Etiologies, demographics, management, and outcomes vary widely among patients with acute pancreatitis around the world, according to an analysis of data from the prospective, international APPRENTICE patient registry.

In some cases – particularly in regard to therapeutic interventions – the differences are “strikingly divergent” and demonstrate a “lag behind current evidence,” Bassem Matta, MD, of the University of Pittsburgh Medical Center, and colleagues reported in Clinical Gastroenterology and Hepatology.

Findings of a disproportionately higher rate of opioid prescribing during hospitalization and at discharge at North American sites are especially alarming, the investigators said.

Demographics and etiologies

The most common etiologies among 1,612 patients in the registry, which collects data from individuals with acute pancreatitis at six centers in Europe, three centers in India, five centers in Latin America, and eight centers in North America, were biliary (45%) and alcoholic (21%), and severity was mild in 65% of patients, moderate in 23%, and severe in 12%, they noted.

The predominant etiology in Latin America was biliary (78%), whereas the predominant etiology in India was alcoholic (45%).

The mean age of patients in Europe was 58 years, which is older than the mean age of 46 years for all regions represented in the registry, and comorbid conditions were also more common among patients in Europe (73% vs. 50% overall), the investigators found.

In addition to age differences, significant geographic differences were seen with respect to sex, ethnicity, and race distributions. Patients from Indian sites, for example, were mostly men (75%), were younger in age (median, 39 years), and were more likely to have alcoholic etiology (45% vs. 14% in the other areas). Most of the Latin American patients were women (67%), were young (median, 43 years), and most often had biliary etiology (78% vs. 37% elsewhere).

In contrast, European and North American subjects had a relatively equal sex distribution and an overall older age (median, 58 years).

“Observed differences in etiology and demographics likely reflect a tight interconnection between age, sex, and etiology,” the investigators wrote.


Analgesic utilization was “markedly variable” across the world, they said, explaining that nonsteroidal anti-inflammatory drugs (NSAIDs) were the mainstay of pain management in Europe (68%), whereas Indian sites used tramadol in 91% of patients.

Latin American centers frequently used opioids (59%), NSAIDs (48%), and tramadol (34%).

However, opioid analgesics were used in 93% of patients in North America, compared with 27% of patients in the other regions, and 64% vs. 2.7% of patients in North American vs. the other regions were discharged on opioid analgesics.

This is of particular concern in light of a meta-analysis showing no difference in efficacy between opioids and nonsteroidal anti-inflammatory drugs for pain control in acute pancreatitis, the investigators said, noting that “[i]t is not entirely clear why such divergences exist between North American centers compared to the rest of the world.

“Notably, no clear statements are included in the current societal guidelines addressing optimal strategies for analgesia in [acute pancreatitis],” they added.

Also of note, the rate of endoscopic retrograde cholangiopancreatography (ERCP) – which guidelines based on strong evidence say should be limited to urgent cases among biliary acute pancreatitis patients with suspected cholangitis or biliary obstruction – was much higher at North American sites (44.7% vs. 21.9% overall) and post-ERCP pancreatitis was significantly more common at North American sites (19% vs. 2.8% in the other geographic areas), they said.

However, these differences were mostly driven by two North American sites, which classified 50 out of 90 and 22 out of 62 enrolled patients, respectively, as having post-ERCP pancreatitis.

Further, cholecystectomies were performed at the time of hospital admission in 60% of patients in Latin America, compared with 15% overall.

Another notable difference in management related to intravenous fluid use; similar amounts were administered during the first 24 hours in India and Latin America (3-3.2 liters), but in Europe the average was 2.5 liters, and while lactated Ringers and normal saline were the main types of fluid used, lactated Ringers was the dominant type used in India (92%), but was rarely used in Latin America (7%).


The overall median length of stay was 8 days, and overall mortality during hospitalization was 2.8%. In patients with mild disease, the shortest lengths of stay were in North America (4 vs. 7 days in other regions), and severe disease was more common in India (23% vs. 9% elsewhere).

Intensive care unit admissions were highest at Indian centers, and in-hospital mortality was highest in Europe (5.7%), compared with 3.3% in India, 2.3% in Latin America, and 0.6% in North America, they said.

Mortality during the initial hospital stay among patients with severe acute pancreatitis was 44% in Europe, compared with 15% in the other three regions.

Multivariable regression analyses adjusting for potential confounders such as age, sex, body mass index, Charlson score, etiology, and transfer status showed that the odds of severe acute pancreatitis were 11.2 times higher in Europe, 7 times higher in India, and 5.6 times higher in Latin America, compared with North America.

The odds ratios for mortality during hospitalization among patients with severe disease were 10.4 in Europe, 4.2 in India, and 8.3 in Latin America, compared with North America.

Implications of the findings

Around the world, acute pancreatitis is a leading cause of gastrointestinal-related hospital admissions, and incidence is reportedly increasing in the United States and Europe, the investigators said, noting that about 20% of patients develop severe disease with relatively high morbidity and mortality.

Multiple advances in management have emerged over the last decade, but it is unclear whether those recent advances have gained traction worldwide, they added.

The APPRENTICE registry was created as a response to the lack of prospective, multinational data and the current study aimed to assess the geographic differences in patient characteristics, management, and outcomes across four geographic areas.

The findings, which represent “a bird’s eye view” of regional variation, underscore a need for “adequately powered, multicenter, randomized controlled trials comparing the efficacy of different fluid resuscitation protocols” in acute pancreatitis patients, the investigators said.

Further, “the interventions specific to each region are in certain aspects strikingly divergent, and in many occasions lag behind current evidence,” they wrote, noting the largely variable length-of-stay outcomes and mortality rates.

“In addition to depicting key features of [acute pancreatitis], the results from this study may serve as a reference guide for designing future clinical trials,” they concluded.

The authors reported having no disclosures.

SOURCE: Matt B et al. Clin Gastroenterol Hepatol. 2019. doi: 10.1016/j.cgh.2019.11.017.