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12 April 2023: Clinical Research  

Clinical Evaluation of Continuous Renal Replacement Therapy Combined with Peritoneal Lavage for Severe Acute Pancreatitis: A Retrospective Cohort Study

Wen-zhu Jiang1EF, Hong-jie Zhao2BC, Lu Chen3DF, Xiao-dong Tang3DF, Zhicheng Deng3AE*

DOI: 10.12659/MSM.939314

Med Sci Monit 2023; 29:e939314

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Abstract

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BACKGROUND: We aimed to investigate the clinical efficacy of continuous renal replacement therapy (CRRT) in combination with peritoneal lavage for the treatment of severe acute pancreatitis.

MATERIAL AND METHODS: We retrospectively reviewed data from 52 patients with severe acute pancreatitis between January 2014 and December 2021 at Jiangyin People’s Hospital. The patients were divided into 2 groups: CRRT (n=26) and CRRT in combination with peritoneal lavage (n=26). The following results and outcomes were retrospectively compared: procalcitonin, interleukin-6, and C-reactive protein levels, duration of systemic inflammatory response, Acute Physiology and Chronic Health Evaluation II (APACHE II) scores, abdominal distention relief time, abdominal pain relief time, length of intensive care unit stay, length of hospital stay, inpatient hospital costs, incidence of complications, and mortality.

RESULTS: There were significant differences in interleukin-6 and procalcitonin levels and APACHE-II scores after 3 and 7 days of treatment. The duration of systemic inflammatory response, abdominal distention relief time, abdominal pain relief time, length of intensive care unit stay, and length of hospital stay were considerably shorter in the combination group than in the CRRT group (P<0.01). Inpatient hospital costs were significantly lower in the combination group than in the CRRT group (P<0.01). However, incidence of complications and mortality showed no significant differences between the 2 groups.

CONCLUSIONS: CRRT combined with peritoneal lavage is an important adjuvant therapy in the early stages of acute severe acute pancreatitis and has better clinical efficacy than CRRT alone.

Keywords: Peritoneal Lavage, Severity of Illness Index, Acute Disease, Pancreas, Humans, Continuous Renal Replacement Therapy, Pancreatitis, Interleukin-6, procalcitonin, Abdominal Pain, Systemic Inflammatory Response Syndrome

Background

Severe acute pancreatitis (SAP) is an inflammatory disorder of the pancreas that results in a hyperdynamic and hypermetabolic process caused by the self-digestion of pancreatic acinar cells and other factors, such as pro-inflammatory cytokines and chemokines. It is a dangerous gastrointestinal condition characterized by sustained organ failure for >48 h and has a high mortality rate [1–3]. The production of a substantial number of inflammatory mediators in the early stages of SAP can result in a systemic inflammatory response syndrome (SIRS) [4] and inflammatory cell infiltration [5–8].

Early organ failure, defined as organ failure occurring within the first 3 days after onset, is linked to mortality in patients with SAP. According to a report [9], the death rate of patients with SAP with early organ failure can be 15% to 20%. It is well known that a treatment window of 48 to 72 h after commencement is required to avoid additional harm, by neutralizing inflammatory cytokines [10]. It is critical to provide suitable early treatment, correct severity assessment, sufficient infusion therapy, and a more comprehensive treatment according to the patient’s circulation and breathing, which can increase the treatment success rate. Clinical physicians often adopt less invasive techniques, including continuous renal replacement therapy (CRRT) or peritoneal lavage (PL) to treat SAP.

CRRT is commonly performed in the Intensive Care Unit (ICU) [11–13]. CRRT is advantageous for cytokine elimination [14] and cardiovascular function [15–17], in addition to supporting failing kidneys. Although multiple studies [6,13,18] showed that early application can enhance outcomes, the benefits of CRRT remain controversial. Xu et al reported that early CRRT had no benefit for patients with SAP with early organ failure [19]. Lin et al demonstrated that it is unclear whether CRRT could reduce mortality and avoid local or systemic complications [20].

PL has been used for patients with SAP and intraperitoneal fluids. It can eliminate toxins and metabolites from the peritoneal cavity, reduce systemic absorption, and influence SIRS and organ failure [21–23]. Some reports have demonstrated that PL can reduce cardiopulmonary complications [24–28]; however, a comprehensive evaluation of 10 randomized controlled trials including 469 patients showed that PL did not lead to a significant change in death and complications [23]. Dong et al demonstrated that PL did not confer clinical benefit in patients with SAP [29].

Because previous studies demonstrated that CRRT or PL monotherapy was controversial in critically ill patients with SAP, we combined these 2 technologies to treat SAP. To investigate the impact of CRRT combined with PL, we retrospectively analyzed the data of patients with SAP in our department.

Material and Methods

From January 2014 to December 2021, a total of 52 patients with SAP were admitted to our hospital. SAP was diagnosed in accordance with the Atlanta criteria [2]. According to the Declaration of Helsinki and its amendments, informed written consent was obtained from each patient. This study was approved by the Medical Ethics Committee of the hospital.

Patients in both groups were treated with nil by mouth, oxygen administration, nasogastric aspiration, intravenous fluid resuscitation, nutritional support, prophylactic antibiotics, and appropriate analgesic-antispasmodic therapy. CRRT was initiated when the SIRS score was >2 and/or persistent organ failure occurred (>48 h), stage 3 acute kidney injury developed complications, or when fluid overload caused respiratory compromise (PaO2/FiO2 <200) [30].

We percutaneously inserted a double-lumen catheter into the femoral vein or right internal jugular vein to establish temporary vascular access. The blood flow rate was 200 to 220 mL/min. The dialyzer was changed every 4 to 12 h using the predilution mode. The surface area was set to 1.8 to 2.1 m2. Hemofiltration was continuously performed for 24 h; we used 3000 mL 0.9% saline (Baxter) as the replacement solution. According to the specific conditions of the patients, the electrolyte composition was adjusted and the acid-base imbalance was modified. Low-molecular-weight heparin was administered at the start of continuous venovenous hemofiltration to prevent clotting. In patients with a bleeding tendency, heparin was replaced with potassium citrate.

For PL, a 12 F pigtail catheter was inserted into the pelvic cavity and peritoneal dialysate was changed every 2 to 4 h. The process was continued for approximately 7 days.

The selection criteria were as follows: according to the Atlanta criteria, SAP as defined by persistent organ failure that persists for >48 h; organ failure as defined by the presence of at least 1 of the following: renal, pulmonary, or circulatory failure; Ranson score >3 [31]; and Acute Physiology and Chronic Health Evaluation II (APACHE-II) score >8 [32].

Exclusion criteria included biliary pancreatitis with need for emergency surgery, endoscopic retrograde cholangiopancreatography, percutaneous transhepatic gallbladder drainage, and abdominal compartment syndrome.

CT Severity Index score [33] and biochemical and hematologic characteristics, including procalcitonin (PCT), interleukin-6 (IL-6), and C-reactive protein (CRP) levels were reviewed. The following clinical parameters were recorded: duration of SIRS, APACHE-II scores, abdominal distention relief time, abdominal pain relief time, length of ICU stay, length of hospital stay, inpatient hospital costs, incidence of complication, and mortality.

All data were statistically analyzed using SPSS 19.0 software. The t test was used for normally distributed quantitative data, U-test for non-normally distributed quantitative data, and χ2 test or Fisher exact test for categorical data. P<0.05 represents a statistically significant difference.

Results

Table 1 displays the intergroup comparison of patients’ baseline clinical characteristics. At admission, the 2 groups were compared in terms of age, sex, body mass index, etiology, creatinine, serum amylase, total-bilirubin, PCT, IL-6, CRP, triglycerides, APACHE-II, Ranson scores, CT Severity Index score, and multiple organ failure. The patients in the combined group were 42.3±11.8 years old and the CRRT group was 43.6±12.1 years old (P=0.696). The causes of pancreatitis in the combined group were gallstones (n=12), alcohol abuse (n=4), hyperlipidemia (n=6), and other (n=4), while those in the CRRT group were gallstones (n=15), alcohol abuse (n=4), hyperlipidemia (n=5), and other (n=2) (P=0.822). There were no significant differences in creatinine, serum amylase, total bilirubin, PCT, IL-6, CRP, triglycerides, APACHE-II scores, Ranson scores, CT Severity Index score, and multiple organ failure between the 2 groups. Table 2 shows the intergroup comparison of CRP, PCT, IL-6, and APACHE-II scores at 3 and 7 days after treatment. At 3 and 7 days after treatment, CRP, PCT, IL-6, and APACHE-II scores significantly decreased (P<0.05). The duration of SIRS was 3.5±2.1 in the combined group and 6.7±2.8 in the CRRT group (P<0.01). The length of ICU stay was 15.3±1.2 in the combined group and 20.6±2.4 in the CRRT group (P<0.01). The abdominal distention relief time, abdominal pain relief time, and length of hospital stay were considerably shorter in the combined group than in the CRRT group (P<0.01). Inpatient hospital costs were significantly lower in the combined group than in the CRRT group (P<0.01). Incidence of complication and mortality showed no significant difference between the 2 groups. The complications in the combined group were acute respiratory distress syndrome (n=2), acute renal failure (n=1), abdominal infection (n=1), and multiple organ dysfunction syndrome (n=1), while in the CRRT group they were acute respiratory distress syndrome (n=2), acute renal failure (n=1), circulatory failure (n=1), and multiple organ dysfunction syndrome (n=2). One patient died of multiple organ failure (MOF) in the combined group, and 3 patients died during treatment in the CRRT group; 2 died of MOF and 1 died because of circulatory failure.

Discussion

The first peak of death in SAP occurs during the acute response period because of multiple organ insufficiency or MOF [34,35]. Less invasive techniques, including CRRT and PL, have been gradually used to attenuate the “hits” of SAP by clinical physicians for patients with SAP. We used CRRT combined with PL to treat SAP. The advantage of PL is that it has not only the ability to purify ascites but also to treat peritoneal exudate [36]. Physicians can observe and calculate the retained fluid accurately. It is simple and easy to perform at the bedside in critically ill patients.

Several studies reported that, when performed early, CRRT was beneficial in critically ill patients [11,37]. CRRT can remove some inflammatory mediators, including endotoxins and IL-6, in the blood through adsorption and convection, which can prevent the response process of inflammatory factors, restore the dynamic balance of anti-inflammatory and pro-inflammatory factors, and improve the internal environment. For patients with hyperlipidemia, CRRT not only removes the etiology, but is also a comprehensive treatment. However, a previous study suggested that CRRT has no benefit on the prognosis of critically ill patients [19].

In this study, we combined CRRT and PL to treat SAP patients with a Ranson score >3 points and an APACHE-II score >8 points. We found that CRP, PCT, and IL-6 levels in the combined group were significantly lower than those in the CRRT group, and the duration of SIRS, abdominal distention relief time, and abdominal pain relief time were shorter. This indicated that the combined application of CRRT and PL not only quickly removed harmful and toxic substances and various chemical media in ascites and blood, but also purified blood and maintained hemodynamic stability compared with CRRT alone. The Ranson and APACHE-II scores are currently widely used clinically to evaluate the severity of acute pancreatitis. In this study, we found that the APACHE-II scores in the combined group were considerably lower than those in the CRRT group. Only 1 patient died of MOF, and the rest were free of the risk of early death in the combination group. In the CRRT group, 2 patients died of MOF and 1 died because of circulatory failure. Patients in the combined group had shorter ICU and hospital stays and lower hospital costs than patients in the CRRP group, which indicated that CRRT and the combined application of PL could help improve the prognosis of patients. However, this study also demonstrated that CRP, PCT, and IL-6 levels did not completely return to normal after early combined treatment, and we further found that CRP, PCT, and IL-6 levels increased after treatment in some cases, which suggested that pancreatic necrosis may exist. Regular enhanced CT and fine-needle aspiration might be used for the early detection of local pancreatic complications and to re-evaluate the extent of pancreatic necrosis, infection, combined organ dysfunction, and disease progression. Appropriate treatment methods, including percutaneous drainage and necrotic tissue debridement, were performed in the later phase. In this study, there were 2 cases of lung infection and sepsis, 1 case of pancreatic abscess and intestinal fistula, and 2 cases of infectious pancreatic necrosis in the later stages in the combined group, while 1 case of lung infection and sepsis, 2 cases of bleeding, 4 cases of infectious pancreatic necrosis happened in the CRRT group, which demonstrated that SAP required integrated treatment after the acute phase.

This study has some limitations. The number of samples included in this research was limited. This is a retrospective study and more research, for example a prospective study, is needed to prove the point of this paper. However, this study indicated that CRRT with PL was beneficial in patients with SAP compared with CRRT alone.

Conclusions

CRRT combined with PL is an important adjuvant therapy in the early stage of acute severe pancreatitis and has good clinical efficacy.

In the future, well-designed large-scale comparison studies will be necessary to acquire a better understanding of this issue.

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