Research Article - Biomedical Research (2017) Volume 28, Issue 12
Impacts of different hemofiltration methods on the prognosis of patients with sepsis
Jilu Ye*, Xuehua Pu and Xiaofeng Chen
Department of Critical Care Medicine, Jiangsu Taizhou People's Hospital, Taizhou, Jiangsu Province, PR China
- *Corresponding Author:
- Jilu Ye
Department of Critical Care Medicine
Jiangsu Taizhou People's Hospital, PR China
Accepted on April 29, 2017
The aim of this study was to explore the therapeutic effects of Continuous High-Volume Hemofiltration (CHVHF) in treating sepsis combined with Multiple Organ Dysfunction Syndrome (MODS). A total of 100 patients with sepsis induced by various causes in combination with MODS (S-MODS) and who were treated in the Department of Critical Care Medicine of our hospital from March 2013 to December 2015 were selected and randomly divided into group A (n=53, for CHVHF) or group B (n=47, for common volume hemofiltration, CVHF). The post-treatment changes of observation indexes were then compared and analysed. Patients in group A exhibited an improvement in body temperature and heart rate (P<0.01), while their Color Index (CI), Mean Artery Pressure (MAP), Systemic Vascular Resistance Index (SVRI), and Stroke Volume Index (SVI) all tended to be stable (P<0.01). Meanwhile, their MODS scores and APACHEII scores decreased significantly (P<0.01), and their Procalcitonin (PCT) and Arterial Blood Lactate level (ABL) improved after treatment. Therefore, CHVHF can stabilize the vital signs and hemodynamics of S-MODS patients as well as improve their tissue perfusion and restore organ functions.
Sepsis, Continuous hemofiltration, Multiple organ dysfunction syndrome.
In addition to the lethal nature of sepsis, some patients with severe sepsis can develop Multiple Organ Dysfunction Syndrome (MODS) despite timely treatments that reduce inflammation or resolve the underlying lesion. In this way, sepsis has become a major public health problem  as well as one of the major causes of death in critically ill patients. Indeed, if septic shock occurs, the mortality can be as high as 50% . According to statistics from the US Centers for Disease Control and Prevention (CDC), 75 million people suffer from sepsis each year. Among these individuals, approximately 9% develop severe sepsis and 3% develop septic shock, which is also the main cause of death in Intensive Care Units (ICU) [3,4]. Researchers have focused on developing a treatment paradigm that improves the overall recovery of patients experiencing sepsis. Among the systematic treatment regimens currently being developed for sepsis, hemofiltration has become one controversial focus. Recent studies have shown that High-Volume Hemofiltration (HVHF) can clear in vivo harmful substances for patients with sepsis, thereby improving the prognosis of sepsis. HVHF is a widely used Continuous Venovenous Hemofiltration (CVVH)-based blood filtration technology. Recently, Continuous High Volume Hemofiltration (CHVHF) has been developed , which has improved the clearance of solutes with large and medium molecular weights. Studies have shown that CHVHF can effectively improve the prognosis of patients with sepsis and,when performed as early as possible, can achieve better results . Currently, many pre-clinical studies [7-10] and early clinical trials [11-13] have shown great promise; however, the results of multi-center clinical studies are disappointing [14,15]. Moreover, it is still not clear yet whether CHVHF can effectively control the conditions of post-sepsis MODS. This study applied CHVHF and CVHF separately to treat S-MODS patients to compare and analyse the efficacy of these two treatment regimens in resolving sepsis in patients.
Information and Intervention
A total of 100 S-MODS patients treated in the Department of Critical Care Medicine of our hospital from March 2013 to December 2015 were selected and randomly divided into group A (n=53, for CHVHF) or group B (n=47, for CVHF). There was no statistical difference in the sex, age, and inflammation type between the two groups (χ2=0.023, P=0.879; t=0.818, P=0.416; χ2=0.756, P=0.505, Table 1). All patients were diagnosed according to the "International treatment guidelines of 2008 SSC severe sepsis and septic shock" , while the "Marshall Table of multiple organ dysfunction syndrome in 1995 (MODS table)"  was used to score organ dysfunction. All patients belonged to the low-output and high-resistance type as well as scored more than 5 points on the MODS table. Patients were excluded if they were pregnant, had chronic renal failure, were<18 years of age, or receiving immunosuppressive therapy.
|Item||A (n=53)||B (n=47)||t/χ2||P|
|Age (years)||45.03 ± 5.33||44.20 ± 4.75||0.818||0.416|
|Severe pneumonia (n)||11||9||0.756||0.505|
|Acute purulent inflammation (n)||9||9|
|Severe pancreatitis (n)||8||7|
|Severe multiple injuries (n)||10||9|
|Postoperative abdominal infection (n)||8||7|
|Digestive perforation combined with abdominal infection (n)||7||6|
Table 1. Comparison of general information between the two groups.
This study was conducted in accordance with the declaration of Helsinki. This study was conducted with approval from the Ethics Committee of Taizhou People's Hospital. Written informed consent was obtained from all participants.
All patients were catheterized in the internal jugular vein or the femoral vein to establish the vascular approach. Either a heparin-free method was used to maintain an Activated Partial Thromboplastin Time (APTT) of 40-60 s, or low molecular weight heparin or common heparin was used to achieve anticoagulation . The two groups underwent CHVHF simultaneously, with the treatment in group A persisting for 24-30 h each with a substitution amount of 50-60 ml/(kg•h) and a blood flow amount as 200-250 ml/min. Treatment in group B was identical, except that the substitution amount in group B was only 30 ml/(kg•h).
The changes in body Temperature (T), Heart Rate (HR), MODS score, and APACHEII score of the two groups at different time periods before and after CHVHF were recorded and analysed. Changes in Procalcitonin (PCT) level, Arterial Blood Lactate level (ABL), and hepatonephric function were evaluated in arterial and venous blood samples, which were obtained before and after CHVHF. The Cardiac Index (CI), invasive arterial pressure (MAP), Systemic Vascular Resistance Index (SVRI), Stroke Volume Index (SVI), and Central Venous Pressure (CVP) of the two groups were monitored before and after CHVHF.
SPSS13.0 was used to analyse data. Measurement data were analysed using the chi-squared test, while count data were analysed using an independent sample t test. Intergroup comparisons were performed using the F test (univariate analysis of variance), with P<0.05 being assumed to indicate a statistically significant difference.
Among the 53 S-MODS patients in group A, 40 patients were cured and discharged, 4 patients stopped undergoing treatment for various reasons, and 9 patients died, with the mortality rate being 17.1%. Meanwhile, among the 47 S-MODS patients in group A, 35 patients were cured and discharged, 5 patients stopped undergoing treatment for various reasons, and 9 patients died, with the mortality rate being 19.1%. These was no statistically significant difference in the overall mortality between the two groups (χ2=0.650, P=0.885) (Table 2).
|Group||n||Cured||Giving-up treatment||Death||Mortality (%)|
Table 2. Disease outcomes and mortalities in the two groups.
The post-treatment T and HR in the two groups were both significantly reduced, with the pre- and post-treatment MODS scores and APACHEII scores exhibiting statistically significant differences (t=7.059, P<0.01; t=12.014, P<0.01; t=4.639, P<0.01; t=10.306, P<0.01; respectively). Due to the reduction in indexes, such as T, HR, MODS score, and APACHEII score, it can be concluded that the patient’s vital signs were stabilizing. The post-treatment T, HR, MODS score, and APACHEII score in group A were more significantly reduced than in group B (t=6.867, P<0.01; t=4.300, P<0.01; t=1.697, P=0.043; t=4.367, P<0.01; respectively) (Table 3).
|Group||n||T||HR||MODS score||APACHEII score|
|A||53||38.6 ± 0.8||37.2 ± 1.0||7.059||<0.01||121.7 ± 14.5||90.0 ± 12.6||12.014||<0.01||7.9 ± 3.3||5.3 ± 2.4||4.639||<0.01||17.1 ± 3.3||9.2 ± 4.5||10.306||<0.01|
|B||47||38.7 ± 0.8||38.4 ± 0.7||2.055||0.042||120.9 ± 14.2||101.1 ± 13.2||7.435||<0.01||7.9 ± 3.3||6.2 ± 2.9||2.817||0.04||17.1 ± 3.4||12.9 ± 3.9||5.91||<0.01|
Table 3. Changes of vital signs in the two groups before and after treatment.
Hemodynamic changes before and after treatment
All patients exhibited significant improvements after undergoing CHVHF for 48 h and 72 h, with their CI, MAP, SVRI, and SVI, gradually stabilizing as well as exhibiting a statistically significant difference before and after treatment (F=30.026, P<0.01; F=87.950, P<0.01; F=367.944, P <0.01; F=217.257, P<0.01; respectively). The patients in group A exhibited a more notable increase in CI, MAP, and SVI after treatment than did group B. Similarly, group A exhibited a more notable decrease in CAP and SVRI after treatment than did group B (t=-2.764, P=0.004; t=-4.731, P<0.01; t=5.273, P <0.01; t=-5.839, P<0.01; respectively) (Tables 4 and 5).
|Before||48 h later||72 h later||F||P||Before||48 h later||72 h later||F||P|
|A||53||2.0 ± 1.0||3.9 ± 1.9||4.5 ± 2.1||30.026||<0.001||77.0 ± 5.3||86.5 ± 6.8||92.4 ± 5.9||87.95||<0.001|
|B||47||2.5 ± 1.0||3.3 ± 1.4||3.5 ± 1.4||8.025||<0.001||76.8 ± 5.1||81.1 ± 4.4||86.1 ± 7.4||20.54||<0.001|
Table 4. Hemodynamic changes before and after treatment.
|Before||48 h later||72 h later||F||P||Before||48 h later||72 h later||F||P|
|A||53||2768 ± 213||1985 ± 163||1850 ± 185||367.944||<0.001||33.0 ± 6.8||55.0 ± 6.1||57.2 ± 6.9||217.257||<0.001|
|B||47||2766 ± 211||2299 ± 194||2043 ± 180||165.413||<0.001||32.5 ± 6.0||44.0 ± 6.1||48.5 ± 8.0||69.964||<0.001|
Table 5. Hemodynamic changes before and after treatment.
Changes in hepatonephric function before and after treatment
The PCT and ABL values of the patients in group A were significantly increased when compared to normal values before treatment, but gradually decreased to within normal ranges after treatment. The patients exhibited hepatonephric dysfunction before treatment, which gradually became normal after treatment. Furthermore, the differences in PCT and ABL before CHVHF and at 24 h, 48 h, and 72 h after CHVHF were statistically significant (F=21.210, P<0.01; F=76.410, P<0.01; F=86.060, P<0.01; F=199.800, P<0.01; F=120.900, P<0.01; F=162.100, P<0.01; respectively) (Table 6).
|Item||Before CHVHF||24 h after CHVHF||48 h after CHVHF||72 h after CHVHF||F||P|
|PCT (μg/L)||7 ± 3||5 ± 3||3 ± 2||2 ± 1||21.21||<0.01|
|ABL (mmol/L)||6.8 ± 2.7||3.4 ± 2.1||2.7 ± 1.7||1.7 ± 0.9||76.41||<0.01|
|ALT (U/L)||123.4 ± 41.5||68.2 ± 24.1||51.4 ± 21.6||45.2 ± 18.7||86.06||<0.01|
|TBIL (μmol/L)||35.1 ± 8.1||19.3 ± 4.5||16.3 ± 4.0||11.3 ± 3.2||199.8||<0.01|
|BUN (mmol/L)||25.4 ± 6.1||14.2 ± 4.4||12.3 ± 4.3||9.0 ± 3.7||120.9||<0.01|
|Scr (μmol/L)||173.9 ± 31.5||117.9 ± 27.2||89.2 ± 30.3||67.3 ± 11.5||162.1||<0.01|
Table 6. Changes of PCT, ABL, and hepatonephric function in group A.
While sepsis is common, with approximately 18 million cases of sepsis annually, it is an emergent threat . In the ICU, approximately 41% of critically ill patients develop sepsis, with sepsis being the main cause of death among critically ill patients in ICU. The rate of death in sepsis-caused secondary MODS has been reported to range from 32% to 61%. MODS normally occur in late sepsis and are caused by interactions between a large number of inflammatory mediators and proinflammatory substances that are released following ischemiareperfusion, infection, or other factors. This represents a “waterfall effect” that reflects the activation of an inflammatory cascade . Immune imbalance is the main cause of S-MODS. Therefore, in order to fundamentally reduce the mortality of sepsis, imbalances in the immune system must be corrected. Continuous hemofiltration can help reduce the rate of mortality in sepsis as it can correct the abnormally increased level of blood vasoactive substances via its filtration, adsorption, and diffusion activities . HVHF is an important method of Continuous Renal Replacement Therapy (CRRT), and the use of HVHF can decrease mortality and improve prognosis because it enables a reduction in the severity of paralysis of the immune system, thereby reducing the risk of secondary infection. CRRT can effectively correct the acidbase and electrolyte imbalance in patients with sepsis, and comprehensively reduce the concentration peaks of a variety of inflammatory mediators in vivo. Therefore, early CRRT can reduce the impact of inflammatory mediators on hemodynamics and endothelial cells as well as downregulate the overall inflammatory response in a temporally appropriate manner [22,23]. In sepsis, anaerobic metabolism results in a high level and low clearance rate of ABL. HVHF can effectively address this severe lactic acidosis . Furthermore, it can also improve inflammation-damaged organ function, particularly hepatonephric function, and greatly improve oxygenation in patients with ARDS [25,26].
In a comparison with CVHF, we found that CHVHF can significantly reduce the body temperature and heart rate of patients with S-MODS as well as reduce their MODS and APACHEII scores. Furthermore, these differences were statistically significant, which is consistent with many other Chinese studies, thereby indicating that CHVHF can help stabilize the vital signs of S-MODS patients .
This study demonstrated that CHVHF can significantly improve SVI, CI, and MVP in S-MODS patients as well as reduce ABL and central venous pressure. Furthermore, CHVHF can interfere with the synthesis of such cardiovascular composites, such as endothelin and myocardial depressant factor , which indicates that CHVHF can improve the hemodynamics of and tissue perfusion in S-MODS patients. It further demonstrates that this therapy has an important role in recovering organ functions in S-MODS patients [29,30]. PCT is a highly specific serological index for the diagnosis of sepsis, and the results of this study demonstrated that PCT gradually decreased to normal after CHVHF, thereby demonstrating the significant role of CHVHF as a potential therapy for sepsis.
In summary, CHVHF can stabilize the vital signs of patients with S-MODS as well as improve their hemodynamics, tissue perfusion, and organ functions. Therefore, CHVHF can be considered a promising therapy for S-MODS.
This study was supported by Social development project of Taizhou City, Jiangsu Province (TS2013010).
Conflict of Interest
All authors have no conflict of interest regarding this paper.
- Moore JX, Donnelly JP, Griffin R, Howard G, Safford MM. Defining Sepsis Mortality Clusters in the United States. Crit Care Med 2016; 44: 1380-1387.
- Moran JL, Graham PL, Rockliff S, Bersten AD. Updating the evidence for the role of corticosteroids in severe sepsis and septic shock: a Bayesian meta-analytic perspective. Crit Care 2010; 14: 134.
- Paul M, Shani V, Muchtar E, Kariv G, Robenshtok E, Leibovici L. Systematic review and meta-analysis of the efficacy of appropriate empiric antibiotic therapy for sepsis. Antimicrob Agents Chemother 2010; 54: 4851-4863.
- Beale R, Janes JM, Brunkhorst FM, Dobb G, Levy MM, Martin GS, Ramsay G, Silva E, Sprung CL, Vallet B, Vincent JL, Costigan TM, Leishman AG, Williams MD, Reinhart K. Global utilization of low-dose corticosteroids in severe sepsis and septic shock: a report from the PROGRESS registry. Crit Care 2010; 14: 102.
- Du C, Cai H, Shao S, Yan Q. Efficacies of continuous high volume hemofiltration in severe sepsis patients with multiple organ dysfunction syndrome. Zhonghua Yi Xue Za Zhi 2015; 95: 210-213.
- Romero CM, Downey P, Hernandez G. High volume hemofiltration in septic shock. Med Intensiva 2010; 34: 345-352.
- Bellomo R, Kellum JA, Gandhi CR, Pinsky MR, Ondulik B. The effect of intensive plasma water exchange by hemofiltration on hemodynamics and soluble mediators in canine endotoxemia. Am J Respir Crit Care Med 2000; 161: 1429-1436.
- Kellum JA, Song M, Venkataraman R. Hemoadsorption removes tumor necrosis factor, interleukin-6, and interleukin-10, reduces nuclear factor-kappaB DNA binding,and improves short-term survival in lethal endotoxemia. Crit Care Med 2004; 32: 801-905.
- Ito M, Kase H, Shimoyama O, Takahashi T. Effects of polymyxin B-immobilized fiber using a rat cecal ligation and perforation model. ASAIO J 2009; 55: 246-250.
- Peng ZY, Carter MJ, Kellum JA. Effects of hemoadsorption on cytokine removal and short-term survival in septic rats. Crit Care Med 2008; 36: 1573-1577.
- Honore PM, Jamez J, Wauthier M, Lee PA, Dugernier T, Pirenne B, Hanique G, Matson JR. Prospective evaluation of short-term, high-volume isovolemic hemofiltration on the hemodynamic course and outcome in patients with intractable circulatory failure resulting from septic shock. Crit Care Med 2000; 28: 3581-3587.
- Ratanarat R, Brendolan A, Piccinni P, Dan M, Salvatori G. Pulse high-volume haemofiltration for treatment of severe sepsis: effects on hemodynamics and survival. Crit Care 2005; 9: 294-302.
- Vincent JL, Laterre PF, Cohen J, Burchardi H, Bruining H, Lerma FA, Wittebole X, De Backer D, Brett S, Marzo D, Nakamura H, John S. A pilot-controlled study of a polymyxin B-immobilized hemoperfosion cartridge in patients with severe sepsis secondary to intra-abdominal infection. Shock 2005; 23: 400-405.
- Cole L, Bellomo R, Hart G, Journois D, Davenport P. A phase II randomized, controlled trial of continuous hemofiltration in sepsis. Crit Care Med 2002; 30: 100-106.
- Payen D, Mateo J, Cavaillon JM, Fraisse F, Floriot C, Vicaut E; Hemofiltration and Sepsis Group of the Collège National de Reanimation et de Medecine durgence des Hôpitaux extra-Universitaires. Impact of continuous venovenous hemofiltration on organ failure during the early phase of severe sepsis: a randomized controlled trial. Crit Care Med 2009; 37: 803-810.
- Ronco C, Ricci Z, De Backer D, Kellum JA, Taccone FS, Joannidis M, Pickkers P, Cantaluppi V, Turani F, Saudan P, Bellomo R, Joannes-Boyau O, Antonelli M, Payen D, Prowle JR, Vincent JL. Renal replacement therapy in acute kidney injury: controversy and consensus. Crit Care 2015; 19: 146.
- Xu C, Fan K, Xie L, Chen W, Wang L. Evaluation of optimized continuous venovenous hemodiafiltration therapy efficiency in severe burn patients with sepsis. Burns Trauma 2014; 2: 125-129.
- De Simone N, Racsa L, Bevan S, Matevosyan K, Valley T, Girod C, Sarode R. Therapeutic plasma exchange in the management of sepsis and multiple organ dysfunction syndrome: a report of three cases. J Clin Apher 2014; 29: 127-131.
- Sun Z, Ye H, Shen X, Chao H, Wu X, Yang J. Continuous venovenous hemofiltration versus extended daily hemofiltration in patients with septic acute kidney injury: a retrospective cohort study. Crit Care 2014; 18: 1-9.
- Iba T. The obstacles that should be overcome to develop new anticoagulants for severe sepsis. Crit Care Med 2014; 42: e248-249.
- Bomsztyk K, Mar D, An D, Sharifian R, Mikula M, Gharib SA, Altemeier WA, Liles WC, Denisenko O. Experimental acute lung injury induces multi-organ epigenetic modifications in key angiogenic genes implicated in sepsis-associated endothelial dysfunction. Crit Care 2015; 19: 1-13.
- Kleber A, Altmeyer S, Wolf B, Wolf A, Volk T, Fink T, Kubulus D. Impact of melatonin receptor deletion on intracellular signaling in spleen cells of mice after polymicrobial sepsis. Inflamm Res 2014; 63: 1023-1033.
- Combes A, Brechot N, Amour J, Cozic N, Lebreton G, Guidon C, Zogheib E, Thiranos JC, Rigal JC, Bastien O, Benhaoua H, Abry B, Ouattara A, Trouillet JL, Mallet A, Chastre J, Leprince P, Luyt CE. Early high-volume hemofiltration versus standard care for post-cardiac surgery shock. The HEROICS Study. Am J Respir Crit Care Med 2015; 192: 1179-1190.
- Cheungpasitporn W, Zand L, Dillon JJ, Qian Q, Leung N. Lactate clearance and metabolic aspects of continuous high-volume hemofiltration. Clin Kidney J 2015; 8: 374-377.
- Guo J, Huang W, Yang XN, Jin T, Altaf K, Javed MA, Lin ZQ, Huang ZW, Xue P, Johnstone M, Sutton R, Xia Q. Short-term continuous high-volume hemofiltration on clinical outcomes of severe acute pancreatitis. Pancreas 2014; 43: 250-254.
- Yang W, Hong J, Zeng Q, Tao J, Chen F, Dang R, Liang Y, Wu Z, Yang Y. Improvement of oxygenation in severe acute respiratory distress syndrome with high-volume continuous veno-venous hemofiltration. Glob Pediatr Health 2016; 3: 2333794.
- Tsao CM, Li KY, Chen SJ, Ka SM, Liaw WJ, Huang HC, Wu CC. Levosimendan attenuates multiple organ injury and improves survival in peritonitis-induced septic shock: studies in a rat model. Crit Care 2014; 18: 1-12.
- Spoto S, Valeriani E, Costantino S. Nosography of systemic inflammatory response syndrome, sepsis, severe sepsis, septic shock, and multiple organ dysfunction syndrome in internal medicine patients. Italian J Med 2015; 9: 243-251.
- Hoareau GL, Epstein SE, Palm C, Ybarra W, Jandrey KE. Resolution of anuric acute kidney injury in a dog with multiple organ dysfunction syndrome. J Vet Emerg Crit Care (San Antonio) 2014; 24: 724-730.
- Bugedo G, Florez J, Ferres M, Roessler E, Bruhn A. Hantavirus cardiopulmonary syndrome successfully treated with high-volume hemofiltration. Rev Bras Ter Intensiva 2016; 28: 190-194.