Comparision of the hemostatic efficacy from the combined bipolar probe coagulation with epinephrine injection and the bipolar proble coagulation alone in the treatment of peptic ulcer

Objectives: This study compared the combined bipolar probe coagulation with epinephrine injection during endoscopic process with the bipolar probe coagulation alone in the treatment for patients suffering from peptic ulcer bleeding.

Journal of military pharmaco-medicine No7-2016 COMPARISION OF THE HEMOSTATIC EFFICACY FROM THE COMBINED BIPOLAR PROBE COAGULATION WITH EPINEPHRINE INJECTION AND THE BIPOLAR PROBLE COAGULATION ALONE IN THE TREATMENT OF PEPTIC ULCER BLEEDING Le Quang Duc*; Tran Viet Tu**; Nguyen Quang Duat** SUMMARY Objectives: This study compared the combined bipolar probe coagulation with epinephrine injection during endoscopic process with the bipolar probe coagulation alone in the treatment for patients suffering from peptic ulcer bleeding Subjects and methods: Patients who were endoscopically confirmed of peptic ulcer bleeding (active or visible vessel) during the period from January, 2010 through December, 2014, were prospectively randomized into two groups The control group was treated by the bipolar probe coagulation alone (group 1); and the study group was treated by the combined bipolar probe coagulation with epinephrine injection during the endoscopic process (group 2) The primary outcomes, in terms of initial hemostasis, rate of recurrent bleeding within 72 hours, blood transfusion volume after the intervention, duration of hospital stay, and the potential risk of blood transfusion after the intervention were assessed Results: The common rate of initial hemostasis was 97.5% (95.1% and 100% in group and 2, respectively); the rate of recurrent bleeding in group 1: 5.2%, and group 2: 0% showing the remarkable success of hemostasis in group (100%) compared to group (90.2%) (p = 0.043); the blood transfusion after the intervention in group and were 792.9 ± 125.56 (p = 0.370) and 557.7 ± 41.76 mL, respectively; duration of hospital stay were 9.6 ± 3,01 and 8.9 ± 3.12 days (p = 0.167) As such, the combination method showed the reduction of the potential risk of blood transfusion after the intervention from 1.28 - 1.39 times in comparison with the bipolar probe coagulation alone method Conclusion: The combined bipolar probe coagulation with epinephrine injection during the endoscopic process was proved more effective than the bipolar probe coagulation alone in the treatment of patients suffering from peptic ulcer bleeding * Key words: Peptic ulcer bleeding; Hemostasis; Electrical oagulation BACKGROUND Peptic ulcer bleeding is a common emergency, and can be life-threatening if patients are not treated timely Endoscopic hemostasis is an effective treatment method for peptic ulcer bleeding reducing the ratio of dead and surgery [2, 4, 6] There are many methods of endoscopic hemostasis, in which coagulation injection and probe coagulation are commonly used [2] Recently, some activists have conducted the combination method and observed the effectiveness in hemostasis for peptic ulcers [7] However, there has not been any study discussing and comparing the effectiveness among these methods * Haiduong General Hospital ** 103 Hospital Corresponding author: Le Quang Duc (bsquangduc@gmail.com) 22 Journal of military pharmaco-medicine No7-2016 Therefore, this study is aiming at: Compare the hemostatic efficacy between the bipolar probe coagulation alone and the combined bipolar probe coagulation with epinephrine injection during the endoscopic process SUBJECTS AND METHODS Subjects of the study 122 selected patients among 1,252 patients suffering from peptic ulcer bleeding who were being treated at the Internal Digestive Department of the General Hospital of Haiduong from 01 - 2010 to 12 - 2014 * Diagnostic criteria: Symptoms including vomiting of blood or black stool; active bleeding of Forrest IA, B showed in endoscopy taken within 24 hours after admission, and the ulcer with high-risk of Forrest II A, B * Exclusion criteria: Peptic bleeding by no ulcer, bleeding ulcer with clean bottoms, large ulcers by stomach cancer, patient who does not agree to participate the study Methods * Study method: Patients were selected in the two groups in the form of coupling, based on classifications by gender and age: alone method group (group 1) and the combined method group (group 2) The epinephrine injection was conducted before the probe coagulation The step of conduction included: using the 25G needle associating with the gold probe (7 Fr) to inject a dose of - mL adrenalin 1/10.000 into plots around the bleeding point Probe coagulation was conducted after that around or directly into the vessels or the bleeding point with the intensity of 10 - 15 in - 10 seconds The entire intervention was implemented using the Olympus-CV 240 endoscopic system, the ICC-ERBE 300 probe coagulation system, the bipolar interject gold probe (Boston Scientific) which is the probe association with the injection needle and the probe coagulation needle Patients were clinically monitored, re-tested, screened after 72 hours If bleeding recurrence was found, endoscopic hemostasis shall be applied again * Criteria for evaluation: - Primary hemostasis: (1) Hemostasis: no evident of bleeding via endoscopic after the last hemostasis: no flow of blood; (2) If the bleeding is on-going: other endoscopical hemostasis shall be conducted (such as combination of injection and probe coagulation or clip hemostasis, etc.); (3) If the bleeding keeps going: patient shall be intervented by surgery Monitoring of bleeding recurrence based on the symptoms such as vomiting of red blood or discharging of black tool, or continuous reduction of Hb within 24h If the bleeding recurrence was suspicious, endoscopic would be conducted again right away and the treatment would be taken again from the beginning - Assessment after 72 hour: (1) Good (entire ulcers was hemostasised, no evident of bleeding); (2) Average (primary hemostasis, bleeding recurrence afterward causing reintervention, then being success within 72 hours); (3) Poor (hemostasis failed at the primary endoscopical intervention and 23 Journal of military pharmaco-medicine No7-2016 other method had to be used including surgery, or the patient was dead) Assessment of hemostasis (first time, second time or third time if bleeding recurrence over and over): “Success” if no blood flow was found; “Fail” if bleeding is on-going or recurrent Assessment of intervention duration; assessment of the ratio of recurrent bleeding, the volume of transfused blood, duration of hospital stays and some other criteria were included The studied data were processed by SPSS 15.0 using percentage algorithm (%,) average algorithm accepting standard deviations, % comparison, and average values Test t-student was used for square algorithm and Mann-Whitney was used with appropriate deviations for accreditation test RESULTS General features Table 1: Age, gender and the status of blood coagulation before intervention Research targets Average age Total, n (%) Group 1, n (%) Group 2, n (%) 55.4 ± 16.83 55.4 ± 16.78 55.3 ± 17.02 (15 - 91) (15 - 87) (15 - 91) 61/38 42/19 42/19 Gender (male/female) p 0.957 Male patients took 68.9% Male/female ratio = 2.2/1 There was no difference in terms of age and gender between the two groups Table 2: RBC count, hemoglobin and hematocrit concentration, and blood transfusion before intervention Features Volume of erythrocytes (T/L) Concentration of hemoglobin (g/L) Hematocrit (%) Ratio of blood transfusion before intervention Volume of blood transfusion before intervention (mL) Total Group Group 2.9 ± 0.91 2.8 ± 0.92 2.9 ± 0.90 (1,11 - 1,53) (1.11 - 5.13) (1,38 - 5.06) 82.7 ± 25.90 79.7 ± 24.47 85.8 ± 27.12 (25 - 144) (25 - 138) (41 - 144) p 0.729 0.200 25.5 ± 7.66 24.9 ± 7.38 25.9 ± 7.95 (10.2 - 43.5) (10.2 - 42.2) (12.8 - 43.5) 80/122 (65.6%) 44/61 (72.1%) 36/61 (59.0%) 0.127 n = 54 502.8 ± 23.95 (250 - 1,250) n = 30 533.3 ± 33.33 (250 - 1,250) n = 24 464.58 ± 33.31 (250 - 750) 0.423 0.450 There was no difference in terms of volume of hemoglobin as well as volume of blood transfusion between the two groups before and after intervention The ratio of patients who had blood transfused as well as volume of blood transfusion before intervention also showed no difference 24 Journal of military pharmaco-medicine No7-2016 Table 3: Endoscopic picture before hemostasis Endoscopic pictures before hemostasis Total Group Group n (%) n (%) n (%) p Forrest classification Forrest IA (1.6) (1.6) (1.6) Forrest IB 39 (32.0) 20 (32.8) 19 (31.1) 0.845 Forrest IIA 28 (23.0) 14 (23.0) 14 (23.0) Forrest IIB 53 (43.4) 26 (42.6) 27 (44.3) 0.856 Total 122 (100) 61 (100) 61 (100) Location of ulcer Stomach 30 (24.6) 17 (27.9) 13 (21.3) 0.400 Duodenum 86 (70.5) 41 (67.2) 45 (73.8) 0.427 Stomach + duodenum (4.9) (4.9) (4.9) Ulcer size < cm 25 (20.5) 12 (19.7) 13 (21.3) 0.823 - cm 91 (74.6) 46 (75.4) 45 (73.8) 0.836 > cm (4.9) (4.9) (4.9) Endoscopic pictures were mainly seen in Forrest IB, IIA and IIB with respective ratios 32.0%, 23.0% and 43.4% The ratio of Forrest IA was rarely seen taking only 1.6% There was no difference between the two groups in terms of bleeding level The common location of ulcer was seen at duodenum The ratio ulcer location at duodenum/stomach = 2.4/1 Ulcer sizes of about - cm took 74.6% There was no difference between the two groups in terms of location and size of ulcer Results from the endoscopic intervention Table 4: Pictures of primary hemostasis Hemostatic result Total, n (%) Group 1, n (%) Group 2, n (%) p Picture of primary hemostasis Complete hemostasis 119 (97.5) 58 (95.1) 61 (100) Incomplete hemostasis (2.5) (4.9) On-going bleeding 0 0.079 Ratio of bleeding recurrence Yes (2.6) (5.2) No 116 (97.4) 55 (94.8) 61 (100) 0.072 25 Journal of military pharmaco-medicine No7-2016 Results from the first time hemostasis Success 116 (95.1) 55 (90.2) 61 (100) Fail (4.9) (9.8) 0.012 General results of hemostasis Good 116 55 (90.2) 61 (100) Average 3 (4.9) Poor 3 (4.9) The ratio of complete hemostasis after intervention was 97.5%, in which group was 95.1%, group was 100% 4.9% in group showed incomplete hemostasis therefore other endoscopic hemostasis methods were mobilized There was no case of impossible intervention via endoscopy Group showed the bleeding recurrence ratio of 5.2%, which reflected no statistical meaning of p = 0.072 in comparison with group Table 5: Volume of blood transfusion after intervention and the duration of hospital stays Feature Total (n = 54) Group (n = 28) Group (n = 26) p Volume of blood transfusion after intervention 679.6 ± 510.23 (250 - 3,000) 792.9 ± 664.40 (250 - 3,000) 557.7 ± 212.92 (250 - 1,000) 0.091 9.3 ± 3.07 (3 - 22) 9.7 ± 3.01 (4 - 18) 8.9 ± 3.04 (3 - 22) 0.167 Duration of hospital stays There was no difference in terms of volume of blood transfusion and duration of hospital stays between the two groups Assessment of risks factors after intervention Table 6: Ratio of required blood transfusion among the sub-groups of light and heavy blood lost Ratio of required blood transfusion HR Group with high blood lost (required blood transfusion before intervention) Group with low blood lost (no requirement of blood transfusion before intervention) Group (n = 30) Group (n = 24) p1 = 16/30 (53.3%) p2 = 10/24 (41.7%) n = 31 n = 37 p1 = 14/31 (45.2%) p2 = 12/37 (32.4%) p1/p2 = 1.28 p1/p2 = 1.39 Group with high blood lost: risk of blood transfusion again in group was 1.28 time higher than group Group with low blood lost: risk of blood transfusion again in group was 1.39 time higher than group 26 Journal of military pharmaco-medicine No7-2016 DISCUSSION General features *Age and gender: Average age of the studied groups was 55.4 ± 16.83, the youngest was 15 and the highest was 91 years old Among the 122 patients, male took 68.9%, male/female ratio = 2.24 This ratio was similar with the ratio of the studies from in-country activist such as Tran Viet Tu [3], and from outcountry activist such as Bianco et al 75% [5], Chau et al 64.9% and 70,5%, Soon et al 73.0% [9] There was no difference in terms of average age and gender ratio between the two studied groups * Clinical and subclinical features: Regarding the CBC value, average hemoglobin concentration was 82.8 ± 25.91 g/L, similarly to the study taken by Bianco [5] Results showed that majority of patients suffered from average to high blood lost levels and this feature is shown similarly in both groups * Characteristics of peptic ulcers: In this study, the endoscopic pictures were mainly Forrest IB, IIA and IIB with respective ratios of 32.0%, 23.0% and 43.4% The ratio of Forrest IA was rarely seen taken 1.6% Majority of ratios were similar to the studies conducted by in and out country activists, but showed lower ratio of Forrest IA compared with the studies conducted by Dao Van Long [1], Tran Viet Tu [2] Ulcer size of more than cm took 79.5% associating with potential risk of bleeding and high blood lost The observation of endoscopical pictures showed no difference in terms of ulcers’ characteristics Results from the endoscopic intervention Results from endoscopic intervention were assessed based on the primary hemostasis The overall results from the combined groups reached 100% The bipolar probe coagulation alone group reached 95.1%; the other 4.9% of patients was seen on-going bleeding, therefore other endoscopic hemostatic methods including hemostatic injection and clipping were applied Although the intervention of endoscopic alone was effective in the treatment of ulcer in stomach and duodenum, a small recurrent ratio remained [2] As such, later studies tried to improve the results by the combined methods Based on different hemostatic theories, adrenalin was proved to be the active factor for hemostasis inside the endogenous arteries resulting vasoconstriction and therefore making it easier for coagulation The thermal probe can result in the artery inflow causing organizational coagulation and therefore activate the coagulation in the arteries and cause the swelling which help to pinch the artery Via each probe point, the blood flow would be seen decreasing and coagulating completely [4, 6] This study showed the good result on 100% of patients in their initial hemostasis This result fit with the conclusion by Bianco and Chau confirming the role of adrenalin associating with other methods [5] 27 Journal of military pharmaco-medicine No7-2016 The long-term hemostasis was assessed by the clinical criteria such as color of discharge of patients was gradually brighten and the picture of ulcer bottom was clean After 72h, patients were re-endoscopically tested The general hemostatic result in the combined group was 100% good Assessment of post-intervention risks The result showed that the primary hemostasis in the combined group was remarkable good compared to the bipolar probe coagulation alone group The analysis of post-intervention criteria such as the duration of hospital stays and the volume CONCLUSION The bipolar probe coagulation alone and the combined bipolar probe coagulation with epinephrine injection were proved to be effective in treatment of peptic ulcer bleeding Particularly, the combination of the bipolar probe coagulation alone associating with adrenalin injection during the endoscopic process showed better result 100% of patients enjoyed the complete hemostasis only after the first intervention reducing the risk of blood re-transfusion after intervention from 1.28 - 1.39 compared to the bipolar probe coagulation alone of blood transfusion after the intervention were conducted However, no difference REFERENCES in terms of statistical meaning were found Dao Van Long, Vu Truong Khanh et al Assessment of results of hemostasis using adrenalin 1/10.000 injection during endoscopic process in association with high dose of rabeprazole in intravenous for patients of peptic ulcer bleeding The Vietnam Journal of Digestive Science Episol VII 2012, No 28, pg.1827-1834 The volume of blood transfusion in the combined group was lower than the other groups (p = 0.167) By deeply analyzing this criterion, the data in the table showed that the hazard ratio (HR) was increased from 1.28 to 1.39 It means that the risk of blood transfusion in the group is higher than in the group from 1.28 (in the sub-group with high blood lost need blood transfusion before intervention) Le Quang Duc, Tran Viet Tu, Nguyen Quang Duat Treatment of peptic ulcer bleeding due to ulcers in stomach and duodenum by the bipolar probe coagulation to 1.39 (in the sub-group with low blood lost - during endoscopic process Journal of Vietnam no blood transfusion before intervention Medicine 2014, No 2, pp.58-61 was needed) This parameter once again Tran Viet Tu Study of effectiveness of proved the effectiveness of the combined some injection liquids using for hemostasis bipolar probe coagulation with epinephrine during endoscopic process in the treatment of injection in the treatment for peptic ulcer peptic ulcer bleeding Medical doctorate thesis bleeding Military Medical University 2004 28 Journal of military pharmaco-medicine No7-2016 Barkun A, Toubouti Y, Bardou M et al Endoscopic hemostasis in peptic ulcer bleeding for patients with high-risk lesions: a series of meta-analyses Gastrointest Endosc 2009, 69, pp.786-799 Kataoka M, Kawai T et al Clinical evaluation of emergency endoscopic hemostasis with bipolar forceps in non-variceal upper gastrointestinal bleeding Dig Endosc 2010, 22 (2), pp.151-155 Bianco MA, Rotondano G, Marmo R et al Combined epinephrine and bipolar probe coagulation vs bipolar probe coagulation alone for bleeding peptic ulcer: a randomized, controlled trial Gastrointest Endosc 2004, 60 (6), pp.910-915 Paspatis A, Charoniti I et al A prospective, randomized comparison of 10-Fr versus 7-Fr bipolar electrocoagulation catheter in combination with adrenaline injection in the endoscopic treatment of bleeding peptic ulcers Am J Gastroenterol 2003, 98 (10), pp.2192-2197 Gralnek I, Dumonceau J et al Diagnosis and management of nonvariceal upper gastrointestinal hemorrhage: European Society of Gastrointestinal Endoscopy (ESGE) Guideline 2015 Endoscopy 2015, 47 (10), a1-46 doi: 10.1055/s-0034-1393172 Epub 2015 Sep 29 Soon MS, Wu SS, Chen YY et al Monopolar coagulation versus conventional endoscopic treatment for high-risk peptic ulcer bleeding: a prospective, randomized study Gastrointest Endosc 2003, 58 (3), pp.323-329 29 ... hemostasis bipolar probe coagulation with epinephrine during endoscopic process in the treatment of injection in the treatment for peptic ulcer peptic ulcer bleeding Medical doctorate thesis bleeding... bipolar probe coagulation with epinephrine injection were proved to be effective in treatment of peptic ulcer bleeding Particularly, the combination of the bipolar probe coagulation alone associating... gender and age: alone method group (group 1) and the combined method group (group 2) The epinephrine injection was conducted before the probe coagulation The step of conduction included: using the