Original articleProspective analysis of efficacy and safety of an individualized-midazolam-dosing protocol for sedation during prolonged bronchoscopy
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)
- et al.
A comparative evaluation of propofol and midazolam as sedative agents in fiberoptic bronchoscopy
Chest
(1993) - et al.
Benzodiazepine and opioid sedation attenuate the sympathetic response to fiberoptic bronchoscopy. Prophylactic labetalol gave no additional benefit. Results of a randomized double-blind placebo-controlled study
Respir Med
(2008) - et al.
A phase 3, randomized, double-blind study to assess the efficacy and safety of fospropofol disodium injection for moderate sedation in patients undergoing flexible bronchoscopy
Chest
(2009) - et al.
Endobronchial ultrasonography using a guide sheath increases the ability to diagnose peripheral pulmonary lesions endoscopically
Chest
(2004) - et al.
Real-time endobronchial ultrasound-guided transbronchial needle aspiration of mediastinal and hilar lymph nodes
Chest
(2004) - et al.
The role of EBUS-TBNA for the diagnosis of sarcoidosis--comparisons with other bronchoscopic diagnostic modalities
Respir Med
(2009) - et al.
Midazolam sedation to produce complete amnesia for bronchoscopy: 2 years' experience at a district general hospital
Respir Med
(1999) - et al.
Comparison of midazolam with propofol for sedation in outpatient bronchoscopy
Br J Anaesth
(1993) - et al.
Do all patients require supplemental oxygen during flexible bronchoscopy?
Chest
(2001) - et al.
The challenge of NSCLC diagnosis and predictive analysis on small samples. Practical approach of a working group
Lung Cancer
(2012)
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Safety and Efficacy of Flexible Bronchoscopy in Elderly Patients: A Retrospective Comparative Study
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Inhalation of 50% Oxygen Does Not Impair Respiratory Depression During Midazolam Sedation
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Present address: Department of Respiratory Medicine, Tsushima Municipal Hospital, Tsushima, Japan.