The effect of exchange transfusion on mortality in neonatal sepsis: a meta-analysis
European journal of pediatrics. 2021
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.
The premature closure of ROMPA clinical trial: mortality reduction in septic shock by plasma adsorption
BMJ open. 2019;9(12):e030139
OBJECTIVES Coupled Plasma Filtration and Adsorption (CPFA) use in septic shock remains controversial. The objective is to clarify whether the application of high doses of CPFA in addition to the current clinical practice could reduce hospital mortality in septic shock patients in Intensive Care Units at 28 days and at 90 days follow-up. DESIGN We designed a prospective randomised clinical trial, Reduccion de la Mortalidad Plasma-Adsorcion (ROMPA), to demonstrate an absolute mortality reduction of 20% (alpha=0.05; 1-beta=0.8; n=190 (95x2)). SETTING Being aware of the pitfalls associated with previous medical device trials, we developed a training programme to improve CPFA use (especially clotting problems). The protocol was approved by the ethics committees of all participating centres. Circumstances beyond our control produced a change in recruitment conditions unacceptable to ROMPA researchers and the trial was discontinued. PARTICIPANTS By closure, five centres from an initial 10 fulfilled the necessary trial criteria, with 49 patients included, 30 in the control group (CG) and 19 in the intervention group (IG). INTERVENTION CPFA. MAIN OUTCOME MEASURES Hospital mortality at 28 days and 90 days follow-up. RESULTS After 28 days, 14 patients died (46.7%) from the CG and 11 (57.9%) from the IG, not reaching statistical significance (p=0.444). At 90 days, 19 patients had died (63.3%) from the CG and 11 patients (57.9%) from the IG, (p=0.878). The adjustment by propensity score or the use of the Kaplan-Meier technique failed to achieve statistical difference, neither by Intention to Treat nor by the Actual Intervention Received. CONCLUSION We herewith present the results gained from the prematurely closed trial. The results are inconclusive due to low statistical power but we consider that this data is of interest for the scientific community and potentially necessary for any ensuing debate. REGISTER NCT02357433 in clinicaltrials.gov.
Effect of continuous plasma filtration adsorption on treatment of severely burned patients with sepsis
Zhonghua Shao Shang Za Zhi = Zhonghua Shaoshang Zazhi = Chinese Journal of Burns. 2018;34((6)):370-373.
Objective: To investigate effect of continuous plasma filtration adsorption on treatment of severely burned patients with sepsis. Methods: In January 2014 to September 2017, 86 severely burned patients with sepsis, conforming to the study criteria, were admitted to our hospital and divided into into routine treatment group and continuous plasma filtration group according to the random number table method, with 43 patients in each group. Patients in routine treatment group were treated with routine treatment after admission. Patients in continuous plasma filtration group were treated with blood filter, blood purification machine, and plasma separator for continuous plasma filtration adsorption on the basis of the routine treatment group on the second day after admission. The course of treatment in the 2 groups was 7 d. The total effective treatment rate, changes of leukocyte count (WBC), usea nitrogen, serum creatinine, neutrophile CD64, procalcitonin, and C reactive protein (CRP) before and after treatment, and mortality on 28 days after treatment of patients in 2 groups were analyzed and compared. Results: (1) The total effective treatment rate of patients in continuous plasma filtration group was 88.37% (38/43), which was significantly higher than that of the routine treatment group [65.12% (28/43), chi(2)=6.515, P=0.018]. (2) After treatment, WBC, urea nitrogen, serum creatinine, neutrophils CD64, procalcitonin, and CRP of patients in continuous plasma filtration group were significantly lower those in routine treatment group (t=6.305, 4.420, 18.537, 13.435, 12.975, 14.234, P<0.05). WBC, urea nitrogen, serum creatinine, neutrophile CD64, procalcitonin, and CRP of patients in 2 groups after treatment were significantly lower than those before treatment (t=9.459, 9.130, 25.438, 35.467, 23.471, 23.601, 3.802, 5.662, 12.067, 25.694, 20.720, 12.437, P<0.05). (3) On 28 days after treatment, mortality of patients in continuous plasma filtration group was 6.98% (3/43), which was significantly lower than that in routine treatment group [25.58% (11/43)], chi(2)=5.460, P=0.023. Conclusions: Continuous plasma filtration adsorption is effective in treating severely burned patients with sepsis, which can alleviate inflammatory reaction mediated by inflammatory cytokine with good prognosis.
Double volume exchange transfusion in severe neonatal sepsis
Indian Journal of Pediatrics. 2016;83((2)):107-13.
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.
Efficacy of coupled plasma filtration adsorption (CPFA) in patients with septic shock: a multicenter randomised controlled clinical trial
BMJ Open. 2014;4((1)):e003536.
OBJECTIVES Coupled plasma filtration adsorption (CPFA, Bellco, Italy), to remove inflammatory mediators from blood, has been proposed as a novel treatment for septic shock. This multicenter, randomised, non-blinded trial compared CPFA with standard care in the treatment of critically ill patients with septic shock. DESIGN Prospective, multicenter, randomised, open-label, two parallel group and superiority clinical trial. SETTING 18 Italian adult, general, intensive care units (ICUs). PARTICIPANTS Of the planned 330 adult patients with septic shock, 192 were randomised to either have CPFA added to the standard care, or not. The external monitoring committee excluded eight ineligible patients who were erroneously included. INTERVENTIONS CPFA was to be performed daily for 5 days, lasting at least 10 h/day. PRIMARY AND SECONDARY OUTCOME MEASURES The primary endpoint was mortality at discharge from the hospital at which the patient last stayed. Secondary endpoints were: 90-day mortality, new organ failures and ICU-free days within 30 days. RESULTS There was no statistical difference in hospital mortality (47.3% controls, 45.1% CPFA; p=0.76), nor in secondary endpoints, namely the occurrence of new organ failures (55.9% vs 56.0%; p=0.99) or free-ICU days during the first 30 days (6.8 vs 7.5; p=0.35). The study was terminated on the grounds of futility. Several patients randomised to CPFA were subsequently found to be undertreated. An a priori planned subgroup analysis showed those receiving a CPFA dose >0.18 L/kg/day had a lower mortality compared with controls (OR 0.36, 95% CI 0.13 to 0.99). CONCLUSIONS CPFA did not reduce mortality in patients with septic shock, nor did it positively affect other important clinical outcomes. A subgroup analysis suggested that CPFA could reduce mortality, when a high volume of plasma is treated. Owing to the inherent potential biases of such a subgroup analysis, this result can only be viewed as a hypothesis generator and should be confirmed in future studies. CLINICALTRIALSGOV NCT00332371; ISRCTN24534559.
The efficacy and safety of therapeutic apheresis in sepsis and septic shock: a systematic review and meta-analysis
A randomised controlled trial of plasma filtration in severe paediatric sepsis
Critical Care & Resuscitation. 2013;15((3):):198-204.
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.
Plasmapheresis in severe sepsis and septic shock: a prospective, randomised, controlled trial
Intensive Care Medicine. 2002;28((10):):1434-9.
OBJECTIVE To determine the therapeutic efficacy and safety of plasmapheresis in the treatment of patients with severe sepsis and septic shock. DESIGN Prospective, randomised, clinical trial with a planned, midstudy, interim analysis. SETTING Intensive care unit in a university hospital in Archangels, Russia. PATIENTS Consecutive patients with severe sepsis or septic shock. INTERVENTIONS One hundred and six patients were randomised to receive either standard therapy or an add-on treatment with plasmapheresis. MEASUREMENTS AND RESULTS The primary endpoint was 28-day survival. Septic shock was diagnosed in 57% of the plasmapheresis-treated patients and 54% of the control patients. Mean APACHE III score at entry was 56.4 in the plasmapheresis group and 53.5 in the control group. The 28-day, all-cause mortality rate was 33.3% (18/54) in the plasmapheresis group and 53.8% (28/52) in the control group. This represents a relative risk for fatal outcome in the plasmapheresis group of 0.61, an absolute risk reduction of 20.5% and a number of patients needed to treat of 4.9. Apart from six transient episodes of hypotension and one allergic reaction to fresh frozen plasma, no adverse reactions were attributable to the plasmapheresis treatment in this study. CONCLUSIONS Plasmapheresis may be an important adjuvant to conventional treatment to reduce mortality in patients with severe sepsis or septic shock. Plasmapheresis is a safe procedure in the treatment of septic patients. A prospective randomised multicentre trial is warranted to confirm our results and to determine which subgroups of septic patients will benefit most from this treatment modality.
Continuous plasmafiltration in sepsis syndrome. Plasmafiltration in Sepsis Study Group
Critical Care Medicine. 1999;27((10):):2096-104.
OBJECTIVE To assess the effect of plasmafiltration (PF) on biochemical markers of inflammation, cytokines, organ dysfunction, and 14-day mortality in human sepsis. DESIGN Multicenter, prospective, randomized, controlled clinical trial. SETTING Seven university-affiliated intensive care units. PATIENTS Thirty patients (22 adults, eight children) with new (<24 hrs) clinical evidence of infection and sepsis syndrome were enrolled. Fourteen of 30 (nine adults, five children) were randomized to PF. INTERVENTIONS All patients received protocol-driven supportive intensive care, and those randomized to PF received continuous plasma exchange for 34 hrs using a hollow-fiber plasma filter. MEASUREMENTS AND MAIN RESULTS Illness severity and risk of death were calculated with the Pediatric Risk of Mortality (children) and the Acute Physiology and Chronic Health Evaluation II (adults) scales. Plasma samples (0, 6, 24, and 48 hrs) were assayed for acute-phase proteins (albumin, globulin, C-reactive protein, alpha1-antitrypsin, haptoglobin), inflammatory mediators (complement fragment C3, thromboxane B2), and cytokines (interleukin-6, granulocyte colony-stimulating factor, leukemia inhibitory factor). Sieving coefficients were estimated from filtrate concentrations at 3 hrs. The two groups were matched for incidence of septic shock (13 of 14 vs. 11 of 16), refractory shock (three of 14 vs. six of 16), bacteremia (six of 14 vs. five of 16), severity of illness, and calculated risk of death (0.68 vs. 0.64). There was no difference in mortality. Eight of 14 PF patients (57%) and eight of 16 controls (50%) survived for 14 days (p = .73, Fisher's exact test). Multiple logistic regression revealed age (odds ratio, 16.4:1; 95% confidence interval, 2.12-infinity) and shock (10.6:1; 1.32-infinity) as significant predictors of death; plasmafiltration was associated with a nonsignificant reduction in the risk of death (odds ratio, 1.78:1; 95% confidence interval, 0.20-18.1). The mean (SD) number of organs failing in the first 7 days in the PF group was 2.57 (0.94) vs. 2.94 (0.85) in controls (p = .37, Mann-Whitney U test). Both groups had similarly elevated plasma concentrations of all inflammatory mediators except complement fragment C3 at study entry. Leukemia inhibitory factor was detectable in four patients only. PF did not influence mean concentrations of interleukin-6, granulocyte colony-stimulating factor, thromboxane B2, total white cell count, neutrophil count, or platelet count, but it was associated with significant reductions of alpha1-antitrypsin, haptoglobin, C-reactive protein, and complement fragment C3 in the first 6 hrs (p < .05). The sieving coefficients for all inflammatory mediators approached unity. CONCLUSIONS PF caused a significant attenuation of the acute-phase response in sepsis. There was no significant difference in mortality, but there was a trend toward fewer organs failing in the PF group that suggests that this procedure might be beneficial.
Exchange transfusion in septic neonates with sclerema: effect on immunoglobulin and complement levels
Indian Pediatrics. 1997;34((1):):20-5.
OBJECTIVE To study the effect of exchange transfusion (ET) on the levels of immunoglobulins (Ig) and C3 in neonatal sepsis with sclerema. DESIGN Randomized controlled trial in a referral neonatal unit of a teaching hospital. SUBJECTS Consecutive culture positive septic neonates with sclerema were enrolled and were randomized to undergo ET (study group, n = 20) or no ET (controls, n = 20). RESULTS Mortality was 50% in the study group and 95% in controls. Gram negative organisms accounted for 85% in study group and 90% in controls. IgG, IgA and IgM levels rose significantly while C3 levels did not show significant rise 12-24 hours after ET. Ig and C3 levels did not change significantly in the controls. CONCLUSION ET with fresh whole blood in septicemic newborns with sclerema improves survival, particularly in the more premature group and significantly enhances, IgG, IgA and IgM levels.