Anesth Analg 2006;102:1427-1430
© 2006 International Anesthesia Research Society
doi: 10.1213/01.ane.0000204317.78586.07
ANESTHETIC PHARMACOLOGY
Bronchial Mucus Transport Velocity in Patients Receiving Propofol and Remifentanil Versus Sevoflurane and Remifentanil Anesthesia
Thomas Ledowski, MD,DEAA*,
Michael J. Paech, DM, FANZCA*
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Bhavesh Patel, MBBS,FRCA*, and
Stephan A. Schug, FANZCA, FFPMANZCA*
*Department of Anaesthesia and Pain Medicine, Royal Perth Hospital; and School of Medicine and Pharmacology, The University of Western Australia, Perth, Australia
Address correspondence and reprint requests to Thomas Ledowski, MD, DEAA, Royal Perth Hospital, Department of Anaesthesia and Pain Medicine, Wellington Street Campus, Perth WA 6000, Australia. Address e-mail to thomas.ledowski{at}health.wa.gov.au.
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Abstract
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Volatile anesthetics reduce ciliary beat frequency in vitro. It has been reported that impaired bronchial mucus transport velocity (BTV) is associated with significantly increased pulmonary complications. In this study, we sought to determine in vivo differences in BTV, comparing patients having total IV anesthesia (TIVA) with propofol and remifentanil to anesthesia with sevoflurane and remifentanil. Twenty-two patients scheduled for elective general surgery were randomized to one of two groups: TIVA (propofol/remifentanil) or SEVO (sevoflurane/remifentanil). Thirty minutes after tracheal intubation, BTV was assessed by fiberoptic observation of the movement of methylene blue dye applied to the dorsal surface of the right main bronchus. BTV was significantly reduced in the SEVO group compared with the TIVA group (mean, 1.5 ± 0.7 [0–2.3] versus 4.8 ± 2.1 [2.3–8.8] mm/min; P < 0.0001). Anesthesia with sevoflurane may lead to significantly impaired bronchociliary clearance in comparison to TIVA. This could have implications for perioperative pulmonary complications, in particular in patients at risk for pulmonary complications.
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Introduction
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Volatile anesthetics reduce the cilia beat frequency in vitro (1,2). In vivo, isoflurane-based anesthesia resulted in a significantly lower cilia beat frequency when compared with propofol (3). These findings suggest that patients having an anesthetic with a volatile inhaled anesthetic might have impairment of their bronchial mucus transport. The aim of this prospective randomized trial was to investigate bronchial mucus transport velocity (BTV) among patients having either total IV anesthesia (TIVA) with propofol and remifentanil or anesthesia with sevoflurane and remifentanil.
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Methods
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After approval by the regional ethics committee and written informed consent, 22 patients (ASA physical status I-II) undergoing elective general surgery (appendectomy or cholecystectomy) were randomized by sealed-envelope allocation to receive either total IV anesthesia (TIVA) with propofol and remifentanil (group TIVA) or anesthesia with sevoflurane and remifentanil (group SEVO). Patients with a history of respiratory tract pathology, expected difficult airway, atopy, smoking, or those using drugs known to influence the bronchial mucus transport velocity (BTV) (ß-adrenoceptor antagonists, cortisone, atropine, theophylline, and catecholamines) were excluded from the study. The induction of anesthesia was standardized. After the insertion of a peripheral IV cannula, remifentanil infusion was commenced at 0.5 µg · kg–1 · min–1. Two minutes later, a bolus of propofol 2 mg/kg was administered and rocuronium 0.6 mg/kg given for neuromuscular block. Sixty seconds after the administration of rocuronium, patients were tracheally intubated using an endotracheal tube size 7.5 mm (interdermal [ID]) for woman and 8.0 mm (ID) for men. The cuff was inflated with 10 mL of air. The lungs of the patients were ventilated using a pressure-controlled mode with a maximum pressure of 20 cm H2O and a positive end-expiratory pressure (PEEP) of 5 cm H2O. A circle anesthetic breathing system (AESTIVA 5TM; Datex Ohmeda Inc., Madison, WI) with an antimicrobial filter for air humidification (THERMOVENT HEPATM; Portex Inc., Keene, NH) was used. Fresh gas flow was 2 L/min with an inspired oxygen fraction (Fio2) of 0.5 in an oxygen-air mix. Ventilation rate and maximum airway pressure were adjusted to maintain a normal end-tidal CO2 (33–43 mm Hg). In the TIVA group, anesthesia was maintained with propofol using the target-controlled infusion (TCI) mode (IVAC TCITM; Alaris Medical Systems, Hamshire, United Kingdom), targeting a plasma concentration of 2–4 µg/mL, and with remifentanil infused at 0.1–0.5 µg · kg–1 · min–1. In the SEVO group, patients received sevoflurane (end-tidal, 1.5–2.5 vol%) and remifentanil (0.1–0.5 µg · kg–1 · min–1). In both groups, the dose of the drugs was adjusted to clinical need within the given limits. Preferably, the dose of remifentanil was adjusted as the first step to keep the dose of sevoflurane and propofol as stable as possible and achieve a steady-state concentration of these drugs.
Thirty minutes after tracheal intubation and with the patient in supine position, a swivel connector (BODAI PEEP SAFETM; Sontek Medical Inc., Hingham, MA) was inserted between the tracheal tube and the circle system. BTV was assessed using a modification of the method described by Keller and Brimacombe (4) and Sackner et al. (5) (Fig. 1). A fiberscope (VIDEOSCOPE TYPE PI60TM; Olympus Optical CO GmbH, Hamburg, Germany) was passed through the swivel connector, and the right main bronchus was visualized. A 16-gauge epidural catheter (Portex) with the tip cut off to achieve one single, end-standing hole, was inserted into the working channel of the scope. The catheter was inserted until it was seen through the lens of the scope and was almost touching the mucus membrane of the right main bronchus. A drop of 1% methylene blue dye (approximately 0.02 mL) was inserted into the epidural catheter and flushed through with an air-filled 1-mL syringe to place it onto the posterior surface of the bronchial mucosa. The time required to apply the dye was approximately 1 min. After placement of the dye, the lens of the bronchoscope was positioned neutrally and moved up to the proximal margin of the drop. The scope was marked where it entered the swivel connector and removed from the tube. The distance between the connector and the mark was considered the baseline value. Two, 4, and 6 min after the application of the dye, the position of the proximal margin of the dye was determined again by the method described (Fig. 1). The mean of the three assessments was calculated and divided by 2 to give the BTV in millimeters per minute. Nasal core body temperature, doses of remifentanil, propofol, and sevoflurane, end-tidal CO2, Fio2, maximum airway pressure and PEEP, ventilation rate, and tidal volumes were all recorded at the times of BTV assessment. Two investigators (TL and BP) performed all assessments. For each assessment, the investigators were blinded to the previous marks on the scope by using the scope's video screen, rather than looking at the scope lens itself.
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Figure 1. Method of bronchial mucus transport velocity (BTV) assessment. (A) After placement of a drop of 1% methylene blue dye on the dorsal surface of the right main bronchus, the bronchoscope is marked at the entry point of the swivel connector (*) and removed thereafter. (B) Two, 4, and 6 min later, the bronchoscope is pushed back in and its tip levelled with the position of the methylene blue. The bronchoscope is marked again at the entry point of the swivel connector, and the distance to the first mark is assessed.
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For sample size estimation, we used the data (mean, sd) published by Keller and Brimacombe (4) and calculated a number of 11 patients per group to detect a difference of at least 3 mm/min (a value demonstrated by Konrad et al. (6) to be clinically significant) with a power of 80%. Statistical analysis was performed using two-factor analysis of variance, Spearman correlation coefficient, and 
2 test. The Kolmogorov-Smirnov test was used for testing the data for normal distribution, and the homogeneity of variance test (Levene statistic) was used to test for the equality of group variances. The 
error was 0.05 and ß error 0.2. Unless otherwise stated, data are presented as mean ± sd. In addition, the ranges of BTV are reported for both groups (in parenthesis).
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Results
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Twenty-two subjects (age, 18–75 yr) were included in the trial. The BTV-related data of one patient of the TIVA group had to be excluded because he admitted after surgery to be a smoker. The groups showed no significant differences regarding type of surgery, age, body weight, height, body temperature, Fio2, end-tidal CO2, peak airway pressures, and remifentanil dosage (Table 1). None of these variables showed a significant correlation with BTV. In the SEVO group, the mean end-tidal sevoflurane concentration at the time of BTV assessment was 1.8 ± 0.5 vol/%. In the TIVA group, the mean TCI target concentration of propofol was 3.5 ± 0.9 µg/mL.
Compared with TIVA, SEVO resulted in a significantly lower BTV (SEVO, 1.5 ± 0.7 [0–2.3] mm/min, versus TIVA, 4.8 ± 2.1 [2.3–8.8] mm/min; P < 0.0001; Fig. 2).
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Figure 2. Bronchial mucus transport velocity (BTV) (mean, sd, and range) in patients anesthetized with either sevoflurane and remifentanil (SEVO) or propofol and remifentanil (total IV anesthesia [TIVA]). *Significantly different, P < 0.0001.
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Discussion
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Mucociliary clearance is an important protective mechanism within the upper and lower respiratory tract whereby inhaled particles and microorganisms are removed from the tracheobronchial system (4). Retention of secretions, atelectasis, and lower respiratory tract infections are potential consequences arising from impaired bronchociliary clearance. Konrad at al (7) demonstrated a significantly reduced BTV in smokers compared with nonsmokers, and pulmonary complications were found more often among smokers. The correlation between a low BTV and the incidence of pulmonary complications has also been shown in ventilated intensive care unit patients (6). A number of anesthesia-related factors, such as drugs (8) (catecholamines, theophylline, cortisone, atropine, and ß-adrenoceptor antagonists), large oxygen concentration (9), dry anesthetic gases (10), trauma caused by suction procedures (11), and the presence of a cuffed tracheal tube (4,12) decrease mucociliary clearance. In addition, the anesthetic used seems to play an important role, such that volatile inhaled anesthetics, such as halothane, isoflurane, and enflurane, depress ciliary function in vitro (1,2).
In this trial, anesthesia with sevoflurane and remifentanil led to significantly more depression of BTV when compared with BTV during TIVA with propofol and remifentanil. These findings support the results of Raphael and Butt (3) who found a significantly reduced ciliary beat frequency (–21%) in patients anesthetized with isoflurane compared with propofol. In contrast, Konrad et al. (13) did not find a difference in BTV between preoperative values and those assessed at the end of an anesthesia regimen with isoflurane and fentanyl. However, a different technique (technetium labeled albumin microspheres) to determine BTV could have contributed to this finding. In our study, we did not expose patients to different concentrations of sevoflurane in a controlled manner; instead, they individually received different doses within a range of 1.5–2.5 vol%. In fact, the exact dose of the volatile anesthetic might not play an important role; comparing the results of two studies performed by Raphael et al. (1,2), the cilia function was depressed to a very similar extent after 1 or 3 minimum alveolar anesthetic concentrations of halothane, enflurane, or isoflurane.
Because we did not assess a preoperative baseline value in awake patients, we cannot comment on whether BTV was depressed by propofol or remifentanil. A study by Padda et al. (14) suggests that propofol has no effect on mucus secretion or clearance, although this has only been tested in anesthetized dogs. There is no study addressing the effect of remifentanil on BTV; however, Selwyn et al. (15) reported no effect of morphine on ciliary beat clearance in vitro. Comparing our data with the results of Keller and Brimacombe (4), our results match their findings in tracheally intubated patients.
The question remains as to how clinically relevant our in vivo findings are. Because we did not assess any clinical outcome variable, this study did not address this issue. However, a comparison of the mean difference between groups in this trial (3.3 mm/min) with the results of previous, outcome-orientated studies, suggests our findings may have clinical relevance. Comparing smokers and nonsmokers under general anesthesia, Konrad et al. (7) found a mean difference of 5.8 mm/min for BTV in the right main bronchus. They also reported a significantly more frequent rate of pulmonary complications in the group of smokers. In another study, the same authors (6) reported a BTV difference of 3.5 mm/min (left main bronchus) and 4.7 mm/min (right main bronchus) between patients with or without pulmonary complications. Although several factors are likely to impact clinical outcome in ventilated patients, it is plausible that impairment of bronchial ciliary function may be relevant.
In conclusion, sevoflurane significantly depresses BTV in patients without lung disease, compared to TIVA. Although not addressed in this study, this might have clinical implications with respect to postoperative respiratory complications, in particular for patients with preexisting risk factors for retention of secretions, atelectasis, and pulmonary infection.
We would like to thank Mr. Roy Wyatt, Senior technician, Department of Anesthesia and Pain Medicine, Royal Perth Hospital, Australia, for his enthusiastic help with the clinical set up.
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Footnotes
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Accepted for publication January 4, 2006.
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References
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Abstract
Introduction
