Is aggressive intravenous fluid prescription the answer to reduce mortality in severe pancreatitis? The FLIP study: Fluid resuscitation in pancreatitis

Julia McGovern,Samuel J Tingle,Northern Surgical Trainees Research Association (NOSTRA),Stuart Robinson,John Moir 한국간담췌외과학회 2023 Annals of hepato-biliary-pancreatic surgery Vol.27 No.4

Backgrounds/Aims: Acute pancreatitis is an emergency presentation, which can range from mild to life threatening. Intravenous fluids are the cornerstone of management. Although the WATERFALL trial described the optimal fluid rate in mild/moderate pancreatitis, this trial excluded patients with moderate-severe/severe pancreatitis. The aim of this study was to establish clinical practice regarding intravenous fluid administration in acute pancreatitis and assess its effect on mortality. Methods: Prospective multi-centre audit of patients with acute pancreatitis was conducted. Data were collected regarding intravenous fluid administration within 72 hours of admission. The primary outcome was 30-day mortality. Multivariable logistic regression was used to identify predictors of 30-day mortality. Results: Those with severe pancreatitis received more fluid; median 5.7 L versus 4 L in 72 hours (p = 0.003). Participants with severe pancreatitis who died within 30 days received a median of 2,750 mL in the first 24 hours, compared to 4,000 mL in those who survived. The following factors were significant predictors of 30-day mortality: age, Glasgow score, C-reactive protein, ischaemic heart disease, and pancreatitis aetiology. Overall, volume of intravenous fluid was not associated with mortality. However, the effect of intravenous fluid volume on mortality differed significantly depending on pancreatitis severity. In severe pancreatitis, increased volume of intravenous fluid was associated with significant reductions in mortality (odds ratio = 0.655; 0.459–0.936; p = 0.020). Conclusions: In severe pancreatitis, more aggressive fluid prescription was associated with decreased mortality; however, this was not the case in milder disease. Further prospective trials guiding fluid resuscitation in severe pancreatitis are needed, as the impact of fluid on this population appears to differ from that in those with milder disease.

Association Between Pancreatitis and Subsequent Risk of Pancreatic Cancer: a Systematic Review of Epidemiological Studies

Tong, Gui-Xian,Geng, Qing-Qing,Chai, Jing,Cheng, Jing,Chen, Peng-Lai,Liang, Han,Shen, Xing-Rong,Wang, De-Bin Asian Pacific Journal of Cancer Prevention 2014 Asian Pacific journal of cancer prevention Vol.15 No.12

This study aimed to summarize published epidemiological evidence for the relationship between pancreatitis and subsequent risk of pancreatic cancer (PC). We searched Medline and Embase for epidemiological studies published by February $5^{th}$, 2014 examining the risk of PC in pancreatitis patients using highly inclusive algorithms. Information about first author, year of publication, country of study, recruitment period, type of pancreatitis, study design, sample size, source of controls and attained age of subjects were extracted by two researchers and Stata 11.0 was used to perform the statistical analyses and examine publication bias. Odds ratios (ORs) with 95% confidence intervals (CIs) were calculated with the random effects model. A total of 17 articles documenting 3 cohort and 14 case-control studies containing 14,667 PC cases and 17,587 pancreatitis cases were included in this study. The pooled OR between pancreatitis and PC risk was 7.05 (95%CI: 6.42-7.75). Howeever, the pooled ORs of case-control and cohort studies were 4.62 (95%CI: 4.08-5.22) and 16.3 (95%CI: 14.3-18.6) respectively. The risk of PC was the highest in patients with chronic pancreatitis (pooled OR=10.35; 95%CI: 9.13-11.75), followed by unspecified type of pancreatitis (pooled OR=6.41; 95%CI: 4.93-8.34), both acute and chronic pancreatitis (pooled OR=6.13; 95%CI: 5.00-7.52), and acute pancreatitis (pooled OR=2.12; 95%CI: 1.59-2.83). The pooled OR of PC in pancreatitis cases diagnosed within 1 year was the highest (pooled OR=23.3; 95%CI: 14.0-38.9); and the risk in subjects diagnosed with pancreatitis for no less than 2, 5 and 10 years were 3.03 (95%CI: 2.41-3.81), 2.82 (95%CI: 2.12-3.76) and 2.25 (95%CI: 1.59-3.19) respectively. Pancreatitis, especially chronic pancreatitis, was associated with a significantly increased risk of PC; and the risk decreased with increasing duration since diagnosis of pancreatitis.

카바메이트 중독 후 발생한 급성췌장염

박요섭 ( Joseph Park ),김용원 ( Yong Won Kim ),오세현 ( Se Hyun Oh ),차용성 ( Yong Sung Cha ),차경철 ( Kyoung Chul Cha ),김오현 ( Oh Hyun Kim ),이강현 ( Kang Hyun Lee ),황성오 ( Sung Oh Hwang ),김현 ( Hyun Kim ) 대한임상독성학회 2014 대한임상독성학회지 Vol.12 No.2

Purpose: Carbamate insecticides are potent cholinesterase inhibitors capable of causing severe cholinergic toxicity. Use of carbamate rather than organophosphate insecticides has been increasing. Compared with organophosphate poisoning, relatively few studies have investigated carbamate-associated acute pancreatitis. We investigated general characteristics and pancreatitis of carbamate poisoning and the predictors, among those readily assessed in the emergency department. Methods: We performed a retrospective review of consecutive patients, aged over 18 years, who were admitted between January 2008 and April 2012 to an emergency department (ED) of an academic tertiary care center for treatment of carbamate poisoning. Patients who exhibited poisoning by any other material, except alcohol, were excluded. After application of exclusion criteria, patients were divided according to carbamate-induced pancreatitis and non-pancreatitis groups. Results: A total of 41 patients were included in this study. Among these 41 patients, the prevalence of acute pancreatitis was 36.6% (15 patients). Initial blood chemistry tests showed a statistically higher glucose level in the pancreatitis group, compared with the non-pancreatitis group (222, IQR 189-284 vs. 137, IQR 122-175 mg/dL, P<0.05). Regarding clinical courses and outcomes, a significantly higher proportion of patients developed pneumonia [10 (66.7%) vs. 6 (23.1%), P<0.05] and had a longer hospital stay (7 days, IQR 6-12 vs. 5 days, IQR 2-11, P<0.05), but no difference in mortality, in the pancreatitis group vs. the non-pancreatitis group. In multivariate analysis, the initial glucose was showing significant association with the presentation of carbamate-induced acute pancreatitis (odds ratio 1.018, 95% confidence interval 1.001-1.035, P<0.05). Conclusion: Carbamate-induced acute pancreatitis is common, but not fatal. Initial serum glucose level is associated with acute pancreatitis.

The Risk Factors for Acute Pancreatitis after Endoscopic Ultrasound Guided Biopsy

( Afonso Ribeiro ),( Akash Goel ) 대한소화기학회 2018 대한소화기학회지 Vol.72 No.3

Background/Aims: The risk of developing pancreatitis induced by endoscopic ultrasound-guided fine needle aspiration (EUS FNA) is relatively small. However, patients undergoing sampling through the normal pancreatic parenchyma or the pancreatic duct may have a higher rate of pancreatitis. Here, we determine the factors associated with increased risk of acute pancreatitis in patients undergoing FNA through normal pancreatic parenchyma/pancreatic duct. Methods: In this prospective study at a tertiary cancer center, patients undergoing sampling through the pancreatic duct or ≥5 mm of the normal parenchyma between December 2013 and September 2017 were included. Post-EUS induced pancreatitis was diagnosed by the presence of abdominal pain with an amylase or lipase level higher than three times normal value. Results: A total of 712 patients underwent pancreatic EUS FNA. A total of 163 patients were included in the high-risk group. Mean age was 63 years, 82 females, mean number of needle-passes was 3.3 (range, 1-7). Fifteen patients (15/163, 9.2%) developed pancreatitis after EUS FNA through the pancreatic parenchyma compared with only one case among the control group (<5 mm of normal parenchyma) (0.18%, 1/549, p<0.0001). Several factors appeared to be associated with pancreatitis, including young age, solid lesion, and a recent history of acute pancreatitis. By logistic regression, a prior history of recent pancreatitis was the only statistically significant factor associated with post-EUS-guided biopsy pancreatitis (p=0.008). Conclusions: Patients with a recent history of acute pancreatitis undergoing EUS FNA through 5 mm or more of the normal pancreatic parenchyma are at a much greater risk of acute pancreatitis. (Korean J Gastroenterol 2018;72:135-140)

내시경 역행성 담췌관 조영술 후 발생한 췌장염의 예측인자로서 혈청 procalcitonin의 효용성

김종범,이봉규,서영호,이남훈,이정민,박승욱,안홍주,이상선,송호영 대한췌담도학회 2012 대한췌담도학회지 Vol.17 No.2

Backgrounds/Aims: Pancreatitis is the most common complication of endoscopic retrograde cholangiopancreatography (ERCP). We wanted to evaluate serum procalcitonin as a marker for early prediction of post-ERCP pancreatitis. Methods: Prospective single center study of 94 patients undergoing ERCP between November 2011 and July 2012 were performed. Blood samples for serum procalcitonin were obtained immediately, 4 hours, and 24 hours after ERCP. The definition of post-ERCP pancreatitis and the grade of its severity were based on consensus criteria Result: The incidence of post-ERCP pancreatitis was 16.0% (15 patients). Thirteen had mild pancreatitis, 2 had moderate pancreatitis, and none had severe pancreatitis. The procalcitonin levels in post-ERCP pancreatitis group and no pancreatitis group were 0.28±0.38 vs. 0.47±0.58 ng/ml for immediately, 0.31±0.42 vs. 0.45±0.53 ng/ml for 4 hours and 0.28±0.39 vs. 0.46±0.46 ng/ml for 24 hours. The levels of serum procalcitonin were not significantly different between post-ERCP pancreatitis group and no pancreatitis group (p=0.129 for immediately, p=0.275 for 4 hours, and p=0.266 for 24 hours) Conclusion: There was no significant difference in the level of serum procalcitonin level between post-ERCP pancreatitis and no pancreatitis group.

Screening of Sera from Patients with Pancreatitis by an Apoptosis Assay of Skin-derived Cells

석애은,손병관,이지영,정광현,이유림,김두진,차병헌,강희규 대한소화기학회 2019 대한소화기학회지 Vol.74 No.4

Background/Aims: An excessive inflammatory response is typical in acute pancreatitis and a significant cause of early mortality in severe acute pancreatitis. This is believed to be caused by inflammatory molecules or upregulated cytokine levels in the serum of patients. The aim of this study was to identify the serum-mediated apoptosis-inducing effects in acute pancreatitis patients. Methods: A skin tissue-derived cell line, BJ, was treated for 24 hours with the sera of 22 healthy volunteers (control) and 71 acute pancreatitis patients (22 with gallstone pancreatitis, 16 with alcoholic pancreatitis, and 11 with pancreatitis with other causes) collected at the time of hospital admission (active) and discharge (resolved). Apoptosis was analyzed by flow cytometry. Results: The average percentage of living cells, early apoptotic cells, and late apoptotic cells ranged from 78.8% to 85.0%, 5.5% to 7.3%, and 7.7% to 13.1%, respectively. The number of live cells increased significantly using the serum from the resolved state of gallstone-induced pancreatitis. In addition, the number of early apoptotic cells increased significantly using the serum from the resolved state of pancreatitis with other causes. The number of late apoptotic cells decreased significantly with the serum from the resolved state compared to the active state of gallstone- and alcohol-induced pancreatitis. Conclusions: Serum samples from patients with pancreatitis induced a change in the apoptosis profiles of skin-derived cells. These results indicate changes in the serum components in patients with acute pancreatitis.

Acute Pancreatitis Secondary to Ciprofloxacin Therapy in Patients with Infectious Colitis

안지원,이현정,성혜영,정대영,김진일,조세현,박수헌,한준열,김재광 대한내과학회 2011 대한내과학회 추계학술대회 Vol.2011 No.1

Ciprofloxacin is considered to be a safe and effective treatment of acute infectious colitis. However, this drug, albeit rarely, may cause drug-induced pancreatitis. This study was conducted to analyze the clinical features of pancreatitis caused by ciprofloxacin. Method: From January 2007 to March 2011, we registered 227 patients who were hospitalized infectious colitis at St. Mary`s hospital, Seoul, Korea. All the patients received ciprofloxacin therapy for a treatment of infectious colitis. We observed a few cases of rare adverse events; ciprofloxacin-induced acute pancreatitis diagnosed by the Naranjo algorithm. Results: During ciprofloxacin therapy, 7 of 227 patients (3.1%) were met rare adverse events (4 males and 3 females with a mean age of 46.9±17.4 years; range: 24-71). They were diagnosed to probable pancreatitis secondary to ciprofloxacin by the Naranjo algorithm; pancreatic enzyme was sporadically elevated with ciprofloxacin use. After ciprofloxacin administration, the average time interval until development of pancreatitis was 5.5 days (range: 4-7). In abdominal computed tomography, pancreatic swelling and homogenous enhancement was noted in 3 of 7 patients. Complicating acute pancreatitis was completely resolved gradually after the cessation of ciprofloxacin administration. Mean recovery time was 11.3 days (range: 8-15). Conclusion: We observed that ciprofloxacin-induced pancreatitis may occur with an incidence of approximately 3%. Drug-induced pancreatitis by ciprofloxacin displays a short latency, suggesting an idiosyncratic hypersensitivity reaction. If pancreatitis was detected early, the prognosis was very good. During ciprofloxacin use, practitioners should be aware that drug-induced pancreatitis can occur during ciprofloxacin therapy. And regular screening of chemical profiles is warranted.

Type 2 Autoimmune Pancreatitis (Idiopathic Duct-Centric Pancreatitis) Highlighting Patients Presenting as Clinical Acute Pancreatitis: A Single- Center Experience

Dong Wook Oh,Tae Jun Song,Sung-Hoon Moon,Jin Hee Kim,Joo Nam Lee,Seung Mo Hong,Joune Seup Lee,Seok Jung Jo,Dong Hui Cho,Do Hyun Park,Sang Soo Lee,Dong-Wan Seo,Sung Koo Lee,Myung-Hwan Kim 거트앤리버 소화기연관학회협의회 2019 Gut and Liver Vol.13 No.4

Background/Aims: Type 2 autoimmune pancreatitis (AIP) has been considered extremely rare in East Asia. This study aimed to clarify the prevalence, clinical characteristics and radiological findings of type 2 AIP highlighting patients presenting as acute pancreatitis in a single center. Methods: Type 2 AIP patients were classified according to International Consensus Diagnostic Criteria. Radiological findings were compared between type 2 AIP presenting as acute pancreatitis and gallstone pancreatitis. Results: Among 244 patients with AIP, 27 (11.1%) had type 2 AIP (definite, 15 [55.5%] and probable 12 [44.5%]). The median age of patients with type 2 AIP was 29 years (interquartile range, 20 to 39 years). Acute pancreatitis was the most common initial presentation (n=17, 63%) while obstructive jaundice was present in only one patient. Ulcerative colitis (UC) was associated with type 2 AIP in 44.4% (12/27) of patients. Radiological pancreatic imaging such as delayed enhancement of diffusely enlarged pancreas, homogeneous enhancement of focal enlargement/ mass, absent/minimal peripancreatic fat infiltration or fluid collection, and multifocal main pancreatic duct narrowings were helpful for differentiating type 2 AIP from gallstone pancreatitis. During follow-up (median, 32.3 months), two patients (2/25, 8%) experienced relapse. Conclusions: In South Korea, type 2 AIP is not as rare as previously thought. Overall, the clinical profile of type 2 AIP was similar to that of Western countries. Type 2 AIP should be considered in young UC patients with acute pancreatitis of uncertain etiology.

급성 췌장염에서 췌장염의 중증도에 따른 폐의 조직학적 변화

김광희(Kwang Hee Kim),현진해(Jin Hai Hyun),김영식(Young Sik Kim),김창덕(Chang Duck Kim) 대한내과학회 1998 대한내과학회지 Vol.55 No.3

N/A Objectives: About 60% of all deaths due to acute pancreatitis occur within the first 7 days of onset and associated with acute lung injuries, Lung injury include pulmonary infiltration, pulmonary edema, pleural effusion, and adult respiratory ditress syndrome. But it is unclear whether the acute lung injury is related with severity of pancreatitis. In this study, we have evaluated the association between acute lung injury and severity of pancreatitis in experimental acute pacreatitis. Methods: Twenty-one male Sprague-Dawley rat (30-250 g B.wt) were used There were three groups: control (group 1, n=7), edematous pancreatitis (group 2, n=7), and necrotizing pancreatitis (group 3, n=7). For inducing a edematous paruxeatitis, rat was received a 4 hour intravenous infusion of cerulein (5μ/kg/hr). For a necrotizing pancrewtitis, rat was received intraductal injection of taurocholate (5%, 0.lml/100 g B.wt). After pancreatitis was induced, the pancreas, lung and blood were prepared for biochemical and histologic changes each other. Bronchoalveolar lavage (BAL) was also taken. Results: Cerulein induced edematous pancreatitis and taurocholate induced necrotizing pancreatitis. Amylase was significantly increased in edematous and necrotizing pancreatitis. BAL findings showed that neutrophil was increased from 2% to 49% in necrotizing pancreatitis. The severity of lung injury was more severe in neerotizing pnncreatitis than edematous pancreatitis. Conclusion: These observations suggest that the lung injury was strongly associated with severity of acute pancreatitis and neutraphil may be capable of important role in the development of lung injury.

Cerulein 유발 급성 췌장염에 대한 nafamostat mesilate의 예방 효과

이준규 ( Jun Kyu Lee ),박주경 ( Joo Kyoung Park ),이상협 ( Sang Hyub Lee ),윤원재 ( Won Jae Yoon ),류지곤 ( Ji Kon Ryu ),김용태 ( Yong Tae Kim ),정현채 ( Hyun Chae Jung ),윤용범 ( Yong Bum Yoon ) 대한내과학회 2007 대한내과학회지 Vol.72 No.4

목적: 급성 췌장염의 동물 모델에 있어서 여러 가지 단백 분해 효소 억제제들의 예방 효과가 입증되어 있으나 질병 발생 이후에야 약물이 투여되는 실제 임상 상황에서는 단백 분해 효소 억제제들의 급성 췌장염 대한 치료 효과는 확실하지 않다. 본 연구자는 대부분의 동물실험에서 췌장염 유발 전에 투여되었으며, 유발 전과 후에 각각 투여하여 그 결과를 비교한 실험은 찾아보기 어렵다는 사실에 착안하여, 약물의 투여 시점이 급성췌장염의 예방 혹은 치료 효과에 중요하다는 가설을 세우고 단백 분해 효소 억제제인 nafamostat mesilate (NM)을 췌장염 유도 전후에 각각 생쥐에 투여하여 그 효과를 비교하였다. 방법: 생쥐에서 콜레시스토키닌(cholecystkinin) 유사 물질인 cerulein을 반복적으로 복강내 투여하여 급성췌장염을 유발시키면서 투여 전후에 각각 NM를 정맥내 주사하고 혈청 아밀라제 및 리파아제, 췌장 조직내 MPO (myeloperoxidase) 활성도, 조직학적 변화 등을 측정하여 각군에 있어서 염증의 정도를 비교하였다. 또한 간 군에 있어서 p38 MAPK (mitogen-activated protein kinase)와 그의 활성형인 phosphor-p38 MAPK, 그리고 IL-6(interleukin-6)의 췌장 조직 내에서의 발현 양상을 살펴보았다. 결과: Cerulein의 반복적인 복강내 투여를 통해 급성췌장염이 성공적으로 유발되었다. NM을 췌장염 유발 전에 투여할 경우 예방 효과가 있었던 반면, 유발 후에 투여하였을 경우에는 그 효과가 확실하지 않았다. 급성췌장염이 발생한 군에서는 p38 MAPK에 비하여 phosphor-p38 MAPK의 발현이 증가되어 있었던 반면, 각 군 간에 있어서 IL-6의 발현에는 차이가 없었다. 결론: NM을 급성췌장염 발생 이후 치료목적으로 사용할 경우 그 효과는 확실하지 않으나, 내시경적역행성 담췌관조영술과 같이 급성췌장염의 발생이 예상되는 경우에 예방을 위해 미리 투여하는 것은 효과가 있을 것으로 기대된다. Background: Many protease inhibitors show a protective effect for acute pancreatitis as seen in animal models. In previous studies, the protease inhibitors were administered before induction of pancreatitis, and there are few published reports examining effects when these agents were administered after induction of pancreatitis. The timing of drug administration may provide an explanation for the ineffectiveness of protease inhibitors for the treatment of patients with acute pancreatitis. Herein, we assessed the protective effect of nafamostat mesilate (NM), a potent protease inhibitor, in a mouse model of cerulean-induced pancreatitis and compared the results of administering the drug before and after the induction of pancreatitis. Methods: Cerulein, a cholecystokinin analogue, was injected into mice intraperitoneally to induce pancreatitis. The mice received intravenous NM administration before and after the induction of pancreatitis. The serum concentration of amylase and lipase was measured, histological changes were measured, and the tissue expression of myeloperoxidase was measured to assess the degree of inflammation. Expression of p38 MAPK (mitogen-activated protein kinase), phospho-p38 MAPK, and IL-6 (interleukin-6) in tissue was evaluated. Results: Acute pancreatitis was induced successfully by intraperitoneal injection of cerulein. Acute pancreatitis could be prevented when NM was administered before the induction of pancreatits. However, the effect was not guaranteed when given after the induction of pancreatitis. For a group of mice with induced pancreatitis, tissue expression of phospho-p38 MAPK was prominent and there was no marked difference in the expression of IL-6 between groups with or without induced pancreatitits. Conclusions: Although the efficacy of NM for treatment of acute pancreatitis is doubtful, pretreatment with NM for an expected condition like endoscopic retrograde cholangiopancreatography (ERCP), might be helpful for the prevention of pancreatitis. (Korean J Med 72:340-351, 2007)