The forced oscillation technique (FOT) is a simple and noninvasive means of assessing respiratory mechanics. Forced oscillations are superimposed on tidal breathing, avoiding the need for any exertional breathing maneuvers or interference with normal respiration and providing clinical advantages over conventional lung function testing for both adults and children.1 The main outputs of FOT are respiratory resistance (Rrs) and respiratory reactance (Xrs), measured over a wide range of oscillatory frequencies.2 Rrs is calculated from pressure and flow signals and is a measure of central and peripheral airway calibers responsible for the resistance exerted from the oropharynx to the lung and chest wall. Xrs is derived from pressure in phase with volume and is directly related to dynamic compliance and inertia. These parameters are more sensitive than spirometry in detecting pulmonary diseases, such as asthma and chronic obstructive pulmonary disease (COPD).1,3,4 Ventilator-induced lung injury (VILI) and endotracheal intubation may also affect respiratory mechanics, and FOT is capable of detecting respiratory changes. We performed a pilot study to determine whether FOT could assess the effects of general anesthesia and positive pressure ventilation on respiratory mechanics.
This prospective study was approved by the ethics committee of Osaka Medical College, Osaka, Japan, with all participants providing written informed consent. Forty patients with ASA physical status classification I to II underwent general anesthesia for 16 superficial procedures, including 15 transurethral and 9 laparoscopic procedures, between September and November 2013. Patients with a history of asthma or asthmatic symptoms, such as coughing or wheezing at rest, and patients who had taken oral steroids or had a respiratory tract infection or exacerbation within the previous 3 months, were excluded from the study. However, patients diagnosed with COPD according to the Global Initiative for Chronic Obstructive Lung Disease (GOLD) guidelines,5 and former and current smokers without COPD or asthma, were not excluded.
Traditional spirometry was performed the day before surgery. On the day of surgery, anesthesia was induced with intravenous propofol 2 mg/kg, rocuronium 0.8 mg/kg, and an infusion of remifentanil at 0.5 μg/kg/min. After tracheal intubation (with a cuffed tube of internal diameter 7.0 mm for women and 8.0 mm for men), anesthesia was maintained with sevoflurane 1.0% to 1.5% and remifentanil 0.25 to 0.5 μg/kg/min. Volume-controlled ventilation consisted of a 0.4 fraction of inspired oxygen and a tidal volume of 8 mL/kg predicted body weight. An oxygen mask was provided postoperatively and oxygen administered at 4 L/min for 4 hours. Patients were permitted to walk in their wards on the first postoperative day and did so. None required positive end-expiratory pressure.
Participants were classified into 2 groups by anesthesia duration: 20 underwent anesthesia for ≥2 hours (group L) and the other 20 underwent anesthesia for <2 hours (group S). Forced oscillation was measured using standard techniques the day before surgery and on the first postoperative day using a MostGraph-01 device (Chest MI, Tokyo, Japan). Rrs and Xrs were recorded in the sitting position with participants breathing normally through a mouthpiece while wearing a nose clip. To minimize artifacts from vibrations, an investigator supported the patient’s cheeks. Measurements were taken for approximately 40 seconds at a time. Data showing the serial values of each component every 0.2 seconds were archived.6
Rrs is reported as R5 (Rrs at 5 Hz), R20 (Rrs at 20 Hz), and R5 minus R20. R5 represents low-frequency resistance and R20 high-frequency resistance. Rrs can be plotted on a 3-dimensional graph that shows how each parameter is influenced by forced oscillatory frequency and the respiratory cycle (Fig. 1). Xrs is reported as X5 (Xrs at 5 Hz), resonance frequency (Fres), and area of low Xrs (ALX). Rrs and Xrs parameters can be plotted on 2-dimensional graphs to represent flow, resistance, and reactance (Figs. 2 and 3). In this study, we showed results of all parameters; however, we focused on difference in R5 due to anesthetic time between the 2 groups.
The standard deviation was considered to be 0.5 and the expected difference in R5 to be 0.5 cm H2O/L/sec, because our preliminary data for postoperative R5 patients undergoing a short operation were 2.54 ± 0.27 cm H2O/L/s (mean ± SD), while that for a long operation were 3.14 ± 0.60 cm H2O/L/s. The cutoff of 2 hours was chosen before data collection. The sample size was determined from our preliminary study of R5 in 5 patients for each group. The sample size required to obtain an 80% power goal between 2 groups, at an α error level of 5% and expecting a between-group difference of 0.5 cm H2O/L/s in R5, was 38 subjects. All results are presented as mean ± SD. The Student t test with unequal variance (Welch method) or the χ2 test was used to compare all parameters in this study. All statistical analyses except for analysis of covariance (ANCOVA) were performed using GraphPad Prism 5 software (GraphPad Software, La Jolla, CA). Statistical significance was defined as P < 0.05. ANCOVA were performed using SPSS Statistics, ver.22 (IBM, Armonk, NY).
There were no significant differences in the demographic characteristics between the 2 groups, including preoperative spirometry findings (Tables 1 and 2). The 2 groups underwent various procedures. Group L included more abdominal laparoscopic surgeries, and group S included more transurethral surgeries. Intraoperative infusion volume was significantly greater in group L than in group S. Postoperatively, R5 was found to increase significantly from baseline in group L by 2 different statistical methods (P = 0.029 with the Student t test with unequal variances and P = 0.033 with ANCOVA; Table 3). No patient needed a bronchodilator or expectorant agent, and none had intra- or postoperative respiratory failure or airway troubles.
We observed FOT changes in patients undergoing surgery for >2 hours. These changes were indicative of narrowing or obstruction of the bronchi and bronchioles, suggesting that positive pressure ventilation with endotracheal intubation during general anesthesia may alter airway mechanics in a method broadly similar to, but to a lesser extent than, asthma or COPD.1,7 Our results suggested that operations of long duration enhance Rrs, increasing tissue resistance and reducing lung compliance. Postoperative respiratory deterioration (increased R5) may be due to (1) edema of the vocal folds caused by an endotracheal tube, (2) proximal and peripheral airway edema caused by excessive infusion volume or the Trendelenburg position, (3) a septum, (4) asthma, and/or (5) VILI. Because this is the first report comparing pre- and postoperative status using the FOT method, the mechanisms underlying respiratory deterioration could not be determined, except for VILI. Tidal volume is a key factor in avoiding VILI. High tidal volume ventilation can cause damage, including inflammatory cell infiltration, hyaline membranes, increased vascular permeability, and pulmonary edema.8 A recently adopted lung-protective strategy consists of low tidal volume ventilation (6–8 mL/kg predicted body weight), along with positive expiratory pressure and recruitment maneuvers.9 Neuromuscular blocking is thought to be important because it can prevent patients from “fighting” the ventilator, which may aggravate VILI.9
In obstructive lung disease, Rrs has been reported to increase, and Xrs to decrease, at lower oscillatory frequencies.10 These increases in R5 and reductions in X5 have been found to correlate with the severity of COPD.3,11,12 The diagnostic sensitivity of FOT is reportedly superior to that of conventional pulmonary function tests, such as spirometry, in asthma and COPD, with FOT able to detect changes in airway mechanics not evident with spirometry alone.4 A study of respiratory parameters during artificial ventilation with FOT through a tracheal tube13 suggested that modifications to the MostGraph-01 technique could allow measurements to be taken during spontaneous breathing or mechanical ventilation.
This study had several limitations. The intraoperative infusion volume was greater in patients anesthetized for ≥2 hours than in patients anesthetized for <2 hours. Moreover, perioperative urine output could not be measured. This pilot study did not include standardization for postoperative infusion. These limitations are likely to have affected our results because the intra- and postoperative fluid balance alters alveolar function and Rrs. Furthermore, patients in this study underwent several procedures that may have resulted in differences in postoperative status, such as pain, difficulty in holding a mouthpiece, or tenesmus caused by a urethral catheter. This study also included more laparoscopic surgical cases in group L and more transurethral resections of bladder tumors in group S. Our results could have been affected not only by the anesthetic time but also by the procedures. Nevertheless, all patients were able to walk to see the anesthesiologists the day after surgery, and there were no difficulties in obtaining respiratory impedance measurements. It was difficult to define patients with COPD because spirometry cannot detect COPD without flow restriction. Although computed tomography can evaluate this type of COPD, this procedure was not performed in all patients. Another limitation of our study was the relatively small sample size. Further studies are needed to better evaluate changes in perioperative respiratory mechanics, such as Rrs and reactance, including the influence of tidal volume, positive end-expiratory pressure, and recruitment maneuvers in different types of surgery; the period of weaning from a ventilator in patients undergoing long operations; and the clinical significance of our findings on postoperative outcomes.14,15 Not only R5 but also the other parameters can be analyzed to investigate the respiratory mechanics of artificial ventilation with intubation. FOT may result in slight changes in clinical situations, which could not be detected by spirometry or blood gas examination. However, FOT may help in understanding the mechanism underlying these changes and may be supportive in the treatment of patients with postoperative asthma or respiratory inflammatory diseases.
In conclusion, FOT is a clinical tool to assess the effects of perioperative ventilation strategies on respiratory mechanics.
Name: Yosuke Kuzukawa, MD.
Contribution: This author wrote this manuscript and contributed to data collection.
Attestation: Yosuke Kuzukawa approved the final manuscript and is the archival author.
Name: Junko Nakahira, MD, PhD.
Contribution: This author contributed to study design and data analysis, and prepared the manuscript.
Attestation: Junko Nakahira attests to the integrity of the original data and the analysis reported in this manuscript, approved the final manuscript, and is also the archival author.
Name: Toshiyuki Sawai, MD, PhD.
Contribution: This author contributed to data analysis and helped to prepare the manuscript.
Attestation: Toshiyuki Sawai also attests to the integrity of the original data and the analysis reported in this manuscript and approved the final manuscript.
Name: Toshiaki Minami, MD, PhD.
Contribution: This author contributed to study design and helped to prepare the manuscript.
Attestation: Toshiaki Minami approved the final manuscript.
This manuscript was handled by: Maxime Cannesson, MD, PhD.
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