A comparative study of dexmedetomidine with midazolam and midazolam alone for sedation during elective awake fiberoptic intubation

doi:10.1016/j.jclinane.2009.02.016

Journal of Clinical Anesthesia

Volume 22, Issue 1, February 2010, Pages 35-40

https://doi.org/10.1016/j.jclinane.2009.02.016 Get rights and content

Abstract

Study Objective

To evaluate the efficacy of dexmedetomidine with midazolam (DEX-MDZ) versus midazolam only (MDZ) for sedation during awake fiberoptic intubation (AFOI).

Design

Randomized, double-blinded study.

Setting

Academic medical center.

Subjects

55 ASA physical status I, II, III, and IV patients, aged 18-85 years, scheduled for non-emergency surgery with AFOI.

Interventions

All patients received intravenous (IV) glycopyrrolate 0.2 mg premedication, oxygen by nasal cannula, and topical local anesthetics to the airway. MDZ subjects received IV midazolam 0.05 mg/kg with additional doses to achieve a Ramsay Sedation Scale (RSS) score of ≥ 2. DEX-MDZ patients received midazolam 0.02 mg/kg followed by dexmedetomidine one μg/kg, then an infusion of dexmedetomidine 0.1 μg/kg/hr and titrated to 0.7 μg/kg/hr to achieve RSS≥2.

Measurements

Observers' Assessment of Alertness/Sedation (OAA/S) and RSS were evaluated. The anesthesiologist rated AFOI ease of placement. Two observers rated patients' comfort and reaction to placement at three time points: preoxygenation, at introduction of the fiberoptic laryngoscope, and at introduction of the endotracheal tube (ET) before surgery. Following surgery, patients were asked if they recalled the AFOI and also to rate their satisfaction with the intubation.

Results

DEX-MDZ patients were significantly calmer and more cooperative during AFOI and had fewer adverse reactions to AFOI than did the MDZ patients. They also were more satisfied with the AFOI (P < 0.001) than were the midazolam-only patients. There were no significant hemodynamic differences between the two subject groups.

Conclusions

Dexmedetomidine in combination with low doses of midazolam is more effective than midazolam alone for sedation in AFOI.

Introduction

Awake fiberoptic intubation (AFOI) is indicated for patients with an anticipated difficult intubation because of their anatomy, airway trauma, morbid obesity, or unstable cervical spine injuries [1]. The term “AFOI” is used to distinguish this procedure from fiberoptic intubation performed during general anesthesia. Although patients may be sedated for AFOI, it is essential that they be responsive and capable of maintaining their airway without assistance. The most common complications of this procedure are hypoxemia and aspiration [2].

Benzodiazepines combined with opioids are commonly used for anxiolysis and/or analgesia during AFOI. Unfortunately, this combination of drugs can cause respiratory depression, placing the patient at risk for hypoxemia and aspiration. In a study of volunteers, Bailey et al reported that the combination of midazolam and fentanyl increased the frequency of hypoxemia in 11 of 12 subjects and produced apnea in 6 of 12 subjects [3].

Dexmedetomidine has not been associated with respiratory depression when used alone, in spite of the deep levels of sedation it can produce [4], [5], [6]. Furthermore, dexmedetomidine facilitates a decrease in salivary secretions, which is a desirable effect during fiberoptic intubation [6]. Dexmedetomidine alone has been used for sedation and analgesia in patients with unstable cervical spines who undergo fiberoptic intubation prior to surgery [7]^⁎. Grant et al used dexmedetomidine in three patients without any other sedatives or analgesics [7]. Patients received three different infusion rates ranging from 0.3 to 0.7 μg/kg/hr following a loading dose of one μg/kg over 10 minutes. All patients were sedated without respiratory depression and were able to perform a neurological evaluation after fiberoptic intubation. The effects of dexmedetomidine in decreasing sympathetic activity and providing cooperative sedation without respiratory depression may be beneficial for difficult airway patients undergoing AFOI. Dexmedetomidine injection is currently approved for sedation for up to 24 hours in intubated and mechanically ventilated patients in an intensive care setting.

In this study, a dexmedetomidine-midazolam combination was compared with midazolam alone for sedation during elective oral AFOI in adult patients.

Section snippets

Experimental procedure

This double-blinded (patient and assessor), randomized comparison study was conducted with the Ohio State University Institutional Review Board approval and written, informed consent. All adult patients undergoing AFOI for non-emergency surgery were potential candidates for this study. Patients were excluded from this study if they were: 1) prisoners, 2) pregnant, 3) mentally ill, 4) under the age of 18 years, 5) known or admitted alcohol or drug abusers, or 6) allergic to the drugs involved in

Results

A total of 58 patients were enrolled in the study. Three enrolled patients were excluded because they underwent a nasal intubation. Twenty-four MDZ patients and 31 DEX-MDZ patients completed all aspects of the study. Mean age (MDZ 48.8 ± 15.8 yrs; DEX-MDZ 43.0 ± 17.8 yrs), mean weight (MDZ 99.7 ± 31.5 kg; DEX-MDZ 120.0 ± 42.8 kg), median ASA physical status (MDZ, III; DEX-MDZ, III), and median Mallampati airway class (MDZ, 3; DEX-MDZ, 3) of the experimental groups were statistically similar.

Discussion

When performing AFOI, anesthesiologists may find it difficult to provide enough sedation for patients to be comfortable and cooperative, while at the same time avoiding airway compromise from too much sedation. The ideal sedation provides patient comfort and maintenance of spontaneous respiration without altering airway function. The patients receiving dexmedetomidine with midazolam had sedation and intubation conditions equal to the patients receiving midazolam alone. The number of FOS

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Whereas, dexmedetomidine has gained popularity as a preferred medication for conscious sedation.4 It also has anxiolytic, amnestic, analgesic, as well as antisialogogue properties.5 Dexmedetomidine has a respiratory sparing effect even when administered in large doses.6,7
Awake fiberoptic intubation (AFOI) is usually performed in patients with an anticipated difficult airway. Various sedation regimens are used during AFOI, however, most of them cause respiratory depression. The present study aims to compare the effectiveness of fentanyl with ketamine versus dexmedetomidine in search of a better sedation regimen which would achieve desirable intubating conditions and hemodynamic stability without causing respiratory depression.
This is a single centered randomized, double-blind clinical trial. Patients of both sexes between age 18–55 years and ASA (American Society of Anesthesiologists) physical status I–II with an anticipated difficult airway were randomly divided into two groups of thirty each. Group FK patients received intravenous fentanyl and ketamine, and group DX patients received dexmedetomidine, until Ramsay sedation scale ≥ 2. Heart rate (HR), mean blood pressure (MBP), oxygen saturation (SpO₂), respiratory rate (RR), endoscopy time, intubation time, first end-tidal carbon dioxide (ETCO₂) after intubation, endoscopist satisfaction score, and patient discomfort score were recorded during the study period. The level of recall was assessed on the next postoperative day.
Endoscopist satisfaction score was better in group DX patients (p < 0.05). There was a smaller variation in HR and MBP from baseline with dexmedetomidine compared to fentanyl with ketamine. First ETCO₂ after intubation was higher in group FK patients (p < 0.05). No significant difference was found in patient discomfort score, intubation time, RR, SpO₂ and level of recall of the event.
The use of dexmedetomidine in AFOI provides better intubating conditions and hemodynamic stability compared to fentanyl with ketamine.
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Prospective, randomized, blinded, clinical study.
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Dogs were assigned to four groups: medetomidine 15 μg kg^–1 (positive control group), medetomidine 10 μg kg^–1 and midazolam 0.2 mg kg^–1, medetomidine 5 μg kg^–1 and midazolam 0.3 mg kg^–1, and medetomidine 5 μg kg^–1 and midazolam 0.2 μg kg^–1. The same clinician assessed sedation after administration at T2.5 minutes and T5 minutes using a composite simple descriptive sedation scale ranging between 0 and 15 (0 = no sedation; 15 = profound sedation). The dose of propofol for induction, quality of induction, ease of intubation and any adverse events were recorded.
There was no significant difference in sedation scores between treatment groups at T2.5 minutes or T5 minutes (p = 0.82 and p = 0.63, respectively). Administration of midazolam in combination with medetomidine resulted in 71% of dogs displaying paradoxical behaviours (p < 0.0001) such as agitation, excitation, restlessness, aggression and vocalization, which was different from pre-sedation. Propofol requirement was not different between groups. Induction and tracheal intubation quality was smooth in all groups.
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We searched globally recognized electronic databases, including PubMed, Cochrane Central and EMBASE, to retrieve relevant randomized controlled trials (RCTs) of anaesthetic medications for ERCP. Network meta-analysis was conducted by evaluating the procedure time, adverse effects and drug requirements. The cumulative probability P value was utilized to rank the medications under examination.
Seventeen RCTs that examined 1877 patients were included in this research. Under good convergence and efficiency, data analysis was performed using a consistency model. For the comparison of procedure times, we found that a combination of dexmedetomidine and ketamine (P = 0.19) or propofol plus pethidine (P = 0.18) seemed to be the two best medications for reducing procedure time. Additionally, midazolam combined with dexmedetomidine plus pethidine seemed to be the safest application for ERCP (P = 0.36). Propofol plus alfentanil also exhibited a good safety value (P = 0.28). For evaluation of drug requirements, the whole network connection could not be established; thus, comparisons in two subgroups were conducted. The results showed that midazolam combined with dexmedetomidine plus pethidine (P = 0.41) and propofol plus refentanil (P = 0.94) were superior to others in decreasing drug requirements.
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Original contributionA comparative study of dexmedetomidine with midazolam and midazolam alone for sedation during elective awake fiberoptic intubation☆

Abstract

Study Objective

Design

Setting

Subjects

Interventions

Measurements

Results

Conclusions

Introduction

Section snippets

Experimental procedure

Results

Discussion

J Clin Anesth

Br J Anaesth

J Oral Maxillofac Surg

Airway management

Frequent hypoxemia and apnea after sedation with midazolam and fentanyl

Anesthesiology

Clinical uses of alpha2-adrenergic agonists

Anesthesiology

The effects of increasing plasma concentrations of dexmedetomidine in humans

Anesthesiology

Respiratory effects of dexmedetomidine in the surgical subject requiring intensive care

Crit Care Med

Validity and reliability of the Observer's Assessment of Alertness/Sedation Scale: study with intravenous midazolam

J Clin Psychopharmacol

Original contribution
A comparative study of dexmedetomidine with midazolam and midazolam alone for sedation during elective awake fiberoptic intubation☆