Comparison of Endoscopic Injection Sclerotherapeutic Agents in Nonvariceal Upper GI Bleeding: A Retrospective Study

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1 Article ID: WMC Comparison of Endoscopic Injection Sclerotherapeutic Agents in Nonvariceal Upper GI Bleeding: A Retrospective Study Corresponding Author: Dr. Ibrahim Masoodi, Gastroenterologist, Division of Gastroenterology&Hepatology King Fahad Medical city Riyadh, Saudi Arabia Submitting Author: Dr. Ibrahim Masoodi MD.DM(Gastroenterology)FACP, Gastroenterologist, Division of Gastroenterology &Hepatology King Fahad Medical city, Dabab street Riyadh, Saudi Arabia Article ID: WMC Article Type: Original Articles Submitted on:29-aug-2011, 02:41:20 PM GMT Article URL: Subject Categories:GASTROENTEROLOGY Published on: 30-Aug-2011, 01:52:20 PM GMT Keywords:Non variceal upper GI bleeding, SRH, Injection sclerotherapy, Adrenaline How to cite the article:jahan R, Masoodi I, Yattoo G N, Shah A R, Zargar S A, Javid G, Singh C, Chalkoo M. Comparison of Endoscopic Injection Sclerotherapeutic Agents in Nonvariceal Upper GI Bleeding: A Retrospective Study. WebmedCentral GASTROENTEROLOGY 2011;2(8):WMC Source(s) of Funding: There was no special funding required for this study Competing Interests: NIL WebmedCentral > Original Articles Page 1 of 12

2 Comparison of Endoscopic Injection Sclerotherapeutic Agents in Nonvariceal Upper GI Bleeding: A Retrospective Study Author(s): Jahan R, Masoodi I, Yattoo G N, Shah A R, Zargar S A, Javid G, Singh C, Chalkoo M Abstract Background:Endoscopic Injection of various agents has proved to be cost effective in controlling bleeding with least complications in bleeding ulcers. Methods: In this retrospective study the records of the patients with non variceal UGI bleed along with final outcome admitted in SKIMS Srinagar(June Sep 2002 )were analyzed.we observed that 51 /123 had no endoscopic therapy and were taken as controls, 72 patients were taken as study group and were divided in three groups. 26 patients had received only injection adrenaline, 23 (sclerosant agent)and 23 (adrenaline +sclerosant) Outcome measured were arrest of bleed, re bleed, transfusion requirement hospital stay surgery and mortality. Both study group and control group had been given Inj. Omeprazole80mg IV bolus followed by 8mg/hr infusion for 72hrs Results:In the study group 55(76.38%) patients had achieved hemostasis compared to 22(43.13) in control group (p=0.00) 16(22.2%) patients in study group had re bleed compared to control group where 25/51(49%) had re bleed. (p=0.002).however, no statistical significant difference was observed in re bleeding rates among three subgroups. Transfusion requirement in the study group was significantly lower compared to controls (3.67±3.06 vs. 6.57±4.37 units; p=0.001)and no significant difference in transfusion requirement among three subgroups. Hospital stay was significantly lower in study group compared to control group (9.64±2.41vs14.04±3.08 days p= Conclusion: Injection sclerotherapy reduced re bleeding rates need for surgery, transfusion requirement and decreased hospital stay. However, none of the sclerosants conferred supremacy over another as far as these study parameters were considered.non variceal Upper GI bleed patients with SRH must receive injection therapy with an available sclerotherapeutic agent Introduction Upper GI bleed continues to be one of the most important medical emergencies. Despite of decrease in ulcer diseases the reported mortality has not changed over past 30 years which continues to be around 10 %.Mortality even rises to 20% for age more than 80 years. Several endoscopic hemostatic modalities have been developed to reduce the mortality rates by preventing further bleeding and obviate the need for high risk surgery. Researchers generally have agreed that active bleeding (sputters or oozing ) is the most important endoscopic predictor of persistent or recurrent bleed. Aggressive rather than conservative management is recommended for a patient with a non bleeding visible vessel who has any of the following characteristic characteristics on admission: age over 60 years, volume of blood transfusion greater than 500ml:shock;and coffee ground fluid in the stomach. Patients with peptic ulcer and spurting hemorrhage carry an 85% incidence of further hemorrhage and a mortality of rate of 50%. Endoscopic treatment has emerged as the first line of treatment in addition to Proton pump inhibitors in patients with stigmata of recent hemorrhage. Various endoscopic methods like electrocautery, Nd.YAG/Argon Laser, heater probes and injection therapy are effective for hemostasis of non variceal bleeding. Meta analysis of randomized controlled trials of non variceal hemorrhage have noted significant reductions in re bleeding rates, transfusion requirements, need for surgery with endoscopic hemostasis. Injection therapy of non variceal bleeds using epinephrine or alcohol is common in Asia and Europe and combinations using various agents like ethyl alcohol. Polidocanol, hypertonic saline or combinations of these are becoming popular. Epinephrine being effective in controlling active hemorrhage and large volumes without causing much tissue damage can be used. Sclerosants cause more tissue inflammation and damage but are more effective in vascular thrombosis. In our setting at SKIMS, Sringer a tertiary care center of J and K state various endoscopic techniques have been used in the treatment of non variceal UGI bleeds for last years.various agents i.e. adrenaline alone, sclerol alone, adrenaline and sclerol have been WebmedCentral > Original Articles Page 2 of 12

3 used effectively with good results. In this retrospective study we tried to analyze whether injection sclerotherapy affected the outcome compared to controls and to see which had been an ideal sclerosing agent in the management of non variceal UGI bleed.. Methods This retrospective study was carried out in SKIMS Sringer from June 1997 to Sep 2000.The records of the patients with Non variceal UGI bleed along with the final outcome after endoscopic treatment injection sclerotherapy, using different sclerosing agents were retrieved from the endoscopic laboratory. Additional information was taken from surgical and medical files and death records of Medical records section SKIMS.Srinagar 123 patients with peptic ulcer bleed formed the study group and out of 123 patients, 51 patients had been managed conservatively without injection sclerotherapy on IV omeprazole 80mg IV bolus followed by 8mg/hr infusion for 72hrs. These were taken as control group. 72 patients (age and gender matched) had received injection sclerotherapy in addition to conservative treatment as above. This group was divided in 3 sub groups as under:- 1.Those who had received injection adrenaline alone.(5-15ml) 2.Those who had received Sclerosant alone.(4-6ml) 3.Those who had received both Adrenaline and sclerosant (5-15mladrenaline and 4-6ml sclerosant) The detailed history as recorded in the files was analyzed with emphasis on presentation Hemet emesis / melena, previous APD disease and number of bleeds, history of analgesic use, smoking, alcohol abuse and any co morbid illness. Patient s clinical record as sensorium, vitals (pulse /BP and postural drop) was recorded. endoscopic findings as location of bleeding site, SRH, Sclerotherapy agent and volume used and whether hemostasis was achieved after single injection or with multiple injections was noted.patients laboratory parameters complete blood count, kidney function tests were also recorded.the outcome parameters were arrest of bleeding, no of transfusion required, hospital stay, surgery and mortality. Patients were excluded if they had documented bleeding tendency i.e. had low platelet count, prolonged prothrombin time or were on anticoagulation.or had bleeding gastric cancer. The hemoglobin and hematocrit had been checked at least once daily and blood transfusion had been given if the hemoglobin dropped to less than 8gm/dl Intravenous Pantoprazole80mg IV bolus followed by 8mg /hr for 72hrs was given to both study and control group. If unstable vital signs or continued tarry or bloody stools were observed during hospitalization, an emergency endoscopy had been performed to give endotherapy. Rebleeding was defined as blood in the stomach 24hrs after therapy :bleeding in the ulcer base at endoscopy presence of unstable vital signs and continued tarry,bloody stools or Hemet emesis after therapy.a visible vessel at endoscopy was defined as a red or black spot elevated from the ulcer base that was resistant to washing and was often associated with fresh clot in the ulcer base.shock was defined as systolic blood pressure less than 100mm Hg and a pulse rate greater than 100beats /minute accompanied by cold sweating, pallor and oliguria. Initial hemostasis was defined as no hemorrhage persisting for 5 minutes and more and ultimate hemostasis was defined as no melena or Hemet emesis with no hemoglobin drop after 30 days after treatment. Patients were operated if they had continued bleed even after repeat endotherapy, needed more than 6 units of blood transfusion in 24hrs, and had hemodynamic instability due to ongoing bleed, STATISTICAL ANALYSIS:- Descriptive statistics were used for age / gender matched distribution. ANOVA test was used for comparison studies between different groups for number of transfusions / hospital stay surgery and mortality. Chi-square / Mann Whitney U Tests were used for studying haemostatic effects. A probability value i.e. p Results The study and control groups were age and gender matched as shown in Table 1. Melena was seen in 63(87.55%) and Hemet emesis in 33(45.8%) in study group. in the control group melena was seen in 46(90.1%) and Hemet emesis in 20(39.2%). Table 2 shows the sites of bleeding and SRH in two groups Of the 72 patients included in the study group 68(94.4%) achieved initial hemostasis (5-10hrs) compared to controls where initial hemostasis was not achieved. (p- Value=0.00). Comparison of various subgroups in the study group revealed that patients assigned to sclerosant group hemostasis were achieved in all 23 (100%) patients. However, there was no significant difference observed when inter group analysis was done. Table 4 In adrenaline group initial hemostasis was achieved in WebmedCentral > Original Articles Page 3 of 12

4 24(92.3%) compared to controls where none of the patients achieved initial hemostasis. This was statistically significant (p value0.000) Table 4 In the 3rd group where combination of sclerosant and adrenaline was used. It was observed that in 21 (91.3%) hemostasis was achieved and none of the controls achieved hemostasis (p value=0.000) Table 4 Rebleed: Out of 72 patients in the study group 16 (22.2%) patients had re bleeds compared to 25/52(49%) in the control group which was statistically significant (p value= 0.002).However, there was no statistical difference observed when intergroup analysis was done among three sclerosing agents viz 5(21.7%) in sclerosant alone and in sclerosant and adrenaline group 6(26.1%) had re bleeding Table 3 Number of transfusions required in the study group ranged from 1-10units and mean requirement of blood transfusion was 3.67±3.06. In control group the requirement of blood transfusion was 1-16 units with mean number of blood transfusion requirement of 6.57± 4.37 units (p value=0.001) Table 3 Hospital stay: In the study group hospital stay ranged from 2-12 days (mean stay 9.64 ±2.41days) compared to controls where hospital stay ranged from 3-16 days with mean stay of ±3.08 days. Intergroup comparison however, revealed no significant difference between three groups. Table 3 Surgery; The frequency of surgery in control group was times higher than in study group. However, the difference didn t reach statistical significance (Pvalue=.273) Table 3 Mortality ;- There was 3.64 times higher mortality in control group than in study group but this didn t reach statistical significance (pvalue0.62)table 3. Discussion Therapeutic endoscopy in the treatment of active bleeding ulcers has been documented to decrease the requirement of no of units of blood transfusion, re bleeding rate, emergency surgery and mortality. The injection therapy has the attraction of demanding little extra equipment beyond an upper gastrointestinal endoscope and very less complication rates. In our study we observed that endoscopic injection sclerotherapy was definitely the preferred first line of management for the non variceal UGI bleeds in patients with SRH than treating these patients conservatively on PPI alone.these findings are in accordance with other workers13,14. The most popular Sclerosants for injection of bleeding ulcers are polidocanol and ethanol. The efficacy and tissue effects of these Sclerosants have been studied in experimental animals. Polidocanol causing hemostasis by bowel wall spasm and acute edema, followed by inflammation and sclerosis. But most of the studies, including the only controlled trial also utilized preinjection with adrenaline15,16,17 All authors advocating Sclerosant injection have cautioned against injecting extra volume. Perforation and gastric wall necrosis although in less than 1% of patients have been reported after injection sclerotherapy of bleeding ulcers. Conflicting reports are available regarding use of additional sclerosants in GI bleed. Sclerosants such as ethanol, polidocanol and ethanolamine are equally effective as adrenaline but carry more risk 18,19 other study has proved that combination therapy with adrenaline and ethanol may improve haemostasis and shorten hospital stay for patients with spurting haemorrhage 20 we did not observe any advantage of using combination of adrenaline and sclerosants as for as hospital stay, blood transfusion and rebleeding rates are concerned. We observed a significant advantage of using injection sclerotherapy in addition to PPI. Out of 72 patients initial hemostasis was achieved in 68 patients (94.4%) in the study group while no patient achieved initial hemostasis in the control group. However, in inter group comparison we observed no significant advantage using sclerosants or adrenaline or with combination. Initial and late hemostasis with sclerosant was 100% and 78.3% with adrenaline. 92.3% and 78.39% respectively. Palmer et al observed similar results21, however Rutgarts P et al22 observed that combination (Polidocanol +adrenaline) was superior than adrenaline alone for bleeding ulcers In further analysis we observed that control group had significantly longer hospital stay than study group, this is in accordance with other workers 23,24 however, in the intergroup analysis hospital stay did not show any difference. It is possible that initial hemostasis was achieved by all agents and ultimate hemostasis was irrespective of the agent used. Control group had undergone 2.08 times more surgical interventions than study group; however, this did not reached statistical significance. Similar results have been reported by other workers15,17 although no specific advantage was observed by any specific methodology. Injection sclerotherapy has been seen to achieve better hemostasis than conservative approaches irrespective of agent used in previous studies as well. In a trial involving 113 patients with active bleeding and non bleeding vessels, Panes et al 25 demonstrated that injection of epinephrine followed by 1%polidochanol reduced the rate of recurrent bleeding from 43%to5%, transfusion requirement and hospital WebmedCentral > Original Articles Page 4 of 12

5 stay with no reduction in mortality. However, the difference in numbers of patients undergoing surgery didn t reach statistical significance and also mortality wasn t affected by any of approaches. Conclusion(s) Our study confirms the observation that endoscopic sclerotherapy in non variceal bleeds significantly reduces blood transfusion requirement, hospital stay, and need for surgery and re bleed rates. However, ascertanity of an ideal sclerosing agent could not be made as all the 3 agents alone or in combination were effective. None of these conferred supremacy over each other as far as above studied parameters was considered and we advocate use of any available agents in patients with peptic ulcer bleed with signs of recent hemorrhage. References 1. Celi?ski K, Cichoz-Lach H, Madro A, S?omka M, Kasztelan-Szczerbi?ska B, Dworza?ski T. Non-variceal upper gastrointestinal bleeding--guidelines on management J Physiol Pharmacol Aug;59 Suppl 2: Silverstein FE,Gilbert DA,Tedesco FJ,Buenger NK, Persing J. The national ASGE survey on upper gastrointestinal bleeeing. Gastrointest Endosc1981:27: Tajima A, Koizumi K, Suzuki K, Higashi N, Takahashi M, Shimada T, Terano A, Hiraishi H, Kuwayama H J Proton pump inhibitors and recurrent bleeding in peptic ulcer disease. Gastroenterol Hepatol Dec;23 4. Murthy S, Keyvani L, Leeson S, Targownik LE Intravenous versus high-dose oral proton pump inhibitor therapy after endoscopic hemostasis of high-risk lesions in patients with acute nonvariceal upper gastrointestinal bleeding. Dig Dis Sci Jul;52(7): Epub 2007 Mar Sanowski RA, Waring JP. Endoscopic injection therapy for non-variceal bleeding lesions of the upper gastrointestinal tract.j.clin Gastroenterol 1989:11: Chung SCS, Leung JWC, Steele RJC,Crofts TJ Li AKC. Endoscopic injection of adrenaline for actively bleeding ulcers: a randomized trial.bmj1988:296: Lin HJ, Hsieh YH, Tseng GY, Perng CL, Chang FY, Lee SD. A prospective, randomized trial of largeversus small-volume endoscopic injection of epinephrine for peptic ulcer bleeding. Gastrointest Endosc May;55(6): Lin HJ, Lee FY, Tsai YT, Lee CH. What kind of non bleeding visible vessel in a peptic ulcer needs aggressive therapy Endoscopy: 1990:22: Lin HJ, Lo WC, Cheng YC, Perng CL. Role of intravenous omeprazole in patients with high-risk peptic ulcer bleeding after successful endoscopic epinephrine injection: a prospective randomized comparative trial. Am J Gastroenterol Mar;101(3): Pimple W.Boecki O, WaclawuczekHW, HeinermassM. Estimation of the mortality rate of patients with severe gastroduodenal hemorrhage with the aid of new scoring system.endoscopy1987:19: Bleau BL,Gastout CJ Rebleeding from peptic ulcer associated with adhesive clots a randomized controlled study, comparing endoscopic therapy and medical therapy GI endoscopy 1995:41: J.Blanzo, S.Sanz.J.Such, J.C.Espinos, C.Guarner. Endoscopic hemostasis by local injection of epinephrine and polidocanol in bleeding ulcer.a prospective Randomized trial.endoscopy 20(1988) Bateller R,Lach J,Salmeron JM.Endoscopic sclerotherapy in upper gastrointestinal bleeding due to Mallory Weiss syndrome.am.j.gastroenterol.1994:89: Park KG, Steele RJ, and Masson J. Endoscopic injection of adrenaline for benign esophageal ulcer haemorhage.br.j.surg.1994:81: Asaki S. Efficacy of endoscopic pure ethanol injection method for gastrointestinal ulcer bleeding.world J Surg Mar;24(3): Sugawa C, Fujita Y, Ikeda T, Walt AJ. Endoscopic hemostasis of bleeding of the upper gastrointestinal tract by local injection of ninety-eight per cent dehydrated ethanol. Surg Gynecol Obstet Feb;162(2): Wordehoff D, Gros H..Endoscopic haemostasis by injection therapy in high risk patients. Endoscopy 1982 :14: Choudari CP, Palmer KR..Endoscopic injection therapy for bleeding peptic ulcer; a comparison of adrenaline alone with adrenaline plus ethanolamine oleate. Gut. 1994;35(5): Chung SC, Leong HT, Chan AC, Lau JY, Yung MY, Leung JW, et al. Epinephrine or epinephrine plus alcohol for injection of bleeding ulcers: a prospective randomized trial. Gastrointest Endosc. 1996;43(6): Lin HJ, Perng CL, Lee SD. Is sclerosant injection mandatory after an epinephrine injection for arrest of WebmedCentral > Original Articles Page 5 of 12

6 peptic ulcer haemorrhage A prospective, randomised, comparative study. Gut. 1993;34(9): Tajima A, Koizumi K, Suzuki K, Higashi N, Takahashi M, Shimada T, Terano A, Hiraishi H, Kuwayama H J Proton pump inhibitors and recurrent bleeding in peptic ulcer disease. Gastroenterol Hepatol Dec; Kubba AK, Palmer KR. Role of endoscopic injection therapy in the treatment of bleeding peptic ulcer. Br J Surg Apr;83(4): Leung JWC and Chung SCS. Endoscopic injection injection of adrenaline in bleeding peptic ulcers, Gastrointestinal Endosc:1987:33: Oxner RB, Simmonds NJ, Gertner DJ, Nightingale JM, Burnham WR. Controlled trial of endoscopic injection treatment for bleeding from peptic ulcers with visible vessels Lancet Apr 18;339(8799): Adamsen S, Bendix J, Kallehave F, Moesgaard F, Nilsson T, Wille-Jørgensen P. Clinical practice and evidence in endoscopic treatment of bleeding peptic gastroduodenal ulcer. Scand J Gastroenterol Mar;42(3): WebmedCentral > Original Articles Page 6 of 12

7 Illustrations Illustration 1 Tables 1: Base line characteristics of study and control groups. Characteristics study group control group N= 72 N=51 Age (yr) Mean 37.60± ±14.7 Range Gender (No of patients) Male /Females 62 /10 44/7 Condition at presentation WebmedCentral > Original Articles Page 7 of 12

8 No of patients Hemet emesis 33(45.8%) 20(39.2%) Melena 63(87.5%) 46(90.1%) Shock 11(15.2%) 10(19.6%) NSAID use, past 7 days (No of patients) 13(18%) 5(9.8%) Associated medical illness Cardiac /Pulmonary/renal 10(13.8%) 12(23.5%) Smokers (no) 45(62.5%) 13(25.4%) WebmedCentral > Original Articles Page 8 of 12

9 Illustration 2 Table 2: Endoscopic features of study and control groups. Endoscopic features Study group Control group Location of bleed Gastric 28(38.8%) 19(37.2%) Duodenal 44(61.1%) 32(62.7%) Stigmata of recent hemorrhage Clot 7(9.7%) 9(17.6%) Ooze 32(44.4%) 19(37.2%) Spurt 15(20.8%) 12(23.5%) Vessel 18(25%) 11(21.5%) Sclerosant amount 3-5ml nil WebmedCentral > Original Articles Page 9 of 12 Hemostasis achieved24-48hours 55(76%) 22(43.13)

10 Illustration 3 Table 3: Major outcome in the study group and controls. Study group Control group Pvalue Hemostasis achieved 68(94.4%) Rebleed 16(22.2%) 25(49%) Mean number of Transfusion required 3.67± ± Hospital stay (mean no of days) 9.64± ± Surgery required 12(16.7%) 15(29.4%) Mortality 3(4.2%) 7(13.7%) 0.05 WebmedCentral > Original Articles Page 10 of 12

11 Illustration 4 Table 4: Comparison of major outcome in subgroups of study group Sclerosant Adrenaline Sclerosant &adrenaline controls Hemostasis 23(100%) 24(92.3%) 21(91.3%) 0 (p= 0, 00) (p= 0, 00) (p= 0, 00) Rebleed 5(21.7%) 5(19.2%) 6(26.1%) 25(49%) (p=0.027) (p=0.011) (p=0.05) (p=0.002) Mean no of Transfusion required 3.67± ± ± ±4.37 (p=0.005) (p =0.004) (p=.024) (p = 0.001) Hospital stay ±3.08 (p=0.008) (p=0.002) (p=0.017) (p=.008) Surgery 12(16.7%) 5(19.2%) 4(17.4%) 15(29.4%) (p=0.129) (p=0.335) (p=0.273) (p=0.092) Mortality 1(4.4%) 2(7.7%) 0 7(13.7%) WebmedCentral > Original Articles Page 11 of 12 (p=0.229) (p=0.436) (p=0.062) (p=0.5)

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