Dexmedetomidine sedation for awake fiberoptic intubation

Seminars in Anesthesia, Perioperative Medicine and Pain (2006) 25, 65-70

Dexmedetomidine sedation for awake fiberoptic intubation Richard J. Unger, MD,a and Christopher J. Gallagher, MDb a

From the Scripps Memorial Hospital, La Jolla, California; and the Department of Anesthesiology, University of Miami/Jackson Memorial Hospital, Miami, Florida

b

KEYWORDS: Dexmedetomidine; Awake intubation; Cooperative sedation; Conscious sedation; Fiberoptic intubation

The awake fiberoptic intubation (AFI) is an important part of the anesthesiologist’s armamentarium. As well as being technically challenging, it is also uncomfortable and stressful for all involved. We discuss the use of an alpha-2 agonist, dexmedetomidine, to help the clinician and patient through this procedure. The advantages of dexmedetomidine are that it produces a unique “Cooperative Sedation,” which reduces discomfort in the patient and assists in the topicalization of the airway. Most importantly, dexmedetomidine does not produce significant respiratory depression, so the airway may be secured in the safest manner possible. We discuss the history of sedation for AFI, other medications, as well as guidelines and pitfalls in the use of dexmedetomidine. © 2006 Elsevier Inc. All rights reserved.

“In dreams begin responsibility.” William Butler Yeats Responsibilities, 1914 And as our patients face the dreamland of general anesthesia, we take on the responsibility for keeping their airway safe and secure. In case of doubt, the safest, surest route is the awake intubation. Just look at the ASA Difficult Airway Algorithm1 and the ASA Difficult Airway Algorithm Modified for Trauma.2 Awake intubation keeps popping up again and again, like some beachball you try to push under the water. There’s no keeping it down! OK fine, so we do the awake intubation. No problem, right? No sooner said than done? Who hasn’t seen this scenario: “AAAAAAGH! GAAAAAAAAAAAAAAAAGH!” Damn! I thought he was topicalized. “Hold still Mr. Smith!” Turning to the cart, maybe just a

Address reprint requests and correspondence: Richard J. Unger, MD, 7372 Eads Avenue, La Jolla, CA 92037. E-mail: [email protected].

0277-0326/$ -see front matter © 2006 Elsevier Inc. All rights reserved. doi:10.1053/j.sane.2006.01.004

little more midazolam. Just a touch, a touch of fentanyl, you know, zap that cough reflex. “Gaaaaaaaaaaaaaaaak!” “Um, doctor, his heart rate is pretty. . .” “THANK YOU, I KNOW, LET ME JUST GET THIS!” Thank God, he’s finally quieted down. Where are those cords, I saw them just a second ago. BOOP BOOP BOOP BOOP. “S#&ⴱ!!! Gimme the mask, gimme the mask!” Sound familiar? Telling someone, “Just intubate them awake” is like most advice. You can’t argue with it, and it just plain makes sense. But then implementing this great advice can be a real headache. On the tennis court, for example, people give me this advice: “Just hit it in all the time.” Well, shucks, great advice. Wonderful advice. If I would just follow that advice, I’d beat Roger Federer at Wimbledon every time. But it’s hard to “hit it in every time.” And it’s hard to “just intubate them awake”. Awake intubation can give you adverse hemodynamic

66 Table 1

Seminars in Anesthesia, Perioperative Medicine and Pain, Vol 25, No 2, June 2006 Site of action of Dexmedetomidine

History of difficult intubation or mask ventilation Anticipated difficult laryngoscopy on physical examination Aspiration risk in patients unsuitable for rapid sequence inductions Need for neurological assessment after intubation Potential loss of airway secondary to mass effect, infection, bleeding

consequences3 and cause trauma— epistaxis, for example. And a number of scenarios make awake intubation nearly impossible: intoxicated and uncooperative patient, C-spine injury where the patient may thrash around and worsen neurologic injury. Some patients with difficult airways may not cooperate due to developmental delays, closed head injury sequelae, or chromosomal abnormalities. Sedation for awake intubation has its own list of misery, as illustrated above.4 Mix and match some narcotic and benzodiazepine, and the synergistic effect may convert your “awake” intubation into an “asleep, oh hell, what do I do now?” intubation. Any magic bullet out there? Is dexmedetomidine (who are we kidding, you read the chapter title, what else were we going to talk about?) the magic bullet? Well, not exactly, but it gets pretty close to being that magic bullet. Let’s see how. There are a multitude of indications for awake fiberoptic intubation (AFI)5 (Table 1): history of difficult airway, anticipated difficult direct visualization of larynx, trauma, mass, or infection in the upper airway, and need for neurologic assessment after intubation. There are but a few, but absolute contraindications to AFI do exist (Table 2). Local anesthesia is an integral part of awake airway management, but that will not be discussed in this essay. Instead, we will focus on the safe methods of sedating patients who have indications for AFI. Patient cooperation is paramount when attempting to do AFI, and in addition to informed consent and patient acceptance, judicial administration of intravenous agents can greatly and safely aid the anesthesiologist when facing a patient in need of AFI. Typically, the better a patient understands and cooperates with topical and regional anesthesia of the airway, the more effective will be the local anesthetics and the better the patient and staff will tolerate the procedure! Our focus in this essay will be to explain the advantages of dexmedetomidine to facilitate these procedures and explain its advantage over more traditional agents. How does dexmedetomidine compare with other sedative agents? To better understand the advantages of dexmedetomidine, it will be useful to understand the other agents which have been used before dexmedetomidine was available.

Premedication Premedication is an essential component of AFI. We use premedicants to reduce secretions, enhance hemodynamic stability, create amnesia, and reduce anxiety. Benzodiazepines including midazolam and lorazepam will effectively reduce anxiety and create amnesia. Caution’s the byword when you use these drugs along with dexmedetomidine because dexmedetomidine is synergistic with all sedative medications.6 How about narcotics? No need to use them. Dexmedetomidine plus a little bit of benzodiazepine provides you all the sedation your need. Plus, by avoiding narcotics, you avoid their respiratory depression. Vagolytic and antisialogogues such as glycopyrrolate are essential premeds to patients undergoing AFI. A dry mouth enhances the efficacy of local anesthetics,7 enhances visualization of the airway, and helps prevent the bradycardia seen with alpha-2 agonists. Recent work has shown that younger patients with more predominant vagal tone will have a safer journey with alpha-2 agonists if pre-treated with glycopyrrolate.8 Other antisialogogues such as hyoscine and atropine have been used, but in themselves have potent CNS side effects. What is the one symptom of atropine poisoning? “Mad as a hatter.” Atropine crosses into the brain and you get a central cholinergic effect. Now you’ve converted your awake intubation into a “madhouse” intubation! Glycopyrrolate is a quaternary ammonium and does not cross the blood– brain barrier, therefore causing no sedation and CNS side effects. Typically, adults given 0.2-0.3 mg of glycopyrrolate will have effective drying of the mucosal membranes with no adverse effects on heart rate. That is, the glycopyrrolate will not cause a tachycardia and will not allow a bradycardia.

Conscious sedation Almost all patients require some form of intravenous sedation before AFI. This makes the term AWAKE fiberoptic intubation a bit of a misnomer. Sedation is needed for anxiety and pain associated with the procedure. Important goals of intravenous sedation include maintenance of airway patency and ventilatory drive. Dexmedetomidine is a medication that provides these unique characteristics. The term “Cooperative Sedation” has been aptly coined in relation to the unique sedation achieved with dexmedetomidine.

Table 2 (AFI)

Contraindications for awake fiberoptic intubation

Refusal Uncooperative patient Bleeding (unable to visualize) Local anesthetic allergy or toxicity

Unger and Gallagher Table 3

Dexmedetomidine Sedation

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Comparative pharmacologic properties of drugs for conscious sedation for AFI

Narcotics Ketamine Benzodiazepines Propofol Droperidol Dexmedetomidine

Rapid onset with a short half-life

Sedation with orientation and arousability

Analgesia

** * * **** * ***

*** * ** ** ** ****

**** ** * ** ** ***

Before we discuss the specific advantages of alpha-2 agonists, let’s look at the older agents that have had some success.

Alpha-2 agonist alternative pharmacologic therapies (Table 3) Ketamine No thanks! Ketamine increases secretions, causes tachycardia, and disorients patients. The one time ketamine may come in handy is for the uncooperative and IV-less patient of whom you are trying to “get control.” The IM ketamine dart is just the ticket in such a case.9

Narcotics Narcotics including morphine, fentanyl, alfentanil, remifentanil, and others have been used to help with sedation of patients undergoing AFI. Narcotics will slow ventilation, cause muscle rigidity, have a delayed onset of action, and alter the sensorium (ie, not “Cooperative Sedation”). The advantages of narcotics include reversibility and suppression of airway reflexes.10

Anxiolysis

Easily titrated

Lack of secretions

Respiratory stability

Useful in Hypovolemic patients

** ** **** ** * ****

*** ** ** **** * ***

*** * *** ** ** ****

* *** ** ** *** ****

** **** *** ** *** *

and droperidol, and often made for a very cooperative patient, but the patient often had bad recollections when Innovar was used.12 In some circles Innovar became known as a “chemical straight-jacket.” Droperidol should probably be reserved for patients who won’t tolerate other sedatives due to their cardiovascular condition. Using droperidol has another potential headache, or should we say heartache: prolongation of the Q-T interval. This is an extremely cloudy and controversial issue, but potentially serious. In light of recent FDA “Dear Doctor” letters warning of the dangers of Droperidol, you may encounter some resistance to using this drug.13,14

Benzodiazepines Benzodiazepines are good choices for amnesia, anxiolysis, and sedation, but have no analgesic properties. Benzodiazepines are associated with respiratory depression, and don’t have the cooperative component which is produced by dexmedetomidine. Small amounts of midazolam (0.02-0.04 mcg/kg) may be a useful adjunct to dexmedetomidine to produce amnesia. In addition, there is a specific reversal agent for benzodiazepines. Let’s just come right out and say it: a little bit of midazolam, 1-2 mg in your average adult, is usually all the “additional stuff” you need when you do a dexmedetomidine awake intubation!

Propofol Propofol is a phenol derivative which often causes pain on injection. Since propofol has been introduced, many have used it as part of a cocktail for AFI. Propofol causes less respiratory depression than narcotics and is easily used by intravenous infusion. The disadvantage of propofol is that the airway reflexes may be blunted in a deeply sedated patient, potentially leading to regurgitation, loss of airway, bradypnea, and hypotension.11

Droperidol Droperidol is a butyrophenol derivative and does provide excellent sedation, especially when combined with fentanyl and midazolam. Innovar was a combination drug of fentanyl

Dexmedetomidine Dexmedetomidine is an alpha-2 agonist. As such it has unique properties, which makes it useful when you are taking care of patients with difficult airways. Other alpha-2 agonists have been around for years, used both with humans and animals. Since most of us aren’t vets and few of us remember those obscure compounds, let’s concentrate on the “PLAYER” in the alpha-2 arena: DEXMEDETOMIDINE. Dexmedetomidine is the most specific agent available to bind to the alpha-2 receptor. When alpha-2 agonists are present, there is stimulation of the alpha-2 receptor, which causes a negative feedback, causing less neurotransmitter (norepinephrine or epinephrine) at the postsynaptic receptor (alpha-1 receptor) (Figure

68

Seminars in Anesthesia, Perioperative Medicine and Pain, Vol 25, No 2, June 2006 Who knows, perhaps dexmedetomidine will prove useful in preventing cardiovascular complications in those of us doing AFI’s! Dexmedetomidine will potentiate the effects of intravenous and inhaled anesthetic agents by between 20-80%. AFTER a loading dose of dexmedetomidine, make sure you use less general anesthetic.15 You’re already halfway there! Since dexmedetomidine is a vasodilator and sympatholytic, authors and practitioners alike have advocated fluid loading and vagolytic therapy with agents such as glycopyrrolate. There have been many recent reports in the literature of using dexmedetomidine as part of the intravenous sedation of AFI.9,19-21 We will present a case typical of our own experience, which we hope will help you use dexmedetomidine in a safe and effective manner.

Case study

Figure 1 Site of action of alpha-2 agonists. (Color version of figure is available online.)

1). The various central nervous system subclass of alpha-2 receptors block the CNS effects of catecholamines, which include anxiolysis, sedation, and analgesia. Most of these effects are mediated specifically at the locus coeruleus and spinal cord.15 Dexmedetomidine has the unique property of “Cooperative Sedation.”16 This allows patients to better work with the medical staff to facilitate intubation. This includes cooperation while the airway is topicalized, the bronchoscope is passed, and after the endotracheal tube is in to verify an intact neurological system. Dexmedetomidine does not have any direct effect on the heart. At low dose ranges (up to 0.7 mcg/kg/hour), there is direct vasodilation. Ramsay and Ebert have used higher doses; Ramsay advocates doses which are an order of magnitude higher than in the package insert in patients with difficult airways. Unfortunately, Ebert and others have shown that these higher doses lead to arterial and pulmonary hypertension, reduced cardiac output, and obtundation. These issues make high-dose dexmedetomidine undesirable for AFI.17,18 Alpha-2 agonists have been shown to attenuate the perioperative catecholamine response. AFI will produce an obvious catecholamine response from patient, staff, and physician! Just look in an operating room when and AFI isn’t going well! “HOLD STILL!” “KEEP YOUR HAND DOWN!” “HOLD HIM DOWN!”

The patient is a 37-year-old (80 kg, 178 cms) white male who was involved in a motorcycle accident 2 days prior (Table 4). He had an unstable cervical spine fracture but was neurologically intact. The patient had no significant previous medical history except for social alcohol and marijuana use. Physical exam revealed a patient who was extremely anxious. Vital signs were as follows: BP 148/94, HR 112, RR 24, SaO2 96%. There were no other significant injuries or findings on physical examination. Laboratory and radiologic findings other than the cervical fracture were within normal limits. The neurosurgeon requested an AFI so that we wouldn’t need to manipulate his neck and would be able to do a quick neurological assessment after the endotracheal tube was correctly positioned. The patient had been NPO for 12 hours. He was brought into the pre-operative area. We rounded up all the usual suspects, including informed consent, detailing the need for AFI. We explained that the patient will be sedated for this procedure, but his cooperation during this procedure would help the intubation be accomplished more safely and comfortably.

Table 4 for AFI

Essential steps for safely using dexmedetomidine

Monitor patients ECG, oxygen saturation, EtCO2, and blood pressure Have staff who are experienced in AFI Have all essential airway equipment, including suction and oxygen Administer glycopyrrolate 0.2–0.3 mg IV Load dexmedetomidine 0.5–1.0 mcg/kg over 10–20 minutes Use continuous infusion of dexmedetomidine @ 0.2–0.7 mcg/kg/hour for as long as indicated Sparingly use benzodiazepines to assure amnesia, eg, 1–2 mg midazolam Use regional and topical anesthesia as necessary to assure patient comfort

Unger and Gallagher

Dexmedetomidine Sedation

Non-invasive monitors were placed which included: ECG, pulse-oximetry, and blood pressure monitors. The rhythm strip of ECG was examined to verify there was no presence of first degree or greater heart block. (Dexmedetomidine should not be given in the presence of heart block because of possible complications of life threatening heart block.) A free flowing 18-gauge IV was started, and the patient was then given a dose of glycopyrrolate 0.3 mg intravenously. A dexmedetomidine loading dose was then given. At the standard dilution of 4 mcg/ml, we loaded the patient with 80 mcg/10 minutes. This works out to a rate of 120 ml/hour ⫻ 10 minutes. Simultaneously, the patient was given 2 mg of midazolam IV, and we began to prep the patient for an AFI by application of topical anesthesia of the airway. This was accomplished in the following manner: 1% neosynephrine drops were applied as well as 4% lidocaine ointment that was applied to progressively larger nasal trumpets from 28-34 french. Supplemental oxygen was administered by nasal cannula at 4 liters/minute. By this time, the dexmedetomidine infusion was nearly complete, and the patient was very sleepy but arousable [Ramsay Sedation Scale (RSS) 2-3]. The dexmedetomidine infusion was started at 0.4 mcg/kg/hour (8 cc/hour). We then proceeded to use nebulized and atomized 4% lidocaine. The patient was very cooperative, and we applied the local anesthetic to the airway when the patient would inspire. A #7 Mallinckrodt endotracheal tube (ETT) was then gently passed into the left nares after the tip was lubricated with lidocaine ointment and softened with warmed saline. Then, the ETT was atraumatically passed into the hypopharynx. After attaching oxygen to the working channel of the bronchoscope, the fiberoptic bronchoscope was slowly passed through the vocal cords on the first pass. The unique cooperative sedation afforded by the dexmedetomidine allows the practitioner to more easily pass the bronchoscope into appropriate position in the trachea. This is due to the fact that the patient can work with you and take deep breaths as you advance the scope, facilitating correct placement! After the bronchoscope was positioned, the endotracheal tube was advanced over the bronchoscope and the pilot balloon was carefully inflated. The patient was then reassured that he wouldn’t be able to phonate, and would be shortly going to sleep. The ETT was confirmed to be in the right location by fiberoptic visualization, auscultation of the chest, ballottement, and confirmation of EtCO2. Vital signs were stable throughout the induction. The neurosurgeon performed a quick neurological examination, which included having the patient move all four extremities and checking sensation to light touch. General anesthesia was then induced with a relatively small dose of propofol (100 mg) and neuromuscular relaxation was achieved with 50 mg of rocuronium. Anesthesia was maintained with sevoflurane, nitrous oxide and 250 mcg of fentanyl. The dexmedetomidine infusion was main-

69 tained at 0.4 mcg/kg/hour. A brief episode of hypotension was treated with two boluses of 5 mg of ephedrine. Three hours later, at the conclusion of the case, the anesthetic vapors were turned off and recovery from neuromuscular blockers was assured with the aide of the nerve stimulator. The patient was then transported with the endotracheal tube in situ and dexmedetomidine infusion running at a rate of 0.4 mcg/kg/hour to the ICU. Once in the ICU, the patient was awake, adequate head lift was affirmed, and the trachea was extubated. The patient maintained his vital signs within a normal range and dexmedetomidine infusion was continued until the bag was empty about 3 hours later. The patient was intact neurologically, had minimal pain and a very successful outcome. Dexmedetomidine was extremely useful in this case because it calmed the patient before the procedure began, allowed us to toplicalize his airway, and the unique profile of the drug kept his oxygenation and ventilation intact. In addition, after the tube was confirmed in correct position, the patient was comfortable and cooperative as we did a cursory neurological evaluation. At the conclusion of the case, the patient awoke comfortably with the endotracheal tube in place, without undue amounts of coughing or agitation. Sometimes, airway compromise can result after this surgical procedure because of local trauma. Pain, agitation, and coughing can further compromise the airway. The analgesia, anxiolysis, and cooperative sedation associated with dexmedetomidine are very useful in the post-operative period in this subset of patients. The combination of the unique sedative properties, natural type sleep, cooperation, anxiolysis, and beneficial sympathectomy make dexmedetomidine an ideal drug for most awake fiberoptic intubations.

Practical tips for using dexmedetomidine for AFI Indications Indications include conscious sedation in a patient when it is essential to maintain ventilatory drive and have the patient cooperate with the invasive procedure. The medication also has the advantage of being sympatholytic creating a more stable peri-induction period.

Contra-indications Contra-indications include: hypovolemia, hypotension, aortic stenosis, cardiogenic shock, septic shock, idiopathic hypertrophic sub-aortic stenosis (IHSS), pulmonary hypertension, heart block (without back-up pacemaker present).

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Dosing Intravenously load 1 mcg/kg of dexmedetomidine over 10-20 minutes (distribution T1/2 6 minutes). Follow loading dose with continuous infusion at 0.2-0.7 mcg/kg/hour.

Caution Dose other sedatives, anxiolytics, and analgesics with caution, as alpha-2 agonists are synergistic with these other agents. Typically a small amount of midazolam (1-2 mgs intravenously) will be useful.

Discussion In the literature, research lab, and operating room, dexmedetomidine is finding a place as a pharmacologic adjunct for AFI. Ebert and Maze wrote an editorial on Ramsay’s series of dexmedetomidine cases. In this editorial, Ebert and Maze eloquently sing the praises of this “wonder drug”22: Ramsay and Luterman’s interesting series of cases provides another arrow in the quiver of clinicians for the management of surgical patients with compromised airways. We anticipate further comparative studies to establish the clinical role of dexmedetomidine in difficult airway algorithms. In difficult airway workshops and academic research, dexmedetomidine is rapidly finding a place. There are at least five separate reports in the literature discussing the utility of dexmedetomidine in this difficult clinical scenario.9,18-21 The largest of these is by Avistsian et al. They retrospectively report on 20 cases where dexmedetomidine was used to help facilitate AFI. None of their patients had any desaturation episodes. Thirteen patients developed post induction hypotension (perhaps due to the fact that induction doses of intravenous agents weren’t altered enough?), which was promptly corrected with boluses of ephedrine and phenylephrine. One patient needed a single small (10 mcg) bolus of epinephrine to treat more refractory hypotension. In all cases, the AFI was recorded as “smooth,” with good patient tolerance and no airway obstruction during the procedure. Dexmedetomidine is being discovered as a very useful drug in select patients for select procedures in both the operating room and intensive care unit. With well over 700 cases of dexmedetomidine use in our group, we have found the drug most useful. For us, the difficult airway and awake intubation means dexmedetomidine. The unique sedation with arousability, lack of respiratory depression, complete anxiolysis, and moderate analgesia make dexmedetomidine the best available drug in this area. In addition, the sympatholytic effects of dexmedetomidine can be extremely useful during this procedure to blunt the hemodynamic and cardiac response to the resultant high catecholamine levels. Caution is the word when using dexmedetomidine. Patients should be euvolemic, have no evidence of inadequate perfusion, or have any evidence of impaired intra cardiac conduction. When faced with hypotension secondary to dexmedetomidine, the clinician can usually easily treat this

with typically available vasopressor agents. Once used, dexmedetomidine will nearly always make the awake fiberoptic intubation easier for patient and clinician.

References 1. Miller CD: Management of the difficult intubation in closed malpractice claims. ASA Newsletter 64:13-16,19, 2000 2. Wilson WC: Trauma: airway management ASA difficult airway algorithm modified for trauma —and five common trauma intubation scenarios. ASA Newsletter 69:9-16, 2005 3. Ovassapian A, Yelich SJ, Dykes HM, et al: Blood pressure and heart rate changes during awake fiberoptic nsasotracheal intubation. Anesh Analg 62:951-954, 1983 4. Bailey PL, Pace NL, Ashburn MA, et al: Frequent hypoxemia and apnea with sedation with midazolam and fentanyl. Anesthesiology 73:826-830, 1990 5. Batra YK, Mathewm PJ: Airway management with endotracheal intubation (including awake intubation and blind intubation.) Indian J Anaesth 49:263-268, 2005 6. Bol CJJ, Vogelaar JPW, Tang JP, et al: Quantification of pharmacodynamic interactions between dexmedetomidine and midazolam in the rat. J Pharmacol Exp Ther 294:347-355, 2000 7. Watanabe H, Lindren L, Rosenberg P, et al: Glycopyrronium prolongs topical anaesthesia of the oral mucosal and enhances absorption of lignocaine. Br J Anaestha 70:94-95, 1993 8. Peden CJ, Cloote AH, Stratford N, et al: The effect of intravenous dexmedetomidine premedication on the dose requirement of propofol to induce loss of consciousness in patients receiving alfentanil. Anaesthesia 56:408-413, 2001 9. Scher C, Gitlin M: Dexmedetomidine and low-dose ketamine provide adequate sedation for awake fibreoptic intubation. Can J Anesth 50: 607-610, 2003 10. Reusche MD, Talmage DE: Remifentanil for conscious sedation and analgesia during awake fiberoptic tracheal intubation: a case report with pharmoacokinetic simulations. J Clin Anesth 11:64-68, 1999 11. Kakodkar P, Lua S, Sear J, et al: Target controlled propofol for awake fiberoptic intubation. Difficult Airway Society Abstracts Edinburgh, 1999 12. Kallos T, Smith TC: The respiratory effects of Innovar given for premedication. Br J Anaesth 41:303-306, 1969 13. Habib AS, Gan TJ: Food and drug administration black box warning on the perioperative use of droperidol: a review of the cases. Anesth Analg 96:1377-1379, 2003 14. Scuderi PE: You (still) can’t disprove the existence of dragons. Anesthesiology 102:1081-1082, 2005 15. Gertler R, Brown C, Mitchell DH, et al: Dexmedetomidine: a novel sedative agent. Baylor University Medical Center Proceedings 14:1321, 2001 16. Belleville JP, Ward DS, Bloor BC, et al: Effects of intravenous dexmedetomidine in humans. I. Sedation, ventilation and metabolic rate. Anesthesiology 77:1125-1133, 1992 17. Ebert TJ, Hall JE, Barney JA, et al: The effects of increasing plasma concentrations of dexmedetomidine in humans. Anesthesiology 93: 382-394, 2000 18. Ramsay MAE, Luterman DL: Dexmedetomidine as a total intravenous anesthetic agent. Anesthesiology 101:787-790, 2004 19. Jooste E, Ohkawa S, Sun L: Fiberoptic intubation with dexmedetomidine in two children with spinal cord impingements. Anesth Analg 101:1248, 2005 20. Avitsian R, Lin J, Lotto M, et al: Dexmedetomidine and awake fiberoptic intubation for possible cervical spine myelopathy. Neurosurg Anesthesiol 17:97-99, 2005 21. Maroof M, Khan R, Jain D, et al: Dexmedetomidine is a useful adjunct for awake intubation. Can J Anesth 52:776-777, 2005 22. Ebert T, Maze M: Dexmedetomidine: another arrow for the clinician’s quiver. Anesthesiology 101:568-570, 2004