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Single versus double volume exchange transfusion in jaundiced newborn infants

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Authors

Thayyil S, Milligan DWA

Background - Methods - Results - Characteristics of Included Studies - References - Data Tables & Graphs


Dates

Date edited: 22/08/2006
Date of last substantive update: 31/07/2006
Date of last minor update: / /
Date next stage expected 31/08/2008
Protocol first published: Issue 1, 2004
Review first published: Issue 4, 2006

Contact reviewer

Dr Sudhin Thayyil

Neonatal Unit
Addenbrookes Hospital
Hills Road
Cambridge
UK
CB2 2QQ
Telephone 1: + 44 01223 217678
Telephone 2: + 44 01223 217064

E-mail: monicalall@aol.com

Contribution of reviewers

ST: conceived of the idea for the review, wrote the first draft of protocol and review, extracted data
DWAM: Helped in writing of protocol and review, extracted data, contacted experts in the field for unpublished data.

Internal sources of support

Addenbrookes Hospital, Cambridge, UK
Royal Victoria Infirmary, Newcastle Upon Tyne, UK
Royal London Hospital, London, UK

External sources of support

  • None noted.

What's new

  • None noted.

Dates

Date review re-formatted: / /
Date new studies sought but none found: / /
Date new studies found but not yet included/excluded: / /
Date new studies found and included/excluded: / /
Date reviewers' conclusions section amended: / /
Date comment/criticism added: / /
Date response to comment/criticisms added: / /

Synopsis

Extremely high levels of bilirubin (severe jaundice) can lead to brain damage. Severe jaundice in newborns can occur as a result of a variety of causes including rhesus hemolytic disease, ABO incompatibility, atypical antibodies etc. Removal of blood from the affected infant and replacing with fresh blood from the blood bank (exchange transfusion) is used as a treatment for severe jaundice in newborn infants. The affected infant's blood is removed in small portions and equal volume of blood is replaced during exchange transfusion. Traditionally twice the blood volume of baby is removed and the replaced with fresh blood. Exchange transfusion has been shown to reduce brain damage in severely jaundiced babies; however, exchange transfusion is associated with serious adverse events including death. It is likely that the complications of exchange transfusion would increase with amount of blood exchanged. This review was undertaken to examine if single volume (removal of blood equivalent to the blood volume of the baby) is as effective as double volume (removal of twice blood volume of the baby) in reducing the brain damage and bilirubin levels in newborn infants with severe jaundice.

Only one randomised trial fulfilled the criteria for inclusion in the analysis. This study compared single and double volume exchange transfusion in jaundice due to ABO hemolytic jaundice. The study found no significant difference in bilirubin levels following exchange. This study did not look at any long term neurodevelopmental outcome (brain damage). Based on the available data, there is insufficient evidence to support or refute the use of single volume exchange transfusion as opposed to double volume exchange transfusion in jaundiced newborns.

Abstract

Background

Double volume exchange transfusion is commonly used in newborns with severe jaundice in order to prevent kernicterus and other toxicity related to hyperbilirubinemia. Most commonly, exchange transfusions are used in infants with rhesus hemolytic disease.

Objectives

To compare the effectiveness of single volume exchange transfusion (SVET) with that of double volume exchange transfusion (DVET) in producing survival without disability and reducing bilirubin levels in newborn infants with severe jaundice.

Search strategy

MEDLINE, EMBASE (Excerpta Medica online), The Cochrane Central Register of Controlled Trials (CENTRAL, The Cochrane Library), SCISEARCH (Science Citation Index), Reference lists from the articles identified in the search of the databases, and from review articles were searched through March 2006. Personal communication with experts in the field was used to identify unpublished data.

Selection criteria

All Randomised and quasi randomised control trials comparing single volume and double volume exchange transfusions in jaundiced newborn infants were included.

Data collection & analysis

Safety and efficacy of single and double volume exchange compared with regards to long term neurodevelopment, reduction in bilirubin levels and other complications during exchange transfusion. Data was evaluated separately with regards to the cause of jaundice. Relative risk (RR) and weighted mean difference (WMD) were calculated for dichotomous and continuous variables respectively. 95% confidence intervals were used and a fixed effects model was assumed.

Main results

Only one study fulfilled the criteria (Amato 1988). 20 full term babies requiring exchange transfusion for hemolytic jaundice due to ABO incompatibility were randomly allocated to receive single or double volume exchange transfusion. Base line characteristics of both groups were similar with regards to birth weight 3260 (SD 390) g vs. 3350 SD (410) g, gestational age 39 (SD 1) week vs. 40 (SD 0.8) week, immediate pre exchange bilirubin level 199 (SD 33) micromol/L vs. 216 (SD 55) micromol/L. Both groups were treated equally apart from the volume of blood used for exchange transfusion. Total bilirubin levels immediately after exchange transfusion were not significantly different in either group. No long term neurodevelopmental outcome was examined in this study.

Reviewers' conclusions

There was insufficient evidence to support or refute the use of single volume exchange transfusion as opposed to double volume exchange transfusion in jaundiced newborns. A change from the current practice of double volume exchange transfusions for severe jaundice in newborns infant, cannot be recommended on current evidence.

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Background

Exchange transfusion (ET) in neonates is commonly used to remove antibody coated red blood cells and/or products of hemolysis in various immune (e.g. rhesus incompatibility, ABO incompatibility) or non immune hemolytic anemias (e.g. G6PD deficiency and other red cell enzyme deficiencies) or to remove bacterial toxins in cases of severe sepsis (Hoontrakoon 1998). ET involves incremental removal of blood from the affected infant and replacement with fresh donor blood. Estimating the blood volume of newborn as 80 - 90 ml/kg, exchange involving replacement of 80-90 ml/kg has been termed as single volume exchange transfusion (SVET) and that involving 160 - 180 ml/kg termed as double volume exchange transfusion (DVET).

Prior to the introduction of exchange transfusion, liveborn infants with severe rhesus hemolytic disease had a 35-40% mortality, with a 90% risk of severe neurological damage among survivors (Diamond 1948). A reduction in mortality to 20% and reduction in adverse neurological outcome to 30% was observed following the introduction of double volume exchange transfusion (Diamond 1948).

Although exchange transfusion achieved its goal of reducing mortality, it has become apparent over the years that the outcome of many of the sensitised infants who underwent exchange transfusion would have been no worse if they had not been treated (Lucey 1966). Over the past few decades, major advances have been made in prevention (e.g. rhesus immunoglobulin) and treatment (e.g. intrauterine transfusions, intensive phototherapy) of rhesus hemolytic disease, so that use of exchange transfusion, especially within twelve hours of birth, has become uncommon. Most centres reporting outcomes in the management of severe Rhesus isoimmune hemolytic anaemia have shown markedly improved survival rates during the past 25 years, and much of this is attributable to improved antenatal management. Of equal importance, long-term neurodevelopmental outcome in these infants is excellent (Maisels 1999).

The efficacy of ET with regards to long term neurological outcome is related to the etiology of hyperbilirubinemia and the population in which ET is undertaken. ABO incompatibility often results in a less severe hemolytic disease, needing fewer exchange transfusions compared to rhesus incompatibility (Kanto 1978). In developing countries, babies with severe jaundice may be referred late (with babies already showing signs of kernicterus), and therefore exchange transfusion may not be useful in preventing neurological damage. Bilirubin encephalopathy occurs at lower serum bilirubin levels in preterm infants and the threshold for exchange transfusion is usually lower. Sub-group analyses will be done to compare single and double volume exchanges in these populations.

Efficacy and complications of exchange transfusion can also depend upon the route (peripheral vs. umbilical) (Merchant 1992), size of aliquots, method of exchange (continuous vs. push pull) (Schober 1990) and use of albumin during exchange. Use of intrauterine transfusions (Grannum 1988) and metalloporphyrins can reduce the need of ET (Dennery 2001). Sub-group analyses will be done with regards to different techniques used for exchange transfusion.

Mortality directly attributable to ET (reported to be at least 1%) is often due to unexplained cardiac arrest, cardiac arrhythmia or air embolism (Boggs 1960). Severe necrotising enterocolitis and bowel perforation requiring surgery occur in about 1% (Lucey 1969). Other major complications include severe bleeding or coagulopathy requiring intervention, and severe bradycardia or apnea during or following exchange. There are several reports of portal vein thrombosis and portal hypertension occurring following exchange transfusion using umbilical route (Yadav 1993).

It is likely that the complications of exchange would increase with the duration of exchange and volume of blood exchanged. Therefore, a double volume exchange is potentially more hazardous than single volume exchange. With improved outcomes of jaundiced babies without exchange, the risk: benefit ratio of exchange transfusion may well have changed. It is important to examine if limiting the procedure to a single volume exchange minimises adverse effects without compromising long term outcome.

This review aims to examine whether there is any evidence supporting the continued use of double, as opposed to single, volume exchanges with regards to efficacy (especially in terms of long term neurodevelopmental outcome) and safety.

Objectives

Primary

  • To compare the effectiveness of single volume exchange transfusion (SVET) with double volume exchange transfusion (DVET) in reducing bilirubin levels and improving survival without disability at two years or longer in newborns with severe jaundice.

Secondary

  • To compare the frequency of adverse events related to single and double volume exchange transfusions.
Subgroups analysis will be conducted based on the different etiologies for hyperbilirubinemia. Within each sub group effectiveness of SVET was compared with DVET with regards to reduction in bilirubin level and improving survival without disability at two years or more.
  • Single versus double volume exchange transfusion in Rhesus hemolytic disease
  • Single versus double volume exchange transfusion in hemolytic disease other than Rhesus hemolytic disease
  • Single versus double volume exchange transfusion in newborn infants without hemolysis
  • Single versus double volume exchange transfusion in preterm babies ( less than/or equal to 28 weeks, 29 - 32 weeks, 33 - 36 weeks)
  • Single versus double volume exchange transfusion according to serum bilirubin level ( less than/or equal to 200 micromoles/L, 201 - 399 micromoles/L, > 399 micromoles/L)
  • Single versus double volume exchange transfusion in newborns infants with established kernicterus
  • Single versus double volume exchange transfusion in newborn infants in whom metalloporphyrins have been used

Criteria for considering studies for this review

Types of studies

All randomised and quasi randomised control trials.

Types of participants

Term and preterm newborn infants (up to 28 days of life) requiring exchange transfusion for jaundice or elevated serum bilirubin (SBR). No specific cut off bilirubin level for exchange was required for inclusion. The bilirubin level for exchange transfusion was defined in individual studies. No birth weight or gestational age restrictions were applied. Preterm infants were defined as those born at less than 37 weeks gestational age. Hemolysis was defined as hyperbilirubinemia in association with either major or minor blood group incompatibility, or a red cell enzyme defect where a positive antibody test or evidence of hemolysis (e.g. fragmented red blood cells on blood film examination, raised reticulocyte count ) is also present. Kernicterus was defined as a neurological deficit including athetoid cerebral palsy, impaired upward gaze and deafness, isolated conditions like auditory neuropathy or dys-synchrony (AN/AD), and subtle bilirubin-induced neurological dysfunction (BIND) (Dennery 2001; Shapiro 2005).

Types of interventions

Single volume exchange transfusion (intervention) (80 - 90 ml/kg) or double volume (control) (160 - 180 ml/kg) exchange transfusion. Exchange transfusions were done either by central or peripheral route using push pull technique, continuous method or by an automated device. No restrictions on volume of aliquots for each cycle of ET, type of blood for ET, age of blood used for ET, infusion of albumin or replacement of electrolytes during exchange were placed. Infants may have received phototherapy and/or metalloporphyrins either prior to exchange and/or subsequently or had intrauterine transfusions in addition to exchange transfusion.

ET was defined as any procedure in which whole blood was removed from the circulation and replaced with either fresh whole blood or diluted packed red blood cells. Phototherapy was defined as the use of artificial light to photoisomerise unconjugated bilirubin. A continuous technique for ET was defined as one in which two catheters were used and withdrawal and infusion of blood occurred simultaneously. A 'push-pull' technique for ET was defined as one in which one catheter was used and withdrawal and infusion of blood occurred sequentially. Central or peripheral vascular catheters was defined as catheters whose tip lies within the thorax or abdomen, or all other sites, respectively (Mills 2003)

Types of outcome measures

Primary

  • Neurological deficits consistent with kernicterus at two year of age including athetoid cerebral palsy, impaired upward gaze and deafness, auditory neuropathy or dys-synchrony (AN/AD), and subtle bilirubin-induced neurological dysfunction (BIND) (Shapiro 2005).
  • Death before 28 days of age
  • Life-threatening events during transfusion
  • Relative or absolute change in serum bilirubin immediately after exchange transfusion from the pre exchange level.

Secondary

  • Total number of exchange transfusions
  • Hemoglobin (g/dl) or hematocrit (%) measured 3 - 6 weeks after exchange transfusion
  • Thrombocytopenia or coagulopathy following exchange, receiving intervention
  • Infection attributable to exchange transfusion
  • Portal vein thrombosis and/or portal hypertension following exchange transfusion
  • Necrotising enterocolitis within 72 hours of exchange

Neurological deficits or neurodisabilty was defined as any of deafness, cerebral palsy or cognitive delay (score more than two standard deviations below the mean for any recognised test for neurodevelopment, e.g. Bayley Scales). Cardiac arrest, cardiac arrythmia or air embolism were considered as life threatening events. Portal vein thrombosis was defined on the basis of diagnosis on ultrasound doppler and/or percutaneous splenic portal venography (Flores 1997). Necrotising enterocolitis was staged according to Bell's staging and stage II or more was considered significant (Bell 1978). Only thrombocytopenia or deranged coagulation that received an intervention to correct the abnormality was considered significant. Infection attributable to ET was defined as isolation of a pathogenic organism (not considered as a contaminant) from blood or any deep sites within 72 hours of exchange.

Search strategy for identification of studies

The search strategy used to identify studies was according to the guidelines of the Cochrane Neonatal Review Group. No language restrictions were applied. Key words used were [Exchange transfusion] AND [jaundice OR newborn OR neonates OR Neo* OR bilirubin OR prematurity OR premat* AND CLINICAL TRIAL / RANDOMISED CONTROL TRIAL].

  • MEDLINE was searched from 1966 to March 2006
  • EMBASE (Excerpta Medica online) was searched from 1980 to March 2006
  • The Cochrane Central Register of Controlled Trials (Issue 1, 2006 The Cochrane Library),
  • SCISEARCH (Science Citation Index) and Reference Update was searched in March 2006
  • Reference lists from the above, and from review articles
  • Personal communication with experts in the field to identify unpublished data

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Methods of the review

The standard methods of the Cochrane Collaboration and its Neonatal Review Group were used. The methodological quality of each eligible trial was assessed by both authors, and the authors were not blinded to trial author, institution or journal of publication. The following criteria were used: blinding of allocation, blinding of intervention, completeness of follow-up, blinding of outcome measures. Criteria were assessed as Yes/No/Can't tell. Having decided which trials to include, both authors independently extracted the data and compared results. Disagreements were resolved by consensus.

The safety and efficacy of SVET and DVET were analysed in the following sub-groups: Rhesus hemolytic disease, hemolytic disease other than rhesus disease, infants without hemolysis, preterm babies, infants with established kernicterus, infants treated with metalloporphyrins and for various pre-exchange serum bilirubin levels. Further sub-group analyses was not undertaken on method of exchange transfusion (continuous vs push pull), route of exchange (peripheral vs central) and aliquot size because of insufficient data.

The standard statistical methods of the Cochrane Collaboration were used. For dichotomous and continuous variables, the relative risk (RR) and weighted mean difference (WMD) were calculated respectively. 95% confidence intervals were used and a fixed effects model was assumed. Heterogeneity in the study population was prospectively addressed by subgrouping on the basis of different etiologies of hyperbilirubinemia. Sub grouping was also done on the method of exchange transfusion to avoid heterogeneity related to intervention. Statistical heterogeneity was examined by I2 test.

Description of studies

See table of Characteristics of Included Studies

Searching revealed only one randomised control trial (Amato 1988) comparing single and double volume exchange transfusion in jaundiced neonates.

Included Studies

Amato 1988 (Amato 1988)

Amato et al studied 20 full term newborn infants with hyperbilirubinemia due to ABO incompatibility, requiring exchange transfusion. The diagnosis of ABO isoimmunization was made on the basis of clinical data, mother infant blood group incompatibility, positive direct or indirect Coombs test, high reticulocyte count and hyperbilirubinemia. The study was done at two centers over a one year period. 84 babies were admitted to the two intensive care units with hyperbilirubinemia due to ABO incompatibility. Babies who had perinatal asphyxia (Apgar score < 4 at one minutes and < 6 at five minutes), babies with congenital malformations, suspected or proven bacterial infection, respiratory distress and babies who had hyperbilirubinemia due to maternal drugs, polycythemia, skin hematomas, cephalhematoma were excluded. No patients were treated with phenobarbitone. Indication for exchange transfusion was bilirubin levels according to the modified Polacek curves (Cockington 1979)

Twenty term babies who met the inclusion criteria, and in whom a decision to exchange was taken, were randomised into two groups i.e. one group receiving SVET and the other group receiving DVET. Packed cells (2/3 red cell volume and 1/3 plasma) suspended in plasma was used for exchange. No immunoglobulin or clotting factors were present. The mean hemoglobin level of the blood units was 20 g/dl (SD 3.1) and hematocrit 68% (SD 5).

Base line characteristics were similar with regards to birth weight 3260g (SD 390) vs. 3350g SD (410), gestational age 39 (SD 1) week vs. 40 (SD 0.8) weeks, 5 min Apgar scores 7.5 (SD 0.6) vs. 7.8 (SD 0.8) and age at exchange transfusion 17.2 (SD 6.3) hours vs. 18.7 (SD 6.2) hours in babies who received single volume and double volume exchange transfusion. The immediate pre exchange hemoglobin levels 16.7 (SD 2.4) g/dL vs. 16.6 (SD 2.5) g/dL, platelet levels 253 (SD 83) x 109/L vs. 298 (SD 95) x 109/L, rate of rise in bilirubin 199 (SD 33) micromol/L vs. 216 (SD 55) micromols/L and bilirubin level 199 (SD 33) micromol/L vs. 216 (SD 55) micromol/L were similar single and double volume exchange groups. Both groups were treated equally apart from the volume of blood used for exchange transfusion.

Single volume exchange transfusion transfused 80 ml/kg and double volume exchange 180 ml/kg. Exchange transfusion was performed through umbilical vein over one hour using a disposable exchange transfusion set in 10 ml aliquots. No additional calcium or albumin was given. No deficit was created. Continuous phototherapy was started immediately after ET using double blue light phototherapy. Babies were given 10% dextrose at 120 ml/kg and once bilirubin levels were less than 205 mmol/L, phototherapy was discontinued. None of the babies required more than one exchange transfusion.

Excluded Studies

No other studies comparing single and double volume exchange transfusions were found. Several case series were found on double volume exchange transfusions and one case series on single volume exchange transfusion (Soulie 1999). Soulie et al retrospectively reviewed 60 exchange transfusions in 48 newborns (26 babies with Rhesus hemolytic disease) who had single volume exchange transfusion (0.72 - 1 times blood volume exchanged), with satisfactory lowering of bilirubin levels. However, no long term neurological effects were examined.

Methodological quality of included studies

Characteristics of Included Studies

Amato 1988 (Amato 1988)

Full details are provided in the Table, Characteristics of Included Studies.
Method of subject allocation: Table of random numbers was used for randomisation.
Concealment of allocation: There was no mention of allocation concealment.
Masking of caregivers: This was not done in the study.
Completeness of outcome assessment: Outcomes were reported in all randomised infants up to 3 months.
Masking of outcome assessment: We could not ascertain if this was done in the study.

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Results

Only one small randomised control of 20 patients has been found comparing SVET with DVET (Amato 1988). All the results presented below pertain to this study.

Primary Outcomes

Neurological deficits consistent with kernicterus at two year of age:

The study did not report any neurodevelopmental outcome and the follow up was only for 3 months.

Death before 28 days of age:

No mortality was seen in either the group at three month follow up.

Life-threatening events during transfusion:

No major events occurred in either group. Few infants had bradycardia and mild vomiting. The authors considered this to be of no clinical significance and these events were equally scattered in both the groups.

Change in serum bilirubin after exchange transfusion:

Total bilirubin levels (mean) immediately after exchange transfusion was 130 (SD 24) micromol/L in single volume group and 143 (SD 47) micromol/L in double volume exchange transfusion group and the difference was not statistically significant (Outcome 01.01). Duration of phototherapy (mean) in both the groups following exchange transfusion was similar 45.4 (SD 17.7) hours and 38.1 (SD 16.4) hours [p>0.05] in SVET and DVET respectively). Rebound (mean) increase in serum bilirubin following the exchange transfusion was similar in both groups 64.9 (SD 16.7) micromols vs 73.7 (SD 41.4) micromol/L [p>0.05]. The time that bilirubin levels were evaluated is not noted.

Secondary Outcomes

Total number of exchange transfusions:

None of the babies needed a second exchange transfusion in either group.

Hemoglobin (g/dl) or hematocrit (%) measured 3-6 weeks after exchange transfusion:

No significant difference was seen in either group at 10 days and at three month follow up after exchange. The mean haemoglobin immediately post exchange was higher in double volume group 20.4 g/dl (SD 2.1) than single volume exchange transfusion group 18.3 (SD1.1) g/dL (p = 0.01) (Outcome 01.02). This was not a secondary outcome planned in the review.

Thrombocytopenia or coagulopathy following exchange, receiving intervention:

No intervention was needed in any of the groups in the study. Mean platelet levels immediately post exchange was significantly lower in double volume group. At 10 days post exchange there was no difference in platelet levels (Outcome 01.03).

Infection attributable to exchange transfusion:

This outcome was not reported.

Portal vein thrombosis and/or portal hypertension following exchange:

This outcome was not reported.

Necrotising enterocolitis within 72 hours of exchange:

None of the infants developed necrotising enterocolitis.

Discussion

Only one trial was eligible for the review. This was a small study comparing SVET with DVET in babies with hemolytic jaundice due to ABO incompatibility (Amato 1988). The study noted no significant difference in the short term outcomes (fall in bilirubin and anemia at 10 days) examined in this study between single volume and double volume exchange transfusions. Immediate post exchange platelet levels were higher in SVET group and hemoglobin levels were higher in DVET group. No interventions were required to correct this, and at 10 days post exchange no statistically significant difference was noted. The follow up of study infants was only for three months, and neurodevelopmental outcomes were not studied.

When introduced in the 1940's, exchange transfusion (double volume) was shown to reduce the incidence of kernicterus in Rhesus hemolytic disease (Diamond 1948). Early exchange transfusions were often performed early in order to remove hemolysed cells, rather than to reduce serum bilirubin. Studies have shown that the double volume exchange removes 80 - 85 % of RBC and single volume exchange removes about 65% of the circulating RBCs (Lathe 1955; Sproul 1961).

Forfar et al measured the bilirubin mass removed during exchange transfusion and correlated this with the volume of exchange. The bilirubin removed was 45% higher than the fall in serum bilirubin (Forfar 1958). This is because of the movement of bilirubin from the tissues into the blood during exchange. The bilirubin removed correlated with the volume of exchange (r = +0.34). An extra 20 - 70% increase in amount of bilirubin was noticed when single volume is increased to a double volume exchange. An exchange volume of 160 - 180 ml/kg resulted in optimum removal of bilirubin. Further increase in exchange volume did remove more bilirubin, but to a much lesser extent. Authors have considered lowering of total body bilirubin, rather than serum bilirubin, more important in prevention of kernicterus and, therefore, recommended double volume exchange transfusion as opposed to single volume in Rhesus hemolytic disease.

The spectrum of hemolytic jaundice and indications for exchange transfusion in jaundice has changed markedly in the past decade in developed countries following the increased use of Rhesus anti D. Exchange transfusion for Rhesus incompatibility has become uncommon and early exchange transfusions are hardly undertaken these days. It is not clear the same criteria for the exchange volume used in cases of Rhesus isoimmunization would apply to jaundiced babies without Rhesus hemolytic disease ( e.g. ABO incompatibility). Since the hemolysis is much lesser, one could argue that single volume exchange transfusion is as effective as double volume exchange for non Rhesus hemolysis with regards to neurodevelopmental outcome and may lead to fewer side effects. However, currently there is insufficient evidence to support a change in the common practice from double volume exchange to single volume exchange for non Rhesus conditions.

Reviewers' conclusions

Implications for practice

Based on the available data there is insufficient evidence to support or refute the use of single volume exchange transfusion as opposed to double volume exchange transfusion in jaundiced newborns. In Rhesus hemolytic disease there is a strong physiological base for continuing with the current practice of using double volume exchange transfusions.

Implications for research

Consideration should be given to the establishment of an adequately powered trials comparing single volume and double volume exchange transfusion with regards to long term neurological outcome, especially in jaundice not related to Rhesus hemolytic disease.

Acknowledgements

  • None noted.

Potential conflict of interest

  • None noted.

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Characteristics of studies

Characteristics of Included Studies

Study Methods Participants Interventions Outcomes Notes Allocation concealment
Amato 1988 Prospective Randomised
Control trial

Blinding of intervention: No
Complete follow up:Yes
Blinding of outcome assessments: Can't tell

20 full term infants with jaundice due to ABO hemolytic disease Single volume (80 ml/kg) vs double volume exchange transfusions(180 ml/kg) Bilirubin, platelets and hamoglobin level after exchange transfusion, duration of phototherapy, need of further exchange transfusion and adverse events during exchange transfusion B

Characteristics of excluded studies

Study Reason for exclusion
Soulie 1999 Retrospective case series on single volume exchange transfusion. No comparison with double volume exchange is given

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References to studies

Included studies

Amato 1988

{published data only}

* Amato M, Blumberg A, Hermann U Jr, Zurbrugg R. Effectiveness of single versus double volume exchange transfusion in newborn infants with AB0 hemolytic disease. Helvetica Paediatrica Acta 1988;43:177-86.

Excluded studies

Soulie 1999

{published data only}

Soulie JC, Larsen M, Andreu G, Berry M, Gabai A et al. Retrospective study of exchange transfusion for newborn infants with reconstituted blood. Review of 60 exchanges. Transfusion Clinique et Biologique 1999;6:166-73.

* indicates the primary reference for the study

Other references

Additional references

Bell 1978

Bell MJ, Ternberg JL, Feigin RD, Keating JP, Marshall R, Barton L, Brotherton T. Neonatal necrotizing enterocolitis. Therapeutic decisions based upon clinical staging. Annals of Surgery 1978;187:1-7.

Boggs 1960

Boggs TR, Westphal MC. Mortality of exchange transfusion. Pediatrics 1960;26:745-55.

Bollmann 1988

Bollmann R, Schilling H, Ihle W, Mockel A, Zienert A. Intrauterine exchange transfusion in Rh immunization. Zentralblatt fur Gynakologie 1988;110:54-9.

Bowman 1998

Bowman, JM. RhD hemolytic disease of the newborn. New England Journal of Medicine 1998;339:1775-7.

Ceccon 1993

Ceccon ME, Diniz EM, Ramos JL, Vaz FA. Exchange transfusion in newborn infants with perinatal hemolytic disease. Efficacy of the procedure. Revista Paulista de Medicina 1993;111:348-53.

Cockington 1979

Cockington R. A guide to the use of phototherpay in the management of neonatal hyperbilirubinemia. Journal of Pediatrics 1979;95:281-5.

Comley 1968

Comley A, Wood B. Albumin administration in exchange transfusion for hyperbilirubinaemia. Archives of Diseases in Childhood 1968;43:151-4.

Dennery 2001

Dennery PA, Seidman DS, Stevenson DK. Neonatal hyperbilirubinemia. New England Journal of Medicine 2001;344:581-90.

Diamond 1948

Diamond LK. Replacement transfusion as a treatment for erythroblastosis fetalis. Pediatrics 1948;2:520-4.

Flores 1997

Flores J, Yanez P, Ramirez R. Portal vein thrombosis in children. Presentation, treatment and outcome. Journal of Pediatric Gastroenterology & Nutrition 1997;25:481.

Fok 1990

Fok TF, So LY, Leung KW, Wong W, Feng CS, Tsang SS. Use of peripheral vessels for exchange transfusion. Archives of Diseases in Childhood 1990;65:676-8.

Forfar 1958

Forfar JO, Keay AJ, Elliot WD, Cumming RA. Exchange transfusion in neonatal hyperbilirubinemia. Lancet 1958;2:1131-7.

Funato 1989

Funato M, Shimada S, Tamai H, Taki H, Yoshioka Y. Automated exchange transfusion and exchange rate. Acta Paediatrica Japonica 1989;31:572-7.

Grannum 1988

Grannum PA, Copel JA, Moya FR, Scioscia AL, Robert JA, Winn HN et al. The reversal of hydrops fetalis by intravascular intrauterine transfusion in severe isoimmune fetal anemia. American Journal of Obstetrics and Gynaecology 1988;158:914-9.

Hoontrakoon 1998

Hoontrakoon S, Suputtamongkol Y. Exchange transfusion as an adjunct to the treatment of severe falciparum malaria. Tropical Medicine & International Health 1998;3:156-61.

Kanto 1978

Kanto WP Jr, Marino B, Godwin AS, Bunyapen C. ABO hemolytic disease: a comparative study of clinical severity and delayed anemia. Pediatrics 1978;62:365-9.

Lathe 1955

Lathe GH. Exchange transfusion as a means of removing bilirubin in haemolytic disease of newborn. British Medical Journal 1955;22:192-6.

Luban 1998

Luban NL. Hemolytic disease of the newborn: progenitor cells and late effects. New England Journal of Medicine 1998;338:830-1.

Lucas 1998

Lucas A, Abbott R. Neonatal necrotising enterocolitis. BPSU Annual Report 1996/7 1998;11.

Lucey 1966

Lucey JF. Diagnosis and treatment of the fetus with erythroblastosis. Pediatric Clinics of North America 1966;13:1117-30.

Lucey 1969

Lucey JF. Colonic perforation after exchange transfusion. New England Journal of Medicine 1969;280:724.

Maisels 1999

Maisels MJ. Is exchange transfusion for hyperbilirubinemia in danger of becoming extinct? Pediatric Research 1999;45:210.

Maisels 2001

Maisels MJ, Newman TB. Bilirubin and neurological dysfunction—do we need to change what we are doing? Pediatric Research 2001;50:677-8.

Merchant 1992

Merchant RH, Sakhalkar VS, Rajadhyaksha SB. Exchange transfusions via peripheral vessels. Indian Pediatrics 1992;29:457-60.

Mills 2003

Mills JF, Woodgate PG. Exchange transfusion for neonatal jaundice (Cochrane Protocol). In: The Cochrane Database of Systematic Reviews, Issue 3, 2003.

Schober 1990

Schober PH. Automated exchange transfusion in premature and newborn infants with hyperbilirubinemia using a peripheral arteriovenous vascular access device. Wiener Klinische Wochenschrift 1990;102:471-5.

Shapiro 2005

Shapiro SM. Definition of the clinical spectrum of kernicterus and bilirubin-induced neurologic dysfunction (BIND). Journal of Perinatology 2005;25:54-9.

Soorani 2001

Soorani-Lunsing I, Woltil HA, Hadders-Algra M. Are moderate degrees of hyperbilirubinemia in healthy term neonates really safe for the brain? Pediatric Research 2001;50:701-5.

Sproul 1961

Sproul A, Smith L. Bilirubin equilibration during exchange transfusion in hemolytic disease of newborn. Journal of Pediatrics 1961;65:12-26.

Stockman 2001

Stockman JA 3rd. Overview of the state of the art of Rh disease: history, current clinical management, and recent progress. Journal of Pediatric Hematology and Oncology 2001;23:554-62.

Valaes 1963

Valaes T. Bilirubin distribution and dynamics of bilirubin removed by exchange transfusion. Acta Paediatrica Scandinavia 1963;49:87-92.

Wennberg 1978

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Data and analyses

01 Single volume vs double volume exchange transfusion for ABO hemolytic disease

Comparison or outcome Studies Participants Statistical method Effect size
01.01 Immediate post exchange serum bilirubin level (micromol/L) 1 20 WMD (fixed), 95% CI -13.00 [-45.71, 19.71]
01.02 Hemoglobin 10 days post exchange (g/dl) 1 20 WMD (fixed), 95% CI 0.20 [-0.81, 1.21]
01.03 Platelet count 10 days post exchange (n X 1000, 000, 000/L) 1 20 WMD (fixed), 95% CI 24.00 [-52.66, 100.66]

Contact details for co-reviewers

DR DAVID DWA MILLIGAN

CONSULTANT NEONATAOLOGIST
PAEDIATRICS
RVI, NEWCASTLE
Ward 35, Leazes Wing
Royal Victoria Infirmary
Newcastle upon Tyne
UK
NE1 4LP
Telephone 1: +44 191 282 5034
Facsimile: +44 191 282 5038

E-mail: d.w.a.milligan@ncl.ac.uk


This review is published as a Cochrane review in The Cochrane Library, Issue 4, 2006 (see http://www.thecochranelibrary.com External Web Site Policy for information). Cochrane reviews are regularly updated as new evidence emerges and in response to feedback. The Cochrane Library should be consulted for the most recent version of the review.