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Polymyxin B-immobilized hemoperfusion and mortality in critically ill adult patients with sepsis/septic shock: a systematic review with meta-analysis and trial sequential analysis

Intensive Care Medicine Aims and scope Submit manuscript

A Correction to this article was published on 16 January 2018

This article has been updated

Abstract

Purpose

Polymyxin B-immobilized hemoperfusion (PMX-HP) is an adjuvant therapy for sepsis or septic shock that clears circulating endotoxin. Prior trials have shown that PMX-HP improves surrogate endpoints. We aimed to conduct an evidence synthesis to evaluate the efficacy and safety of PMX-HP in critically ill adult patients with sepsis or septic shock.

Methods

We searched for randomized controlled trials (RCTs) in MEDLINE, EMBASE, the Cochrane Library, the Health Technology Assessment Database, CINAHL, “Igaku Chuo Zasshi”, the National Institute of Health Clinical Trials Register, the World Health Organization International Clinical Trials Registry Platform, the University Hospital Medical Information Network Clinical Trials Registry, the reference lists of retrieved articles, and publications by manufacturers of PMX-HP. The primary outcomes were 28-day all-cause mortality, the number of patients with at least one serious adverse event, and organ dysfunction scores. The GRADE methodology for the certainty of evidence was used.

Results

Six trials (857 participants; weighted mean age 62.5 years) proved eligible. Patient-oriented primary outcomes were assessed. The pooled risk ratio (RR) for 28-day mortality associated with PMX-HP was 1.03 [95% confidence interval (CI) 0.78–1.36; I 2 = 25%; n = 797]. The pooled RR for adverse events was 2.17 (95% CI 0.68–6.94; I 2 = 0%; n = 717). Organ dysfunction scores over 24–72 h after PMX-HP treatment did not change significantly (standardized mean difference − 0.26; 95% CI − 0.64 to 0.12; I 2 = 78%; n = 797). The certainty of the body of evidence was judged as low for both benefit and harm using the GRADE methodology.

Conclusions

There is currently insufficient evidence to support the routine use of PMX-HP to treat patients with sepsis or septic shock.

Registration

PROSPERO International Prospective Register of Systematic Reviews (CRD42016038356).

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Fig. 1
Fig. 2

Change history

  • 16 January 2018

    Owing to an oversight by the authors, Figure 2 in this article was not the version intended for publication. The correct Figure 2, reproduced here, features footnote symbols and Figure 2b includes three studies as described in the main text.

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Acknowledgements

We thank Mr. Toshiyuki Suwa at Osaka University for his assistance with the search strategy design in Japanese databases, Ms. Tara Landry at Montreal General Hospital, McGill University Health Centre, for her peer review of the MEDLINE search strategy, Prof. Vladimir Saenko at Nagasaki University for helping to review trial reports in Russian, Ms. Ayumi Horie at Hyogo Prefectural Amagasaki General Medical Center for obtaining the Japanese full-text articles, Toray Industries, Inc. for providing the list of published/unpublished trials and conference proceedings, assisting to get contact with an author of the included study, and all the corresponding persons of ongoing trials for providing information of the current status of the trials. No specific compensation was provided to these individuals.

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Authors and Affiliations

Authors

Contributions

Drs. TF and SMB had full access to all the data in the study and take responsibility for the integrity of the data and the accuracy of the data analysis. Study concept and design: TF, SMB, RG, YK, RF, and TAF. Acquisition of data: TF, SMW, KD, RG, YK, RF, JV, DP, RR, and CR. Analysis and interpretation of data: TF, SMB, YK, TAF, JV, DP, RR, and CR. Drafting of the manuscript: TF, TAF, SMB, and KD. Critical revision of the manuscript for important intellectual content: RF, RG, YK, JV, DP, RR, CR. All authors gave final approval of the version to be published and agreed to be accountable for all aspects of this work.

Corresponding author

Correspondence to Sean M. Bagshaw.

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Funding

TF is supported by the Japan Society for the Promotion of Science (JSPS) and has received a grant from JSPS. This study was funded in part by Grant-in-Aid for JSPS Research Fellow JP16J10320 to TF. SMB is supported by a Canada Research Chair in Critical Care Nephrology and is a steering committee member of the EUPHRATES trial. He has consulted and received speaking fees from Baxter Healthcare Corp. TAF has received lecture fees from Eli Lilly, Janssen, Meiji, Mitsubishi-Tanabe, MSD, and Pfizer. He has received royalties from Igaku-Shoin and Nihon Bunka Kagaku-sha publishers. He has received research support from Mitsubishi-Tanabe and Mochida. KD received lecture fees from Asahi Kasei Medical Crop, Baxter Healthcare Corp., and Toray Medical Corp. JLV, DP, RB, and CR were engaged in the clinical trials included in this review, and provided some of the data not reported in their published papers. None of these funding organizations have contributed to the study design; collection, management, analysis, and interpretation of data; writing of the report, or the decision to submit the report for publication. Toray Industries provided some of the data included in this review, as noted in the body of the article.

Conflicts of interest

The authors declare that they have no conflicts of interest.

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Fujii, T., Ganeko, R., Kataoka, Y. et al. Polymyxin B-immobilized hemoperfusion and mortality in critically ill adult patients with sepsis/septic shock: a systematic review with meta-analysis and trial sequential analysis. Intensive Care Med 44, 167–178 (2018). https://doi.org/10.1007/s00134-017-5004-9

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