Endobronchial ultrasonography (EBUS) using a radial probe through the working channel of the flexible bronchoscope has been used to locate enlarged mediastinal and hilar lymph nodes.1 As technology advanced, a new convex probe with the ability to perform real-time EBUS-guided transbronchial needle aspiration (EBUS-TBNA) was developed in 2002.2 This technique has enabled obtaining a qualitative diagnosis of mediastinal lesions under local anesthesia. It allows us to extirpate not only cells but pieces of tissues using a 21-gauge full-length steel needle. Furthermore, close follow-up examination is possible as it is minimally invasive and safe even in patients with preoperative chemotherapy and those suspected of having recurrence.
Effectiveness and safety of EBUS-TBNA have been widely reported. In the diagnosis and staging of lung cancer, large-scale prospective studies have reported its sensitivity between 89% and 95.7%, specificity and positive predictive values (PPV) of 100%, and a negative predictive value (NPV) between 96.9% and 98.9%.2–5 One of the studies showed that sensitivity, specificity, and accuracy of EBUS-TBNA were better than those of computed tomography and positron emission tomography.3 Moreover, in the patients with suspected metastatic lung cancer, Fujisawa et al6 showed that sensitivity, specificity, and accuracy were 87.5%, 100%, and 91.3%, respectively, which are similar to the values in primary lung cancer.
Furthermore, some prospective studies have assessed the usefulness of EBUS-TBNA in patients with suspected sarcoidosis.7,8 In these studies, EBUS-TBNA was diagnostic in 85% to 91.8% of patients. Moreover, a retrospective study has evaluated the usefulness of EBUS-TBNA in the diagnosis of lymphoma and mediastinal cyst, as well as goiter.9,10
In terms of the methods of anesthesia while performing EBUS-TBNA, there are differences among institutions, such as general anesthesia (GA), moderate sedation using midazolam, one of the water-soluble, short-acting benzodiazepines, or meperidine (MP). There is no single established method of anesthesia at present. Although it is necessary to ensure patient safety while performing EBUS-TBNA, there are only a few reports evaluating most preferred methods of anesthesia during the procedure. In our department, EBUS-TBNA was being performed under GA until May 2008, but since then we have switched to local anesthesia and moderate sedation using intravenous MP. We conducted a retrospective study assessing the efficacy of MP for EBUS-TBNA.
Patients who underwent EBUS-TBNA between January 2006 and December 2009 at the Kameda Medical Center were retrospectively analyzed. We classified the patients into 2 groups, procedures that were performed under sedation with intravenous MP versus those performed under GA. Furthermore, we divided the MP cases into 2 groups, patients above 65 years of age (elderly patients) and the others (young patients), to assess the safety of MP among the elderly. Information was gathered on patient demographics, size of the lesion, duration of the procedure, number of aspirates, and complications and their management. Specificity, sensitivity, PPV, NPV, and diagnostic accuracy of EBUS-TBNA were calculated for both the groups.
Our patients were routinely monitored using a continuous pulse oximeter and electrocardiogram, and blood pressure was measured every 2.5±5 minutes.
We used the χ2 test, Fisher, and Student t distribution test for comparison between both the groups and analyzed using Microstat version 2. Significance was set at P value less than 0.05 in all statistical analyses. This study was approved by our institutional review board.
A total of 60 patients were recruited into the intravenous MP study, with the MP group comprising 31 patients and the GA group 29. The indications for EBUS-TBNA included mediastinal lymphadenopathy (N=50, 83.3%), abnormal positron emission tomography (N=8, 13.3%), and lesions suspicious for mediastinal tumors (N=2, 3.3%). In 24 patients (60%), metastasis involving the mediastinum or recurrence of a malignant tumor (including 14 lung cancer cases) was suspected. There were no differences between the MP and GA patients' backgrounds in terms of mean age, weight, physical status (American Society of Anesthesiologists grade), and size of the lesions (Table 1). Although the examination time (44.1 min vs. 50.9 min; P=0.11) was not different, the mean number of aspirations for the MP cases was less than that of the GA cases (2.7 times vs. 3.2 times; P<0.05).
Although the lowest saturation of peripheral oxygen (SpO2) during the examination of the MP cases was lower than that of the GA cases (93.6% vs. 97.6%; P<0.05), GA cases required more vasopressor for the decline in blood pressure than MP cases (Table 2). There was no difference in the number of cases that had the lowest heart rate (HR) below 50 beats per minute. Only 1 patient in the MP group required additional midazolam because of increased restlessness during the examination. There were no complications in either group.
In the diagnosis of metastasis for primary lung cancer, sensitivity, specificity, PPV, NPV, and accuracy for the MP group were 80%, 100%, 100%, 71.4%, and 85.7%, respectively; and for metastasis or recurrence of other malignancy in the MP cases, they were 60%, 100%, 100%, 71.4%, and 80% (Table 3), respectively. There were no statistical differences in these data compared with the GA group. In both groups, the patients were suspected of having sarcoidosis; diagnosis was established by EBUS-TBNA.
In the comparison between the elderly and younger patients, the mean body weight of the former group was lower than that of the latter group; there was no statistically significant difference in the physical status, examination time, and the frequency or degree of complications (Table 4).
EBUS-TBNA provides a qualitative diagnosis of mediastinal lesions under local anesthesia. Its safety and efficacy have been adequately established. Its simplicity and minimally invasive nature allow for follow-up examinations whenever required. However, most patients feel apprehensive because they are alert under local anesthesia during the procedure.11 Therefore, proper sedation is required for a safe examination, which would enhance the receptivity of reexamination when needed.12,13
Bronchoscopy guidelines recommend the use of sedation except in cases with a specific contraindication.14 A wide variety of drugs, such as midazolam, diazepam, and MP, have been used for this indication.15–17 Midazolam is a water-soluble benzodiazepine with a half-life of about 2 hours, a rapid onset, and short duration of action, and has a sedative effect.18 However, it causes transient apnea and a decrease in blood pressure depending on the dose. Extreme caution has been recommended with its use in the elderly because of a strong association between the dose required and age.19
In contrast, although MP is also a short-acting drug with a half-life of 3.2 hours, it produces respiratory depression. Its cardiovascular depressant effect is greater than that of morphine, especially in elderly patients with liver disorders.18 It is required to increase the dose of sedative drugs to the point at which somnolence or retrograde amnesia is achieved. It has been reported that there is no difference in terms of the level of sedation or retrograde amnesia between midazolam and MP.16 In Japan, each institution has its own choice of sedative drugs such as midazolam or MP, and diazepam and propofol have also been used in some institutions.
EBUS-TBNA could add to the duration of the procedure. Thus, adequate degree of sedation is required during its performance. Incidentally, very few articles deal with this issue. At our institution, we have used MP of 35 mg for sedation during EBUS-TBNA. The aim of this study was to assess its efficacy during EBUS-TBNA. Despite the retrospective analysis, we were able to show the validity as we monitored all the patients' vital parameters (SpO2, blood pressure, and HR) during the examination.
To begin with its safety, it was ascertained that although the lowest SpO2 during the examination using MP cases was lower than that of the GA cases, GA cases required more vasopressor for a decline in blood pressure than MP cases. On account of its sedative effect, MP produces respiratory and cardiovascular depression as well. Although we provided appropriate oxygen to keep the patients' SpO2 over 95%, the MP cases tended to result in transient hypoxia (for few seconds) because of hypoventilation, which originated from cough during the anesthesia of the trachea or the bronchi. In contrast, the GA cases kept SpO2 over 97% presumably by the suppression of the cough because of the anesthesia and muscle relaxant. As for the MP cases, there was only 1 case which needed added drugs for sedation. There were no complications during or after the examination in any of the MP or GA cases.
In earlier studies, the efficacy of EBUS-TBNA in the diagnosis and assessment of mediastinal and hilar lymphadenopathy has been reported.2–6 Our study showed that sensitivity, specificity, PPV, NPV, and accuracy were 60% to 80%, 100%, 100%, 71.4%, and 80% to 85.7%, respectively. These data were a little lower than those of other studies possibly because of the limited number of cases and the experience of the operators. However, the data were not statistically significantly different compared with the GA cases that had excellent results (Table 4).
Furthermore, we also analyzed the safety of MP for elderly patients.20 In our analysis of MP-sedated patients, the percentage of elderly and young patients with the lowest SpO2 under 90% was 18.8% and 0%, respectively. The percentage of elderly and young patients with HR below 50 beats per minute was 6.5% and 6.7%, respectively. There was no statistically significant difference between the 2 groups for both SpO2 and HR. EBUS-TBNA under intravenous sedation with MP was suggested to be feasible and was as safe as GA, even for elderly patients.
The use of MP for bronchoscopy is often discouraged because of its long elimination half-life and higher intraprocedural blood pressure measurements.21 In addition, the active metabolite, nor-meperidine, can precipitate seizures, especially in patients with renal insufficiency. MP has also been associated with more nausea as compared with other narcotics, such as fentanyl.22 However, in our analysis, MP had a potential to be one of the effective drugs for sedation during EBUS-TBNA regardless of the patient's age. We should further analyze its safety and efficacy by carrying out prospective studies.
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