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.
Prophylactic intravenous calcium therapy for exchange blood transfusion in the newborn
The Cochrane Database of Systematic Reviews. 2017;((10)):CD011048.
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
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.
The effect of different blood components on exchange transfusion outcomes
JPMA - Journal of the Pakistan Medical Association. 2012;62((3, Suppl 2):):S45-8.
BACKGROUND Exchange transfusion (ET) has been known as an effective treatment in sever neonatal jaundice. Prescribing appropriate blood group makes an important role in patient's outcome and no single component is unequivocally the best. The purpose of this study was to evaluate the effect of ABO compatible packed cell, dried O, and routine O groups on exchange transfusion outcomes. METHODS This multicenter clinical trial study is the combination of two studies which were conducted at three university hospitals (Isfahan University of Medical Sciences, Isfahan, Iran). A hundred full term infants with more than 2.5 kg body weight, serum bilirubin > or = 20 mg/dl and confirmed ABO-Hemolytic Disease of the Newborn (HDN) were participated in first study. Among 40 infants, 20 underwent the exchange transfusion with O packed cell (group 1) and other 20 were transfused with O dried packed cell (Hematocrit = 90%) (group 2). In the second study with the same eligibility criteria with first study, among the 60 infants, 30 had exchange transfusion with O packed cell (group 3) and the rest were transfused with infant isogroup (group 4). Serum bilirubin and hemoglobin (Hb) were evaluated before and 6, 12, 24 and 48 hours after the exchange transfusion. RESULTS The means of Hb after the exchange transfusion were 14.3 mg/dl in group 1, 15.62 mg/dl in group 2, 14.98 mg/dl in group 3 and 14.30 mg/dl in group 4 with significantly higher in group 2 compared with others (p = 0.02). The mean of the bilirubin after the exchange transfusion had no statistical significant difference between the four groups (p > 0.05). The mean of Hb and bilirubin before exchange transfusion had no statistically difference between all groups (p > 0.05). The mean of bilirubin before the exchange transfusion in infants who had two transfusion was significantly higher than the mean of the bilirubin before the exchange transfusion in infants with one time transfusion (p = 0.05). There was no significant difference between four groups in exchange transfusion frequency (p > 0.05). DISCUSSION This study indicated that the level of bilirubin before exchange transfusion is the only important factor which sometimes causes the necessity of second or third exchange.
Indian Journal of Pediatrics. 1997;64((4):):541-6.
461 consecutive inborn babies, delivered during the period September 1993-March 1994 were subjected to a microhematocrit assessment at 6 hours of age to determine the incidence of polycythemia. 47 babies (inborn and out born), admitted to the neonatal unit with confirmed polycythemia were studied for clinical and laboratory abnormalities. These 47 babies were then randomly assigned to receive partial exchange transfusion with either normal saline or fresh plasma. The incidence of polycythemia was 27 of 461 (5.8%). 23 of 27 (85.1%) were term babies and 15 of 27 (55.5%) were small for gestational age. 14 of 27 (51.1%) babies had mothers who had pregnancy induced hypertension. Feeding problems (16/47) and lethargy (25/47) were the commonest symptoms (34% and 51% respectively). 25 of 47 (51%) babies had hypoglycemia and 5 of 47 (10.6%) had hypocalcemia. Thrombocytopenia was seen in 13/47 (27.65%) of cases. 24 babies received normal saline and 23 received fresh plasma for partial exchange transfusion. The immediate post-exchange fall in hematocrit was significant in both groups and this was well sustained over the following 48 hours. However, improvement in clinical and laboratory parameters was more remarkable with fresh plasma. Polycythemia appears to be a real clinical entity in neonates in India and babies with known risk factors should be actively screened for this condition. Once diagnosis is established special attempts should be made to rule out hypoglycemia. For treatment of polycythemia fresh plasma is preferable for partial exchange transfusion but normal saline appears to be an adequate substitute.
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.
Exchange transfusion in neutropenic septicemic neonates: effect on granulocyte functions
Acta Paediatrica. 1993;82((11):):939-43.
Depletion neutropenia caused by overwhelming bacterial infection is associated with fatal outcome and is an objective indicator of the severity of sepsis. Studies on controlled evaluation of exchange transfusion in the management of severe neonatal sepsis have not considered neutropenia as an inclusion criterion, and randomized, controlled trials on evaluation of neutrophil functions after exchange transfusion are scarce. This prompted us to carry out the present study. Septicemic neonates were enrolled if they had neutropenia and were randomized to undergo exchange transfusion (study group, n = 20) or not (controls, n = 10). Granulocyte functions were assessed using the nitro blue tetrazolium (NBT) reduction test and the staphylococcidal index. Blood was drawn for granulocyte function tests once from controls and donors, and before, immediately after and 6 h after exchange transfusion in the study group. Mortality was 35% in the study group and 70% in controls. Gram-negative organisms accounted for 80% in the study group and 90% in controls. Mean total leukocyte count and neutrophil count increased significantly immediately after exchange transfusion and 6 h later. Absolute band count decreased significantly immediately after exchange transfusion and increased 6 h later. NBT reduction in septicemic neonates in the study group, as well as in controls, was significantly decreased as compared to donor cells. NBT reduction improved significantly immediately after exchange transfusion and 6 h later. The values of the percentage of viable staphylococci recovered from neutrophils also improved significantly immediately after exchange transfusion and 6 h later.(ABSTRACT TRUNCATED AT 250 WORDS)
The role of exchange transfusions in the management of low-birth-weight infants with and without severe respiratory distress syndrome. II. Further observations and studies of mechanisms of action
Journal of Pediatrics. 1976;89((2):):279-85.
Exchange transfusion, as a form of therapy, was contrasted with the use of fresh frozen plasma or conventional supportive care alone in the management of 19 infants with birth weights of less than 1,000 gm, without severe respiratory distress, and in the management of 82 infants, birth weights less than 2,000 gm, with severe respiratory distress whose disease manifested itself within the first 24 hours of life. Survival for more than five days was similar, regardless of therapy, in infants weighing less than 1,000 gm without severe RDS. In contrast, the use of exchange transfusion significantly decreased the case fatality rate of infants with severe RDS. In the groups receiving exchange transfusion, the mortality rate was 41%, whereas the groups receiving either plasma or supportive care alone the mortality was 80%. Study of coagulation factors and red cell concentrations of fetal hemoglobin and of 2,3-DPG failed to demonstrate any relationship between either improvement in coagulation or oxygen unloading and the improved survival of infants receiving exchange transfusion. Following exchange transfusion there was a significant decrease in the ratio of FIO2 to PaO2, suggesting that pulmonary perfusion and/or ventilation was improved by the procedure.