Blood purification treatment initiated at the time of sepsis diagnosis effectively attenuates serum HMGB1 upregulation and improves patient prognosis

Zheng, Shixiang; Weng, Qinyong; Wu, Wenwei; Ding, Guohua

doi:10.3892/etm.2017.4854

Cited by 9 publications

(12 citation statements)

References 37 publications

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“…Two trials had four treatment arms. 43,58 Twenty trials used a hemoperfusion technique, 13 used hemofiltration or hemodiafiltration, 4 trials combined hemofiltration with hemoperfusion, and 2 trials used plasma exchange. In three cases we received further information from corresponding authors.…”

Section: Search Results and Study Characteristicsmentioning

confidence: 99%

Blood Purification and Mortality in Sepsis and Septic Shock

et al. 2019

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Editor’s Perspective What We Already Know about This Topic What This Article Tells Us That Is New Background Sepsis and septic shock are severe inflammatory conditions related to high morbidity and mortality. We performed a systematic review with meta-analysis of randomized trials to assess whether extracorporeal blood purification reduces mortality in this setting. Methods Electronic databases were searched for pertinent studies up to January 2019. We included randomized controlled trials on the use of hemoperfusion, hemofiltration without a renal replacement purpose, and plasmapheresis as a blood purification technique in comparison to conventional therapy in adult patients with sepsis and septic shock. The primary outcome was mortality at the longest follow-up available. We calculated relative risks and 95% CIs. The grading of recommendations assessment, development and evaluation methodology for the certainty of evidence was used. Results Thirty-seven trials with 2,499 patients were included in the meta-analysis. Hemoperfusion was associated with lower mortality compared to conventional therapy (relative risk = 0.88 [95% CI, 0.78 to 0.98], P = 0.02, very low certainty evidence). Low risk of bias trials on polymyxin B immobilized filter hemoperfusion showed no mortality difference versus control (relative risk = 1.14 [95% CI, 0.96 to 1.36], P = 0.12, moderate certainty evidence), while recent trials found an increased mortality (relative risk = 1.22 [95% CI, 1.03 to 1.45], P = 0.02, low certainty evidence); trials performed in the United States and Europe had no significant difference in mortality (relative risk = 1.13 [95% CI, 0.96 to 1.34], P = 0.15), while trials performed in Asia had a positive treatment effect (relative risk = 0.57 [95% CI, 0.47 to 0.69], P < 0.001). Hemofiltration (relative risk = 0.79 [95% CI, 0.63 to 1.00], P = 0.05, very low certainty evidence) and plasmapheresis (relative risk = 0.63 [95% CI, 0.42 to 0.96], P = 0.03, very low certainty evidence) were associated with a lower mortality. Conclusions Very low-quality randomized evidence demonstrates that the use of hemoperfusion, hemofiltration, or plasmapheresis may reduce mortality in sepsis or septic shock. Existing evidence of moderate quality and certainty does not provide any support for a difference in mortality using polymyxin B hemoperfusion. Further high-quality randomized trials are needed before systematic implementation of these therapies in clinical practice.

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Section: Search Results and Study Characteristicsmentioning

confidence: 99%

Blood Purification and Mortality in Sepsis and Septic Shock

et al. 2019

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“…Gibot et al[ 30 ] (2007) demonstrated that serum HMGB1 levels greater than 4000 pg/mL (4 ng/mL) on the third evaluation day patients with septic shock were associated with a higher risk of death, with an odds ratio equal to 5.5 and ranging from 1.3-23.6 considering the 95% confidence interval. However, as occurred in the current study, the authors found no significant association between HMBG1 and the clinical and laboratory parameters that make up the SOFA score when these were assessed separately[ 30 , 31 ]. Other authors have failed to demonstrate an association between serum HMGB1 levels and patient survival in other clinical situations[ 32 , 33 ].…”

Section: Discussionmentioning

confidence: 48%

Association between thrombomodulin and high mobility group box 1 in sepsis patients

Rodrigues¹,

Rodrigues²,

Rodrigues³

et al. 2020

WJCCM

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BACKGROUND High mobility group box 1 (HMGB1) has been studied as a molecule associated with severe outcomes in sepsis and thrombomodulin (TM) seems to decrease HMGB1 activity. AIM To investigate the role of the thrombomodulin/high mobility group box 1 (T/H) ratio in patients with sepsis and their association with their clinic, testing the hypothesis that higher ratios are associated with better outcomes. METHODS Twenty patients diagnosed with sepsis or septic shock, according to the 2016 criteria sepsis and septic shock (Sepsis-3), were studied. Patients were followed until they left the intensive care unit or until they achieved 28 d of hospitalization (D28). The following clinical outcomes were observed: Sequential Organ Failure Assessment (SOFA) score; Need for mechanical pulmonary ventilation; Presence of septic shock; Occurrence of sepsis-induced coagulopathy; Need for renal replacement therapy (RRT); and Death. RESULTS The results showed that patients with SOFA scores greater than or equal to 12 points had higher serum levels of TM: 76.41 ± 29.21 pg/mL vs 37.41 ± 22.55 pg/mL among those whose SOFA scores were less than 12 points, P = 0.003. The T/H ratio was also higher in patients whose SOFA scores were greater than or equal to 12 points, P = 0.001. The T/H ratio was, on average, three times higher in patients in need of RRT (0.38 ± 0.14 vs 0.11 ± 0.09), P < 0.001. CONCLUSION Higher serum levels of TM and, therefore, higher T/H ratio in the first 24 h after the diagnosis of sepsis were associated with more severe disease and the need for renal replacement therapy, while those with better clinical outcomes and those who were discharged before D28 showed a tendency for lower T/H ratio values.

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“…Table 1), and the mean age was 59 years. Twenty-one studies started treatment within 24 h of sepsis diagnosis [9, 19, 36, 37, 41, 44-46, 48-53, 56, 58, 60, 62, 65, 68, 69]. In the other studies, treatment was initiated up to 6 days from diagnosis of sepsis.…”

Section: Resultsmentioning

confidence: 99%

“…These included 2,729 patients, of whom 1,393 (51%) were randomized to the treatment arm (online suppl. [49,68], and 1 used plasma exchange [36].…”

Section: Study Characteristicsmentioning

confidence: 99%

Effect of Extracorporeal Blood Purification on Mortality in Sepsis: A Meta-Analysis and Trial Sequential Analysis

et al. 2020

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Objective: The objective of this study was to conduct a meta-analysis and trial sequential analysis (TSA) of published randomized controlled trials (RCTs) to determine whether mortality benefit exists for extracorporeal blood purification techniques in sepsis. Data Sources: A systematic search on MEDLINE, Embase, and the Cochrane Central Register of Controlled Trials for RCTs was performed. Study Selection: RCTs investigating the effect of extracorporeal blood purification device use on mortality among critically ill septic patients were selected. Data Extraction: Mortality was assessed using Mantel-Haenszel models, and I2 was used for heterogeneity. Data are presented as odds ratios (OR); 95% confidence intervals (CIs); p values; I2. Using the control event mortality proportion, we performed a TSA and calculated the required information size using an anticipated intervention effect of a 14% relative reduction in mortality. Data Synthesis: Thirty-nine RCTs were identified, with 2,729 patients. Fourteen studies used hemofiltration (n = 789), 17 used endotoxin adsorption devices (n = 1,363), 3 used nonspecific adsorption (n = 110), 2 were cytokine removal devices (n = 117), 2 used coupled plasma filtration adsorption (CPFA) (n = 207), 2 combined hemofiltration and perfusion (n = 40), and 1 used plasma exchange (n = 106). On conventional meta-analysis, hemofiltration (OR 0.56 [0.40–0.79]; p < 0.001; I2 = 0%), endotoxin removal devices (OR 0.40 [0.23–0.67], p < 0.001; I2 = 71%), and nonspecific adsorption devices (OR 0.32 [0.13–0.82]; p = 0.02; I2 = 23%) were associated with mortality benefit, but not cytokine removal (OR 0.99 [0.07–13.42], p = 0.99; I2 = 64%), CPFA (OR 0.50 [0.10–2.47]; p = 0.40; I2 = 64%), or combined hemofiltration and adsorption (OR 0.71 [0.13–3.79]; p = 0.69; I2 = 0%). TSA however revealed that based on the number of existing patients recruited for RCTs, neither hemofiltration (TSA-adjusted CI 0.29–1.10), endotoxin removal devices (CI 0.05–3.40), nor nonspecific adsorption devices (CI 0.01–14.31) were associated with mortality benefit. Conclusion: There are inadequate data at present to conclude that the use of extracorporeal blood purification techniques in sepsis is beneficial. Further adequately powered RCTs are required to confirm any potential mortality benefit, which may be most evident in patients at greatest risk of death.

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Blood purification treatment initiated at the time of sepsis diagnosis effectively attenuates serum HMGB1 upregulation and improves patient prognosis

Cited by 9 publications

References 37 publications

Blood Purification and Mortality in Sepsis and Septic Shock

Blood Purification and Mortality in Sepsis and Septic Shock

Association between thrombomodulin and high mobility group box 1 in sepsis patients

Effect of Extracorporeal Blood Purification on Mortality in Sepsis: A Meta-Analysis and Trial Sequential Analysis

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