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Survival Benefits of Therapeutic Plasma Exchange in Severe Sepsis and Septic Shock: A Systematic Review and Meta-analysis
Lee OPE, Kanesan N, Leow EH, Sultana R, Chor YK, Gan CS, Lee JH
Journal of intensive care medicine. 2023;:8850666231170775
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Editor's Choice
Abstract
OBJECTIVES To summarize the role of therapeutic plasma exchange (TPE) in critically ill adults and children with severe sepsis. DATA COLLECTION A systematic search was performed using the following databases: Medline, EMBASE, CINAHL, and Cochrane from January 1990 till December 2022. Comparative studies of TPE in severe sepsis were selected. Adult and pediatric data were analyzed separately. DATA SYNTHESIS Eight randomized control trials and 6 observational studies (n = 50,142 patients) were included. Centrifugal TPE was the most common modality (209/280, 74.6% adults and 952/1026, 92.7% children). Every TPE study utilized different volume exchanges. Most TPE sessions (1173/1306, 89.8%) employed fresh frozen plasma (FFP) as replacement fluid and heparin as anticoagulant. Adults with severe sepsis supported with TPE using FFP had lower mortality (risk ratio, RR: 0.64 [95% confidence interval, CI: 0.49, 0.84]) compared to those who did not. In contrast, TPE was associated with increased mortality in septic children without thrombocytopenia-associated multiorgan failure (RR: 2.23, 95% CI: 1.93, 2.57). There was no difference in outcomes in patients supported with centrifugal and membrane TPE. In both populations, patients supported on TPE as a continuous regime had poorer outcome. CONCLUSION Current evidence indicates that TPE is a potential adjunct therapy in adults with severe sepsis but not in children.
PICO Summary
Population
Critically ill adults and children with severe sepsis or septic shock (14 studies, n= 50,142).
Intervention
Therapeutic plasma exchange (TPE) alone, or in combination with hemofiltration, hemadsorption, or conventional treatment of sepsis.
Comparison
Various comparators, including: other forms of blood purification therapy, immunomodulation and conventional treatment.
Outcome
Centrifugal TPE was the most common modality (209/280, 74.6% adults and 952/1,026, 92.7% children). Every TPE study utilized different volume exchanges. Most TPE sessions (1,173/1,306, 89.8%) employed fresh frozen plasma (FFP) as replacement fluid and heparin as anticoagulant. Adults with severe sepsis supported with TPE using FFP had lower mortality (risk ratio (RR), 0.64 [95% confidence interval (CI) [0.49, 0.84]) compared to those who did not. In contrast, TPE was associated with increased mortality in septic children without thrombocytopenia-associated multiorgan failure (RR, 2.23; 95% CI [1.93, 2.57]). There was no difference in outcomes in patients supported with centrifugal and membrane TPE. In both populations, patients supported on TPE as a continuous regime had poorer outcome.
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Blood Purification for Adult Patients With Severe Infection or Sepsis/Septic Shock: A Network Meta-Analysis of Randomized Controlled Trials
Chen, J. J., Lai, P. C., Lee, T. H., Huang, Y. T.
Critical care medicine. 2023
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Abstract
OBJECTIVES This study aimed to conduct a comprehensive and updated systematic review with network meta-analysis (NMA) to assess the outcome benefits of various blood purification modalities for adult patients with severe infection or sepsis. DATA SOURCES We conducted a search of PubMed, MEDLINE, clinical trial registries, Cochrane Library, and Embase databases with no language restrictions. STUDY SELECTION Only randomized controlled trials (RCTs) were selected. DATA EXTRACTION The primary outcome was overall mortality. The secondary outcomes were the length of mechanical ventilation (MV) days and ICU stay, incidence of acute kidney injury (AKI), and kidney replacement therapy requirement. DATA SYNTHESIS We included a total of 60 RCTs with 4,595 participants, comparing 16 blood purification modalities with 17 interventions. Polymyxin-B hemoperfusion (relative risk [RR]: 0.70; 95% CI, 0.57-0.86) and plasma exchange (RR: 0.61; 95% CI, 0.42-0.91) were associated with low mortality (very low and low certainty of evidence, respectively). Because of the presence of high clinical heterogeneity and intransitivity, the potential benefit of polymyxin-B hemoperfusion remained inconclusive. The analysis of secondary outcomes was limited by the scarcity of available studies. HA330 with high-volume continuous venovenous hemofiltration (CVVH), HA330, and standard-volume CVVH were associated with shorter ICU stay. HA330 with high-volume CVVH, HA330, and standard-volume CVVH were beneficial in reducing MV days. None of the interventions showed a significant reduction in the incidence of AKI or the need for kidney replacement therapy. CONCLUSIONS Our NMA suggests that plasma exchange and polymyxin-B hemoperfusion may provide potential benefits for adult patients with severe infection or sepsis/septic shock when compared with standard care alone, but most comparisons were based on low or very low certainty evidence. The therapeutic effect of polymyxin-B hemoperfusion remains uncertain. Further RCTs are required to identify the specific patient population that may benefit from extracorporeal blood purification.
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An inquiry into the treatment of sepsis using plasma exchange therapy: A systematic review and meta-analysis
Zhang L, Zhao XY, Guo SY, Jiang J, Wang G, Weng YB
International wound journal. 2023
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Abstract
Sepsis is a potentially lethal condition that occurs when the body's response to infection damages tissue and organs. The production of inflammatory mediators typically assists in defending the body against infection; however, an overreaction to inflammation can cause coagulation problems, vascular endothelial damage, and organ hypoperfusion. Blood purification methods, such as plasmapheresis, can effectively remove inflammatory mediators from plasma. The purpose of this meta-analysis was to explore the efficacy of plasma exchange for sepsis treatment as noted in recent studies. The authors searched the Pubmed (Medline), Cochrane Central Register of Controlled Trials (The Cochrane Library), Embase (Ovid), and Scopus databases and included controlled clinical studies that compared plasmapheresis or plasma filtration with conventional treatment in patients with severe sepsis. The Newcastle-Ottawa Scale literature quality assessment tool was used to assess the risk of bias. The primary study outcome was all-cause mortality. The random effects model was adopted for conducting the meta-analysis. Among the 1013 records found, the study included 5 trials, all of which carried a low risk of bias. The use of plasmapheresis was associated with a longer stay in the intensive care unit (odds ratio [OR], 0.85, 95% confidence interval [CI], 0.39-1.32, heterogeneity [I(2) ] = 0%), a significant reduction in all-cause mortality (OR, 0.54, 95% CI, 0.33-0.89, I(2) = 70%), and reduced mortality (OR, 0.29, 95% CI, 0.13-0.67, I(2) = 0%) in adults; the results for children differed from this (OR, 0.79, 95% CI, 0.36-1.72, I(2) = 89%). Four trials reported no adverse events; one trial reported an adverse event related to plasma exchange, including an instance of hypotension in one patient. Plasmapheresis appeared to be an effective treatment for patients suffering from sepsis. A large number of additional randomised controlled trials are needed to confirm this finding.
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Coupled plasma filtration adsorption for the treatment of sepsis or septic shock: a systematic review and meta-analysis
Li, Y., Li, H., Guo, J., Wang, Y., Zhang, D.
BMC infectious diseases. 2022;22(1):714
Abstract
BACKGROUND The effect of coupled plasma filtration adsorption (CPFA) for the treatment of sepsis or septic shock is controversial. A systematic review and meta-analysis was performed to evaluate the impact of CPFA on all-cause mortality in patients with sepsis or septic shock. METHODS We searched the PubMed, Cochrane, and Embase databases for randomized controlled trials (RCTs) and cohort studies from inception to the 1st of May 2022. We included studies involving patients (˃ 14 years) with sepsis or septic shock. All authors reported our primary outcome of all-cause mortality (hospital mortality, 28-day mortality or 30-day mortality). Results were expressed as odds ratio (OR) with accompanying 95% confidence interval (CI). RESULTS Six studies including 537 patients were included. The primary outcome of this meta-analysis showed that the all-cause mortality was about 54.2% (119/243 in the CPFA group and 172/294 in the control group). There was no statistically significant difference in the all-cause mortality between two groups (odds ratio [OR] = 0.75; 95% CI 0.53 to 1.06; P = 0.11; Chi(2) = 14.04; I(2) = 64%). CONCLUSIONS The treatment of CPFA failed to decrease all-cause mortality of sepsis or septic shock patients. Further large-scale randomized controlled trials (RCTs) evaluating the ability of this therapy to improve clinical outcomes are still required to confirm these results.
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The efficacy and safety of plasma exchange in patients with sepsis and septic shock: a systematic review and meta-analysis
Rimmer, Houston BL, Kumar A, Abou-Setta AM, Friesen C, Marshall JC, Rock G, Turgeon AF, Cook DJ, Houston DS, et al
Critical Care (London, England). 2014;18((6):):699.
Abstract
INTRODUCTION Sepsis and septic shock are leading causes of intensive care unit (ICU) mortality. They are characterized by excessive inflammation, upregulation of procoagulant proteins and depletion of natural anticoagulants. Plasma exchange has the potential to improve survival in sepsis by removing inflammatory cytokines and restoring deficient plasma proteins. The objective of this study is to evaluate the efficacy and safety of plasma exchange in patients with sepsis. METHODS We searched MEDLINE, EMBASE, CENTRAL, Scopus, reference lists of relevant articles, and grey literature for relevant citations. We included randomized controlled trials comparing plasma exchange or plasma filtration with usual care in critically ill patients with sepsis or septic shock. Two reviewers independently identified trials, extracted trial-level data and performed risk of bias assessments using the Cochrane Risk of Bias tool. The primary outcome was all-cause mortality reported at longest follow-up. Meta-analysis was performed using a random-effects model. RESULTS Of 1,957 records identified, we included four unique trials enrolling a total of 194 patients (one enrolling adults only, two enrolling children only, one enrolling adults and children). The mean age of adult patients ranged from 38 to 53 years (n=128) and the mean age of children ranged from 0.9 to 18 years (n=66). All trials were at unclear to high risk of bias. The use of plasma exchange was not associated with a significant reduction in all-cause mortality (risk ratio (RR) 0.83, 95% confidence interval (CI) 0.45 to 1.52, I(2) 60%). In adults, plasma exchange was associated with reduced mortality (RR 0.63, 95% CI 0.42 to 0.96; I(2) 0%), but was not in children (RR 0.96, 95% CI 0.28 to 3.38; I(2) 60%). None of the trials reported ICU or hospital lengths of stay. Only one trial reported adverse events associated with plasma exchange including six episodes of hypotension and one allergic reaction to fresh frozen plasma. CONCLUSIONS Insufficient evidence exists to recommend plasma exchange as an adjunctive therapy for patients with sepsis or septic shock. Rigorous randomized controlled trials evaluating clinically relevant patient-centered outcomes are required to evaluate the impact of plasma exchange in this condition.
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Blood purification and mortality in sepsis: a meta-analysis of randomized trials
Zhou, F., Peng, Z., Murugan, R., Kellum, J. A.
Critical Care Medicine. 2013;41(9):2209-20
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Abstract
OBJECTIVES Although blood purification improves outcomes in animal studies of sepsis, results of clinical trials have been mixed. We conducted a systematic review and meta-analysis of randomized trials to determine the association between various blood purification techniques and all-cause mortality in humans with sepsis. DATA SOURCES We searched for relevant studies in MEDLINE, EMBASE, and the Cochrane Library database from January 1966 to May 2012. STUDY SELECTION Inclusion required a diagnosis of sepsis and comparison of blood purification techniques including hemofiltration, hemoperfusion, plasma exchange, or hemodialysis with no blood purification (control group). DATA EXTRACTION Two authors independently selected studies and extracted data. Summary statistics, risk ratios, and CIs were calculated using random-effects modeling. Study quality was assessed using Jadad score, and publication bias was assessed using funnel plots and Egger's statistic. DATA SYNTHESIS Overall, blood purification decreased mortality compared with no blood purification (35.7% vs 50.1%; risk ratio, 0.69 [95% CI, 0.56-0.84]; p<0.001; 16 trials, n=827). However, these results were driven mainly by hemoperfusion (risk ratio, 0.63 [95% CI, 0.50-0.80]; p<0.001; 10 trials, n=557) and plasma exchange (risk ratio, 0.63 [95% CI, 0.42-0.96]; p=0.03; two trials, n=128). Pooling of all trials of blood purification for treatment of sepsis was no longer associated with lower mortality (risk ratio, 0.89 [95% CI, 0.71-1.13]; p=0.36; eight trials, n=457) after excluding trials using polymyxin B hemoperfusion. CONCLUSIONS Blood purification techniques including hemoperfusion, plasma exchange, and hemofiltration with hemoperfusion were associated with lower mortality in patients with sepsis. These results were mainly influenced by studies using polymyxin B hemoperfusion from Japan.
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The efficacy and safety of therapeutic apheresis in sepsis and septic shock: a systematic review and meta-analysis
Rimmer EK, Houston BL, Kumar A, Abou-Setta A, Friesen C, Turgeon AF, Cook DJ, Houston DS, Zarychanski R
Blood. 2013;122((21):):1119.
