Efficacy and safety of blood purification in the treatment of deep burns: A systematic review and meta-analysis.

INTRODUCTION: This meta-analysis aimed to systematically review and evaluate randomized controlled trials (RCTs) and cohort studies examining the efficacy and safety of blood purification in the treatment of patients with deep burns. METHODS: The PubMed, Cochrane Library, and Embase databases and relevant references were systematically searched for RCTs and cohort studies published until the end of September 2020 to investigate the potential of blood purification in improving the prognosis of severely burned patients. The primary outcome of this systematic review was overall patient mortality; secondary outcomes included the incidence of sepsis and infection prevention (vital signs and routine blood tests). RESULTS: A total of 6 RCTs and 1 cohort study were included, with a total of 538 burn patients (274 patients who received blood purification and 264 control patients). Compared with patients who received conventional treatment, those treated with blood purification displayed significant 2-day reduction in mortality and sepsis with relative risks of 0.62 and 0.41, respectively (95% confidence intervals [CIs], 0.74-0.82 and 0.25-0.67, respectively; P < .05). In terms of vital signs and blood biochemistry, the respiratory rates and blood urea nitrogen levels of patients in the blood purification group 3 days post-treatment were significantly higher than those in the control group (randomized standard deviations (SMDs), 0.78 and 0.77, respectively; 95% CIs, 0.33-1.23 and 1.22-0.31, respectively; P < .05). However, there were no significant differences between groups on day 3 with regard to temperature (P = .32), heart rate (P = .26), white blood cell count (P = .54), or neutrophil count (P = .74), potentially owing to the small sample size or the relatively short intervention time. Heterogeneous differences existed between the groups with respect to blood urea nitrogen (SMD = -1.22; 95% CI, -2.16 to -0.40; P < .00001) and Cr (SMD = -3.13; 95% CI, -4.92 to -1.33; P < .00001) on day 7. No systematic adverse events occurred. CONCLUSIONS: Blood purification treatment for deep burn patients can significantly reduce the mortality rate and the incidence of complications.

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

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.

Favorable Outcome of an Exclusively Posttransplant Prophylactic Strategy After Heart Transplantation in Recipients With High Immunological Risk.

BACKGROUND: Management of the increasing number of sensitized heart transplant candidates has become a recurrent issue. Rather than using pretransplant desensitization therapies, we used a posttransplant prophylactic strategy. Our aim was to describe outcomes in transplant recipients with preformed donor-specific anti-HLA antibodies (pfDSA) managed with this strategy. METHODS: A posttransplant protocol was applied to patients transplanted with pfDSA, consisting of perioperative management of DSA (polyvalent immunoglobulins +/- perioperative plasmapheresis sessions, according to DSA level, as well as induction therapy) and systematic treatment of subsequent antibody-mediated rejection (AMR), even when subclinical. We performed a retrospective analysis of this prospective protocol. The study included all consecutive first recipients of a noncombined heart transplant performed between 2009 and 2015 at our center. The primary endpoint was all-cause mortality. Secondary endpoints included primary graft dysfunction, early posttransplant bleeding, rejection, and cardiac allograft vasculopathy-free survival. RESULTS: A total of 523 patients were studied, including 88 (17%) and 194 (37%) transplanted with DSA mean fluorescence intensity (MFI) of 500 to 1000 and greater than 1000, respectively. The median follow-up period was 4.06 years. Survival was not significantly different between groups. Rejection-free survival was worse in patients with pfDSA MFI >1000, evidenced by a fourfold increase in the risk of antibody-mediated rejection. The incidence of primary graft dysfunction and cardiac allograft vasculopathy-free survival did not significantly differ between groups. Perioperative plasmapheresis increased the risk for transfusion of packed red blood cells. CONCLUSIONS: This exclusively posttransplant prophylactic strategy achieved favorable outcomes in heart transplant recipients with pfDSA.

Lower In-Hospital Mortality with Plasma Exchange than Plasmapheresis in a Subgroup Analysis of 374 Lupus Patients.

BACKGROUND: Apheresis treatment includes plasmapheresis (PP) and plasma exchange (PE), and these terms are commonly used interchangeably. Nevertheless, the two procedures are carried out differently. The aims of this study were to investigate the mortality rate of patients who underwent therapeutic apheresis and compare the mortality rate between PP and PE. METHODS: We conducted a medical chart review retrospective study. All identified subjects (n = 436) were over 20 years old with at least one ICD-9-CM intervention code plasmapheresis or plasma exchange and at least one diagnosis code with rheumatic disease. All of them were hospitalized to Chang Gung Memorial Hospital between 1st of January, 2000, and 31st of December, 2014. RESULTS: 436 nonoverlapping patients had never received PE and/or PP before 1 Jan, 2000. Among all the patients, 350 received PE, 63 received PP, and 23 received both therapies. Female patients accounted for 85.09% of patients. The overall mortality rate was 4.65% in the PE subgroup, 4.76% with combination therapy, and 13.46% in the PP subgroup. There were 374 patients diagnosed as SLE, which is the majority of overall patients who received PE and/or PE. In multivariate analysis, PE was the sole independent factor predictor of survival in SLE subgroup patients (p = 0.02, exp(B) = 0.314, 95% CI 0.12-0.81). CONCLUSIONS: We showed that both PP and PE were used in treating a variety of autoimmune disorders. Plasmapheresis was preferentially carried out in patients with peripheral neuropathy. In 374 lupus patients treated with either PE or PP, PE is superior to PP in reducing in-hospital mortality.

A comparison of desensitization methods: Rituximab with/without plasmapheresis in ABO-incompatible living donor liver transplantation.

BACKGROUND: Plasmapheresis is a desensitization method used prior to ABO-incompatible (ABO-I) living donor liver transplantation. However, studies on its usefulness in the rituximab era are lacking. METHODS: Fifty-six adult patients underwent ABO-I living donor liver transplantation between January 2012 and October 2015. A single dose of rituximab (300 mg/m2) was administered 2 weeks before surgery with plasmapheresis in all patients until February 2014 (RP group, n = 26). Patients were administered rituximab only, without plasmapheresis between March 2014 and October 2015 (RO group, n = 30). RESULTS: The 6-, 12- and 18-month overall survival rates were 92.3%, 80.8% and 76.9% in the RP group and 96.6%, 85.4% and 85.4% in the RO group, respectively (P = 0.574). When the initial isoagglutinin titers < 16, neither group showed a rebound rise of isoagglutinin titers. For patients with initial isoagglutinin titers ≥ 16, the rebound rise of isoagglutinin titers was more prominent in the RP group. There was no difference in time-dependent changes in B cell subpopulations and ABO-I-related complications. CONCLUSIONS: Sufficient desensitization for ABO-I living donor liver transplantation can be achieved using rituximab alone. This desensitization strategy does not affect the isoagglutinin titers, ABO-I-related complications and patient survival.

The effect of plasmapheresis on treating disseminated intravascular coagulation (DIC) caused by a Hemiscorpius lepturus (Gadim) sting.

INTRODUCTION: The highest mortality from scorpion stings in Iran is due to the stings of a particular type of scorpion known as Hemiscorpius lepturus (H. lepturus, Gadim in local language). The present study aimed at investigating the use of plasmapheresis to treat severe cases of H. lepturus stings. METHOD: This pilot study was a randomized clinical trial conducted from June 2015 to June 2016 in Razi hospital of Ahvaz, Iran. Twenty-nine patients who had been stung by H. lepturus and admitted to ICU because of disseminated intravascular coagulation (DIC) were randomly assigned into control (15 patients, supportive treatments) and plasmapheresis (14 patients, supportive treatments + plasmapheresis) groups, and the patient outcomes were compared between the two groups. FINDINGS: Eighteen patients were female (62%), and the mean of patient age was 24 ± 7. Most of the sting cases had occurred in the torso (15 patients, 52%). Only 10 patients (34%) arrived in the hospital within 12 h of being stung. There was no significant difference between the two groups in terms of the demographic and sting features. In the plasmapheresis group, hemoglobin level was significantly lower, while the PT and INR were measurably higher. In total, the plasmapheresis group experienced 29 sessions of treatment (an average of two sessions for each patient). Overall, 19 patients (66%) expired, whereas 10 patients (34%) experienced recovery with or without complications. The rate of recovery was significantly higher in the plasmapheresis group compared with controls, with eight patients (57%) in the plasmapheresis group surviving compared with two (14%) in the control group (p=.045). The duration of hospitalization was higher in the plasmaphersis group (p < .001). A comparison of the dead and recovered patients' features indicated that the dead patients arrived in the hospital significantly later than the recovered ones, and they also had lower platelet counts. CONCLUSIONS: The findings of this small-scale pilot study show that using plasmapheresis in treating DIC in patients stung by H. lepturus can prevent death and encourage recovery. However, prior to using plasmapheresis as a routine treatment for severe cases of people stung by this scorpion or other similar ones, further controlled studies with a larger sample size are needed.

Renal vasculitis presenting with acute kidney injury.

Renal failure secondary to ANCA-associated vasculitis represents a clinical and therapeutic challenge. In this study, we aimed to assess the treatment response rates and long-term outcomes of vasculitis patients presenting with renal failure. This retrospective study included 151 patients with renal vasculitis from three hospitals who underwent a renal biopsy between 1997 and 2014. Patients with renal failure which required dialysis at the onset were compared to those presenting with more preserved renal function. The primary end point was treatment response and patient surivival. Patients with severe renal involvement had a lower response to treatment compared to those having preserved renal function (26.6 versus 93.4%; p < 0.001). Dialysis-dependent patients who received plasmapheresis in addition to immune suppressants associated a higher rate of renal recovery (41.6 versus 12.5%; p = 0.05). A higher incidence of severe infections was observed among patients with severe renal involvement (38.4 versus 18.1%, p = 0.01). The mortality rate was significantly higher among vasculitis patients presenting with renal failure (53.8 versus 22.2%, p = 0.001). Global survival at 1 and 5 years was 60 and 47% in patients requiring dialysis compared with 90 and 80% among those with more preserved renal function (p < 0.001). After multivariate adjustment, the need for dialysis remained as an independent predictor of death (HR 2.5; 95% CI 1.1-5.7; p = 0.03). The presence of severe renal dysfunction represents an independent risk factor for patient survival in renal vasculitis. Patients requiring dialysis associate a lower response rate to immunosuppressive therapy and a higher incidence of severe infections.

[Therapy of ANCA-associated vasculitis with severe renal manifestation under routine conditions]. / Therapie der ANCA-assoziierten Vaskulitis mit schwerer renaler Beteiligung unter Routinebedingungen.

INTRODUCTION: In the MEPEX trial the poor prognosis of antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis with severe renal manifestation (AAVr) could be significantly improved in the first year by plasmapheresis. How and to what extent is this knowledge of AAVr therapy implemented into routine practice and what effectiveness and adverse events resulted? METHODS: This was a retrospective cohort study in which all patients who received remission induction therapy for AAVr under routine clinical conditions (RCC) in this hospital from 2009 to 2014 after publication of the MEPEX trial (n = 22) were compared with those in the plasmapheresis arm of the MEPEX trial (n = 70). Endpoints were dialysis-dependent chronic kidney disease and mortality after 3 and 12 months and severe life-threatening adverse events during the first 12 months. RESULTS: All patients with AAVr were treated by plasmapheresis under RCC. The two groups showed no differences with respect to the rate of dialysis dependency (after 3 months RCC 14 % versus MEPEX 16 %, P = 1.00 and after 12 months RCC 23 % versus MEPEX 14 %, P = 0.55) or mortality (after 3 months RCC 18 % versus MEPEX 16 %, P = 0.75 and after 12 months RCC 18 % versus MEPEX 27 %, P = 0.57). The rate of severe life-threatening adverse events was similar under RCC and under controlled study conditions (64 % versus 69 %, P = 0.87). CONCLUSION: Under RCC there is a high quality of medical treatment for AAVr. All patients received plasmapheresis for remission induction with comparable effectiveness and safety compared to controlled study conditions.

Plasmapheresis therapy in ANCA-associated vasculitides: A single-center retrospective analysis of renal outcome and mortality.

BACKGROUND: The evidence of the benefit of plasmapheresis in renal and survival outcomes in patients with severe manifestations of ANCA-associated vasculitides is inconsistent. PURPOSE: To address whether plasmapheresis is associated with improvement in renal function and survival at 12 months in patients with severe manifestations of ANCA-associated vasculitides. PATIENTS AND METHODS: Single-center retrospective comparative cohort of 24 patients with granulomatosis with polyangiitis or microscopic polyangiitis that received plasmapheresis adjunctive to conventional therapy (steroids and immunosuppressants), matched 1:1 according to age, estimated glomerular filtration rate (eGFR) and disease activity with 24 patients treated with standard treatment only. Comorbidities, demographic, clinical, treatment and laboratory characteristics were recorded. RESULTS: After 12 months both groups showed improvement in eGFR (19.0 ± 14.34 to 41.61 ± 37.77 ml/min, p = 0.003 in plasmapheresis group; 23.16 ± 14.71 to 39.86 ± 25.67 ml/min, p = 0.001 in conventional therapy group). No differences were found between groups (p = 0.68). Patients free of dialysis at 12 months after intervention increased in the plasmapheresis group from 9/24 (38%) to 12/24 (50%), p = 0.5; and in the conventional therapy group from 19/24 (79%) to 22/24 (92%), p = 0.25. Difference between groups was significant at 12 months (p = 0.001). Survival at 12 months after intervention was 79% in the plasmapheresis group and 96% in the conventional therapy group (p = 0.08). The main cause of death was infectious and a tendency for a higher prevalence of severe infections was observed in patients that received plasmapheresis (p = 0.07). CONCLUSION: Both plasmapheresis and conventional therapy improved eGFR at 12 months after intervention. Dialysis independence and survival were similar between groups. J. Clin. Apheresis 31:411-418, 2016. © 2015 Wiley Periodicals, Inc.

Outcomes Following ABO-Incompatible Kidney Transplantation Performed After Desensitization by Nonantigen-Specific Immunoadsorption.

BACKGROUND: For desensitization of ABO-incompatible kidney transplant recipients we recently proposed nonantigen-specific immunoadsorption (IA) and rituximab. METHODS: We now compared clinical outcomes of 34 ABO-incompatible living-donor kidney recipients who were transplanted using this protocol with that of 68 matched ABO-compatible patients. In addition, we analyzed efficacy and cost of nonantigen-specific as compared to blood group antigen-specific IA. RESULTS: Before desensitization, the median isoagglutinin titer of 34 ABO-incompatible patients was 1:64 (Coombs technique). Patients received a median of 7 preoperative IA treatments. Twenty-four patients had a median of 2 additional plasmapheresis treatments to reach the preoperative target isoagglutinin titer of 1:8 or less. After a median postoperative follow-up of 22 months, overall graft survival in the ABO-incompatible group was not significantly different from that in ABO-compatible patients (log-rank P = 0.20), whereas patient survival tended to be lower (log-rank P = 0.05). The incidence of rejection episodes was 15% in both groups. The ABO-incompatible kidney recipients had a higher incidence of BK virus replication (P = 0.04) and nephropathy (P = 0.01) and showed more often colonization with multidrug resistant bacteria (P = 0.02). In comparison to blood group antigen-specific IA, nonantigen-specific IA showed equal efficacy but was associated with reduction in cost. CONCLUSIONS: Clinical outcomes of ABO-incompatible patients desensitized with a nonantigen-specific IA device and rituximab do not differ from that of matched ABO-compatible patients although a trend toward reduced patient survival was noted. Special attention must be paid to the higher incidence of BK virus infection in recipients of ABO-incompatible grafts.

Chemotherapy with or without plasmapheresis in acute renal failure due to multiple myeloma: a meta-analysis.

BACKGROUND/AIM: The clinical benefits of plasmapheresis in the management of multiple myeloma-induced acute renal failure remain controversial. In this study, we conducted a meta-analysis to quantitatively evaluate the clinical efficacy of chemotherapy with or without plasmapheresis in the treatment of multiple myeloma patients with renal failure. METHODS: Randomized controlled trials evaluating clinical efficacy of plasmapheresis were identified by searching PubMed (from 1980 to November 2013) and EMBASE (from 1980 to November 2013). Outcomes subjected to meta-analysis were 6-month survival and dialysis-dependent rate. RESULTS: Three randomized controlled studies were selected for meta-analysis. A total of 63 patients received chemotherapy only and 84 patients were given both chemotherapy and plasmapheresis. No difference was observed in 6-month survival rate between plasmapheresis and control group (75% vs. 66.7%; risk ratio, 0.92; 95% CI, 0.76 - 1.11; p = 0.39). 6-month dialysis-dependent ratio was significantly lower in patients treated with both chemotherapy and plasmapheresis than chemotherapy only (15.6% vs. 37.2%; risk ratio, 2.02; 95% CI, 1.03 - 3.96; p = 0.04). CONCLUSION: Our meta-analysis results showed that plasmapheresis used as an adjunct to chemotherapy had a benefit in the management of dialysisdependent multiple myeloma patients with renal failure.

Push-pull sorbent-based pheresis treatment in an experimental canine endotoxemia model: preliminary report.

The Biologic-DTPF System (DTPF), an extracorporeal blood treatment device with potential to treat sepsis, was tested in a preliminary study using a canine endotoxemia model. Six dogs were used and they formed four treatment groups, as control group (n=1) and three groups based on the type of sorbent present in the plasma filter (PF) system: sham treatment with no sorbent (n=1), charcoal as sorbent (n=2), and charcoal/silica as sorbent ("silica" group, n=2). Cardiodynamic data were recorded before treatment and every 30 minutes, and blood samples were collected to determine blood chemistry and to detect the levels of endotoxin and selected plasma cytokines: interleukin-1 (IL-1), interleukin-6 (IL-6), and tumor necrosis factor (TNF). The dogs were given Escherichia coli endotoxin (2 mg/kg) as an intravenous drip (extended over a period of 30 minutes). Thirty minutes after the end of infusion all animals except the control were treated with the DTPF system for four hours. To determine the effect of treatment, data collected at one hour from the initiation of treatment until the end of treatment were compared between control and treated dogs. The endotoxin levels in the control dog were higher (P < 0.05) than other groups. The control dog had lower levels of TNF than other groups. The control dog had similar levels of IL-1 (P > 0.05) and higher levels (P < 0.05) at 4 hours into treatment compared to other groups. The control dog had similar levels of IL-6 as other groups (P > 0.05). In the control dog, the mean arterial pressure (MAP) fell and then remained low but stable at 1-4 hours. The charcoal group had lower MAP than the control dog at 1-4 hours (P < 0.05). The silica group had higher MAP levels similar to the control dog. After treatment, the control dog had higher (P < 0.05) values of hematocrit, hemoglobin, calcium, potassium, and albumin compared to the treated groups. As expected for a system removing plasma during sepsis, the DTPF System had some adverse effects on the physiologic status of the dogs, especially when loaded with charcoal sorbent only. The findings of the present study suggest that the filters are capable of eliminating endotoxin and there is some evidence of cytokine removal. Although the charcoal dogs did poorly, addition of silica to the sorbent offset any negative effects. Further work is underway to improve the efficiency of the system, primarily to enhance the capacity of the sorbents for cytokines. A more realistic canine sepsis model with mortality after several days (the Escherichia coli- infected intraperitoneal clot) will also be considered in future studies.

Plasmapheresis in the management of heparin-induced thrombocytopenia.

This study investigated the role of plasmapheresis in the treatment of severe heparin-induced thrombocytopenia (HIT). Patients diagnosed with HIT were divided into three experimental groups. Sixteen patients did not receive plasmapheresis (control). Twenty-one patients received plasmapheresis within 4 days of onset of thrombocytopenia (early group). Seven patients received plasmapheresis 4 days or later after onset (late group). Most patients underwent a second plasmapheresis 24 to 48 hours after the first, when clinically indicated, and platelet aggregation tests became negative in 75% of these patients. Heparin administration was discontinued after 1.4 days in the early group of patients and 4.2 days in the late group, as compared with 2.4 days in the control group. The 30-day mortality rate was 4.8% among patients in the early group and 57% in the late group, as compared with 32% in the control group. Platelet recovery time, incidence of thrombotic events, and length of hospital stay were similar in the early group and controls, but were somewhat higher in the late group. Thus, plasmapheresis within 4 days of the onset of thrombocytopenia reduced mortality in HIT patients, whereas plasmapheresis after 4 days was not beneficial. There were no adverse events related to plasmapheresis. These findings suggest that plasmapheresis may be useful in the treatment of HIT when initiated within 4 days of onset of thrombocytopenia.

The effect of serial therapeutic plasmapheresis on platelet count, coagulation factors, plasma immunoglobulin, and complement levels.

One hundred therapeutic plasmaphereses were carried out at biweekly intervals in seven patients, without morbidity or mortality, using the IBM 2997 blood fraction separator. In standardised procedures, 1.5 times the calculated plasma volume was replaced with an electrolyte solution containing 4% salt-free human albumin. Anticoagulation was achieved using a whole venous blood to acid-citrate dextrose ratio of 11 to 1. Median flow rates, plasma collection, and procedure times were respectively 40 ml/minute, 20 ml/minute, and 3 hours. Haemoglobin and total white cell counts were not significantly affected by the procedures. In contrast, platelet count, fibrinogen, immunoglobulin levels, total haemolytic complement, as well as C3 and C4 fractions fell, and the prothrombin and partial thromboplastin times were lengthened by the exchanges. All these measurements had returned to normal within 24 hours, apart from the fibrinogen, which took between 48 and 72 hours, and the immunoglobulin level, which required 35 days to return to baseline. In a further patient, more detailed studies (n = 13) were carried out to characterise the behaviour of antithrombin III and factor VIII. Both levels were markedly reduced immediately following the procedure and, like fibrinogen, had returned to normal within 48 hours. These data indicate that in an isovolemic plasmapheresis there was a transient but rapidly reversible effect on all the factors studied, with fibrinogen level, antithrombin III, and factor VIII returning more slowly to normal than the others, and immunoglobulin levels responding the slowest. None of these changes was associated with clinically significant haemostatic abnormalities.(ABSTRACT TRUNCATED AT 250 WORDS)