Inhaled NO at a crossroads in cardiac surgery: current need to improve mechanistic understanding, clinical trial design and scientific evidence.

Inhaled nitric oxide (NO) has been used in pediatric and adult perioperative cardiac intensive care for over three decades. NO is a cellular signaling molecule that induces smooth muscle relaxation in the mammalian vasculature. Inhaled NO has the unique ability to exert its vasodilatory effects in the pulmonary vasculature without any hypotensive side-effects in the systemic circulation. In patients undergoing cardiac surgery, NO has been reported in numerous studies to exert beneficial effects on acutely lowering pulmonary artery pressure and reversing right ventricular dysfunction and/or failure. Yet, various investigations failed to demonstrate significant differences in long-term clinical outcomes. The authors, serving as an advisory board of international experts in the field of inhaled NO within pediatric and adult cardiac surgery, will discuss how the existing scientific evidence can be further improved. We will summarize the basic mechanisms underlying the clinical applications of inhaled NO and how this translates into the mandate for inhaled NO in cardiac surgery. We will move on to the popular use of inhaled NO and will talk about the evidence base of the use of this selective pulmonary vasodilator. This review will elucidate what kind of clinical and biological barriers and gaps in knowledge need to be solved and how this has impacted in the development of clinical trials. The authors will elaborate on how the optimization of inhaled NO therapy, the development of biomarkers to identify the target population and the definition of response can improve the design of future large clinical trials. We will explain why it is mandatory to gain an international consensus for the state of the art of NO therapy far beyond this expert advisory board by including the different major players in the field, such as the different medical societies and the pharma industry to improve our understanding of the real-life effects of inhaled NO in large scale observational studies. The design for future innovative randomized controlled trials on inhaled NO therapy in cardiac surgery, adequately powered and based on enhanced biological phenotyping, will be crucial to eventually provide scientific evidence of its clinical efficacy beyond its beneficial hemodynamic properties.

Impact of Heparin- or Nonheparin-Coated Circuits on Platelet Function in Pediatric Cardiac Surgery.

BACKGROUND: Extracorporeal circuit coating has been shown to improve coagulation derangements during pediatric cardiopulmonary bypass (CPB). This study compared platelet function and hemostasis activation in pediatric cardiac surgery conducted with nonheparin coating (Balance; Medtronic, Minneapolis, MN) versus heparin-based coating (Carmeda; Medtronic) circuits. METHODS: A prospective, randomized, double-center trial was conducted in children older than 1 month undergoing congenital heart disease treatment. Blood samples were collected at baseline (T0), 15 minutes after the start of CPB (T1), and 15 minutes (T2) and 1 hour after the conclusion of CPB (T3). The primary end point of the study was to detect potential differences in ß-thromboglobulin levels between the two groups at T2. Other coagulation and platelet function indicators were analyzed as secondary end points. RESULTS: The concentration of ß-thromboglobulin increased significantly at T2 in both groups. However, there was no significant difference between the groups across all time points. There was no difference in the secondary end points between the groups. CONCLUSIONS: The two circuits showed similar biological effects on platelet function and coagulation. This observation may be useful in optimizing the conduct of CPB and in rationalizing its cost for the treatment of congenital heart disease.

New Modalities for the Administration of Inhaled Nitric Oxide in Intensive Care Units After Cardiac Surgery or for Neonatal Indications: A Prospective Observational Study.

BACKGROUND: Nitric oxide (NO) has a well-known efficacy in pulmonary hypertension (PH), with wide use for 20 years in many countries. The objective of this study was to describe the current use of NO in real life and the gap with the guidelines. METHODS: This is a multicenter, prospective, observational study on inhaled NO administered through an integrated delivery and monitoring device and indicated for PH according to the market authorizations. The characteristics of NO therapy and ventilation modes were observed. Concomitant pulmonary vasodilator treatments, safety data, and outcome were also collected. Quantitative data are expressed as median (25th, 75th percentile). RESULTS: Over 1 year, 236 patients were included from 14 equipped and trained centers: 117 adults and 81 children with PH associated with cardiac surgery and 38 neonates with persistent PH of the newborn. Inhaled NO was initiated before intensive care unit (ICU) admission in 57%, 12.7%, and 38.9% with an initial dose of 10 (10, 15) ppm, 20 (18, 20) ppm, and 17 (11, 20) ppm, and a median duration of administration of 3.9 (1.9, 6.1) days, 3.8 (1.8, 6.8) days, and 3.1 (1.0, 5.7) days, respectively, for the adult population, pediatric cardiac group, and newborns. The treatment was performed using administration synchronized to the mechanical ventilation. The dose was gradually decreased before withdrawal in 86% of the cases according to the usual procedure of each center. Adverse events included rebound effect for 3.4% (95% confidence interval [CI], 0.9%-8.5%) of adults, 1.2% (95% CI, 0.0%-6.7%) of children, and 2.6% (95% CI, 0.1%-13.8%) of neonates and methemoglobinemia exceeded 2.5% for 5 of 62 monitored patients. Other pulmonary vasodilators were associated with NO in 23% of adults, 95% of children, and 23.7% of neonates. ICU stay was respectively 10 (6, 22) days, 7.5 (5.5, 15) days, and 9 (8, 15) days and ICU mortality was 22.2%, 6.2%, and 7.9% for adults, children, and neonates, respectively. CONCLUSIONS: This study confirms the safety of NO therapy in the 3 populations with a low rate of rebound effect. Gradual withdrawal of NO combined with pulmonary vasodilators are current practices in this population. The use of last-generation NO devices allowed good compliance with recommendations.

BNP response during Berlin Heart® support in child: a case report.

A five-year-old boy is presented to Necker hospital for a dilated hypertrophic cardiomyopathy. The implantation of the Berlin Heart Excor® ventricular assist device was performed. This pediatric-sized Berlin Heart® device provides mechanical support for young infants and children of all ages to sustain the failing cardiac circulation over several months, until either recovery of myocardial function or heart transplantation. It remains difficult to identify patients with sufficient recovery and the right time for explantation of the Berlin Heart®. Currently, the decision as to whether a patient should be weaned from the system is mainly based on echocardiographic data. Humoral biomarker, associated to echocardiographic features, would be helpful to identify children who might recover without heart transplantation. We observed that our young patient presented highly elevated BNP plasma levels before mechanical support, and a significant decrease during Berlin Heart® support. Monitoring levels of BNP can be helpful to detect appropriate unloading of the heart as a precondition for recovery. During pump-stop maneuvers, BNP should be regarded in combination with clinical and hemodynamic status of the patients, associated with echocardiographic data.

Extracorporeal Membrane Oxygenation Can Save Lives in Children With Heart or Lung Failure After Liver Transplantation.

The risk of cardiac or lung failure after liver transplantation (LT) is significant. In rare cases, the usual intensive care techniques fail to maintain organ oxygenation with a risk of multiorgan dysfunction. Although extracorporeal membrane oxygenation (ECMO) is a difficult and risky procedure, it can be proposed as life-saving. Four children with either acute pulmonary (three) or cardiac (one) failure after LT, and the criteria that decided the use of ECMO (level of ventilation and results, dosage of inotropic drugs, cardiac ultrasound, blood lactate) were retrospectively reported. These patients, 1-11 years old, were treated with either veno-arterial (three) or veno-venous (one) ECMO. Two experienced a full recovery, with 3 and 6 years of follow-up. Two died of systemic inflammatory response syndrome (SIRS) due to ECMO, and relapse of heart failure due to the underlying disease. Although our patients' survival was only 50%, we showed that ECMO can be useful in children after LT. It should be considered before the development of irreversible multiorgan failure.

A comparison of pulse oximetry and cerebral oxygenation in children with severe sleep apnea-hypopnea syndrome: a pilot study.

Near infrared spectroscopy (NIRS) has been used to assess the impact of obstructive sleep apnea-hypopnea syndrome (OSAHS) on cerebral oxygenation. However, the relationship between the variations in the cerebral tissue oxygen saturation (ΔTOI) and pulse oximetry (ΔSpO2 ) has not been assessed in children with OSAHS. Consecutive clinically stable children with severe OSAHS [apnea-hypopnea index (AHI) >15 events h-1 ] diagnosed during a night-time polygraphy with simultaneous recording of cerebral oxygenation with NIRS (NIRO-200NX, Hamamatsu Photonics KK) were included between September 2015 and June 2016. Maximal ΔSpO2 (SpO2 drop from the value preceding desaturation to nadir) and concomitant variations in transcutaneous carbon dioxide (ΔPtcCO2 ), maximal ΔTOI and maximal variations in cerebral oxygenated (O2 Hb) and deoxygenated (HHb) haemoglobin were reported. The relationships between ΔSpO2 , ΔPtcCO2 and ΔTOI, ΔO2 Hb and ΔHHb were investigated. The data from five children (three boys, aged 9.6 ± 6.7 years, AHI 16-91 events h-1 ) were analysed. Strong correlations were found between ΔSpO2 and ΔTOI (r = 0.887, P < 0.001), but also with ΔO2 Hb and ΔHHb with a particular pattern in the youngest child with a dark skin pigmentation. Mean ΔSpO2 was 20 ± 17% and mean ΔTOI was 8 ± 7%. Maximal ΔSpO2 of approximately 70% were coupled with ΔTOI of no more than 35%. ΔPtcCO2 correlated only weakly with the cerebral oxygenation indexes. This pilot study shows a strong relationship between pulse oximetry and cerebral oxygenation in children with OSAHS, with lower changes in TOI compared to SpO2 . Future studies should address the clinical impact of respiratory events on cerebral oxygenation and its consequences.

Platelet-mapping assay for monitoring antiplatelet therapy during mechanical circulatory support in children: A retrospective observational study.

INTRODUCTION: The complex hemostatic changes associated with Berlin Heart (BH) implantation in children require a challenging antithrombotic treatment. The aim of this retrospective analysis was to evaluate the thromboelastography (TEG)-platelet mapping (PM) assay to monitor antiplatelet therapy in children implanted with a BH. METHODS: TEG-PM was performed in 4 BH-implanted patients receiving dipyridamole and aspirin, and 9 healthy volunteers. Patients' antiplatelet therapy was adjusted to TEG-PM results. Light transmission aggregometry (LTA) was also available for 2 of these patients. RESULTS: Between 2009 and 2014, 4 BH-implanted patients received a dual antiplatelet therapy monitored by TEG-PM. In 2 patients, 18 of 34 tracings were atypical, because the maximum amplitude due to fibrin never stabilized, which made difficult antiplatelet therapy adjustment as recommended by BH's guidelines. To overcome this difficulty, TEG-PM and LTA were next performed in parallel. However, both methods led to different decisions to adjust antiplatelet therapy in 57% of the cases. In order to better understand this atypical tracing, TEG-PM was also performed in 9 volunteers and surprisingly 3 of them had the same atypical tracing. This atypical tracing was corrected by adding apyrase, suggesting that adenosine diphosphate (ADP) participates to spontaneous platelet activation in heparinized samples. In addition, we evidenced a high variability in the responses of TEG-PM with ADP in volunteers. CONCLUSIONS: Antiplatelet therapy monitoring in BH-implanted children remains challenging, as TEG-PM is sensitive to several preanalytical and analytical conditions.

Pharmacokinetics, hemodynamic and metabolic effects of epinephrine to prevent post-operative low cardiac output syndrome in children.

INTRODUCTION: The response to exogenous epinephrine (Ep) is difficult to predict given the multitude of factors involved such as broad pharmacokinetic and pharmacodynamic between-subject variabilities, which may be more pronounced in children. We investigated the pharmacokinetics and pharmacodynamics of Ep, co-administered with milrinone, in children who underwent open heart surgical repair for congenital defects following cardiopulmonary bypass, including associated variability factors. METHODS: Thirty-nine children with a high risk of low cardiac output syndrome were prospectively enrolled. Ep pharmacokinetics, hemodynamic and metabolic effects were analyzed using the non-linear mixed effects modeling software MONOLIX. According to the final model, an Ep dosing simulation was suggested. RESULTS: Ep dosing infusions ranged from 0.01 to 0.23 µg.kg-1.min-1 in children whose weight ranged from 2.5 to 58 kg. A one-compartment open model with linear elimination adequately described the Ep concentration-time courses. Bodyweight (BW) was the main covariate influencing clearance (CL) and endogenous Ep production rate (q0) via an allometric relationship: CL(BWi) = θCL x (BWi)3/4 and q0(BWi) = θq0 x (BWi )3/4. The increase in heart rate (HR) and mean arterial pressure (MAP) as a function of Ep concentration were well described using an Emax model. The effect of age was significant on HR and MAP basal level parameters. Assuming that Ep stimulated the production rate of plasma glucose, the increases in plasma glucose and lactate levels were well described by turnover models without any significant effect of age, BW or exogenous glucose supply. CONCLUSIONS: According to this population analysis, the developmental effects of BW and age explained a part of the pharmacokinetic and pharmacodynamics between-subject variabilities of Ep administration in critically ill children. This approach ultimately leads to a valuable Ep dosing simulation which should help clinicians to determine an appropriate a priori dosing regimen.

Predictive performance of urine neutrophil gelatinase-associated lipocalin for dialysis requirement and death following cardiac surgery in neonates and infants.

BACKGROUND AND OBJECTIVES: Urine neutrophil gelatinase-associated lipocalin (uNGAL) has been shown to accurately predict and allow early detection of AKI, as assessed by an increase in serum creatinine in children and adults. The present study explores the accuracy of uNGAL for the prediction of severe AKI-related outcomes in neonates and infants undergoing cardiac surgery: dialysis requirement and/or death within 30 days. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: Prospective, observational cohort study conducted in a tertiary referral pediatric cardiac intensive care unit, including 75 neonates and 125 infants undergoing surgery with cardiopulmonary bypass between August 1, 2010, and May 31, 2011. Urine samples were collected before surgery and at median of five time points within 48 hours of bypass. Urine NGAL was quantified as absolute concentration, creatinine-normalized concentration, and absolute excretion rate, and a clusterization algorithm was applied to the individual uNGAL kinetics. The accuracy for the prediction of the outcome was assessed using receiver-operating characteristic areas, likelihood ratios, diagnostic odds ratios, net reclassification index, integrated reclassification improvement, and number needed to screen. RESULTS: A total of 1176 urine samples were collected. Of all patients, 8% required dialysis and 4% died. Three clusters of uNGAL kinetics were identified, including patients with significantly different outcomes. The uNGAL level peaked between 1 and 3 hours of bypass and remained high in half of all patients who required dialysis or died. The uNGAL levels measured within 24 hours of bypass accurately predicted the outcome and performed best after normalization to creatinine, with varying cutoffs according to the time elapsed since bypass. The number needed to screen to correctly identify the risk of dialysis or death in one patient varied between 1.5 and 2.6 within 12 hours of bypass. CONCLUSIONS: uNGAL is a valuable predictive tool of dialysis requirement and death in neonates and infants with AKI after cardiac surgery.

Limitations of early serum creatinine variations for the assessment of kidney injury in neonates and infants with cardiac surgery.

BACKGROUND: Changes in kidney function, as assessed by early and even small variations in serum creatinine (ΔsCr), affect survival in adults following cardiac surgery but such associations have not been reported in infants. This raises the question of the adequate assessment of kidney function by early ΔsCr in infants undergoing cardiac surgery. METHODOLOGY: The ability of ΔsCr within 2 days of surgery to assess the severity of kidney injury, accounted for by the risk of 30-day mortality, was explored retrospectively in 1019 consecutive neonates and infants. Patients aged ≤ 10 days were analyzed separately because of the physiological improvement in glomerular filtration early after birth. The Kml algorithm, an implementation of k-means for longitudinal data, was used to describe creatinine kinetics, and the receiver operating characteristic and the reclassification methodology to assess discrimination and the predictive ability of the risk of death. RESULTS: Three clusters of ΔsCr were identified: in 50% of all patients creatinine decreased, in 41.4% it increased slightly, and in 8.6% it rose abruptly. Mortality rates were not significantly different between the first and second clusters, 1.6% [0.0-4.1] vs 5.9% [1.9-10.9], respectively, in patients aged ≤ 10 days, and 1.6% [0.5-3.0] vs 3.8% [1.9-6.0] in older ones. Mortality rates were significantly higher when creatinine rose abruptly, 30.3% [15.1-46.2] in patients aged ≤ 10 days, and 15.1% [5.9-25.5] in older ones. However, only 41.3% of all patients who died had an abrupt increase in creatinine. ΔsCr improved prediction in survivors, but not in patients who died, and did not improve discrimination over a clinical mortality model. CONCLUSIONS: The present results suggest that a postoperative decrease in creatinine represents the normal course in neonates and infants with cardiac surgery, and that early creatinine variations lack sensitivity for the assessment of the severity of kidney injury.

Levosimendan in a neonate with severe coarctation of aorta and low cardiac output syndrome.

We report successful use of levosimendan after failed balloon angioplasty in a critically ill neonate with coarctation of aorta (CoA) and severe low cardiac output syndrome (LCOS). Treatment with levosimendan improved left heart function, and decreased lactate and brain natriuretic peptide levels. To our knowledge, this is the first report on the safe and successful use of levosimendan in the management of LCOS due to severe CoA in a neonate awaiting surgical repair.

Neonatal cardiopulmonary bypass.

Cardiac surgery with cardiopulmonary bypass is routinely used in neonates who require early repair of congenital heart diseases. However, the bypass temperature and use of deep hypothermic circulatory arrest, the composition of the priming and the acceptable degree of hemodilution, the prophylactic use of antifibrinolytic agents and steroids, the choice of myocardial protection, the best PaO2, and even the pump flow, are still subjects of debate, despite major improvements in neonatal bypass over the last decade. Nevertheless, there are some techniques that have reached a near-consensus and are highly recommended in neonates: the use of minaturized bypass circuits to reduce blood product transfusions and inflammation, ultrafiltration, and the continuous monitoring of mixed venous and regional oxygen saturations to assess adequacy of perfusion. Nevertheless, surprisingly many different techniques may lead to the same results and mortality rate. As operative mortality rates have declined, the comparison endpoints between techniques have moved and focus on morbidity rates, extubation delay, ICU and hospital length of stay; in other words, the cost and (of course) the late functional outcome are certainly the new goals of neonatal cardiopulmonary bypass.

Cold histidine-tryptophan-ketoglutarate solution and repeated oxygenated warm blood cardioplegia in neonates with arterial switch operation.

BACKGROUND: The present study aimed to compare myocardial protection, as assessed by cardiac troponin-I release, and short-term outcomes between two groups of neonates undergoing the arterial switch operation (ASO) with either Custodiol cardioplegia (Custodiol HTK, Köhler Chemie GmbH, Bensheim, Germany) or repeated oxygenated warm blood cardioplegia. METHODS: A total of 218 neonates were enrolled retrospectively from February 2007 through February 2011. All analyses were stratified on the type of procedure (ASO±ventricular septal defect closure ± aortic arch repair). Troponin concentrations within the first week of surgery were analyzed using mixed models for repeated measurements. To counteract the confounding effect of the coronary anatomy, a sensitivity analysis was conducted after 1:1 matching. RESULTS: Overall 30 patients had Custodiol cardioplegia, and 188 had warm blood cardioplegia. High-risk coronary anatomy (single right coronary artery giving rise to the left, intramural course) was associated with higher troponin concentrations and a higher 30-day mortality rate postoperatively, and was more prevalent in the Custodiol group when compared with the warm blood cardioplegia group. Postoperative troponin concentrations were higher in the Custodiol group both before (p<0.001) and after matching on the coronary anatomy (p=0.03). The 30-day mortality rate was higher in the Custodiol group, 10% versus 1.1% (p=0.009), but only a nonsignificant trend was noted after matching. CONCLUSIONS: The use of Custodiol cardioplegia in neonates undergoing ASO was associated with a larger troponin release when compared with warm blood cardioplegia, suggesting poor myocardial protection. The difference noted in 30-day mortality was not due to the use of Custodiol.

Early elevation of cardiac troponin I is predictive of short-term outcome in neonates and infants with coronary anomalies or reduced ventricular mass undergoing cardiac surgery.

OBJECTIVE: The present study aimed to assess the usefulness of routine monitoring of cardiac troponin I concentrations within 24 hours of surgery (cTn-I<24h) in neonates and infants undergoing cardiac surgery. METHODS: The added predictive ability of a high peak cTn-I<24h (within the upper quintile per procedure) for a composite outcome, including 30-day mortality and severe morbidity, was assessed retrospectively. The predicted risk for the composite outcome was estimated from a logistic regression model including preoperative and intraoperative variables. Adding a high peak cTn-I<24h to the risk model resulted in reclassification of the predicted risk. It also allowed quantification of the improvement in reclassification and discrimination by the difference between c-indexes, the Net Reclassification and the Integrated Discrimination Indexes (NRI and IDI). RESULTS: Overall, 1023 consecutive patients were included. Adding a high peak cTn-I<24h to the model resulted in no improvement in reclassification or discrimination in the overall population (difference between c-indexes: 0.011 [-0.004 to 0.029], NRI = 0.06, P = .22, IDI = 0.02, P = .06), except in a subgroup of patients undergoing the arterial switch operation with or without ventricular septal defect closure and/or aortic arc repair, anomalous origin of the left coronary artery from the pulmonary artery repair, truncus arteriosus repair, Norwood procedure, and Sano modification, in whom NRI = 0.23 (P = .005) and IDI = 0.05 (P < .001). CONCLUSIONS: Patients with coronary anomalies and patients with reduced ventricular mass should benefit from the routine monitoring of cTn-I concentrations after surgery for congenital cardiac disease.

Early initiation of peritoneal dialysis in neonates and infants with acute kidney injury following cardiac surgery is associated with a significant decrease in mortality.

Association between early renal replacement therapy and better survival has been reported in adults with postoperative kidney injury, but not in children undergoing cardiac surgery. We conducted a retrospective cohort study of 146 neonates and infants requiring peritoneal dialysis following cardiac surgery in a tertiary referral hospital. A propensity score was used to limit selection bias due to timing of dialysis, and included baseline and intraoperative characteristics, requirement for postoperative extracorporeal membrane oxygenation, and creatinine clearance variation. Inverse probability of treatment weighting resulted in good balance between groups for all baseline and intraoperative variables. After weighting, 30-day and 90-day mortality were compared between the 109 patients placed on dialysis early, within the first day of surgery, and those with delayed dialysis, commencing on the second day of surgery or later, using logistic regression and survival analysis. Mortality was 28.1% at 30 days, and was 36.3% during follow-up. Early dialysis was associated with a 46.7% decrease in the 30-day and a 43.5% decrease in the 90-day mortality rate when compared with delayed dialysis. All other short-term outcome variables were similar. Thus, initiation of peritoneal dialysis on the day of or the first day following surgery was associated with a significant decrease in mortality in neonates and infants with acute kidney injury.

High-dose aprotinin, blood product transfusions, and short-term outcome in neonates and infants: a pediatric cardiac surgery center experience.

BACKGROUND: The efficacy of aprotinin, the most popular antifibrinolytic agent in congenital cardiac surgery, was still uncertain in small infants when its prophylactic use was suspended for safety reasons. The aim of this study is to describe associations between the prophylactic use of high-dose aprotinin, the need for blood product transfusions, and short-term outcome in neonates and infants with cardiac surgery. METHODS/MATERIALS: This retrospective study included all patients younger than 1 year undergoing surgery with cardiopulmonary bypass through 42 months, before and after withdrawal of aprotinin. Each patient who received aprotinin was matched with a control with similar baseline and surgical characteristics, who have not received any antifibrinolytic agent. Associations between the use of aprotinin and the exposure to red blood cells, fresh frozen plasma, and platelet transfusions were estimated from a logistic regression model, and the exposure to additional transfusions from a polytomous regression model. RESULTS: Matching resulted in two groups of 283 patients each, well balanced except for the priming volume and the ultrafiltration rate, larger in the aprotinin group. After adjustment for the priming volume and ultrafiltration rate, there was no significant association between the use of aprotinin, the exposure to any blood product transfusion, or the exposure to additional transfusions, the rate of re-exploration for bleeding, and short-term outcome. Two patients in the control group required re-exploration for bleeding. CONCLUSIONS: No association was found between the prophylactic use of aprotinin, blood product transfusions, and short-term outcome in this population of neonates and infants.

High-frequency oscillatory ventilation and short-term outcome in neonates and infants undergoing cardiac surgery: a propensity score analysis.

INTRODUCTION: Experience with high-frequency oscillatory ventilation (HFOV) after congenital cardiac surgery is limited despite evidence about reduction in pulmonary vascular resistance after the Fontan procedure. HFOV is recommended in adults and children with acute respiratory distress syndrome. The aim of the present study was to assess associations between commencement of HFOV on the day of surgery and length of mechanical ventilation, length of Intensive Care Unit (ICU) stay and mortality in neonates and infants with respiratory distress following cardiac surgery. METHODS: A logistic regression model was used to develop a propensity score, which accounted for the probability of being switched from conventional mechanical ventilation (CMV) to HFOV on the day of surgery. It included baseline characteristics, type of procedure and postoperative variables, and was used to match each patient with HFOV with a control patient, in whom CMV was used exclusively. Length of mechanical ventilation, ICU stay and mortality rates were compared in the matched set. RESULTS: Overall, 3,549 neonates and infants underwent cardiac surgery from January 2001 through June 2010, 120 patients were switched to HFOV and matched with 120 controls. After adjustment for the delay to sternal closure, duration of renal replacement therapy, occurrence of pulmonary hypertension and year of surgery, the probability of successful weaning over time and the probability of ICU delivery over time were significantly higher in patients with HFOV, adjusted hazard ratios and 95% confidence intervals: 1.63, 1.17 to 2.26 (P = 0.004). and 1.65, 95% confidence intervals: 1.20 to 2.28 (P = 0.002) respectively. No association was found with mortality. CONCLUSIONS: When commenced on the day of surgery in neonates and infants with respiratory distress following cardiac surgery, HFOV was associated with shorter lengths of mechanical ventilation and ICU stay than CMV.