Neonatal exchange transfusions in tertiary and non-tertiary hospital settings, New South Wales, 2001-2012.

AIM: To describe neonatal exchange transfusions in New South Wales (NSW) before and after release in January 2007 of a NSW Health guideline regarding exchange transfusions in tertiary and non-tertiary hospitals. METHODS: The study population included neonates receiving exchange transfusion in NSW hospitals, 2001-2012. Linked birth and hospital data for mothers and babies were used to describe birth characteristics and maternal and neonatal conditions. Exchange transfusions were identified in hospital data and compared for 2001-2006 and 2007-2012. Maternal and neonatal characteristics were compared with χ2 and Wilcoxon signed-rank tests. RESULTS: Between 2001 and 2012, there were 286 exchange transfusions performed for 281 neonates in NSW hospitals. The number of exchange transfusions decreased from 187 in 184 neonates for 2001-2006 to 99 in 97 neonates 2007-2012 (P < 0.001). The percentage of exchange transfusions performed at tertiary hospitals increased from 85% in 2001-2006 to 91% in 2007-2012, although this was not statistically significant (P = 0.16). Most neonates requiring exchange transfusion were born in tertiary hospitals: 62% for 2001-2006 and 69% for 2007-2012. Among those born in a non-tertiary hospital, the percentage transferred or admitted to a tertiary hospital for exchange transfusion was 63% in 2001-2006 and 77% in 2007-2012. CONCLUSION: Between 2001 and 2012, there was a decrease in neonatal exchange transfusions in NSW. After the 2007 guideline there was a non-significant increase in the proportion of exchange transfusions performed at tertiary hospitals. Although rare, exchange transfusions are still expected to occur occasionally in non-tertiary hospitals, requiring continuing support for this procedure in these settings.

Revisiting the Criteria for Exchange Transfusion for Severe Neonatal Hyperbilirubinemia in Resource-Limited Settings.

BACKGROUND: Exchange transfusion (ET) for severe neonatal hyperbilirubinemia (SNH) is frequently undertaken in low- and middle-income countries (LMIC), in sharp contrast to the prevailing practice in high-income countries. However, the criteria for initiating this procedure in settings with limited resources for treating infants with SNH have not been systematically explored. OBJECTIVE: To identify key considerations for initiating ET in resource-poor countries to curtail its unnecessary use for the prevention of kernicterus. METHODS: A review of the existing guidelines and literature on the management of neonatal hyperbilirubinemia worldwide was conducted to identify criteria and underlying factors for initiating ET. RESULTS: There is a dearth of evidence from randomized clinical trials to support clear criteria for indicated ET worldwide. Because risk assessment for kernicterus based solely on the levels of total serum bilirubin (TSB) has often proved inadequate, a combination of plasma/serum bilirubin estimation and clinical evaluation for acute bilirubin encephalopathy (ABE) has been recommended for predicting the risk of kernicterus. However, there is a lack of consistency regarding the TSB levels for which ET should be initiated in relation to the clinical signs/symptoms of ABE and hemolytic disorders. CONCLUSIONS: A decision-making framework that combines TSB thresholds and evidence of neurotoxicity is needed for evaluating the risk of kernicterus and prioritising infants for ET in LMICs to curtail unnecessary interventions.

Total serum bilirubin exceeding exchange transfusion thresholds in the setting of universal screening.

OBJECTIVE: To describe the incidence and predictors of total serum bilirubin (TSB) levels that meet or exceed American Academy of Pediatrics (AAP) exchange transfusion (ET) thresholds in the setting of universal screening. STUDY DESIGN: We conducted a retrospective cohort analysis of electronic data on 18 089 newborns ≥35 weeks gestation born at Northern California Kaiser Permanente Medical Care Program hospitals implementing universal TSB screening in 2005 to 2007, with chart review for subjects with TSB levels reaching the AAP threshold for ET. RESULTS: The outcome developed in 22 infants (0.12%); 14 (63.6%) were <38 weeks gestation. Only one infant received an ET; none of the infants had documented sequelae. The first TSB was at least high-intermediate risk on the AAP risk-nomogram for all 22 infants and high-risk for those ≥38 weeks, but was less than the phototherapy level in 15 infants (68%). Of these 15 infants, 2 failed phototherapy and 13 did not have a TSB repeated in <24 hours. However, re-testing all infants at high-intermediate risk or greater would have required 2166 additional bilirubin tests. CONCLUSION: Screening was sensitive but not specific for predicting exchange threshold.

Blood exchange transfusion for infants with severe neonatal hyperbilirubinemia.

Blood exchange transfusion has become a rare event in most developed countries. As a result, many pediatricians may not have performed or even seen one. However, it remains a frequent emergency rescue procedure for severe neonatal hyperbilirubinemia in many underdeveloped regions of the world. Conventionally, exchange transfusion has been performed via a central umbilical venous catheter by pull-push cycle method and recently peripheral artery/peripheral vein has emerged as an alternative, isovolumetric route. Continuous arterio-venous exchange is possibly more effective though its automation has not been successful. Concerns for procedural and operator related adverse events have been raised in the context of declining indications. A required continued expertise for this life-saving intervention, in the face of rare but critical hyperbilirubinemia and/or unrecognized hemolytic diseases, deserves adaptation of newer technologies to make neonatal exchange transfusion a safer and more effective procedure. Technological innovations and simulation technologies are urgently needed.

[Evolution of neonatal transfusion practices: current recommendations]. / Évolution des pratiques transfusionnelles en néonatalogie: recommandations actuelles.

Newborns and particularly preterm infants are a population at high risk of transfusion. The implementation of strategies to prevent transfusion by reducing blood loss, use of recombinant human erythropoietin, administration of iron and vitamins and delayed umbilical cord clamping have reduced the frequency of transfusions neonatal periods. The emergence of more stringent recommendations on indications for transfusion has been involved in this development. Various transformations and qualifications for red cell concentrates, platelet concentrates and fresh frozen plasma must be known to better adapt the blood products to newborn term and preterm according to their pathologies. Preparing pediatric units from a single donor for repeated transfusions reduces the allo-immune and infectious risks.

Efficacy, safety and cost-efficiency of using an alternative technique for automated exchange transfusion in pediatric patients with sickle cell disease.

BACKGROUND: Sickle cell disease (SCD) patients suffer complications requiring simple and/or exchange transfusion. In 1999 we developed an automated exchange technique using infusion pumps and vascular catheters (IV Pump Method). OBJECTIVE: To prove that IV Pump Method is cost-efficient, and as safe and effective as automated cell separators. METHODS: Retrospective chart review of SCD patients requiring exchange transfusion admitted to PICU from 2003-2009. Evaluated method used, complications, costs, and Hemoglobin S% (HgS%) change, excluding patients not requiring exchange transfusion. RESULTS: Cost-reduction with IV Pump Method is around $1000. Average HgS% reduction using IV Pump Method was 30.3 vs. 28.8 in Blood Cell Separator group (p = 0.84). We had no complications or mortalities, with the majority of patients being male (p = 0.03) and on the oldest age group (11-19 y/o) for both methods. CONCLUSION: The IV Pump Method is a safe, effective, and cost-efficient alternative to perform exchange transfusion.

Efficacy and safety of exchange transfusion as an adjunct therapy for severe Plasmodium falciparum malaria in nonimmune travelers: a 10-year single-center experience with a standardized treatment protocol.

BACKGROUND: Even in circumstances where optimal antimalarial and supportive treatment is available, severe Plasmodium falciparum malaria is still associated with a significant case fatality. Although exchange transfusion (ET) has been considered as a controversial adjunct therapy, we have not encountered any case fatality since ET was introduced as a standard adjunct therapy for patients with severe malaria. STUDY DESIGN AND METHODS: In this retrospective cohort study of 25 patients with severe malaria, the efficacy and safety of ET as an adjunct to parenteral antimalarial treatment (which was implemented in our hospital starting in 1998) were evaluated and compared with 31 historical control patients who were treated with conventional parenteral antimalarial treatment in the period before ET was added to the standard of care for severe malaria (generally before 1997). RESULTS: The parasite clearance times (PCT)(25%), PCT(50%), PCT(75%) and PCT(90%) were all significantly shorter for patients treated with ET than for patients treated with parenteral quinine only. The shorter PCTs in the ET group were the result of a more rapid parasite clearance in the early phases after initiation of ET. CONCLUSION: No case fatalities were observed in the ET group. The complications that were observed with ET were more likely related either to the multiorgan dysfunction associated with severe malaria or to side effects of parenteral quinine rather than to the ET procedure. ET may be safely executed in a setting with intensive care facilities and availability of safe blood products and should be considered as a beneficial adjunct treatment to parenteral antimalarial therapy.

Range of UK practice regarding thresholds for phototherapy and exchange transfusion in neonatal hyperbilirubinaemia.

OBJECTIVE: To establish the range of opinion regarding thresholds at which phototherapy and exchange transfusion are used to treat neonatal hyperbilirubinaemia in the UK. DESIGN: A survey of existing charts and guidelines collected from around the UK. Threshold levels were extracted from the charts and entered into an Excel spreadsheet. Filters were applied to analyse subsets of guidelines, and calculations were carried out to analyse the rate of rise of bilirubin (in micromol/l/h) between the origin and the plateau, where this was possible. RESULTS: Of 263 hospitals contacted, 163 submitted guidelines, of which most were in the form of individual charts. There was wide variation in the choice of the threshold levels at which treatment was recommended, particularly in preterm babies. At 28 weeks, for example, the range at which phototherapy was recommended extended from 100 micromol/l to 250 micromol/l, and the upper limit was even higher if data from units which used a single guideline for preterm babies of all gestations were included. There was variation in the choice of the origin of the graph and the time at which the plateau commenced (and hence the slope), whether "sickness" criteria should be adopted, and what those criteria should be. Many charts were confusing, poorly presented, sketchily drawn and lacked proper gridlines or axis labels. CONCLUSIONS: For such a vitally important topic it is disappointing that there is little existing consensus and no national guidance in the UK. Guidelines for England, Wales and Northern Ireland will be available from 2010, when the National Institute for Health and Clinical Excellence completes its review.

Exchange transfusion using peripheral vessels is safe and effective in newborn infants.

OBJECTIVES: The purpose of this study was to compare the efficiency and safety of exchange transfusion by using peripheral arteries and veins with that of conventional exchange transfusion via the umbilical vein in treating neonatal pathologic hyperbilirubinemia. PATIENTS AND METHODS: We retrospectively reviewed the medical charts of all neonates who had undergone exchange transfusion at our institution from January 1995 to December 2006. Causes of jaundice, efficiency of exchange transfusion in lowering serum bilirubin concentrations, adverse events, and outcomes were recorded. Data were compared between neonates who had undergone exchange transfusion via the peripheral arteries and veins method and those who had undergone exchange transfusion via the umbilical vein method. Data were also compared between stable neonates (body weight > 1500 g without medical problems other than jaundice) and unstable neonates. RESULTS: A total of 123 exchange-transfusion procedures were performed in 102 neonates in the 12-year study period: 24 were performed via the umbilical vein method and 99 via the peripheral vessels method. A total of 87 procedures were performed in 75 stable neonates and 36 in 27 unstable neonates. There was no significant difference in reduction of serum bilirubin level from circulation or the duration of procedures between the 2 methods. Eight neonates died before discharge, but none of the deaths seem to have been attributable to the exchange-transfusion procedure. Severe adverse events occurred more commonly in the umbilical vein group than the peripheral arteries and veins group in the stable neonates. All of the severe and minor events resolved completely without noticeable sequelae before discharge. CONCLUSIONS: Exchange transfusion using peripheral arteries and veins is efficient and effective in reducing serum bilirubin from circulation and is associated with few adverse events. This method should be considered for all neonates requiring exchange transfusion for treatment of neonatal hyperbilirubinemia.

Is exchange transfusion a possible treatment for neonatal hemochromatosis?

Neonatal hemochromatosis is a rare congenital disorder of the liver associated to a poor prognosis. Liver transplantation is often required, since no effective medical treatment has been found. Despite mounting evidence of an alloimmune etiology of this condition, exchange transfusion has never been proposed as a specific treatment for neonatal hemochromatosis. Here we describe two siblings affected by neonatal hemochromatosis. The first, a female, died at 18 days of severe coagulopathy and acute renal failure, diagnosed as affected by neonatal hemochromatosis only when the second sibling was suspected as being affected by the same disease. The second child showed a rapidly worsening coagulopathy which was treated with two exchange transfusions, followed by rapid clinical and laboratory improvement, before reaching a definite diagnosis of neonatal hemochromatosis. He is healthy at present after a follow-up of 12 months. Although exchange transfusion has never been considered as treatment for neonatal hemochromatosis, this case suggests that it could be a feasible treatment option for children affected by this disease, as for other alloimmune conditions.

Phototherapy and exchange transfusion for neonatal hyperbilirubinaemia: neonatal academic hospitals' consensus guidelines for South African hospitals and primary care facilities.

The purpose of this document is to address the current lack of consensus regarding the management of hyperbilirubinaemia in neonates in South Africa. If left untreated, severe neonatal hyperbilirubinaemia may cause kernicterus and ultimately death and the severity of neonatal jaundice is often underestimated clinically. However, if phototherapy is instituted timely and at the correct intensity an exchange transfusion can usually be avoided. The literature describing intervention thresholds for phototherapy and exchange transfusion in both term and preterm infants is therefore reviewed and specific intervention thresholds that can be used throughout South Africa are proposed and presented graphically. A simplified version for use in a primary care setting is also presented. All academic heads of neonatology departments throughout South Africa were consulted in the process of drawing up this document and consensus was achieved.

Jaundice in the preterm infant.

Around 80 per cent of preterm infants develop hyperbilirubinaemia characterised by jaundice. This condition is most commonly treated with phototherapy and/or exchange transfusion. There is conflicting evidence regarding the management of preterm infants receiving phototherapy, including fluid management regimes, thermoregulation and prevention of other complications. A though phototherapy appears to effectively treat preterm jaundice, aspects of its use remain controversial and its apparent success is not evidence based. Research must continue to facilitate the development of effective treatment and the establishment of evidence-based guidelines.

Sickle cell thalassemia in pregnancy: a case report.

A 31-year-old pregnant woman at 20 weeks' gestation was sent to our hospital for fever, anemia, and arthralgias. As she was known to be a double heterozygote for beta-thalassemia and hemoglobin S, a diagnosis of hemolytic anemia caused by sickled red cells vasocclusive crises was made. The patient was submitted to partial exchange transfusion (PET) with a complete recovery. A second PET was performed at 36 weeks' gestation, and elective cesarean section was performed at 37 weeks, with the birth of a normal female neonate.

Effect of exchange transfusion with a red blood cell substitute on neonatal hemodynamics and organ blood flows.

The present study was designed to evaluate the effect of a perfluorocarbon erythrocyte substitute on hemodynamics in the newborn lamb. Isovolumic double volume exchange transfusions were performed with perfluorocarbon emulsion (FC-43) on lambs who were ventilated to maintain normal acid base status. Hematocrit, fluorocrit, viscosity, arterial gas tensions, mean arterial pressure, and heart rate were determined before (control) and after (exchange) exchange transfusion. A radiolabeled microsphere technique was used and cardiac output, organ blood flow, organ vascular resistance, and oxygen delivery were calculated. As the hematocrit and viscosity decreased and the fluorocrit increased, there was a significant increase in PaO2 as well as a significant decrease in A-a gradient and oxygen content. There was no significant change in the acid-base status or the hemodynamic profile (heart rate, stroke volume, cardiac output, and mean arterial pressure). Blood flow to the heart and brain showed a significant increase, whereas flow to the cortex of the kidney showed a significant decrease. There was no significant change in flow to the gastrointestinal tract. Organ vascular resistance in the brain significantly decreased, increased in the kidney, and showed no significant change in the heart and gastrointestinal tract. Oxygen delivery significantly decreased in all organs except the heart. These data suggest that perfluorocarbon emulsions can acutely maintain hemodynamic stability in the newborn lamb and that the intrinsic properties of perfluorocarbons allow for the preservation of adequate oxygenation and acid-base status.

Oxygen extraction ratio: a valid indicator of transfusion need in limited coronary vascular reserve?

We have described whole body oxygen (O2) extraction ratio (ER) as a reliable indicator of transfusion need in acute normovolemic anemia. In normal hearts, myocardial lactate production (-LACT), indicating anaerobic metabolism, does not occur until the ER greater than 50% and Hct less than 10%. It is not known if the ER is valid in the setting of limited coronary vascular reserve. This study assesses the effect of a critical left anterior descending (LAD) coronary stenosis on the compensation to acute blood loss anemia. Adult dogs were anesthetized, paralyzed, and mechanically ventilated. A critical LAD stenosis was created in seven animals (STEN). There were seven controls (CON). Animals underwent isovolemic exchange transfusion with 6% HES until cardiac failure (CF). Catheters were placed in the aorta, pulmonary artery, and anterior interventricular coronary vein. Cardiac failure occurred at Hct = 8.6% +/- 0.4% in the CON and 17.0% +/- 0.5% in the STEN animals. Cardiac output increased in the CON, but not in the STEN animals. Blood flow in the LAD increased in the CON but not the STEN animals. -LACT began in the CON and STEN animals at Hct less than 20% and coincided with an ER greater than 50% in both groups. We conclude that CF occurs at a higher hematocrit with a critical LAD stenosis. The whole body ER greater than 50% remains a valid indicator of myocardial metabolism in anemia in the presence of limited coronary vascular reserve. The ER may be a useful guide to transfusion therapy.

Importance of purification on transfusional efficacy of hemoglobin solutions.

It has only been realized quite recently how important is the purification of hemoglobin solution for use in transfusion and several techniques have been published. We used ion exchange chromatography with which the main "contaminants" (glycoproteins, enzymes, phospholipids) are absorbed by the gel, whereas hemoglobin is not retained. The solutions studied here are non-modified hemoglobin and its homologue pyridoxylated hemoglobin (PLP-Hb). Physico-chemical analyses, usually undertaken to characterize hemoglobin solutions, show no difference before and after purification, except that the enzymatic activity almost disappears. In order to appreciate the benefits of purification, total exchange transfusions were carried out on rats. Without reperfusion, purification of the hemoglobin solution allowed a significantly longer survival time which was even more significant with PLP-Hb solution. Urinary loss did not seem to be affected by purification. With reperfusion in order to compensate these renal losses, PLP-Hb solutions gave survival times up to three days. However, the inevitable death of the animals poses the problem of instability of these purified solutions following enzyme loss.

Thrombotic thrombocytopenic purpura treated with plasma exchange or exchange transfusions.

Of 40 patients with thrombotic thrombocytopenic purpura, 17 were treated with plasma exchange, 15 with exchange transfusions, and 6 with both types of therapy. One patient died before being treated and another patient was seen but not treated. Plasma exchange was performed daily for a mean of seven exchanges per patient. The replacement fluid during plasma exchange was fresh frozen plasma in all cases. The complete response rates for each type of treatment were as follows: 88% for plasma exchange (15 patients), 47% for exchange transfusions (7 patients), and 67% for exchange transfusions and plasma exchange (4 patients). Clinical and laboratory factors were examined for any statistically significant association with therapy response. Treatment with plasma exchange was statistically the initial factor most strongly associated with prognosis. Paresis, paresthesias, seizures, mental status change, and coma showed no association with response to treatment. Some of the laboratory factors that did not show significant association with treatment response were the initial creatinine, hemoglobin, platelet count, lactate dehydrogenase, and total bilirubin. This study supports the hypothesis that plasma exchange has significantly improved the prognosis of patients with thrombotic thrombocytopenic purpura. These patients should be treated aggressively regardless of the severity of their symptoms.