Continuous hemofiltration improves the prognosis of bacterial sepsis complicated by liver dysfunction in children

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Abstract

Background

Liver dysfunction is an independent risk factor for poor prognosis of patients with sepsis. The aim of this study is to evaluate the effects of continuous hemofiltration in patients with bacterial sepsis complicated by liver dysfunction.

Methods

We retrospectively analyzed the medical records of 27 cases of bacterial sepsis with liver dysfunction admitted to pediatric intensive care unit (PICU) of Shanghai Children’s Hospital between January 2013 and December 2016.

Results

28-day mortality and length of PICU stay were significantly reduced in the continuous hemofiltration group ( n = 16) compared with the conventional management group ( n = 11) (31.3% vs. 72.7%, 9 [4–23] vs. 14 [4–36], respectively, both P < 0.05). The interval time between PICU admission and continuous hemofiltration initiation was (22.06 ± 17.68) h, and the median time of continuous hemofiltration duration was 48 h (31–70 h). After 72 h hemofiltration, the levels of total bilirubin (TBIL), direct bilirubin (DBIL), total bile acids (TBA), ammonia, lactate (Lac), TNF-α and IL-6 were significantly decreased in the continuous hemofiltration group. Moreover, multivariate logistic regression analysis indicated that continuous hemofiltration treatment and the TBIL level were independently associated with 28-day mortality of patients with bacterial sepsis complicated by liver dysfunction.

Conclusions

Continuous hemofiltration significantly decreases the serum levels of TBIL, DBIL, TBA, Lac, ammonia, TNF-α, IL-6, and improves 28-day mortality of patients with bacterial sepsis complicated by liver dysfunction.

Electronic supplementary material

The online version of this article (10.1186/s12887-018-1243-3) contains supplementary material, which is available to authorized users.

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Most cited references 15

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Continuous renal replacement therapy: a worldwide practice survey. The beginning and ending supportive therapy for the kidney (B.E.S.T. kidney) investigators.

Shigehiko Uchino, Rinaldo Bellomo, Hiroshi Morimatsu … (2007)

Little information is available regarding current practice in continuous renal replacement therapy (CRRT) for the treatment of acute renal failure (ARF) and the possible clinical effect of practice variation. Prospective observational study. A total of 54 intensive care units (ICUs) in 23 countries. A cohort of 1006 ICU patients treated with CRRT for ARF. Collection of demographic, clinical and outcome data. All patients except one were treated with venovenous circuits, most commonly as venovenous hemofiltration (52.8%). Approximately one-third received CRRT without anticoagulation (33.1%). Among patients who received anticoagulation, unfractionated heparin (UFH) was the most common choice (42.9%), followed by sodium citrate (9.9%), nafamostat mesilate (6.1%), and low-molecular-weight heparin (LMWH; 4.4%). Hypotension related to CRRT occurred in 19% of patients and arrhythmias in 4.3%. Bleeding complications occurred in 3.3% of patients. Treatment with LMWH was associated with a higher incidence of bleeding complications (11.4%) compared to UFH (2.3%, p = 0.0083) and citrate (2.0%, p = 0.029). The median dose of CRRT was 20.4 ml/kg/h. Only 11.7% of patients received a dose of > 35 ml/kg/h. Most (85.5%) survivors recovered to dialysis independence at hospital discharge. Hospital mortality was 63.8%. Multivariable analysis showed that no CRRT-related variables (mode, filter material, drug for anticoagulation, and prescribed dose) predicted hospital mortality. This study supports the notion that, worldwide, CRRT practice is quite variable and not aligned with best evidence.

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Causes and Outcomes of Sepsis in Southeast Asia: A Multinational Multicentre Cross-sectional Study

Direk Limmathurotsakul (2017)

Background A better understanding of pathogens causing sepsis is important for management and antimicrobial selection. Here, we explored the causative pathogens of sepsis in Southeast Asia (SEA). Methods We prospectively recruited children (age≥30 days and <18 years) and adults (age≥18 years) at 13 public hospitals in Indonesia (n=3), Thailand (n=4) and Viet Nam (n=6). Hospitalised patients with suspected or documented community-acquired infection, with ≥3 diagnostic criteria for sepsis according to the Surviving Sepsis Campaign 2012, and within 24 hours of admission were enrolled. Blood from every patient, and nasopharyngeal swab, urine, stool and cerebrospinal fluid, if indicated, were collected for reference diagnostic tests. This study was registered with ClinicalTrials.gov, number NCT02157259. Findings From December 2013 to December 2015, 1,578 patients (763 children and 815 adults) were enrolled. Dengue viruses (n=122, 8%), Leptospira spp. (n=95, 6%), rickettsial pathogens (n=96, 6%), Escherichia coli (n=76, 5%) and influenza viruses (n=65, 4%) were commonly identified in both age groups, while Plasmodium spp. (n=12, 1%) and Salmonella enterica serovar Typhi (n=3, 0.2%) were rarely observed. Emerging pathogens identified included hantaviruses (n=28, 2%), non-typhoidal Salmonella spp (n=21, 1%), Streptococcus suis (n=18, 1%), Acinetobacter spp. (n=12, 1%), and Burkholderia pseudomallei (n=5, 0.3%). 28-day mortality was 2% in children (14/731) and 13% in adults (108/804). Severe sepsis was identified on enrolment in 27% of children (204/763) and 68% of adults (550/815), and was associated with increased mortality (adjusted odds ratio 5.3, 95% confidence interval 2.7–10.4, p<0.001). Interpretation Sepsis in SEA is caused by a wide range of known and emerging pathogens, and is associated with substantial mortality. Funding National Cancer Institute (HHSN261200800001E) and National Institute of Allergy and Infectious Diseases, National Institutes of Health, and Wellcome Trust (106680/B/14/Z and 106698/B/14/Z).

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Hepatic response to sepsis: interaction between coagulation and inflammatory processes.

N Marín, C Vinsonneau, A J Levert-Mignon … (2001)

a) To review the hepatic response to sepsis and to establish how this response contributes to coagulation and inflammatory processes; b) to review the physiologic and biochemical mechanisms that suggest hepatic dysfunction may occur during sepsis, enhance procoagulant and proinflammatory activities, and participate in the potential evolution to multiple organ dysfunction syndrome. A summary of published medical literature from MEDLINE search files and published reviews on liver function in experimental and human sepsis. In sepsis, the liver plays a major role in host defense mechanisms. Kupffer cells are responsible for bacterial scavenging, bacterial products inactivation, and inflammatory mediators clearance and production. Hepatocytes, via receptors for many proinflammatory cytokines, modify their metabolic pathway toward gluconeogenesis, amino-acid uptake, and increased synthesis of coagulant and complement factors and protease inhibitors. The acute-phase protein (APP) response also contributes to the procoagulant state, especially by enhancing the inhibition of protein C (alpha1-antitrypsin and alpha2-macroglobulin) and by decreasing liver synthesis of protein C and antithrombin (negative APPs). Elevated C-reactive protein levels (positive APPs) promote the expression of tissue factor by mononuclear cells. Increased liver production of thrombin-activatable fibrinolytic inhibitor (positive APPs) enhances fibrinolysis inhibition. Conversely, such hepatic inflammatory and coagulation processes in sepsis may alter the function of this organ. Indeed, the liver can be injured by activated Kupffer cells that release chemokines, attract blood neutrophils into the liver, and activate them. Neutrophils up-regulate their surface adhesion molecules, tissue factor, and Kupffer cells, whereas tissue factor pathway inhibitor and thrombomodulin are almost undetectable in endothelial cells. This may lead to microcirculatory disturbances, fibrin deposition, hepatocyte injury, endotoxin and bacteria spillover, and multiple organ failure. In sepsis, the liver participates in host defense and tissue repair through hepatic cell cross-talk that controls most of the coagulation and inflammatory processes. When this control is not adequate, a secondary hepatic dysfunction may occur and may sometimes lead to bacterial products spillover, enhanced procoagulant and inflammatory processes, and in turn, multiple organ failure and death.

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Author and article information

Contributors

Yun Cui: cuiyun0815@163.com

Xi Xiong: xiongxi3@163.com

Fei Wang: wangf1264@shchildren.com.cn

Yuqian Ren: renyuqian@yeah.net

Chunxia Wang: karencx0465@163.com

Yucai Zhang:

ORCID: http://orcid.org/0000-0002-4905-3600

zyucai2018@163.com

Journal

Journal ID (nlm-ta): BMC Pediatr

Journal ID (iso-abbrev): BMC Pediatr

Title: BMC Pediatrics

Publisher: BioMed Central (London )

ISSN (Electronic): 1471-2431

Publication date (Electronic): 11 August 2018

Publication date PMC-release: 11 August 2018

Publication date Collection: 2018

Volume: 18

Electronic Location Identifier: 269

Affiliations

[1 ]ISNI 0000 0004 0368 8293, GRID grid.16821.3c, Department of Critical Care Medicine, Shanghai Children’s Hospital, , Shanghai Jiao Tong University, ; No.355 Luding Road, Putuo District, Shanghai, 200062 China

[2 ]ISNI 0000 0004 0368 8293, GRID grid.16821.3c, Institute of Pediatric Critical Care, , Shanghai Jiao Tong University, ; No.355 Luding Road, Putuo District, Shanghai, 200062 China

Author information

Yucai Zhang http://orcid.org/0000-0002-4905-3600

Article

Publisher ID: 1243

DOI: 10.1186/s12887-018-1243-3

PMC ID: 6087006

PubMed ID: 30098593

SO-VID: dcbc6ad0-446d-48fc-97c3-afdab60e8fdb

License:

Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License ( http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver ( http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.

History

Date received : 12 December 2017

Date accepted : 3 August 2018

Funding

Funded by: Science and Technology Commission of Shanghai Municipality

Award ID: 16411970300

Award ID: 17411968900

Award Recipient : Yun Cui Yucai Zhang

Funded by: Shanghai Municipal Education Commission-Gaofeng Clinical Medicine Grant support

Award ID: DLY201618

Award Recipient : Yucai Zhang

Funded by: Shanghai Municipal Education Commission-Gaofeng Clinical Medicine Grant support

Award ID: 20171928

Award Recipient : Chunxia Wang

Funded by: New Advanced Technology Project at the Shanghai City Hospital Development Center

Award ID: SHDC12014116

Award Recipient : Yucai Zhang

Funded by: Science and Technology Commission of Shanghai Municipality

Award ID: 18411951000

Award Recipient : Yucai Zhang

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ScienceOpen disciplines: Pediatrics

Keywords: continuous hemofiltration,bacterial sepsis with liver dysfunction,mortality,children

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ScienceOpen disciplines: Pediatrics

Keywords: continuous hemofiltration, bacterial sepsis with liver dysfunction, mortality, children

Continuous hemofiltration improves the prognosis of bacterial sepsis complicated by liver dysfunction in children

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Abstract

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Chinese Journal of School Health

Most cited references 15

Continuous renal replacement therapy: a worldwide practice survey. The beginning and ending supportive therapy for the kidney (B.E.S.T. kidney) investigators.

Causes and Outcomes of Sepsis in Southeast Asia: A Multinational Multicentre Cross-sectional Study

Hepatic response to sepsis: interaction between coagulation and inflammatory processes.

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