As the acuity and complexity of pediatric patients with congenital cardiac disease have increased, there are many noncardiac issues that may be present in these patients. These noncardiac problems may affect clinical outcomes in the cardiac intensive care unit and must be recognized and managed. The Pediatric Cardiac Intensive Care Society sought to provide an expert review of some of the most common challenges of the respiratory, gastrointestinal, hematological, renal, and endocrine systems in pediatric cardiac patients. This review provides a brief overview of literature available and common practices.
BenavidezOJGauvreauKDel NidoPBachaEJenkinsKJ. Complications and risk factors for mortality during congenital heart surgery admissions. Ann Thorac Surg. 2007;84(1):147–155.
2.
SkinnerMLHalsteadLARubinsteinCSAtzAMAndrewsDBradleySM. Laryngopharyngeal dysfuction after the norwood procedure. J Thorac Cardiovasc Surg. 2005;130(5):1293–301.
LawMAMcMahonWSHockMKZaccagniHJBorasionSAltenJA. Balloon angioplasty for the treatment of left innominate vein obstruction related chylothorax after congenital heart surgery. Congenit Heart Dis. 2015;10(4):155–163.
5.
LopezCMGarcia-GueretaL. Community-acquired respiratory infections in young children with congenital heart disease in the palivizumab era. Pediatr Infect Dis J. 2010;29(12):1077–1082.
6.
MoynihanKBarlowAAlphonsoN. Impact of viral respiratory pathogens on outcomes after pediatric cardiac surgery. Pediatr Crit Care Med. 2017;18(3):219–227.
7.
WilsonMNBergeronLMKakadeA. Airway management following pediatric cardiothoracic surgery. Otolaryngol Head Neck Surg. 2013;149(4):621–627.
8.
ZuckerbergALefton-GreifM. Nutrition and Metabolism in the Critically Ill Child with Cardiac Disease. In NicholsDUngerleiderRSpevakP. eds, Critical Heart Disease in Infants and Children. Philadelphia, PA: Mosby; 2013:379–403.
9.
SavlaJJItkinMRossanoJWDoriY. Post-operative chylothorax in patients with congenital heart disease. J Am Coll Cardiol. 2017;69(19):2410–2422.
10.
MukherjeeDZhangYChangDCVricellaLABrennerJIAbdullahF. Outcomes analysis of necrotizing enterocolitis within 11 958 neonates undergoing cardiac surgical procedures. Arch Surg. 2010;145(4):389–392.
11.
PolinRAPollackPFBarlowB. Necrotizing enterocolitis in term infants. J Pediatr. 1976;89(3):460–462.
12.
ChristensenRDLambertDKBaerVLGordonPV. Necrotizing enterocolitis in term infants. Clin Perinatol. 2013;40(1):69–78.
13.
MottaCScottWMahonyL. The association of congenital heart disease with necrotizing enterocolitis in preterm infants: a birth cohort study. J Perinatol. 2015;35(11):949–953.
14.
NatarajanGAnneSRAggarwalS. Outcomes of congenital heart disease in late preterm infants: double jeopardy?Acta Paediatr. 2011;100(8):1104–1107.
15.
McElhinneyDBHedrickHLBushDM. Necrotizing enterocolitis in neonates with congenital heart disease: risk factors and outcomes. Pediatrics. 2000;106(5):1080–1087.
16.
JeffriesHEWellsWJStarnesVAWetzelRCMoromisatoDY. Gastrointestinal morbidity after Norwood palliation for hypoplastic left heart syndrome. Ann Thorac Surg. 2006;81(3):982–987.
17.
SlickerJSables-BausSLambertLM. Perioperative feeding approaches in single ventricle infants: a survey of 46 centers. Congenit Heart Dis. 2016;11(6):707–715.
18.
HowleyLWKaufmanJWymoreE. Enteral feeding in neonates with prostaglandin-dependent congenital cardiac disease: international survey on current trends and variations in practice. Cardiol Young. 2012;22(2):121–127.
19.
FivezTKerklaanDMesottenD. Early versus late parenteral nutrition in critically ill children. N Engl J Med. 2016;374(12):1111–1122.
20.
WillisLThureenPKaufmanJWymoreESkillmanHda CruzE. Enteral feeding in prostaglandin-dependent neonates: is it a safe practice?J Pediatr.2008;153(6):867–869.
21.
BeckerKCHornikCPCottenCM. Necrotizing enterocolitis in infants with ductal-dependent congenital heart disease. Am J Perinatol. 2015;32(7):633–638.
22.
BraudisNJCurleyMABeaupreK. Enteral feeding algorithm for infants with hypoplastic left heart syndrome poststage I palliation. Pediatr Crit Care Med. 2009;10(4):460–466.
23.
SimsicJMCarpenitoKRKirchnerK. Reducing variation in feeding newborns with congenital heart disease. Congenit Heart Dis. 2017;12(3):275–281.
24.
del CastilloSLMcCulleyMEKhemaniRG. Reducing the incidence of necrotizing enterocolitis in neonates with hypoplastic left heart syndrome with the introduction of an enteral feed protocol. Pediatr Crit Care Med. 2010;11(3):373–377.
25.
LiSKrawczeskiCDZappitelliM. Incidence, risk factors, and outcomes of acute kidney injury after pediatric cardiac surgery—a prospective multicenter study. Crit Care Med. 2011;39(6):1493.
26.
BlinderJJGoldsteinSLLeeV-V. Congenital heart surgery in infants: effects of acute kidney injury on outcomes. J Thorac Cardiovasc Surg. 2012;143(2):368–374.
27.
MorganCJZappitelliMRobertsonCM. Risk factors for and outcomes of acute kidney injury in neonates undergoing complex cardiac surgery. J Pediatr. 2013;162(1):120–127.e121.
28.
KrawczeskiCDGoldsteinSLWooJG. Temporal relationship and predictive value of urinary acute kidney injury biomarkers after pediatric cardiopulmonary bypass. J Am Coll Cardiol. 2011;58(22):2301–2309.
29.
MachadoMNNakazoneMAMaiaLN. Acute kidney injury based on KDIGO (Kidney Disease Improving Global Outcomes) criteria in patients with elevated baseline serum creatinine undergoing cardiac surgery. Rev Bras Cir Cardiovasc. 2014;29(3):299–307.
30.
LassniggASchmidERHiesmayrM. Impact of minimal increases in serum creatinine on outcome in patients after cardiothoracic surgery: do we have to revise current definitions of acute renal failure?. Crit Care Med. 2008;36(4):1129–1137.
31.
CooperDSClaesDGoldsteinSL. Novel urinary biomarkers remain elevated years after acute kidney injury following cardiac surgery in children. J Am Coll Cardiol. 2013;61(10_S).
32.
KellumJALameireN; KDIGO AKI Guideline Work Group. Diagnosis, evaluation and management of acute kidney injury: a KDIGO summary (part 1). Crit Care. 2013;17(1):204.
33.
SutherlandSMZappitelliMAlexanderSR. Fluid overload and mortality in children receiving continuous renal replacement therapy: the prospective pediatric continuous renal replacement therapy registry. Am J Kidney Dis. 2010;55(2):316–325.
34.
HassingerABWaldELGoodmanDM. Early postoperative fluid overload precedes acute kidney injury and is associated with higher morbidity in pediatric cardiac surgery patients. Pediatr Crit Care Med. 2014;15(2):131–138.
35.
WilderNSYuSDonohueJE. Fluid overload is associated with late poor outcomes in neonates following cardiac surgery. Pediatr Crit Care Med. 2016;17(5):420–427.
36.
ZappitelliMBernierP-LSaczkowskiRS. A small post-operative rise in serum creatinine predicts acute kidney injury in children undergoing cardiac surgery. Kidney Int. 2009;76(8):885–892.
37.
KwiatkowskiDMGoldsteinSLKrawczeskiCD. Biomarkers of acute kidney injury in pediatric cardiac patients. Biomarkers. 2012;6(3):273–282.
38.
ChawlaLSKellumJA. Acute kidney injury in 2011: biomarkers are transforming our understanding of AKI. Nat Rev Nephrol. 2012;8(2):68–70.
39.
VanmassenhoveJVanholderRNaglerEVan BiesenN. Urinary and serum biomarkers for the diagnosis of acute kidney injury: an in-depth review of the literature. Nephrol Dial Transplant. 2013;28(2):254–273.
40.
HassingerABBackerCLLaneJCHaymandSWangDWaldEL. Predictive power of serum cystatin C to detect acute kidney injury and pediatric-modified RIFLE class in children undergoing cardiac surgery. Pediatr Crit Care Med. 2012;13(4):435–440.
41.
SpahillariAParikhCRSintK; TRIBE-AKI Consortium. Serum cystatin C–versus creatinine-based definitions of acute kidney injury following cardiac surgery: a prospective cohort study. Am J Kidney Dis. 2012;60(6):922–929.
42.
MeerschMSchmidtCVan AkenH. Urinary TIMP-2 and IGFBP7 as early biomarkers of acute kidney injury and renal recovery following cardiac surgery. PLoS One. 2014;9(3):e93460.
43.
MeerschMSchmidtCVan AkenH. Validation of cell-cycle arrest biomarkers for acute kidney injury after pediatric cardiac surgery. PLoS One. 2014;9(10).
44.
BasuRKWongHRKrawczeskiCD. Combining functional and tubular damage biomarkers improves diagnostic precision for acute kidney injury after cardiac surgery. J Am Coll Cardiol. 2014;64(25):2753–2762.
45.
Stafford-SmithMPodgoreanuMSwaminathanM; Perioperative Genetics and Safety Outcome Study (PEGASUS) Investigative Team. Association of genetic polymorphisms with risk of renal injury after coronary bypass graft surgery. Am J Kidney Dis. 2005;45(3):519–530.
46.
Cardinal-FernándezPFerrueloAMartín-PellicerA. Genetic determinants of acute renal damage risk and prognosis: a systematic review. Med Intensiva (English Edition). 2012;36(9):626–633.
47.
CostelloJMThiagarajanRRDionneRE. Initial experience with fenoldopam after cardiac surgery in neonates with an insufficient response to conventional diuretics. Pediatr Crit Care Med. 2006;7(1):28–33.
48.
AxelrodDMAnglemyerATSherman-LevineSF. Initial experience using aminophylline to improve renal dysfunction in the pediatric cardiovascular ICU. Pediatr Crit Care Med. 2014;15(1):21–27.
49.
KwiatkowskiDMAxelrodDMSutherlandSMTesoroTMKrawczeskiCD. Dexmedetomidine is associated with lower incidence of acute kidney injury after congenital heart surgery. Pediatr Crit Care Med. 2016;17(2):128–134.
50.
AxelrodDMSutherlandSMAnglemyerA. A double-blinded, randomized, placebo-controlled clinical trial of aminophylline to prevent acute kidney injury in children following congenital heart surgery with cardiopulmonary bypass. Pediatr Crit Care Med. 2016;17(2):135–143.
CostelloJMMastersonCDAllanCK. Impact of empiric nesiritide or milrinone infusion on early postoperative recovery following Fontan surgery: a randomized, double-blind, placebo-controlled trial. Circ Heart Fail. 2014;7(4):596–604.
53.
AhmadTJacksonKRaoVS. Worsening renal function in acute heart failure patients undergoing aggressive diuresis is not associated with tubular injury. Circulation. 2018:137(19):2016-2028.
54.
SampathSMoranJLGrahamPLRockliffSBerstenADAbramsKR. The efficacy of loop diuretics in acute renal failure: assessment using Bayesian evidence synthesis techniques. Crit Care Med. 2007;35(11):2516–2524.
55.
MehtaRLPascualMTSorokoS. Diuretics, mortality, and nonrecovery of renal function in acute renal failure. JAMA. 2002;288(20):2547–2553.
SasserWCDabalRJAskenaziDJ. Prophylactic peritoneal dialysis following cardiopulmonary bypass in children is associated with decreased inflammation and improved clinical outcomes. Congenit Heart Dis. 2014;9(2):106–115.
BojanMGioanniSVouhéPRJournoisDPouardP. Early initiation of peritoneal dialysis in neonates and infants with acute kidney injury following cardiac surgery is associated with a significant decrease in mortality. Kidney Int. 2012;82(4):474–481.
60.
StrombergDFraserCDJrSorofJM. Peritoneal dialysis: an adjunct to pediatric postcardiotomy fluid management. Tex Heart Inst J. 1997;24(4):269.
61.
AlkanTAkçevinATürkogluH. Postoperative prophylactic peritoneal dialysis in neonates and infants after complex congenital cardiac surgery. ASAIO J. 2006;52(6):693–697.
62.
ChienJCHwangBTWengZCMengLCLeePC. Peritoneal dialysis in infants and children after open heart surgery. Pediatr Neonatol. 2009;50(6):275–279.
63.
KwiatkowskiDMMenonSKrawczeskiCD. Improved outcomes with peritoneal dialysis catheter placement after cardiopulmonary bypass in infants. J Thoracic Cardiovasc Surg. 2015;149(1):230–236.
64.
AverbuchNBirkEFrenkelG. Percutaneous intraperitoneal catheters in neonates following open heart surgery. J Intensive Care Med. 2014;29(3):160–164.
65.
KwiatkowskiDMGoldsteinSLCooperDSNelsonDPMoralesDLKrawczeskiCD. Peritoneal dialysis vs furosemide for prevention of fluid overload in infants after cardiac surgery: a randomized clinical trial. JAMA Pediatrics. 2017;171(4):357–364.
66.
VinchiFDe FranceschiLGhigoA. Hemopexin therapy improves cardiovascular function by preventing heme-induced endothelial toxicity in mouse models of hemolytic diseases. Circulation. 2013;127(12):1317–1329.
67.
DaQTeruyaMGuchhaitPTeruyaJOlsonJSCruzMA. Free hemoglobin increases von Willebrand factor-mediated platelet adhesion in vitro: implications for circulatory devices. Blood. 2015;126(20):2338–2341.
68.
TranPLPietropaoloMGValerioL. Hemolysate-mediated platelet aggregation: an additional risk mechanism contributing to thrombosis of continuous flow ventricular assist devices. Perfusion. 2016;31(5):401–408.
69.
SmithAMcCullohRJ. Hemopexin and haptoglobin: allies against heme toxicity from hemoglobin not contenders. Front Physiol. 2015;6:187.
70.
LimSKFerraroBMooreKHalliwellB. Role of haptoglobin in free hemoglobin metabolism. Redox Rep. 2001;6(4):219–227.
71.
Vermeulen WindsantICde WitNCSertorioJT. Hemolysis during cardiac surgery is associated with increased intravascular nitric oxide consumption and perioperative kidney and intestinal tissue damage. Front Physiol. 2014;5:340.
72.
SulkowskiJPCooperJNPearsonEG. Hemolysis-associated nitric oxide dysregulation during extracorporeal membrane oxygenation. J Extra Corpor Technol. 2014;46(3):217–223.
73.
RicciZPezzellaCRomagnoliS. High levels of free haemoglobin in neonates and infants undergoing surgery on cardiopulmonary bypass. Interact Cardiovasc Thorac Surg. 2014;19(2):183–187.
74.
MamikonianLSMamoLBSmithPBKooJLodgeAJTuriJL. Cardiopulmonary bypass is associated with hemolysis and acute kidney injury in neonates, infants, and children. Pediatr Crit Care Med. 2014;15(3):e111–e119.
75.
GbadegesinRZhaoSCharpieJBrophyPDSmoyerWELinJJ. Significance of hemolysis on extracorporeal life support after cardiac surgery in children. Pediatr Nephrol. 2009;24(3):589–595.
76.
SteinhornRHIsham-SchopfBSmithCGreenTP. Hemolysis during long-term extracorporeal membrane oxygenation. J Pediatr. 1989;115(4):625–630.
77.
BetrusCRemenappRCharpieJ. Enhanced hemolysis in pediatric patients requiring extracorporeal membrane oxygenation and continuous renal replacement therapy. Ann Thorac Cardiovasc Surg. 2007;13(6):378–383.
78.
BarrettCSJaggersJJCookEF. Pediatric ECMO outcomes: comparison of centrifugal versus roller blood pumps using propensity score matching. ASAIO J. 2013;59(2):145–151.
79.
ByrnesJMcKamieWSwearingenC. Hemolysis during cardiac extracorporeal membrane oxygenation: a case-control comparison of roller pumps and centrifugal pumps in a pediatric population. ASAIO J. 2011;57(5):456–461.
80.
CorneliusAMRileyJBSchearsGJBurkhartHM. Plasma-free hemoglobin levels in advanced vs. conventional infant and pediatric extracorporeal life support circuits. J Extra Corpor Technol. 2013;45(1):21–25.
81.
LouSMacLarenGBestDDelzoppoCButtW. Hemolysis in pediatric patients receiving centrifugal-pump extracorporeal membrane oxygenation: prevalence, risk factors, and outcomes. Crit Car Med. 2014;42(5):1213–1220.
82.
NealJRQuintanaEPikeRBHoyerJDJoyceLDSchearsG. Using daily plasma-free hemoglobin levels for diagnosis of critical pump thrombus in patients undergoing ECMO or VAD support. J Extra Corpor Technol. 2015;47(2):103–108.
83.
LubanNLWongECHenrich LoboRParyPDukeS. Intravenous immunoglobulin-related hemolysis in patients treated for Kawasaki disease. Transfusion. 2015;55(suppl 2):S90–S94.
84.
PendergrastJWillie-RamharackKSampsonLLarocheVBranchDR. The role of inflammation in intravenous immune globulin-mediated hemolysis. Transfusion. 2015;55(suppl 2):S65–S73.
85.
L’AcquaCBandyopadhyaySFrancisRO. Red blood cell transfusion is associated with increased hemolysis and an acute phase response in a subset of critically ill children. Am J Hematol. 2015;90(10):915–920.
86.
XuZYangMWangXWangZ. The influence of different operating conditions on the blood damage of a pulsatile ventricular assist device. ASAIO J. 2015;61(6):656–663.
87.
LevinAPSaeedOWilleyJZ. Watchful waiting in continuous-flow left ventricular assist device patients with ongoing hemolysis is associated with an increased risk for cerebrovascular accident or death. Circ Heart Fail. 2016;9(5):pii: e002896.
88.
WhitsonBAEckmanPKamdarF. Hemolysis, pump thrombus, and neurologic events in continuous-flow left ventricular assist device recipients. Ann Thorar Surg. 2014;97(6):2097–2103.
89.
LamBKCosgroveDMBhudiaSKGillinovAM. Hemolysis after mitral valve repair: mechanisms and treatment. Ann Thorac Surg. 2004;77(1):191–195.
90.
NaikAVBhalgatPSBhadaneNSJoshiSV. Very early onset traumatic hemolysis following mitral valve repair in a pediatric patient. Indian Heart J. 2016;68(suppl 2):S237–S240.
91.
GuptaUValenciaGKhanMSMoralesM. A rare case of hemolytic anemia in a pediatric patient due to ring dehiscence after mitral valve repair: utility of real-time three-dimensional imaging and management. Pediatr Cardiol. 2014;35(1):180–182.
92.
HaasNAKockLBertramH. Interventional VSD-closure with the Nit-Occlud(R) Le VSD-Coil in 110 patients: early and midterm results of the EUREVECO-Registry. Pediatr Cardiol. 2017;38(2):215–227.
93.
MulvaneySGrechV. Haemolysis after Amplatzer device closure of ventricular septal defect. Images Paediatr Cardiol. 2007;9(3):4–5.
94.
RaoDSBarikRSiva PrasadA. Hemolysis induced by PMIVSD occluder. Indian Heart J. 2016;68(suppl 2):S60–S63.
95.
HayesCShafiHMasonHKlapperE. Successful reduction of plasma free-hemoglobin using therapeutic plasma exchange: a case report. Transfus Apher Sci. 2016;54(2):253–255.
96.
GrawJAMayeurCRosalesI. Haptoglobin or hemopexin therapy prevents acute adverse effects of resuscitation after prolonged storage of red cells. Circulation. 2016;134(13):945–960.
97.
IrwinDCBaekJHHassellK. Hemoglobin-induced lung vascular oxidation, inflammation, and remodeling contribute to the progression of hypoxic pulmonary hypertension and is attenuated in rats with repeated-dose haptoglobin administration. Free Radic Biol Med. 2015;82:50–62.
98.
HoffmanTMWernovskyGAtzAM. Efficacy and safety of milrinone in preventing low cardiac output syndrome in infants and children after corrective surgery for congenital heart disease. Circulation. 2003;107(7):996–1002.
99.
WernovskyGWypijDJonasRA. Postoperative course and hemodynamic profile after the arterial switch operation in neonates and infants. A comparison of low-flow cardiopulmonary bypass and circulatory arrest. Circulation. 1995;92(8):2226–2235.
100.
Soto-RiveraCLAgusMSDSawyerJEMacraeDJ. Pediatric cardiac intensive care society 2014 consensus statement: pharmacotherapies in cardiac critical care hormone replacement therapy. Pediatr Crit Care. 2016;17(3):S59–S68.
101.
WaldELPrezeEEickhoffJCBackerCL. The effect of cardiopulmonary bypass on the hypothalamic-pituitary-adrenal axis in children. Pediatr Crit Care. 2011;12(2):190–196.
102.
ShoreSNelsonDPPearlJM. Usefulness of corticosteroid therapy in decreasing epinephrine requirements in critically ill infants with congenital heart disease. Am J Cardiol. 2001;88(5):591–594.
103.
SuominenPKDickersonHAMoffettBS. Hemodynamic effects of rescue protocol hydrocortisone in neonates with low cardiac output syndrome after cardiac surgery. Pediatr Crit Care. 2005;6(6):655–659.
104.
NeunhoefferFRenkHHofbeckM. Safety, efficacy and response to a hydrocortisone rescue therapy protocol in children with refractory hypotension after cardiopulmonary bypass. Pediatr Cardiol. 2015;36(3):640–645.
105.
AndoMParkIWadaNTakahashiY. Steroid supplementation: a legitimate pharmacotherapy after neonatal open heart surgery. Ann of Thoracic Surg. 2005;80(5):1672–1678.
106.
RobertSMBorasinoSDabalRJClevelandDCHockKMAltenJA. Postoperative hydrocortisone infusion reduces the prevalence of low cardiac output syndrome after neonatal cardiopulmonary bypass. Pediatr Crit Care. 2015;16(7):629.
107.
MastropietroCWBarrettRDavalosMC. Cumulative corticosteroid exposure and infection risk after complex pediatric cardiac surgery. Ann of Thorac Surg. 2013;95(6):2133.
108.
PurdyIBSinghNBrownWLVangalaSDevaskarUP. Revisiting early hypothyroidism screening in infants with Down syndrome. J Perinatol. 2014;34(12):936–940.
109.
PortmanMAFearneyhoughCNingX-HDuncanBWRosenthalGLLupinettiFM. Triiodothyronine repletion in infants during cardiopulmonary bypass for congenital heart disease. J Thorac Cardiovasc Surg. 2000;120(3):604–608.
110.
BaysalASasmazelAYildirimAKocakTSunarHZeybekR. The effects of thyroid hormones and interleukin-8 levels on prognosis after congenital heart surgery. Turk Kardiyol Dem Ars. 2010;38(8):537–543.
111.
SouzaTFHoshalSGAlbeirutiR. Transient secondary hypothyroidism and thyroid hormone replacement therapy in pediatric postoperative cardiopulmonary bypass. Curr Cardiol Rev2018.
