Original Article| Volume 35, ISSUE 10, P2875-2888, October 2021

Download started.


Deep Hypothermic Circulatory Arrest in the Pediatric Population Undergoing Cardiac Surgery With Electroencephalography Monitoring: A Systematic Review and Meta-Analysis

Published:January 29, 2021DOI:


      Cardiac surgery for repair of congenital heart defects poses unique hazards to the developing brain. Deep hypothermic circulatory arrest (DHCA) is a simple and effective method for facilitating a bloodless surgical field during congenital heart defect repair. There are, however, some concerns that prolonged DHCA increases the risk of nervous system injury. The electroencephalogram (EEG) is used in adult and, to a lesser extent, pediatric cardiac procedures as a neuromonitoring method. The present study was performed to assess outcomes following DHCA with EEG monitoring in the pediatric population.


      In this systematic review and meta-analysis, the PubMed, Cochrane Central Register of Controlled Trials, Scopus, Institute of Science Index, and Embase databases were searched from inception for relevant articles. A fixed- or random-effects model, as appropriate, was used.


      Surgical setting.


      Pediatric population (≤18 y old).


      DHCA (18°C) with EEG monitoring.

      Measurements and Main Results

      Nineteen articles with 1,267 pediatric patients ≤18 years were included. The event rate of clinical and EEG seizures among patients who underwent DHCA was 12.9% and 14.9%, respectively. Mortality was found to have a 6.3% prevalence. A longer duration of DHCA was associated with a higher risk of EEG seizure and neurologic abnormalities. In addition, seizures were associated with increased neurologic abnormalities and neurodevelopmental delay.


      EEG and neurologic abnormalities were common after DHCA. A longer duration of DHCA was found to lead to more EEG seizure and neurologic abnormalities. Moreover, EEG seizures were more common than clinical seizures. Seizures were found to be associated with increased neurologic abnormalities and neurodevelopmental delay.

      Key Words

      To read this article in full you will need to make a payment

      Purchase one-time access:

      Academic & Personal: 24 hour online accessCorporate R&D Professionals: 24 hour online access
      One-time access price info
      • For academic or personal research use, select 'Academic and Personal'
      • For corporate R&D use, select 'Corporate R&D Professionals'


      Subscribe to Journal of Cardiothoracic and Vascular Anesthesia
      Already a print subscriber? Claim online access
      Already an online subscriber? Sign in
      Institutional Access: Sign in to ScienceDirect


        • Rappaport LA
        • Wypij D
        • Bellinger DC
        • et al.
        Relation of seizures after cardiac surgery in early infancy to neurodevelopmental outcome.
        Circulation. 1998; 97: 773-779
        • Ziganshin BA
        • Elefteriades JA.
        Deep hypothermic circulatory arrest.
        Ann Cardiothorac Surg. 2013; 2: 303
        • Kamiya H
        • Hagl C
        • Kropivnitskaya I
        • et al.
        The safety of moderate hypothermic lower body circulatory arrest with selective cerebral perfusion: A propensity score analysis.
        J Thorac Cardiovasc Surg. 2007; 133: 501-509
        • Williams WG.
        Surgical outcomes in congenital heart disease: Expectations and realities.
        Eur J Cardiothorac Surg. 2005; 27: 937-944
        • Oster ME
        • Lee KA
        • Honein MA
        • et al.
        Temporal trends in survival among infants with critical congenital heart defects.
        Pediatrics. 2013; 131: e1502-e1508
        • Jonas RA.
        Deep hypothermic circulatory arrest: Current status and indications. Semin Thorac Cardiovasc Pediatr Card.
        Surg Annu. 2002; 5: 76-88
        • Bellinger DC
        • Wypij D
        • Kuban KCK
        • et al.
        Developmental and neurological status of children at 4 years of age after heart surgery with hypothermic circulatory arrest or low-flow cardiopulmonary bypass.
        Circulation. 1999; 100: 526-532
        • Newburger JW
        • Jonas RA
        • Wernovsky G
        • et al.
        A comparison of the perioperative neurologic effects of hypothermic circulatory arrest versus low-flow cardiopulmonary bypass in infant heart surgery.
        N Engl J Med. 1993; 329: 1057-1064
        • Hagl C
        • Khaladj N
        • Peterss S
        • et al.
        Hypothermic circulatory arrest with and without cold selective antegrade cerebral perfusion: Impact on neurological recovery and tissue metabolism in an acute porcine model.
        Eur J Cardiothorac Surg. 2004; 26: 73-80
        • Helmers S
        • Kull L
        • Constantinou J
        • et al.
        Electroencephalographic monitoring of infants during repair of complex cardiac defects.
        Am J Electroneurodiagnostic Technol. 1996; 36: 133-147
        • Clancy RR
        • McGaurn SA
        • Wernovsky G
        • et al.
        Risk of seizures in survivors of newborn heart surgery using deep hypothermic circulatory arrest.
        Pediatrics. 2003; 111: 592-601
        • Brunberg JA
        • Reilly EL
        • Doty DB.
        Central nervous system consequences in infants of cardiac surgery using deep hypothermia and circulatory arrest.
        Circulation. 1974; 50: II60-II68
        • Gaynor JW
        • Nicolson SC
        • Jarvik GP
        • et al.
        Increasing duration of deep hypothermic circulatory arrest is associated with an increased incidence of postoperative electroencephalographic seizures.
        J Thorac Cardiovasc Surg. 2005; 130: 1278-1286
        • Bellinger DC
        • Jonas RA
        • Rappaport LA
        • et al.
        Developmental and neurologic status of children after heart surgery with hypothermic circulatory arrest or low-flow cardiopulmonary bypass.
        N Engl J Med. 1995; 332: 549-555
        • Shellhaas R
        • Chang T
        • Tsuchida T
        • et al.
        American Clinical Neurophysiology Society's guideline on continuous EEG monitoring in neonates.
        J Clin Neurophysiol. 2011; 28: 611-617
        • Miller G
        • Rodichok LD
        • Baylen BG
        • et al.
        EEG changes during open heart surgery on infants aged 6 months or less: Relationship to early neurologic morbidity.
        Pediatr Neurol. 1994; 10: 124-130
        • Liberati A
        • Altman DG
        • Tetzlaff J
        • et al.
        The PRISMA statement for reporting systematic reviews and meta-analyses of studies that evaluate health care interventions: Explanation and elaboration.
        PLoS Med. 2009; 6e1000100
        • Waqas A
        • Elhady M
        • Dila KS
        • et al.
        Association between maternal depression and risk of infant diarrhea: A systematic review and meta-analysis.
        Public Health. 2018; 159: 78-88
        • Morsy S
        • Khalil SM
        • Doheim MF
        • et al.
        Efficacy of ethyl-EPA as a treatment for Huntington disease: A systematic review and meta-analysis.
        Acta Neuropsychiatrica. 2019; 31: 175-185
        • Conolly S
        • Arrowsmith JE
        • Klein AA.
        Deep hypothermic circulatory arrest continuing education in anesthesia.
        Crit Care Pain. 2010; 10 (138e142)
        • DerSimonian R
        • Laird N.
        Meta-analysis in clinical trials.
        Control Clin Trials. 1986; 7: 177-188
        • Higgins JP
        • Thompson SG
        • Deeks JJ
        • et al.
        Measuring inconsistency in meta-analyses.
        Br Med J. 2003; 327: 557
        • Nguyen AV
        • Thanh LV
        • Kamel MG
        • et al.
        Optimal percutaneous coronary intervention in patients with ST-elevation myocardial infarction and multivessel disease: An updated, large-scale systematic review and meta-analysis.
        Int J Cardiol. 2017; 244: 67-76
        • Zintzaras E
        • Lau J.
        Synthesis of genetic association studies for pertinent gene–disease associations requires appropriate methodological and statistical approaches.
        J Clin Epidemiol. 2008; 61: 634-645
        • Munafo MR
        • Flint J.
        Meta-analysis of genetic association studies.
        Trends Genet. 2004; 20: 439-444
        • Mantel N
        • Haenszel W.
        Statistical aspects of the analysis of data from retrospective studies of disease.
        J Natl Cancer Inst. 1959; 22: 719-748
        • Sherif NA
        • Zayan AH
        • Elkady AH
        • et al.
        Mast cell mediators in relation to dengue severity: A systematic review and meta-analysis.
        Rev Med Virol. 2020; 30: e2084
        • Sallam A
        • Alkhatip AAAMM
        • Kamel MG
        • et al.
        The diagnostic accuracy of noninvasive methods to measure the intracranial pressure: A systematic review and meta-analysis [e-pub ahead of print].
        Anesth Analg. 2020;
        • Abdellatif M
        • Ghozy S
        • Kamel MG
        • et al.
        Association between exposure to macrolides and the development of infantile hypertrophic pyloric stenosis: A systematic review and meta-analysis.
        Eur J Pediatr. 2019; 178: 301-314
        • de Ferranti S
        • Gauvreau K
        • Hickey PR
        • et al.
        Intraoperative hyperglycemia during infant cardiac surgery is not associated with adverse neurodevelopmental outcomes at 1, 4, and 8 years.
        Anesthesiology. 2004; 100: 1345-1352
        • Austin III, EH
        • Edmonds Jr, HL
        • Auden SM
        • et al.
        Benefit of neurophysiologic monitoring for pediatric cardiac surgery.
        J Thorac Cardiovasc Surg. 1997; 114: 707-717
        • Bellinger DC
        • Wypij D
        • Kuban KC
        • et al.
        Developmental and neurological status of children at 4 years of age after heart surgery with hypothermic circulatory arrest or low-flow cardiopulmonary bypass.
        Circulation. 1999; 100: 526-532
        • Bellinger DC
        • Wypij D
        • du Plessis AJ
        • et al.
        Developmental and neurologic effects of alpha-stat versus pH-stat strategies for deep hypothermic cardiopulmonary bypass in infants.
        J Thorac Cardiovasc Surg. 2001; 121: 374-383
        • Bellinger DC
        • Wypij D
        • Rappaport LA
        • et al.
        Neurodevelopmental status at eight years in children with dextro-transposition of the great arteries: The Boston Circulatory Arrest Trial.
        J Thorac Cardiovasc Surg. 2003; 126: 1385-1396
        • Algra SO
        • Jansen NJ
        • van der Tweel I
        • et al.
        Neurological injury after neonatal cardiac surgery: A randomized, controlled trial of 2 perfusion techniques.
        Circulation. 2014; 129: 224-233
        • du Plessis AJ
        • Jonas RA
        • Wypij D
        • et al.
        Perioperative effects of alpha-stat versus pH-stat strategies for deep hypothermic cardiopulmonary bypass in infants.
        J Thorac Cardiovasc Surg. 1997; 114: 991-1001
        • Gaynor JW
        • Jarvik GP
        • Gerdes M
        • et al.
        Postoperative electroencephalographic seizures are associated with deficits in executive function and social behaviors at 4 years of age following cardiac surgery in infancy.
        J Thorac Cardiovasc Surg. 2013; 146: 132-139
        • Helmers SL
        • Wypij D
        • Constantinou JE
        • et al.
        Perioperative electroencephalographic seizures in infants undergoing repair of complex congenital cardiac defects.
        Electroencephalogr Clin Neurophysiol. 1997; 102: 27-36
        • Huang JH
        • Su ZK
        • Wang SM.
        Near-infrared spectroscopy monitoring of brain oxygen in infant cardiac surgery.
        Asian Cardiovasc Thorac Ann. 2007; 15: 194-199
        • Iwamoto I
        • Baba H
        • Koga Y
        • et al.
        The relation between EEG and mental development following cardiac surgery performed under simple deep hypothermia in children.
        The Jpn J Surg. 1990; 20: 158-162
        • Mavroudis CD
        • Mensah-Brown KG
        • Ko TS
        • et al.
        Electroencephalographic response to deep hypothermic circulatory arrest in neonatal swine and humans.
        Ann Thorac Surg. 2018; 106: 1841-1846
        • Raja R
        • Johnston JK
        • Fitts JA
        • et al.
        Post-transplant seizures in infants with hypoplastic left heart syndrome.
        Pediatr Neurol. 2003; 28: 370-378
        • Rodriguez RA
        • Edmonds Jr, HL
        • Auden SM
        • et al.
        Auditory brainstem evoked responses and temperature monitoring during pediatric cardiopulmonary bypass.
        Can J Anaesth. 1999; 46: 832-839
        • Naim MY
        • Gaynor JW
        • Chen J
        • et al.
        Subclinical seizures identified by postoperative electroencephalographic monitoring are common after neonatal cardiac surgery.
        J Thorac Cardiovasc Surg. 2015; 150: 169-180
        • du Plessis AJ.
        Neurologic complications of cardiac disease in the newborn.
        Clin Perinatol. 1997; 24: 807-826
        • Huang JH
        • Su ZK
        • Wang SM.
        Near-infrared spectroscopy monitoring of brain oxygen in infant cardiac surgery.
        Asian Cardiovasc Thorac Ann. 2007; 15: 194-199
        • McCullough JN
        • Zhang N
        • Reich DL
        • et al.
        Cerebral metabolic suppression during hypothermic circulatory arrest in humans.
        Ann Thorac Surg. 1999; 67: 1895-1899
        • Nakashima K
        • Todd MM.
        Effects of hypothermia on the rate of excitatory amino acid release after ischemic depolarization.
        Stroke. 1996; 27: 913-918
        • Stecker MM
        • Cheung AT
        • Pochettino A
        • et al.
        Deep hypothermic circulatory arrest: II. Changes in electroencephalogram and evoked potentials during rewarming.
        Ann Thorac Surg. 2001; 71: 22-28
        • James ML
        • Andersen ND
        • Swaminathan M
        • et al.
        Predictors of electrocerebral inactivity with deep hypothermia.
        J Thorac Cardiovasc Surg. 2014; 147: 1002-1007
        • Newman MF
        • Kirchner JL
        • Phillips-Bute B
        • et al.
        Longitudinal assessment of neurocognitive function after coronary-artery bypass surgery.
        N Engl J Med. 2001; 344: 395-402
        • Ballweg JA
        • Wernovsky G
        • Gaynor JW.
        Neurodevelopmental outcomes following congenital heart surgery.
        Pediatr Cardiol. 2007; 28: 126-133
        • Gaynor JW
        • Wernovsky G
        • Jarvik GP
        • et al.
        Patient characteristics are important determinants of neurodevelopmental outcome at one year of age after neonatal and infant cardiac surgery.
        J Thorac Cardiovasc Surg. 2007; 133 (1344-53.e1343)
        • Kurth CD
        • Steven JL
        • Montenegro LM
        • et al.
        Cerebral oxygen saturation before congenital heart surgery.
        Ann Thorac Surg. 2001; 72: 187-192
        • Galli KK
        • Zimmerman RA
        • Jarvik GP
        • et al.
        Periventricular leukomalacia is common after neonatal cardiac surgery.
        J Thorac Cardiovasc Surg. 2004; 127: 692-704
        • Andropoulos DB
        • Mizrahi EM
        • Hrachovy RA
        • et al.
        Electroencephalographic seizures after neonatal cardiac surgery with high-flow cardiopulmonary bypass.
        Anesth Analg. 2010; 110: 1680-1685
        • McQuillen PS
        • Nishimoto MS
        • Bottrell CL
        • et al.
        Regional and central venous oxygen saturation monitoring following pediatric cardiac surgery: Concordance and association with clinical variables.
        Pediatr Crit Care Med. 2007; 8: 154-160
        • Priestley MA
        • Golden JA
        • O'Hara IB
        • et al.
        Comparison of neurologic outcome after deep hypothermic circulatory arrest with alpha-stat and pH-stat cardiopulmonary bypass in newborn pigs.
        J Thorac Cardiovasc Surg. 2001; 121: 336-343
        • Kurth DC
        • O'Rourke MM
        • O'Hara IB
        Comparison of pH-state and alpha-stat cardiopulmonary bypass on cerebral oxygenation and blood flow in relation to hypothermic circulatory arrest in piglets.
        Anesthesiology. 1998; 89: 110-118
        • Murkin J
        • Martzke J
        • Buchan A
        • et al.
        A randomized study of the influence of perfusion technique and pH management strategy in 316 patients undergoing coronary artery bypass surgery: II. Neurologic and cognitive outcomes.
        J Thorac Cardiovasc Surg. 1995; 110: 349-362
        • Wong P
        • Barlow C
        • Hickey P
        • et al.
        Factors associated with choreoathetosis after cardiopulmonary bypass in children with congenital heart disease.
        Circulation. 1992; 86: II118-II126
        • Jonas RA
        • Bellinger DC
        • Rappaport LA
        • et al.
        Relation of pH strategy and developmental outcome after hypothermic circulatory arrest.
        J Thorac Cardiovasc Surg. 1993; 106: 362-368
        • Goldberg CS
        • Bove EL
        • Devaney EJ
        • et al.
        A randomized clinical trial of regional cerebral perfusion versus deep hypothermic circulatory arrest: Outcomes for infants with functional single ventricle.
        J Thorac Cardiovasc Surg. 2007; 133: 880-887
        • Visconti KJ
        • Rimmer D
        • Gauvreau K
        • et al.
        Regional low-flow perfusion versus circulatory arrest in neonates: One-year neurodevelopmental outcome.
        Ann Thorac Surg. 2006; 82: 2207-2213
        • Vuylsteke A
        • Sharples L
        • Charman G
        • et al.
        Circulatory arrest versus cerebral perfusion during pulmonary endarterectomy surgery (PEACOG): A randomised controlled trial.
        Lancet. 2011; 378: 1379-1387
        • Wallois F
        • Mahmoudzadeh M
        • Patil A
        • et al.
        Usefulness of simultaneous EEG–NIRS recording in language studies.
        Brain Lang. 2012; 121: 110-123
        • Tomita Y
        • Vialatte F-B
        • Dreyfus G
        • et al.
        Bimodal BCI using simultaneously NIRS and EEG.
        IEEE Trans Biomed Eng. 2014; 61: 1274-1284
        • Fazli S
        • Mehnert J
        • Steinbrink J
        • et al.
        Enhanced performance by a hybrid NIRS–EEG brain computer interface.
        NeuroImage. 2012; 59: 519-529
        • Rosengarten B
        • Kaps M.
        A simultaneous EEG and transcranial Doppler technique to investigate the neurovascular coupling in the human visual cortex.
        Cerebrovasc Dis. 2010; 29: 211-216

      Linked Article