Exchange Transfusion In Infants Research Articles

Technical Report: Diagnosis and Management of Hyperbilirubinemia in the Newborn Infant 35 or More Weeks of Gestation.

Severe hyperbilirubinemia is associated with kernicterus. Informed guidance on hyperbilirubinemia management, including preventive treatment thresholds, is essential to safely minimize neurodevelopmental risk. To update the evidence base necessary to develop the 2022 American Academy of Pediatrics clinical practice guideline for management of hyperbilirubinemia in the newborn infant ≥35 weeks' gestation. PubMed. English language randomized controlled trials and observational studies. Excluded: case reports or series, nonsystematic reviews, and investigations focused on <35-weeks' gestation infants. Topics addressed in the previous clinical practice guideline (2004) and follow-up commentary (2009) were updated with new evidence published through March 2022. Evidence reviews were conducted for previously unaddressed topics (phototherapy-associated adverse effects and effectiveness of intravenous immune globulin [IVIG] to prevent exchange transfusion). New evidence indicates that neurotoxicity does not occur until bilirubin concentrations are well above the 2004 exchange transfusion thresholds. Systematic review of phototherapy-associated adverse effects found limited and/or inconsistent evidence of late adverse effects, including cancer and epilepsy. IVIG has unclear benefit for preventing exchange transfusion in infants with isoimmune hemolytic disease, with a possible risk of harm due to necrotizing enterocolitis. The search was limited to 1 database and English language studies. Accumulated evidence justified narrowly raising phototherapy treatment thresholds in the updated clinical practice guideline. Limited evidence for effectiveness with some evidence of risk of harm support the revised recommendations to limit IVIG use.

Intravenous Immunoglobulin Use in Hemolytic Disease Due to ABO Incompatibility to Prevent Exchange Transfusion.

IntroductionIntravenous immunoglobulin (IVIG) has been widely used to treat the hemolytic disease of the newborn (HDN). Although it has been shown that IVIG treatment reduces the duration of phototherapy and hospitalization, the use of IVIG in hemolytic disease due to ABO incompatibility has been controversial in recent years. This study aimed to investigate the role of IVIG in the prevention of exchange transfusion in infants with ABO HDN who presented with bilirubin levels at or above the level of exchange transfusion.Materials and MethodsThis study evaluated the data of infants with ABO HDN in the Turkish Neonatal Jaundice Online Registry. The infants with ABO HDN who met the total serum bilirubin level inclusion criteria (within 2–3 mg/dL of exchange transfusion or even above exchange transfusion level) were included in the study according to the guidelines from the American Academy of Pediatrics and the Turkish Neonatal Society. All patients were managed according to the unit protocols recommended by these guidelines and received light-emitting diode (LED) phototherapy. Infants who only received LED phototherapy, and who received one dose of IVIG with LED phototherapy were compared.ResultsDuring the study period, 531 term infants were included in the study according to inclusion criteria. There were 408 cases in the phototherapy-only group, and 123 cases in the IVIG group. The demographic findings and the mean bilirubin and reticulocyte levels at admission were similar between the groups (p > 0.05), whereas the mean hemoglobin level was slightly lower in the IVIG group (p = 0.037). The mean age at admission was earlier, the need for exchange transfusion was higher, and the duration of phototherapy was longer in the IVIG group (p < 0.001, p = 0.001, and p < 0.001, respectively). The rate of re-hospitalization and acute bilirubin encephalopathy (ABE) was higher in the IVIG group (p < 0.001 and p = 0.01, respectively).ConclusionIn this study, we determined that one dose of IVIG did not prevent an exchange transfusion nor decrease the duration of phototherapy in infants, who had bilirubin levels near or at exchange transfusion level, with hemolytic disease due to ABO incompatibility.

Treatment criteria for infants with hyperbilirubinemia in Japan

With the availability of blue light-emitting diode phototherapy devices capable of delivering high-intensity irradiance, neonatologists in Japan are requesting revisions of the 1992 Kobe University treatment criteria for hyperbilirubinemia using total serum/plasma bilirubin (TB) and serum unbound bilirubin (UB) threshold values, especially for indications for exchange transfusion (ET). Retrospective data analysis of 1,184 infants born between January 2012 and November 2014 when the 1992 criteria were followed, we applied revised criteria proposed in 2017 to these infants to assess consequent changes in treatment recommendations. We found that the estimated number of infants with ET indications decreases from 48 to 20, with intensive phototherapy recommended for the remaining 28. Also, the estimated number of infants with phototherapy indications decreases from 446 to 195. We conclude that use of the revised criteria will lead to judicious use and reduction of phototherapy and ET in infants with hyperbilirubinemia.

Immunoglobulin for alloimmune hemolytic disease in neonates.

Exchange transfusion and phototherapy have traditionally been used to treat jaundice and avoid the associated neurological complications. Because of the risks and burdens of exchange transfusion, intravenous immunoglobulin (IVIg) has been suggested as an alternative therapy for alloimmune hemolytic disease of the newborn (HDN) to reduce the need for exchange transfusion. To assess the effect and complications of IVIg in newborn infants with alloimmune HDN on the need for and number of exchange transfusions. We performed electronic searches of CENTRAL, PubMed, Embase (Ovid), Web of Science, CINAHL (EBSCOhost), Academic Search Premier, and the trial registers ClinicalTrials.gov and controlled-trials.com in May 2017. We also searched reference lists of included and excluded trials and relevant reviews for further relevant studies. We considered all randomized and quasi-randomized controlled trials of IVIg in the treatment of alloimmune HDN. Trials must have used predefined criteria for the use of IVIg and exchange transfusion therapy to be included. We used the standard methods of Cochrane and its Neonatal Review Group. We assessed studies for inclusion and two review authors independently assessed quality and extracted data. We discussed any differences of opinion to reach consensus. We contacted investigators for additional or missing information. We calculated risk ratio (RR), risk difference (RD) and number needed to treat for an additional beneficial outcome (NNTB) for categorical outcomes. We calculated mean difference (MD) for continuous variables. We used GRADE criteria to assess the risk of bias for major outcomes and to summarize the level of evidence. Nine studies with 658 infants fulfilled the inclusion criteria. Term and preterm infants with Rh or ABO (or both) incompatibility were included. The use of exchange transfusion decreased significantly in the immunoglobulin treated group (typical RR 0.35, 95% CI 0.25 to 0.49; typical RD -0.22, 95% CI -0.27 to -0.16; NNTB 5). The mean number of exchange transfusions per infant was also significantly lower in the immunoglobulin treated group (MD -0.34, 95% CI -0.50 to -0.17). However, sensitivity analysis by risk of bias showed that in the only two studies in which the treatment was masked by use of a placebo and outcome assessment was blinded, the results differed; there was no difference in the need for exchange transfusions (RR 0.98, 95% CI 0.48 to 1.98) or number of exchange transfusions (MD -0.04, 95% CI -0.18 to 0.10). Two studies assessed long-term outcomes and found no cases of kernicterus, deafness or cerebral palsy. Although overall results show a significant reduction in the need for exchange transfusion in infants treated with IVIg, the applicability of the results is limited because of low to very low quality of evidence. Furthermore, the two studies at lowest risk of bias show no benefit of IVIg in reducing the need for and number of exchange transfusions. Based on these results, we have insufficient confidence in the effect estimate for benefit of IVIg to make even a weak recommendation for the use of IVIg for the treatment of alloimmune HDN. Further studies are needed before the use of IVIg for the treatment of alloimmune HDN can be recommended, and should include blinding of the intervention by use of a placebo as well as sufficient sample size to assess the potential for serious adverse effects.

A decision-making tool for exchange transfusions in infants with severe hyperbilirubinemia in resource-limited settings.

Late presentation and ineffective phototherapy account for excessive rates of avoidable exchange transfusions (ETs) in many low- and middle-income countries. Several system-based constraints sometimes limit the ability to provide timely ETs for all infants at risk of kernicterus, thus necessitating a treatment triage to optimize available resources. This article proposes a practical priority-setting model for term and near-term infants requiring ET after the first 48 h of life. The proposed model combines plasma/serum bilirubin estimation, clinical signs of acute bilirubin encephalopathy and neurotoxicity risk factors for predicting the risk of kernicterus based on available evidence in the literature.

327 Excessively High Bilirubin and Exchange Transfusion in Very Low Birth Weight Infants

Objective: To evaluate the distribution of peak serum bilirubin levels in very low birth weight (VLBW) infants and the performance of exchange transfusion in infants with excessively high bilirubin levels. Methods: A population based observational study using data collected by the Israel National VLBW Infant Database. The study sample comprised 13,499 infants of 24 to 33 weeks gestation. Two definitions of excessively high peak bilirubin levels which might be considered as threshold levels for performance of exchange transfusion were used. Firstly, a bilirubin level of ≥ 15 mg/dL for all infants (PSB-15), and secondly, incremental bilirubin levels ranging from 12-17 mg/dL according to gestational age (PSB-GA). Multivariable logistic regression analyses were performed to examine the factors associated with performance of exchange transfusion. Results: Four hundreds sixty eight (3.5%) and 1035 infants (7.7%) infants in the PSB-15 and in the PSB-GA groups respectively had peak serum bilirubin levels above thresholds for exchange transfusion. Exchange transfusion's were performed in only 66 (14.1%) of these infants in the PSB-15 group and 91 (8.8%) in the PSB-GA group. In both groups performance of exchange transfusion was significantly associated with peak serum bilirubin levels, with an odds ratio of 1.38 for each mg/dL increase above the threshold level. Conclusion: Exchange transfusion was performed in only 9-14% of VLBW infants with excessively high bilirubin levels. This may be related to an absence of definitive guidelines or the possible belief that the risks of exchange transfusion outweigh the potential risk of bilirubin induced neurological injuries.

Intravenous immune globulin reduces the need for exchange transfusions in Rhesus and AB0 incompatibility

To conduct a quality control review of a single institution experience with intravenous immune globulin in the treatment of Rhesus and AB0 incompatibility. Intravenous immune globulin as treatment for Rhesus and AB0 incompatibility was introduced in our hospital in 1998. We performed a chart review of 176 infants with Rhesus or AB0 incompatibility treated in our hospital between 1993 and 2003, divided into a historical control group (1993-1998) and a treatment group (1999-2003). The project was approved through institutional ethics procedures. The use of exchange transfusion as a therapeutic modality was significantly reduced in the cohort treated with intravenous immune globulin (OR 0.11; 95% CI 0.046-0.26, p < 0.001). We found no difference between the intravenous immune globulin group and the infants receiving only exchange transfusion as far as the duration of phototherapy. Infants with Rhesus incompatibility had a higher need for top-up transfusions than those with AB0 incompatibility. This study supports the evidence from previous studies suggesting that intravenous immune globulin significantly reduces the need for exchange transfusion in infants with Rhesus and AB0 incompatibility.

Exchange transfusion in infants with extreme hyperbilirubinemia: an experience from a developing country

To determine the clinical and epidemiological features of infants with extreme hyperbilirubinemia who require exchange transfusion (ET). Term and near-term infants admitted to a paediatric hospital over a 5-year period in La Paz, Bolivia, were included in the study if they met the following criteria: age less than 30 days; total serum bilirubin (TSB) levels > or =428 micromol/L (> or =25 mg/dL) on admission and if they had undergone an ET. Fifty-six infants were identified during the study period. Most of them were exclusively breastfed (98.2%). Median age at admission was 7 days. Weight loss of more than 12% since birth, as well as dehydration, was registered in more than one-third of cases. Extreme hyperbilirubinemia was considered as secondary to increased enterohepatic circulation (EHC) in most cases (73%). The mean TSB level on admission was 531.8 micromol/L (31.1 mg/dL). Fifteen infants (26.8%) showed signs of acute bilirubin encephalopathy (ABE). Early ABE was reversible after ET in most cases but all infants with advanced ABE developed severe kernicteric sequelae. Nine patients (16.1%) developed adverse events attributable to ET. Dehydration and weight loss in breastfed infants appeared to be an important factor associated with extreme hyperbilirubinemia and secondary brain damage during the first week of life. This may well be avoided if signs of ABE and its associated conditions are identified appropriately by follow-up programmes.

Historical Perspectives

“The experimental hypothesis, in short, must always be based on prior observation.”—Claude Bernard (1) Modern adult intensive care started in Denmark in 1952 in response to the high mortality from the respiratory complications seen with a devastating epidemic of poliomyelitis. Anesthetists and physiologists created a new discipline when they collaborated to make sequential measurements of cardiorespiratory variables, then aggressively corrected abnormal conditions. (2) When modern neonatal intensive care emerged a decade later, it followed the same philosophy. The start of modern neonatology was stimulated in large part by an expanding understanding of: 1) the circulatory and respiratory physiology of adaptation to extrauterine life, 2) how those adjustments could fail, and 3) the pathophysiology of hyaline membrane disease. (3)(4)(5)(6)(7)(8)(9)(10) (The monograph by Dawes (3) gives an excellent overview of the relevant animal research). This research had reached a point where it could be applied to clinical care if the necessary physiologic measurements could be made in newborns. To this end, investigators began to catheterize the umbilical arteries of newborns to measure blood gas tensions and pH, with several investigators also measuring aortic pressures. (9)(11)(12)(13) Such invasive techniques were highly controversial initially, but they gradually became the accepted methodology for monitoring the sick neonate. (12) The use of oxygen in preterm infants who had cardiorespiratory distress was an important component of this change in approach to the sick infant. The standard had been to use no more than 40% oxygen to prevent retrolental fibroplasia (retinopathy of prematurity). However, it was obvious that this approach would be insufficient to relieve hypoxia in some infants and would produce hyperoxia in others. Avery and Oppenheimer (13) observed an increase in deaths due to …

Preventing kernicterus: Almost there

Preventing kernicterus: Almost there

CBV during exchange transfusion in infants with erythroblastosis.

Since the introduction of postpartal and prepartal Anti-D-prophylaxis (Bowman et al., 1978; Thornton et al., 1989), the rate of sensibilisation to the rhesus system has decreased in Germany from 1:20.000 before prophylaxis to 1:1.000 today (Maas et al., 1991). There is, however, little chance that the future could hold an even lower incidence of infants with isoimmunisation caused by Rhesus incompatibility, since prophylaxis has a constant failure rate. In addition, there are other types of isoimmunisations caused by other blood groups, especially anti-c, Kell and Duffy, where no prophylaxis is yet possible. Therefore exchange transfusion (ET) will continue to be a part of the postnatal management in neonates suffering from Morbus haemolyticus.

Cerebral blood volume changes during exchange transfusions in infants born at or near term

We investigated the effects on cerebral hemodynamics of blood pressure changes during exchange transfusions in infants born at or near term, using near infrared spectroscopy in eight stable infants (mean gestational age, 36.2 ± 1.3 weeks) who underwent a total of 21 exchange transfusions for erythroblastosis fetalis (rhesus hemolytic disease). Changes in mean arterial blood pressure derived from an indwelling umbilical arterial catheter, transcutaneous arterial oxygen and carbon dioxide tension, as well as changes in cerebral oxygenated hemoglobin (HbO 2), deoxygenated hemoglobin (HbR), and total hemoglobin (Hb tot =HbO 2 + HbR), were recorded continuously from 15 minutes before until the completion of the exchange transfusion. Relative change(s) in cerebral blood volume (dCBV) were calculated as follows: dCBV =change in Hb tot × 0.89/Venous hemoglobin. Changes in mean arterial blood pressure and dCBV were observed during all exchange transfusions; a decrease was found during the withdrawal period and an increase during the infusion period. The mean response of dCBV to a change in mean arterial blood pressure was 0.011 ml · 100 gm - 1 · mm Hg. Multivariate analysis showed that dCBV were primarily associated with changes in mean arterial blood pressure, followed by changes in arterial oxygen tension and in exchange cycle duration. We conclude that in stable term and near-term infants, hemorrhagically induced blood pressure changes provoke dCBV. (J P EDIATR 1994;125:617-21)

Serum opsonic activity and peripheral neutrophil counts before and after exchange transfusion in infants with early onset group B streptococcal septicemia.

Serum opsonic antibody activity and peripheral neutrophil counts were measured in 41 infants who received an exchange transfusion of fresh whole blood for early onset group B streptococcal septicemia. Immature and mature neutrophils increased significantly in the peripheral blood post-exchange transfusion among survivors. Increases in opsonic antibody levels did not reach statistical significance following exchange transfusion. It is possible that exchange transfusion with fresh whole blood may enhance mobilization of neutrophils in infants with adequate bone marrow storage pools. A prospective controlled study is required to evaluate properly the role of exchange transfusion in infants with group B streptococcal sepsis.

Immunologic factors in human melanoma ???metastatic??? to products of gestation (with exchange-transfusion in infant to mother)

Immunologic factors in human melanoma ???metastatic??? to products of gestation (with exchange-transfusion in infant to mother)

Roentgen aspects of umbilical vascular catheterization in the newborn. The problem of catheter placement.

Radiographic examination represents the only method for the exact localization of intravascular catheters. There has been, however, no review of the technic of umbilical arterial and venous catheterization in newborn infants in the radiographic literature. Moreover, in the evaluation of films of infants with the respiratory distress syndrome, cardiac disorders, or abdominal abnormalities, the radiologist tends to concentrate on anatomical and physiological pathology and pays little attention to the localization or significance of catheters positioned below the diaphragm. Indeed, he may fail to consider the potential complications of the use of such catheters. Catheterization of the umbilical vein was utilized by Diamond et al. (1) in 1946 for the purpose of exchange transfusion in infants with erythroblastosis fetalis. Later, catheterization of the vein, as well as of the umbilical artery, was used for angiocardiography (3) and now is employed quite routinely for withdrawal of blood for gas analysis and for the introduction of fluids or blood into the vascular system in infants with the respiratory distress syndrome. To understand the positioning of umbilical catheters, knowledge of the anatomy of the neonatal vascular circulation is essential. Figure 1 illustrates this circulation diagrammatically. The course of the catheter into the aorta is relatively simple. It passes caudally in the umbilical artery, angulates near the dome of the bladder to enter the hypogastric artery, and then goes posteriorly and craniad to the common iliac and thence to the abdominal aorta. The course of the venous catheter is more complicated. Following passage through the umbilical vein, the catheter traverses the ductus venosus (which remains patent for the first fifteen to twenty days of life) and then enters the inferior vena cava. It may enter the right atrium or pass through the foramen ovale into the left atrium. The catheter may be diverted into the portal sinus and thence into a portal vein, or it may enter the splenic or inferior mesenteric veins. Introduction of a catheter into the aorta is relatively easy since the only difficulty encountered is the angulation at the confluence of the umbilical and hypogastric arteries. The placement of the venous catheter is much more difficult. When catheterization is performed in cases of respiratory distress syndrome, the optimum location of the catheter tip is in the relatively short segment of inferior vena cava near the diaphragm, proximal to the entrance of the hepatic vein and below the right auricle. Dunn (2) in 1966 correlated the length of catheter from the umbilical vein to this point in the inferior vena cava with the size of the infant and found that the catheter length varied from 5 to 10.5 cm. He felt that the ratio of the catheter length to the shoulder-umbilicus length was most reliable.

Methods of storage of whole blood.

To the Editor:— Indications for Transfusion of Freshly Drawn by Harold A. Oberman, MD ( 199 :93, 1967) is an excellent review of the clinical situations that require freshly drawn blood. Another currently available method of storing whole blood with no added acid-citrate-dextrose (ACD) solution is the use of the blood pack 500-ml ion exchange (Fenwal, JB2). This is a cationic ion exchange resin (sodium cycle) with no nutrient or buffer. The plastic column substitutes sodium ion for calcium ion. Blood so collected can be used for six days and is especially valuable in exchange transfusions in infants and in other patients when excess citrate and low calcium levels need to be avoided. The red blood cells, the platelets, the leukocytes, the coagulation factors, and the potassium and ammonium are at least comparable to that of ACD-stored blood.

Fresh and stored citrated blood for exchange transfusions.

The technique of exchange transfusion in infants has been perfected through experience with thousands of procedures in medical centers in this country and abroad. Reliable methods have been developed and used with gratifying results. In the great majority of these transfusions, an anticoagulant solution of acid citrate dextrose USP (ACD solution) has been used for the donor blood, although several authors have reported using heparinized blood with satisfactory results. 1-5 Complications during exchange transfusion due to high potassium levels in stored blood were recognized soon after the procedure came into general use. The need for caution in using stored blood has been emphasized repeatedly, 1,6-10 although in at least one study blood stored up to 4 days did not cause hyperkalemia in the recipient infants despite moderately elevated potassium levels in the blood at the time it was used.8 A variety of complications have been ascribed directly and indirectly to

Experimental observations on cardiac arrhythmia during exchange transfusion in rabbits

Summary There have been a number of reports of cardiac arrhythmia during exchange transfusion in infants suffering from hemolytic disease. Exchange transfusion was performed in rabbits, simulating human transfusion as closely as possible. The electrocardiographic changes were followed to compare citrated with heparinized blood. The effects of raising the potassium content and lowering the temperature of the donor blood were also observed. Exchange transfusion with hyperpotassemic citrated blood was fatal to 15 of 19 rabbits. Twelve of the 15 deaths resulted from ventricular fibrillation. Ventricular fibrillation did not occur in rabbits given citrated blood of normal potassium content or heparinized blood. The onset of ventricular fibrillation was delayed by the prophylactic injection of calcium gluconate. When the temperature of the donor blood was lowered there were recognizable electrocardiographic changes, but they were not associated with an increased incidence of ventricular fibrillation or a higher mortality.

Heme pigment and bilirubin rebound following exchange transfusion in infants with erythroblastosis fetalis: Summer and Goulson: p. 30

Heme pigment and bilirubin rebound following exchange transfusion in infants with erythroblastosis fetalis: Summer and Goulson: p. 30

The Use of Heparinized Blood for Exchange Transfusion in Infants

The mortality rate and neurological sequelae from hemolytic disease of the newborn have been vastly reduced by the use of the exchange transfusion.1,2Yet this lifesaving procedure itself is associated with severe complications and can cause death.3-5Stored citrated blood has been implicated as the cause of many of these untoward reactions. These include convulsions, retching, clinical signs of shock,6heart block,7decreased cardiac stroke volume,8increased venous pressure,3cardiac irregularities,3generalized irritability,9and even death.3-5,9 Many of these deleterious effects of stored citrated blood have been circumvented by use of fresh heparinized whole blood. Previous reports,3,10-12although limited in number, do indicate the general lack of toxicity of fresh heparinized blood. It is the purpose of this paper to detail the clinical experience in 152 exchange transfusions conducted with heparinized fresh blood. These exchanges were performed at the University