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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
THE AMERICAN JOURNAL OF GASTROENTEROLOGY © 2003 by Am. Coll. of Gastroenterology Published by Elsevier Inc.
Vol. 98, No. 10, 2003 ISSN 0002-9270/03/$30.00 doi:10.1016/S0002-9270(03)00697-X
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 Gregorios A. Paspatis, M.D., Ioanna Charoniti, M.D., Nikolaos Papanikolaou, M.D., Emmanouil Vardas, M.D., and Gregorios Chlouverakis, Ph.D. Department of Gastroenterology, Benizelion General Hospital; and School of Education, University of Crete, Heraklion, Crete, Greece
OBJECTIVES: Our study compared the efficacy of bipolar electrocoagulation (gold probe) with 10-Fr (group A) versus 7-Fr (group B) catheter after adrenaline injection in the treatment of bleeding peptic ulcers. METHODS: A total of 77 consecutive patients with endoscopic evidence of peptic ulcer with active bleeding or a nonbleeding visible vessel were randomly assigned to one of the above protocols. Thirty-nine patients (31 male, eight female, mean age 62 yr) were included in group A and 38 (28 male, 10 female, mean age 61 yr) in group B. RESULTS: The initial hemostasis rate, rebleeding rate, duration of hospital stay, volume of blood transfused, number of operations needed, and number of deaths were not significantly different between the two groups. The mean number of electrocoagulations and the subsequent mean duration of electrocoagulations were significantly higher in group B patients (7.0 ⫾ 3.8 and 14.1 ⫾ 7.6 s, respectively) compared with those of group A (4.6 ⫾ 2.6 and 9.3 ⫾ 5.3 s, respectively) (p ⬍ 0.01). Multivariate stepwise logistic regression analysis revealed that among sex, age, location of bleeding, ulcer size, endoscopic severity of bleeding, and the size of the gold probes, lesser endoscopic severity of bleeding (2 ⫽ 31.1, p ⬍ 0.01), large size of the gold probe (2 ⫽ 23.9, p ⬍ 0.01), and small ulcer size (2 ⫽ 13.4, p ⬍ 0.01) were the only factors significantly associated with a smaller number of electrocoagulations. CONCLUSIONS: In this study, the use of large-size gold probes was significantly associated with a lower number of electrocoagulations, resulting in the reduction of electrocoagulation duration. However, the clinical relevance of these findings is questionable because the efficacy of both sizes of gold probe after adrenaline injection in the treatment of bleeding peptic ulcers was similar. (Am J Gastroenterol 2003;98: 2192–2197. © 2003 by Am. Coll. of Gastroenterology)
INTRODUCTION Acute upper GI bleeding is a common emergency situation. Despite the introduction of endoscopy, therapeutic endoscopy, and acid suppressive therapy over the last 25 yr, mortality is still approximately 10% (1–3). We have recently published similar epidemiological data in Greece (4). In most cases (80%), upper GI bleeding stops spontaneously. In the rest of the cases, however, when upper GI bleeding persists, endoscopic hemostasis is valuable. A meta-analysis has shown that therapeutic endoscopy provides a clinically important reduction in morbidity and mortality in patients with acute, nonvariceal upper GI bleeding (5). Many methods, including laser, thermal contact probes (such as the heater probe or bipolar probes), and injection therapy have been proved to be clinically useful (6 –13). The gold probe is a bipolar catheter used in peptic bleeding and is produced in 7-Fr and 10-Fr sizes. Morris et al. (14) have previously reported that 10-Fr bipolar probes were significantly more effective than 7-Fr probes in controlling canine arterial bleeding and that the histological depth of injury after coagulation was not significantly different with the two probes. Combined endoscopic treatment with adrenaline injection and gold or heater probe treatment offers significant advantages, such as prevention of rebleeding and reduction of the need for blood transfusion and operation (15–18). The primary objective of this study was to compare the efficacy of bipolar electrocoagulation (gold probe) with 10-Fr (group A) versus 7-Fr (group B) catheter after adrenaline injection in the treatment of bleeding peptic ulcers. The secondary objective was to compare the requirement for blood transfusion or surgery, mortality, and length of hospital stay between the two groups. To the best of our knowledge, this is the only prospective, randomized study in humans that compares the clinical effectiveness of bipolar electrocoagulation with 10-Fr versus 7-Fr catheter in the prevention of gastroduodenal ulcer bleeding.
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MATERIALS AND METHODS Patients admitted to Benizelion General Hospital with hematemesis or melena underwent upper GI endoscopy within 24 h of admission. Patients with fresh hematemesis and those who were hemodynamically unstable underwent endoscopy after initial resuscitation. Male or female patients older than 16 yr were eligible for inclusion in this study if they presented with an actively bleeding ulcer (spurting or oozing) or a nonbleeding visible vessel (NBVV). NBVV was defined as an elevated red or black spot that protruded from the ulcer crater, was resistant to washing, and was often associated with the freshest clot in the ulcer crater (19). Patients with an NBVV had to show one of the following signs of recent bleeding: coffee ground or blood in the stomach or duodenum; shock; or initial Hb less than 10 g/dl. Exclusion criteria were 1) age less than 16 yr, 2) bleeding tendency (taking anticoagulant therapy, platelet count less than 50,000/mm3, or prothrombin time more than 30% above the control), 3) having more than one bleeding lesion (unless one ulcer could clearly be identified as the source of bleeding), 4) having malignant peptic ulcers, and 5) pregnancy. At the time of endoscopy, a table of random numbers was used to assign patients (regardless of clinical presentation) to receive either local injection of adrenaline followed by 10-Fr gold probe or local injection of adrenaline followed by 7-Fr gold probe. Olympus therapeutic endoscopes and an injector were used to perform endoscopic injection. Adrenaline 1/10,000, 0.5–1.0 ml was injected into and around the bleeding point until the bleeding was controlled. Thereafter, the bleeding point was electrocoagulated with a 7-Fr or a 10-Fr gold probe (Microvasive, Boston Scientific, Natick, MA) set at 3 for 2 s as forcefully as possible. The same electrocoagulation procedure was repeated until hemostasis was achieved. Bipolar electrocoagulation was performed with a 50-W bipolar generator with irrigation (Meditron, BI-2000, Hackensack, NJ). The number of electrocoagulations and the total time of electrocoagulation in each patient were recorded. Although no measurement of force of application was made, we attempted to standardize this by having all procedures performed by the same endoscopist. One biopsy specimen was obtained from the gastric antrum after the cessation of bleeding, and the presence of Helicobacter pylori was checked by a rapid urease test. The endpoint of treatment was defined as cessation of bleeding and flattening of the NBVV. Initial hemostasis was defined as no bleeding for 5 min after endoscopic treatment. Patients who did not attain initial hemostasis with the above procedure were considered treatment failures. These patients were then treated with an alternative endoscopic treatment or surgical intervention. Outcome variables included the initial hemostasis rate, rebleeding rate, permanent hemostasis rate, duration of hospital stay, volume of blood transfused, and the number of
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operations needed. Mortality and morbidity associated with treatment were evaluated within a 30-day period after the procedure. Rebleeding was defined as a new bleeding episode during hospitalization after the initial bleeding had stopped and was based on clinical evidence of hemodynamic instability, recurrent hematemesis, passage of fresh melena, or fresh blood in the nasogastric tube accompanied by a drop in Hb concentration more than could be explained by hemodilution. These patients underwent an emergency endoscopy and were treated endoscopically or surgically. Permanent hemostasis was defined as successful initial hemostasis and absence of recurrent bleeding within the period of hospitalization. Shock was defined as systolic pressure of less than 100 mm Hg and pulse rate greater than 100 beats/min accompanied by cold sweating, pallor, and oliguria. Coexisting illnesses other than the GI bleeding were classified as mild, moderate, severe, or life-threatening diseases (20). After the endoscopic treatment, patients were treated with omeprazole 40 mg i.v. every 6 h for 3 days, followed by 20 mg/day p.o. for 2 months. Triple therapy was given if the urease test was positive. All patients were monitored in hospital for at least 4 days and underwent an endoscopy before being discharged, to ascertain that the ulcer base was clear. Continuous data were compared with unpaired Student t or Mann-Whitney tests, as appropriate. Categoric variables were tested with corrected 2 or two-sided Fisher exact tests for univariate comparisons, as appropriate. Criterion for statistical significance was p ⬍ 0.05. Significant covariates were entered into a multivariate stepwise logistic regression model to identify those that contain independent information. The threshold values for entry into and removal from the model were, respectively, 5% and 10%. The statistical computer package SPSS 10 (SPSS, Chicago, IL) was used. The sample size was calculated to achieve a statistical power of 90% at 5% type I error. Based on a previous study in animals (14), in which the failure in hemostasis after electrocoagulation with 10-Fr probe was 5% and after electrocoagulation with 7-Fr probe was 50%, for the present study a sample size of 33 patients was required for each group.
RESULTS During a 3-yr period, peptic ulcers with active bleeding (oozing or spurting) or NBVV were found in 81 patients. Four patients were excluded from the study because of bleeding tendency (n ⫽ 3) and malignancy (n ⫽ 1). There were 77 patients enrolled in the study. A total of 39 patients were included in group A and 38 in group B. Clinical and demographic data concerning the studied groups are presented in Table 1. The assessment of the outcome in both groups is presented in Table 2.
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Table 1. Clinical Parameters of Patients at Study Entry Group A (n ⫽ 39)
Group B (n ⫽ 38)
p
Age (yr)* 62.7 ⫾ 20.1 61.2 ⫾ 15.9 Sex (male/female) 31/8 28/10 Location of ulcer Duodenum 20 18 Gastric mucosa 17 16 Anastomosis 2 4 Endoscopic findings of bleeding Spurting 3 3 Ooozing 18 17 NBVV 18 18 Positive Helicobacter pylori 25 24 Mean haemoglobin (g/dl)* 9.3 ⫾ 0.6 9.4 ⫾ 0.7 Patients in shock 9 10 Patients who used NSAIDs 18 18 Patients with severe underlying 11 9 disease Ulcer size (ⱖ2 cm/⬍2 cm) 9/30 7/31
ns ns ns
ns
ns ns ns ns ns ns
NSAIDs ⫽ nonsteroidal antiinflammatory drugs. * Results are expressed as mean ⫾ SD.
In group A, the two patients who failed to achieve initial hemostasis received further endoscopic treatment with hemoclips. Of the two patients, one underwent an emergency operation because of uncontrolled bleeding, even after the endoscopic treatment with hemoclips, and recovered uneventfully. In the second patient the endoscopic treatment with hemoclips was satisfactory; however the patient had a rebleeding episode 48 h after initial hemostasis, which was treated successfully with further gold probe treatment with a 10-Fr catheter. Unfortunately, the patient died 15 days later because of serious cardiopulmonary complications. Of the three rebleeding patients, two underwent an emergency operation. One recovered uneventfully, whereas the second died 30 days later owing to serious cardiopulmonary complications. The third patient received further gold probe treatment with a 10-Fr catheter and recovered uneventfully. In group B, the two patients who failed to achieve initial hemostasis received further endoscopic treatment with heTable 2. Assessment of Outcome According to Treatment Group A (n ⫽ 39)
Group B (n ⫽ 38)
p
Initial haemostasis 37 36 ns Rebleeding 3 3 ns Emergency operations 3 2 ns Deaths 2 1 ns Permanent haemostasis 34 33 ns Median (range) hospital 6 (4–30) 6 (4–35) ns stay (days) Mean transfusion 2.4 ⫾ 2.2 2.8 ⫾ 2.8 ns requirements (U)* Mean number of 4.6 ⫾ 2.6 7.0 ⫾ 3.8 p ⬍ 0.01 electrocoagulations* Mean number of seconds of 9.3 ⫾ 5.3 14.1 ⫾ 7.6 p ⬍ 0.01 electrocoagulations* * Results are expressed as mean ⫾ SD.
moclips. Of the two patients, one recovered uneventfully. In the other patient the endoscopic treatment with hemoclips was unsatisfactory, and he underwent an emergency operation and died 1 month later because of intra-abdominal infection. Of the three rebleeding patients, one underwent an emergency operation and recovered uneventfully. Two received further gold probe treatment with a 10-Fr catheter and recovered uneventfully. The initial hemostasis rate, rebleeding rate, permanent hemostasis rate, duration of hospital stay, volume of blood transfused, number of operations, and the number of deaths were not statistically different between the two groups (Table 2). On the other hand, the mean number of electrocoagulations and the subsequent mean duration of electrocoagulations were significantly higher in group B than in group A patients (Table 2). In the three patients who died, a severe or life-threatening illness coexisted, and they were older than 80 yr. The differences in the mean number of electrocoagulations according to endoscopic severity of bleeding in both groups were statistically significant (Table 3). The differences in the mean number of electrocoagulations according to ulcer size in the two groups were also statistically significant (Table 4). All the patients whose initial hemostasis failed had ulcers with a diameter of 2 cm or more. Among the six patients who experienced a rebleeding episode, four had ulcers with a diameter of 2 cm or more. Half of the rebleeding patients were treated surgically, and their ulcers had diameters of 2 cm or more. All patients who were treated surgically had ulcers with diameters of 2 cm or more. Multivariate stepwise logistic regression analysis revealed that among sex, age, location of bleeding, endoscopic severity of the bleeding, size of the gold probes, and ulcer size, the last three were independently and significantly associated with the number of electrocoagulations. More specifically, reduced severity of the endoscopic bleeding (2 ⫽ 31.1, p ⬍ 0.01), large size of the gold probe (2 ⫽ 23.9, p ⬍ 0.01), and small ulcer size (2 ⫽ 13.4, p ⬍ 0.01) are more likely to necessitate a lower number of electrocoagulations. There was no complication of perforated ulcer. One aspiration pneumonia was reported in one patient; he was medically treated and recovered uneventfully.
DISCUSSION The National Institute of Health consensus conference recommended that ulcers with active bleeding or NBVV should be treated endoscopically (21). The present study compared and evaluated the effectiveness of bipolar electrocoagulation with 10-Fr versus 7-Fr catheter after adrenaline injection in the treatment of bleeding peptic ulcers. The primary outcome was that the efficacy and safety of both sizes of gold probe after adrenaline injection were similar. Indeed, the initial hemostasis rate, rebleeding rate, permanent hemostasis rate, duration of hospital stay, volume of blood
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Table 3. Mean Number of Electrocoagulations in the Two Groups According to Endoscopic Severity of Bleeding Group A (n) Mean number of electrocoagulations* Group B (n) Mean number of electrocoagulations*
NBVV
Oozing
Spurting
18 3.0 ⫾ 1.0 18 4.3 ⫾ 1.7
18 5.1 ⫾ 1.2 17 8.2 ⫾ 1.3
3 12.0 ⫾ 2.0 3 16.6 ⫾ 3.0
p p ⬍ 0.01 p ⬍ 0.01
* Results are expressed as mean ⫾ standard deviation.
transfused, number of operations, and the number of deaths were not different between the two groups. In our study, small-size gold probes, which do not require the use of therapeutic endoscopes, were as effective as large gold probes in the treatment of bleeding peptic ulcers. The use of large-size gold probes was significantly associated with a lower number of electrocoagulations, resulting in a reduction of electrocoagulation duration. It has been reported that the higher effectiveness of 10-Fr bipolar probes compared with 7-Fr probes in terms of controlling bleeding in experimental models might be partially explained by the increased force of application possible with the larger probes (14, 22). In an article on optimal technique for bipolar electrocoagulation treatment of bleeding lesions, Laine (22) recommends placing the tip of the endoscope as close as possible to bleeding lesion and applying the maximum possible force with a relatively low-wattage settings, with prolonged periods of electrocoagulation. In this animal study (22), it was also shown that consecutive 2-s pulses produced depths of coagulation similar to those from single long pulses of identical duration. These recommendations were followed in the present study. Because the aim of the present study was to compare between two different sizes of gold probe, we preferred the use of consecutive 2-s pulses to a single long pulse of identical duration. In the present study, the duration of electrocoagulation was less than that used in older studies (7, 11, 12). However, in those studies, bipolar electrocoagulation was used as endoscopic monotherapy. In a recent study in which a combination endoscopic therapy of adrenaline injection plus bipolar electrocoagulation was used, the duration of electrocoagulation was roughly similar to that in our study (15). A previous study in a canine model has shown that when heater probe and bipolar electrocoagulation were used with sufficient appositional force to tamponade blood flow, they were consistently effective in direct coagulation of 1.5– 2.0-mm arteries. Arteries larger than 2 mm were not consistently coagulated (23). A pathological study has shown
that the mean diameter of arteries underlying clinically bleeding gastric ulcers is 0.7 mm (range, 0.1–1.8 mm) (19). It has been documented that the addition of contact probe or laser treatment after adrenaline injection in the treatment of bleeding peptic ulcers is valuable in achieving hemostasis, as well as in reducing rebleeding. Laser treatment after adrenaline injection was more effective than adrenaline injection alone in achieving hemostasis (8, 24). However, the complexity and the high cost of laser treatment for bleeding peptic ulcers limits its use. Chung et al. (16) showed that the addition of heater probe thermocoagulation after endoscopic treatment with adrenaline injection for ulcers with spurting hemorrhage seems to reduce rebleeding and the need for emergency surgery and should be performed even if bleeding is initially controlled by adrenaline injection. Similar results have been reported by Tekant et al. (17). Lin et al. (15) have found that gold probe treatment after adrenaline injection was better than adrenaline injection alone in preventing rebleeding and decreasing the need for blood transfusion. Lau et al. (25) have shown that in patients with peptic ulcers and recurrent bleeding after initial endoscopic control of bleeding, endoscopic retreatment reduces the need for surgery without increasing the risk of death and is associated with fewer complications than surgery. In our series, half of the patients with recurrent bleeding after initial endoscopic control were treated endoscopically and the rest surgically. The major adverse prognostic factors that predict failure of endoscopic hemostasis (shock, ulcer size, endoscopic severity of bleeding, and initial Hb) (26) were similar in both groups. More specifically, it has recently been reported that large ulcers with severe bleeding at presentation predict failure of endoscopic combined treatment with adrenaline injection and heater probe (26). The results of multivariate stepwise logistic regression in our series are comparable with these data. In our study, all patients in whom initial hemostasis failed (as well as all who were operated on and
Table 4. Mean Number of Electrocoagulations in the Two Groups According to Ulcer Size Group A (n) Mean number of electrocoagulations* Group B (n) Mean number of electrocoagulations* * Results are expressed as mean ⫾ SD.
Ulcer Size ⬍ 2 cm
Ulcer Size ⱖ 2 cm
30 3.8 ⫾ 1.5 31 6.0 ⫾ 2.5
9 7.3 ⫾ 3.7 7 11.7 ⫾ 5.0
p p ⬍ 0.05 p ⬍ 0.05
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the majority of who rebled) had ulcers with diameters of 2 cm or more. Gold probes have recently been improved. A needle can be advanced to the tip of the probe, and therefore the gold probe can be used to stop bleeding by electrocoagulation alone or by injection plus electrocoagulation (27). Unfortunately, this device was not available in our department. Our study was scheduled to be performed by one endoscopist in an unblinded fashion. Obviously, it was impossible for technical reasons to organize the present study in a blinded fashion. This design, with a single endoscopist, created advantages and disadvantages. The design reduced the potential bias in areas like the force of probe application and the interpretation of the endoscopic findings and endoscopic treatment. On the other hand, it is very difficult to rule out the possibility that the endoscopist subconsciously used fewer pulses with the 10-Fr probe according to the hypothesis. These potential sources of bias were unavoidable. Most endoscopic studies in upper GI bleeding have as principal outcomes the hemostasis rate, rebleeding rate, and transfusion requirements, as well as the surgical operations needed. Indeed, outcomes such as mortality and length of hospital stay require much larger sample sizes to demonstrate differences. We calculated our sample size according to a previous study in an animal model (14). As mentioned above, in our study there were no differences between the two groups with regard to all clinical outcomes. However, given the small number of patients included in each group, larger, prospective, randomized studies in this topic would be desirable. We used high doses of i.v. omeprazole after the initial endoscopic treatment of bleeding peptic ulcers because it is recommended by recent studies. It has been demonstrated that after initial endoscopy to control bleeding peptic ulcers, a high-dose infusion of proton pump inhibitors reduced recurrent bleeding and improved patient outcome (28). It has also been shown that p.o. omeprazole administration is comparable to endoscopic ethanol injection therapy for prevention of rebleeding in patients with NBVV or adherent clots (29). The role of second-look endoscopy in the literature is still unclear; however, we preferred to check our patients with a second endoscopy before discharging them, to confirm that the ulcer base was clear (30, 31). In conclusion, in this study the use of the large-size gold probe was significantly associated with a lower number of electrocoagulations, resulting in the reduction of electrocoagulation duration. However, the clinical relevance of these findings is questionable because the efficacy and safety of both sizes of gold probe after adrenaline injection in the treatment of bleeding peptic ulcers were similar. These results should be confirmed in larger studies.
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Reprint requests and correspondence: Gregorios A. Paspatis, M.D., G. Georgiadou 17, Heraklion, Crete 71305, Greece. Received Jan. 9, 2002; accepted Apr. 24, 2003.
REFERENCES 1. Blatchford O, Davidson LA, Murray WR, et al. Acute upper gastrointestinal haemorrhage in west of Scotland: Case ascertainment study. BMJ 1997;315:510 –4. 2. Vreeburg EM, Snel P, de Bruijne JW, et al. Acute upper gastrointestinal bleeding in the Amsterdam area: Incidence, diagnosis, and clinical outcome. Am J Gastroenterol 1997;92: 236 –43. 3. Rockall TA, Logan RF, Devlin HB, et al. Incidence of and mortality from acute upper gastrointestinal haemorrhage in the United Kingdom. Steering Committee and members of the National Audit of Acute Upper Gastrointestinal Haemorrhage. BMJ 1995;311:222–6. 4. Paspatis GA, Matrella E, Kapsoritakis A, et al. An epidemiological study of acute upper gastrointestinal bleeding in Crete, Greece. Eur J Gastroenterol Hepatol 2000;12:1215–20. 5. Cook DJ, Guyatt GH, Salena BJ, et al. Endoscopic therapy for acute nonvariceal upper gastrointestinal hemorrhage: A metaanalysis. Gastroenterology 1992;102:139 –48. 6. Lin HJ, Wang K, Perng CL, et al. Heater probe thermocoagulation and multipolar electrocoagulation for arrest of peptic ulcer bleeding. A prospective, randomized comparative trial. J Clin Gastroenterol 1995;21:99 –102. 7. Laine L. Multipolar electrocoagulation in the treatment of peptic ulcers with nonbleeding visible vessels. A prospective, controlled trial. Ann Intern Med 1989;110:510 –4. 8. Loizou LA, Bown SG. Endoscopic treatment for bleeding peptic ulcers: Randomised comparison of adrenaline injection and adrenaline injection ⫹ Nd:YAG laser photocoagulation. Gut 1991;32:1100 –3. 9. Fullarton GM, Birnie GG, Macdonald A, et al. Controlled trial of heater probe treatment in bleeding peptic ulcers. Br J Surg 1989;76:541–4. 10. Chung SC, Leung JW, Sung JY, et al. Injection or heat probe for bleeding ulcer. Gastroenterology 1991;100:33–7. 11. Laine L. Multipolar electrocoagulation versus injection therapy in the treatment of bleeding peptic ulcers. A prospective, randomized trial. Gastroenterology 1990;99:1303–6. 12. Laine L. Multipolar electrocoagulation in the treatment of active upper gastrointestinal tract hemorrhage. A prospective controlled trial. N Engl J Med 1987;316:1613–7. 13. Rutgeerts P, Gevers AM, Hiele M, et al. Endoscopic injection therapy to prevent rebleeding from peptic ulcers with a protruding vessel: A controlled comparative trial. Gut 1993;34: 348 –50. 14. Morris DL, Brearley S, Thompson H, et al. A comparison of the efficacy and depth of gastric wall injury with 3.2 and 2.3-mm bipolar probes in canine arterial hemorrhage. Gastrointest Endosc 1985;31:361–3. 15. Lin HJ, Tseng GY, Perng CL, et al. Comparison of adrenaline injection and bipolar electrocoagulation for the arrest of peptic ulcer bleeding. Gut 1999;44:715–9. 16. Chung SS, Lau JY, Sung JJ, et al. Randomised comparison between adrenaline injection alone and adrenaline injection plus heat probe treatment for actively bleeding ulcers. BMJ 1997;314:1307–11. 17. Tekant Y, Goh P, Alexander DJ, et al. Combination therapy using adrenaline and heater probe to reduce rebleeding in patients with peptic ulcer haemorrhage: A prospective randomized trial. Br J Surg 1995;82:223–6.
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18. Jensen DM. Where next with endoscopic ulcer hemostasis? Am J Gastroenterol 2002;97:2161–5. 19. Swain CP, Storey DW, Bown SG, et al. Nature of the bleeding vessel in recurrently bleeding gastric ulcers. Gastroenterology 1986;90:595–608. 20. Greenfield S, Apolone G, McNeil BJ, et al. The importance of co-existent disease in the occurrence of postoperative complications and one-year recovery in patients undergoing total hip replacement. Comorbidity and outcomes after hip replacement. Med Care 1993;31:141–54. 21. Consensus Development Panel. Consensus statement on therapeutic endoscopy and bleeding ulcers. Gastrointest Endosc 1990;36:S62–5. 22. Laine L. Determination of the optimal technique for bipolar electrocoagulation treatment. An experimental evaluation of the BICAP and Gold probes. Gastroenterology 1991;100:107– 12. 23. Johnston JH, Jensen DM, Auth D. Experimental comparison of endoscopic yttrium-aluminum-garnet laser, electrosurgery, and heater probe for canine gut arterial coagulation. Importance of compression and avoidance of erosion. Gastroenterology 1987;92:1101–8. 24. Rutgeerts P, Vantrappen G, Broeckaert L, et al. Comparison of endoscopic polidocanol injection and YAG laser therapy for bleeding peptic ulcers. Lancet 1989;1:1164 –7. 25. Lau JY, Sung JJ, Lam YH, et al. Endoscopic retreatment compared with surgery in patients with recurrent bleeding
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Vol. 98, No. 10, 2003 ISSN 0002-9270/03/$30.00 doi:10.1016/S0002-9270(03)00697-X
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 Gregorios A. Paspatis, M.D., Ioanna Charoniti, M.D., Nikolaos Papanikolaou, M.D., Emmanouil Vardas, M.D., and Gregorios Chlouverakis, Ph.D. Department of Gastroenterology, Benizelion General Hospital; and School of Education, University of Crete, Heraklion, Crete, Greece
OBJECTIVES: Our study compared the efficacy of bipolar electrocoagulation (gold probe) with 10-Fr (group A) versus 7-Fr (group B) catheter after adrenaline injection in the treatment of bleeding peptic ulcers. METHODS: A total of 77 consecutive patients with endoscopic evidence of peptic ulcer with active bleeding or a nonbleeding visible vessel were randomly assigned to one of the above protocols. Thirty-nine patients (31 male, eight female, mean age 62 yr) were included in group A and 38 (28 male, 10 female, mean age 61 yr) in group B. RESULTS: The initial hemostasis rate, rebleeding rate, duration of hospital stay, volume of blood transfused, number of operations needed, and number of deaths were not significantly different between the two groups. The mean number of electrocoagulations and the subsequent mean duration of electrocoagulations were significantly higher in group B patients (7.0 ⫾ 3.8 and 14.1 ⫾ 7.6 s, respectively) compared with those of group A (4.6 ⫾ 2.6 and 9.3 ⫾ 5.3 s, respectively) (p ⬍ 0.01). Multivariate stepwise logistic regression analysis revealed that among sex, age, location of bleeding, ulcer size, endoscopic severity of bleeding, and the size of the gold probes, lesser endoscopic severity of bleeding (2 ⫽ 31.1, p ⬍ 0.01), large size of the gold probe (2 ⫽ 23.9, p ⬍ 0.01), and small ulcer size (2 ⫽ 13.4, p ⬍ 0.01) were the only factors significantly associated with a smaller number of electrocoagulations. CONCLUSIONS: In this study, the use of large-size gold probes was significantly associated with a lower number of electrocoagulations, resulting in the reduction of electrocoagulation duration. However, the clinical relevance of these findings is questionable because the efficacy of both sizes of gold probe after adrenaline injection in the treatment of bleeding peptic ulcers was similar. (Am J Gastroenterol 2003;98: 2192–2197. © 2003 by Am. Coll. of Gastroenterology)
INTRODUCTION Acute upper GI bleeding is a common emergency situation. Despite the introduction of endoscopy, therapeutic endoscopy, and acid suppressive therapy over the last 25 yr, mortality is still approximately 10% (1–3). We have recently published similar epidemiological data in Greece (4). In most cases (80%), upper GI bleeding stops spontaneously. In the rest of the cases, however, when upper GI bleeding persists, endoscopic hemostasis is valuable. A meta-analysis has shown that therapeutic endoscopy provides a clinically important reduction in morbidity and mortality in patients with acute, nonvariceal upper GI bleeding (5). Many methods, including laser, thermal contact probes (such as the heater probe or bipolar probes), and injection therapy have been proved to be clinically useful (6 –13). The gold probe is a bipolar catheter used in peptic bleeding and is produced in 7-Fr and 10-Fr sizes. Morris et al. (14) have previously reported that 10-Fr bipolar probes were significantly more effective than 7-Fr probes in controlling canine arterial bleeding and that the histological depth of injury after coagulation was not significantly different with the two probes. Combined endoscopic treatment with adrenaline injection and gold or heater probe treatment offers significant advantages, such as prevention of rebleeding and reduction of the need for blood transfusion and operation (15–18). The primary objective of this study was to compare the efficacy of bipolar electrocoagulation (gold probe) with 10-Fr (group A) versus 7-Fr (group B) catheter after adrenaline injection in the treatment of bleeding peptic ulcers. The secondary objective was to compare the requirement for blood transfusion or surgery, mortality, and length of hospital stay between the two groups. To the best of our knowledge, this is the only prospective, randomized study in humans that compares the clinical effectiveness of bipolar electrocoagulation with 10-Fr versus 7-Fr catheter in the prevention of gastroduodenal ulcer bleeding.
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MATERIALS AND METHODS Patients admitted to Benizelion General Hospital with hematemesis or melena underwent upper GI endoscopy within 24 h of admission. Patients with fresh hematemesis and those who were hemodynamically unstable underwent endoscopy after initial resuscitation. Male or female patients older than 16 yr were eligible for inclusion in this study if they presented with an actively bleeding ulcer (spurting or oozing) or a nonbleeding visible vessel (NBVV). NBVV was defined as an elevated red or black spot that protruded from the ulcer crater, was resistant to washing, and was often associated with the freshest clot in the ulcer crater (19). Patients with an NBVV had to show one of the following signs of recent bleeding: coffee ground or blood in the stomach or duodenum; shock; or initial Hb less than 10 g/dl. Exclusion criteria were 1) age less than 16 yr, 2) bleeding tendency (taking anticoagulant therapy, platelet count less than 50,000/mm3, or prothrombin time more than 30% above the control), 3) having more than one bleeding lesion (unless one ulcer could clearly be identified as the source of bleeding), 4) having malignant peptic ulcers, and 5) pregnancy. At the time of endoscopy, a table of random numbers was used to assign patients (regardless of clinical presentation) to receive either local injection of adrenaline followed by 10-Fr gold probe or local injection of adrenaline followed by 7-Fr gold probe. Olympus therapeutic endoscopes and an injector were used to perform endoscopic injection. Adrenaline 1/10,000, 0.5–1.0 ml was injected into and around the bleeding point until the bleeding was controlled. Thereafter, the bleeding point was electrocoagulated with a 7-Fr or a 10-Fr gold probe (Microvasive, Boston Scientific, Natick, MA) set at 3 for 2 s as forcefully as possible. The same electrocoagulation procedure was repeated until hemostasis was achieved. Bipolar electrocoagulation was performed with a 50-W bipolar generator with irrigation (Meditron, BI-2000, Hackensack, NJ). The number of electrocoagulations and the total time of electrocoagulation in each patient were recorded. Although no measurement of force of application was made, we attempted to standardize this by having all procedures performed by the same endoscopist. One biopsy specimen was obtained from the gastric antrum after the cessation of bleeding, and the presence of Helicobacter pylori was checked by a rapid urease test. The endpoint of treatment was defined as cessation of bleeding and flattening of the NBVV. Initial hemostasis was defined as no bleeding for 5 min after endoscopic treatment. Patients who did not attain initial hemostasis with the above procedure were considered treatment failures. These patients were then treated with an alternative endoscopic treatment or surgical intervention. Outcome variables included the initial hemostasis rate, rebleeding rate, permanent hemostasis rate, duration of hospital stay, volume of blood transfused, and the number of
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operations needed. Mortality and morbidity associated with treatment were evaluated within a 30-day period after the procedure. Rebleeding was defined as a new bleeding episode during hospitalization after the initial bleeding had stopped and was based on clinical evidence of hemodynamic instability, recurrent hematemesis, passage of fresh melena, or fresh blood in the nasogastric tube accompanied by a drop in Hb concentration more than could be explained by hemodilution. These patients underwent an emergency endoscopy and were treated endoscopically or surgically. Permanent hemostasis was defined as successful initial hemostasis and absence of recurrent bleeding within the period of hospitalization. Shock was defined as systolic pressure of less than 100 mm Hg and pulse rate greater than 100 beats/min accompanied by cold sweating, pallor, and oliguria. Coexisting illnesses other than the GI bleeding were classified as mild, moderate, severe, or life-threatening diseases (20). After the endoscopic treatment, patients were treated with omeprazole 40 mg i.v. every 6 h for 3 days, followed by 20 mg/day p.o. for 2 months. Triple therapy was given if the urease test was positive. All patients were monitored in hospital for at least 4 days and underwent an endoscopy before being discharged, to ascertain that the ulcer base was clear. Continuous data were compared with unpaired Student t or Mann-Whitney tests, as appropriate. Categoric variables were tested with corrected 2 or two-sided Fisher exact tests for univariate comparisons, as appropriate. Criterion for statistical significance was p ⬍ 0.05. Significant covariates were entered into a multivariate stepwise logistic regression model to identify those that contain independent information. The threshold values for entry into and removal from the model were, respectively, 5% and 10%. The statistical computer package SPSS 10 (SPSS, Chicago, IL) was used. The sample size was calculated to achieve a statistical power of 90% at 5% type I error. Based on a previous study in animals (14), in which the failure in hemostasis after electrocoagulation with 10-Fr probe was 5% and after electrocoagulation with 7-Fr probe was 50%, for the present study a sample size of 33 patients was required for each group.
RESULTS During a 3-yr period, peptic ulcers with active bleeding (oozing or spurting) or NBVV were found in 81 patients. Four patients were excluded from the study because of bleeding tendency (n ⫽ 3) and malignancy (n ⫽ 1). There were 77 patients enrolled in the study. A total of 39 patients were included in group A and 38 in group B. Clinical and demographic data concerning the studied groups are presented in Table 1. The assessment of the outcome in both groups is presented in Table 2.
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Table 1. Clinical Parameters of Patients at Study Entry Group A (n ⫽ 39)
Group B (n ⫽ 38)
p
Age (yr)* 62.7 ⫾ 20.1 61.2 ⫾ 15.9 Sex (male/female) 31/8 28/10 Location of ulcer Duodenum 20 18 Gastric mucosa 17 16 Anastomosis 2 4 Endoscopic findings of bleeding Spurting 3 3 Ooozing 18 17 NBVV 18 18 Positive Helicobacter pylori 25 24 Mean haemoglobin (g/dl)* 9.3 ⫾ 0.6 9.4 ⫾ 0.7 Patients in shock 9 10 Patients who used NSAIDs 18 18 Patients with severe underlying 11 9 disease Ulcer size (ⱖ2 cm/⬍2 cm) 9/30 7/31
ns ns ns
ns
ns ns ns ns ns ns
NSAIDs ⫽ nonsteroidal antiinflammatory drugs. * Results are expressed as mean ⫾ SD.
In group A, the two patients who failed to achieve initial hemostasis received further endoscopic treatment with hemoclips. Of the two patients, one underwent an emergency operation because of uncontrolled bleeding, even after the endoscopic treatment with hemoclips, and recovered uneventfully. In the second patient the endoscopic treatment with hemoclips was satisfactory; however the patient had a rebleeding episode 48 h after initial hemostasis, which was treated successfully with further gold probe treatment with a 10-Fr catheter. Unfortunately, the patient died 15 days later because of serious cardiopulmonary complications. Of the three rebleeding patients, two underwent an emergency operation. One recovered uneventfully, whereas the second died 30 days later owing to serious cardiopulmonary complications. The third patient received further gold probe treatment with a 10-Fr catheter and recovered uneventfully. In group B, the two patients who failed to achieve initial hemostasis received further endoscopic treatment with heTable 2. Assessment of Outcome According to Treatment Group A (n ⫽ 39)
Group B (n ⫽ 38)
p
Initial haemostasis 37 36 ns Rebleeding 3 3 ns Emergency operations 3 2 ns Deaths 2 1 ns Permanent haemostasis 34 33 ns Median (range) hospital 6 (4–30) 6 (4–35) ns stay (days) Mean transfusion 2.4 ⫾ 2.2 2.8 ⫾ 2.8 ns requirements (U)* Mean number of 4.6 ⫾ 2.6 7.0 ⫾ 3.8 p ⬍ 0.01 electrocoagulations* Mean number of seconds of 9.3 ⫾ 5.3 14.1 ⫾ 7.6 p ⬍ 0.01 electrocoagulations* * Results are expressed as mean ⫾ SD.
moclips. Of the two patients, one recovered uneventfully. In the other patient the endoscopic treatment with hemoclips was unsatisfactory, and he underwent an emergency operation and died 1 month later because of intra-abdominal infection. Of the three rebleeding patients, one underwent an emergency operation and recovered uneventfully. Two received further gold probe treatment with a 10-Fr catheter and recovered uneventfully. The initial hemostasis rate, rebleeding rate, permanent hemostasis rate, duration of hospital stay, volume of blood transfused, number of operations, and the number of deaths were not statistically different between the two groups (Table 2). On the other hand, the mean number of electrocoagulations and the subsequent mean duration of electrocoagulations were significantly higher in group B than in group A patients (Table 2). In the three patients who died, a severe or life-threatening illness coexisted, and they were older than 80 yr. The differences in the mean number of electrocoagulations according to endoscopic severity of bleeding in both groups were statistically significant (Table 3). The differences in the mean number of electrocoagulations according to ulcer size in the two groups were also statistically significant (Table 4). All the patients whose initial hemostasis failed had ulcers with a diameter of 2 cm or more. Among the six patients who experienced a rebleeding episode, four had ulcers with a diameter of 2 cm or more. Half of the rebleeding patients were treated surgically, and their ulcers had diameters of 2 cm or more. All patients who were treated surgically had ulcers with diameters of 2 cm or more. Multivariate stepwise logistic regression analysis revealed that among sex, age, location of bleeding, endoscopic severity of the bleeding, size of the gold probes, and ulcer size, the last three were independently and significantly associated with the number of electrocoagulations. More specifically, reduced severity of the endoscopic bleeding (2 ⫽ 31.1, p ⬍ 0.01), large size of the gold probe (2 ⫽ 23.9, p ⬍ 0.01), and small ulcer size (2 ⫽ 13.4, p ⬍ 0.01) are more likely to necessitate a lower number of electrocoagulations. There was no complication of perforated ulcer. One aspiration pneumonia was reported in one patient; he was medically treated and recovered uneventfully.
DISCUSSION The National Institute of Health consensus conference recommended that ulcers with active bleeding or NBVV should be treated endoscopically (21). The present study compared and evaluated the effectiveness of bipolar electrocoagulation with 10-Fr versus 7-Fr catheter after adrenaline injection in the treatment of bleeding peptic ulcers. The primary outcome was that the efficacy and safety of both sizes of gold probe after adrenaline injection were similar. Indeed, the initial hemostasis rate, rebleeding rate, permanent hemostasis rate, duration of hospital stay, volume of blood
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Table 3. Mean Number of Electrocoagulations in the Two Groups According to Endoscopic Severity of Bleeding Group A (n) Mean number of electrocoagulations* Group B (n) Mean number of electrocoagulations*
NBVV
Oozing
Spurting
18 3.0 ⫾ 1.0 18 4.3 ⫾ 1.7
18 5.1 ⫾ 1.2 17 8.2 ⫾ 1.3
3 12.0 ⫾ 2.0 3 16.6 ⫾ 3.0
p p ⬍ 0.01 p ⬍ 0.01
* Results are expressed as mean ⫾ standard deviation.
transfused, number of operations, and the number of deaths were not different between the two groups. In our study, small-size gold probes, which do not require the use of therapeutic endoscopes, were as effective as large gold probes in the treatment of bleeding peptic ulcers. The use of large-size gold probes was significantly associated with a lower number of electrocoagulations, resulting in a reduction of electrocoagulation duration. It has been reported that the higher effectiveness of 10-Fr bipolar probes compared with 7-Fr probes in terms of controlling bleeding in experimental models might be partially explained by the increased force of application possible with the larger probes (14, 22). In an article on optimal technique for bipolar electrocoagulation treatment of bleeding lesions, Laine (22) recommends placing the tip of the endoscope as close as possible to bleeding lesion and applying the maximum possible force with a relatively low-wattage settings, with prolonged periods of electrocoagulation. In this animal study (22), it was also shown that consecutive 2-s pulses produced depths of coagulation similar to those from single long pulses of identical duration. These recommendations were followed in the present study. Because the aim of the present study was to compare between two different sizes of gold probe, we preferred the use of consecutive 2-s pulses to a single long pulse of identical duration. In the present study, the duration of electrocoagulation was less than that used in older studies (7, 11, 12). However, in those studies, bipolar electrocoagulation was used as endoscopic monotherapy. In a recent study in which a combination endoscopic therapy of adrenaline injection plus bipolar electrocoagulation was used, the duration of electrocoagulation was roughly similar to that in our study (15). A previous study in a canine model has shown that when heater probe and bipolar electrocoagulation were used with sufficient appositional force to tamponade blood flow, they were consistently effective in direct coagulation of 1.5– 2.0-mm arteries. Arteries larger than 2 mm were not consistently coagulated (23). A pathological study has shown
that the mean diameter of arteries underlying clinically bleeding gastric ulcers is 0.7 mm (range, 0.1–1.8 mm) (19). It has been documented that the addition of contact probe or laser treatment after adrenaline injection in the treatment of bleeding peptic ulcers is valuable in achieving hemostasis, as well as in reducing rebleeding. Laser treatment after adrenaline injection was more effective than adrenaline injection alone in achieving hemostasis (8, 24). However, the complexity and the high cost of laser treatment for bleeding peptic ulcers limits its use. Chung et al. (16) showed that the addition of heater probe thermocoagulation after endoscopic treatment with adrenaline injection for ulcers with spurting hemorrhage seems to reduce rebleeding and the need for emergency surgery and should be performed even if bleeding is initially controlled by adrenaline injection. Similar results have been reported by Tekant et al. (17). Lin et al. (15) have found that gold probe treatment after adrenaline injection was better than adrenaline injection alone in preventing rebleeding and decreasing the need for blood transfusion. Lau et al. (25) have shown that in patients with peptic ulcers and recurrent bleeding after initial endoscopic control of bleeding, endoscopic retreatment reduces the need for surgery without increasing the risk of death and is associated with fewer complications than surgery. In our series, half of the patients with recurrent bleeding after initial endoscopic control were treated endoscopically and the rest surgically. The major adverse prognostic factors that predict failure of endoscopic hemostasis (shock, ulcer size, endoscopic severity of bleeding, and initial Hb) (26) were similar in both groups. More specifically, it has recently been reported that large ulcers with severe bleeding at presentation predict failure of endoscopic combined treatment with adrenaline injection and heater probe (26). The results of multivariate stepwise logistic regression in our series are comparable with these data. In our study, all patients in whom initial hemostasis failed (as well as all who were operated on and
Table 4. Mean Number of Electrocoagulations in the Two Groups According to Ulcer Size Group A (n) Mean number of electrocoagulations* Group B (n) Mean number of electrocoagulations* * Results are expressed as mean ⫾ SD.
Ulcer Size ⬍ 2 cm
Ulcer Size ⱖ 2 cm
30 3.8 ⫾ 1.5 31 6.0 ⫾ 2.5
9 7.3 ⫾ 3.7 7 11.7 ⫾ 5.0
p p ⬍ 0.05 p ⬍ 0.05
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the majority of who rebled) had ulcers with diameters of 2 cm or more. Gold probes have recently been improved. A needle can be advanced to the tip of the probe, and therefore the gold probe can be used to stop bleeding by electrocoagulation alone or by injection plus electrocoagulation (27). Unfortunately, this device was not available in our department. Our study was scheduled to be performed by one endoscopist in an unblinded fashion. Obviously, it was impossible for technical reasons to organize the present study in a blinded fashion. This design, with a single endoscopist, created advantages and disadvantages. The design reduced the potential bias in areas like the force of probe application and the interpretation of the endoscopic findings and endoscopic treatment. On the other hand, it is very difficult to rule out the possibility that the endoscopist subconsciously used fewer pulses with the 10-Fr probe according to the hypothesis. These potential sources of bias were unavoidable. Most endoscopic studies in upper GI bleeding have as principal outcomes the hemostasis rate, rebleeding rate, and transfusion requirements, as well as the surgical operations needed. Indeed, outcomes such as mortality and length of hospital stay require much larger sample sizes to demonstrate differences. We calculated our sample size according to a previous study in an animal model (14). As mentioned above, in our study there were no differences between the two groups with regard to all clinical outcomes. However, given the small number of patients included in each group, larger, prospective, randomized studies in this topic would be desirable. We used high doses of i.v. omeprazole after the initial endoscopic treatment of bleeding peptic ulcers because it is recommended by recent studies. It has been demonstrated that after initial endoscopy to control bleeding peptic ulcers, a high-dose infusion of proton pump inhibitors reduced recurrent bleeding and improved patient outcome (28). It has also been shown that p.o. omeprazole administration is comparable to endoscopic ethanol injection therapy for prevention of rebleeding in patients with NBVV or adherent clots (29). The role of second-look endoscopy in the literature is still unclear; however, we preferred to check our patients with a second endoscopy before discharging them, to confirm that the ulcer base was clear (30, 31). In conclusion, in this study the use of the large-size gold probe was significantly associated with a lower number of electrocoagulations, resulting in the reduction of electrocoagulation duration. However, the clinical relevance of these findings is questionable because the efficacy and safety of both sizes of gold probe after adrenaline injection in the treatment of bleeding peptic ulcers were similar. These results should be confirmed in larger studies.
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Reprint requests and correspondence: Gregorios A. Paspatis, M.D., G. Georgiadou 17, Heraklion, Crete 71305, Greece. Received Jan. 9, 2002; accepted Apr. 24, 2003.
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