Original article
Prospective analysis of efficacy and safety of an individualized-midazolam-dosing protocol for sedation during prolonged bronchoscopy

https://doi.org/10.1016/j.resinv.2013.09.003Get rights and content

Abstract

Background

Newer more advanced techniques in bronchoscopy may require longer procedure times, although a standard protocol for sedation during prolonged bronchoscopy has not yet been defined.

Methods

We designed a prospective, non-randomized, single-arm study (UMIN trial number 000003971) using patient questionnaires and vital sign monitoring to assess the efficacy and safety of a standardized midazolam dosing protocol based on gender and age for use during bronchoscopy. The loading dose of midazolam was 0.075 mg/kg for men ≤65 years old and women ≤70 and 0.05 mg/kg for men ≥66 years and women ≥71 years, with subsequent doses of one-half the loading dose to be administered every 20 min. The primary endpoint was tolerability and secondary endpoints included anxiety and recall of procedure, willingness to undergo repeat procedure, and complications. Safety was evaluated in terms of monitored changes in blood pressures, ECG, oxygen saturation, and CO2 content in expiration during the procedure.

Results

A total of 204 patients were included in the study. Overall, 163 patients (79.9%) reported “no distress” during the procedure, 185 patients (90.7%) reported “no anxiety,” and 175 (85.8%) replied that they would accept a repeat procedure, if necessary. The mean minimum oxygen saturation was 90.2% and the mean maximum expiratory CO2 level was 37.7 mmHg. There were no serious complications related to the protocol.

Conclusions

The midazolam dosing protocol examined in this study was safe and effective. It is simple, and it could easily be translated to routine clinical practice.

Introduction

Flexible bronchoscopy is frequently used for the diagnosis or management of pulmonary disorders. In order to minimize patient discomfort, sedation is recommended when there is no contraindication [1]. The ideal sedative will be safe, easy to use, effective, and economical. Several trials have been conducted to determine the best sedation methods for patients undergoing bronchoscopy [2], [3], and benzodiazepines such as midazolam, opioids, and propofol or fospropofol (a prodrug of propofol) have all been recommended [4], [5], [6], but no standard protocol has been established, and neither ideal initial doses nor timing of additional doses have been specified. The advanced techniques and equipment that have been introduced to the field of respiratory endoscopy, including endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) and EBUS-guided transbronchial lung biopsy [7], have allowed greater diagnostic yield, but they are more complicated and may require longer examination times [8]. Thus, it is important to determine the most suitable sedation methods for bronchoscopic procedures. The short-acting benzodiazepine midazolam is one of the most commonly used sedatives, and it has been proven safe even for patients with stable respiratory failure [9]. Various reports and international guidelines have recommended initial doses of midazolam ranging from 0.07 mg/kg to 0.67 mg/kg [1] and have also demonstrated that 2 mg/body of midazolam with or without opiates is sufficient for initial sedation during bronchoscopy. Although there is still no standardized method for incremental dosing of midazolam, it is recognized that incremental dosing is required because sufficient sedation usually will not be achieved by a single dose [1]. In previous trials, additional injections of midazolam have been administered according to the operator's discretion, based mainly on the assessment of patient's condition [1], [9]. This method carries a risk of overdose. In addition, it may be difficult to ensure effective sedation in the absence of an established protocol during routine clinical practice. The bispectral index (BIS) and the observer assessment of alertness/sedation score (OAA/S) are both used for assessing levels of sedation [10]. The BIS is largely non-invasive and is a useful indicator of the depth of anesthesia during bronchoscopy, but it requires electroencephalography (EEG) and electromyography (EMG) data, which may limit its availability in the daily clinical setting. We conducted a pilot study (unpublished data) examining the efficacy of midazolam sedation during bronchofiber examination at our institution in which we administered a single dose of 0.05 mg/kg midazolam at the start of the examination without any additional injections. We found that patients had significantly increased discomfort and anxiety levels when the examination lasted longer than 20 min, and we discovered that male patients younger than 66 years and female patients younger than 71 years experienced greater discomfort than older patients. Thus, we determined that midazolam dose should be adjusted based on sex and age. It was under these circumstances that we proposed a simple method of midazolam administration using individualized (mg/kg) metered initial doses and timed additional dosages for sedation during bronchoscopy. The current study was performed to assess the efficacy and safety of this protocol.

Section snippets

Study design

This was a prospective, non-randomized, single-center study (trial number: UMIN 000003971). The Nagoya University Hospital Institutional Review Board approved the protocol (Nagoya University approval no. 908-2, approval date; May 21, 2010). The study was performed in accordance with the ethical standards of the Declaration of Helsinki. All patients provided written informed consent.

Patients

Consecutive patients ≥20 years of age who underwent diagnostic bronchoscopy in Nagoya University Hospital between

Baseline characteristics

During the study period, we performed bronchoscopy for 257 consecutive patients at a single hospital. Eight patients who underwent therapeutic bronchoscopy (four with argon plasma coagulation, two with endobronchial tumor resection with snare, and two with endobronchial Watanabe spigot insertion) were excluded. Among the 249 remaining patients who underwent only diagnostic bronchoscopy, there were 37 who did not meet the eligibility criteria: 20 because of inability to answer the questionnaire

Discussion

Recent progress and new techniques in bronchoscopy have led to greater diagnostic yields, but prolonged examination times. Transbronchial biopsy of peripheral nodules using an endobronchial ultrasound probe with a guide sheath allows diagnosis even for peripheral lesions of ≤10 mm in diameter [12], [13] and transbronchial needle aspiration biopsy (TBNA) of enlarged mediastinal lymph nodes using an EBUS scope has become a mainstay in the diagnosis of sarcoidosis or the staging of lung cancer [14]

Conflict of interest

The authors have no conflict of interest.

Funding/support

This study was supported in part by Health and Labor Science research grants from the Ministry of Health, Labor, and Welfare (No. 22590857).

Acknowledgments

The authors thank Professor Kaoru Shimokata for his continuous helpful advice in preparing the manuscript.

References (22)

  • British Thoracic Society Bronchoscopy Guidelines Committee, British Thoracic Society guidelines on diagnostic flexible...
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    1

    Present address: Department of Respiratory Medicine, Tsushima Municipal Hospital, Tsushima, Japan.

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