Abstract

OBJECTIVE The aim of this systematic scoping review is to identify and categorize the outcome measures that have been reported in clinical studies, where therapeutic plasma exchange (TPE) has been used as an intervention in any clinical settings, excluding thrombotic thrombocytopenic purpura (TTP). METHODS We searched electronic databases using a predefined search strategy from inception to October 9, 2020. Two reviewers independently screened and extracted data. RESULTS We included 42 studies (37 RCTs and 5 prospective cohort studies) grouped into six main categories (neurology, immunology, renal, rheumatology, hematology, and dermatology). Primary outcomes were defined in eight studies (19%, 8/42) and were categorized as efficacy (five studies) or patient reported outcomes (three studies). A power calculation was reported in six studies (75%, 6/8): five neurology studies (mainly patient reported outcomes) and a single immunological study (efficacy outcome). Disease-specific efficacy outcomes were dependent on the clinical setting of the population receiving TPE. Most of the trials (43%, 18/42) were undertaken in patients with neurology conditions where clear, disease-specific, clinical outcome measures were used, including neurological disability scales (11/18, 61%), change in neurological examination (9/18, 50%), and functional improvement scores (7/18, 39%). For other conditions, the reporting of disease-specific outcomes was poorly reported. Safety outcomes were mainly related to replacement fluid type rather than being disease-specific. The most common outcome reported was hypotension (19%, 8/42), and this was primarily in patients exchanged with albumin. CONCLUSION Future clinical studies to determine which fluid replacement option is most efficacious and safe should use disease-specific outcomes, as a trial in one therapeutic area may not necessarily translate to another therapeutic area. Patient reported outcomes are not universally reported for all disease areas. Safety measures focused primarily on fluid safety.

Abstract

Although antimicrobials are the cornerstone of neonatal sepsis management, adjunctive therapies are required to improve outcomes. The aim of our study was to evaluate the effect of exchange transfusion (ET) on mortality (primary outcome) in neonatal sepsis, as well as on immunoglobulin, complement and neutrophil levels and assess its complications (secondary outcomes). Databases searched include PubMed, NCBI, Google Scholar, CINHAL, Ovid and Scopus. Randomized controlled trials (RCTs), controlled observational studies (COSs) and uncontrolled observational studies (UOSs) reporting mortality data from using ET in neonatal sepsis were included. Studies with additional interventions, non-septic ET indications and populations aged > 28 days were excluded. Data extracted include demographics, features of study, sepsis and ET, as well as mortality rates, immunological and laboratory changes and complications. Data was meta-analysed and displayed using forest plots. The meta-analysis of 14 studies (3 RCTs, 11 COSs) revealed a mortality benefit in septic neonates who underwent ET-RR 0.72 (CI 0.61-0.86, p = 0.01) and a significant increase in pooled immunological parameters (immunoglobulin, complement levels) (SMD 1.13, [0.25, 2.02], p = 0.02) and neutrophil levels (SMD 1.07 [0.04, 2.11], p = 0.03) compared to controls. The descriptive analysis of 9 UOSs revealed thrombocytopenia as the most frequently reported complication (n = 48). Moderate-high risk of bias was largely due to inadequate sample sizes and follow-up durations.Conclusion: Currently, the use of ET in neonatal sepsis is not directly recommended due to low certainty of evidence, inadequate power and moderate-high risk of bias and heterogeneity.Trial registration: PROSPERO (CRD42020176629) ( https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=176629 ) What is Known: • Exchange transfusion is one of the adjunctive methods for treatment of neonatal sepsis. What is New: • The pooled analysis of all studies shows that exchange transfusion has a low certainty of evidence in the context of neonatal mortality. However, at this point, this intervention cannot be refuted or recommended due to heterogeneity of studies and inadequate power.

Abstract

OBJECTIVE To study the clinical effect and safety of double filtration plasmapheresis (DFPP) combined with double pulse therapy with methylprednisolone (MP) and cyclophosphamide (CTX) in the treatment of children with severe Henoch-Schonlein purpura nephritis (HSPN). METHODS A total of 60 children with severe HSPN who were admitted to the hospital from January 2014 to March 2018 were enrolled and were randomly divided into an observation group and a control group (n=30 each). In addition to routine treatment, the children in the control group were given MP+CTX pulse therapy. Those in the observation group were given DFPP treatment in addition to the treatment in the control group, with three courses of treatment in total. After three courses of treatment, the two groups were compared in terms of 24-hour urinary protein, urinary microproteins, renal function parameters, adverse reactions, and clinical outcome. RESULTS After three courses of treatment, the observation group had significantly greater reductions in 24-hour urinary protein, urinary albumin, urinary immunoglobulin G, urinary beta2-microglobulin, serum creatinine, and blood urea nitrogen than the control group (P<0.05). After the treatment ended, the observation group had a significantly shorter time to achieve remission than the control group (P<0.05). No serious adverse reactions, such as hemorrhagic cystitis, thrombocytopenia, and hemolysis, were observed, and there was no significant difference in the overall incidence rate of adverse reactions between the two groups (P>0.05). CONCLUSIONS Compared with MP+CTX pulse therapy alone in the treatment of severe HSPN in children, DFPP combined with MP+CTX pulse therapy can further alleviate renal injury and improve clinical outcome and does not increase the incidence rate of adverse reactions.

Abstract

BACKGROUND Data on clinical applications of blood purification techniques in children are scarce. The aim of this review is to offer a clinical overview, as complete as possible, on blood purification in children with hyper-inflammatory syndromes (HS). METHODS A review of the literature using the PubMed, EMBASE, Web of Science, and Scopus databases, on the most recent data about blood purification in children was conducted until June 2018. Except for three randomized controlled trials (RCTs) on Plasma-exchange (PE), no RCTs, but only observational studies or case reports were found regarding other blood purification techniques in children. RESULTS High Volume Hemofiltration (HVHF) in two non-randomized trials did not significantly reduce 28-day mortality in children. PE was not associated with reduced mortality in pediatric patients with septic shock, but the small number of patients enrolled is an important limitation. The use of polymixin B and other adsorbing columns in children with septic shock and HS is increasing, but results are still limited by the observational nature of the studies. CONCLUSIONS Based on the low-level of available evidence, no conclusions can be drawn regarding the efficacy and safety of blood purification in children. Further research with more clinically robust data is needed to determine the impact of different extracorporeal blood purification techniques (EBPTs) in this pediatric population.

Abstract

BACKGROUND In acquired thrombotic thrombocytopenic purpura (TTP), an immune-mediated deficiency of the von Willebrand factor-cleaving protease ADAMTS13 allows unrestrained adhesion of von Willebrand factor multimers to platelets and microthrombosis, which result in thrombocytopenia, hemolytic anemia, and tissue ischemia. Caplacizumab, an anti-von Willebrand factor humanized, bivalent variable-domain-only immunoglobulin fragment, inhibits interaction between von Willebrand factor multimers and platelets. METHODS In this double-blind, controlled trial, we randomly assigned 145 patients with TTP to receive caplacizumab (10-mg intravenous loading bolus, followed by 10 mg daily subcutaneously) or placebo during plasma exchange and for 30 days thereafter. The primary outcome was the time to normalization of the platelet count, with discontinuation of daily plasma exchange within 5 days thereafter. Key secondary outcomes included a composite of TTP-related death, recurrence of TTP, or a thromboembolic event during the trial treatment period; recurrence of TTP at any time during the trial; refractory TTP; and normalization of organ-damage markers. RESULTS The median time to normalization of the platelet count was shorter with caplacizumab than with placebo (2.69 days [95% confidence interval {CI}, 1.89 to 2.83] vs. 2.88 days [95% CI, 2.68 to 3.56], P=0.01), and patients who received caplacizumab were 1.55 times as likely to have a normalization of the platelet count as those who received placebo. The percentage of patients with a composite outcome event was 74% lower with caplacizumab than with placebo (12% vs. 49%, P<0.001). The percentage of patients who had a recurrence of TTP at any time during the trial was 67% lower with caplacizumab than with placebo (12% vs. 38%, P<0.001). Refractory disease developed in no patients in the caplacizumab group and in three patients in the placebo group. Patients who received caplacizumab needed less plasma exchange and had a shorter hospitalization than those who received placebo. The most common adverse event was mucocutaneous bleeding, which was reported in 65% of the patients in the caplacizumab group and in 48% in the placebo group. During the trial treatment period, three patients in the placebo group died. One patient in the caplacizumab group died from cerebral ischemia after the end of the treatment period. CONCLUSIONS Among patients with TTP, treatment with caplacizumab was associated with faster normalization of the platelet count; a lower incidence of a composite of TTP-related death, recurrence of TTP, or a thromboembolic event during the treatment period; and a lower rate of recurrence of TTP during the trial than placebo. (Funded by Ablynx; HERCULES ClinicalTrials.gov number, NCT02553317 .).

Abstract

BACKGROUND Exchange blood transfusion (EBT) is a form of whole blood transfusion in which the total blood volume is replaced within a few hours. In perinatal and neonatal medicine, EBT is most often used in the management of severe anaemia or severe hyperbilirubinaemia in the first week of life. Hypocalcaemia, one of the common morbidities associated with EBT, is thought to arise from the chelating effects of the citrate commonly used as an anticoagulant in the donor's blood. This disorder manifests with muscular and nervous irritability and cardiac arrhythmias. OBJECTIVES To determine whether the use of prophylactic calcium reduces the risk of hypocalcaemia-related morbidities and death among newborn infants receiving EBT. SEARCH METHODS We used the standard search strategy of the Cochrane Neonatal Review group to search the Cochrane Central Register of Controlled Trials (CENTRAL 2016, Issue 5), MEDLINE via PubMed (1966 to 29 June 2016), Embase (1980 to 29 June 2016), and CINAHL (1982 to 29 June 2016). We also searched clinical trials databases, conference proceedings, and the reference lists of retrieved articles for randomised controlled trials and quasi-randomised trials. SELECTION CRITERIA All randomised and quasi-randomised trials of prophylactic intravenous calcium in EBT for newborns. DATA COLLECTION AND ANALYSIS Two review authors independently assessed and extracted data on methods, participants, interventions, and outcomes (mean total and ionised serum calcium before and after EBT and the presence of adverse events such as hypoglycaemia, apnoea, cardiac arrest, and death immediately after EBT). We reported results as means difference (MD) with 95% confidence intervals (CI) for continuous outcomes and risk ratio (RR) and risk differences (RD) and 95% CIs for dichotomous outcomes. We assessed quality using the Cochrane 'Risk of bias' assessment tool and the GRADE system. MAIN RESULTS We found only one quasi-randomised trial with 30 participants that met our inclusion criteria. In the small trial, total and ionised serum calcium levels were measured immediately before and immediately after EBT. All the participants were included in the final analysis and all the important outcomes were reported. Primary outcomesThere was one death in each group (RR 1.00, 95% CI 0.07 to 14.55; RD 0.00, 95% CI -0.18 to 0.18; participants = 30; studies = 1). The study did not report the presence of cardiac arrhythmias within one week of EBT and the number of infants with serum calcium levels (total less than 8 mg/dL (2 mmol/L) or ionised less than 4.4 mg/dL (1.1 mmol/L)).Pair-wise comparison of EBT with intravenous 10% calcium gluconate versus EBT without intravenous calcium (change from baseline) showed mean total serum calcium was raised in the intervention group compared to the control group (MD -0.46, 95% CI -0.81 to -0.11; participants = 30; studies = 1). Very low-quality evidence also indicated an increase in the levels of mean ionised serum calcium in the intervention group compared to the control group (MD -0.22, 95% CI -0.33 to -0.11; participants = 30; studies = 1). Secondary outcomesAdverse reactions to intravenous calcium therapy included cardiac arrest in one neonate in the intervention arm (RR 3.00, 95% CI 0.13 to 68.26; RD 0.07, 95% CI -0.10 to 0.23; participants = 30; studies = 1). There was apnoea and hypoglycaemia (RR 1.00, 95% CI 0.07 to 14.55; RD 0.00, 95% CI -0.18 to 0.18; participants = 30; studies = 1) in the two neonates who died. Data were not available for other major secondary outcomes such as the number of infants with reduced serum magnesium, reduced parathormone, increased calcitonin, presence of seizures, carpopedal spasm, jitteriness and prolonged QTc interval on electrocardiography within one week of EBT. AUTHORS' CONCLUSIONS Very low-quality data from one quasi-randomised controlled trial suggested that the mean serum total and ionised calcium increased in the study group but decreased in the control group immediately after EBT. However, the mean values of total and ionised cal

Abstract

OBJECTIVES To study the efficacy and safety of double volume exchange transfusion (DVET) in neonates>1000 g birth weight with severe sepsis. METHODS Eighty-three neonates weighing >1000 g with severe sepsis were randomly assigned to DVET or standard therapy (ST) group. Primary outcome was mortality by 14 d from enrollment. RESULTS A 21 % reduction in mortality, albeit non-significant, by 14 d from enrollment was observed in DVET group in comparison to ST group [RR: 0.79 (95 % C.I 0.45-1.3); p 0.4]. A similar trend in mortality reduction was observed with early mortality and mortality by discharge in DVET group. No difference was observed in normalization of dysfunctional organs by 14 d. Cardiovascular and hematological system benefitted the most, followed by renal dysfunction with DVET. A significant improvement in post DVET IgG, IgA, IgM, C3 and base deficit was observed. No serious adverse effects occurred following DVET. CONCLUSIONS In neonates >1000 g with severe sepsis, DVET was associated with a trend towards decrease in mortality by 14 d from enrollment. A significant improvement in immunoglobulin and complement C3 levels and acid base status were observed following DVET. DVET is a safe procedure in severely sick and septic neonates.

Abstract

BACKGROUND Our goal was to perform a scoping systematic review of the literature on the use of plasmapheresis or plasma exchange (PE) for refractory status epilepticus (RSE) in children. METHODS Articles from MEDLINE, BIOSIS, EMBASE, Global Health, Healthstar, Scopus, Cochrane Library, the International Clinical Trials Registry Platform, clinicaltrials.gov (inception to May 2016), reference lists of relevant articles, and gray literature were searched. The strength of evidence was adjudicated using both the Oxford and GRADE methodology by two independent reviewers. RESULTS Twenty-two original articles were identified, with 37 pediatric patients. The mean age of the patients was 8.3 years (age median: 8.5, range: 0.6 years-17 years). Seizure response to PE therapy occurred in 9 of the 37 patients (24.3%) included in the review, with 7 patients (18.9%) displaying resolution of seizures and 2 patients (5.4%) displaying a partial reduction in seizure volume. Twenty-eight of the 37 patients (75.7%) had no response to PE therapy. No adverse events were recorded. CONCLUSIONS Oxford level 4, GRADE D evidence exists to suggest little to no benefit of PE in pediatric RSE. Routine application of PE for pediatric RSE cannot be recommended at this time.

Abstract

OBJECTIVE To determine whether plasma filtration improves 28-day survival in infants and children with severe sepsis. DESIGN A multicentre randomised controlled trial. SETTING Paediatric intensive care units in teaching hospitals. PATIENTS Forty-eight infants and children with severe sepsis. INTERVENTIONS Patients were randomly assigned to receive plasma filtration (n = 25) or standard therapy (n = 23) for the treatment of septic shock. The primary outcome measure was 28-day survival. Secondary outcome measures included the number of failed organ systems on Day 7, a requirement for extracorporeal membrane oxygenation (ECMO), and the modified Glasgow outcome score (MGOS) at 6 months (where 1 is normal and 6 is dead). RESULTS The trial was stopped early due to poor recruitment. Patients in the plasma filtration group had higher initial disease severity as measured by serum lactate level, inotrope score and MGOS. Ten (40%) children died in the plasma filtration group and 4 (17%) died in the control group. With intention-to-treat analysis and adjustment for lactate level, ventilation index, inotrope score and MGOS at admission using logistic regression, the odds ratio for death with plasma filtration was 1.20 (95% CI, 0.23-6.20; P = 0.82). The median number of failing organ systems at 7 days was 2 (interquartile range [IQR], 1-4) in the plasma filtration group versus 2 (IQR, 1-3) in the control group. Two children in the plasma filtration group required ECMO for 2.5 and 123 hours, and one child in the control group required ECMO for 45 hours. The median MGOS at 6 months was 4 (IQR, 2-6) in the plasma filtration group and 2 (IQR, 1-4) in the control group. CONCLUSIONS Our study did not recruit enough patients to test the hypothesis that addition of plasma filtration to our standard care protocol reduces 28-day mortality in children with severe sepsis. However, mortality in the treatment and control groups was not significantly different after adjustment for severity of illness at the time of randomisation.

Abstract

OBJECTIVE Evaluation of two-stage single-volume exchange transfusion (TSSV-ET) in decreasing the post-exchange rebound increase in serum bilirubin level, with subsequent reduction of the need for repeated exchange transfusions. METHODS The study included 104 neonates with hyperbilirubinemia needing exchange transfusion. They were randomly enrolled into two equal groups, each group comprised 52 neonates. TSSV-ET was performed for the 52 neonates and the traditional single-stage double-volume exchange transfusion (SSDV-ET) was performed to 52 neonates. RESULTS TSSV-ET significantly lowered rebound serum bilirubin level (12.7 +/- 1.1 mg/dL), compared to SSDV-ET (17.3 +/- 1.7 mg/dL), p < 0.001. Need for repeated exchange transfusions was significantly lower in TSSV-ET group (13.5%), compared to 32.7% in SSDV-ET group, p < 0.05. No significant difference was found between the two groups as regards the morbidity (11.5% and 9.6%, respectively) and the mortality (1.9% for both groups). CONCLUSION Two-stage single-volume exchange transfusion proved to be more effective in reducing rebound serum bilirubin level post-exchange and in decreasing the need for repeated exchange transfusions.