Continuous Regional Arterial Infusion Research Articles

Effects of nitroglycerin combined with continuous regional arterial infusion on severe acute pancreatitis, triglyceride, inflammatory factors and prognosis

Abstract Background: To evaluate the effects of nitroglycerin combined with continuous regional arterial infusion (CRAI) on severe acute pancreatitis (SAP), triglyceride (TG), inflammatory factors and prognosis. Methods: SAP patients were randomly divided into control and observation groups (n=169). The control group was treated with intravenous infusion of nitroglycerin once daily for 2 d, while the observation group was treated with nitroglycerin combined with CRAI for 7 d. Their hospitalization time, abdominal pain relief time, abdominal distension relief time and intestinal function recovery time were recorded. The levels of inflammatory factors, and TG were measured. Their liver and kidney functions, hemorheological indices, prognosis, and adverse reactions were evaluated. Results: The observation group had significantly shorter hospitalization time, abdominal pain relief time, abdominal distension relief time, and intestinal function recovery time than those of the control group (P<0.05). After treatment, the levels of interleukin-6, tumor necrosis factor-alpha, endothelin, thromboxane A2 and TG significantly decreased in contrast with those before treatment in both groups, especially in the observation group (P<0.05). The hemorheological indices were significantly improved after treatment compared with those before treatment in both groups, and the observation group had better indices (P<0.05). The Acute Physiology and Chronic Health Evaluation-II score declined significantly in both groups after treatment, and the observation group had a more obvious decrease (P<0.05). During follow-up, similar incidence rates of adverse reactions were observed for both groups (P>0.05). Conclusion: Nitroglycerin combined with CRAI is prominently effective for treating SAP, which can facilitate the health recovery and reduce the incidence of microcirculation disturbance-induced adverse events such as organ failure.

Continuous regional arterial infusion of the protease inhibitor for severe acute pancreatitis

Continuous regional arterial infusion of the protease inhibitor for severe acute pancreatitis

Continuous regional arterial infusion versus intravenous administration of the protease inhibitor nafamostat mesilate for predicted severe acute pancreatitis: a multicenter, randomized, open-label, phase 2 trial

BackgroundContinuous regional arterial infusion (CRAI) of protease inhibitor nafamostat mesilate (NM) is used in the context of predicted severe acute pancreatitis (SAP) to prevent the development of pancreatic necrosis. Although this therapy is well known in Japan, its efficacy and safety remain unclear.MethodsThis investigator-initiated and -driven, multicenter, open-label, randomized, controlled trial (UMIN000020868) enrolled 39 patients with predicted SAP and low enhancement of the pancreatic parenchyma on computed tomography (CT). Twenty patients were assigned to the CRAI group, while 19 served as controls and were administered NM at the same dose intravenously (IV group). The primary endpoint was the development of pancreatic necrosis as determined by CT on Day 14, judged by blinded central review.ResultsThere was no difference between the CRAI and IV groups regarding the percentages of participants who developed pancreatic necrosis (more than 1/3 of the pancreas: 25.0%, range 8.7–49.1% vs. 15.8%, range 3.4–39.6%, respectively, P = 0.694; more than 2/3 of the pancreas: 20%, range 5.7–43.7% vs. 5.3%, range 0.1–26.0%, respectively, P = 0.341). The early analgesic effect was evaluated based on 24-h cumulative fentanyl consumption and additional administration by intravenous patient-controlled analgesia. The results showed that the CRAI group used significantly less analgesic. There were two adverse events related to CRAI, namely bleeding and splenic infarction.ConclusionsCRAI with NM did not inhibit the development of pancreatic necrosis although early analgesic effect of CRAI was superior to that of IV. Less-invasive IV therapy can be considered a viable alternative to CRAI therapy.

Sa1386 – Continuous Regional Arterial Infusion of Protease Inhibitors Can Reduce Short-Term Mortality in Patients with Severe Acute Pancreatitis: A Retrospective Multicenter Study

Sa1386 – Continuous Regional Arterial Infusion of Protease Inhibitors Can Reduce Short-Term Mortality in Patients with Severe Acute Pancreatitis: A Retrospective Multicenter Study

Efficacy and safety of continuous regional arterial infusion to treat patients with severe acute pancreatitis

Objective To investigate the efficacy and safety of continuous regional arterial infusion (CRAI) in patients with severe acute pancreatitis (SAP). Methods One hundred SAP patients (including 41 gallstone, 26 alcoholism, 13 hypertriglyceridemia, 11 after heavy meals, and 9 unknown) who were admitted into our hospital from January 2013 to October 2017 were assigned to the CRAI group (n=58) and the control group (n=42). The levels of laboratory measurements, hospitalization time and costs, complications and outcomes were compared between the two groups. Results On the sixth and tenth day of treatment, the levels of white blood cell, hemodiastase, urine amylase, blood glucose, blood calcium and APACHE-II score improved in both the 2 groups. The degrees of improvement in the CRAI group were better than that in the control group. The abdominal pain relief time [(3.3±1.2)d vs. (5.9±2.3)d], hemodiastase recovery time [(7.9±1.8)d vs. (13.3±2.5)d], and hospitalization stay [(21.3±3.6)d vs. (32.4±4.3)d] were shorter in the CRAI group. The costs were similar in the two groups. Retroperitoneal infection, pancreatic pseudocyst, and pancreatic drainage were less in the CRAI group. The improved and cure rates were 94.8% and 70.7% in the CRAI group, which were higher than those in the control group (71.4% and 47.6%, respectively). Moreover, the ineffective treatment and mortality rates were 5.2% and 1.7% in the CRAI group, which were lower than those in the control group (28.6% and 14.3%, respectively). Conclusions CRAI was an efficacious and safe treatment for patients with SAP. It can be used as an alternative to other effective treatments. Key words: Severe acute pancreatitis (SAP); Continuous regional arterial infusion (CRAI); Interventional therapy

Research progress of regional arterial infusion for treating severe acute pancreatitits

Severe acute pancreatitis is one of clinical common critical disease, which characterized by dangerous pathogenic conditions and complex pathogenesis. There are still lack of effective drugs and treatment methods. Continuous regional arterial infusion could remarkably increase the local drug concentration, and enhance the therapeutic effect, which has been applied in the treatment of severe acute pancreatitis. The selection of artery and treatment drug are the two key points of regional arterial infusion for severe acute pancreatitits, the high selectivity of artery and composed infusion of treatment drug is the ideal option for treatment of severe acute pancreatitis. Key words: Severe acute pancreatitis; Regional arterial infusion; Treatment

Continuous Regional Arterial Infusion in Acute Pancreatitis Management (Review)

It is a literature review for the use of continuous regional arterial infusion of protease inhibitors and antibacterial drugs in acute pancreatitis management. The technique of drug administration and the results of randomized clinical trial are described.

Continuous Regional Arterial Infusion of Protease Inhibitors Has No Efficacy in the Treatment of Severe Acute Pancreatitis: A Retrospective Multicenter Cohort Study.

ObjectiveThe aim of this study is to assess the effectiveness of continuous regional arterial infusion (CRAI) of protease inhibitors in patients with severe acute pancreatitis (SAP) including acute necrotizing pancreatitis.MethodsThis retrospective study was conducted among 44 institutions in Japan from 2009 to 2013. Patients 18 years or older diagnosed with SAP according to the criteria of the Japanese Ministry of Health, Labour and Welfare study group (2008) were consecutively enrolled. We evaluated the association between CRAI of protease inhibitors and mortality, incidence of infection, and the need for surgical intervention using multivariable logistic regression analysis.ResultsOf 1159 patients admitted, 1097 patients with all required data were included for analysis. Three hundred and seventy-four (34.1%) patients underwent CRAI of protease inhibitors and 723 (65.9%) did not. In multivariable analysis, CRAI of protease inhibitors was not associated with a reduction in mortality, infection rate, or need for surgical intervention (odds ratio [OR] 0.79, 95% confidence interval [CI] 0.47–1.32, P = 0.36; OR 0.97, 95% CI 0.61–1.54, P = 0.89; OR 0.76, 95% CI 0.50–1.15, P = 0.19; respectively).ConclusionsContinuous regional arterial infusion of protease inhibitors was not efficacious in the treatment of patients with SAP.

Comparison of the efficacy of continuous i.v. infusion versus continuous regional arterial infusion of nafamostat mesylate for severe acute pancreatitis.

Continuous regional arterial infusion (CRAI) of protease inhibitors may be effective in the treatment of severe acute pancreatitis (SAP), but it is more invasive than i.v. infusion. The purpose of this study was to examine the effectiveness of continuous i.v. infusion (CIVI) for SAP compared with CRAI by unifying the dose and the administration period of nafamostat mesylate. This study comprised 32 patients with SAP who were divided into two groups: the CRAI group and the CIVI group. The protease inhibitor, nafamostat mesylate, was continuously infused at a rate of 200 mg/day for 5 days in both groups. Clinical outcomes including in-hospital mortality were examined. There were no significant between-group differences in in-hospital mortality and 90-day mortality. The duration from admission to treatment was significantly shorter in the CIVI group (median, 7 h vs. 2 h, P = 0.0001; CRAI group vs. CIVI group). The rate of mechanical ventilation was significantly less in the CIVI group than in the CRAI group (93% vs. 47%, P = 0.007). The CIVI group showed a tendency toward decreased length of intensive care unit stay (median, 13 days vs. 4 days, P = 0.085) and hospital stay (median, 19 days vs. 11 days, P = 0.072). Total costs during hospitalization were significantly lower in the CIVI group (median, $18,320 vs. $11,641, P = 0.049). The effectiveness of CIVI with early nafamostat mesylate treatment after the development of SAP could be equivalent to, or better than, that of CRAI.

Continuous Regional Arterial Infusion of Protease Inhibitors for Treatment of Severe Acute Pancreatitis: Systematic Review and Meta-Analysis.

We performed a systematic review and meta-analysis of observational studies and randomized controlled trials (RCTs) to assess the benefit and risk of continuous regional arterial infusion (CRAI) of protease inhibitors (CRAIpis) in patients with severe acute pancreatitis (SAP) or acute necrotizing pancreatitis (ANP). The search was performed using the key words "pancreatitis" and "regional arterial infusion." All language studies involving adult cases of SAP or ANP, which assessed the impact of the CRAIpis, were included. Our analysis included 8 observational studies and 2 RCTs from 376 potentially relevant articles. With regard to the observational studies, the CRAIpi was significantly associated with decreased both mortality (odds ratio, 0.40; 95% confidential interval [CI], 0.25-0.64; P = 0.0001) and the need for urgent surgical intervention (odds ratio, 0.22; 95% CI, 0.12-0.3; P < 0.0001). In the RCTs, the application of CRAIpi tends to decrease the mortality but does not reach the significance (risk reduction, -0.12; 95% CI, -0.36-0.12; P = 0.33). The CRAIpi has the potential to reduce the mortality or the need for urgent surgical intervention in cases of SAP or ANP. Further, large multicenter trials are needed to refute or confirm our findings.

Mo1344 Continuous Regional Arterial Infusion of Protease Inhibitors Showed No Efficacy in Treatment of Severe Acute Pancreatitis: A Retrospective Multi-Center Study

Mo1344 Continuous Regional Arterial Infusion of Protease Inhibitors Showed No Efficacy in Treatment of Severe Acute Pancreatitis: A Retrospective Multi-Center Study

Continuous regional arterial infusion for the treatment of severe acute pancreatitis: a meta-analysis

Continuous regional arterial infusion (CRAI) is a drug delivery system, which dramatically increases the drug concentration in the pancreas. Previous clinical and basic studies have demonstrated the possible therapeutic efficacy of CRAI for severe acute pancreatitis (SAP). This meta-analysis of all published randomized controlled trials (RCTs) was conducted to assess the efficacy and safety of CRAI for the treatment of SAP. Up to August 10, 2014, RCTs comparing CRAI with intravenous infusion for SAP in PubMed, Embase, EBSCO, MEDLINE, Science Citation Index Expanded, Cochrane Library, China Academic Journals Full-Text Database, Chinese Biomedical Literature Database, and Chinese Scientific Journals Database were selected by two independent reviewers. The relative risk (RR) and their 95% confidence intervals (CI) for duration of elevated serum amylase and urine amylase, duration of abdominal pain, infection rate, incidence of complication, overall mortality, curative rate, hospital stay and details of subgroup analysis were extracted. Meta-analyses were made using the software Review Manager (RevMan version 5.10). Six RCTs with 390 patients meeting the inclusion criteria were included in the final analysis. Compared with intravenous infusion route, CRAI significantly shortened the duration of elevated urine amylase (MD=-2.40, 95% CI=-3.20, -1.60; P<0.00001) and the duration of abdominal pain (MD=-1.46, 95% CI=-1.94, -0.98; P<0.00001), decreased the incidence of complication (RR=0.35, 95% CI=0.15, 0.81; P=0.01) and overall mortality (RR=0.25, 95% CI=0.08, 0.78; P=0.02), shortened the duration of hospital stay (MD=-10.36, 95% CI=-17.05, -3.68; P=0.002), and increased the curative rate (RR=1.66, 95% CI=1.13, 2.46; P=0.01). No mortality and catheter-related infections due to CRAI administration was reported in these studies. Subgroup analysis showed that the combination of drug administration via CRAI did not significantly improve the outcomes. CRAI is effective for the treatment of SAP, and the combination of drug administration via CRAI did not have a significant effect on the improvement of the outcomes.

I-2．重症急性膵炎における膵局所動注療法のエビデンスとガイドライン

1996年に急性壊死性膵炎に対する動注療法の有用性が報告されて以来，RCTを含めて動注療法の有用性を支持する多数のエビデンスが集積されている．一方，DPCデータベースを用いた最近のpropensity score matching解析研究では動注群と非動注群との間に死亡率，interventionの頻度に差がみられなかったと報告されている．重症急性膵炎に対する動注療法の有用性はいまだ確立されていないことから，ガイドライン2015（第4版）では，重症急性膵炎に対する動注療法は推奨度なしと記載された．

Usefulness of Continuous Regional Arterial Infusion with Doripenem and Protease Inhibitors for Severe Acute Pancreatitis

Usefulness of Continuous Regional Arterial Infusion with Doripenem and Protease Inhibitors for Severe Acute Pancreatitis

Efficacy of Continuous Regional Arterial Infusion With Low-Molecular-Weight Heparin for Severe Acute Pancreatitis in a Porcine Model

Administration of heparin or its derivatives has been proved to be beneficial in the treatment of severe acute pancreatitis (SAP). However, drugs administered by conventional intravenous way are difficult to reach the pancreatic tissue and may cause bleeding complications due to coagulation and microcirculatory disturbance following initiation of SAP. In this study, we aimed to assess the effects of low-molecular-weight heparin (LMWH) administered with continuous regional arterial infusion (CRAI) technique in a porcine model of SAP. Following baseline measurements, 18 animals were divided into three groups: CRAI group (LMWH infused through placed arterial catheter), venous group (LMWH infused through central venous catheter), and SAP control group. We used retrograde intraductal infusion of sodium taurocholate to induce SAP. Global hemodynamic profiles, urine output, systemic oxygenation, and inflammatory and serum biochemical parameters of the animals were studied. At the end of the experiment, histological examination of pancreas, intestine, and lung was performed. Continuous regional arterial infusion with LMWH remarkably stabilized hemodynamic profiles, improved systemic oxygenation and peripheral perfusion, alleviated histological injury of pancreas (especially for the necrosis scale), and downregulated inflammatory response when compared with the other two groups. Moreover, serum D-dimer level also decreased most significantly in the CRAI group (474 ± 144 vs. 664 ± 155 µg/L in the venous group and 945 ± 351 µg/L in the controls at the end), partly indicating ameliorated coagulation disorders in the study group. No bleeding complication was observed in the CRAI group, whereas two animals in the venous group presented gastrointestinal hemorrhage. Continuous regional arterial infusion with LMWH exhibits strong therapeutic effects in the course of SAP with great safety. Human studies using this novel therapy are required to assess these potential benefits in the clinical setting.

Does higher hospital volume improve the patient outcome in acute pancreatitis?

Over the past decade, many studies have shown a significant association between the volume of hospital services and patient outcomes for a wide variety of medical conditions [1–3]. As regards acute pancreatitis, several population-based studies have shown higher hospital volume to be associated with better outcomes [4–6]. Especially, a lower mortality rate, shorter length of hospital stay and lower total costs had been shown with higher hospital volume. However, acute pancreatitis has a wide range of severity and mortality; especially severe acute pancreatitis has a high mortality rate and longer length of hospital stay. In clinical situations, several severity scoring systems have been used for judging the severity grading and making decisions for how to treat patients depending on the grading all over the world. Furthermore, various potentially effective treatments for acute pancreatitis, e.g. enteral nutrition, continuous hemofiltration, continuous regional arterial infusion, and endoscopic treatments, etc. are performed for severe acute pancreatitis. However, effectiveness and cost-performance analyses of those techniques have not been proven at this time. In addition, the mortality rate of each institution was not described, even for high volume centers. That is to say, a lot of clinicians have a great deal of concern about the volume–outcome relationship in order to perform effective treatments and decide referral patterns to improve mortality rates. In the current context, Professor Hamada et al. [7] are to be congratulated for performing the extremely large-scale study about clinical outcomes of acute pancreatitis based on the Japanese administrative database associated with the diagnostic procedure combination system (DPC). This is the first study to have successfully adjusted for baseline disease severity using an established scoring system to evaluate the volume–outcome relationship in acute pancreatitis. Unlike other analyses, this study focused on the hospital–volume relationship and severity of acute pancreatitis based on the Japanese Severity Scoring system [8]. Additionally, the researchers include adjustments for severity grading and assessment of the potential non-linear relationship between hospital volume and outcomes by means of restricted cubic spline (RCS) functions. As a result, the median length of hospital stay was 14 days (range 10–22 days) in Japan. Their analysis demonstrated that the median hospital volume was 22.4 (range 1–82 case/year), and higher hospital volume was associated with shorter length of stay (overall relationship p 0.001), however not evident in in-hospital mortality and total costs. Using the same Japanese DPC system database, Murata et al. [8] showed that increased hospital volume, which was categorized into tertiles, was significantly associated with decreased relative risk of in-hospital mortality in both patients with mild and severe acute pancreatitis. Meanwhile Professor Hamada et al. used the annual number of cases, not categorized, admitted to each individual hospital and mentioned that the correlation between the patients in the same hospital can be taken into account with using generalized estimating equations (GEE). Exactly this groundbreaking method was performed. So what is the key to have a better outcome and an effective utilization of medical resources? The clinical This comment refers to the article available at doi:10.1007/s00535013-0888-9.

Usefulness of Early-phase Peritoneal Lavage for Treating Severe Acute Pancreatitis

To improve the prognosis of severe acute pancreatitis, preventing infectious complications, particularly infected pancreatic necrosis, is important. The present study evaluated the efficacy of peritoneal lavage for improving the prognosis of patients with severe acute pancreatitis. We retrospectively reviewed the cases of 23 consecutive patients with severe acute pancreatitis who were treated with peritoneal lavage. Peritoneal lavage was started within 72 hours after the initial onset of symptoms in 20 patients (87%). The duration of peritoneal lavage, which was significantly correlated with the number of prognostic factors according to the revised Japanese criteria, Ranson score and serum C-reactive protein level at the start of peritoneal lavage, was a median of seven (3-22) days. There were no adverse events associated with the peritoneal lavage. Eight patients (35%) concurrently underwent continuous regional arterial infusion. Five days after starting peritoneal lavage, the patients' clinical conditions significantly improved. Overall, the survival rate was 96%. One patient (4%) died due to rupture of a pseudoaneurysm of the splenic artery. Complications occurred in seven patients (30%). Infectious complications were observed in three patients (13%) (one patient developed infected pancreatic necrosis and bacteremia, and two patients developed bacteremia). Pseudocysts and pancreatic fistulas developed in five and one patient, respectively. The incidence of complications was lower in the patients receiving peritoneal lavage within 72 hours from the initial onset of symptoms than in the remaining patients (20% vs. 100%; p=0.005). We speculate that peritoneal lavage reduces the mortality and incidence of complications in patients with severe acute pancreatitis.

Treatment of severe acute pancreatitis

Acute pancreatitis is an acute inflammatory process of the pancreas with variable involvement of other regional tissues or other organ systems. The severe form of the disease occurs in 10-20% of cases, and usually requires prolonged hospitalization due to a frequent local and systemic complications. Additionally, considerable mortality despite diagnostic and therapeutic advances, makes this disease a serious health problem nowadays. The aim of this study was to conduct a review of randomized controlled trials to determine differences in the efficiency between standard methods of treatment for severe acute pancreatitis and new treatment ways in terms of decreased mortality. Search of the 'Medline' database of original scientific papers and systematic review articles was made, using a combination of the following keywords: acute pancreatitis, treatment, mortality. In total 914 papers were found, published in the last 13 years; 14 of 64 randomized controlled clinical trials met the selection criteria and were eligible for inclusion. From a total of 16 papers, the conservative treatment was related to 11, which includes some of the new treatment methods, while the effects of new methods of treatment have been the subject of research in the four studies. Combined endoscopic and surgical treatment was applied in only one study. The largest sample of 290 patients was included in the study with platelet activation factor antagonist, while the smallest sample of 22 patients was used in the study that compared total parenteral with enteral nutrition. Continuous regional arterial infusion of protease inhibitors in combination with antibiotics, intravenous supplementation of alanyl-glutamine dipeptide and the early, high-volume continuous veno-venous hemofiltration showed the best results in the treatment of patients with severe acute pancreatitis. Also, the use of low molecular weight heparin and enteral nutrition significantly reduced mortality.

重症急性膵炎における膵局所動注療法の有用性と適応

重症急性膵炎における膵局所動注療法の有用性と適応

Correction: Continuous Regional Arterial Infusion with Fluorouracil and Octreotide Attenuates Severe Acute Pancreatitis in a Canine Model

Correction: Continuous Regional Arterial Infusion with Fluorouracil and Octreotide Attenuates Severe Acute Pancreatitis in a Canine Model