Effect of high-dose intravenous vitamin C therapy on the prognosis in patients with moderately severe and severe acute pancreatitis: protocol of a prospective, randomized, double-blinded, placebo-controlled study.

Introduction: Acute pancreatitis is a common gastrointestinal disease. The mortality of patients affected by severe acute pancreatitis (SAP) remains high. It is unclear whether high-dose intravenous vitamin C (HDIVC) therapy could improve the prognosis of these patients. The current prospective, randomized, double-blinded, placebo-controlled study will explore the effect of high-dose intravenous vitamin C therapy on the prognosis in patients with moderately severe and severe acute pancreatitis. Methods and design: A total of 418 participants with moderately severe and severe acute pancreatitis who meet the eligible criteria will be randomly assigned in a 1:1 ratio to receive treatment with HDIVC (200 mg/kg/24 h) or placebo (saline) for a period of 7 days. The primary outcome is 28-day mortality in these patients. The secondary outcomes include organ functions and interventions, laboratory tests, healthcare, and 90-day mortality. Ethics and dissemination: This protocol was approved by the institutional ethics board of the Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China (Registration Number: 2019-90). The report of the study will be published in peer-reviewed journals and presented at conferences, both nationally and internationally. Clinical trial registration: Chinese Clinical Trial Registry (ChiCTR1900022022). Version 1.5.

High-Dose Vitamin C Alleviates Pancreatic Necrosis by Inhibiting Platelet Activation Through the CXCL12/CXCR4 Pathway in Severe Acute Pancreatitis.

Background: Platelet activation in the early stage of pancreatitis is the key step developing into pancreatic necrosis. Studies suggested that vitamin C (Vit C) can inhibit platelet activity by targeting CXCL12/CXCR4 pathway. High-dose Vit C were showed to reduce pancreatic necrosis in severe acute pancreatitis (SAP) but the mechanism remains unclear. Here we speculate high-dose Vit C reduce pancreatic necrosis by inhibiting platelet activation through downregulating CXCL12/CXCR4 pathway. Methods: The pancreatic microcirculation of rats was observed by intravital microscopy. The platelet activity of SAP rats treated with or without high-dose Vit C was analyzed by platelet function test. Besides, the activity of platelets preincubated with high-dose Vit C or vehicle from SAP patients was also evaluated. Then, the TFA (CXCR4 agonist) and rCXCL12 were used to neutralize the effect of high-dose Vit C in SAP rats treated with high-dose Vit C. Meanwhile, the levels of enzymes and inflammatory cytokines in rat plasma, and rats' pancreatic histopathology and mortality were assessed. Results: Platelets from animals and patients with SAP are more sensitive to agonists and are more easily activated. Administration of high-dose Vit C significantly ameliorated excessive activation of platelets in SAP rats, ultimately increasing the microvessel density and inducing microthrombus and blood stasis; these results were consistent with clinical sample analysis. Moreover, high-dose Vit C significantly inhibited the release of amylase, lipase, TNF-α, and IL-6 in SAP rat plasma, reducing pancreatic damage and the mortality of SAP rats. However, using TFA and rCXCL12 significantly reversed the effect of high-dose Vit C on excessive activation of platelets, aggravating microcirculation impairment and pancreatic damage. Conclusion: The present study suggests that high-dose Vit C can ameliorate pancreatic necrosis by improving microcirculation disorders of SAP. For the first time, the underlying mechanism is related with inhibiting platelet activation through the CXCL12/CXCR4 pathway.

High-dose vitamin C on sepsis: Protocol of a prospective, multi-centered, double-blinded, randomized, and placebo-controlled superiority study.

Background: Sepsis is an inflammatory syndrome with life-threatening organ dysfunction and high mortality. In the recent 10 years, high-dose intravenous injection of vitamin C, the first-line antioxidant of humans, has received highlighted attention in the field of critical care. The study aims to examine the efficacy and safety of high-dose intravenous injection of vitamin C in the treatment of sepsis. Methods and design: Here, we are conducting a prospective, multi-centered, double-blinded, randomized, and placebo-controlled superiority study named High-Dose Vitamin C on Sepsis (HDVCOS). A total of 620 participants diagnosed with sepsis in four participating sites across China that satisfy the eligibility criteria will be randomized at a ratio of 1:1 to receive treatment with a high-dose intravenous injection of vitamin C (200 mg/kg/24 h) or placebo (saline) for 4 days. The primary outcome is 28 days of mortality. The secondary outcomes include the incidence of organ failure, Sequential Organ Failure Assessment (SOFA) score change, organ support, the relationship between plasma vitamin C concentration and outcomes, and adverse events. Conclusion: The findings of this study will provide potential evidence for high-dose intravenous injection of vitamin C in the treatment of sepsis. Clinical trial registration: [http://www.chictr.org.cn/showprojen.aspx?proj=29851], identifier [ChiCTR1800017633].

The impact of fluid resuscitation via colon on patients with severe acute pancreatitis.

Severe acute pancreatitis (SAP) is a life-threatening disease. Fluid Resuscitation Via Colon (FRVC) may be a complementary therapy for early controlled fluid resuscitation. But its clinical application has not been reported. This study aims to explore the impact of FRVC on SAP. All SAP patients with the first onset within 72 h admitted to the hospital were included from January 2014 to December 2018 through electronic databases of Ruijin hospital and were divided into FRVC group (n = 103) and non-FRVC group (n = 78). The clinical differences before and after the therapy between the two groups were analyzed. Of the 181 patients included in the analysis, the FRVC group received more fluid volume and reached the endpoint of blood volume expansion ahead of the non-FRVC group. After the early fluid resuscitation, the inflammation indicators in the FRVC group were lower. The rate of mechanical ventilation and the incidence of hypernatremia also decreased significantly. Using pure water for FRVC was more helpful to reduce hypernatremia. However, Kaplan-Meier 90-day survival between the two groups showed no difference. These results suggest that the combination of FRVC might benefit SAP patients in the early stage of fluid resuscitation, but there is no difference between the prognosis of SAP patients and that of conventional fluid resuscitation. Further prospective study is needed to evaluate the effect of FRVC on SAP patients.

High Dose Intravenous Vitamin C for Preventing The Disease Aggravation of Moderate COVID-19 Pneumonia. A Retrospective Propensity Matched Before-After Study.

Background: Coronavirus disease 2019 (COVID-19) pandemic is continuing to impact multiple countries worldwide and effective treatment options are still being developed. In this study, we investigate the potential of high-dose intravenous vitamin C (HDIVC) in the prevention of moderate COVID-19 disease aggravation. Methods: In this retrospective before-after case-matched clinical study, we compare the outcome and clinical courses of patients with moderate COVID-19 patients who were treated with an HDIVC protocol (intravenous injection of vitamin C, 100 mg/kg/day, 1 g/h, for 7 days from admission) during a one-month period (between March 18 and april 18, 2020, HDIVC group) with a control group treated without the HDIVC protocol during the preceding two months (January 18 to March 18, 2020). Patients in the two groups were matched in a 1:1 ratio according to age and gender. Results: The HDIVC and control groups each comprised 55 patients. For the primary outcomes, there was a significant difference in the number of patients that evolved from moderate to severe type between the two groups (HDIVC: 4/55 vs. control: 12/55, relative risk [RR] = 0.28 [0.08, 0.93], P = 0.03). Compared to the control group, there was a shorter duration of systemic inflammatory response syndrome (SIRS) (P = 0.0004) during the first week and lower SIRS occurrence (2/21 vs 10/22, P = 0.0086) on Day 7 (6-7 days after admission). In addition, HDIVC group had lower C-reactive protein levels (P = 0.005) and higher number of CD4+ T cells from Day 0 (on admission) to Day 7 (P = 0.04)." The levels of coagulation indicators, including activated partial thromboplastin time and D-dimer were also improved in the HDIVC compared to the control group on Day 7. Conclusion: HDIVC may be beneficial in limiting disease aggravation in the early stage of COVID-19 pneumonia, which may be related to its improvements on the inflammatory response, immune function and coagulation function. Further randomized controlled trials are required to augment these findings.

Epidemiology, species distribution, and outcome of nosocomial Candida spp. bloodstream infection in Shanghai: an 11-year retrospective analysis in a tertiary care hospital.

BACKGROUND: The incidence of Candida bloodstream infections (BSIs), has increased over time. In this study, we aimed to describe the current epidemiology of Candida BSI in a large tertiary care hospital in Shanghai and to determine the risk factors of 28-day mortality and the impact of antifungal therapy on clinical outcomes. METHODS: All consecutive adult inpatients with Candida BSI at Ruijin Hospital between January 1, 2008, and December 31, 2018, were enrolled. Underlying diseases, clinical severity, species distribution, antifungal therapy, and their impact on the outcomes were analyzed. RESULTS: Among the 370 inpatients with 393 consecutive episodes of Candida BSI, the incidence of nosocomial Candida BSI was 0.39 episodes/1000 hospitalized patients. Of the 393 cases, 299 (76.1%) were treated with antifungal therapy (247 and 52 were treated with early appropriate and targeted antifungal therapy, respectively). The overall 28-day mortality rate was 28.5%, which was significantly lower in those who received early appropriate (25.5%) or targeted (23.1%) antifungal therapy than in those who did not (39.4%; P = 0.012 and P = 0.046, respectively). In multivariate Cox regression analysis, age, chronic renal failure, mechanical ventilation, and severe neutropenia were found to be independent risk factors of the 28-day mortality rate. Patients who received antifungal therapy had a lower mortality risk than did those who did not. CONCLUSIONS: The incidence of Candida BSI has increased steadily in the past 11 years at our tertiary care hospital in Shanghai. Antifungal therapy influenced short-term survival, but no significant difference in mortality was observed between patients who received early appropriate and targeted antifungal therapy.

Effect of high-dose intravenous vitamin C on point-of-care blood glucose level in septic patients: a retrospective, single-center, observational case series.

INTRODUCTION: High-dose vitamin C is an essential adjunctive drug for sepsis treatment. This study aimed to determine if high-dose vitamin C could lead to erroneous point-of-care glucose testing results. METHODS AND MATERIALS: This retrospective, single-center, observational case series involved septic patients treated with high-dose vitamin C. We monitored their paired point-of-care glucose and laboratory glucose levels for statistical analysis. The glucose oxidase-peroxidase colorimetric method and hexokinase spectrophotometric method were applied for point-of-care glucose and laboratory glucose monitoring, respectively. Parkes Consensus Error Grid Analysis was used to assess the clinical influence of paired blood glucose values. Subgroup analyses were conducted to explore the effect of different vitamin C dosages and various renal function levels on point-of-care glucose readings. RESULTS: During a 3-year period, 82 eligible septic patients who accepted at least three days of high-dose vitamin C treatment were included in this study. Compliance with ISO15197:2013 criteria was met in 30 (36.59%) paired values, a proportion considerably lower than the minimum criteria for accuracy. Subgroup analysis showed that worse renal function or higher vitamin C dosage could lead to greater bias in point-of-care glucose readings; however, these inaccuracies rarely represented a clinical risk. CONCLUSIONS: High-dose intravenous ascorbate acid infusion may interfere with point-of-care glucose testing results. Thus, laboratory glucose measurements are recommended for more accurate results. Nonetheless, the inaccuracies magnitude of point-of-care glucose readings does not represent a significant clinical risk when physicians alter clinical action based on these results.

Vitamin C supplementation is necessary for patients with coronavirus disease: An ultra-high-performance liquid chromatography-tandem mass spectrometry finding.

To administer vitamin C (VC) with precision to patients with the coronavirus disease (COVID-19), we developed an ultra-high-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) method to assess plasma VC concentrations. 31 patients with COVID-19 and 51 healthy volunteers were enrolled. VC stability was evaluated in blood, plasma, and precipitant-containing stabilizers. A proportion of 7.7 % of VC was degraded in blood at room temperature (RT) (approximately 20-25 °C) at 1.5 h post administration with respect to the proportion degraded at 0.5 h, but without statistical difference. VC was stable in plasma for 0.75 h at RT, 2 h at 4 °C, 5 days at -40 °C, and 4 h in precipitant-containing stabilizer (2 % oxalic acid) at RT. The mean plasma concentration of VC in patients with COVID-19 was 2.00 mg/L (0.5-4.90) (n = 8), which was almost 5-fold lower than that in healthy volunteers (9.23 mg/L (3.09. 35.30)) (n = 51). After high-dose VC treatment, the mean VC concentration increased to 13.46 mg/L (3.93. 34.70) (n = 36), higher than that in healthy volunteers, and was within the normal range (6-20 mg/L). In summary, we developed a simple UPLC-MS/MS method to quantify VC in plasma, and determined the duration for which the sample remained stable. VC levels in patients with COVID-19 were considerably low, and supplementation at 100 mg/kg/day is considered highly essential.

Vitamin C attenuates vancomycin induced nephrotoxicity through the reduction of oxidative stress and inflammation in HK-2 cells.

BACKGROUND: Oxidative stress is one of the possible mechanisms in vancomycin (VCM) induced nephrotoxicity. Some studies suggested that high dose Vitamin C (VC) has protective effect against the nephrotoxicity in mice, but the underlying molecular mechanism is not mentioned. We investigated the potential targets of high dose VC against oxidative stress and inflammation induced by VCM in renal tubular epithelial cells. METHODS: We conducted an in vitro study using an immortalized proximal tubule epithelial cell line from a normal adult human kidney (HK-2). RESULTS: VCM added to HK-2 cells caused an increase of cell death, oxidative stress and expression of inflammatory cytokines. Co-treatment with 0.5 and 1 mM VC attenuated 4-8 mM VCM induced cell death and increased the cell viability to 58-90%. VC significantly decreased lipid peroxidation and increased superoxide dismutase activity. The upregulations of NF-κB, TNF-α and IL-6 in HK-2 cells under 4 mM VCM were also reversed by 0.5 mM VC through the inhibition of oxidative stress. CONCLUSIONS: This study showed for the first time that VC can attenuate the VCM induced nephrotoxicity by decreasing lipid peroxidation and expression of inflammatory cytokines, and increasing superoxide dismutase 2 (SOD2) activity, this effect may relate to the regulation of ROS/NF-κB pathway.

Beneficial aspects of high dose intravenous vitamin C on patients with COVID-19 pneumonia in severe condition: a retrospective case series study.

BACKGROUND: Coronavirus disease 2019 (COVID-19) is a global public health event without specific therapeutic agents till now. We aim to determine if high dose intravenous vitamin C (HDIVC) was effective for COVID-19 patients in severe condition. METHODS: COVID-19 patients admitted in Shanghai Public Health Clinical Center from January 22, 2020 to April 11, 2020 were retrospectively scrolled. The enrolled patients were those with confirmed diagnosis of severe or critical COVID-19 pneumonia, who received HDIVC within 24 hours after disease aggravation. Main clinical outcomes obtained from 3-5 days (day 3) and 7-10 days (day 7) after HDIVC were compared to the ones just before (day 0) HDIVC. RESULTS: Totally, twelve patients were enrolled including six severe [age of mean, 56; interquartile range (IQR), 32-65 years, 3 men] and six critical (age of mean, 63; IQR, 60-82 years, 4 men) patients. The dosage of vitamin C [median (IQR), mg/kg (body weight)/day] were [162.7 (71.1-328.6)] for severe and [178.6 (133.3-350.6)] for critical patients. By Generalized estimating equation (GEE) model, C-reactive protein (CRP) was found to decrease significantly from day 0 to 3 and 7 (severe: 59.01±37.9, 12.36±22.12, 8.95±20.4; critical: 92.5±41.21, 33.9±30.2, 59.56±41.4 mg/L). Lymphocyte and CD4+ T cell counts in severe patients reached to normal level since day 3. Similar improving trends were observed for PaO2/FiO2 (severe: 209.3±111.7, 313.4±146, 423.3±140.8; critical: 119.9±52.7, 201.8±86.64, 190.5±51.99) and sequential organ failure assessment score (severe: 2.83±1.72, 1.33±1.63, 0.67±1.03; critical: 6.67±2.34, 4.17±2.32, 3.83±2.56). Better improving effect was observed in severe than critical patients after HDIVC. CONCLUSIONS: HDIVC might be beneficial in aspects of inflammatory response, immune and organ function for aggravation of COVID-19 patients. Further clinical trials are in warrant. TRIAL REGISTRATION: This trial has been retrospectively registered in Chinese Clinical Trail Registry (ChiCTR2000032716) on May 8, 2020. http://www.chictr.org.cn/showproj.aspx?proj=53389.

High-dose vitamin C alleviates pancreatic injury via the NRF2/NQO1/HO-1 pathway in a rat model of severe acute pancreatitis.

BACKGROUND: Oxidative stress plays a pivotal role in the progress of severe acute pancreatitis (SAP). Vitamin C (VC) is the most important antioxidant in plasma. However, the effects of an intravenous administration of high-dose VC and the mechanisms by which it exerts its antioxidant function in an experimental model of SAP have not been determined. METHODS: Sodium taurocholate was used to induce rat pancreatic injury and AR42J cells injury. After the establishment of SAP model, SAP rat and injured AR42J cells were treated with VC. For the injured AR42J cells, small interfering RNA-mediated knockdown of NRF2 was conducted after VC treatment. The histopathological characteristics, the apoptosis of pancreatic acinar cells, oxidative stress markers and levels of enzymes, biochemical indicators, and inflammatory cytokines were examined in vivo and in vitro. Furthermore, the mortality of rats was assessed. RESULTS: In vivo and in vitro results demonstrated that VC treatment ameliorated apoptosis of pancreatic acinar cells, as evidenced by the increase in Bcl-2, Bcl-XL, and MCL-1 expressions and decrease in Bax and cleaved caspase-3 expression along with decreased TUNEL-positive cells. Also, we found that the elevation of MDA and decrease of SOD, GPx, GSH/GSSG, and T-AOC induced by SAP were reversed by VC treatment in vivo and in vitro, and VC treatment increased expressions of Nrf2, NQO1, and HO-1 in SAP model at protein and gene level, indicating that VC attenuated oxidative stress via the NRF2/NQO1/HO-1 pathway. Meanwhile, it was found that sodium taurocholate significantly induced the release of amylase, lipase, IL-1ß, and IL-6 in rat plasma and AR42J cells, which were declined by VC treatment. In vitro results also revealed that these alterations in sodium taurocholate-injured AR42J cells due to VC treatment was attenuated by NRF2 knockdown. In addition, VC at a dose of 500 mg/kg decreased the levels of lactic acid, Cre, NGAL, AST, and ALT in the plasma of SAP rats, suggesting the improvement of renal and pancreatic injury and liver function of SAP rats. Furthermore, the mortality of SAP rats was 50%, which declined to 30% after VC treatment. CONCLUSIONS: The present study suggests that high-dose of VC ameliorate pancreatic injury of SAP via the NRF2/NQO1/HO-1 pathway to inhibit oxidative stress.

[High dose vitamin C significantly reduces the nephrotoxicity of vancomycin in critically ill patients].

OBJECTIVE: To observe the changes of renal function in critically ill patients using vancomycin and analyze the renal protective effect of high dose vitamin C (VC) on vancomycin nephrotoxicity. METHODS: Retrospective analysis was carried out to enroll the patients who were hospitalized in emergency intensive care unit (ICU) of Ruijin Hospital Affiliated to Shanghai Jiao Tong University School of Medicine from January 2012 to October 2019. All patients were administered with vancomycin or VC infusion in addition. According to the infusion of vancomycin alone or in combination with VC, the patients were divided into vancomycin group and vancomycin in combination with VC group; vancomycin group was further divided into two groups according to before vancomycin or after vancomycin usage; combination group were further divided into two groups according to before VC use or after VC. The initial dosage of vancomycin was calculated according to the actual weight of the patient and adjusted according to the renal function. The dosage of VC was determined according to the disease severity of the patient, and the dosage range was 50-200 mg×kg-1×d-1, continuously infused into the body. The age, gender, weight and renal function etc. were recorded and analyzed. RESULTS: A total of 245 patients who met the requirements were included in the analysis. There were 127 patients in the vancomycin group and 118 patients in the combination group. The causes of patients admitted to ICU were pulmonary infection, sepsis, severe acute pancreatitis, etc. Among them, pulmonary infection accounted for 63.0% in vancomycin group, while severe acute pancreatitis accounted for 61.9% in combination group. The quick sequential organ failure assessment (qSOFA) score of combination group was significantly higher than that of vancomycin group [1.0 (0, 1.0) vs. 0 (0, 0.2), P < 0.01], its basic renal function was also significantly worse [serum creatinine (SCr, µmol/L): 98.0 (65.0, 178.2) vs. 56.0 (42.2, 71.0), blood urea nitrogen (BUN, mmol/L): 11.30 (6.48, 18.38) vs. 4.70 (3.45, 8.10), both P < 0.05], and the average daily dose of vancomycin was also significantly lower than that of vancomycin group (mg×kg-1×d-1: 23.0±9.4 vs. 26.6±8.5, P < 0.01). Compared with vancomycin before administration, the renal function was getting worse significantly after vancomycin administration [SCr (µmol/L): 68.0 (50.2, 104.5) vs. 56.0 (42.2, 71.0), BUN (mmol/L): 5.35 (3.75, 9.83) vs. 4.70 (3.45, 8.10), both P < 0.05]. Combination with VC significantly improved renal function compared with that before VC treatment [SCr (µmol/L): 79.0 (58.0, 129.0) vs. 98.0 (65.0, 178.2), P < 0.05; BUN (mmol/L): 9.60 (6.10, 18.30) vs. 11.30 (6.48, 18.38), P > 0.05] and shortened the length of ICU stay [days: 28.5 (14.8, 54.2) vs. 37.0 (25.0, 55.0), P < 0.01]. CONCLUSIONS: The incidence of drug-induced renal injury caused by vancomycin is high. Intravenous high dose VC can significantly reduce the nephrotoxicity of vancomycin and shorten the length of hospital stay. When vancomycin is used in critically ill patients, VC can be used in combination to reduce or avoid drug-induced renal injury, improve curative effect and reduce toxic effects.

Vitamin C treatment attenuates hemorrhagic shock related multi-organ injuries through the induction of heme oxygenase-1.

BACKGROUND: Vitamin C (VitC) has recently been shown to exert beneficial effects, including protecting organ function and inhibiting inflammation, in various critical care conditions, but the specific mechanism remains unclear. Induction of heme oxygenase (HO)-1, a heat shock protein, has been shown to prevent organ injuries in hemorrhagic shock (HS) but the relationship between VitC and HO-1 are still ill-defined so far. Here we conducted a systemic in vivo study to investigate if VitC promoted HO-1 expression in multiple organs, and then tested if the HO-1 induction property of VitC was related to its organ protection and anti-inflammatory effect. METHODS: Firstly, to determine the HO-1 induction property of VitC, the HO-1 level were measured in tissues including kidney, liver and lung of the normal and HS model of Sprague-Dawley (SD) rats after VitC treatment (100 mg/kg body weight). Secondly, to testify if VitC prevented HS related organ injuries via inducing HO-1, the HS model of rats were separately pre- and post-treated with VitC, and some of them also received Zinc protoporphyrin (Znpp), a specific HO-1 inhibitor. The HO-1 activity in tissues was tested; the organ injuries (as judged by histological changes in tissues and the biochemical indicators level in serum) and inflammatory response in tissues (as judged by the level of pro-inflammatory cytokines Tumor necrosis factor-α and Interleukin-6 ) were analyzed. RESULTS: The HO-1 mRNA and protein level in kidney, liver, and lung were highly induced by VitC treatement under normal and HS conditions. The HO-1 activity in tissues was enhanced by both VitC pre- and post-treatment, which was shown to improve the organ injuries and inhibit the inflammatory response in the HS model of rats. Of note, the beneficial effects of VitC were abolished after HO-1 activity was blocked by Znpp. CONCLUSIONS: VitC led to a profound induction of HO-1 in multiple organs including the kidney, liver and lung, and this property might be responsible for the organ protection and inflammation inhibitory effects of both pre- and post-treatment with VitC in HS.

Formalized therapeutic guideline for hyperlipidemic severe acute pancreatitis.

AIM: To investigate a formalized therapeutic guideline for hyperlipidemic severe acute pancreatitis (HL-SAP). METHODS: Thirty-two consecutive patients with severe acute pancreatitis were included in the clinical trial. All of them met the following five criteria for admission to the study, namely the Atlanta classification and stratification system for the clinical diagnosis of SAP, APACHEII score more than 8, time interval for therapeutic intervention less than 72 hours after onset of the disease, serum triglyceride (TG) level 6.8 mmol/l or over, and exclusion of other etiologies. They were divided into severe acute pancreatitis group (SAP, 22 patients) and fulminant severe acute pancreatitis group (FSAP, 10 patients). Besides the conventional therapeutic measures, Penta-association therapy was also applied in the two groups, which consisted of blood purification (adsorption of triglyceride and hemofiltration), antihyperlipidemic agents (fluvastatin or lipanthyl), low molecular weight heparin (fragmin), insulin, topical application of Pixiao (a traditional Chinese medicine) over the whole abdomen. Serum triglyceride, pro-inflammatory cytokines and anti-inflammatory cytokines were determined before blood purification (PF), at the end of blood purification (AFE) and on the 7th day after onset of the disease (AF7) respectively. Simultaneously, severity of the diseases was assessed by the APACHE II system. PROGNOSIS was evaluated by non-operation cure rate, absorption rate of pseudocyst, time interval pseudocyst absorption, hospital stay and survival rate. RESULTS: Serum triglyceride level (mmol/L), TNFalpha (U/ml) concentration and APACHE II score were significantly decreased (P<0.05) at AFE and AF7, as compared with PF. However, serum IL-10 concentration (pg/ml) was increased significantly (P<0.001) at AFE, and decreased significantly (P<0.05) at AF7 when compared with PF. OPERATIONS: The First surgical intervention time was 55.8+/-42.6 days in SAP group (5 patients) and 12.2+/-6.6 days in FSAP group (7 patients), there was a significant difference between the two groups (P=0.02). The number of operations in the two groups was 1.33+/-0.5 vs 3.5+/-1.2 (P=0.0037), respectively. PROGNOSIS: Non-operation cure rate, absorption rate of pseudocyst, hospital stay and survival rate in SAP group and FSAP group were 100% (22/22) vs 11.1% (1/9), 77.3% (17/22) vs 11.1% (1/9), 54.2+/-35.9 vs 99.1+/-49.5 days (P=0.008) and 100%(22/22) vs 66.7% (6/9) (P=0.0044). The time for absorption of pseudocyst was 135.1+/-137.5 days in SAP group. CONCLUSION: Penta-association therapy is an effective guideline in the treatment of hyperlipidemic severe acute pancreatitis at its early stage (within 72 hours).