Comparison on Oral versus Intravenous Proton Pump Inhibitors for Prevention of Bleeding after Endoscopic Submucosal Dissection of Gastric Lesions

Yeoun Su Jung; Kyeong Ok Kim; Si Hyung Lee; Byung Ik Jang; Tae Nyeun Kim

doi:10.4166/kjg.2016.67.2.74

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Jung, Kim, Lee, Jang, and Kim: Comparison on Oral versus Intravenous Proton Pump Inhibitors for Prevention of Bleeding after Endoscopic Submucosal Dissection of Gastric Lesions

Original Article

Korean J Gastroenterol 2016;67(2):74-80.

Published online: 4 October 2016

DOI: https://doi.org/10.4166/kjg.2016.67.2.74

Comparison on Oral versus Intravenous Proton Pump Inhibitors for Prevention of Bleeding after Endoscopic Submucosal Dissection of Gastric Lesions

Yeoun Su Jung, Kyeong Ok Kim, Si Hyung Lee, Byung Ik Jang, Tae Nyeun Kim

Department of Internal Medicine, Yeungnam University College of Medicine, Daegu, Korea

Correspondence to: Kyeong Ok Kim, Department of Internal Medicine, Yeungnam University College of Medicine, 170 Hyeonchung-ro, Nam-gu, Daegu 42415, Korea. Tel: +82-53-620-3835, Fax: +82-53-623-8038, E-mail: cello7727@naver.com

Received 10 November 2015 Revised 29 January 2016 Accepted 4 February 2016

This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/3.0/) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

Background/Aims

Although intravenous proton pump inhibitor (PPI) has been used for the prevention of post endoscopic submucosal dissection (ESD) bleeding, the route of administration has not been confirmed. The aim of the present study was to compare the efficacy of intravenous and oral PPI administration for the prevention of delayed post ESD bleeding.

Methods

Total 166 consecutive patients were randomly assigned to 30 mg lansoprazol twice a day (PO group) and 120 mg pantoprazole intravenous injection (IV group) for 48 hours. Finally, 65 patients in PO group and 87 patients in IV group were analyzed. After ESD, all patients underwent follow up endoscopy after 24 hours and were observed the symptoms of bleeding up to 60 days after ESD.

Results

Age, sex and use of anticoagulants were not different between groups. At follow up endoscopy after 24 hours, oozing and exposed vessel was noted in 4.6% of PO group and 8.0% of IV group and there was no significant difference. Delayed bleeding occurred in 4 of 65 patients (6.2%) in the PO group and 8 of 87 patients (9.2%) in the IV group (p＞0.999). By multivariate analysis, oozing or exposed vessels at follow up endoscopy were risk factors for delayed bleeding (OR=17.5, p=0.022).

Conclusions

There was no significant difference in the delayed bleeding, length of hospital stay according to the administration route. Bleeding stigmata at follow up endoscopy was risk factor of delayed bleeding. Oral PPI administration can cost-effectively replace IV PPI for prevention of post ESD bleeding.

Keywords: Endoscopic submucosal dissection, Proton pump inhibitors, Hemorrhage

References

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Fig. 1.

Treatment protocol of the groups. POD, post-operative day; PO, per oral; IV, intravenous; ESD, endoscopic submucosal dissection; bid, twice a day; qd, once a day.

Fig. 2.

Flow chart of study participants. PO, per oral; IV, intravenous; PPI, proton pump inhibitor; f/u, follow up.

Table 1.

Baseline Characteristics of 151 Analyzed Patients

	PO group (n=65)	IV group (n=87)	p-value
Age (yr)	62.0±8.8	62.6±9.6	0.702
Male	45 (69.2)	64 (73.6)	0.557
Laboratory findings
Hemoglobin (g/dL)	13.2±1.5	13.5±1.5	0.181
BUN (mg/dL)	15.1±5.2	14.9±6.0	0.884
Creatinine (mg/dL)	1.5±5.2	0.9±0.7	0.272
Underlying disease	36 (55.4)	36 (41.4)	0.087
Diabetes mellitus	10 (15.4)	8 (9.2)	0.243
Hypertension	24 (36.9)	26 (29.9)	0.361
Cerebro-cardiovascular	8 (12.3)	2 (2.3)	0.019
Others^*	6 (9.2)	7 (8.0)	0.796
Anticoagulation	15 (23.1)	13 (14.9)	0.201
Warfarin	0 (0)	0 (0)	−
Aspirin	14 (21.5)	13 (14.9)	0.293
Clopidogrel	2 (3.1)	2 (2.3)	＞0.999
Cilostazole	1 (1.5)	0	0.428
Discontinuation period (day)	9.1±6.2	7.5±1.7	0.352

Values are presented as mean±SD or n (%).

PO, per oral; IV, intravenous.

^*Malignancy (breast, thyroid, brain), chronic hepatitis B, benign prostate hypertrophy.

Table 2.

Endoscopic and Microscopic Findings of the Lesion

	PO group (n=65)	IV group (n=87)	p-value
Location (long axis)			0.340
Antrum	37 (56.9)	56 (64.4)
Angle	8 (12.3)	14 (16.1)
Proximal body	4 (6.2)	4 (4.6)
Mid body	4 (6.2)	2 (2.3)
Distal body	8 (12.3)	8 (9.2)
Fundus/cardia	1 (1.5)	3 (3.4)
Pylorus	3 (4.6)	0 (0)
Location (short axis)			0.502
Anterior wall	8 (12.3)	9 (10.3)
Posterior wall	15 (23.1)	18 (20.7)
Lesser curvature	29 (44.6)	33 (37.9)
Great curvature	13 (20.0)	27 (31.0)
Resection style			＞0.999
En bloc	63 (96.9)	83 (95.4)
Piecemeal	2 (3.1)	4 (4.6)
Pathologic sample size (cm²)	7.0±5.0	6.5±4.0	0.425
Microscopic findings			0.077
Tubular adenoma	30 (46.2)	30 (34.5)
High grade dysplasia	2 (3.1)	11 (12.6)
AdenoCa WD	24 (36.9)	29 (33.3)
AdenoCa MD	8 (12.3)	10 (11.5)
Gastritis	1 (1.5)	7 (8.0)
Follow up GFS			0.292
Clean ulcer	23 (35.4)	21 (24.1)
Spurting	0 (0)	0 (0)
Oozing	2 (3.1)	7 (8.0)
Exposed vessel	1 (1.5)	0 (0)
Adherent clot	8 (12.3)	11 (12.6)
Red spot	31 (47.7)	48 (55.2)
Stigmata at follow up GFS	3 (4.6)	7 (8.0)	0.517

Values are presented as n (%) or mean±SD.

PO, per oral; IV, intravenous; AdenoCa, adenocarcinoma; WD, well differentiated; MD, moderate differentiated; GFS, gastrofiberscopy.

Table 3.

Comparison of Bleeding after Endoscopic Submucosal Dissection

	PO group	IV group	p-value
Bleeding during procedure	14 (21.5)	13 (14.9)	0.293
Delayed bleeding	4 (6.2)	8 (9.2)	0.558
Symptomatic bleeding	2 (3.1)	3 (3.4)	＞0.999
Non-symptomatic bleeding	2 (3.1)	5 (5.7)	0.699
Onset of delayed bleeding (hr)			0.236
Within 24	2 (50)	7 (87.5)
24–72	0 (0)	0 (0)
Over 72	2 (50)	1 (12.5)
Mortality	0 (0)	0 (0)	−
Hospital stay (day)	4.5±0.8	4.6±1.3	0.445

Values are presented as n (%) or mean±SD.

PO, per oral; IV, intravenous.

Table 4.

Comparisons between Rebleeding Group and Nonbleeding Group

	Rebleeding (n=12)	Nonbleeding (n=140)	p-value
Operator (A/B/C/D)	6/0/3/3	40/3/78/19	0.180
Size of lesion (cm²)	6.98±3.28	6.68±4.55	0.827
PPI administration route (PO/IV)	4/8	61/79	0.558
Hospital stay (day)	5.8±1.7	4.5±1.0	0.010

Values are presented as n only or mean±SD.

PO, per oral; IV, intravenous.

Table 5.

Risk Factors Associated with Post ESD Symptomatic Bleeding (n=5)

	B	p-value	OR (95% CI)
Endoscopic stigma	3.401	0.001	30.000 (4.296–209.508)
Malignant pathologic findings	0.085	0.936	0.919 (0.117–7.222)
Size of lesion	0.165	0.575	1.179 (0.663–2.095)
Location of lesion	0.358	0.565	1.431 (0.423–4.842)
PPI administration route	−0.004	0.997	0.996 (0.114–8.702)

Statistics were analyzed by backward stepwise method in logistic regression analysis.

ESD, endoscopic submucosal dissection; B, regression coefficient; PPI, proton pump inhibitor.

Table 6.

Risk Factors Associated with Post ESD Symptomatic Bleeding after 24 Hours (n=3)

	B	p-value	OR (95% CI)
Endoscopic stigma	2.303	0.073	10 (0.807–123.990)
Malignant pathologic findings	0.370	0.780	1.447 (0.108–19.456)
Size of lesion	0.131	0.679	1.140 (0.613–2.121)
Location of lesion	0.667	0.321	1.949 (0.521–7.294)
PPI administration route	−0.887	0.491	0.412 (0.033–5.145)

Statistics were analyzed by backward stepwise method in logistic regression analysis.

ESD, endoscopic submucosal dissection; B, regression coefficient; PPI, proton pump inhibitor.

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