A Phase IIIb, Randomized, Double-blind, Placebo-controlled, Multicenter Study Evaluating the Safety and Efficacy of Dexmedetomidine for Sedation During Awake Fiberoptic Intubation

Abstract

GABA-mediated sedatives have respiratory depressant properties that may be detrimental in patients with difficult airways. In this randomized, double-blind, multicenter, Phase IIIb Food and Drug Administration study, safety and efficacy of dexmedetomidine compared with placebo were evaluated as the primary sedative for awake fiberoptic intubation (AFOI). Patients were randomized to receive dexmedetomidine or saline. Patients were sedated with dexmedetomidine or rescue midazolam to achieve targeted sedation (Ramsay Sedation Scale ≥ 2) before topicalization and throughout AFOI. Primary efficacy endpoint was percentage of patients requiring rescue midazolam; secondary efficacy endpoints were total dose of rescue midazolam, percentage requiring additional rescue nonmidazolam medications, anesthesiologist's assessment of ease of subject care, and patient recall and satisfaction 24 hours postoperatively. Less rescue midazolam was required to maintain Ramsay Sedation Scale ≥2 (47.3% vs. 86.0%, P < 0.001), and supplemental midazolam dose was lower (1.07 ± 1.5 mg vs. 2.85 ± 3.0 mg, P < 0.001) with dexmedetomidine compared with placebo. More Mallampati Class IV patients treated with dexmedetomidine were successfully intubated without midazolam than with placebo (66.7% vs. 8.3%, P = 0.009). Dexmedetomidine decreased blood pressure and heart rate compared with placebo patients sedated with midazolam. Patients and anesthesiologists showed favorable satisfaction responses in both groups. Adverse events and patient recall were similar in both groups. Dexmedetomidine is effective as the primary sedative in patients undergoing AFOI. Some patients may require small supplemental doses of midazolam, in addition to dexmedetomidine, to achieve sufficient sedation for AFOI. Dexmedetomidine provides another AFOI option for sedation of patients with difficult airways.

Dexmedetomidine versus Midazolam for Conscious Sedation in Postoperative Patients Undergoing Flexible Bronchoscopy: A Randomized Study

“…As a more highly selective α 2 -adrenoreceptor agonist than clonidine, dexmedetomidine has been shown to blunt haemodynamic responses during intubation and extubation whilst the patient is conscious. 27,28 In the present study, patients sedated with dexmedetomidine displayed fewer sympathetic responses to bronchoscopy compared with those sedated with midazolam. Fox et al 29 concluded that adequate midazolam-alfentanil sedation could blunt the sympathetic response to bronchoscopy, and that prophylactic labetalol had no additional advantageous effects on haemodynamic stability.…”

Sedation for flexible bronchoscopy: current and emerging evidence

“…It has the advantage of only causing mild respiratory depression at higher doses but does have sympathomimetic and vagolytic actions that may lead to bradycardia and hypotension [83]. These features are useful to attenuate the sympathetic response to intubation which it has been shown to do safely and effectively in flexible bronchoscopy for awake intubation [84] and in upper and lower gastrointestinal endoscopy [85][86][87], but it does require continuous cardiovascular monitoring to avoid unwanted complications. For upper gastrointestinal endoscopy dexmedetomidine resulted in a shorter recovery time and increased patient satisfaction when compared to midazolam [86].…”

A randomised comparative study of dexmedetomidine and midazolam for sedation during awake fiberoptic intubation in laproscopic cholecystectomy patients

“…Many agents have been reported to provide sedation for intubation including fentanyl, ketamine, midazolam, remifentanil, propofol, and dexmedetomidine. [1][2][3][4][5] Dexmedetomidine, an α2-adrenoceptor agonist, may be a wondrous drug for use during fiberoptic intubation as it produces sedation and analgesia without concomitant depressing respiratory function. 6,7 Thus, dexmedetomidine possess numerous properties that make it a convenient drug for use in managing patients with difficult airways.…”