The efficacy and safety of plasma exchange in patients with sepsis and septic shock: a systematic review and meta-analysis
Critical Care (London, England). 2014;18((6):):699.
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.
A comparison of methods of pathogen inactivation of FFP
Vox Sanguinis. 2011;100((2):):169-78.
Introduction Current methods for pathogen inactivation of plasma involve four major processes using solvent-detergent (SD), methylene blue (MB), amotosalen and riboflavin as additives. Three of these methods involve the use of visible or ultraviolet light. Methods A comparison of the four methods was made using publications in Medline, Pubmed, Embase and Biosis to obtain data on the logistics of use, the quality of the plasma proteins and the effectiveness of pathogen inactivation. Results Three of the methods, MB, amotosalen and riboflavin, are designed for use in a blood bank; the SD method is generally applied at a centralized manufacturing centre and involves large plasma pools. All methods result in a reduction in protein values with the per cent retention of FVIII activity in the range of 67-78% and fibrinogen of 65-84%. Protein S and alpha(2) -antiplasmin are lower following solvent-detergent treatment. Alterations in fibrinogen structure have been reported with methylene blue. Discussion Three of the methods are designed for small volume use in a blood bank. All four methods have some effect on the coagulant proteins; however, the final concentrations are within regulated limits. While there is variability in the effectiveness against pathogens, direct comparison is difficult because of the methodologies used. Nonetheless, all are effective in inactivating HIV and other lipid-enveloped pathogens. Clinical studies on the effectiveness of these products are surprisingly sparse, and no randomized clinical trials have yet been performed with amotosalen or riboflavin plasmas.
Early results of a randomized trial of blood conservation methods in patients undergoing radical prostatectomy
Transfusion Alternatives in Transfusion Medicine. 2006;8((1s):):67. Abstract No. P30.
Does cryosupernatant plasma improve outcome in thrombotic thrombocytopenic purpura? No answer yet
British Journal of Haematology. 2005;129((1):):79-86.
A randomized prospective trial compared cryosupernatant plasma (CSP) to fresh frozen plasma (FFP) for treatment of thrombotic thrombocytopenic purpura (TTP). A total of 236 patients were required: 28 patients were treated with CSP and 24 with FFP within 30 months. There were no differences in survival at 1 month. By day 9, 17 of 26 patients with CSP and 18 of 24 with FFP had a platelet count >100 x 10(9)/l. At entry, von Willebrand factor (VWF) multimers were normal in all patients (range 1. 1-3. 95 IU/ml). ADAMTS-13 levels showed large variations ranging from 10% to 100% activity. At entry, no individual had <5% VWF cleaving protease. By day 9 (end of cycle), 89% (FFP) and 67% (CSP) had levels >50% of the controls. At 6 months some patients showed inhibitors to the enzyme in spite of adequate or normal platelet counts. The data from this study do not show an apparent advantage to the use of CSP in TTP. A large number of patients will be required to determine appropriate replacement therapy. We were not able to find a statistically significant relationship between the low level of protease activity at presentation of TTP and response.
Feasibility of blinding in a randomized controlled trial comparing preoperative autologous blood donation and acute normovolemic hemodilution in adult cardiac surgery
BACKGROUND Acute normovolemic hemodilution and preoperative autologous donation have been shown to be effective techniques for decreasing the exposure of patients to allogeneic blood during cardiac surgery. They have not, however, been compared to each other, because of perceived difficulties in blinding in such a clinical study. The feasibility of blinding was tested in a pilot trial. STUDY DESIGN AND METHODS Ten patients were randomly assigned to undergo preoperative autologous blood donation or acute normovolemic hemodilution during cardiac surgery. Patients were blinded during this process by shielding of the arm and by insertion of an intravenous line in each patient. Every attempt was made to blind the clinical staff during and after surgery. The effectiveness of this blinding was determined by using a questionnaire. RESULTS In the 10 cases, six patients, four surgeons, and one anesthetist answered, "I do not know," with respect to whether preoperative autologous blood donation had occurred. The remaining people interviewed believed the blinding was unsuccessful. However, correct answers were given by 75 percent of the patients (95% CI, 19-99%), 83 percent of the surgeons (95% CI, 36-99.6%), and 66 percent of the anesthetists (95% CI, 29.9-92.5%). The frequency of correct answers did not differ significantly from the 50 percent expected by chance, but the CIs are wide. CONCLUSIONS Blinding of patients and all members of the surgical team during both the preoperative donation process and acute normovolemic hemodilution in the operating theater was successful most of the time, as the frequency of correct answers did not differ significantly from the 50 percent expected by chance. However, more accurate estimates of the success of blinding require a study with a larger sample. It is possible that, with a larger series, the physician's ability to determine patient assignment would be significantly better than that by chance alone.
Treatment of Guillain-Barré syndrome: a cost-effectiveness analysis
Journal of Clinical Apheresis. 1999;14((3):):107-13.