Surgical and Medical Utility of Dexmedetomidine- Induced Sedation: A Case-Based Examination

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1 BROUGHT TO YOU BY This Special Report is supported by MARCH 2010 DISCLAIMER: This monograph is designed to be a summary of information. While it is detailed, it is not an exhaustive clinical review. McMahon Publishing, Hospira, and the author neither affirm nor deny the accuracy of the information contained herein. No liability will be assumed for the use of this educational review, and the absen ce of typographical errors is not guaranteed. Readers are strongly urged to consult any relevant primary literature. Copyright 2010, McMahon Publishing, 545 West 45th Street, New York, NY Printed in the USA. All rights reserved, including the right of reproduction, in whole or in part, in any form. Surgical and Medical Utility of Dexmedetomidine- Induced Sedation: A Case-Based Examination Fred E. Shapiro, DO Assistant Professor of Anaesthesia Harvard Medical School Department of Anesthesiology, Critical Care and Pain Medicine Beth Israel Deaconess Medical Center Boston, Massachusetts Charles Scott Brudney, MB, BCh, FRCA Medical Director SICU Department of Veterans Affairs Medical Center Assistant Professor Duke University Medical Center Durham, North Carolina Michael A. E. Ramsay, MD, FRCA Chairman, Department of Anesthesiology and Pain Management Baylor University Medical Center Dallas, Texas Trevor S. Sutton, MD, MBA Cardiac Anesthesiologist Vassar Brothers Medical Center North American Partners in Anesthesia Poughkeepsie, New York Distributed by McMahon Publishing Introduction The management of patient comfort in the perioperative and intensive care settings involves the use of numerous medications working in harmony to achieve a desired level of consciousness and analgesia. The goals of sedation and pain management are to keep patients comfortable, relieve pain, and reduce the anxiety that often accompanies medical/surgical procedures; protect the agitated patient from self-harm or from interfering with critical medical treatments and status assessments. 1-4 The ideal sedative should provide predictable effects, a rapid onset, and a quick recovery. It should be easy to administer and titrate, and cause few adverse events. Other desirable attributes include little or no interaction with other drugs and minimal or no

2 2 accumulation of metabolites, leaving no withdrawal effects. 5 Any agent that can be used to induce sedation while maintaining arousability also may allow the patient to cooperate with the clinician this can be particularly beneficial in the operating room setting for specific interventions (eg, awake fiber-optic intubation, and select neurologic procedures). It is also consistent with today s approach to ICU sedation management whereby every attempt is made to maintain an ICU patient s comfort with milder depths of sedation than was common practice just a few years ago. The impact that sedation has on respiratory drive as well as the impact on the ability of clinicians to communicate with their patients and perform frequent and accurate medical assessments are believed to have exerted detrimental effects on ICU outcomes. Deep sedation in the ICU is associated with longer ICU and hospital stays, an increased risk for ventilator-associated pneumonia, and subsequent higher hospital costs. 6,7 A wide variety of agents are used for sedation; however, many of the currently available agents have specific drawbacks that limit their practical utility across the full spectrum of patients and clinical situations that practitioners face every day. 2 For example, general anesthetics require full respiratory support, can be associated with hypotension and prolonged recovery, and only are appropriate for deep sedation. Opioid analgesics (eg, fentanyl, morphine) have poor sedative properties and are associated with respiratory depression, hypotension, and impaired gastrointestinal motility, sometimes leading to postoperative nausea and vomiting (PONV). 8 Propofol, a short-acting hypnotic agent, lacks analgesic properties and its use often is limited by hypotension and respiratory depression particularly when used in combination with opioid analgesics. Furthermore, there is an increasing recognition of the risks associated with long-term administration of propofol, such as propofol infusion syndrome, metabolic acidosis, hyperlipidemia, and enlarged or fatty liver which have limited its use to only a few days in the ICU. 9 The use of benzodiazepines is also associated with respiratory depression, paradoxical increases in agitation in the elderly or delirious patient, and the potential for drug accumulation, leading to prolonged recovery periods or withdrawal symptoms. 8 The limitations of these agents translate into suboptimal outcomes for many patients requiring sedation. The drawbacks of traditional sedatives led to the search for other drugs with different mechanisms of action, pharmacokinetic and pharmacodynamic properties and alternative efficacy, and tolerability profiles. The discovery that the α2-receptor agonist, clonidine, has opioid-sparing properties and can alleviate withdrawal symptoms encouraged the investigation of other α2-receptor agonists for use as IV sedatives. 10,11 Dexmedetomidine (Precedex, Hospira) is a short-acting sedative that is much more selective for the α2-receptor than clonidine. Dexmedetomidine produces effective mild to moderate sedation. It also is able to reduce the dosage of opioids necessary to provide adequate analgesia. Dexmedetomidine is also unique in that it can reduce autonomic nervous system activity via a central sympatholytic effect. Dexmedetomidine exerts these properties through its action at multiple sites, including supraspinal (locus ceruleus), spinal, and peripheral sites. 12,13 When given as an IV infusion, dexmedetomidine demonstrates linear, concentration-dependent kinetics. 14 The drug is metabolized extensively in the liver and excreted renally as methyl and glucuronide conjugates. 14 The short distribution half-life of dexmedetomidine (6 min) makes it an ideal drug for IV titration. 14 The recommended dexmedetomidine dose varies according to indication. 14 For example, for the sedation of mechanically ventilated patients in the ICU, sedation can be maintained by a continuous IV infusion of 0.2 to 0.7 mcg/kg per hour. In contrast, procedural sedation can be accomplished using a maintenance infusion usually initiated at 0.4 to 0.6 mcg/kg per hour and titrated to achieve desired clinical effect with doses ranging from 0.2 to 1 mcg/ kg per hour. An optional loading infusion of up to 1 mcg/kg administered over 10 to 20 minutes may be used to speed the time to onset when necessary. In patients previously sedated with other agents, a loading infusion is generally not necessary. When used alone as a primary sedative agent, dexmedetomidine begins to exert significant sedative effects 10 to 15 minutes after initiating a loading dose infusion. After each dose adjustment, it generally takes approximately 25 minutes to reach peak sedative effects. Dose reductions should be considered for elderly patients or those with impaired hepatic or renal function. 14 Moderate reductions in blood pressure and heart rate should be anticipated with dexmedetomidine infusions. Clinically significant episodes of bradycardia and sinus arrest have been reported with dexmedetomidine. The most common adverse events experienced with dexmedetomidine therapy in clinical trials are hypotension and bradycardia, and these may necessitate medical intervention such as decreasing or stopping the infusion, administration of IV fluids, elevation of lower extremities, or the administration of vasoactive or pressor agents such as atropine, ephedrine, or glycopyrrolate. 14 As a result, care should be taken when dexmedetomidine is administered to patients who are hypovolemic, chronic hypertensives, and to the elderly. It should also be used with caution in patients with advanced heart block or severe ventricular dysfunction. Conversely, transient hypertension can occur with administration of a loading dose. 14 Dexmedetomidine appears to have little potential for interaction with drugs metabolized by the cytochrome P450 system, and co-administration of dexmedetomidine with sevoflurane, isoflurane, propofol, alfentanil, and midazolam may result in enhancement of sedative, hypnotic, or anesthetic effects. 14 Because dexmedetomidine exerts its sedative effects via a different mechanism of action from those of the GABAmimetic agents, it produces different physiologic effects from the benzodiazepines or propofol and these differences can offer distinct advantages over other sedative agents in a variety of clinical situations and patient types. For example, patients receiving dexmedetomidine often appear sedated, calm and comfortable, yet these patients are able to be easily aroused when stimulated without titrating down or discontinuing the sedative infusion. 15,16 This can facilitate care during an ICU stay as well as during many operating room procedures. This quality of sedation with dexmedetomidine can allow communication during sensitive surgical or radiologic procedures as well as an increased ability to conduct accurate and frequent physical and neurologic assessments without sedative interruption

3 while in the ICU. When dexmedetomidine-sedated patients are not stimulated, they quickly return to a comfortable and sedated state. 17,18 Dexmedetomidine is also associated with minimal respiratory depression, which can facilitate accurate spontaneous breathing trials and ventilator weaning attempts without the need for discontinuing the sedative infusion in order to accurately assess the respiratory status of the patient and his or her ability to be weaned from invasive or noninvasive mechanical ventilation. 19 Dexmedetomidine also exerts sympatholytic effects which can be beneficial in those patients for whom a modest reduction in heart rate and blood pressure can prove beneficial. This is often the case in many cardiovascular procedures, during emergence from general anesthesia, and in patients undergoing alcohol withdrawal treatment with benzodiazepines but still requiring adjunctive sedation because of agitation. 18 These properties make dexmedetomidine well suited for use in a variety of surgical and intensive care situations. The following monograph is a case-based examination of the use of dexmedetomidine in various medical and surgical contexts and provides an overview of relevant data from clinical studies. Case 1 Managing Sedation Needs in the Agitated Patient Undergoing Treatment for Alcohol Withdrawal Charles Scott Brudney, MB, BCh, FRCA A 72-year-old retired engineer sustained a left intertrochanteric hip fracture after a ground-level fall at home. He was transported via ambulance to the local emergency department and was admitted to the orthopedics service. His medical history revealed hyperlipidemia controlled with statin therapy, and mild asthma requiring occasional albuterol use. He underwent operative hip repair the following morning without any apparent complications. Three days after the procedure the intended day of discharge he developed progressively worsening delirium and visual hallucinations. He became mildly tachycardic and hypertensive. Internal medicine consultation was obtained for evaluation of delirium. Chest x-ray, urinalysis, and complete blood count were normal, and basic chemistries and electrolytes were notable only for mild hypomagnesemia. During examination and an interview, the patient was clearly delirious, with his attention waxing and waning. Hand tremors, diaphoresis, elevated blood pressure, and tachycardia also were noted. When asked about the patient s alcohol use, his spouse confided that he typically drank one-fifth of whiskey daily. The last time he drank was on the day of his hospitalization. Based on a presumed diagnosis of alcohol withdrawal, the treating physician corrected hypomagnesemia, began daily thiamine therapy, and instituted treatment with IV lorazepam based on the hospital s established Clinical Institute Withdrawal Assessment (CIWA) protocol. The patient s level of agitation and symptoms worsened over the next 24 hours despite escalating doses of lorazepam (4 to 8 mg every 30 min) and the patient was admitted to the intensive care unit. In an effort to reduce the risk for respiratory compromise associated with high doses of lorazepam and better manage the patient s level of agitation the treating physician began IV dexmedetomidine at an initial dose of 0.2 mcg/kg per hour with subsequent titration to 0.7 mcg/kg per hour as an adjunctive sedative. Administration of IV lorazepam was continued as a part of the protocol for patients undergoing treatment for alcohol withdrawal. It was continued and reduced in parallel because of the additive pharmacodynamic sedative effects of dexmedetomidine when used with other sedatives or opioidbased analgesics. Using this regimen, the patient s agitation abated and he was resting comfortably, although still arousable with excellent respiratory status. His blood pressure and heart rate normalized, visual hallucinations resolved, and his tremor was notably decreased. After 24 hours, dexmedetomidine was tapered to discontinuation and low-dose oral lorazepam was administered. His symptoms continued to resolve over the next 48 hours, allowing for discharge with arrangements for alcohol cessation counseling (Figure 1). Discussion Alcohol withdrawal is a syndrome of autonomic instability and increased sympathetic output, resulting in anxiety, agitation, tremor, profuse sweating, elevated blood pressure, increased heart rate, anorexia, and reduced sleep. 20 In severe cases, the syndrome may progress to include fever, hallucinations, seizure, and even death. 20 The complication is not uncommon in the hospital setting, as hospitalized patients abruptly lose access to alcohol and may be unaware of the degree of their alcohol dependency or may not confide the extent of the problem to the treating physician. The primary treatment for alcohol withdrawal is judicious benzodiazepine administration, often guided by the established 3

4 4 A 72-year-old man develops progressively worsening delirium and visual hallucinations as well as mild tachycardia and hypertension 3 days following (intended day of discharge) surgery to repair a left intertrochanteric hip fracture. Internal medicine consultation was obtained for evaluation of delirium: chest x-ray, urinalysis, and CBC. Basic chemistries and electrolytes notable for mild hypomagnesemia. Physical examination: Patient clearly delirious. Hand tremors, diaphoresis, elevated BP, and tachycardia also were noted. Patient history including interviews with family and/or spouse to assess degree of alcohol use reveals that patient consumes on average one-fifth of whiskey daily. The last time he drank was on the day of hospitalization. Treating physician diagnoses alcohol withdrawal, corrects hypomagnesemia, begins daily thiamine therapy and treatment with IV lorazepam (4 mg every 30 min). Patient s symptoms worsen over next 24 hours despite lorazepam dose escalation (to 8 mg every 30 min). Risk for respiratory compromise if dose is escalated further. Treating physician initiates IV dexmedetomidine at an initial dose of 0.2 mcg/kg per hour with subsequent titration to 0.7 mcg/kg per hour. IV lorazepam reduced in parallel because of the added pharmacodynamic sedative effects of dexmedetomidine when used with other sedatives or opioid-based analgesics. Patient s agitation abates. BP and heart rate normalized. Visual hallucinations resolved, and hand tremor reduced. After 24 hours, dexmedetomidine was tapered to discontinuation and low-dose oral lorazepam was administered. Symptoms continued to resolve over the next 48 hours, allowing for discharge with arrangements for alcohol cessation counseling. Figure 1. Proposed algorithm for the management of sedation in the agitated patient undergoing treatment for alcohol withdrawal. BP, blood pressure; CBC, complete blood count; IV, intravenous CIWA protocol. 20 Studies have shown that benzodiazepines can be administered to patients with mild to moderate withdrawal in the outpatient setting; for patients with severe symptoms, an inpatient setting is preferred. 21 Benzodiazepines have several advantages including prevention of seizures, agitation, and delirium. 21 Both the half-life and route of administration should be considered when administering benzodiazepines. 21 Benzodiazepines act via the central inhibitory γ-aminobutyric acid (GABA) receptor, which can paradoxically worsen delirium and produce respiratory depression over time. 21 Additionally, some patients have refractory alcohol withdrawal despite treatment with high-dose benzodiazepines, possibly because of low endogenous GABA levels or acquired conformational changes in the GABA receptor. 22,23 The observation that dexmedetomidine can decrease hyperarousal states through its central α2-receptor agonist activity (and not by stimulating GABA receptors) led to the investigation of its adjunctive use in patients being treated for alcohol withdrawal. 12 Investigators have reported the use of adjunctive dexmedetomidine for sedation in patients undergoing treatment for refractory alcohol withdrawal. Darrouj and colleagues described the case of a 30-year-old man who developed delirium tremens despite aggressive benzodiazepine treatment, including a continuous midazolam infusion. 24 The IV dexmedetomidine was started at an initial dose of 0.2 mcg/kg per hour and titrated to 0.7 mcg/kg per hour resulting in immediate improvement in confusion and agitation. 24 A similar experience was described by Rovasalo and colleagues. In their case, a 50-year-old man developed confusion, tremor, agitation, diaphoresis, tachycardia, and seizure 3 days after abruptly engaging in alcohol abstinence. 25 Despite administration of 360 mg of diazepam and haloperidol 12.5 mg orally over the next 48 hours, the patient s agitation worsened. 25 Dexmedetomidine therapy was initiated (0.5 mcg/kg per hour over 10 min, followed by mcg/kg per hour over 90 min, 0.1 mcg/kg per hour over 6 h, and, 0.05 mcg/kg per hour over 8 h), which alleviated symptoms of agitation within 2 hours of initiation. Prieto and colleagues conducted a retrospective chart review of all patients in a Medical-Surgical ICU who were diagnosed as undergoing alcohol withdrawal syndrome (AWS) and received dexmedetomidine. 26 They highlight the results of 19 such patients with mean age of 59±9 years and mean APACHE II score of 19±6. 26 Previously, these patients had failed benzodiazepine therapy alone or in combination with other agents. 26 Using extubation and/or control of agitation and other AWS symptoms as clinical end points, AWS was successfully managed in 68% of patients evaluated in this challenging patient population. The median infusion rate of dexmedetomidine was found to be 0.34 mcg/kg per hour (range, 0.13 to 1.66). 26 It failed to provide additional agitation control in 3 patients and 3 others required discontinuation, two due to hypotension and one for unknown reasons. 26 Dexmedetomidine was found to reduce mean systolic and diastolic blood pressure in this patient population by 10% and heart rate by 6%. 26 The authors found dexmedetomidine to be a safe and effective adjunctive sedative agent for patients undergoing treatment for alcohol withdrawal, while facilitating extubation, controlling agitation, and reducing autonomic hyperactivity. 26 Its use was not associated

5 with significant respiratory depression, heart block, or bradycardia. However, because of a lack of anticonvulsant activity, they do not recommend dexmedetomidine be used alone to treat patients undergoing treatment for alcohol withdrawal. 26 These data suggest that dexmedetomidine can serve a clinical role as an adjunctive sedative agent for patients undergoing alcohol withdrawal. However, large-scale randomized studies are required to definitively determine the role of dexmedetomidine in treating patients with either benzodiazepine sensitive or benzodiazepine-resistant alcohol withdrawal. Case 2 Ventilator Weaning of the Agitated Patient Charles Scott Brudney, MB, BCh, FRCA A 72-year-old man with a history of ischemic cardiomyopathy and ejection fraction less than 40% experienced progressive weight gain and orthopnea over a 1-week period. He awoke with extreme dyspnea at rest and perioral cyanosis. His spouse called 911 and medics arrived to find the patient in acute respiratory distress with oxygen saturation of 70% and clinical evidence of tiring. He was intubated in the field and brought to the local emergency department, where plain chest films revealed pulmonary edema; laboratory testing demonstrated B-type natriuretic peptide greater than 2,000 pg/ ml with negative cardiac enzymes, and electrocardiogram was notable for the absence of ischemic changes. He was admitted to the medical ICU for mechanical ventilation with a presumptive diagnosis of acute systolic congestive heart failure. Propofol and fentanyl were administered for sedation analgesia while the patient was on mechanical ventilation, and diuresis was initiated with IV furosemide (80 mg IV every 8 h). Over the next 48 hours, total urine output exceeded 10 L and the patient s oxygen needs decreased. Follow-up chest x-rays showed resolution of pulmonary edema. According to local hospital protocol, propofol and fentanyl were weaned to facilitate spontaneous breathing trial (SBT), but the patient became acutely agitated and would not cooperate with assessments or instructions. Propofol and fentanyl were restored to their previous rates to re-establish sedation analgesia. In order to facilitate SBT while maintaining patient comfort, dexmedetomidine was started at 0.7 mcg/kg per hour. Once the patient settled on dexmedetomidine about 20 to 30 minutes fentanyl was weaned along with propofol which was weaned by 10 mcg/kg per minute every 5 minutes until the infusion was off several hours later. The patient became arousable but remained calm and was able to respond appropriately to instructions and indicate that he remained comfortable. An SBT was conducted with favorable results and the patient was subsequently extubated. He was able to maintain his respiratory status without further support and was weaned off dexmedetomidine over the next 2 hours without complication (Figure 2). Discussion It can be difficult to maintain sedation in mechanically ventilated patients for a prolonged period of time, and long-term A 72-year-old man is admitted to the ICU with a presumptive diagnosis of acute systolic congestive heart failure. Patient history includes ischemic cardiomyopathy and ejection fraction less than 40%. Taken to ED after his wife called 911. Patient had experienced progressive weight gain and orthopnea over a 1-week period and awoke with extreme dyspnea at rest and perioral cyanosis. Intubated by paramedics. Propofol and fentanyl administered for sedation analgesia while the patient was on mechanical ventilation, and diuresis was initiated with IV furosemide (80 mg IV every 8 h). Over the next 48 hours, total urine output exceeded 10 L and oxygen needs decreased. Follow-up chest x-rays showed resolution of pulmonary edema. Propofol and fentanyl weaned to facilitate SBT. Patient becomes acutely agitated and refuses to cooperate with assessments or instructions. Propofol and fentanyl restored to previous rates. Dexmedetomidine initiated at 0.7 mcg/kg per hour to facilitate SBT. Fentanyl and propofol weaned over several hours. Patient became arousable but remained calm; able to respond appropriately to instructions and indicated that he was comfortable. SBT performed with favorable results and patient is extubated. Patient maintains respiratory status without further support; weaned off dexmedetomidine over the next 2 hours without complication. Figure 2. Proposed algorithm for the management of sedation during ventilator weaning of an agitated patient. ED, emergency department; ICU, intensive care unit; IV, intravenous; SBT, spontaneous breathing trial 5

6 sedation can result in difficulties weaning from the ventilator. 27 Benzodiazepines are the mainstay of sedative treatment in the ICU and can effectively induce anxiolysis, hypnosis, and amnesia 28 ; however, benzodiazepines also can cause respiratory depression, prolong weaning times from mechanical ventilation, and induce hypotension; and the propylene glycol found in this preparation can induce toxicity following prolonged lorazepam use. 28 Alternatively, propofol is very effective at maintaining short-term sedation in mechanically ventilated patients, but is associated with various adverse effects and toxicities (eg, hypotension, dystonia, propofol infusion syndrome) and must be weaned in order to facilitate SBT. Each patient will respond differently to propofol and dexmedetomidine; however, by reducing propofol gradually over time, weaning off dexmedetomidine is possible without significant complication. 5,9 In contrast, dexmedetomidine is associated with minimal respiratory depression, which facilitates sedation in the intubated patients and allows extubation without the need to discontinue the drug infusion. 16,18 Dexmedetomidine sedation also may be continued during the postextubation period, providing flexibility in the timing of tracheal extubation and making the drug useful during the ventilator weaning process. 14,15,18 In a small study of 25 patients who failed previous attempts at weaning and extubation secondary to agitation, substituting dexmedetomidine (1 mcg/kg bolus followed by an infusion of mcg/kg per hour) for their existing sedation regimen resulted in successful extubation of 65% of patients. 29 Dexmedetomidine appears to maintain adequate sedation without hemodynamic instability or respiratory drive depression. As a result, it may facilitate weaning ICU patients off mechanical ventilation. 6 A 50-year-old woman presented for preoperative evaluation for an upper and lower blepharoplasty, rhytidectomy, and liposuction of the abdomen, hips, and thighs. The surgeon indicated that she would use a carbon dioxide laser and requested that no supplemental oxygen be used during the case in order to reduce the risk for a fire hazard. On her initial interview, the patient was anxious, talkative, and understood that she would not be totally asleep. She admitted that she did not want to be aware of anything and claimed a high tolerance for pain medication. On physical examination, airway evaluation revealed a Mallampati Class III with mouth opening less than 2 fingerbreadths and prominent front teeth. Neck exam revealed a receding jaw and anterior larynx (hyomental distance <3 cm). Review of the medical records revealed that a difficult airway was noted during a general anesthetic for a gynecologic procedure performed 2 years before. Intubation required multiple attempts with Macintosh and Miller blades, changes in head and pillow positions, and ultimately a successful fiber-optic intubation with several anesthesiologists present. The anesthetic also was remarkable for a brief episode of intraoperative bronchospasm with oxygen desaturation from 97% to 93%, which was treated with 100% oxygen, deepening of the inhalation agent, and the addition of in-line albuterol via the endotracheal tube. She was extubated at the end of the procedure and admitted overnight for refractory PONV and pain control. Based on these findings, the anesthesiologist required an anesthetic regimen to induce sedation, reduce anxiety, and allow the patient to maintain her respiration, thus reducing the need for supplemental oxygen and lowering the risk for a fire hazard in the context of carbon dioxide laser use. Because Case 3 Managing Sedation in Cosmetic Surgery Fred E. Shapiro, DO dexmedetomidine maintains respiratory stability, there is less of a need for sedatives and use of room air, thus decreasing the risk for combustion seen in aesthetic facial surgery. Midazolam (2 mg) was given in the holding area and the patient was transported to the operating room where loading doses of dexmedetomidine (1 mcg/kg) and ketamine (0.50 mg/kg) were given over 10 to 15 minutes. After finishing the loading doses, a dexmedetomidine infusion (0.4 mcg/kg per hour) was initiated. A propofol infusion (20 mcg/kg per minute) was started during the sterile preparation and drape, and was titrated based on the patient s hemodynamic and respiratory stability, and overall response to the injection of local anesthetic into the surgical area. The patient underwent the procedure with stable hemodynamics and without agitation or bronchospasm. The entire procedure was performed without the use of supplemental oxygen. At the conclusion of surgery, all infusions were stopped as the surgical dressings were being placed. The patient was alert within 5 to 10 minutes and was able to move by herself to the transport bed. She did not experience PONV and was discharged in good condition, reporting a satisfactory anesthesia experience (Figure 3). Discussion In this case, the use of dexmedetomidine allowed maintenance of respiratory status and oxygenation without the use of supplemental oxygen. This is significant considering the patient s report of past bronchospasm and the desire to avoid using supplemental oxygen to reduce the risk for fire related to the use of a carbon dioxide laser.

7 A 50-year-old woman presents for preoperative evaluation for an upper and lower blepharoplasty, rhytidectomy, and liposuction of the abdomen, hips, and thighs. Surgeon plans to use CO2 laser and thus requests that no supplemental oxygen be used. Patient interview patient is anxious, talkative, and understands that she would not be totally asleep, which concerns her. Claims a high tolerance for pain medication. Physical exam airway evaluation reveals a Mallampati Class III with mouth opening less than 2 fingerbreadths and prominent front teeth. Neck exam reveals a receding jaw and anterior larynx (hyomental distance <3 cm). Patient history Difficult airway noted during a general anesthetic for a gynecologic procedure performed 2 years prior. Required multiple intubation attempts, and intraoperative bronchospasm with oxygen desaturation from 97% to 93% which was treated with 100% oxygen, deepening of the inhalation agent, and the addition of in-line albuterol via the endotracheal tube reported. Patient admitted overnight for refractory PONV and pain control. For this cosmetic procedure, midazolam (2 mg) administered in the holding area. Patient transported to the OR, where loading doses of dexmedetomidine (1 mcg/kg) and ketamine (0.50 mg/kg) given over 10 to 15 minutes. Dexmedetomidine infusion (0.4 mcg/kg per hour) initiated. Propofol infusion (20 mcg/kg per minute) started during the sterile preparation and drape; titrated based on the patient s hemodynamic and respiratory stability, and overall response to the injection of local anesthetic into the surgical area. Patient undergoes procedure with stable hemodynamics and without agitation or bronchospasm. Procedure performed without the use of supplemental oxygen. All infusions stopped as surgical dressings were placed. The patient was alert within 5 to 10 minutes and was able to move by herself to the transport bed. No PONV reported. Figure 3. Proposed algorithm for the management of sedation during cosmetic surgery. PONV, postoperative nausea and vomiting The safety benefits are particularly impressive when considering the closed claims analysis of injuries associated with monitored anesthesia care (MAC). Investigators reported that more than 40% of claims associated with MAC involved death or permanent brain damage. 30 The most common mechanism of injury was respiratory depression (21%) due to a combination of sedative drugs. 30 Additionally, the use of electrocautery in the presence of supplemental oxygen during facial surgery resulted in 17% of the claims. 30 Clinical studies confirm the benefits of dexmedetomidine; in a retrospective review of 142 consecutive rhytidectomies, Taghinia and colleagues compared the use of standard anesthesia (propofol, ketamine, fentanyl, and midazolam) with and without dexmedetomidine. 31 The investigators reported that dexmedetomidine use decreased the need for standard anesthetics dramatically, 31 and it was associated with lower mean blood pressure and heart rate in the perioperative period, fewer incidents and duration of oxygen desaturation, decreased requirements for other intraoperative sedatives or analgesics, and a decreased need for postoperative antiemetics. 31 Case 4 Managing Sedation in Bariatric Surgery A 42-year-old man with a body mass index greater than 50 kg/m 2 presented for preoperative evaluation for Roux-en-Y gastric bypass surgery. His medical history was notable for hypertension, type 2 diabetes, hyperlipidemia, and obstructive sleep apnea (OSA), all of which were likely related to his super morbid obesity. His past surgical history was notable for cholecystectomy, 1 year, during which intubation was exceedingly difficult. Based on available records, it appeared that awake intubation was attempted, but his airway was lost and conversion to rapid-crash intubation that fortunately was successful. The patient had vivid recollections of the episode, and reports Michael A. E. Ramsay, MD, FRCA not being able to move, not being able to breathe, and feeling like [he] was going to die. Because of this experience, he had considerable anxiety over how the planned procedure would work. Based on this information and confirmation of a difficult airway, the anesthesiologist planned to use dexmedetomidine to facilitate awake intubation, while also treating the patient s heart rate and blood pressure through dexmedetomidine s sympatholytic effects. Before the procedure, the patient was given dexmedetomidine (1 mcg/kg for 10 min) until he achieved a relaxed and sedated, but still arousable state. He was placed in a sitting position 7

8 8 to allow for easier respiratory excursion. Dexmedetomidine was decreased to 0.7 mcg/kg per hour, and topical lidocaine was applied to the mouth and airway. The patient was able to cooperate with the anesthesiologist when asked to open his mouth or push out his tongue. He allowed insertion of a direct laryngoscope, but the vocal cords could not be visualized. With the patient still able to control his respiration and maintain his airway, a video-assisted laryngoscope was used to establish the airway and allow intubation. Following securing the airway, propofol 100 mg, and then vecuronium 5 mg were administered intravenously. The patient was maintained on inhalational sevoflurane 1% to 2% and intravenous fentanyl 250 mcg was administered throughout the procedure. Depth of anesthesia was assessed with vital signs and a brain function monitor. Throughout the procedure, the patient had very stable hemodynamics. Approximately 20 to 30 minutes before the end of the procedure, dexmedetomidine was reinitiated at a dose of 0.7 mcg/ kg per hour. At the end of the 90-minute procedure, inhalational anesthesia was discontinued while dexmedetomidine was maintained to facilitate extubation and minimize opioid needs. The patient was moved to a sitting position and extubated. The patient was taken to the recovery unit, and dexmedetomidine dose was decreased to 0.3 mcg/kg per hour. Over the next 3 to 4 hours, no opioids were required and the patient maintained his airway without respiratory support (Figure 4). The following morning, the patient confided that he could recall the awake intubation and stated, it was like night and day compared to [his] previous experience. He requested documentation of this preferable method of intubation in his medical record should future surgeries be required. Discussion A significant proportion of the US adult population is either obese or morbidly obese, and the problem is further magnified in the clinical population. 32 Obesity results in considerable morbidity and mortality because of its association with cardiovascular disease, diabetes, hyperlipidemia, and OSA. 33 Bariatric surgery is an effective strategy for reversing obesity and can result in alleviation of these comorbid conditions. 33 However, the very same comorbidities associated with obesity also can increase the risk for perioperative complications. 33 For example, obesity often results in difficulties in establishing an airway, whereas obesity-related respiratory comorbidities (eg, OSA, obesity hypoventilation syndrome, restrictive lung disease) increase the risk for opioid-induced respiratory complications. Furthermore, coronary artery disease (CAD) is more prevalent in the obese population, which increases the risk for perioperative myocardial infarction. 33 This case study illustrates the benefits of dexmedetomidine for multiple issues when dealing with obese patients undergoing bariatric surgery, including facilitation of awake fiber-optic intubation, cardiovascular stability, and reduction of opioid requirements, thereby reducing the risk for opioid-induced respiratory compromise and adverse gastrointestinal events (eg, ileus, PONV) that might otherwise impede recovery. 33 By virtue of its ability to lower heart rate, dexmedetomidine may be useful in patients with underlying CAD. 33 These benefits have been confirmed in clinical studies. Indeed, several groups have reported excellent success with the use of dexmedetomidine as a sole agent in case series of patients undergoing awake intubation In this context, the ability of dexmedetomidine to preserve respiratory function and the patient s ability to cooperate with the anesthesiologist is augmented by its antisialogogue properties, which provides a dry field for the anesthesiologist. A 42-year-old man with BMI >50 kg/m 2 presents for preoperative evaluation for Roux-en-Y gastric bypass surgery. Patient history hypertension, type 2 diabetes, hyperlipidemia, OSA. Past surgical history includes cholecystectomy, 1 year before, during which intubation was difficult. As a result, patient has considerable anxiety about the planned procedure. Anesthesiologist plans to use dexmedetomidine to facilitate awake intubation, while also preserving the patient s ability to cooperate and maintain his respiratory status and airway. Patient is administered dexmedetomidine (1 mcg/kg per hour for 10 min) until sedation is achieved. He is still arousable. Patient is placed in a sitting position to allow for easier respiratory excursion. Dexmedetomidine decreased to 0.7 mcg/kg per hour and topical lidocaine applied to mouth and airway. Patient allows insertion of direct laryngoscope, but vocal cords cannot be visualized. Video-assisted laryngoscope used to establish airway and allow intubation. Propofol 100 mg and then vecuronium 5 mg administered by IV. Patient maintained on inhalational sevoflurane 1% to 2% and intravenous fentanyl 250 mcg administered throughout the procedure. Depth of anesthesia was assessed with vital signs and a brain function monitor. Toward the end of the procedure, dexmedetomidine was reinitiated. At the end of the 90-minute procedure, inhalational anesthesia was discontinued while dexmedetomidine was maintained. Patient moved to a sitting position and extubated. Patient taken to recovery unit. Dexmedetomidine decreased to 0.3 mcg/kg per hour. No opioids required. Patient maintained airway without respiratory support. Figure 4. Proposed algorithm for the management of sedation during bariatric surgery. BMI, body mass index; IV, intravenous; OSA, obstructive sleep apnea

9 Other studies also support the use of dexmedetomidine in patients undergoing bariatric surgery. For example, Tufanogullari and colleagues studied 80 patients undergoing bariatric surgery and reported that adjunctive use of dexmedetomidine ( mcg/kg per hour) resulted in decreased opioid requirements, decreased use of antiemetics, and decreased duration of stay in the recovery unit. 38 Finally, in a study of more than 70 patients undergoing laparoscopic bariatric surgery, Dholakia and colleagues reported that dexmedetomidine infusion was associated with significantly lower opioid requirements and increased the proportion of patients who were eligible for discharge within postoperative day These data clearly demonstrate that dexmedetomidine has properties that are well suited for use in patients undergoing bariatric surgery. Because a significant proportion of patients in all of the surgical populations is obese, the benefits of dexmedetomidine likely apply to a broad set of surgical procedures. Case 5 Use of Dexmedetomidine in Awake Carotid Endarterectomy Trevor S. Sutton, MD, MBA A 66-year-old man presented with transient right eye blindness. Duplex ultrasound of the carotid arteries disclosed 80% stenosis of the right carotid artery with ulcerated plaque involving the right carotid artery bifurcation. Right carotid endartectomy was recommended. The patient s medical history was notable for OSA, emphysema, hypertension, and CAD. The patient was prescribed a continuous positive airway pressure machine for OSA, but he reported noncompliance secondary to severe claustrophobia. The patient denied angina. A cardiac radionuclide study 1 year before showed no inducible ischemia and a left ventricular ejection fraction of 40%. The surgeon requested awake neurologic monitoring during surgery. Thus, a cervical plexus block was performed, and sedation for performance of the regional block was achieved with fentanyl and midazolam. Shortly after the surgical field was draped and before surgical incision the patient became frightened and disinhibited due to claustrophobia. Propofol bolus and infusion were administered in order to achieve cooperative sedation that would allow the surgery to proceed. The patient became apneic and hypotensive. His airway was controlled with mask ventilation, and blood pressure was normalized with phenylephrine. Surgery was cancelled in order to stabilize the patient and re-evaluate him neurologically. The patient returned for preoperative evaluation the following week, and the anesthesiologist was asked to formulate an alternate plan for sedation. The patient stated that he needed something to keep [him] calm during surgery. The surgeon once again requested awake neurologic monitoring. Based on this clinical scenario, the anesthesiologist planned for awake carotid endarterectomy with cooperative sedation. The patient was brought into the operating room with a resting heart rate of 56 beats per minute (bpm). Dexmedetomidine load (0.5 mcg/kg lean body weight) was administered over 20 minutes, with co-administration of glycopyrrolate (0.2 mg 2) to achieve baseline heart rate greater than 60 bpm during dexmedetomidine load. Deep and superficial cervical plexus blocks were performed, and midazolam (1 mg) and fentanyl (25 mcg x 2) were administered for anxiolysis and analgesia, respectively, during performance of regional block. The patient was positioned, and surgical skin preparation and draping were performed. On completion of the dexmedetomidine load, the patient was sedated but easily arousable to voice or light touch. A continuous dexmedetomidine infusion was initiated at 0.2 mcg/kg per hour and maintained at this dose. After surgical incision, the patient was noted to be snoring but arousable to touch. The carotid sheath was opened and the carotid artery was prepared for placement of occlusion clamps; the patient responded promptly and appropriately to verbal commands and expressed no anxiety. Dexmedetomidine infusion was then discontinued in anticipation of carotid artery occlusion. Dexmedetomidine infusion was discontinued 5 minutes prior to the surgeon s request for a heparin bolus, and approximately 8 to 10 minutes prior to carotid artery occlusion. During performance of carotid endarterectomy, the patient remained alert and cooperative with no changes in hemodynamics or respiratory status, and speech and motor examinations were unchanged from preoperative baseline. To prevent thrombosis of the carotid artery and ipsilateral intracranial vessel, heparin was administered, followed by carotid artery occlusion and performance of carotid endarterectomy. The patient remained alert and cooperative with no changes in hemodynamics or respiratory status, and speech and motor examinations were unchanged from preoperative baseline. Five minutes before carotid reperfusion (30 min following discontinuation of dexmedetomidine infusion), the patient became restless. To maintain the patient s comfort, dexmedetomidine infusion was resumed at 0.2 mcg/kg per hour, and supplemental fentanyl (50 mcg) was administered for patient comfort. Carotid reperfusion and closure of the surgical wound proceeded without incident, and the dexmedetomidine infusion was discontinued during closure of the subcutaneous skin layer (Figure 5). 9

10 The patient was awake, comfortable, and neurologically intact at the conclusion of surgery, and recovery was uneventful. The patient was discharged to home following a 23-hour hospital admission. Follow-up with the surgeon after 2 weeks demonstrated excellent neurologic function, and the patient reported that he was pleased with his anesthesia care. A 66-year-old man with transient right eye blindness undergoes right carotid endarterectomy to treat 80% stenosis with ulcerated plaque. Patient history OSA, emphysema, hypertension, and CAD. Noncompliance with CPAP for OSA due to severe claustrophobia. Surgeon requests awake neurologic monitoring during surgery. Cervical plexus block performed. Fentanyl and midazolam used to achieve sedation for performance of the regional block. Patient becomes frightened and disinhibited prior to surgical incision due to claustrophobia. Propofol bolus and infusion administered to achieve cooperative sedation. Patient apneic and hypotensive. Airway controlled with mask ventilation. BP normalized with phenylephrine. Surgery cancelled and rescheduled for the following week. Anesthesiologist plans for awake carotid endarterectomy with cooperative sedation. IV dexmedetomidine load (0.5 mcg/kg lean body weight) administered over 20 min, with co-administration of glycopyrrolate (0.2 mg 2). Deep and superficial cervical plexus blocks performed, and midazolam (1 mg) and fentanyl (25 mcg 2) administered for anxiolysis and analgesia. Patient is sedated but easily arousable to voice or light touch. Continuous IV dexmedetomidine initiated at 0.2 mcg/kg per hour and maintained. Patient responds promptly and appropriately to verbal commands and shows no anxiety. Patient becomes restless 5 min prior to carotid reperfusion (30 min following discontinuation of dexmedetomidine infusion). IV dexmedetomidine resumed at 0.2 mcg/kg per hour, and supplemental fentanyl (50 mcg) administered for patient comfort. Surgery proceeds without incident, and dexmedetomidine infusion discontinued during closure of the subcutaneous skin layer. The patient is awake, comfortable, and neurologically intact at the conclusion of surgery, and recovery is uneventful. Figure 5. Proposed algorithm for the management of sedation in a patient undergoing awake carotid endarterectomy. CAD, coronary artery disease; CPAP, continuous positive airway pressure; IV, intravenous; OSA, obstructive sleep apnea Discussion Awake neurologic examination is a widely used approach for guiding selective shunt placement during carotid endarterectomy. 40 The advantages include high sensitivity and high specificity for identifying cerebral hemisphere ischemia before, during, and after intraoperative carotid artery occlusion. Although regional anesthesia for carotid endarterectomy can be achieved through cervical plexus block anesthesia, the ability to induce safe and effective cooperative sedation yields the added benefit of achieving desired patient comfort while still maintaining the ability to perform continuous neurologic monitoring during surgery. 40 A combination of midazolam, fentanyl, and/or propofol generally provides a good balance of sedation, cooperation, and hemodynamic stability. However, over- or undersedation, restlessness, disinhibition, and occasional respiratory depression may impair the mental status evaluation and require measures to control the airway. 40 As illustrated in this case study, dexmedetomidine allows arousability for evaluation of neurologic status during carotid endarterectomy, while still sedating the patient and assuring patient comfort. In this case, dexmedetomidine provided consistent heart rate and blood pressure lowering capabilities, which can be important in delivering cardiovascular and neurologic outcomes in patients with carotid artery stenosis and the underlying CAD that typically accompanies it. Another benefit in this case is the ability of dexmedetomidine to maintain respiratory status, which is helpful in patients with underlying emphysema and OSA. One notable caution with the use of dexmedetomidine in patients undergoing carotid endarterectomy is the potential for severe bradycardia due to vagal stimulation during carotid manipulation combined with the sympatholytic properties of dexmedetomidine. 40 Clinicians should consider altering the dose and rate of the loading dose (eg, <1 mcg/kg lean body weight over minutes) as well as the use of pharmacologic agents to elevate the heart rate to more than 60 bpm before administration of the dexmedetomidine load. Data from clinical studies support the safety and efficacy of dexmedetomidine for awake carotid endarterectomy. For example, Bekker and colleagues studied the use of dexmedetomidine in 151 patients undergoing awake carotid endarterectomy. They reported that the agent was safe and effective and did not increase the incidence of intra-arterial shunts. 41 Similarly, McCutcheon and colleagues performed a randomized, double-blind study in 56 patients undergoing carotid endarterectomy under regional anesthesia and compared hemodynamic control using dexmedetomidine versus midazolam and fentanyl. 42 The investigators reported that dexmedetomidine was reliable and easily titratable. Additionally, patients receiving dexmedetomidine required fewer intraoperative hemodynamic interventions and required less postoperative analgesic compared with those who received the comparator treatment

11 Conclusion Sedation and analgesia are critical tools for modern medical and surgical care, and optimal use of sedation analgesia is associated with improved outcomes and reduced resource use. Many of the widely used sedative analgesics are associated with particular drawbacks, including hypotension, withdrawal, accumulation, and respiratory depression. In contrast, dexmedetomidine, the central and peripherally acting α2-receptor agonist, can achieve sedation while simultaneously allowing arousability, preventing overactivity of the sympathetic nervous system, and maintaining respiratory drive. Furthermore, the drug has shown efficacy in decreasing the need for opioids, benzodiazepines, and propofol. The clinical properties of dexmedetomidine make it well suited for a variety of clinical indications, including use as an adjunctive sedative in the treatment of alcohol withdrawal, those undergoing mechanical ventilation in the ICU, those undergoing awake carotid endarterectomy, and for bariatric and cosmetic procedures. Short-term sedation has been shown to be safe in studies, although hypotension and bradycardia are the most significant side effects. Regardless, clinical data suggest that dexmedetomidine may be a better choice over several widely used sedative agents in many clinical situations. References American Society of Anesthesiologists Task Force on Sedation and Analgesia by Non-Anesthesiologists. Practice guidelines for sedation and analgesia by non-anesthesiologists. Anesthesiology. 2002;96(4): Jacobi J, Fraser GL, Coursin DB, et al. Clinical practice guidelines for the sustained use of sedatives and analgesics in the critically ill adult. Crit Care Med. 2002;30(1): Association of perioperative Registered Nurses. Recommended practices for managing the patient receiving moderate sedation/ analgesia. AORN J. 2002;75(3): Mirski MA, Lewin JJ. Sedation and pain management in acute neurological disease. Semin Neurol. 2008;28(5): Ostermann ME, Keenan SP, Seiferling RA, Sibbald WJ. Sedation in the intensive care unit. A systematic review. JAMA. 2000;283(11): Coursin DB, Coursin DB, Maccioli GA. Dexmedetomidine. Curr Opin Crit Care. 2001;7(4): Kress JP, Pohlman AS, Michael RN, Hall JB. Daily interruption of sedative infusions in critically ill patients undergoing mechanical ventilation. N Engl J Med. 2000;342(20): Murray MJ, DeRuyter ML, Harrison BA. Opioids and benzodiazepines. Crit Care Clin. 1995;11(5): Kam PC, Cardone D. Propofol infusion syndrome. Anaesthesia. 2007;62(7): Gowing L, Farrell M, Ali R, White JM. Alpha2-adrenergic agonists for the management of opioid withdrawal. Cochrane Database Syst Rev. 2009;2:CD Laisalmi M, Koivusalo AM, Valta P, Tikkanen I, Lindgren L. Clonidine provides opioid-sparing effect, stable hemodynamics, and renal integrity during laparoscopic cholecystectomy. Surg Endosc. 2001;15(11): Nelson LE, Lu J, Guo T, et al. The alpha2-adrenoceptor agonist dexmedetomidine converges on an endogenous sleeppromoting pathway to exert its sedative effects. Anesthesiology. 2003;98(2): Poree LR, Guo TZ, Kingery WS, Maze M. The analgesic potency of dexmedetomidine is enhanced after nerve injury: a possible role for peripheral alpha2-adrenoceptors. Anesth Analg. 1998; 87(4): Precedex (dexmedetomidine HCl) prescribing information. precedex.hospira.com/_docs/precedexpi.pdf. Accessed January 13, Gerlach AT, Dasta JF. Dexmedetomidine: an updated review. Ann Pharmacother. 2007;41(2): Szumita PM, Baroletti SA, Anger KE, Wechsler ME. Sedation and analgesia in the intensive care unit: evaluating the role of dexmedetomidine. Am J Health Syst Pharm. 2007;64(1): Golembiewski J. Dexmedetomidine does it have a role in the perioperative setting? J Perianesth Nurs. 2005;20(4): Phan H, Nahata MC. Clinical uses of dexmedetomidine in pediatric patients. Paediatr Drugs. 2008;10(1): Carollo DS, Nossaman BD, Ramadhyani U. Dexmedetomidine: a review of clinical applications. Curr Opin Anaesthesiol. 2008;21(4): Kosten TR, O Connor PG. Management of drug and alcohol withdrawal. N Engl J Med. 2003;348(18): Lejoyeux M, Solomon J, Ades J. Benzodiazepine treatment for alcohol-dependent patients. Alcohol Alcoholism. 1998; 33(6): Cagetti E, Liang J, Spigelman I, Olsen RW. Withdrawal from chronic intermittent ethanol treatment changes subunit composition, reduces synaptic function, and decreases behavioral responses to positive allosteric modulators of GABAA receptors. Mol Pharmacol. 2003;63(1): Nolop KB, Natow A. Unprecedented sedative requirements during delirium tremens. Crit Care Med. 1985;13(4): Darrouj J, Puri N, Prince E, Lomonaco A, Spevetz A, Gerber DR. Dexmedetomidine infusion as adjunctive therapy to benzodiazepines for acute alcohol withdrawal. Ann Pharmacother. 2008;42(11): Rovasalo A, Tohmo H, Aantaa R, Kettunen E, Palojoki R. Dexmedetomidine as an adjuvant in the treatment of alcohol withdrawal delirium: a case report. Gen Hosp Psychiatry. 2006; 28(4): Prieto MN, Barr J, Tanaka T, et al. Dexmedetomidine: A novel approach to the management of alcohol withdrawal in the ICU. Anesthesiol. 2007;107:A Kollef MH, Levy NT, Ahrens TS, et al. The use of continuous IV sedation is associated with prolongation of mechanical ventilation. Chest. 1998;114(2):

12 28. Ativan (lorazepam) prescribing information. com/pro/lorazepam-injection.html. Accessed January 8, Arpino PA, Kalafatas K, Thompson BT. Feasibility of dexmedetomidine in facilitating extubation in the intensive care unit. J Clin Pharm Ther. 2008;33(1): Bhananker SM, Posner KL, Cheney FW, et al. Injury and liability associated with monitored anesthesia care: a closed claims analysis. Anesthesiology. 2006;104(2): Taghinia AH, Shapiro FE, Slavin SA. Dexmedetomidine in aesthetic facial surgery: improving anesthetic safety and efficacy. Plast Reconstr Surg. 2008;121(1): Hedly AA, Ogden CL, Johnson CL, et al. Prevalence of overweight and obesity among US children, adolescents, and adults, JAMA. 2004;291(23): Ramsay MA. Bariatric surgery: the role of dexmedetomidine. Semin Anesth Periop Med Pain. 2006;25(2): Abdelmalak B, Makary L, Hoban J, Doyle DJ. Dexmedetomidine as sole sedative for awake intubation in management of the critical airway. J Clin Anesth. 2007;19(5): Bergese SD, Khabiri B, Roberts WD, Howie MB, McSweeney TD, Gerhardt MA. Dexmedetomidine for conscious sedation in difficult awake fiberoptic intubation cases. J Clin Anesth. 2007;19(2): Avitsian R, Lin J, Lotto M, Ebrahim Z. Dexmedetomidine and awake fiberoptic intubation for possible cervical spine myelopathy: a clinical series. J Neurosurg Anesthesiol. 2005;17(2): Grant SA, Breslin DS, MacLeod DB, Gleason D, Martin G. Dexmedetomidine infusion for sedation during fiberoptic intubation: a report of three cases. J Clin Anesth. 2004;16(2): Tufanogullari B, White PF, Peixoto MP, et al. Dexmedetomidine infusion during laparoscopic bariatric surgery: the effect on recovery outcome variables. Anesth Analg. 2008;106: Dholakia C, Beverstein G, Garren M, Nemergut C, Boncyk J, Gould JC. The impact of perioperative dexmedetomidine infusion on postoperative narcotic use and duration of stay after laparoscopic bariatric surgery. J Gastrointest Surg. 2007; 11(11): Bekker AY, Basile J, Gold M, et al. Dexmedetomidine for awake carotid endarterectomy: efficacy, hemodynamic profile, and side effects. J Neurosurg Anesthesiol. 2004;16(2): Bekker A, Gold M, Ahmed R, et al. Dexmedetomidine does not increase the incidence of intracarotid shunting in patients undergoing awake carotid endarterectomy. Anesth Analg. 2006;103(4): McCutcheon CA, Orme RM, Scott DA, Davies MJ, McGlade DP. A comparison of dexmedetomidine versus conventional therapy for sedation and hemodynamic control during carotid endarterectomy performed under regional anesthesia. Anesth Analg. 2006;102(3): SR0939

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