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Five-year Experience With Arterial Switch Operation in the First Hours of Life
Accepted Manuscript Title: Five-Year Experience with Arterial Switch Operation in the First Hours of Life Author: Kyrylo Chasovskyi, Yaroslav Mykychak, Nadiia Rudenko, Hanna Vorobyova, Illya Yemets PII: DOI: Reference:
S1043-0679(17)30022-9 http://dx.doi.org/doi: 10.1053/j.semtcvs.2017.01.011 YSTCS 938
To appear in:
Seminars in Thoracic and Cardiovascular Surgery
Please cite this article as: Kyrylo Chasovskyi, Yaroslav Mykychak, Nadiia Rudenko, Hanna Vorobyova, Illya Yemets, Five-Year Experience with Arterial Switch Operation in the First Hours of Life, Seminars in Thoracic and Cardiovascular Surgery (2017), http://dx.doi.org/doi: 10.1053/j.semtcvs.2017.01.011. This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.
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FIVE-YEAR EXPERIENCE WITH ARTERIAL SWITCH OPERATION IN THE FIRST HOURS OF LIFE
Ukrainian Children’s Cardiac Surgery mailing address:
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Ukraine, Kyiv 01135, Chornvola St. 28/1.
Kyrylo Chasovskyi1 M.D., Ph.D., Yaroslav Mykychak2 M.D., Nadiia Rudenko3 M.D., Ph.D., Hanna Vorobyova3 M.D., Ph.D., Illya Yemets2 M.D., Ph.D. 1 Department of Intensive care and Perfusiology, Ukrainian Children's Cardiac Center, Kyiv, Ukraine 2 Department of Cardiac Surgery, Ukrainian Children's Cardiac Center, Kyiv, Ukraine 3 Department of Cardiology, Ukrainian Children's Cardiac Center, Kyiv, Ukraine
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Corresponding author:
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Dr. Kyrylo Chasovskyi, e-mail: [email protected],
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Address: 01135, Ukraine, Kyiv, Chornovola St.28/1
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Phone: +380506232580, Fax: +380442840311
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Disclosures:
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All of the authors declare that there are no conflicts of interest regarding this manuscript.
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Funding for the work:
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No funding was provided for this study.
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This paper was presented in part at 96th Annual Meeting of AATS, May 14-18, 2016
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Key words: blood – CHD, arterial switch operation – neonates - cardiopulmonary bypass
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Word count: 2 930
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Abstract
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Objective: We assesed morbidity after two management strategies for arterial switch operation (ASO) in the single institution: first hours of life surgery and conventional approach.
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Methods: From September 2009 to September 2014, 346 consecutive patients who underwent ASO were enrolled. Study group included 92 patients who underwent ASO in the first 24 hours after birth (Group I). Control group consisted of 254 patients who underwent ASO after 24 h of life in conventional way (Group II). Three outcomes were analyzed: postoperative ventilation time (VT), postextubation hospital length of stay (peLOS), and a composite morbidity index, defined as postoperative VT + peLOS + occurrence of selected major complications.
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Results: Overall 30-day survival was 98% (2 (2%) Group I vs. 5 (2%) Group II, p=1.000). Fifty (13.3%) major complications were observed: 14 (15%) in Group I and 36 (15%) in Group II (p=0.635). Although peLOS and morbidity index did not differ significantly between groups, postoperative VT (42h (24, 67) vs. 27h (22, 47), p=0.008) and total hospital stay were significantly longer in Group II (18d (10, 19) vs. 14d (12,18). A median volume of 80 ml (60-100 ml) of AUCB was collected (80 ml Group 1 vs. 60 ml Group II, p=0.090). Homologous blood cell transfusion was avoided in 70 (78%) Group I patients and 13 (6%) of Group II patients (p<0.001).
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Conclusions: ASO during the initial 24 hours of life has similar outcomes in view of morbidity and mortality compared to the conventional approach.
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Abstract word count: 243 words
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Perspective Statement
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Precise timing for arterial switch operation (ASO) remains disputable. Our results demonstrate similar morbidity and mortality between patients undergoing ASO in the first hours of life vs. days of life. Significantly reduced length of preoperative and total hospital stay with reduced homologous blood exposure were observed in patients who underwent ASO in the first hours of life.
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Central message
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Compared to the conventional approach ASO during the initial 24 hours of life has similar outcomes in view of morbidity and mortality.
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Legend for the Central picture:
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Novel surgical strategy for prenatally diagnosed d-TGA includes collection of umbilical cord blood and surgery within the first hours of life.
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Abbreviations and Acronyms
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ASO
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AUCBT =
autologous umbilical cord blood transfusion
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CHD
=
congenital heart defects
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CPB
=
cardiopulmonary bypass
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d-TGA =
dextrotransposition of the great arteries
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HBT
=
homologous blood transfusion
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ICU
=
intensive care unit
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RBC
=
red blood cells
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UCB
=
umbilical cord blood
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peLOS =
postextubation length of hospital stay
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BAS
=
balloon atrial septostomy
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VT
=
ventilation time
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VSD
=
ventricle septal defect
=
arterial switch operation
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During last two decades Arterial Switch Operation (ASO) has become the main option for
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treatment of neonates with dextrotransposition of the great arteries (d-TGA) [1]. Although the
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conventional approach to surgical management of d-TGA includes waiting for several days after
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birth, prostaglandin (PGE) infusion, balloon septostomy (BAS) the timing for ASO is now debated
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[2]. On the one hand neonates do not tolerate early surgery well but on the other hand delay of
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neonatal ASO for more than three days is associated with increased morbidity and costs of
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treatment [3]. Risks related to BAS, prolonged exposure to PGE and PDA physiology, longer
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duration of hypoxemia and lower cerebral oxygen delivery made up a significant background for an
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earlier ASO [4]. Five years ago we suggested that ASO can be performed within the first hours of
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patient’s life using autologous umbilical cord blood (AUCB) [5]. In the current study we eximined
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morbidity after two surgical strategies for arterial switch operation in a single institution: first hours
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of life and conventional.
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Patients and Methods
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This study was approved by the Institutional Review Board of the Ukrainian Children’s
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Cardiac Center.
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Between September 2009 to September 2014, 346 consecutive neonatal ASO’s were
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performed at the Ukrainian Children’s Cardiac Center. Study group included 92 patients who
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underwent ASO in the first 24 hours after birth (Group I). Control group consisted of 254 patients
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who underwent ASO after 24 h after birth (Group II) at the age less 30 days of life. Patients’
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characteristics are listed in Table 1. Patients with Tausig-Bing anomaly were excluded from this
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study.
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Among the study population 126 (36.4%) neonates with d-TGA were diagnosed prenatally,
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including 87 (95%) of 92 Group I patients and 39 (16%) of 254 Group II patients (Table 1). In
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prenatally diagnosed patients autologous umbilical cord blood (AUCB) was harvested and used
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during surgery. Informed consent (for AUCB collection) was obtained from pregnant women before
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admission to the maternity hospital. Collection procedures were performed in accordance with the
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international standards [7]. Page 5 of 19
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Contraindications for the collection and transfusion of autologous UCB were rhesus and/or
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ABO incompatibility and confirmed maternal viral or bacterial infections. The nearest maternity
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hospitals were selected as a study partners to decrease time between delivery and heart surgery.
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After obstetric examination, the date of delivery was planned to prepare for cardiac operation. In
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prenatally diagnosed neonates surgery was delayed if delivery was unplanned (failed logistics) or
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clinically significant hypoxemia occurred immediately after birth due to restrictive atrial septal
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defect which required BAS (including bed-side). In these patients ASO was performed later, after
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24 h of life and they were included in Group II. Among 39 of prenatally diagnosed patients of
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Group II (Table 1) only 8 patients required BAS, including one at a bed side.
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Perioperative management of these patients was previously described in detail [5, 6]. We
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used full flow cardiopulmonary bypass (200 ml/kg) with moderate hypothermia (28°C) and
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myocardial protection with cold crystalloid cardioplegia (Custodiol HTK). Hct target during
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perfusion was set at a minimum level of 25%.
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Perioperative data were abstracted from the medical records and our institutional database.
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We used morbidity index (Lacour-Gayet and associates, 2011) to assess postoperative course in
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both groups of patients [8]. Morbidity index was calculated from the following three variables with
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a total of 5 points: complications (2 points), ventilation time (VT; 1 point) and postextubation
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length of hospital stay (LOS) after extubation (2 points). We analyzed postoperative morbidity in all
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consecutive cases of ASO with no operative death. Postopertive VT is considered to be a better
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indication of early morbidity compared with intensive care LOS, which is more institutionally
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dependent. In the same time, peLOS is a better reflection of second phase morbidity [8].
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Continuous data were summarized as mean (±standard deviation) or median (25th to 75th
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percentile) and tested for normality using the Shapiro-Wilks test. Data compared between groups
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was analyzed using Student's t test or the Mann-Whitney U test for normal and skewed data
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respectively. Fisher exact test was used for proportions. We used generalized linear modeling for
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the outcomes described. Akaike’s information criterion (AIC in SPSS) was used for higher quality
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model selection in regression analyses. Statistical analysis was performed with the SPSS 22.0
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software (SPSS, Inc., Chicago, IL, USA). A P-value <0.05 was considered statistically significant.
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Considering the fact, that minor portion of patients in Group I received homologous blood
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components during open heart surgery (Table 2), we calculated amount of transfused homologous
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blood only for these patients. It allows us to demonstrate the volume of transfused homologous
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blood components in those patients who underwent ASO in the first 24 hour of life without ability
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to be transfused with AUCB. Oppositely, to calculate the amount of transfused AUCB in Group II
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we analyzed only those patients who were transfused with AUCB.
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Results
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Perioperative characteristics are reported in Table 1. Treatment groups differed significantly
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in regard of age at surgery (4 vs.144 hours, p<0.001), duration of preoperative ICU stay (0 vs. 3
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days, p<0.001), number of patients requiring preoperative intubation/ventilation (1 vs. 62, p<0.001)
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and BAS (1 vs. 201, p<0.001) before ASO. In Group I d-TGA was diagnosed prenatally in 87 cases
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(95%) and AUCB was used in 83 (90%) patients during surgery. In Group II 39 (16%) patients
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were diagnosed prenatally and 16 (6%) patients were transfused with AUCB during surgery. Blood
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products utilization is reported in Table 2. The use of AUCB allows us to reduce significantly the
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need for transfusion of homologous blood components (RBC’s and FFP’s). The volume of
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transfused blood components is reported in Table 3. There were no significant differences between
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the groups for diagnoses, coronary patterns (anatomy), duration of bypass and Cross-clamp times.
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The overall 30-day mortality was 7 (2%). There was no significant difference in mortality between
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groups (Table 1). There were no complications, as defined in Table 1 in 85% of the total cases.
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Fifty (13.3%) major complications were observed: 14 (15%) in Group I and 36 (15%) in Group II
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(p=0.635). Postoperative complications rates in both groups are reported in Table 1. Postoperative
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VT was significantly shorter in Group I when compared to Group II (27 vs. 43 h. p=0.008).
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Morbidity index and peLOS did not differ significantly between groups. Results from Generalized
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Linear Modeling for selected outcomes are reported in Table 4. Results demonstrate that ASO
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performed at the age later than 24 h after birth independently increases ventilation time and
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morbidity index, and decreases postextubation hospital length of stay.
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Discussion
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In this retrospective study, we found that neonates assigned to the conventional surgical
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strategy for d-TGA compared to the first hours of life surgery had similar morbidity and mortality.
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Although ASO is now performed in the early days of patient’s life, precise timing of surgery
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remains institutionally dependent. In most hospitals timing for ASO is ranged between 7 and 28
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days of patient’s life depending of complexity of d-TGA [9, 10]. Delaying ASO for several days is
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seemed to provide benefits like reduction in pulmonary vascular resistance, kidney and liver
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function improvement, initiation of enteral nutrition, evaluation for other congenital anomalies and
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family preparation for surgery [4, 10,]. However, a current trend in performing ASO is being shifted
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to the earlier time frame [4]. One study from the Children’s Hospital of Philadelphia has shown that
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lower mean pre-operative partial pressure of oxygen (PaO2) and longer time to surgery may be
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additive risk factors for the development of periventricular leukomalacia [11]. Another study from
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New York-Presbyterian Morgan Stanley Children’s Hospital suggests that first 3 days of age is the
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ideal time for an ASO [3, 12]. We proved that ASO performed in the first hours of patient’s life was
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feasible and safe surgical strategy for prenatally diagnosed d-TGA [5] and the current study was
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aimed to examine morbidity in neonates who underwent ASO in the first hours of life comparing
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with conventional approach. Although, current study demonstrates no difference in morbidity and
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mortality after the first hours of life surgery and conventional approach, ASO performed later than
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first 24 hours of life was a significant independent risk factor for increased morbidity in this series,
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particularly for postoperative ventilation time and morbidity index. First hours of life surgery was
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available mostly for prenatally diagnosed patients in this study. However five patients in Group I
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were diagnosed postnatally and were operated on between 4 and 24 hours after birth. They were
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admitted to our institution in stable condition, with only one patient intubated and none of them
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required BAS. All of these patients underwent ASO without AUCB as this option is feasable for
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prenataly diagnosed patients only. It seems that early hours of life surgery is possible for postnatally Page 8 of 19
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diagnosed patients too, if diagnosis and transfer are being done in a timely manner. We have found
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only one report describing successful results of heart surgery performed in the first 24 hours of the
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patient’s life [23]. Esposito and associates reported four patients who underwent successful surgical
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correction within 24 h of birth. Two patients with total anomalous pulmonary venous drainage and
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one patient with pulmonary atresia and intact septum were corrected with the aid of profound
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hypothermia by the combined surface and bypass cooling technique. Cardiopulmonary bypass alone
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was used for the fourth patient with aortic stenosis. Their comment was that usual surgical
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techniques can be applied successfully to infants even within 24 h of life.
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Although peLOS was similar between groups in the current srudy it was found that delaying
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surgery (afe at surgery > 24 h) inversely contributed to peLOS in this series. We were not able
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explain this relationship, however mother’s recovery from cesarian section in prenatally diagnosed
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patients may contribute to this too. It is known that prenatal awareness of TGA was associated with
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a higher percentage of induced deliveries and a major increase in the rate of cesarian section [24].
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A cohort of 121 patients was studied (48 prenatal and 73 postnatal diagnoses) and it was shown that
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Induced delivery and cesarian section were more frequent in the prenatal (54.1% and 31%) than in
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the postnatal diagnosis group (19.4% and 8%; p<0.001 and p<0.001, respectively). We have not
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studied that formally, however.
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Accurate prenatal diagnosis reduces maternal and neonatal risk and improves outcomes.
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Studies suggested that prenatally diagnosed patients had earlier BAS and were less likely to require
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mechanical preoperative ventilation [13], had better patient’s condition at presentation and
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improved outcomes [14]. We proposed additional option for prenatally diagnosed patients with d-
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TGA. We assumed that complete surgical repair in the first hours of life in prenatally diagnosed
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neonates would be beneficial due to preventing further development of hypoxemia, eliminating
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prolonged exposure to PGE and PDA physiology, and shortening preoperative ICU stay and
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hospital stay. The study results demonstrate significantly reduced preoperative ICU stay, rates of
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BAS and preoperative ventilation which resulted in significant reduction of total hospital stay in
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patients operated with 24 hours after birth (Table 1). BAS is known to be associated with vascular Page 9 of 19
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trauma, atrial arrhythmias, atrial perforation and tamponade [4]. We did not observe any of those
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complications in the current series. Moreover, we were unable to demonstrate influence of BAS on
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postoperative outcomes. In those neonates, who suffered from significant hypoxemia after birth
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due to restrictive foramen ovale and could not tolerate for two or three hours until surgery, BAS
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was considered as an option to improve oxygenation in the systemic circulation. In the current
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study, among 39 patients of Group II who were diagnosed prenattaly only eight required urgent
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balloon atrial septostomy immediately after birth due to inadequate mixing and occurrence of
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significant hypoxemia which would have led to acute hemodynamic deterioration with increasing in
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serum lactate levels. We have previously found that acutely impaired oxygenation due to inadequate
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mixing resulted in elevated pre bypass lactate levels, measured as a surrogate of tissue perfusion,
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and was significantly associated with elevated intra- and postoperative lactate concentrations,
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followed by compromised outcomes [6]. Several studies also suggested that increased postoperative
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serum lactate is associated with poor outcome [6, 17]. This study shows that elevated lacate level at
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one hour after surgery was independently associated with prolonged postoperative VT and
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morbidity index. Nevertheless, we did not formally test decision-analysis for competing risks in
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which one must weigh the relative risks and benefits of: BAS with PGE and timing of ASO in
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patients with compromised blood mixing and following significant hypoxemia.
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While awaiting ASO, neonates remain at risk for mechanical ventilation, infection, medical
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errors, paradoxical emboli, increased cost for treatment and longer hospital stay [15]. PGE infusion
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can cause apnea and is associated with prolonged preoperative mechanical ventilation [15]. It was
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shown that preoperative ventilation is associated with high resource utilization postoperatively [16].
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In the current study Group I patients had no preop ICU stay and had significantly lower rate of
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preoperative intubation/ventilation (Table 1). Preoperative ventilation rate emerged as a risk factor
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in this series for prolonged postoperative mechanical ventilation. It does not contribute dierectly to
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the first hours of life surgery, however incorporates directly with our assumption.
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Meticulous surgical technique should not be underestimated. In the study there were no
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differences in either diagnosis or coronary patterns (Table 1). Nonetheless, tissue features in the Page 10 of 19
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early hours of patient’s life may raise an issue regarding surgeon’s concerns and technical
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complexity of these patients. A longer CPB is considered to be a surrogate of technical complexity
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and causes morbidity through its adverse physiological effects. Oppositely, a well performed
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coronary transfer with a limited CPB time is usually followed by a simple postoperative course in
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most ASO patients. In terms of length of the operation, we used CPB time to examine its interaction
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with the other variables. CPB duration was not a risk factor for outcomes in this study and was
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similar in both groups suggesting similarity in surgical complexity of the ASO performed either
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conventionally or at the first hours of life (Table 1). The diagnoses and coronary categories (Table
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1) reflect our perceprion of complexity. Coronary anatomy (double loop, single ostium, or
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intramural course) was found to be a risk factor independently increasing morbidity, particulary for
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ventilation time. In the review study published by Pascuali and colleagues single ostium and
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intramural course of coronary artery were considered as important risk factor for mortality [24].
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Redo sternotomy with or without CPB, as well as non cardiac surgeries in the early postoperative
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period were significant risk factors for morbidity in this study. Neither diagnose nor other anatomic
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factors were found to be significant risk factors in this siries.
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Prenatal diagnosis of d-TGA offered one more important option in the management of
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patients with d-TGA: harvesting, processing and transfusion of AUCB during ASO. We previously
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reported that AUCB is efficient and safe alternative to homologous blood components [18]. Median
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volume of harvested AUCB is usually equal to approximately 30% of circulating blood volume in
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neonates with prenatally diagnosed d-TGA [5]. Transfusion of AUCB was not a significant risk
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factor affecting outcomes in our study, except morbidity index. Analysis of transfusion rate
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confirms that AUCB transfusion allows to avoid homologous RBC’s and FFP transfusions
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intraoperatively and during early postoperative period (Table 2). Moreover, transfusion of
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homologous RBC’s was a significant risk factor independently increasing morbidity index and
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peLOS in this series. Several studies have described homologous blood transfusions as a potential
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cause of various complications, such as immunologic reactions that lead to organ dysfunction,
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transmission of infection, and transfusion-related reactions [19, 20]. Owing to the small body Page 11 of 19
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weight (less than 4 kg) and relatively large CPB circuit needed for neonates, the total quantity of
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homologous blood used intraoperatively usually accounts for more than 40% to 50% of their
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circulating blood volume [21]. Although, the volume of transfused homologous blood components
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in our study population is not as much as been reported in other studies, we would suggest
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harvesting and transfusion of AUCB in prenatally diagnosed d-TGA as a significant benefit of the
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first hours of life ASO or early days of life ASO, whatever. From our experience delaying in ASO
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in prenatally diagnosed d-TGA was not a contraindication for AUCB transfusion. We did not tested
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directly the duration of safe storage time for AUCB for open heart surgery. However, 16 of Group
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II patients were transfused with AUCB during operation between 48 and 72 hours after its
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collection, considering its acceptable storage characteristics [22].
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Study Limitations
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An important limitation of this study is that the patients were selected in a non-randomized
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manner, predisposing the analysis to selection bias based on whether the subject was identified
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during the prenatal or postnatal period. Postnatal diagnosis of surgically correctable congenital heart
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disease precludes the use of AUCB.
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Conclusions
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In conclusion, the study shows that ASO in the first hours of life can be performed with
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excellent early results. Significantly reduced length of preoperative and total hospital stay and
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homologous blood exposure were observed in patients who underwent ASO in the first hours of
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life. Compared to the conventional approach ASO during the initial 24 hours of life has similar
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outcomes in view of morbidity and mortality, however delaying surgery for TGA seems to be
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associated with increased morbidity in this series.
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Table 1. PATIENT CHARACTERISTICS Variable
357 358 359 360 361 362 363 364 365 366
Group Ia (n=92) 4 (3,5)[1,5-24] 3.3 (0.6) 87 (95)
Group IIb (n=254) 144 (96, 192)[36-696] 3.4 (0.6) 39 (16%)
p value
Age at surgery (hours), median (IQR)[min-max] <0.001 Weight (kg), mean (SD) 0.174 Prenatally diagnosed, n (%) <0.001 Diagnosis, n (%) N/A TGA-IVS 65 (71) 165 (65) TGA-VSD 25 (27) 77 (30) TGA, VSD, LVOTO 1 (1) 0 TGA, VSD, CoAo 1 (1) 12 (5) Coronary patterns a N/A 1 62 (68) 174 (72) 2 15(17) 43 (18) 3 13 (14) 26 (11) Preop intubation, n (%) 1 (1) 62 (24) <0.001 BAS, n (%) 1 (1) 201 (73) <0.001 CPB time (min), mean (SD) 154 (29) 155 (32) 0.703 Cross-clamp (min), mean (SD) 85 (21) 85 (14) 0.952 Open chest as strategy, No. (%) 4 (4) 5 (2) 0.258 Postoperative ventilation time (hr), median (IQR) 27 (22, 47) 42 (24, 67) 0.008 Complications, n (%) 14 (15) 36 (15) 0.635 Neurologic deficit persisting at discharge, No. (%) 1 (1) 5(2) 1.000 Arrhythmia necessitating permanent pacemaker 1 (1) 2 (0.8) 1.000 Unplanned cardiac reoperations with CPB, No. (%) 0 3 (1.2) 0.568 Phrenic nerve palsy requiring diaphragmatic plication, No. (%) 1 (1) 7 (3) 0.686 Mediastinitis requiring sternum reopening, No. (%) 2 (3) 2 (1) 0.291 Unplanned cardiac reoperations without CPB, No. (%) 5 (5) 12 (5) 0.760 Unplanned noncardiac reoparetions 4 (4) 5 (2) 0.253 LOS (d), median (IQR) Preop ICU 0 3 (2, 4) <0.001 Postextubation 13 (10, 15) 13 (10, 19) 0.744 Total Hospital 14 (12, 18) 18 (14, 24) <0.001 Morbidity indexd, mean (SD) 1 (1, 1,4) 1,1 (0.8, 1.9) 0.471 30-day mortality, n (%) 2 (2) 5 (2) 1.000 a patients underwent ASO in the first 24 hours of life; b patients underwent ASO after 24 hours of life; c Coronary pattern categories: 1 = usual arrangement, 2 = circumflex off right coronary artery, 3 = double loop, single ostium, or intramural. d index, defined as ventilation time + post-extubation hospital length of stay + occurrence of selected major complications; CPB = cardiopulmonary bypass; IQR = interquartile range; IVS = intact ventricular septum; LOS = length of stay; LVOTO = left ventricle outflow tract obstruction; N/A = not applicable; Preop = preoperative; SD = standard deviation; TGA = transposition of the great arteries; VSD = ventricular septal defect; ICU = intensive care unit; AUCB = autologous umbilical cord blood; BAS = balloon atrial septostomy; CoAo – coarctation of the aorta.
367 368
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369
Table 2. BLOOD PRODUCTS UTILIZATION Variable During CPB: AUCB, No of pts. (%) Homologous RBC’s, No of pts. (%) Post CPB: AUCB, No of pts. (%) Homologous RBC’s, No of pts. (%) Homologous FFP *, No of pts. (%) During ICU stay: AUCB, No. (%) Homologous RBC’s, No of pts. (%) Homologous FFP, No of pts. (%)
370 371 372 373 374 375
Group Ia (n=92)
Group IIb (n=254)
p value
83 (90%) 14 (16%)
16 (6%) 237 (93%)
<0.001 <0.001
70 (76%) 11 (7%) 14 (16%)
7 (3%) 200 (79%) 215 (85%)
<0.001 <0.001 <0.001
0 18 (19.6%) 12 (13%)
0 175 (69%) 99 (39%)
N/A <0.001 <0.001
Homologous RBC’s during perioperative course, 22 (24%) 241 (95%) <0.001 No of pts. (%) a patients underwent ASO in the first 24 hours of life; b patients underwent ASO after 24 hours of life; * According to the protocol FFP is not used for priming the circuit AUCB = autologous umbilical cord blood, FFP – fresh frozen plasma; CPB – cardiopulmonary bypass; ICU – intensive care unit; RBC – red blood cells.
376
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377
Table 3. VOLUME OF TRANSFUSED BLOOD COMPONENTS Variable
378 379 380 381 382 383 384
Group Ia
Group IIb
p value
Median ; 25% - 75% During CPB: AUCB, ml 40; 20-50* 50; 22-60* N/A Homologous RBC’s, ml 45; 13-68** 60; 45-80** Post CPB: AUCB, ml 50; 28-60* 0; 0-58* Homologous RBC’s, ml 0; 0-48** 30; 20-50** N/A Homologous FFP transfusion, ml 45; 8-60** 30; 20-50** During ICU stay: AUCB, No. (%) Homologous RBC’s, ml 20; 0-35 30; 0-50 N/A Homologous FFP, ml a patients underwent ASO in the first 24 hours of life; b patients underwent ASO after 24 hours of life; * Calculated for those pts, in whom AUCB was collected and used; ** Calculated for those pts, in whom AUCB were not used. AUCB = autologous umbilical cord blood, FFP – fresh frozen plasma; CPB – cardiopulmonary bypass; ICU – intensive care unit; RBC – red blood cells.
Page 18 of 19
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Table 4. Effect of Perioperative Variables on Three Morbidity Outcomes Postoperative ventilation time age at surgery >24 h coronary patterns* preop ventilation unplanned cardiac reoperations without CPB lactate at 1 h after surgery lactate at the end of CPB peLOS unplanned cardiac reoperations with CPB unplanned noncardiac reoparetions age at surgery >24 h Homologous RBC’s at ICU
B (95% CI)
SE
p Value
0.34 ( 0.12-0.55) 0.49 (0.24-0.37) 0.44 (0.21-0.65)
0.10 0.12 0.12
0.002 <0.001 <0.001
0.86 (0.48-1.2)
0.19
<0.001
0.16 (0.07-0.25) -0.007 ( -0.84-0.07)
0.05 0.04
<0.001 0.849
0.49 (-0.07-1.06)
0.05
0.086
0.29 (-0.006-0.60)
0.15
0.055
-0.28 (-0.43- (-0.13) 0.003 (0.002-0.005)
0.07 0.0008
<0.001 <0.001
0.02
0.002
0.09 0.002 0.0009
0.020 <0.001 <0.001
386
Morbidity index lactate at one hour after 0.065 (0.024-0.10) surgery age at surgery >24 h 0.22 (0.034-0.40) UCB during CPB 0.007 (0.003-0.011) Homologous RBC’s at ICU 0.005 (0.003-0.007) * double loop, single ostium, or intramural course
387
CPB – cardiopulmonary bypass, ICU – intensive care unit, RBC’s- red blood cells
388 389 390 391 392 393
Legend for the Video:
394 395 396 397
Video demonstrates a simple procedure of umbilical cord blood collection. Next two parts show two different patients undergoing arterial switch operation in the first hours of life. I all patients we use conventional techniques of dissection, coronary buttons excision and reimplantation. Tissue handling presents no additional difficulties as demonstrated.
398
Page 19 of 19
S1043-0679(17)30022-9 http://dx.doi.org/doi: 10.1053/j.semtcvs.2017.01.011 YSTCS 938
To appear in:
Seminars in Thoracic and Cardiovascular Surgery
Please cite this article as: Kyrylo Chasovskyi, Yaroslav Mykychak, Nadiia Rudenko, Hanna Vorobyova, Illya Yemets, Five-Year Experience with Arterial Switch Operation in the First Hours of Life, Seminars in Thoracic and Cardiovascular Surgery (2017), http://dx.doi.org/doi: 10.1053/j.semtcvs.2017.01.011. This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.
1 2 3 4 5 6 7 8 9 10 11 12 13
FIVE-YEAR EXPERIENCE WITH ARTERIAL SWITCH OPERATION IN THE FIRST HOURS OF LIFE
Ukrainian Children’s Cardiac Surgery mailing address:
14
Ukraine, Kyiv 01135, Chornvola St. 28/1.
Kyrylo Chasovskyi1 M.D., Ph.D., Yaroslav Mykychak2 M.D., Nadiia Rudenko3 M.D., Ph.D., Hanna Vorobyova3 M.D., Ph.D., Illya Yemets2 M.D., Ph.D. 1 Department of Intensive care and Perfusiology, Ukrainian Children's Cardiac Center, Kyiv, Ukraine 2 Department of Cardiac Surgery, Ukrainian Children's Cardiac Center, Kyiv, Ukraine 3 Department of Cardiology, Ukrainian Children's Cardiac Center, Kyiv, Ukraine
15 16
Corresponding author:
17
Dr. Kyrylo Chasovskyi, e-mail: [email protected],
18
Address: 01135, Ukraine, Kyiv, Chornovola St.28/1
19
Phone: +380506232580, Fax: +380442840311
20 21
Disclosures:
22
All of the authors declare that there are no conflicts of interest regarding this manuscript.
23 24
Funding for the work:
25
No funding was provided for this study.
26 27
This paper was presented in part at 96th Annual Meeting of AATS, May 14-18, 2016
28
Key words: blood – CHD, arterial switch operation – neonates - cardiopulmonary bypass
29
Word count: 2 930
30 31
Page 1 of 19
32
Abstract
33 34
Objective: We assesed morbidity after two management strategies for arterial switch operation (ASO) in the single institution: first hours of life surgery and conventional approach.
35 36 37 38 39 40
Methods: From September 2009 to September 2014, 346 consecutive patients who underwent ASO were enrolled. Study group included 92 patients who underwent ASO in the first 24 hours after birth (Group I). Control group consisted of 254 patients who underwent ASO after 24 h of life in conventional way (Group II). Three outcomes were analyzed: postoperative ventilation time (VT), postextubation hospital length of stay (peLOS), and a composite morbidity index, defined as postoperative VT + peLOS + occurrence of selected major complications.
41 42 43 44 45 46 47
Results: Overall 30-day survival was 98% (2 (2%) Group I vs. 5 (2%) Group II, p=1.000). Fifty (13.3%) major complications were observed: 14 (15%) in Group I and 36 (15%) in Group II (p=0.635). Although peLOS and morbidity index did not differ significantly between groups, postoperative VT (42h (24, 67) vs. 27h (22, 47), p=0.008) and total hospital stay were significantly longer in Group II (18d (10, 19) vs. 14d (12,18). A median volume of 80 ml (60-100 ml) of AUCB was collected (80 ml Group 1 vs. 60 ml Group II, p=0.090). Homologous blood cell transfusion was avoided in 70 (78%) Group I patients and 13 (6%) of Group II patients (p<0.001).
48 49
Conclusions: ASO during the initial 24 hours of life has similar outcomes in view of morbidity and mortality compared to the conventional approach.
50
Abstract word count: 243 words
51 52
Perspective Statement
53 54 55 56 57
Precise timing for arterial switch operation (ASO) remains disputable. Our results demonstrate similar morbidity and mortality between patients undergoing ASO in the first hours of life vs. days of life. Significantly reduced length of preoperative and total hospital stay with reduced homologous blood exposure were observed in patients who underwent ASO in the first hours of life.
58
Central message
59 60
Compared to the conventional approach ASO during the initial 24 hours of life has similar outcomes in view of morbidity and mortality.
61
Page 2 of 19
62 63
Legend for the Central picture:
64 65
Novel surgical strategy for prenatally diagnosed d-TGA includes collection of umbilical cord blood and surgery within the first hours of life.
Page 3 of 19
66
Abbreviations and Acronyms
67
ASO
68
AUCBT =
autologous umbilical cord blood transfusion
69
CHD
=
congenital heart defects
70
CPB
=
cardiopulmonary bypass
71
d-TGA =
dextrotransposition of the great arteries
72
HBT
=
homologous blood transfusion
73
ICU
=
intensive care unit
74
RBC
=
red blood cells
75
UCB
=
umbilical cord blood
76
peLOS =
postextubation length of hospital stay
77
BAS
=
balloon atrial septostomy
78
VT
=
ventilation time
79
VSD
=
ventricle septal defect
=
arterial switch operation
Page 4 of 19
80
During last two decades Arterial Switch Operation (ASO) has become the main option for
81
treatment of neonates with dextrotransposition of the great arteries (d-TGA) [1]. Although the
82
conventional approach to surgical management of d-TGA includes waiting for several days after
83
birth, prostaglandin (PGE) infusion, balloon septostomy (BAS) the timing for ASO is now debated
84
[2]. On the one hand neonates do not tolerate early surgery well but on the other hand delay of
85
neonatal ASO for more than three days is associated with increased morbidity and costs of
86
treatment [3]. Risks related to BAS, prolonged exposure to PGE and PDA physiology, longer
87
duration of hypoxemia and lower cerebral oxygen delivery made up a significant background for an
88
earlier ASO [4]. Five years ago we suggested that ASO can be performed within the first hours of
89
patient’s life using autologous umbilical cord blood (AUCB) [5]. In the current study we eximined
90
morbidity after two surgical strategies for arterial switch operation in a single institution: first hours
91
of life and conventional.
92
Patients and Methods
93
This study was approved by the Institutional Review Board of the Ukrainian Children’s
94
Cardiac Center.
95
Between September 2009 to September 2014, 346 consecutive neonatal ASO’s were
96
performed at the Ukrainian Children’s Cardiac Center. Study group included 92 patients who
97
underwent ASO in the first 24 hours after birth (Group I). Control group consisted of 254 patients
98
who underwent ASO after 24 h after birth (Group II) at the age less 30 days of life. Patients’
99
characteristics are listed in Table 1. Patients with Tausig-Bing anomaly were excluded from this
100
study.
101
Among the study population 126 (36.4%) neonates with d-TGA were diagnosed prenatally,
102
including 87 (95%) of 92 Group I patients and 39 (16%) of 254 Group II patients (Table 1). In
103
prenatally diagnosed patients autologous umbilical cord blood (AUCB) was harvested and used
104
during surgery. Informed consent (for AUCB collection) was obtained from pregnant women before
105
admission to the maternity hospital. Collection procedures were performed in accordance with the
106
international standards [7]. Page 5 of 19
107
Contraindications for the collection and transfusion of autologous UCB were rhesus and/or
108
ABO incompatibility and confirmed maternal viral or bacterial infections. The nearest maternity
109
hospitals were selected as a study partners to decrease time between delivery and heart surgery.
110
After obstetric examination, the date of delivery was planned to prepare for cardiac operation. In
111
prenatally diagnosed neonates surgery was delayed if delivery was unplanned (failed logistics) or
112
clinically significant hypoxemia occurred immediately after birth due to restrictive atrial septal
113
defect which required BAS (including bed-side). In these patients ASO was performed later, after
114
24 h of life and they were included in Group II. Among 39 of prenatally diagnosed patients of
115
Group II (Table 1) only 8 patients required BAS, including one at a bed side.
116
Perioperative management of these patients was previously described in detail [5, 6]. We
117
used full flow cardiopulmonary bypass (200 ml/kg) with moderate hypothermia (28°C) and
118
myocardial protection with cold crystalloid cardioplegia (Custodiol HTK). Hct target during
119
perfusion was set at a minimum level of 25%.
120
Perioperative data were abstracted from the medical records and our institutional database.
121
We used morbidity index (Lacour-Gayet and associates, 2011) to assess postoperative course in
122
both groups of patients [8]. Morbidity index was calculated from the following three variables with
123
a total of 5 points: complications (2 points), ventilation time (VT; 1 point) and postextubation
124
length of hospital stay (LOS) after extubation (2 points). We analyzed postoperative morbidity in all
125
consecutive cases of ASO with no operative death. Postopertive VT is considered to be a better
126
indication of early morbidity compared with intensive care LOS, which is more institutionally
127
dependent. In the same time, peLOS is a better reflection of second phase morbidity [8].
128
Continuous data were summarized as mean (±standard deviation) or median (25th to 75th
129
percentile) and tested for normality using the Shapiro-Wilks test. Data compared between groups
130
was analyzed using Student's t test or the Mann-Whitney U test for normal and skewed data
131
respectively. Fisher exact test was used for proportions. We used generalized linear modeling for
132
the outcomes described. Akaike’s information criterion (AIC in SPSS) was used for higher quality
133
model selection in regression analyses. Statistical analysis was performed with the SPSS 22.0
Page 6 of 19
134
software (SPSS, Inc., Chicago, IL, USA). A P-value <0.05 was considered statistically significant.
135
Considering the fact, that minor portion of patients in Group I received homologous blood
136
components during open heart surgery (Table 2), we calculated amount of transfused homologous
137
blood only for these patients. It allows us to demonstrate the volume of transfused homologous
138
blood components in those patients who underwent ASO in the first 24 hour of life without ability
139
to be transfused with AUCB. Oppositely, to calculate the amount of transfused AUCB in Group II
140
we analyzed only those patients who were transfused with AUCB.
141 142
Results
143
Perioperative characteristics are reported in Table 1. Treatment groups differed significantly
144
in regard of age at surgery (4 vs.144 hours, p<0.001), duration of preoperative ICU stay (0 vs. 3
145
days, p<0.001), number of patients requiring preoperative intubation/ventilation (1 vs. 62, p<0.001)
146
and BAS (1 vs. 201, p<0.001) before ASO. In Group I d-TGA was diagnosed prenatally in 87 cases
147
(95%) and AUCB was used in 83 (90%) patients during surgery. In Group II 39 (16%) patients
148
were diagnosed prenatally and 16 (6%) patients were transfused with AUCB during surgery. Blood
149
products utilization is reported in Table 2. The use of AUCB allows us to reduce significantly the
150
need for transfusion of homologous blood components (RBC’s and FFP’s). The volume of
151
transfused blood components is reported in Table 3. There were no significant differences between
152
the groups for diagnoses, coronary patterns (anatomy), duration of bypass and Cross-clamp times.
153
The overall 30-day mortality was 7 (2%). There was no significant difference in mortality between
154
groups (Table 1). There were no complications, as defined in Table 1 in 85% of the total cases.
155
Fifty (13.3%) major complications were observed: 14 (15%) in Group I and 36 (15%) in Group II
156
(p=0.635). Postoperative complications rates in both groups are reported in Table 1. Postoperative
157
VT was significantly shorter in Group I when compared to Group II (27 vs. 43 h. p=0.008).
158
Morbidity index and peLOS did not differ significantly between groups. Results from Generalized
159
Linear Modeling for selected outcomes are reported in Table 4. Results demonstrate that ASO
Page 7 of 19
160
performed at the age later than 24 h after birth independently increases ventilation time and
161
morbidity index, and decreases postextubation hospital length of stay.
162
Discussion
163
In this retrospective study, we found that neonates assigned to the conventional surgical
164
strategy for d-TGA compared to the first hours of life surgery had similar morbidity and mortality.
165
Although ASO is now performed in the early days of patient’s life, precise timing of surgery
166
remains institutionally dependent. In most hospitals timing for ASO is ranged between 7 and 28
167
days of patient’s life depending of complexity of d-TGA [9, 10]. Delaying ASO for several days is
168
seemed to provide benefits like reduction in pulmonary vascular resistance, kidney and liver
169
function improvement, initiation of enteral nutrition, evaluation for other congenital anomalies and
170
family preparation for surgery [4, 10,]. However, a current trend in performing ASO is being shifted
171
to the earlier time frame [4]. One study from the Children’s Hospital of Philadelphia has shown that
172
lower mean pre-operative partial pressure of oxygen (PaO2) and longer time to surgery may be
173
additive risk factors for the development of periventricular leukomalacia [11]. Another study from
174
New York-Presbyterian Morgan Stanley Children’s Hospital suggests that first 3 days of age is the
175
ideal time for an ASO [3, 12]. We proved that ASO performed in the first hours of patient’s life was
176
feasible and safe surgical strategy for prenatally diagnosed d-TGA [5] and the current study was
177
aimed to examine morbidity in neonates who underwent ASO in the first hours of life comparing
178
with conventional approach. Although, current study demonstrates no difference in morbidity and
179
mortality after the first hours of life surgery and conventional approach, ASO performed later than
180
first 24 hours of life was a significant independent risk factor for increased morbidity in this series,
181
particularly for postoperative ventilation time and morbidity index. First hours of life surgery was
182
available mostly for prenatally diagnosed patients in this study. However five patients in Group I
183
were diagnosed postnatally and were operated on between 4 and 24 hours after birth. They were
184
admitted to our institution in stable condition, with only one patient intubated and none of them
185
required BAS. All of these patients underwent ASO without AUCB as this option is feasable for
186
prenataly diagnosed patients only. It seems that early hours of life surgery is possible for postnatally Page 8 of 19
187
diagnosed patients too, if diagnosis and transfer are being done in a timely manner. We have found
188
only one report describing successful results of heart surgery performed in the first 24 hours of the
189
patient’s life [23]. Esposito and associates reported four patients who underwent successful surgical
190
correction within 24 h of birth. Two patients with total anomalous pulmonary venous drainage and
191
one patient with pulmonary atresia and intact septum were corrected with the aid of profound
192
hypothermia by the combined surface and bypass cooling technique. Cardiopulmonary bypass alone
193
was used for the fourth patient with aortic stenosis. Their comment was that usual surgical
194
techniques can be applied successfully to infants even within 24 h of life.
195
Although peLOS was similar between groups in the current srudy it was found that delaying
196
surgery (afe at surgery > 24 h) inversely contributed to peLOS in this series. We were not able
197
explain this relationship, however mother’s recovery from cesarian section in prenatally diagnosed
198
patients may contribute to this too. It is known that prenatal awareness of TGA was associated with
199
a higher percentage of induced deliveries and a major increase in the rate of cesarian section [24].
200
A cohort of 121 patients was studied (48 prenatal and 73 postnatal diagnoses) and it was shown that
201
Induced delivery and cesarian section were more frequent in the prenatal (54.1% and 31%) than in
202
the postnatal diagnosis group (19.4% and 8%; p<0.001 and p<0.001, respectively). We have not
203
studied that formally, however.
204
Accurate prenatal diagnosis reduces maternal and neonatal risk and improves outcomes.
205
Studies suggested that prenatally diagnosed patients had earlier BAS and were less likely to require
206
mechanical preoperative ventilation [13], had better patient’s condition at presentation and
207
improved outcomes [14]. We proposed additional option for prenatally diagnosed patients with d-
208
TGA. We assumed that complete surgical repair in the first hours of life in prenatally diagnosed
209
neonates would be beneficial due to preventing further development of hypoxemia, eliminating
210
prolonged exposure to PGE and PDA physiology, and shortening preoperative ICU stay and
211
hospital stay. The study results demonstrate significantly reduced preoperative ICU stay, rates of
212
BAS and preoperative ventilation which resulted in significant reduction of total hospital stay in
213
patients operated with 24 hours after birth (Table 1). BAS is known to be associated with vascular Page 9 of 19
214
trauma, atrial arrhythmias, atrial perforation and tamponade [4]. We did not observe any of those
215
complications in the current series. Moreover, we were unable to demonstrate influence of BAS on
216
postoperative outcomes. In those neonates, who suffered from significant hypoxemia after birth
217
due to restrictive foramen ovale and could not tolerate for two or three hours until surgery, BAS
218
was considered as an option to improve oxygenation in the systemic circulation. In the current
219
study, among 39 patients of Group II who were diagnosed prenattaly only eight required urgent
220
balloon atrial septostomy immediately after birth due to inadequate mixing and occurrence of
221
significant hypoxemia which would have led to acute hemodynamic deterioration with increasing in
222
serum lactate levels. We have previously found that acutely impaired oxygenation due to inadequate
223
mixing resulted in elevated pre bypass lactate levels, measured as a surrogate of tissue perfusion,
224
and was significantly associated with elevated intra- and postoperative lactate concentrations,
225
followed by compromised outcomes [6]. Several studies also suggested that increased postoperative
226
serum lactate is associated with poor outcome [6, 17]. This study shows that elevated lacate level at
227
one hour after surgery was independently associated with prolonged postoperative VT and
228
morbidity index. Nevertheless, we did not formally test decision-analysis for competing risks in
229
which one must weigh the relative risks and benefits of: BAS with PGE and timing of ASO in
230
patients with compromised blood mixing and following significant hypoxemia.
231
While awaiting ASO, neonates remain at risk for mechanical ventilation, infection, medical
232
errors, paradoxical emboli, increased cost for treatment and longer hospital stay [15]. PGE infusion
233
can cause apnea and is associated with prolonged preoperative mechanical ventilation [15]. It was
234
shown that preoperative ventilation is associated with high resource utilization postoperatively [16].
235
In the current study Group I patients had no preop ICU stay and had significantly lower rate of
236
preoperative intubation/ventilation (Table 1). Preoperative ventilation rate emerged as a risk factor
237
in this series for prolonged postoperative mechanical ventilation. It does not contribute dierectly to
238
the first hours of life surgery, however incorporates directly with our assumption.
239
Meticulous surgical technique should not be underestimated. In the study there were no
240
differences in either diagnosis or coronary patterns (Table 1). Nonetheless, tissue features in the Page 10 of 19
241
early hours of patient’s life may raise an issue regarding surgeon’s concerns and technical
242
complexity of these patients. A longer CPB is considered to be a surrogate of technical complexity
243
and causes morbidity through its adverse physiological effects. Oppositely, a well performed
244
coronary transfer with a limited CPB time is usually followed by a simple postoperative course in
245
most ASO patients. In terms of length of the operation, we used CPB time to examine its interaction
246
with the other variables. CPB duration was not a risk factor for outcomes in this study and was
247
similar in both groups suggesting similarity in surgical complexity of the ASO performed either
248
conventionally or at the first hours of life (Table 1). The diagnoses and coronary categories (Table
249
1) reflect our perceprion of complexity. Coronary anatomy (double loop, single ostium, or
250
intramural course) was found to be a risk factor independently increasing morbidity, particulary for
251
ventilation time. In the review study published by Pascuali and colleagues single ostium and
252
intramural course of coronary artery were considered as important risk factor for mortality [24].
253
Redo sternotomy with or without CPB, as well as non cardiac surgeries in the early postoperative
254
period were significant risk factors for morbidity in this study. Neither diagnose nor other anatomic
255
factors were found to be significant risk factors in this siries.
256
Prenatal diagnosis of d-TGA offered one more important option in the management of
257
patients with d-TGA: harvesting, processing and transfusion of AUCB during ASO. We previously
258
reported that AUCB is efficient and safe alternative to homologous blood components [18]. Median
259
volume of harvested AUCB is usually equal to approximately 30% of circulating blood volume in
260
neonates with prenatally diagnosed d-TGA [5]. Transfusion of AUCB was not a significant risk
261
factor affecting outcomes in our study, except morbidity index. Analysis of transfusion rate
262
confirms that AUCB transfusion allows to avoid homologous RBC’s and FFP transfusions
263
intraoperatively and during early postoperative period (Table 2). Moreover, transfusion of
264
homologous RBC’s was a significant risk factor independently increasing morbidity index and
265
peLOS in this series. Several studies have described homologous blood transfusions as a potential
266
cause of various complications, such as immunologic reactions that lead to organ dysfunction,
267
transmission of infection, and transfusion-related reactions [19, 20]. Owing to the small body Page 11 of 19
268
weight (less than 4 kg) and relatively large CPB circuit needed for neonates, the total quantity of
269
homologous blood used intraoperatively usually accounts for more than 40% to 50% of their
270
circulating blood volume [21]. Although, the volume of transfused homologous blood components
271
in our study population is not as much as been reported in other studies, we would suggest
272
harvesting and transfusion of AUCB in prenatally diagnosed d-TGA as a significant benefit of the
273
first hours of life ASO or early days of life ASO, whatever. From our experience delaying in ASO
274
in prenatally diagnosed d-TGA was not a contraindication for AUCB transfusion. We did not tested
275
directly the duration of safe storage time for AUCB for open heart surgery. However, 16 of Group
276
II patients were transfused with AUCB during operation between 48 and 72 hours after its
277
collection, considering its acceptable storage characteristics [22].
278
Study Limitations
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An important limitation of this study is that the patients were selected in a non-randomized
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manner, predisposing the analysis to selection bias based on whether the subject was identified
281
during the prenatal or postnatal period. Postnatal diagnosis of surgically correctable congenital heart
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disease precludes the use of AUCB.
283
Conclusions
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In conclusion, the study shows that ASO in the first hours of life can be performed with
285
excellent early results. Significantly reduced length of preoperative and total hospital stay and
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homologous blood exposure were observed in patients who underwent ASO in the first hours of
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life. Compared to the conventional approach ASO during the initial 24 hours of life has similar
288
outcomes in view of morbidity and mortality, however delaying surgery for TGA seems to be
289
associated with increased morbidity in this series.
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References 1. Khairy P, Clair M, Fernandes SM, et al. Cardiovascular Outcomes After the Arterial Switch Operation for D-Transposition of the Great Arteries. Circulation. 2013; 127: 331-9.
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2. Petit CJ, Rome JJ, Wernovsky G, et al. Preoperative brain injury in transposition of the great
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arteries is associated with oxygenation and time to surgery, not balloon atrial septostomy.
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Circulation. 2009; 119:709–16.
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3. Anderson BR, Ciarleglio AJ, Hayes DA, et al. Earlier arterial switch operation improves
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outcomes and reduces costs for neonates with transposition of the great arteries. J Am Coll Cardiol
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2014;63:481–7.
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4. Villafañe J, Regina Lantin-Hermoso M., Bhatt AB, et al. D-transposition of the great
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arteries: hot topics in the current era of the arterial switch operation. Am Coll Cardiol. 2014 August
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5; 64(5): 498–511.
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5. Chasovskyi K, Fedevych O, Vorobiov G, et al. Arterial switch operation in the first hours of life using autologous umbilical cord blood. Ann Thorac Surg 2012;93:1571-6.
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6. K Chasovskyi, O Fedevych, DM McMullan. Tissue perfusion in neonates undergoing open-
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heart surgery using autologous umbilical cord blood or donor blood components. Perfusion. 2015
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Sep; 30(6):499-506.
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7. NetCord-FACT international standards for cord blood collection, banking, and release for administration. 4th ed. Omaha, NE: Foundation for the Accreditation of Cellular Therapy, 2010. 8. Stoica S, Carpenter E, Campbell D, et al. Morbidity of the Arterial Switch Operation. Ann Thorac Surg. 2012 June ; 93(6): 1977-82. 9. Duncan BW, Poirier NC, Mee RB, et al. Selective Timing for the Arterial Switch Operation Ann Thorac Surg 2004; 77:1691–7.
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10. McMahon CJ. Snyder CS, Rivenes SM, Sang CJ, Jr., and. Fraser CD, Jr. Neonatal Arterial
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Switch Operation for Transposition of the Great Arteries in a Patient with Mirror Image
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Dextrocardia and Situs Inversus Totalis. Tex Heart Inst J. 2000; 27(2): 193–195.
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11. Petit CJ, Rome JJ, Wernovsky G, et al. Preoperative brain injury in transposition of the great
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arteries is associated with oxygenation and time to surgery, not balloon atrial septostomy.
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Circulation 2009;119:709–16.
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12. Karamlou T. Optimal Timing for Arterial Switch in Neonates With Transposition of the Great Arteries. JACC Vol. 63, No. 5, 2014:488–9.
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13. Escobar-Diaz MC, Freud LR, Bueno A, et al. Prenatal Diagnosis of Transposition of the
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Great Arteries over a 20-Year Period: Improved but Imperfect. Ultrasound Obstet Gynecol. 2015
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Jun; 45(6): 678–682.
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14. Bonnet D, Coltri A, Butera G, et al. Detection of transposition of the great arteries in fetuses reduces neonatal morbidityand mortality. Circulation 1999;99:916–8.
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15. Butts RJ, Ellis AR, Bradley Sm, Hulsey TC, Atz AM. Effect of prostaglandin duration on
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outcomes in transposition of the great arteries with intact ventricular septum. Congenit Heart Dis.
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2012; 7:387–91.
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16. Dibardino DJ, Allison AE, Vaughn WK, McKenzie ED, Fraser CD. Current expectations for newborns undergoing the arterial switch operation. Ann Surg. 2004; 239:588–96.
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17. Cheung PY, Chui N, Joffe AR, Rebeyka IM, Robertson CM. Western Canadian Complex
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Pediatric Therapies Project, Follow-up Group. Postoperative lactate concentrations predict the
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outcome of infants aged 6 weeks or less after intracardiac surgery: a cohort follow-up to 18 months.
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J Thorac Cardiovasc Surg 2005; 130: 837–843.
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18. K.Chasovskyi, I Yemets. Impact of carbon dioxide tension during cardiopulmonary bypass
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on tissue perfusion in neonates undergoing cardiac surgery using autologous umbilical cord blood.
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Perfusion. 2015 Dec 18. pii: 0267659115624004. [Epub ahead of print].
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19. Ferraris VA, Suellen P, et al. for The Society of Thoracic Surgeons Blood Conservation
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Guideline Task Force. Perioperative blood transfusion and blood conservation in cardiac surgery.
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20. Spiess BD. Blood transfusion: the silent epidemic. AnnThorac Surg 2001;72:1832–7.
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21. Ranucci M, Carlucci C, Isgrò G, et al. Duration of red blood cell storage and outcomes in pediatric cardiac surgery: an association found for pump prime blood. Crit Care 2009; 13:R207.
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22. Zhurova M, Akabutu J, Acker J. Quality of Red Blood Cells Isolated from Umbilical Cord
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Blood Stored at Room Temperature. Journal of Blood Transfusion 2012; doi:10.1155/2012/102809.
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23. Eposito G, Keeton BR, Sutherland GR, Monro JL, Manners JM. Open heart surgery in the
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first 24 hours of life. Pediatr Cardiol 1989;10:33– 6.
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24. Raboisson MJ, Samson C, Ducreux C, Rudigoz RC, Gaucherand P, Bouvagnet P, Bozio A.
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Impact of prenatal diagnosis of transposition of the great arteries on obstetric and early postnatal
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management. Eur J Obstet Gynecol Reprod Biol. 2009 Jan;142(1):18-22.
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25. Pasquali SK, Hasselblad V, Li JS, Kong DF, Sanders SP. Coronary artery pattern and
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outcome of arterial switch operation for transposition of the great arteries: a meta-analysis.
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Circulation. 2002 Nov 12;106(20):2575-80.
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Table 1. PATIENT CHARACTERISTICS Variable
357 358 359 360 361 362 363 364 365 366
Group Ia (n=92) 4 (3,5)[1,5-24] 3.3 (0.6) 87 (95)
Group IIb (n=254) 144 (96, 192)[36-696] 3.4 (0.6) 39 (16%)
p value
Age at surgery (hours), median (IQR)[min-max] <0.001 Weight (kg), mean (SD) 0.174 Prenatally diagnosed, n (%) <0.001 Diagnosis, n (%) N/A TGA-IVS 65 (71) 165 (65) TGA-VSD 25 (27) 77 (30) TGA, VSD, LVOTO 1 (1) 0 TGA, VSD, CoAo 1 (1) 12 (5) Coronary patterns a N/A 1 62 (68) 174 (72) 2 15(17) 43 (18) 3 13 (14) 26 (11) Preop intubation, n (%) 1 (1) 62 (24) <0.001 BAS, n (%) 1 (1) 201 (73) <0.001 CPB time (min), mean (SD) 154 (29) 155 (32) 0.703 Cross-clamp (min), mean (SD) 85 (21) 85 (14) 0.952 Open chest as strategy, No. (%) 4 (4) 5 (2) 0.258 Postoperative ventilation time (hr), median (IQR) 27 (22, 47) 42 (24, 67) 0.008 Complications, n (%) 14 (15) 36 (15) 0.635 Neurologic deficit persisting at discharge, No. (%) 1 (1) 5(2) 1.000 Arrhythmia necessitating permanent pacemaker 1 (1) 2 (0.8) 1.000 Unplanned cardiac reoperations with CPB, No. (%) 0 3 (1.2) 0.568 Phrenic nerve palsy requiring diaphragmatic plication, No. (%) 1 (1) 7 (3) 0.686 Mediastinitis requiring sternum reopening, No. (%) 2 (3) 2 (1) 0.291 Unplanned cardiac reoperations without CPB, No. (%) 5 (5) 12 (5) 0.760 Unplanned noncardiac reoparetions 4 (4) 5 (2) 0.253 LOS (d), median (IQR) Preop ICU 0 3 (2, 4) <0.001 Postextubation 13 (10, 15) 13 (10, 19) 0.744 Total Hospital 14 (12, 18) 18 (14, 24) <0.001 Morbidity indexd, mean (SD) 1 (1, 1,4) 1,1 (0.8, 1.9) 0.471 30-day mortality, n (%) 2 (2) 5 (2) 1.000 a patients underwent ASO in the first 24 hours of life; b patients underwent ASO after 24 hours of life; c Coronary pattern categories: 1 = usual arrangement, 2 = circumflex off right coronary artery, 3 = double loop, single ostium, or intramural. d index, defined as ventilation time + post-extubation hospital length of stay + occurrence of selected major complications; CPB = cardiopulmonary bypass; IQR = interquartile range; IVS = intact ventricular septum; LOS = length of stay; LVOTO = left ventricle outflow tract obstruction; N/A = not applicable; Preop = preoperative; SD = standard deviation; TGA = transposition of the great arteries; VSD = ventricular septal defect; ICU = intensive care unit; AUCB = autologous umbilical cord blood; BAS = balloon atrial septostomy; CoAo – coarctation of the aorta.
367 368
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Table 2. BLOOD PRODUCTS UTILIZATION Variable During CPB: AUCB, No of pts. (%) Homologous RBC’s, No of pts. (%) Post CPB: AUCB, No of pts. (%) Homologous RBC’s, No of pts. (%) Homologous FFP *, No of pts. (%) During ICU stay: AUCB, No. (%) Homologous RBC’s, No of pts. (%) Homologous FFP, No of pts. (%)
370 371 372 373 374 375
Group Ia (n=92)
Group IIb (n=254)
p value
83 (90%) 14 (16%)
16 (6%) 237 (93%)
<0.001 <0.001
70 (76%) 11 (7%) 14 (16%)
7 (3%) 200 (79%) 215 (85%)
<0.001 <0.001 <0.001
0 18 (19.6%) 12 (13%)
0 175 (69%) 99 (39%)
N/A <0.001 <0.001
Homologous RBC’s during perioperative course, 22 (24%) 241 (95%) <0.001 No of pts. (%) a patients underwent ASO in the first 24 hours of life; b patients underwent ASO after 24 hours of life; * According to the protocol FFP is not used for priming the circuit AUCB = autologous umbilical cord blood, FFP – fresh frozen plasma; CPB – cardiopulmonary bypass; ICU – intensive care unit; RBC – red blood cells.
376
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Table 3. VOLUME OF TRANSFUSED BLOOD COMPONENTS Variable
378 379 380 381 382 383 384
Group Ia
Group IIb
p value
Median ; 25% - 75% During CPB: AUCB, ml 40; 20-50* 50; 22-60* N/A Homologous RBC’s, ml 45; 13-68** 60; 45-80** Post CPB: AUCB, ml 50; 28-60* 0; 0-58* Homologous RBC’s, ml 0; 0-48** 30; 20-50** N/A Homologous FFP transfusion, ml 45; 8-60** 30; 20-50** During ICU stay: AUCB, No. (%) Homologous RBC’s, ml 20; 0-35 30; 0-50 N/A Homologous FFP, ml a patients underwent ASO in the first 24 hours of life; b patients underwent ASO after 24 hours of life; * Calculated for those pts, in whom AUCB was collected and used; ** Calculated for those pts, in whom AUCB were not used. AUCB = autologous umbilical cord blood, FFP – fresh frozen plasma; CPB – cardiopulmonary bypass; ICU – intensive care unit; RBC – red blood cells.
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Table 4. Effect of Perioperative Variables on Three Morbidity Outcomes Postoperative ventilation time age at surgery >24 h coronary patterns* preop ventilation unplanned cardiac reoperations without CPB lactate at 1 h after surgery lactate at the end of CPB peLOS unplanned cardiac reoperations with CPB unplanned noncardiac reoparetions age at surgery >24 h Homologous RBC’s at ICU
B (95% CI)
SE
p Value
0.34 ( 0.12-0.55) 0.49 (0.24-0.37) 0.44 (0.21-0.65)
0.10 0.12 0.12
0.002 <0.001 <0.001
0.86 (0.48-1.2)
0.19
<0.001
0.16 (0.07-0.25) -0.007 ( -0.84-0.07)
0.05 0.04
<0.001 0.849
0.49 (-0.07-1.06)
0.05
0.086
0.29 (-0.006-0.60)
0.15
0.055
-0.28 (-0.43- (-0.13) 0.003 (0.002-0.005)
0.07 0.0008
<0.001 <0.001
0.02
0.002
0.09 0.002 0.0009
0.020 <0.001 <0.001
386
Morbidity index lactate at one hour after 0.065 (0.024-0.10) surgery age at surgery >24 h 0.22 (0.034-0.40) UCB during CPB 0.007 (0.003-0.011) Homologous RBC’s at ICU 0.005 (0.003-0.007) * double loop, single ostium, or intramural course
387
CPB – cardiopulmonary bypass, ICU – intensive care unit, RBC’s- red blood cells
388 389 390 391 392 393
Legend for the Video:
394 395 396 397
Video demonstrates a simple procedure of umbilical cord blood collection. Next two parts show two different patients undergoing arterial switch operation in the first hours of life. I all patients we use conventional techniques of dissection, coronary buttons excision and reimplantation. Tissue handling presents no additional difficulties as demonstrated.
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