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Optimal Premedication for Diagnostic Flexible Fiberoptic Bronchoscopy Without Sedation: A Randomized Phase II Study

Korteweg, Christine MD*; van Mackelenbergh, Bibi A. H. A. MD*; Zanen, P. MD, PhD; Schramel, Franz M. N. H. MD, PhD*

Original Article
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Since the introduction of the flexible fiberoptic bronchoscopy (FFB), no consensus has been reached concerning premedication. We investigated the effect of 4 premedication regimes on 6 outcomes (patients' comfort, dyspnea and coughing experienced by the patient, coughing and bronchial secretion observed by the bronchoscopist and supplemental instilled tetracaine) in patients undergoing FFB. Two hundred forty-seven patients underwent 258 FFBs and were randomly selected to receive the following premedication regimes: 0.5 mg atropine intramuscularly and 20 mg codeine (n = 48), 2 mL (0.25 mg/mL) inhaled ipratropium bromide (n = 50), 20 mg codeine (n = 76), and no premedication (n = 84).The amount of endoscopically applied tetracaine was registered during the FFB. Patients and the bronchoscopists filled out a questionnaire and a semiquantitative visual analog scale regarding the previously mentioned outcomes after the procedure. Patient comfort was significantly higher in the patient group using atropine and codeine as premedication (P = 0.001). Female gender and having had a prior bronchoscopy were negative predictors for patient comfort (P = 0.006 and P = 0.021). Patients using codeine or atropine and codeine experienced less coughing (P = 0.044, P = 0.050). In conclusion, codeine showed a beneficial effect on suppressing cough. The role of atropine seems to be limited to its sedative action, improving patients' comfort. However, for this purpose, other sedatives could be preferred. FFB can be performed safely without premedication. Smoking has a negative impact on dyspnea and coughing during FFB.

From the *Departments of Pulmonology and †Statistics, St. Antonius Hospital Nieuwegein, Nieuwegein, The Netherlands.

Reprints: Franz M. N. H. Schramel, MD, PhD, Department of Pulmonology, St. Antonius Hospital, PO Box 2500, 3430 EM Nieuwegein, The Netherlands (e-mail: f.schramel@antonius.net).

Since the introduction of the flexible fiberoptic bronchoscopy (FFB) in 1968, various types of drugs have been used as premedication. 1,2 Several studies have been performed on this subject, but still no consensus exists concerning the optimal premedication. The drugs most commonly prescribed are anticholinergics, sedatives, and codeine. The use of sedatives can increase patients' comfort and tolerance during FFB, 3,4 yet prior studies showed that 50% of life-threatening complications have been related to sedative regimes. 5,6 Therefore, the routine use of sedation before FFB is not strongly supported by data. 5,7 Codeine is given to suppress cough reflex during FFB, resulting in reduced use of topical anaesthetics. 8 Inoue et al. suggested that pretreatment with ipratropium bromide could prevent bronchoconstriction resulting from FFB. 9 The anticholinergic action of atropine is supposed to decrease airway secretions resulting in optimal efficacy of topical anesthetics and improved visibility during FFB. 10–12 Moreover, atropine could prevent cardiac arrhythmias by preventing vasovagal reactions. 10,13 However, several studies questioned the routine use of premedication and, in particular, of anticholinergic medication. 14–17

In this study, we compared our routinely used premedication consisting of codeine and atropine with nebulized ipratropium bromide with just codeine and without premedication. We evaluated the following outcomes: patients' comfort, dyspnea and cough experienced by the patient, cough and secretion observed by the bronchoscopist, and the amount of additional instilled local anesthetics. Our goal was to define the optimal premedication for diagnostic FFB with maximal patient tolerance and comfort and with minimal side effects or complications.

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PATIENTS AND METHODS

Patients referred for diagnostic FFB were eligible for this prospective, randomized phase 2 study. Exclusion criteria were the following: severe hemoptysis, respiratory or hemodynamic instability, and an Eastern Cooperative Oncology Group (ECOG) performance score ≥2. Patients scheduled for therapeutic bronchoscopy were excluded because most of these patients required rigid bronchoscopy under general anesthesia. The diagnostic procedures consisted of examining the bronchial tree with or without forceps biopsy, brushing, and bronchial lavage. Smokers were defined as persons who smoked cigarettes, cigars, or a pipe regardless of the number of pack-years. The study was performed during 2 periods. In the first period (period I), patients were randomly assigned to receive standard premedication consisting of 0.5 mg atropine intramuscularly and 20 mg codeine orally (arm A) or 2 mL nebulized ipratropium bromide (0.25 mg/mL) 30 minutes before bronchoscopy (arm B). In the second period (period II), patients received codeine (arm C) or no premedication at all (arm D). The oropharynx of each patient was sprayed with 10 mL tetracaine (by a nurse on our endoscopy staff) until gag and cough reflexes subsided. Ten milliliters of tetracaine 0.5% was instilled onto the vocal cords under direct vision by the bronchoscopist directly before the investigation. Fourteen experienced bronchoscopists randomly performed the bronchoscopy. Bronchoscopy was performed orally with the patient in the supine or horizontal position. If the patients exhibited severe coughing during the bronchoscopy, intrabronchial supplemental tetracaine was instilled. The amount of endoscopically applied tetracaine was registered during the procedure. All patients were monitored by continuous pulse oximetry (Nellcor N-180 pulse oximeter, Hayward, California). Immediately after the procedure, the bronchoscopist scored the amount of airway secretion and severity of coughing using a semiquantitative visual analog scale (VAS rate, 0–10; 0 = no secretion/cough; 10 = severe secretion/cough). Patients were asked to fill out a questionnaire and a semiquantitative visual analog scale concerning general comfort, cough, and dyspnea sensation within 15 minutes after the procedure (VAS rate, 0–10; 0 = excellent, no cough, no dyspnea; 10 = unbearable, severe cough, severe dyspnea).

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Statistics

Patient characteristics were compared in the 4 study groups using Pearson chi-square. Means and univariate analysis were used for the 6 outcomes (patient comfort, cough and dyspnea experienced by the patient, cough and bronchial secretion observed by the bronchoscopist, and the amount of additional instilled local anesthetic). This was followed by a post-hoc least significant difference test to compare the outcomes among the 4 study groups. The significance level was selected as P < 0.05. Multivariate models were developed for the analysis of the 6 outcomes using logistic regression. Logistic regression can be used to examine the unique contribution of each independent variable to the 6 outcomes. Independent variables for this multivariate model included patient age, gender, smoking status, having or not having had a prior bronchoscopy, and the 3 types of premedication. The 3 types of premedication were compared with no premedication. The cutoff value for the 6 outcomes was selected as 5.

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RESULTS

Two hundred forty-seven patients were eligible and underwent 258 endoscopic procedures. In period I, 48 patients were randomized to arm A consisting of the standard premedication and 50 patients to arm B consisting of nebulized ipratropium bromide. In period II, 76 patients were selected to receive only codeine (arm C) and 84 patients to receive no premedication at all (arm D). No significant differences were seen in patient characteristics and the indications for bronchoscopy (Tables 1 and 2). No complications were seen during or after the procedures.

TABLE 1

TABLE 1

TABLE 2

TABLE 2

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Outcomes

Univariate Analysis

Patients comfort showed a significant difference between the groups (P = 0.046;Fig. 1). Patients in the inhaled ipratropium bromide group experienced more cough during FFB but this did not reach statistical significance. More local anesthetics were needed to control coughing in the patient group using no premedication, but this did not reach statistical significance (Fig. 2).

FIGURE 1.

FIGURE 1.

FIGURE 2.

FIGURE 2.

Multiple comparisons showed a significant difference for patients' comfort when comparing patients with atropine and codeine as premedication to patients without premedication or with codeine only. The patients having atropine and codeine as premedication rated the bronchoscopy as more comfortable than patients with no premedication or with codeine only (P = 0.004, P = 0.035) (Table 3).

TABLE 3

TABLE 3

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Multivariate Analyses

In multivariate analysis, patients' comfort was significantly higher in the patient group using atropine and codeine (P = 0.001;Table 4). Female gender and having had a prior bronchoscopy were both negative predictors for patient comfort (P = 0.006 and P = 0.021;Table 4). Patients who did not smoke experienced significantly less coughing during bronchoscopy (P = 0.020;Table 4). Patients who used codeine only or atropine and codeine experienced less coughing (P = 0.044, P = 0.050;Table 4). Smoking status is the single variable influencing dyspnea experienced by the patient, coughing observed by the bronchoscopist, and the amount of additional tetracaine used (P = 0.030, P = 0.032, P < 0.001;Table 4). Smokers experienced more coughing and dyspnea and they needed more additional tetracaine. Older patients had significantly more bronchial secretion observed by the bronchoscopist (P = 0.032;Table 4).

TABLE 4

TABLE 4

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DISCUSSION

In 1968, Ikeda introduced FFB for diagnostic procedures in the central airways. 18 Since then, pulmonologists have been practicing FFB on a daily basis, but unfortunately, no uniform premedication regimen is being used. Until today, the kind of premedication that is being used is predominantly dependent on the experience of the bronchoscopist. Atropine, nebulized ipratropium bromide, and codeine have been used as premedication. The objective of this study was to find the optimal premedication. To evaluate this, we compared 4 different kinds of premedication regimes, atropine and codeine, nebulized ipratropium bromide, codeine only, and no premedication.

Few studies have been performed concerning the role of codeine in premedication. Tsunezuka et al. described that patients who received codeine as premedication showed a significant reduction in supplemental Xylocaine during FFB. However, these patients also received midazolam. 8 In our study, the difference in the quantity of supplemental tetracaine did not reach statistical significance. However, patients who used codeine and atropine or only codeine did experience significantly less coughing during FFB. Therefore, codeine does seem to have a role in cough suppression during FFB.

Inoue et al. described that topical lidocaine resulted in reduction of forced expiratory volume in 1 second, suggesting that inhaled ipratropium bromide might protect against bronchoconstriction. 9 In our study, no positive effects on any of the variables or practical benefit of nebulized ipratropium bromide in both univariate and multivariate analyses were found. The patients and bronchoscopists in the inhaled ipratropium bromide group even reported higher levels of coughing during the FFB, although these differences did not reach statistical significance.

The patients with atropine and codeine as premedication reported more comfort during FFB than patients without premedication. This positive effect on comfort can probably be attributed to the sedative and cough-suppressive effect of the combination of codeine and atropine. Because we did not investigate the sole use of atropine as premedication, we cannot comment on the unique contribution of atropine. However, several authors stated that atropine as premedication does not affect cough suppression, patients' comfort, or complication rate as a result of arrhythmias or vasovagal reactions during or after the procedure. 13,15,17,19,20 In 2001, the guidelines of the British Thoracic Society have already stated not to use atropine routinely. 21 In our country, recent guidelines stated as well that the routine use of atropine is not mandatory. 22 It is preferred to use other kinds of drugs like benzodiazepines for adequate sedation. However, various studies showing improved patient tolerance used higher doses of sedatives as premedication than generally is recommended, which could have resulted in increased mortality. 23–27

Colt et al. showed that FFB can be performed safely without premedication. 14 In our study, we come to the same conclusion. No complications were seen in any of the 4 groups. Patients without premedication needed more local anesthetic to suppress cough reflex, but this did not reach statistically significance. Williams et al. made the same observation and concluded that this finding had no practical significance. 16

Smokers experienced more coughing, dyspnea, and needed more topical anesthetics during FFB. Therefore, it can be concluded that smoking has a negative effect on patients' tolerance during FFB. Interesting findings in our study were that female gender and having had a prior bronchoscopy both showed a significantly negative effect on patients' comfort. Previous negative experiences during FFB could have an effect on tolerance of following FFBs.

In conclusion, codeine showed a beneficial effect when used as premedication as a result of suppressing cough reflex during FFB. Inhaled ipratropium bromide showed no useful effect. The role of atropine seems to be limited to its sedative action and, for this purpose other sedative medications, could be preferred. FFB can be performed safely without premedication. Smoking has a negative impact on dyspnea and coughing during FFB.

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ACKNOWLEDGMENTS

The authors are indebted to the endoscopy staff for their assistance in performing this study.

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Keywords:

flexible fiberoptic bronchoscopy; premedication; codeine; patients' comfort; anticholinergics

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