Preventing Pancreatitis After ERCP: Risk Stratification Is Important

MONTREAL — Prophylactic administration of allopurinol before endoscopic retrograde cholangiopancreatography does not reduce the risk of postprocedure pancreatitis, compared with placebo, in average-risk patients, but the therapy may be beneficial in a high-risk subgroup, reported Dr. Joseph Romagnuolo of the Medical University of South Carolina, Charleston.

“I think it's probably not worth doing this in average-risk patients and may even be harmful. But we still don't have a whole lot of information about high-risk groups and so I think there's still an unanswered question as to whether it's beneficial in this group,” he said in an interview at the Canadian Digestive Diseases Week.

His randomized, multicenter, placebo-controlled trial found that there was not a significant difference in the rate of postprocedural pancreatitis between 293 patients who received allopurinol 300 mg and 293 patients who received placebo approximately 1 hour before ERCP.

Pancreatitis was defined as pancreatic-type pain requiring medical attention within 24 hours of the ERCP and lasting for more than 24 hours, he said.

The overall rate of pancreatitis was 5.5% in the allopurinol-treated group (mean age 54 years), compared with 4.1% in those receiving placebo (mean age 55.5 years), he noted. About 10% of the study subjects were classified as high-risk patients, and within this subgroup, allopurinol was associated with lower rates of pancreatitis, compared with placebo (6.3% vs. 23.5%).

In contrast, among average-risk patients only, the therapy was associated with higher rates of pancreatitis, compared with placebo (5.4% vs. 1.5%), suggesting “nonsignificant trends toward possible benefit in the high-risk group, and possible harm for the remaining subjects,” according to Dr. Romagnuolo. “In our trial, high risk was defined as suspected sphincter of Oddi dysfunction or if pancreatic therapy was anticipated as a reason for the procedure,” he explained. “So if there were plans to take out a pancreatic stone or stent a stricture, those were all considered high-risk patients.”

Three previous trials have shown discrepant results with allopurinol and post-ERCP pancreatitis, resulting in “clinical equipoise” regarding this intervention, Dr. Romagnuolo explained at the meeting sponsored by the Canadian Association of Gastroenterology. But his study is the first to stratify patients by risk, revealing an important consideration for future trials, he said.

It remains unclear why the therapy might have potential benefit in high-risk patients while being potentially harmful in average-risk patients, but one theory focuses on its impact on ischemic injury, he said. Allopurinol is a xanthine oxidase inhibitor and an antioxidant with antiapoptotic effects. “It can mediate capillary endothelial injury, which may be an early step in the pathogenesis of pancreatitis, especially ischemic pancreatitis. There may be more inflammation and capillary injury in high-risk patients that the allopurinol could help. But allopurinol has some propancreatitis factors that we don't know about, which, in average patients, may be enough to increase their risk.”

Pancreatitis is the most common complication of ERCP, with an overall incidence of 2%–15% and a related mortality of 0.1%–0.5%, Dr. Romagnuolo said. High-risk patients can have post-ERCP pancreatitis rates as high as 20%, underlining the importance of future investigation into the potential benefits of allopurinol prophylaxis in this population, he concluded.

MONTREAL — Prophylactic administration of allopurinol before endoscopic retrograde cholangiopancreatography does not reduce the risk of postprocedure pancreatitis, compared with placebo, in average-risk patients, but the therapy may be beneficial in a high-risk subgroup, reported Dr. Joseph Romagnuolo of the Medical University of South Carolina, Charleston.

“I think it's probably not worth doing this in average-risk patients and may even be harmful. But we still don't have a whole lot of information about high-risk groups and so I think there's still an unanswered question as to whether it's beneficial in this group,” he said in an interview at the Canadian Digestive Diseases Week.

His randomized, multicenter, placebo-controlled trial found that there was not a significant difference in the rate of postprocedural pancreatitis between 293 patients who received allopurinol 300 mg and 293 patients who received placebo approximately 1 hour before ERCP.

Pancreatitis was defined as pancreatic-type pain requiring medical attention within 24 hours of the ERCP and lasting for more than 24 hours, he said.

The overall rate of pancreatitis was 5.5% in the allopurinol-treated group (mean age 54 years), compared with 4.1% in those receiving placebo (mean age 55.5 years), he noted. About 10% of the study subjects were classified as high-risk patients, and within this subgroup, allopurinol was associated with lower rates of pancreatitis, compared with placebo (6.3% vs. 23.5%).

In contrast, among average-risk patients only, the therapy was associated with higher rates of pancreatitis, compared with placebo (5.4% vs. 1.5%), suggesting “nonsignificant trends toward possible benefit in the high-risk group, and possible harm for the remaining subjects,” according to Dr. Romagnuolo. “In our trial, high risk was defined as suspected sphincter of Oddi dysfunction or if pancreatic therapy was anticipated as a reason for the procedure,” he explained. “So if there were plans to take out a pancreatic stone or stent a stricture, those were all considered high-risk patients.”

Three previous trials have shown discrepant results with allopurinol and post-ERCP pancreatitis, resulting in “clinical equipoise” regarding this intervention, Dr. Romagnuolo explained at the meeting sponsored by the Canadian Association of Gastroenterology. But his study is the first to stratify patients by risk, revealing an important consideration for future trials, he said.

It remains unclear why the therapy might have potential benefit in high-risk patients while being potentially harmful in average-risk patients, but one theory focuses on its impact on ischemic injury, he said. Allopurinol is a xanthine oxidase inhibitor and an antioxidant with antiapoptotic effects. “It can mediate capillary endothelial injury, which may be an early step in the pathogenesis of pancreatitis, especially ischemic pancreatitis. There may be more inflammation and capillary injury in high-risk patients that the allopurinol could help. But allopurinol has some propancreatitis factors that we don't know about, which, in average patients, may be enough to increase their risk.”

Pancreatitis is the most common complication of ERCP, with an overall incidence of 2%–15% and a related mortality of 0.1%–0.5%, Dr. Romagnuolo said. High-risk patients can have post-ERCP pancreatitis rates as high as 20%, underlining the importance of future investigation into the potential benefits of allopurinol prophylaxis in this population, he concluded.

MONTREAL — Prophylactic administration of allopurinol before endoscopic retrograde cholangiopancreatography does not reduce the risk of postprocedure pancreatitis, compared with placebo, in average-risk patients, but the therapy may be beneficial in a high-risk subgroup, reported Dr. Joseph Romagnuolo of the Medical University of South Carolina, Charleston.

“I think it's probably not worth doing this in average-risk patients and may even be harmful. But we still don't have a whole lot of information about high-risk groups and so I think there's still an unanswered question as to whether it's beneficial in this group,” he said in an interview at the Canadian Digestive Diseases Week.

His randomized, multicenter, placebo-controlled trial found that there was not a significant difference in the rate of postprocedural pancreatitis between 293 patients who received allopurinol 300 mg and 293 patients who received placebo approximately 1 hour before ERCP.

Pancreatitis was defined as pancreatic-type pain requiring medical attention within 24 hours of the ERCP and lasting for more than 24 hours, he said.

The overall rate of pancreatitis was 5.5% in the allopurinol-treated group (mean age 54 years), compared with 4.1% in those receiving placebo (mean age 55.5 years), he noted. About 10% of the study subjects were classified as high-risk patients, and within this subgroup, allopurinol was associated with lower rates of pancreatitis, compared with placebo (6.3% vs. 23.5%).

In contrast, among average-risk patients only, the therapy was associated with higher rates of pancreatitis, compared with placebo (5.4% vs. 1.5%), suggesting “nonsignificant trends toward possible benefit in the high-risk group, and possible harm for the remaining subjects,” according to Dr. Romagnuolo. “In our trial, high risk was defined as suspected sphincter of Oddi dysfunction or if pancreatic therapy was anticipated as a reason for the procedure,” he explained. “So if there were plans to take out a pancreatic stone or stent a stricture, those were all considered high-risk patients.”

Three previous trials have shown discrepant results with allopurinol and post-ERCP pancreatitis, resulting in “clinical equipoise” regarding this intervention, Dr. Romagnuolo explained at the meeting sponsored by the Canadian Association of Gastroenterology. But his study is the first to stratify patients by risk, revealing an important consideration for future trials, he said.

It remains unclear why the therapy might have potential benefit in high-risk patients while being potentially harmful in average-risk patients, but one theory focuses on its impact on ischemic injury, he said. Allopurinol is a xanthine oxidase inhibitor and an antioxidant with antiapoptotic effects. “It can mediate capillary endothelial injury, which may be an early step in the pathogenesis of pancreatitis, especially ischemic pancreatitis. There may be more inflammation and capillary injury in high-risk patients that the allopurinol could help. But allopurinol has some propancreatitis factors that we don't know about, which, in average patients, may be enough to increase their risk.”

Pancreatitis is the most common complication of ERCP, with an overall incidence of 2%–15% and a related mortality of 0.1%–0.5%, Dr. Romagnuolo said. High-risk patients can have post-ERCP pancreatitis rates as high as 20%, underlining the importance of future investigation into the potential benefits of allopurinol prophylaxis in this population, he concluded.