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 Table of Contents  
ORIGINAL ARTICLE
Year : 2021  |  Volume : 8  |  Issue : 1  |  Page : 13-19

Mild hypothermia with selective antegrade cerebral perfusion during cardiopulmonary bypass and short-term outcomes in children with congenital heart defects


1 Department of Pediatrics, The Children's Hospital of San Antonio, San Antonio; Department of Pediatrics, Baylor College of Medicine, Houston, TX, USA
2 Department of Pediatrics, The Children's Hospital of San Antonio, San Antonio, TX, USA

Date of Submission07-Aug-2020
Date of Decision28-Sep-2020
Date of Acceptance26-Oct-2020
Date of Web Publication08-Jan-2021

Correspondence Address:
Dr. Utpal S Bhalala
Voelcker Clinical Research Center. Research Steering Committee, The Children's Hospital of San Antonio, 315 N. San Saba Street, Suite 1135, San Antonio, TX; Baylor College of Medicine, Houston, TX, USA
USA
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/JPCC.JPCC_125_20

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  Abstract 


Background: Among the known risk factors for children undergoing surgery for congenital heart defect (CHD), temperature and blood flow during cardiopulmonary bypass (CPB), are two risk factors, which may be altered to improve outcomes. Moderate - to - deep hypothermia (MDH), traditionally used, has been associated with short/long-term neurologic sequelae, so there is a move towards mild hypothermia (MH) with selective antegrade cerebral perfusion (SACP).
Aims and Objectives: To assess feasibility of mild hypothermia with selective antegrade cerebral perfusion during cardiopulmonary bypass as a cardiopulmonary bypass strategy in neonates and infants undergoing surgery for congenital heart defect.
Materials and Methods: We conducted a retrospective chart review of neonates and infants who underwent SACP on CPB during CHD surgery at our tertiary care children's hospital between January 2014 and February 2017. We categorized all the patients into 2 groups - MH + SACP or MDH + SACP. We gathered data on preoperative, intra-operative and post-operative parameters. We analyzed comparative data using student t-test and chi-squared test with a significant p-value < 0.05.
Results: There were 6 in the MH + SACP group and 7 in the MDH + SACP group, who underwent SACP on CPB during study period at our children's hospital. All the neonates and infants in the MH + SACP group survived at the hospital discharge with favorable neurologic outcomes. There was no statistically significant difference between the two groups for end organ dysfunction, ventilator days, hospital days, ICU and hospital mortality and PCPC/POPC at hospital discharge.
Conclusions: Mild hypothermia with selective antegrade cerebral perfusion during cardiopulmonary bypass is a feasible cardiopulmonary bypass strategy in neonates and infants undergoing surgery for congenital heart defect.

Keywords: Cardiopulmonary bypass, congenital heart defects, hypothermia, selective antegrade cerebral perfusion


How to cite this article:
Bhalala US, Awadhare P, Thangavelu M, Owens R, Zamora M, Nento D, Appachi E, Mumtaz MA. Mild hypothermia with selective antegrade cerebral perfusion during cardiopulmonary bypass and short-term outcomes in children with congenital heart defects. J Pediatr Crit Care 2021;8:13-9

How to cite this URL:
Bhalala US, Awadhare P, Thangavelu M, Owens R, Zamora M, Nento D, Appachi E, Mumtaz MA. Mild hypothermia with selective antegrade cerebral perfusion during cardiopulmonary bypass and short-term outcomes in children with congenital heart defects. J Pediatr Crit Care [serial online] 2021 [cited 2021 Aug 4];8:13-9. Available from: http://www.jpcc.org.in/text.asp?2021/8/1/13/306481




  Introduction Top


Congenital heart defect (CHD) is the most common type of birth defect in the United States and major cause of death in infancy and childhood. About 40,000 children are affected every year and around 2–3 million people are living with CHDs.[1],[2] Survival of children with CHD has improved over the decades following improved diagnostic abilities and enhanced surgical techniques.[3],[4] However, morbidity remains significant in survivors and is related to the postoperative adverse effects such as end-organ dysfunction, low cardiac output syndrome, and neurologic injury.[5],[6] Neurologic injury is associated with reduced postoperative quality of life, increased length of hospital stay and cost of hospitalization.[6],[7] Cardiopulmonary bypass (CPB) is an integral part of most cardiac surgeries and a potential risk factor known to contribute to the neurologic injury in the pediatric population. Several mechanisms including embolization of gaseous and particulate matter, cerebral hypoperfusion and systemic inflammatory responses have been attributed to cause neurologic injury after CPB.[8] A number of known risk factors such as genetic and constitutional factors for adverse cardiovascular and neurologic outcomes in neonates with CHD are not modifiable. However, temperature and perfusion strategies during CPB are the two important modifiable risk factors known to improve neurologic outcomes. After deep hypothermia was introduced in the 1960s, it was adopted widely for complex cardiac repairs allowing bloodless operative field and decreased cerebral metabolic rate.[9] However, many studies have shown that longer circulatory arrest time and delayed return of cerebral blood flow associated with deep hypothermia cardiac arrest (DHCA) potentially leads to significant neurologic injury.[8],[9],[10],[11] To reduce the cerebral ischemia during DHCA, selective antegrade cerebral perfusion (SACP) has been used, but results are conflicting.[11],[12],[13],[14] Although many centers continue to utilize deep hypothermia with SACP during neonatal aortic arch repair, degree and rate of rewarming is of significant concern.[5] Rewarming from moderate-to-deep hypothermia (MDH) is associated with impaired cerebrovascular autoregulation, which eventually results in neuronal injury.[14],[15] Due to the lesser degree of rewarming associated with mild hypothermia (MH) combined with SACP, it may be a better strategy during CPB.[16],[17],[18] MH for aortic arch repair surgery in adults has been demonstrated to be a safe and effective method of organ protection.[19] Therefore, MH with SACP has been practiced in some institutes, but only little is known about short-term outcomes following MH with SACP in children undergoing CHD surgery. The present study aims to compare the short-term outcomes of traditionally used MDH with SACP versus modern MH with SACP during CPB surgery in the pediatric population.


  Materials and Methods Top


Study design and selection of participants

We conducted the study at the Children's Hospital of San Antonio (CHofSA), a freestanding, 200-bed, tertiary care children's hospital. The Baylor College of Medicine Institutional Review Board and CHofSA feasibility committee approved the study. Due to the retrospective nature of the study, our IRB approved the study with a waiver of informed consent.

We conducted a retrospective chart review of children, who were admitted to cardiac intensive care unit (CICU) following surgical repair of CHDs between January 2014 and February 2017.

Inclusion criteria

  1. Patients below 1 year of age
  2. Neonates and infants who underwent SACP during CPB with MDH or MH during surgical repair of CHD.


Exclusion criteria

  1. Children above 1 year of age
  2. Infants who did not have SACP during CPB.


We divided patients into two groups-MDH + SACP and MH + SACP. We adopted expert consensus [Table 1][20] in our study to define hypothermia-MDH defined as temperature between 14.1°C–28°C and MH defined as temperature between 28.1°C and 34°C. We compared the two groups for preoperative patient characteristics, intraoperative, and postoperative parameters.
Table 1: Expert consensus on classifications of hypothermia in circulatory arrest during aortic arch surgery

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Two cardiothoracic surgeons (DN and MAM) performed all the surgeries and the same group of pediatric cardiothoracic anesthesiologists provided anesthesia to all the patients during the study period. The surgeons decided the CPB technique, the level of hypothermia and need for SACP based on patients' age, surgical complexity, type of surgery, and circulatory time required. During the surgery, the cardiac surgical and the perfusion team provided continuous, unilateral SACP using innominate or right subclavian or right carotid artery cannulation. Once on CPB, the team maintained the patients within MDH or MH temperature ranges and SACP flow rates. After completion of the surgery, the team rewarmed the patients prior to coming off the CPB, and subsequently transferred them to CICU.

We categorized patients for disease severity using the Risk Adjustment for Congenital Heart Surgery (RACHS-1) method.[21] We assessed the neurologic function using pediatric cerebral performance category (PCPC) and pediatric overall performance category (POPC),[22] Functional Status Score (FSS),[23] neuroimaging, and electroencephalogram (EEG). The lowest PCPC and POPC score of 1 represents normal neurologic function, whereas the highest PCPC and POPC score of 6 represents brain death.[22] We assessed the cardiac function using echocardiographic grading of cardiac dysfunction and vasoactive inotrope score. We also assessed renal function using pediatric Risk, Injury, Failure, Loss, End Stage Renal Disease (pRIFLE) criteria,[24] respiratory function by the need for respiratory support and ventilator days, and liver function assessment by liver enzymes and bilirubin.

Our primary outcome was mortality and our secondary outcome measures were ventilator days, length of hospital stay (days), neurologic outcomes, and occurrence of postoperative adverse events such as acute kidney injury, liver dysfunction, and need for transfusions.

Analysis

We conducted statistical analysis using Stata version 12 (StatCorp LLC, College Station, TX, USA). We did univariate analysis as the median and interquartile range (IQR). We used Student's t-test to compare the normally distributed values and Chi-square test to compare proportions between groups (P < 0.05 = Significant).


  Results Top


Between January 2014 and February 2017, 124 CPB surgeries were performed at our children's hospital. Out of these, only 13 neonates and infants underwent SACP on CPB during cardiac surgery. Out of these 13 neonates and infants, 6 received MH + SACP and 7 received MDH + SACP. The median gestational age (median [IQR]) of the patients was 37 (35.6–38.3) weeks in MH + SACP and 38.5 (37.7–39) weeks in MDH + SACP. In both groups, patients fell in the median RACHS-1 category 4. In each group, there were 3 patients each in category 4 and 2 patients each in category 6. Moreover, 1 patient in MH + SACP group and 2 patients in MDH + SACP group were in category 3. The preoperative details are summarized in [Table 2] and [Table 3].
Table 2: Median (interquartile range) for patient characteristics

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Table 3: Preoperative data (median, interquartile range) for mild hypothermia + selective antegrade cerebral perfusion and moderate-to-deep hypothermia + selective antegrade cerebral perfusion

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Intraoperative data

The lowest nasopharyngeal temperature (median [IQR]) was higher in the MH + SACP group (30 [29.5°C–31.3°C]) than in the MDH + SACP group (26 [18°C–28°C]) (P = 0.01). The SACP rate (median [IQR]) was significantly higher in the MH + SACP (104 [98–117.5] cc/kg/min) than in the MDH + SACP group (85 [72.5–100] cc/kg/min) (P = 0.02). The CPB time and aortic cross-clamp time were not significantly different between the two groups. The rate of rewarming (degree/min) was not significantly different for each of MH + SACP and MDH + SACP groups. The rewarming gradient and rewarming time were both significantly lower in MH + SACP (6.25 [4.75–6.63], 60 [31.5–60] [min]) as compared to MDH + SACP (10 [8–18.4], 65 [60–82] [min]) ([P = 0.01], [P = 0.04] respectively) [Table 4] and [Table 5].
Table 4: Congenital heart defect diagnosis and type of surgery in mild hypothermia + selective antegrade cerebral perfusion group and moderate-to-deep hypothermia + selective antegrade cerebral perfusion group

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Table 5: Intra-operative data (median, interquartile range) for mild hypothermia + selective antegrade cerebral perfusion and moderate -to-deep hypothermia + selective antegrade cerebral perfusion

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Postoperative data

The ventilator days and length of hospital stay (days) were not significantly different between the two groups. The two groups did not significantly differ in postoperative cardiac dysfunction, acute kidney injury, liver dysfunction, and need for transfusions. The baseline median (IQR) PCPC and POPC were 1 (1–1), each. The postoperative PCPC and POPC values were not significantly different from the baseline in both the groups. In MDH + SACP group, 1/7 (14%) patient developed several episodes of seizures during postoperative period, whereas in MH + SACP group none of the patients developed seizures in the postoperative period. Abnormal EEG and CT brain were documented in 14% patients in MDH + SACP group and 17% patients in MH + SACP group (P = 0.90). The baseline preoperative median (IQR) FSS in both the groups were 6 (6–6) and postoperative median (IQR) FSS in both the groups were 6 (6–7) (P = 0.53, P = 0.86). Hospital mortality did not significantly differ between the two groups. All the neonates and infants in both the groups survived at the hospital discharge with favorable preoperative and postoperative PCPC/POPC = 1 [Table 6].
Table 6: Postoperative data (median, interquartile range) for mild hypothermia + selective antegrade cerebral perfusion and moderate -to - deep hypothermia + selective antegrade cerebral perfusion

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  Discussion Top


Our study was performed to compare MH versus MDH with SACP and to evaluate the short-term outcomes after CPB during corrective cardiac surgery in neonates and infants. In a small cohort of neonates and infants who had MH + SACP during CPB for aortic arch repair, we found that MH + SACP was a feasible bypass strategy with no significant complications.

During CHD surgeries, hypothermia has been used extensively during CPB for cerebral protection against ischemia. Many studies support the neuroprotective effects of hypothermia through multiple mechanisms of reducing functional and structural metabolic rates, suppression of free radicals, and inhibition of release of excitatory neurotransmitters.[8],[25] Nonetheless, the neurologic complications associated with the use of MDH remain a major concern in the pediatric population.[9] As such, the ideal temperature strategy for congenital cardiac surgery in protecting vital visceral organs is widely debated.[26] With the advent of low flow perfusion strategies, the debate about the use of deep hypothermia has been intensified, and most of the arguments against its use are based upon harmful effects of deep hypothermia.[27] Hence, there has been increased interest in the use of MH for cerebral protection.[19] More recently, SACP with MH or normothermia has been used in aortic arch surgery in adults and it has shown improved neurodevelopmental outcomes.[10],[28] Many studies in adults reported that SACP combined with MH could potentially provide better cerebral protection in aortic arch surgery.[29],[30] A study by Tong et al., in pediatric patients who underwent aortic arch repair support the use of MH and moderate hypothermia as compared to DHCA.[17] A study by Kornilov et al. in infants receiving aortic arch reconstruction demonstrated lower incidence of neurologic complications in SACP with moderate hypothermia as compared to use of DHCA.[12] In our small cohort of neonates and infants who underwent aortic arch repair, we assessed MH and SACP and we demonstrated that the incidence of neurologic complications was not significantly different between MH + SACP and MDH + SACP groups. This is the first pilot study, which demonstrated that MH + SACP is potentially neuroprotective CPB strategy for neonates and infants during aortic arch surgery.

Rewarming after hypothermic CPB has been associated with enhanced risk for cerebral injury.[5] During rewarming from DHCA, the brain may be exposed to extended periods of hyperthermia that exacerbate brain injury.[16] Inadvertent cerebral hyperthermia potentially can lead to a significant temperature-dependent impairment in cerebral vasoreactivity during this period.[14],[15] In addition, the use of MDH has been shown to be associated with loss of cerebral autoregulation.[14],[15],[16] In a study of hypoxic ischemic arrest in swine model, Wang B et al. showed that degree and rate of rewarming from hypothermia was associated with increased neuronal apoptosis.[16] Grigore et al. demonstrated that slow rewarming with mild hypothermic CPB had favorable neurocognitive outcomes 6 weeks after surgery.[15] As compared to moderate hypothermia, lesser degree of rewarming and shorter rewarming time is required with MH.[5] In our study, rewarming gradient and rewarming time was lower in the MH + SACP group as compared to the MDH + SACP group. With MH it is possible to provide neuroprotection and minimize deleterious effects of significant rewarming.[26]

In our study, the median (IQR) length of intensive care unit and hospital stay was 48 (14.5–69.5) and 51 (15.5–101) in MH + SACP group and 22.5 (20.5–95) and 50 (25–98) in MDH + SACP group respectively (P = NS). The possible explanation for the long periods of stay is that, a large number of neonates and infants with complex congenital heart disease are referred to us by regional hospitals which are in remote areas and these hospitals do not have secondary or tertiary level pediatric services. For this reason, these patients are managed in our hospital for an extended period of time until the patients and the families are ready for the discharge.

Our study is the first study which supports the feasibility of MH with SACP in neonates and infants during CPB surgery. There are limitations to this study. This is a retrospective study conducted in a small group from a single center. Ours being a new pediatric cardiac surgery program, during the study period there were only 124 CPB surgeries. Furthermore, as per our inclusion and exclusion criteria, we evaluated only neonates and infants undergoing SACP. Therefore, the sample size was small. In our cohort, the SACP flow rate was much higher in MH + SACP group as compared to MDH + SACP group, which could have biased our results in relation to neurologic outcomes in MH + SACP group. This is one of the limitations of our study. Future randomized control trials with protocolized hypothermia and SACP strategies would potentially avoid such bias.


  Conclusion Top


MH with SACP which is a newly adopted temperature strategy on CPB in neonates and infants diagnosed with CHD is a feasible CPB strategy. Larger, multi-center, prospective, randomized studies are needed to evaluate the long-term outcomes of MH with SACP before it is widely accepted as a standard bypass strategy.

Financial support and sponsorship

This study was supported by the Children's Hospital of San Antonio pediatric cardiothoracic surgery chair endowment funds.

Conflicts of interest

There are no conflicts of interest.



 
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    Tables

  [Table 1], [Table 2], [Table 3], [Table 4], [Table 5], [Table 6]



 

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