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The APACHE III prognostic system: predicting adverse outcome after heater probe therapy
April 1995
• Lansoprazole 15 and 30mg daily in long-term treatment of erosive reflux esophagitis. LGHatlebakk, A.Berstad. MedDept.A, Haukeland University Hospital, Bergen, Norway. Lansoprazole 30rag daily has previously been found to be effective in acute healing of erosive reflux esophagitis. In this single center, double blind randomized study, 118 patients with erosive reflux esophagitis, were given lansoprazole 30mg daily for twelve weeks, and if endoscopically healed and asymptomatic at that time, randomized to treatment with either lansoprazole 15mg or 30mg o.m.. Endoscopy was repeated after 3, 6 and 12 months of maintenance treatment An endoscopic relapse was defined as reappearance of grade 1 or more severe reflux esophagitis. 118 patients were included in the initial healing phase and received lansoprazole 30rag o.m for 12 weeks. 100 patients (84.7%) (79 male, 21 female) were healed and asymptomatic at the end of twelve weeks and were included in the maintenance study. 48 patients were randomized to receive lansoprazole 15mg daily, while 52 patients received lansoprazole 30mg daily. At the end of the 12 months maintenance period, 13 patients (27.1%) receiving lansop~'azole 15rag daily had experienced a relapse of endoscopically verified reflux esophagitis, compared to eight patients (15.4%) treated with lansoprazole 30mg daily (n.s.). A life table analysis showed no statistically significant difference between the two groups. In the 15mg group, 70.8% were kept in symptomatic remission, compared to 84.6% in the 30mg group. 81 patients experienced at least one adverse event, 77.1% of patients receiving lansoprazole 15mg, compared with 84.6% of patients receiving lansoprazole 30mg (n.s.). Conclusion: Lansoprazole proved to be safe and effective maintenance treatment for reflux esophagitis, as both 15mg and 30rag daily kept the majority of patients in endoscopic and symptomatic remission. No statistically significant differences were found in endoscopic relapse, symptomatic relief or occurrence of adverse events.
SHORT SEGMENT BARRETT'S ESOPHAGUS: DIAGNOSIS, SYMI~OMS, .HISTOLOGY, MANOMETRY AND AMBULATORY pH. S.K. Heier, I.R. Willner, W.S. Rosenthal, M. Bantam, L.M. Heier, S.D. Gronowitz, A. Lowy, N. Khan, F. Seif, S. Clark, A. Trehan, A. Khan, A. Hasan. Dept of Med, NY Med Coil, Valhalla, NY. Short segment Barrett's esophagus (SSBE; intestinal metaplasia limited to the region of the GE junction) is assumed to be similar to longer segment Barrett's in pathogenesis, and may contribute to the increased incidence of distal esophageal adenocarcinoma. METHODS: Biopsies were obtained from minimally nodular GE junctions, or normal appearing junctions in patients with a history of chronic reflux symptoms, atypical chest pain, or esophagitis. Biopsies were evaluated for the presence and degree of intestinal metaplasia, with staining for sialomucins and sulfomucins. Metaplasia was classified as SSBE only if the squamocohimuar junction was at or < 2 cm from the LES. Patients with metaplasia were questioned as to the presence of reflux and dysmotility symptoms, and were evaluated with esophageal manometry and ambulatory pH. RESULTS: In 23 patients identified with intestinal metaplasia, indications for endoscopy included abdominal pain (30%), chronic reflux (26%), anemia or bleeding (17%), and dysphagia (9%). Esophagitis > Grade 2 was documented in 22 %. Further questioning elicited symptoms including frequent reflux or heartburn in 61% and atypical chest pain in 17%. Biopsies from other gastric sites revealed metaplasia in 22% (33% of those obtained). Metaplasia of the GE junction was incomplete in all patients, although one also had foe] of complete metaplasia. Ten patients underwent motility. Two patients had achalasia. In the 8 other patients, 5 had abnormalities including segmental aperistalsis (4), poor propagation of peristalsis (3), low LES pressure (1), and low amplitude contractions (1). Two of 5 patients had abnormal upright and supine acid reflux on ambulatory pH monitoring. Manometric findings were compared to patienig with known long segment Barrett's esophagus, all of whom demonstrated either low LES pressure, low amplitude of peristalsis, or poor peristaltic propagation. CONCLUSIONS: Compared to long .segment Barrett's esophagus, SSBE is associated with less severe motility and ambulatory pH abnormalities. Furthermore, the identification of metaplasia in patients with otherwise normal evaluations and in two patients with achalasia suggests that other pathogenic mechanisms may be involved,
Esophageal, Gastric, and Duodenal Disorders
Alll
THE SYMPTOMATIC EFFECT OF A PECTIN-BASED RAFT-FORMING ANTIREFLUX AGENT IN NON-EROSIVE GASTRO-ESOPHAGEAL REFLUX DISEASE: A DOUBLE-BLIND PLACEBO-CONTROLLED TRIAL. T. Havelund, C. Aalykke. Dept. of Medica~ Gastroenterology, Odense, Denmark. In low grade gastro-esophageal reflux disease a non-absorbable drag might be a valuable therapeutic option as regards cost and safety. Aim: To determine the efficacy and safety of a locally acting raft-forming antireflux agent based on pectin (Aflurax, Ferrosan A/S, Copenhagen, Denmark) in relieving predictable symptoms in patients with low grade gastro-esophageal reflux disease. Methods: Sixty-five patients with beartbum as predominant complaint arid normal mucosa or non-erosive/non-ulcerative esophagitis at endoscopy were randomized to treatment with Aflurax, two 1200-mg tablets 30 minutes after meals and at bedtime or corresponding placebo for 4 weeks. Pretreatment, day 15, and day 29 the severity of heartburn was assessed using the ordinal scale: none; mild; moderate; and severe. From diary cards weekly heartburn indices (Gastroenterology 1990;99:629) were also calculated as the number of days with beartbum times its average severity (range 0-21). Results: Sixty-three patients were evaluable at day 15 and 47 patients at day 29 (Aflurax/placebo: 31/32 and 29/18, respectively). The uneven cumulated number of withdrawals at day 29 in the two treatment groups precluded formal statistical analysis of the efficacy variables at this time point. After two weeks patients treated with Aflurax were more relieved from heartburn compared to patients treated with placebo (Table). The daytime heartbum indices (median,[IQR]) for week 1 and 2 were: 5.7 [3.4-9.7] and 5 (0.8-10) on Aflurax versus 10.8 [6.5-13] and 11 [5-14] on placebo (P < 0.05, Mann-Whitney tes0. During nighttime the corresponding heartbum indices were 2.1 [0.1-7.9] and 0.6 [0-4.6] on Aflurax versus 3.7 [0.4-12] and 4.3 [0-10] on placebo (n.s.). Aflurax was in general well tolerated. TABLE. Heartburn severity (number of patients). Pretreatment Day 15" Mild Moderate Severe None Mild Moderate Severe Aflurax 4 18 10 6 14 8 3 Placebo 7 19 7 2 6 13 11 • P < 0.005 for difference between treatment groups (stratified Wilcoxon tes0. Conclusion: In patients with heartburn and without erosive/ulcerative esophagitis at endoscopy the raft-forming anti-reflux agent Aflurax provides better symptomatic relief than placebo.
• THE APACHE III PROGNOSTIC SYSTEM: PREDICTING ADVERSE OUTCOME AFTER HEATER PROBE THERAPY. S.K. Heier, S.D~ Gronowitz I.R. Willner, L.M. Heier, F. Self, A. Trehan, A. Lowy, N. Khan, A. Khan, A. Hasan. Dept of Med, NY Med Coll, Valhalla, NY. The APACHE III prognostic system was developed to predict mortality and other outcomes at the time of IeO admission. The system consists of several components: the Acute Physiology Score (APS); the APACHE Score (AS) incorporating APS, age, and chronic health evaluation; the APACHE Equation, which predicts mortality risk, incorporating AS, length of stay, location (e.g., hospital transfer) and major disease category. We tested whether comorbidity influences outcome after endoscopic therapy of upper GI bleeding using the APACHE III system, and correlated a variety of other factors with outcome. METHODS: 126 consecutive patients with bleeding from benign gastroduodenal ulcersmho underwent heater probe therapy (HPT) were analyzed. Mallory-We]as tears were excluded. Failure of HPT was defined as persistent bleeding, bleeding after repeat HPT, need for alternative therapy, and bleeding which contributes to mortality. We modified the APACHE scoring sytem by determining the APS and length of Stay at the time of endoscopic therapy, whereas location and major disease category were determined at the time of ICU admission for other illness if applicable. In addition, 109 clinical, historical and endoscopic factors were evaluated for association with various outcome endpoints by univariate analysis. RESULTS: Rebleeding occurred in 43 patients (34%), major rebleeding in 30 (24%), 2nd rebleeding after repeat HPT in 17 (13%), failure in 23 (18%), and mortality in 2 (1.6%). Of the three APACHE components tested, the APS correlated best with outcome. Increasing APS was associated with increasingly adverse clinical outcome (Cochran linear trend test, P <0.001). APS > 45 was associated with a significant incidence of failure or major rebleeding (odds ratio [OR] = 7.51; 95% CI, 3.15-17.9). Fifteen of the 109 potential risk factors were selected for use in stepwise multiple logistic regression analysis. After adjusting for overall patient stares with the APS, risk factors also found to be significantly associated with an adverse outcome included a history of diabetes and a transfusion requirement of > 3 units (OR = 4.31, 95% CI 1.48-12.6; OR = 3.94, 95% CI 1.35-11.5, respectively). CONCLUSIONS: Variables other than endoscopic findings can significantly impact on outcome after endoscopic therapy. Degree of comorbidity estimated by severity of physiologic abnormalities, as determined by modified APS, strongly correlates with outcome. Other predictors include the presence of diabetes and transfusion requirements. Consideration should be given to determining APS, and developing predictive equations as assessment tools to guide clinical management.
• Lansoprazole 15 and 30mg daily in long-term treatment of erosive reflux esophagitis. LGHatlebakk, A.Berstad. MedDept.A, Haukeland University Hospital, Bergen, Norway. Lansoprazole 30rag daily has previously been found to be effective in acute healing of erosive reflux esophagitis. In this single center, double blind randomized study, 118 patients with erosive reflux esophagitis, were given lansoprazole 30mg daily for twelve weeks, and if endoscopically healed and asymptomatic at that time, randomized to treatment with either lansoprazole 15mg or 30mg o.m.. Endoscopy was repeated after 3, 6 and 12 months of maintenance treatment An endoscopic relapse was defined as reappearance of grade 1 or more severe reflux esophagitis. 118 patients were included in the initial healing phase and received lansoprazole 30rag o.m for 12 weeks. 100 patients (84.7%) (79 male, 21 female) were healed and asymptomatic at the end of twelve weeks and were included in the maintenance study. 48 patients were randomized to receive lansoprazole 15mg daily, while 52 patients received lansoprazole 30mg daily. At the end of the 12 months maintenance period, 13 patients (27.1%) receiving lansop~'azole 15rag daily had experienced a relapse of endoscopically verified reflux esophagitis, compared to eight patients (15.4%) treated with lansoprazole 30mg daily (n.s.). A life table analysis showed no statistically significant difference between the two groups. In the 15mg group, 70.8% were kept in symptomatic remission, compared to 84.6% in the 30mg group. 81 patients experienced at least one adverse event, 77.1% of patients receiving lansoprazole 15mg, compared with 84.6% of patients receiving lansoprazole 30mg (n.s.). Conclusion: Lansoprazole proved to be safe and effective maintenance treatment for reflux esophagitis, as both 15mg and 30rag daily kept the majority of patients in endoscopic and symptomatic remission. No statistically significant differences were found in endoscopic relapse, symptomatic relief or occurrence of adverse events.
SHORT SEGMENT BARRETT'S ESOPHAGUS: DIAGNOSIS, SYMI~OMS, .HISTOLOGY, MANOMETRY AND AMBULATORY pH. S.K. Heier, I.R. Willner, W.S. Rosenthal, M. Bantam, L.M. Heier, S.D. Gronowitz, A. Lowy, N. Khan, F. Seif, S. Clark, A. Trehan, A. Khan, A. Hasan. Dept of Med, NY Med Coil, Valhalla, NY. Short segment Barrett's esophagus (SSBE; intestinal metaplasia limited to the region of the GE junction) is assumed to be similar to longer segment Barrett's in pathogenesis, and may contribute to the increased incidence of distal esophageal adenocarcinoma. METHODS: Biopsies were obtained from minimally nodular GE junctions, or normal appearing junctions in patients with a history of chronic reflux symptoms, atypical chest pain, or esophagitis. Biopsies were evaluated for the presence and degree of intestinal metaplasia, with staining for sialomucins and sulfomucins. Metaplasia was classified as SSBE only if the squamocohimuar junction was at or < 2 cm from the LES. Patients with metaplasia were questioned as to the presence of reflux and dysmotility symptoms, and were evaluated with esophageal manometry and ambulatory pH. RESULTS: In 23 patients identified with intestinal metaplasia, indications for endoscopy included abdominal pain (30%), chronic reflux (26%), anemia or bleeding (17%), and dysphagia (9%). Esophagitis > Grade 2 was documented in 22 %. Further questioning elicited symptoms including frequent reflux or heartburn in 61% and atypical chest pain in 17%. Biopsies from other gastric sites revealed metaplasia in 22% (33% of those obtained). Metaplasia of the GE junction was incomplete in all patients, although one also had foe] of complete metaplasia. Ten patients underwent motility. Two patients had achalasia. In the 8 other patients, 5 had abnormalities including segmental aperistalsis (4), poor propagation of peristalsis (3), low LES pressure (1), and low amplitude contractions (1). Two of 5 patients had abnormal upright and supine acid reflux on ambulatory pH monitoring. Manometric findings were compared to patienig with known long segment Barrett's esophagus, all of whom demonstrated either low LES pressure, low amplitude of peristalsis, or poor peristaltic propagation. CONCLUSIONS: Compared to long .segment Barrett's esophagus, SSBE is associated with less severe motility and ambulatory pH abnormalities. Furthermore, the identification of metaplasia in patients with otherwise normal evaluations and in two patients with achalasia suggests that other pathogenic mechanisms may be involved,
Esophageal, Gastric, and Duodenal Disorders
Alll
THE SYMPTOMATIC EFFECT OF A PECTIN-BASED RAFT-FORMING ANTIREFLUX AGENT IN NON-EROSIVE GASTRO-ESOPHAGEAL REFLUX DISEASE: A DOUBLE-BLIND PLACEBO-CONTROLLED TRIAL. T. Havelund, C. Aalykke. Dept. of Medica~ Gastroenterology, Odense, Denmark. In low grade gastro-esophageal reflux disease a non-absorbable drag might be a valuable therapeutic option as regards cost and safety. Aim: To determine the efficacy and safety of a locally acting raft-forming antireflux agent based on pectin (Aflurax, Ferrosan A/S, Copenhagen, Denmark) in relieving predictable symptoms in patients with low grade gastro-esophageal reflux disease. Methods: Sixty-five patients with beartbum as predominant complaint arid normal mucosa or non-erosive/non-ulcerative esophagitis at endoscopy were randomized to treatment with Aflurax, two 1200-mg tablets 30 minutes after meals and at bedtime or corresponding placebo for 4 weeks. Pretreatment, day 15, and day 29 the severity of heartburn was assessed using the ordinal scale: none; mild; moderate; and severe. From diary cards weekly heartburn indices (Gastroenterology 1990;99:629) were also calculated as the number of days with beartbum times its average severity (range 0-21). Results: Sixty-three patients were evaluable at day 15 and 47 patients at day 29 (Aflurax/placebo: 31/32 and 29/18, respectively). The uneven cumulated number of withdrawals at day 29 in the two treatment groups precluded formal statistical analysis of the efficacy variables at this time point. After two weeks patients treated with Aflurax were more relieved from heartburn compared to patients treated with placebo (Table). The daytime heartbum indices (median,[IQR]) for week 1 and 2 were: 5.7 [3.4-9.7] and 5 (0.8-10) on Aflurax versus 10.8 [6.5-13] and 11 [5-14] on placebo (P < 0.05, Mann-Whitney tes0. During nighttime the corresponding heartbum indices were 2.1 [0.1-7.9] and 0.6 [0-4.6] on Aflurax versus 3.7 [0.4-12] and 4.3 [0-10] on placebo (n.s.). Aflurax was in general well tolerated. TABLE. Heartburn severity (number of patients). Pretreatment Day 15" Mild Moderate Severe None Mild Moderate Severe Aflurax 4 18 10 6 14 8 3 Placebo 7 19 7 2 6 13 11 • P < 0.005 for difference between treatment groups (stratified Wilcoxon tes0. Conclusion: In patients with heartburn and without erosive/ulcerative esophagitis at endoscopy the raft-forming anti-reflux agent Aflurax provides better symptomatic relief than placebo.
• THE APACHE III PROGNOSTIC SYSTEM: PREDICTING ADVERSE OUTCOME AFTER HEATER PROBE THERAPY. S.K. Heier, S.D~ Gronowitz I.R. Willner, L.M. Heier, F. Self, A. Trehan, A. Lowy, N. Khan, A. Khan, A. Hasan. Dept of Med, NY Med Coll, Valhalla, NY. The APACHE III prognostic system was developed to predict mortality and other outcomes at the time of IeO admission. The system consists of several components: the Acute Physiology Score (APS); the APACHE Score (AS) incorporating APS, age, and chronic health evaluation; the APACHE Equation, which predicts mortality risk, incorporating AS, length of stay, location (e.g., hospital transfer) and major disease category. We tested whether comorbidity influences outcome after endoscopic therapy of upper GI bleeding using the APACHE III system, and correlated a variety of other factors with outcome. METHODS: 126 consecutive patients with bleeding from benign gastroduodenal ulcersmho underwent heater probe therapy (HPT) were analyzed. Mallory-We]as tears were excluded. Failure of HPT was defined as persistent bleeding, bleeding after repeat HPT, need for alternative therapy, and bleeding which contributes to mortality. We modified the APACHE scoring sytem by determining the APS and length of Stay at the time of endoscopic therapy, whereas location and major disease category were determined at the time of ICU admission for other illness if applicable. In addition, 109 clinical, historical and endoscopic factors were evaluated for association with various outcome endpoints by univariate analysis. RESULTS: Rebleeding occurred in 43 patients (34%), major rebleeding in 30 (24%), 2nd rebleeding after repeat HPT in 17 (13%), failure in 23 (18%), and mortality in 2 (1.6%). Of the three APACHE components tested, the APS correlated best with outcome. Increasing APS was associated with increasingly adverse clinical outcome (Cochran linear trend test, P <0.001). APS > 45 was associated with a significant incidence of failure or major rebleeding (odds ratio [OR] = 7.51; 95% CI, 3.15-17.9). Fifteen of the 109 potential risk factors were selected for use in stepwise multiple logistic regression analysis. After adjusting for overall patient stares with the APS, risk factors also found to be significantly associated with an adverse outcome included a history of diabetes and a transfusion requirement of > 3 units (OR = 4.31, 95% CI 1.48-12.6; OR = 3.94, 95% CI 1.35-11.5, respectively). CONCLUSIONS: Variables other than endoscopic findings can significantly impact on outcome after endoscopic therapy. Degree of comorbidity estimated by severity of physiologic abnormalities, as determined by modified APS, strongly correlates with outcome. Other predictors include the presence of diabetes and transfusion requirements. Consideration should be given to determining APS, and developing predictive equations as assessment tools to guide clinical management.