CC BY-NC-ND 4.0 · Endosc Int Open 2020; 08(03): E458-E464
DOI: 10.1055/a-1096-0438
Original article

Impact of balloon inflation on the insertion of endoscopic ultrasound: a prospective, randomized controlled trial

Jinwoo Kang
1  Department of Internal Medicine and Liver Research Institute, Seoul National University Hospital, Seoul National University College of Medicine, Seoul, Korea
2  Department of Internal Medicine, SMG-SNU Boramae Medical Center, Seoul, Korea
,
Sang Hyub Lee
1  Department of Internal Medicine and Liver Research Institute, Seoul National University Hospital, Seoul National University College of Medicine, Seoul, Korea
,
Jae Woo Lee
1  Department of Internal Medicine and Liver Research Institute, Seoul National University Hospital, Seoul National University College of Medicine, Seoul, Korea
3  Department of Internal Medicine, Mediplex Sejong Hospital, Incheon, Korea
,
Dong Kee Jang
1  Department of Internal Medicine and Liver Research Institute, Seoul National University Hospital, Seoul National University College of Medicine, Seoul, Korea
4  Dongguk University College of Medicine, Dongguk University Ilsan Hospital, Goyang, Korea
,
Jin Ho Choi
1  Department of Internal Medicine and Liver Research Institute, Seoul National University Hospital, Seoul National University College of Medicine, Seoul, Korea
,
Young Hoon Choi
1  Department of Internal Medicine and Liver Research Institute, Seoul National University Hospital, Seoul National University College of Medicine, Seoul, Korea
5  Division of Gastroenterology, Department of Internal Medicine, College of Medicine, The Catholic University of Korea, Seoul, Korea
,
Woo Hyun Paik
1  Department of Internal Medicine and Liver Research Institute, Seoul National University Hospital, Seoul National University College of Medicine, Seoul, Korea
,
Dong-Won Ahn
1  Department of Internal Medicine and Liver Research Institute, Seoul National University Hospital, Seoul National University College of Medicine, Seoul, Korea
2  Department of Internal Medicine, SMG-SNU Boramae Medical Center, Seoul, Korea
,
Ji Bong Jeong
1  Department of Internal Medicine and Liver Research Institute, Seoul National University Hospital, Seoul National University College of Medicine, Seoul, Korea
2  Department of Internal Medicine, SMG-SNU Boramae Medical Center, Seoul, Korea
,
Ji Kon Ryu
1  Department of Internal Medicine and Liver Research Institute, Seoul National University Hospital, Seoul National University College of Medicine, Seoul, Korea
,
Yong-Tae Kim
1  Department of Internal Medicine and Liver Research Institute, Seoul National University Hospital, Seoul National University College of Medicine, Seoul, Korea
› Author Affiliations
TRIAL REGISTRATION: Single center, Single-blinded randomized prospective study NCT02924948 at clinicaltrials.gov
 

Abstract

Background and study aims During endoscopic ultrasound (EUS), patients may experience severe discomfort. The radial echoendoscope has a balloon around its tip. Balloon inflation prior to insertion may reduce contact injury and pharyngeal pain. The purpose of this study was to investigate the effect of balloon inflation on pharyngeal pain during insertion.

Patients and methods Patients who underwent radial EUS for pancreatobiliary disease were randomized into standard insertion or balloon-inflated insertion. The primary outcome was the proportion of moderate-to-severe pharyngeal pain. Secondary outcomes were the degree of pharyngeal pain, risk factors for moderate pharyngeal pain, procedure-related adverse events, and pharyngeal pain depending on the experience of the endoscopist.

Results A total of 481 patients were randomized into two groups: standard insertion (238) and balloon inflation (243). No statistically significant differences in proportion of moderate-to-severe pain were found (26.5 % vs. 20.2 %, P = 0.107). Balloon inflation (HR 0.65; 95 % CI (0.42–0.98, P = 0.041) was a protective factor against moderate pain. Balloon inflation reduced the proportion of patients with moderate-to-severe pain when performed by physicians with less than 3months of experience with EUS (44.7 % vs. 25.3 %, P = 0.012).

Conclusion Balloon inflation did not reduce the absolute degree of post-procedural pain with EUS, but it reduced the number of patients with moderate-to-severe pain when performed by physicians with less than 3 months of experience.


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Introduction

Endoscopic ultrasound (EUS) has become an indispensable modality for diagnosis of pancreatobiliary diseases. Studies actively investigating interventional therapy with EUS are expected to widen the clinical application of EUS [1] [2]. Echoendoscope is thicker than the conventional upper gastrointestinal endoscope, and the end of the scope with the transducer is rigid, which causes discomfort during insertion. In addition, visibility is poor during insertion due to the nature of the side-view endoscope [3]. Therefore, echoendoscope is more difficult to insert than the conventional endoscope and may be associated with additional complications. In general, upper endoscopy is associated with minor throat discomfort. In a single prospective study, approximately 2.5 % of patients reported seeking medical services due to such discomfort [4]. In the case of endoscopic retrograde cholangiopancreatography (ERCP), one-third to one-half of patients felt pain and discomfort and 6 % reported moderate-to-severe pain in the neck [5]. In the case of echoendoscope with a thicker diameter and side view, more severe and frequent discomfort can be expected.

A balloon is attached around the tip of the probe, which can be inflated with water through an endoscope. Usually, the balloon is inflated after positioning the echoendoscope appropriately. If the balloon is inflated at the time of insertion, it may reduce pharyngeal mucosal injury and subsequent complications caused by the hard tip of the scope. In this study, we evaluated the degree of neck pain after the procedure with balloon inflation, compared with standard insertion.


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Patients and methods

Patients

A single-blinded, prospective, randomized study was performed from October 2016 to September 2018 at a single tertiary center in Seoul, Korea. This study was approved by the institutional review board of Seoul National University Hospital and registered in ClinicalTrials.gov (NCT02924948). Patients aged at least 20 years who underwent radial EUS for diagnosis of pancreatobiliary disease were enrolled. Patients who underwent linear EUS were excluded from the study. Informed consent was obtained from all patients.

Absent any previous study of complications with EUS, 6 % of patients with moderate-to-severe pharyngeal pain were estimated based on ERCP study [5]. Balloon inflation was assumed to reduce the rate of moderate-to-severe pain by nearly 67 %. A total of 482 subjects including 241 in each group were calculated to provide a power of 80 % and α = 0.05. Randomization was done by assigning patients according to a computer-generated random number list with 1:1 allocation using a random block size of 4 or 6 by personnel not involved in the trial.


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Intervention

All interventions were performed by six clinical fellows (A-F) using a radial-array echoendoscope (GF-UE260; Olympus) with a balloon (MH-303; Olympus) applied at the tip. The first 6 months were studied by A and B, the next year by C and D, and the last 6 months by E and F. Since A and B had 6 to 7 months of EUS experience at the time of study participation, the EUS procedure performed by A and B were classified as more than 6 months. C and D had several days of EUS experience when they participated in the study, and about 1 year of experience at the end of the study participation. The procedures, which were performed by C and D for 1 year, were classified into three categories; less than 3 months, 3 to 6 months, and more than 6 months. E and F had several days of experience with EUS at the time of participation. They accumulated about 6 months of experience at the end of the study. The procedures performed by these patients were divided into two categories; less than 3 months and 3 to 6 months.

After conscious sedation with only midazolam (0.05 mg/kg), the randomized assignments were opened by an attending nurse before inserting EUS. In the case of patients who were assigned to the balloon inflation group, the EUS was inserted with a half-inflated balloon. Except for the insertion, the subsequent procedure was no different between the two groups.

After patients recovered from sedation with full consciousness with the ability to engage in adequate conversation. Nurses who did not participate in the endoscopy procedure evaluated the degree of pharyngeal pain with the Numeric Rating Scale (NRS) which is validated in most settings [6] [7].


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Outcomes

The primary outcome was the rate of moderate-to-severe pharyngeal pain with an NRS score of 4 or more [8] [9] according to the insertion method. Secondary outcomes included the degree of pharyngeal pain, rates of insertion failure at first attempt and balloon loss according to the insertion method, adverse events (AEs), the difference in pain level according to the physicians’ experience. Balloon loss was defined as the balloon not inflating due to damage during insertion. Risk factors for post-procedural pain were also evaluated.


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Statistical analysis

The analyses were performed according to intention-to-treat (ITT) analysis and per-protocol (PP) analysis. ITT analysis was performed with all the subjects and PP analysis was performed after exclusion of subjects who underwent additional endoscopy in the same session. Data are expressed as a number and percentage for categorical variables, and as the mean ± standard deviation (SD) or the median for continuous variables. Significance of differences in clinical parameters between groups was assessed using the chi-squared test or Fisher’s exact test, as appropriate. Continuous variables distributed normally were analyzed using the t-test, otherwise, the Mann-Whitney U test was used. Risk factors for pharyngeal pain were evaluated by logistic regression analysis. Demographic, disease-related, and procedure-related factors were assessed in the analysis. Factors with a significance level of 0.1 based on the univariable analysis were considered in the multivariable analysis. Results were expressed as hazard ratios (HRs) and 95 % confidence interval (CI). Statistical significance was assumed at a confidence level of 0.05. Statistical analyses were performed using SPSS 23 (SPSS, Chicago, Illinois, United States).


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Results

Patients’ clinical characteristics

From October 2016 to September 2018, a total of 1,092 patients underwent radial EUS for evaluation of pancreatobiliary disease. We obtained informed consent from 481 of these patients and registered 238 for standard insertion and 243 for balloon inflation. These patients constituted the ITT population. Fifty-five patients were excluded from the per-protocol analysis because of additional endoscopy in the same session with radial EUS. The per-protocol analysis included 213 cases in standard insertion and 217 cases in balloon inflation ([Fig. 1]). Demographic, disease-related and procedure-related characteristics of the two groups were not significantly different ([Table 1]).

Zoom Image
Fig. 1 Flowchart of the study.
Table 1

Baseline characteristics of patients.

Total

Standard (N = 238)

Balloon (N = 243)

P value

Age (mean, range)

 57.3 (24–80)

 57.1 (26–80)

 57.6 (24–80)

0.675

Gender

0.927

Male

228

112 (47.1 %)

116 (47.7 %)

Female

253

126 (52.9 %)

127 (52.3 %)

Etiology

0.121

Pancreas

232

124 (52.1 %)

108 (44.4 %)

Biliary tract

258

119 (50.0 %)

139 (47.2 %)

Patients' experience

0.581

No

450

221 (92.9 %)

229 (94.2 %)

Yes

 31

 17 (7.1 %)

 14 (5.8 %)

Endoscopistsʼ experience

0.865

 > 6 months

156

 78 (32.8 %)

 78 (32.1 %)

3–6 months

170

 84 (35.3 %)

 86 (35.4 %)

 ≤ 3 months

155

 76 (31.9 %)

 79 (32.5 %)

Observation time (min, mean±SD)

  6.2 ± 4.2

  6.0 ± 3.9

  6.5 ± 4.4

0.232

SD, standard deviation


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Primary outcome

One hundred and twelve patients (23.3 %) reported moderate-to-severe pharyngeal pain after the procedure. The ratio of patients reporting moderate-to-severe pain with an NRS score of 4 or more was slightly lower in the balloon insertion group, without any statistical significance (26.5 % vs. 20.2 %; P = 0.107). In PP analysis, the difference in the ratio of moderate-to-severe pain was also lower in the balloon group but was not statistically significant (23.9 % vs. 16.1 %; P = 0.053, [Table 2]).

Table 2

Primary outcome: moderate-to-severe pharyngeal pain according to the insertion method.

ITT analysis

Standard (N = 238)

Balloon (N = 243)

P value

NRS < 4

175 (73.5 %)

194 (79.8 %)

0.107

NRS ≥ 4

 63 (26.5 %)

 49 (20.2 %)

PP analysis

Standard (N = 213)

Balloon (N = 217)

P value

NRS < 4

162 (76.1 %)

179 (83.9 %)

0.053

NRS ≥ 4

 51 (23.9 %)

 38 (16.1 %)

ITT, intention-to-treat; PP, per-protocol; NRS, numeric rating scale


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Secondary outcomes

Post-procedural pain score was slightly lower in the balloon group, but did not reach statistical significance (2.04 ± 2.39 vs. 1.83 ± 2.11, P = 0.297). Rate of insertion failure at first attempt (standard vs. balloon 8.4 % vs. 5.8 %; P = 0.289) and the rate of balloon loss (standard vs. balloon 8.0 % vs. 6.6 %; P = 0.601) were not significantly different between the two groups. PP analysis did not show any significant differences in those outcomes, either ([Table 3]). During the trial period, no procedure-related AEs such as bleeding, perforation, or subsequent infection occurred.

Table 3

Secondary outcomes according to the insertion method.

ITT analysis

Standard (N = 238)

Balloon (N = 243)

P value

NRS (mean±SD)

  2.04 ± 2.39

  1.83 ± 2.11

0.297

Insertion at 1st attempt

0.289

Success

218 (91.6 %)

229 (94.2 %)

Fail

 20 (8.4 %)

 14 (5.8 %)

Loss of balloon

0.601

No

219 (92.0 %)

227 (93.4 %)

Yes

 19 (8.0 %)

 16 (6.6 %)

Procedure-related complications

  0

  0

ns

PP analysis

Standard (N = 213)

Balloon (N = 217)

P value

NRS (mean±SD)

  1.70 ± 2.17

  1.65 ± 2.01

0.651

Insertion at 1st attempt

0.274

Success

194 (91.1 %)

204 (94.0 %)

Failure

 19 (8.9 %)

 13 (6.0 %)

Loss of balloon

0.854

No

197 (92.5 %)

202 (93.1 %)

Yes

 16 (7.5 %)

 15 (6.9 %)

Procedure-related complications

  0

  0

ns

ITT, intention-to-treat; PP, per-protocol; NRS, numeric rating scale; SD: standard deviation


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Risk factors for pharyngeal pain

Risk factors for moderate-to-severe pharyngeal pain were evaluated according to the various characteristics. Gender, age, observation time, patient’s prior EUS experience, the endoscopist’s experience at time of procedure, and the insertion method were considered as variables in logistic regression analysis. Age and observation time were classified based on interquartile ranges. Female gender and endoscopist's experience with less than 3 months were associated with severe pain, whereas older age ( > 66 years) and balloon inflation were associated with less pain in multivariable analysis ([Table 4]).

Table 4

Risk factors for pharyngeal pain.

Factors

N

Univariable

Multivariable

HR (95 % CI)

P value

HR (95 % CI)

P value

Gender

  • Male

228

1

1

  • Female

253

2.263 (1.434–3.572)

< .001

2.168 (1.349–3.483)

0.001

Age

  •  < 50

121

1

1

  • 50–58

121

0.960 (0.550–1.678)

0.887

0.945 (0.528–1.691)

0.945

  • 59–66

121

0.810 (0.458–1.432)

0.469

0.779 (0.429–1.416)

0.413

  •  > 66

118

0.414 (0.217–0.790)

0.007

0.341 (0.174–0.671)

0.002

Insertion method

  • Standard

238

1

1

  • Balloon

243

0.666 (0.427–1.040)

0.074

0.645 (0.423–0.983)

0.041

Patients‘ experience

  • No

450

1

  • Yes

 31

0.912 (0.383–2.176)

0.836

Observation time (min)

  •  ≤ 3.3

 87

1

  • 3.4–4.9

119

0.935 (0.523–1.675)

0.822

  • 5.0–7.7

116

0.824 (0.452–1.503)

0.528

  •  > 7.7

159

1.057 (0.594–1.882)

0.851

Endoscopistsʼ experience

  •  ≥ 6 months

156

1

1

  • 3~6 months

170

1.015 (0.582–1.773)

0.957

1.095 (0.618–1.942)

0.755

  •  < 3 months

155

2.409 (1.431–4.054)

0.001

2.861 (1.658–4.938)

< 0.001

HR, hazard ratio; CI, confidence interval

We compared the proportion of patients experiencing moderate-to-severe pharyngeal pain according to the insertion method in patients with identified risk factors. No differences based on the insertion method were found in female (30.7 % vs. 22.8 %, P = 0.177) or younger patients (29.1 % vs. 23.6 %, P = 0.367). In patients who were undergoing EUS by endoscopists with less than 3 months’ experience, pain score was significantly higher than in other groups (< 3 months: 2.4, 3 – 6 months: 1.7, > 6 months: 1.7, P = 0.016). However, balloon inflation decreased the proportion of patients experiencing moderate-to-severe pharyngeal pain when performed by endoscopists with less than 3 months’ experience (44.7 % vs. 25.3 %, P = 0.012) ([Fig. 2]).

Zoom Image
Fig. 2 Rates of moderate-to-severe pharyngeal pain according to the physician’s experience with EUS and the insertion method. Fewer patients reported moderate-to-severe pharyngeal pain with inflated balloon when EUS was performed by endoscopists with less than 3 months’ experience of EUS. 

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Discussion

Results of this study indicate that EUS insertion with an inflated balloon was effective in terms of post-procedural pain without disturbing procedure, especially performed by physicians with less than 3 months of experience.

Although there was no statistically significant difference in average pain intensity and rate of moderate-to-severe pain according to insertion method. Balloon inflation tended to be lower than the standard method in both outcomes. In addition, no increase was found in rates of insertion failure or balloon loss with increased diameter due to the inflated balloon. Balloon inflation did not hinder the procedure.

Compared with results of the referenced study, the rate of moderate-to-severe pharyngeal pain after EUS was much higher than expected, while the average pain level was mild (NRS ≤2). Therefore, it is possible that more participants may have been needed to reach statistical significance. There are several reasons for this result. First, the structural difference between endoscope should be considered. Second, the absence of analgesics such as meperidine or fentanyl during conscious sedation may have affected pain level. Third, this study involved a higher proportion of female patients who are known to be more sensitive to pain. In addition, the difference in the proficiency level of the endoscopists may have been influential.

Several factors were identified as associated with pharyngeal pain. Balloon inflation may be a protective factor. During insertion, the portion of the endoscope contacting the mucous membrane is soft and plastic with compliance. Because it has a curved surface, it is expected to reduce mucosal damage due to physical contact. The total force exerted upon insertion and pharyngeal pain caused by force may not be reduced [10] [11] but the possibility of additional pain can be decreased by reduced physical injury.

Younger age was identified as a risk factor for pain. A study showed that younger patients complained of pain after the ERCP procedure [5]. The tone of the upper esophageal sphincter is increased in younger patients, and reflex response to the stimulus is also higher than in the elderly [12]. Therefore, younger patients are more likely to feel greater pain, because greater pressure is needed to offset the elevated muscle tone and reflexes.

Gender was also one of the risk factors for pain. In the study of conventional upper gastrointestinal endoscopy, the rate of pain complaints was higher in women [4]. Higher prevalence of moderate-to-moderate pain in women suggests the effect of gender difference. It is known that women are likely to suffer from more severe pain than men in diseases like irritable bowel syndrome (IBS) [13]. The reason for the lower pain threshold in women is not yet clear. In previous studies, psychosocial factors and behavioral stress related to social learning were the main factors [14] [15]. Recently, the hormonal factor is also postulated as important from a recent gender-specific perspective [13] [16].

Experience level in endoscopy was identified as a major risk factor for pain. The shorter the experience, the harder can be the insertion procedure and greater the risk of complications. In this study, pain associated with insertion was reduced and plateaued after 70 procedures and approximately 3 months of experience. Studies of endoscopy learning curves showed that in the case of EUS, a certain level of technical competence was achieved after 50 to 75 procedures [17] [18] [19]. In this study, a comparable level of technical competence was reached in accordance with previous studies.

Based on these results, we examined conditions under which balloon inflation can alleviate pharyngeal pain. It was effective in reducing the rate of moderate-to-severe pain for physicians with less than 3 months of EUS experience. Because balloon inflation did not significantly increase the rate of insertion failure or balloon loss, it may prevent the risk of pain and complications for unexperienced endoscopists.

Our study has several limitations. First, it was a single-blind trial. Although pain evaluation was made by a third-party nurse not related to the study, possible biases from the operators still remained. Second, we did not evaluate factors from a socioeconomic aspect or quality-of-life perspective. Mental health and quality of life may play an important role in pain thresholds [5] [15]. Third, there were no complications, such as clinically important gastrointestinal bleeding or perforation associated with EUS insertion. Therefore, the role of pain as a surrogate marker was limited.

Our study also has some strengths. First, it is the first prospective study of complications associated with EUS. Second, it identified risk factors for pain during EUS insertion. Third, it showed that balloon inflation can be used to prevent complications by novices. Fourth, although the study did not identify learning curves, it indirectly demonstrated that 3 months is needed to become technically competent in echoendoscope insertion, as the pain associated with insertion was significantly reduced after performing 70 procedures.


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Conclusion

In conclusion, when performed by physicians with EUS experience of fewer than 3 months, the balloon inflation method can reduce the proportion of patients with moderate-to-severe pharyngeal pain.


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Competing interests

The authors declare that they have no conflict of interest.


Corresponding author

Sang Hyub Lee
Associate Professor
Division of Gastroenterology, Department of Internal Medicine and
Liver Research Institute
Seoul National University Hospital
Seoul National University College of Medicine
101 Daehak-ro, Jongno-gu
Seoul, 03080
Korea   
Fax: 82-2-762-9662   

Publication History

Received: 11 October 2019

Accepted: 02 December 2019

Publication Date:
21 February 2020 (online)

© 2020. Owner and Copyright ©

© Georg Thieme Verlag KG
Stuttgart · New York


Zoom Image
Fig. 1 Flowchart of the study.
Zoom Image
Fig. 2 Rates of moderate-to-severe pharyngeal pain according to the physician’s experience with EUS and the insertion method. Fewer patients reported moderate-to-severe pharyngeal pain with inflated balloon when EUS was performed by endoscopists with less than 3 months’ experience of EUS.