these adverse events was found between the dexmedetomidine and propofol groups. The duration of mechanical ventilation was similar for propofol- and dexmedetomidine-treated patients. Compared with dexmedetomidine, propofol was associated with higher rates of adverse neurocognitive events (i.e., agitation, anxiety, delirium) (p = 0.008); the frequency of these adverse events was similar between midazolam and dexmedetomidine groups. Dexmedetomidine versus haloperidol Reade et al.30 conducted a randomized pilot study to evaluate the ability of dexmedetomidine versus continuously infused haloperidol to facilitate extubation in patients with hyperactive delirium who would not tolerate extubation. Delirium was diagnosed utilizing the Intensive Care Delirium Screening Checklist, with fewer than 50% of all patients having a score of ≥4 (delirium present). Assessment of the primary endpoint revealed that patients in the dexmedetomidine group were extubated significantly sooner than those treated with haloperidol (p = 0.016). Assessment of secondary endpoints found that the dexmedetomidine-treated patients had a significantly shorter total length of ICU stay (p = 0.0093) and were discharged significantly earlier (p = 0.0039) than the haloperidol group. A subgroup analysis revealed an increased duration of restraint use and a higher rate of propofol use for supplemental sedation in the haloperidol group. Low- versus high-dose dexmedetomidine In a retrospective study, Jones et al.23 assessed the efficacy of sedation and the frequency of adverse events with low-dose versus high-dose dexmedetomidine (≤0.7 μg/kg/hr i.v. versus >0.7 μg/kg/hr i.v.). Efficacy of sedation in this study was defined as the percentage of RASS scores at goal (−1 to +1). The adverse events assessed were hypotension (mean arterial pressure [MAP] of <60 mm Hg) and bradycardia (heart rate of <50 beats/min). The demographics of the treatment groups were similar, with approximately 61% of all patients being treated in the medical ICU. The mean maximum doses in the low- and high-dose groups were 0.51 and 1.2 μg/kg/hr i.v., respectively. The low-dose group had a significantly higher percentage of RASS scores at goal compared with the high-dose group (p = 0.03) with no significant difference in oversedation. Significantly more patients in the high-dose group experienced undersedation compared with the low-dose group (p = 0.001), possibly denoting an inability of dexmedetomidine to sedate agitated patients with high sedation or analgesic requirements. The frequencies of hypotension and bradycardia were similar between groups. Dosage protocol Gerlach et al.31 validated the use of a dexmedetomidine dosage protocol in 25 patients and 19 matched, historical controls in mixed medical–surgical ICUs. The focus of this protocol was to reduce hypotensive and bradycardic adverse events associated with the use of this sedative. The protocol was designed for use in hemodynamically stable patients (heart rate of >70 beats/min and MAP of >70 mm Hg or systolic blood pressure [SBP] of >100 mm Hg). No loading dose was given, and the initial continuous infusion rate was based on the RASS score. At most, dexmedetomidine dosage was adjusted every 30 minutes with a maximum dosage of 0.7 μg/kg/hr i.v. The dosage was decreased if SBP dropped to less than 100 mm Hg or MAP dropped to less than 50 mm Hg, and therapy was stopped if the patient’s heart rate decreased to less than 50 beats/min. There were no significant differences noted in length of ICU stay, duration of mechanical ventilation, and initial or maximum dosage of dexmedetomidine. A significant difference was noted in the mean ± S.D. number of dosage adjustments (4.8 ± 3.8 in the protocol group versus 7.8 ± 3.9 in the control group, p = 0.014), frequency of hypotension (16% in the protocol group versus 68.4% in the control group, p = 0.0006), and total number of adverse drug reactions (28% in the protocol group versus 78.9% in the control group, p = 0.0019). Based on the results of this study the dexmedetomidine dosage should be adjusted no more often than every 30 minutes, and the minimization of bolus doses may be an appropriate way to avoid the known adverse effects of this agent. Bridge to extubation Three studies assessed adjunctive dexmedetomidine for mechanically ventilated patients receiving baseline pain and agitation management.32,–34 MacLaren et al.32 examined the changes in concomitant therapy requirements and adverse events associated with the addition of dexmedetomidine. This study found that adjunctive dexmedetomidine resulted in decreased sedative requirements but did not affect analgesic needs. However, dexmedetomidine was associated with enhanced agitation, severe pain, and hemodynamic compromise. Two other analyses evaluated the impact of adjunctive dexmedetomidine in patients who were difficult to wean from mechanical ventilation due to agitation.33,34 Shehabi et al.33 found successful extubation in 73.3% of patients receiving a median dexmedetomidine dosage of 0.7 μg/ kg/hr for 62 hours. Arpino et al.34 demonstrated that 65% of patients achieved extubation after an infusion of dexmedetomidine 0.53 μg/kg/hr for 29 hours. The authors of both of these studies concluded that dexmedetomidine is a viable adjunctive option to aid in extubation for patients experiencing agitation with their current pain and agitation regimen. Summary The trials reviewed thus far have limitations that must be considered when evaluating their clinical applicability. Median sedative doses of two GABA-agonist groups compared with dexmedetomidine were 3 mg/hr of lorazepam and 0.056 mg/ kg/hr of midazolam in the MENDS and SEDCOM trials, respectively.25,27 The median weight of patients in the midazolam group in the SEDCOM analysis was 87.8 kg, corresponding to a median midazolam dose of 4.9 mg/hr.27 The recently published MIDEX trial saw a higher median midazolam dosage (0.062 mg/kg/ hr i.v.) used.29 In order to maintain the randomization and blinding of the trials, incremental dosage adjustments were predetermined, and sedative dosages were adjusted without bias for study drug pharmacokinetics. Blind dosage adjustments are likely the reason the median dosages of sedatives were higher than commonly used in clinical practice. This could explain the deeper sedation, longer durations of sedation and mechanical ventilation, and increased prevalence of delirium experienced in those patient groups.27 The benefits of using intermittent bolus therapy with benzodiazepines versus continuous infusions of benzodiazepines versus dexmedetomidine have not been studied. The principle of primary pain management was also not apparent in the trial designs, as many studies relied on opioid bolus therapy to aid in pain and agitation management instead of using continuous opioid infusions.25,27–29 The studies described above found that dexmedetomidine is effective for achieving mild-to-moderate sedation using a dosage-adjustment protocol; however, additional agents (e.g., opioids, other sedatives) may be needed for patients with deeper sedation goals.23,25,27,31 The etiology of increased opioid consumption in dexmedetomidine patients in the MENDS trial is unclear but may be linked to lighter sedation and patients’ increased ability to communicate pain. A secondary reason for increased opioid consumption could be the high percentage of patients with sepsis or acute respiratory distress syndrome (ARDS) who were receiving lung-protective mechanical ventilation, which may increase the need for respiratory-suppressive medications.27 Cardiac surgery Dexmedetomidine versus morphine The DEXCOM randomized trial compared the prevalence of delirium with dexmedetomidine- versus morphine-based sedation in patients undergoing cardiac surgery.35 The frequency of delirium was assessed daily for the first five days after surgery using the CAM-ICU and taking into account nurse-documented behavior within the previous 24 hours. This trial illustrated a trend toward a lower rate of delirium in the dexmedetomidine group, with a significantly shorter duration of delirium (p = 0.0317). A subgroup analysis found a significantly lower frequency of delirium in patients requiring intraaortic balloon pump therapy who were treated with dexmedetomidine versus morphine (p = 0.001). The majority of patients who developed delirium did so within three days after surgery, with no patients developing delirium after four days. The study design did allow for open-label propofol and morphine use to achieve a predefined goal sedation score of 2–4 on the Motor Activity Assessment Scale. Propofol and morphine bolus use was similar between groups. The numbers of patients extubated within 12 hours of surgery were comparable; patients in the dexmedetomidine group requiring more than 12 hours of mechanical ventilation had a shorter time to extubation (p = 0.047) versus those treated with morphine. In a smaller open-label study, Aziz et al.36 randomized 28 adult, mechanically ventilated patients undergoing open-heart surgery to receive continuous infusions of dexmedetomidine or morphine to assess the efficacy of analgesia and sedation management. Sedative dosage was adjusted to a goal sedation score of 2–4 using the Modified Ramsay Sedation Scale, and analgesia was assessed using the Numeric Pain Intensity Scale on which 0 equals no pain and 10 equals severe pain. The mean dosages of dexmedetomidine and morphine used were 1.2 and 13.2 μg/kg/hr i.v., respectively. There were no significant differences in scores on either scale between the dexmedetomidine and morphine groups, though patients in the dexmedetomidine group did have lower mean ± S.D. heart rates (86 ± 2.7 beats/min versus 92 ± 1.5 beats/min, p = 0.028). Dexmedetomidine showed no difference in safety and efficacy compared with continuous morphine therapy. Dexmedetomidine versus GABA agonists Maldonado et al.37 conducted a randomized trial investigating the effects of three sedatives on the development of delirium in patients undergoing cardiac-valve procedures. All patients received standardized intraoperative anesthesia followed by randomization to a dexmedetomidine bolus dose followed by continuous dexmedetomidine infusion, propofol infusion, or midazolam infusion. All patients were allowed the same rescue medications at the same doses. Sedation was assessed with the Ramsay Sedation Scale, using a target score of 3 while intubated and a score of 2 once extubated. Delirium was assessed once daily, evaluating current symptoms and those occurring over the past 24 hours, and was diagnosed using criteria from the Diagnostic and Statistical Manual of Mental Disorders. Haloperidol ≤5 mg given up to every two hours as needed and lorazepam ≤1 mg given every six hours as needed were available for patients diagnosed with delirium. Delirium occurred 15 times more often in the propofol and midazolam groups than in the dexmedetomidine group in the per-protocol analysis (p < 0.001). In the intent-to-treat analysis, the rate of delirium was also significantly lower in the dexmedetomidine group (p < 0.001), though this may not be clinically relevant since no significant differences in length of stay or duration of intubation were observed. Use of rescue medications was similar throughout each group with the exception of fentanyl use. The dexmedetomidine and propofol groups received similar amounts of fentanyl, while the midazolam group required considerably higher doses. Patients developing delirium were associated with longer ICU stays and increased overall hospital costs. In a prospective, descriptive study of clinical practice, Anger et al.38 compared clinical outcomes in 56 matched surgical candidates receiving dexmedetomidine or propofol. All mechanically ventilated patients 18 years of age or older admitted to the cardiac surgery ICU postoperatively who were receiving propofol and met inclusion criteria were matched 1:1 by procedure within 48 hours of each dexmedetomidine enrollment. Primary endpoints evaluated included length of ICU stay and duration of mechanical ventilation. There were no significant baseline demographic differences between the two treatment groups. The mean ± S.D. infusion rates for dexmedetomidine (0.6 ± 0.1 μg/kg/hr i.v.) and propofol (1.5 ± 0.6 mg/kg/hr i.v.) were within the FDA-approved dosing range. There were no significant differences between the dexmedetomidine and propofol groups in mean ± S.D. length of ICU stay (58.67 ± 32.61 hours versus 61 ± 33.1 hours, respectively) and duration of mechanical ventilation (16.21 ± 6.05 hours versus 13.97 ± 4.62 hours, respectively). The rates of hypotension and morphine and nonsteroidal antiinflammatory use were higher in the dexmedetomidine group versus propofol-treated patients (p ≤ 0.05). Barletta et al.39 conducted a retrospective, cohort study of 100 patients to determine the impact of dexmedetomidine on analgesic requirements after coronary artery bypass graft surgery or valvular surgery. Secondary outcomes assessed included quality of sedation, length of mechanical ventilation, adverse drug events, and cost associated with therapy. Patients were matched based on type of surgical procedure and left-ventricular ejection fraction. A significant decrease in the amount of opioid required, expressed as morphine equivalents (MEs), was observed during dexmedetomidine infusion (median, 0 ME; range, 0–10 mg MEs) versus propofol infusion (median, 4 mg MEs; range, 0–33 mg MEs) (p < 0.001). This effect was only seen during the time of study drug infusion and did not continue for the duration of the ICU stay. Length of mechanical ventilation did not significantly differ between the two groups. The occurrence of adverse events, primarily hypotension, was similar between groups. Summary The frequency of delirium after coronary artery bypass surgery ranges between 37% and 52%, with sedative agents possible increasing that risk.40,41 The focus of these trials in cardiac surgery was both the frequency and duration of delirium as well as concomitant opioid use. With the high baseline frequency and our relative lack of understanding regarding pathogenesis and appropriate treatment of delirium, the 3% frequency of delirium reported by Maldonado et al.37 may be attributed to longer dexmedetomidine infusions, masking agitation surrounding extubation. This trend was also observed in the DEXCOM trial, as time to extubation was significantly shorter with dexmedetomidine yet the duration of study drug infusion was comparable. Multiple studies reported similar pain control with dexmedetomidine versus active-comparator groups, concluding that dexmedetomidine has equianalgesic properties.35,36 These results conflict with the study conducted by Anger et al.,38 which showed a statistically significant increase in the need for both opioid and nonopioid pain management. Use in other patient populations Dexmedetomidine versus GABA agonists The ANIST study was designed to establish the cognitive effects of dexmedetomidine versus propofol on awake, intubated patients with and without brain injury.42 This four-phase randomized study used monotherapy with fentanyl, therapy with either dexmedetomidine or propofol and fentanyl, a washout period with fentanyl monotherapy, and fentanyl plus a study drug not formerly used. During the monotherapy phase, fentanyl 0–4 μg/kg/hr i.v. was given for analgesic purposes only to achieve a pain rating of ≤3 (on a Likert scale of 0–10). During the study drug phases, fentanyl dosages were decreased to 1 μg/kg/hr i.v. and adjusted to control pain while dexmedetomidine and propofol dosages of 0.2–0.7 and 20–70 μg/ kg/hr i.v., respectively, were adjusted to produce adequate sedation. The independently evaluated Johns Hopkins Adapted Cognitive Exam (ACE) was used to assess cognition through orientation, language, registration, attention and calculation, and recall. The CAM-ICU was utilized to assess delirium, and sedation was measured using the RASS algorithm (target sedation score of 0–1). There were no differences in concomitant fentanyl use between study drug phases, and both study drug median dosages fell within the predefined dosage ranges. All patients were sedated and maintained at target RASS scores with similar onset of the goal RASS score. Patients receiving propofol therapy had a decrease in ACE scores, while the ACE scores of patients receiving dexmedetomidine increased. The decrease in ACE scores with propofol was independent of baseline ACE scores. Improvement of ACE scores with dexmedetomidine was correlated with cognitive dysfunction before drug initiation. This study found that propofol had a negative effect on cognition while demonstrating the cognition-sparing or cognition-improving effects of dexmedetomidine. Devabhakthuni et al.22 retrospectively reviewed 127 adult mechanically ventilated trauma patients who received propofol, standard-dose dexmedetomidine (≤0.7 μg/kg/hr i.v.), and high-dose dexmedetomidine >0.7 μg/kg/hr i.v. Primary outcomes included significant changes in blood pressure (hypotension, SBP of <80 mm Hg and diastolic blood pressure [DBP] of <50 mm Hg; hypertension, SBP of >180 mm Hg and DBP of >100 mm Hg) and heart rate (bradycardia, heart rate of <40 beats/min; tachycardia, heart rate of >120 beats/min) or a change of >30% from baseline in blood pressure or heart rate. Significantly more patients in the high-dose group developed hypotension than in the standard-dose and propofol groups. The frequencies of hypertension, bradycardia, and tachycardia were similar among the three groups. Overall mortality rates were similar among the groups (10% in the high-dose group, 3% in the standard-dose group, and 12% in the propofol group), lengths of hospital and ICU stay were significantly longer in both dexmedetomidine groups compared with the propofol group (p <0.001 and p = 0.004, respectively), and mechanical ventilation duration was significantly longer with the high-dose dexmedetomidine group compared with the other two groups (14 days versus 9 days with standard-dose dexmedetomidine versus 7 days with propofol; p = 0.008). Concomitant analgesic use was similar among the groups. Patients in the high-dose group had increased requirements for sedation with midazolam (36% versus 17% with standard-dose dexmedetomidine versus 8% with propofol; p = 0.004), and patients in the high-dose group needed more haloperidol for agitation and delirium (50% versus 26% with standard-dose dexmedetomidine versus 24% with propofol; p = 0.02). In a prospective, randomized controlled study, Esmaoglu et al.43 compared dexmedetomidine with midazolam in women with eclampsia requiring termination of pregnancy by caesarean delivery. Primary endpoints included effectiveness of therapy, hemodynamic characteristics, and time in the ICU. Dexmedetomidine was associated with a significant decrease in heart rate and MAP compared with midazolam (p < 0.05). Also, patients treated with dexmedetomidine had a significantly decreased need for nitroglycerin infusions for control of eclampsia compared with midazolam-treated patients (45% versus midazolam 90%, p < 0.05). There was no significant difference in the duration of sedation, time in the ICU, or time spent in the ICU after sedation was discontinued. Neurosurgery and trauma Aryan et al.44 published a retrospective, descriptive review of 39 neurosurgical patients who required ICU care to gather information on dosage, sedative effects, and adverse effects of dexmedetomidine in this patient population. Patient diagnoses included head trauma, arteriovenous malformations, aneurysm or subarachnoid hemorrhage, and elective procedures. All patients included in this study received adequate sedation with or without a loading dose followed by a continuous infusion of dexmedetomidine. The most common adverse effect reported was agitation (n = 10, 26%), measured by the University of California San Diego agitation scale. Intracranial pressure and corresponding cerebral perfusion pressure were not adversely affected by dexmedetomidine, despite episodes of hypotension, elevated blood pressure, and bradycardia, particularly with bolus doses. Hypertension requiring cessation of dexmedetomidine was experienced by 2 patients. The authors concluded that loading doses should be avoided and higher doses may be needed to achieve the desired sedation level in neurosurgical ICU patients. Summary The ANIST trial, similar to trials involving mixed medical–surgical populations,25,27,29 allowed for blind dosage adjustments of sedative medications.42 In contrast with the pharmacokinetics of propofol, more than two hours were needed for both groups to reach and maintain the goal RASS score. The propofol group required more fentanyl than did the dexmedetomidine group, likely due to suboptimal agitation management. High-dose dexmedetomidine in trauma patients is likely indicative of an inability of dexmedetomidine to display adequate agitation management in that patient population and should signal the clinician to explore other avenues of therapy.22 Future directions Patient-controlled sedation Chlan et al. 45 conducted a descriptive pilot study assessing the safety, adequacy, and satisfaction of patient-controlled sedation (PCS) with dexmedetomidine for ≤24 hours of therapy. A total of 17 mechanically ventilated patients were given a 0.5-μg/kg i.v. bolus dose of dexmedetomidine followed by a 0.2-μg/kg/hr i.v. continuous basal infusion of dexmedetomidine. Additional patient-triggered boluses of 0.25 μg/kg i.v. were available every 20 minutes if sedation was deemed inadequate by the patient, and basal infusion rates were adjusted based on bolus use. Four patients required discontinuation of therapy due to adverse events (hypotension or bradycardia), and 6 patients remained on the PCS protocol for 24 hours. Basal infusion rates were steadily increased throughout the duration of the protocol, with 13 of the 17 patients requiring additional sedation or analgesia. Overall, patients and nurses reported favorable results with the PCS protocol, with sedation adequacy ranging from 77% to 100% at each 4-hour assessment interval. Noninvasive ventilation Akada et al.46 investigated the role of dexmedetomidine in patients experiencing difficulty with noninvasive ventilation (NIV) due to agitation. The 10 patients included in this study required NIV due to sudden-onset dyspnea, with 6 patients experiencing postoperative respiratory failure. Dexmedetomidine was initiated with or without a 3-μg/kg i.v. loading dose followed by a continuous infusion of 0.2–0.7 μg/kg/hr i.v., with a goal Ramsay Sedation Scale score of 2–3 and an RASS score of 0 to −2. All patients had a proper response to the sedative, achieving a mean ± S.D. Ramsay Sedation Scale score of 2.94 ± 0.94 and RASS score of −1.23 ± 1.30. Heart rate and arterial blood pressure decreased with therapy. No incidents of bradycardia or excessively low blood pressure were reported. Measures of respiratory status improved with NIV facilitated by sedative therapy. No patients required escalation of respiratory support with invasive ventilation. Alcohol withdrawal Central α2-receptor agonism has been shown to reduce the adrenergic hyperactivity associated with cessation of prolonged alcohol intake.47 Accordingly, dexmedetomidine has been evaluated as an adjunct to standard treatment for alcohol withdrawal syndrome and alcohol withdrawal delirium. Two published case reports detailed the use of dexmedetomidine in patients who did not achieve symptom control with benzodiazepines with or without haloperidol.48,49 Dexmedetomidine use was associated with a decrease in standard treatment doses and possibly avoidance of intubation for airway protection. Although dexmedetomidine appears effective as an adjunctive treatment option for alcohol withdrawal, it does not offer protection against seizures, and further studies are needed to determine its place in therapy. Safety profile Adverse effects associated with dexmedetomidine were similar among the studies examined herein. The most common adverse effects with dexmedetomidine were bradycardia and hypotension, in some cases severe enough to warrant the use of vasoactive support. Other adverse cardiovascular effects reported, owing primarily to the initial α2-receptor effects on systemic circulation followed by central α2-receptor agonism, included tachycardia, hypertension with the need for intervention, a cardiovascular Sequential Organ Failure Assessment score of >1, an increase in arrhythmias, and cardiac arrest.25,27–29,35,36 Case reports of dexmedetomidine-associated bradycardia progressing to pulseless electrical activity and refractory cardiogenic shock also appear in the medical literature.50,51 It is important to note that hemodynamic instability was also reported in patients receiving morphine, lorazepam, midazolam, and propofol. Adverse noncardiovascular events reported included a significant increase in the rates of hyperglycemia and infection (p = 0.02).27 Self-extubation was monitored as a safety endpoint when comparing dexmedetomidine with lorazepam, but the difference between groups was not significant (8% versus 4%), and nearly all patients required rein-tubation to maintain their airways.25 Case reports of severe rash requiring discontinuation of therapy and postoperative drug-induced fever have also been reported.52,53 Role of dexmedetomidine in adult ICU patients Best practices for PAD management in critically ill patients have been linked to improved patient outcomes. Time spent at goal sedation, particularly lighter sedation, is associated with decreased mechanical ventilation time, decreases in hospital and ICU lengths of stay, and a decreased frequency of delirium.5,7,8,35 Dosage-reduction techniques and dose-limiting strategies allow the clinician better control of patient sedation and aid in the daily assessment of therapy.54 Delirium has been shown to be an independent risk factor for increasing mortality, and avoiding independent risk factors, such as lorazepam use, may positively affect clinical outcomes after patients receive sedation and mechanical ventilation.41,55 After proper patient assessment and optimization of pain management, dexmedetomidine may be effective in achieving and maintaining patient-specific sedation goals, especially in patients requiring lighter sedation. Therapy free of coma, defined as deep sedation or a RASS score of −4 to −5, was more common with dexmedetomidine versus lorazepam.25 Other sedative agents have shown the ability to attain and preserve deeper sedation than dexmedetomidine with less need for concomitant sedatives or analgesics.27,–29 Dexmedetomidine imparts light sedation while retaining and possibly improving cognitive function in patients at high risk of adverse mental health outcomes.42,56 In achieving the desired level of sedation, bolus therapy and rapid dosage adjustment may cause more adverse drug events and should be avoided.32,44 Recent studies have been designed without the use of a bolus reflecting this strategy.25,27,29 Although dexmedetomidine has been shown effective in reducing the duration of mechanical ventilation, reductions in ICU and hospital lengths of stay have not been seen.27,29 The duration of mechanical ventilation has been shown to be positively affected when using light sedation goals. Dexmedetomidine has demonstrated its capacity to decrease time requirements of mechanical ventilation as well as aid in extubation after prolonged infusions of high-dose sedatives.28,32 The role as first-line therapy has not been established, though it appears effective as an adjunct for difficult-to-wean, agitated patients.33,34 Specific patient populations, such as those displaying ventilator dyssynchrony or with ARDS, may not benefit from dexmedetomidine therapy, as it does not possess the respiratory-suppressing characteristics of other sedatives and analgesics. Alternatively, dexmedetomidine may facilitate noninvasive ventilation strategies in patients requiring ventilatory support while experiencing agitation, avoiding the need for intubation.46 Delirium in the ICU is often associated with the sedative agent selected and the level of sedation required.41 This change in mental status may be only partly attributable to drug therapy. Evidence suggests that dexmedetomidine is associated with a decrease in delirium incidence as well as a shortened duration of delirium when compared with benzodiazepine therapy.25,27 Other studies found no difference in outcomes when delirium was an endpoint. When evaluating dexmedetomidine in cardiac surgery patients, standard therapy was linked to a higher rate of delirium, with a trend toward increased duration of delirium.35,37 This tendency may reflect the multitude of metabolic changes and effects of organ dysfunction commonly observed in the medical–surgical ICU population. Previous data have suggested that dexmedetomidine has analgesic properties and displays opioid-sparing tendencies when used as a sedative agent.18 Data from recent studies remain in opposition on concomitant analgesic use.25,36,39 It appears that opioid requirements increase with lighter levels of sedation, indicating that patients may be better able to communicate discomfort and the need for more pain control. Also, patients receiving lighter sedation may be less synchronous with ventilator settings and may need opioids to help decrease their respiratory drive to better harmonize with mechanical ventilation. Recent data also suggest a role of dexmedetomidine in intractable pain for palliative care, but further investigation into this use is warranted.57,58 The role of dexmedetomidine, as influenced by the recent literature and new guidelines, appears to be for patients requiring light sedation as an adjunct to baseline PAD management.59 Due to the adverse events associated with rapid dosage adjustment and bolus therapy, dexmedetomidine may not be the best agent for treating acute agitation.31 Doses and durations of therapy exceeding those approved by FDA appear relatively safe, though clinical efficacy has been inconsistent and warrants further investigation.23 Conclusion In medical–surgical ICUs, dexmedetomidine may be a viable nonbenzodiazepine option for patients with a need for light sedation. In cardiac surgery patients, dexmedetomidine appears to offer no advantage over propofol as the initial sedative. The role of dexmedetomidine in unique patient populations such as neurosurgical, trauma, and obstetrics is yet to be established. Footnotes The authors have declared no potential conflicts of interest. References 1 Szumita PM Baroletti SA Anger KE et al. Sedation and analgesia in the intensive care unit: evaluating the role of dexmedetomidine . Am J Health-Syst Pharm . 2007 ; 64 : 37 – 44 . Google Scholar Crossref Search ADS PubMed WorldCat 2 Sessler CN Varney K . Patient-focused sedation and analgesia in the ICU . Chest . 2008 ; 133 : 552 – 65 . Google Scholar Crossref Search ADS PubMed WorldCat 3 Morandi A Brummel N Ely EW . Sedation, delirium and mechanical ventilation: the ‘ABCDE’ approach . Curr Opin Crit Care . 2011 ; 17 : 43 – 4 . Google Scholar Crossref Search ADS PubMed WorldCat 4 Treggiari MM Romand JA Yanez ND et al. Randomized trial of light versus deep sedation on mental health after critical illness . Crit Care Med . 2009 ; 37 : 2527 – 34 . 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TI - Role of dexmedetomidine in adults in the intensive care unit: An update
JF - American Journal of Health-System Pharmacy
DO - 10.2146/ajhp120211
DA - 2013-05-01
UR - https://www.deepdyve.com/lp/oxford-university-press/role-of-dexmedetomidine-in-adults-in-the-intensive-care-unit-an-update-3PLPVK84AD
SP - 767
VL - 70
IS - 9
DP - DeepDyve
ER -