Cite Score:
0.28
ELSEVIER SCOPUS

Complications of Exchange Transfusion in Hospitalized Neonates in Two Neonatal Centers in Hamadan, A Five-Year Experience

AUTHORS

Mohammad Kazem Sabzehei 1 , Behnaz Basiri 1 , * , Maryam Shokouhi 1 , Saadat Torabian 2

AUTHORS INFORMATION

1 Department of Pediatrics, Hamadan University of Medical Sciences, Hamadan, IR Iran

2 School of Medicine, Tehran University of Medical Sciences, Tehran, IR Iran

How to Cite: Sabzehei M K, Basiri B, Shokouhi M, Torabian S. Complications of Exchange Transfusion in Hospitalized Neonates in Two Neonatal Centers in Hamadan, A Five-Year Experience, J Compr Ped. 2015 ; 6(2):e20587. doi: 10.17795/compreped-20587.

ARTICLE INFORMATION

Journal of Comprehensive Pediatrics: 6 (2); e20587
Published Online: May 23, 2015
Article Type: Research Article
Received: May 24, 2014
Revised: January 29, 2015
Accepted: February 3, 2015
Crossmark

Crossmark

CHEKING

READ FULL TEXT
Abstract

Background: Exchange transfusion is commonly used in newborns for immediate treatment of severe hyperbilirubinemia to prevent bilirubin encephalopathy and kernicterus.

Objectives: This study aimed to determine etiology and complications in newborns who received exchange transfusion for severe hyperbilirubinemia over the last five years.

Patients and Methods: A retrospective study was performed on 28 days old infants who received exchange transfusion due to severe hyperbilirubinemia for a period of five years (from October 1st, 2006 through September 30th, 2011) in two neonatal units at Besat and Fatemieh hospitals in Hamadan, Iran. All data about patients’ demographic characteristics, causes of hyperbilirubinemia, frequency, and complications of exchange transfusion were collected from medical records and analyzed using SPSS Version 12.0).

Results: Exchange transfusion was performed in 148 neonates. Eighteen patients (12.2%) received exchange transfusion twice and seventeen patients (11.4%) three times or more. Among 118 neonates 80 (54.9%) were female and the mean gestational age and birth weight were 37.2 ± 2.5 weeks and 2847 ± 699 grams, respectively. The mean maximum total serum bilirubin levels were 27. 7.6 ± 7.28 mg/dL. Hemolytic disease was found in 72 (48.6%) of newborns. The most common cause of hemolysis was ABO incompatibility in 54 (36.5%). The etiologic factors were unidentified in 61 (41.2%) neonates. Complications occurred in 57 (38.5%) neonates and the most common complications were thrombocytopenia in 26 (17.6%) and hypocalcaemia in 17 (11.5%) neonates. Mortality was found in one (0.7%) neonate.

Conclusions: The etiology of exchange transfusion was unidentified in most cases; however, ABO incompatibility was the most prevalent cause of hyperbilirubinemia. Complications were common after exchange transfusion and should be considered carefully.

Keywords

Hyperbilirubinemia Exchange Transfusion Whole Blood Complications Infant Newborn

Copyright © 2015, Iranian Society of Pediatrics. This is an open-access article distributed under the terms of the Creative Commons Attribution-NonCommercial 4.0 International License (http://creativecommons.org/licenses/by-nc/4.0/) which permits copy and redistribute the material just in noncommercial usages, provided the original work is properly cited.

1. Background

About 60% of term and 80% of preterm infants have clinical jaundice in the first week after birth but only 0.02 to 0.16% of them develop severe hyperbilirubinemia (Total Serum Bilirubin (TSB) > 25 mg/dL), which is an emergency because it may cause neonatal bilirubin encephalopathy, which can result in death or irreversible brain damage in survivor (1-3). Intensive phototherapy and exchange transfusion (ET) play important roles in the treatment of severe hyperbilirubinemia of newborns to prevent bilirubin encephalopathy (4). Although the value of exchange transfusion in the treatment of neonatal hyperbilirubinemia is recognized, the bilirubin levels in which ET is necessary remained a matter of disagreement (5-7). ET is effective and considered to be a safe procedure; however, it is not without risks and complications have been reported and mortality rates vary from 0.5 to 3.3%. Therefore, the current recommendations for performing ET are based on balance between the risks of encephalopathy and adverse events related to the procedure (8, 9). Complications of ET may be increased by the amount of blood exchanged. Most of these complications are asymptomatic and transient, such as severe thrombocytopenia, apnea, hypocalcemia, bradycardia, and hyperkalemia, but life threatening infections and even death can occur within seven days after the exchange (10-13).

2. Objectives

The purpose of this study was to investigate the etiology and complications of exchange blood transfusion in a patient population visited in our center over the last five years.

3. Patients and Methods

The medical records of infants, 28 day old, who received exchange transfusion due to severe hyperbilirubinemia in neonatal units at Besat and Fatemieh university hospitals in Hamadan for a period of five years (from October 1st 2006 through September 30th, 2011 ) were reviewed retrospectively. Exchange transfusion was performed by pediatric residents under direct supervision of pediatric professor. The double volume exchange method (170 mg/kg) was completed for approximately 1 - 2 hours by repeatedly removing and replacing a small amount of blood (5 mL/kg) according to standard practice guidelines. Infants’ heart rate and oxygen saturation were monitored during exchange transfusion.

Laboratory investigations were performed such as complete blood counts, direct and total bilirubin, erythrocyte glucose -6- phosphate dehydrogenase (G6PD) level, direct coombs test, maternal and baby blood groups, serum calcium, glucose, sodium, potassium, and blood cultures before and after the exchange.

Intravenous calcium gluconate was used during exchange transfusion to neutralize the effect of citrate in Citrate Phosphate Dextrose Adenine (CPDA) solution. All episodes of complication were recorded up to three days after exchange transfusion. The definition of complications used were as hypoglycemia when serum glucose was < 50 mg/dL, hypocalcemia if serum calcium was < 8 mg/dL (for preterm newborn, 7 mg/dL), hyperkalemia when serum potassium was > 6 meq/dL, thrombocytopenia when platelet count was < 100.000/mm3, bradycardia if heart rate was < 80 beat/minute, apnea cessation of respiration for > 20 seconds, seizure any tonic or clonic movement, necrotizing enterocolitis defined as per bell's criteria. Complications of severe neonatal hyperbilirubinemia, consisting of kernicterus were not included in this study. Exclusion criteria were incomplete records of patients and those older than 28 days old. Statistical analysis was performed using SPSS Version 12.0 (SPSS, Inc, Chicago, USA).

4. Results

There were 6108 neonatal admissions due to neonatal jaundice that exchange transfusion was performed in 148 neonates (2.4%). Among them 68 (45.1%) were male and 80 (54.9%) female. Mean birth weight was 2847 ± 699 grams and mean gestational age of neonates was 37.2 ± 2.5 weeks. Overall, 102 (68.9%) infants were term and 46 (31.1%) preterm. The mean maximum total serum bilirubin was 27.76 ± 7.28 mg/dL and the mean age of exchange transfusion was 4.97 ± 2.65 days (Table 1).

Table 1. Baseline Demographic Characteristics a
CharacteristicValue
Gender
Male68 (45.1)
Female80 (54.9 )
Gestational Age Group
Term102 (68.9)
Preterm 46 (31.1)
Gestational age, wk37.2 ± 2.5
Maximum total serum bilirubin, mg/dL27.76 ± 7.28
Age at exchange transfusion, d4. 97 ± 2.65
Frequency of Exchange Transfusion
One113 (76.4)
Two18 (12.2)
Three17 (11.4)
Complication rate57 (38.5)
Duration of hospital stay, d 6.79 ± 6.64

a Data are presented as No. (%) or mean ± SD.

Among 148 cases, no etiologic factors were identified in 61 (41.2%) neonates, ABO incompatibility was found in 54 (36.5%), RH incompatibility in 15 (10.1%) and G6PD deficiency in 14 (9.5%) neonates (Table 2). During and immediately after exchange transfusion, 57 (38.5%) neonates developed complications. Most complications were thrombocytopenia (17.6%), hypocalcemia (11.5%), hypoglycemia (9.5%), hyperkalemia (5.4%), hyponatremia (4.1%), apnea (4.7%), and septicemia (2%). One (0.7%) neonate died of complications probably attributable to exchange transfusion (Table 3). Comparing variables between term and preterm infants showed no significant difference in complications between the two groups (Tables 4 and 5).

Table 2. Etiology of Neonatal Hyperbilirubinemia
Causes NO (%)
ABO incompatibility54 (36.5)
RH incompatibility15 (10.1)
ABO and RH incompatibility3 (2.0)
G6PD deficiency14 (9.5)
Polycythemia1 (0.7)
Unidentified61 (41.2)
Total 148 (100)
Table 3. Complications of Exchange Transfusion
ComplicationsNo (%)
Thrombocytopenia 26 (17.6)
Hypocalcemia17 ( 11.5)
Hypoglycemia 14 (9.5)
Hyperkalemia 8 (5.4)
Hyponatremia6 (4.1)
Bradycardia12 (8.1)
Apnea7 (4.7)
Necrotizing enterocolitis3 (2)
Septicemia 3 (2)
DIC2 (1.4)
Cardiorespiratory arrest2 (1.4)
Death 1 (0.7)
Table 4. Comparing Variables Between Term and Preterm Infants a
VariablesTerm 102 (68.9)Preterm 46 (31.1)P Value
Gender 0.374
Male 44 (43.1)24 (52.2)
Female58 (56.9)22 (47.8)
Causes0.171
ABO incompatibility42 (41.2)12 (26.1)
RH incompatibility11 (10.8)4 (8.7)
ABO&RH incompatibility2 (2)1 (2.2)
G6PD deficiency11 (10.8)3 (6.5)
Polycythemia0 (0.0)1 (2.2)
Unidentified36 (35.6)25 (54.3)
Complications 0.529
Yes 39 (38.2)18 (39.1)
No63 (61.8)28 (60.9)
Thrombocytopenia 0.400
Yes 19 (18.6)7 (15.2)
No83 (81.4)39 (84.8)
Hypocalcemia0.160
Yes 14 (13.7)3 (6.5)
No88 (86.3)43 (93.5)
Hypoglycemia 0.238
Yes 8 (7.8)6 (13.0)
No94 (92.2)40 (87.0)
Hyperkalemia 0.523
Yes 6 (5.9)2 (4.3)
No96 (94.1)44 (95.7)
Hyponatremia0.273
Yes 3 (2.9)3 (6.5)
No99 (97.1)43 (93.5)
Bradycardia0.545
Yes 8 (7.8)4 (8.7)
No94 (92.2)42 (91.3)
Apnea0.131
Yes 3 (2.9)4 (8.7)
No99 (97.1)42 (91.3)
Necrotizing enterocolitis0.232
Yes 1 (1.0)2 (4.3)
No101 (99.0)44 (95.7)
Septicemia 0.324
Yes 3 (2.9)0 (0.0)
No99 (97.1)46 (100.0)
DIC0.526
Yes 1 (1.0)1 (2.2)
No101 (99.0)45 (97.8)
Cardiorespiratory arrest0.526
Yes 1 (1.0)1 (2.2)
No101 (99.0)45 (97.8)
Death 0.689
Yes 1 (1.0)0 (0.0)
No101 (99.0)46 (100.0)

aValues are presented as No (%).

Table 5. Comparing Variables With and Without Complications
VariablesComplicationsP Value
Yes = 57 (38.5)No = 89 (61.5)
Gender a0.341
Male 29 (42.6)39 (57.4)
Female28 (35.0)52 (65.0)
Gestational age group a0.918
Term39 (38.2)63 (61.8)
Preterm18 (39.1)28 (60.9)
Gestational age, wk b36.8 ± 3.037.5 ± 2.00.120
Birth weight, g b2771 ± 7642894 ± 6560.299
Admission age, d b4.6 ± 3.94.4 ± 2.30.844
Maximum total Serum bilirubin, mg/dL b28.8 ± 8.627.1 ± 6.30.167
Causes a0.145
ABO incompatibility15 (27.8)39 (72.2)
RH incompatibility8 (53.3)7 (46.7)
ABO&RH incompatibility2 (66.7)1 (33.3)
G6PD deficiency4 (28.6)10 (71.4)
Polycythemia0 (0.0)1 (100.0)
Unidentified 28(45.9)33(54.1)
Hospital stay, d b9.0 ± 7.25.3 ± 5.80.001

aValues are presented as No (%).

b Values are presented as mean ± SD.

5. Discussion

Exchange blood transfusion has reminded the gold standard for rapid lowering higher level serum bilirubin concentration and prevention of bilirubin encephalopathy and kernicterus. Although reports show progressive decline over the years in number of neonates who need exchange transfusion because of anti-Rh globulin for mothers and widespread use of phototherapy for neonatal jaundice, it is still required in up to 7% of neonates admitted to nurseries (13).

Despite advances in neonatal care in the recent years, exchange transfusion still remains a high risk procedure with common adverse effects. We observed a high rate of complications associated with exchange transfusion in 57 (38.5%) neonates; however, most of these were asymptomatic and transient. Most common complications in our study were thrombocytopenia (17.6%), hypocalcemia (11.5%), hypoglycemia (9.5%), hyperkalemia (5.4%), and hyponatremia (4.1%), which are similar to the findings of most previous studies (14, 15). Similarly, the rate of serious complication such as necrotizing enterocolitis and septicemia from ET is very low, approximately 1% and prior reports indicated that necrotizing enterocolitis and septicemia are the most common severe complications (11, 12, 16, 17).

Other serious complications of our study were apnea and bradycardia observed in 4.7% and 8.4% of neonates, respectively. Mortality directly attributable to exchange transfusion is reported to be at least 1% and is due to unexplained cardiac arrest, cardiac arrhythmias or air embolism (18). We observed a mortality of 1.4%; while, other studies reported a mortality rate range from 0.66% to 3.2% and (10, 12, 16, 19) Chime and Davutoglu reported no death in their study (20, 21).

Because many complications of exchange transfusion are unavoidable even with careful monitoring, early diagnosis of severe hyperbilirubinemia and phototherapy is the best way to reduce these complications that reduce the need for exchange transfusion in turn.

Multiple exchange transfusion was required in 23.6% of our neonates, which is similar to the findings of Dikshit (22), but more than Abu-Ekteish et al. (23). In our study, no etiologic factors were identified in 61 (41.2%) neonates, a rate reported previously as 17 - 40% (16, 24-27) and ABO incompatibility was observed in 54 (36.5%) neonates, which is similar to other studies (28-30). Rh incompatibility alone or concomitant with ABO incompatibility was observed in 15 (10.1%) and 3 (2.0%) neonates, respectively. The reduction in Rh incompatibility may be due to the use of anti-Rh globulin for Rh negative mothers (31). G6PD deficiency accounted for 14 (9.5%) of all causes of ET in our study. This figure is lesser than Badiee’s study (12), which estimated 19% prevalence of G6PD deficiency and higher than Bhat et al. (32) who reported no patient with G6PD deficiency. This difference in prevalence could be due to racial differences in the prevalence of G6PD deficiency.

This report indicated that complications are common after exchange transfusion despite technological advances in neonatal care and careful monitoring. Therefore, early recognition of infants at risk of severe hyperbilirubinemia and the use of intensive phototherapy can significantly reduce the need of exchange transfusion.

Acknowledgements

Footnote

References

  • 1. Bhutani VK, Johnson LH, Keren R. Diagnosis and management of hyperbilirubinemia in the term neonate: for a safer first week. Pediatr Clin North Am. 2004; 51(4) : 843 -61 [DOI][PubMed]
  • 2. Ebbesen F, Andersson C, Verder H, Grytter C, Pedersen-Bjergaard L, Petersen JR, et al. Extreme hyperbilirubinaemia in term and near-term infants in Denmark. Acta Paediatr. 2005; 94(1) : 59 -64 [PubMed]
  • 3. Hansen TW. Kernicterus in term and near-term infants--the specter walks again. Acta Paediatr. 2000; 89(10) : 1155 -7 [PubMed]
  • 4. Smitherman H, Stark AR, Bhutani VK. Early recognition of neonatal hyperbilirubinemia and its emergent management. Semin Fetal Neonatal Med. 2006; 11(3) : 214 -24 [DOI][PubMed]
  • 5. Watchko JF, Oski FA. Bilirubin 20 mg/dL = vigintiphobia. Pediatrics. 1983; 71(4) : 660 -3 [PubMed]
  • 6. Newman TB, Maisels MJ. Evaluation and treatment of jaundice in the term newborn: a kinder, gentler approach. Pediatrics. 1992; 89(5 Pt 1) : 809 -18 [PubMed]
  • 7. Practice parameter: management of hyperbilirubinemia in the healthy term newborn. American Academy of Pediatrics. Provisional Committee for Quality Improvement and Subcommittee on Hyperbilirubinemia. Pediatrics. 1994; 94(4 Pt 1) : 558 -65 [PubMed]
  • 8. Bowman J. The management of hemolytic disease in the fetus and newborn. Semin Perinatol. 1997; 21(1) : 39 -44 [PubMed]
  • 9. Philip AG. The rise and fall of exchange transfusion. Neo Reviews. 2003; 4 : 169 -74
  • 10. Ip S, Chung M, Kulig J, O'Brien R, Sege R, Glicken S, et al. An evidence-based review of important issues concerning neonatal hyperbilirubinemia. Pediatrics. 2004; 114(1) -53 [PubMed]
  • 11. Jackson JC. Adverse events associated with exchange transfusion in healthy and ill newborns. Pediatrics. 1997; 99(5)[PubMed]
  • 12. Badiee Z. Exchange transfusion in neonatal hyperbilirubinaemia: experience in Isfahan, Iran. Singapore Med J. 2007; 48(5) : 421 -3 [PubMed]
  • 13. Funato M, Tamai H, Shimada S. Trends in neonatal exchange transfusions at Yodogawa Christian Hospital. Acta Paediatr Jpn. 1997; 39(3) : 305 -8 [PubMed]
  • 14. Hoontrakoon S, Suputtamongkol Y. Exchange transfusion as an adjunct to the treatment of severe falciparum malaria. Trop Med Int Health. 1998; 3(2) : 156 -61 [PubMed]
  • 15. Patra K, Storfer-Isser A, Siner B, Moore J, Hack M. Adverse events associated with neonatal exchange transfusion in the 1990s. J Pediatr. 2004; 144(5) : 626 -31 [DOI][PubMed]
  • 16. BulBul A, Okan FF, Kabakoglu Unsur, E. , Nuhoglu, A. . Adverse events associated with exchange transfusion and etiology of severe hyperbilirubinemia in near-term andterm newborns. Turk J Med Sci. 2011; 41(1) : 93 -100
  • 17. Hovi L, Siimes MA. Exchange transfusion with fresh heparinized blood is a safe procedure. Experiences from 1 069 newborns. Acta Paediatr Scand. 1985; 74(3) : 360 -5 [PubMed]
  • 18. Bohggs TR. Westphal MC Mortality of exchange trans-fusion Pediatrics. Pediatrics. 1960; 26(5) : 745 -55
  • 19. Panagopoulos G, Valaes T, Doxiadis SA. Morbidity and mortality related to exchange transfusions. J Pediatr. 1969; 74(2) : 247 -54 [PubMed]
  • 20. Chima RS, Johnson LH, Bhutani VK. Evaluation of adverse events due to exchange transfusion in term and near-term newborns. Pediatr Res. 2001; 49 : 324
  • 21. Davutoglu M, Garipardic M, Guler E, Karabiber H, Erhan D. The etiology of severe neonatal hyperbilirubinemia and complications of exchange transfusion. Turk J Pediatr. 2010; 52(2) : 163 -6 [PubMed]
  • 22. Dikshit SK, Gupta PK. Exchange transfusion in neonatal hyperbilirubinemia. Indian Pediatr. 1989; 26(11) : 1139 -45 [PubMed]
  • 23. Abu-Ekteish F, Daoud A, Rimawi H, Kakish K, Abu-Heija A. Neonatal exchange transfusion: a Jordanian experience. Ann Trop Paediatr. 2000; 20(1) : 57 -60 [PubMed]
  • 24. Sanpavat S. Exchange transfusion and its morbidity in ten-year period at King Chulalongkorn Hospital. J Med Assoc Thai. 2005; 88(5) : 588 -92 [PubMed]
  • 25. Saxena A, Bairwa AL. Indications and Complications of Exchange Transfusion in A Tertiary. Indian J Res. 2014; 3(3) : 12 -3
  • 26. Narang A, Gathwala G, Kumar P. Neonatal jaundice: an analysis of 551 cases. Indian Pediatr. 1997; 34(5) : 429 -32 [PubMed]
  • 27. Begum S, Baki MA, Kundu G, Islam I, Talukdar MK, Fatema K. Exchange Transfusion: Indication and Adverse Effect. Bangladesh Journal of Child Health. 2012; 36(1) : 16 -9
  • 28. Drabik-Clary K, Reddy VV, Benjamin WH, Boctor FN. Severe hemolytic disease of the newborn in a group B African-American infant delivered by a group O mother. Ann Clin Lab Sci. 2006; 36(2) : 205 -7 [PubMed]
  • 29. Huizing K, Roislien J, Hansen T. Intravenous immune globulin reduces the need for exchange transfusions in Rhesus and AB0 incompatibility. Acta Paediatr. 2008; 97(10) : 1362 -5 [PubMed]
  • 30. Sgro M, Campbell D, Shah V. Incidence and causes of severe neonatal hyperbilirubinemia in Canada. CMAJ. 2006; 175(6) : 587 -90 [DOI][PubMed]
  • 31. Woodrow JC. Effectiveness of Rh prophylaxis. Haematologia (Budap). 1974; 8(1-4) : 281 -90 [PubMed]
  • 32. Bhat AW, Churoo BA, Iqbal Q, Sheikh MA, Iqbal J, Aziz R. Complication of exchange transfusion at a tertiary care hospital. Current Pediatric Research. 2011; 15(2)
  • COMMENTS

    LEAVE A COMMENT HERE: