Neonatal Cardiopulmonary Bypass Research Articles

Coagulation Profile of Neonates Undergoing Arterial Switch Surgery With Crystalloid Priming of the Cardiopulmonary Bypass Circuit

ObjectivesThe aim was to evaluate changes in the coagulation profile of cyanotic neonates, to analyze the effects of cardiopulmonary bypass (CPB) with crystalloid priming on their coagulation status, and to determine factors predicting a requirement for hemostasis-derived transfusion. DesignRetrospective cohort. SettingSingle-center, tertiary academic hospital. ParticipantsIn total, 100 consecutive neonates who underwent arterial switch surgery between December 2014 and June 2020. InterventionsRotational thromboelastometry (ROTEM) and coagulation parameters before surgery and before termination of CPB were evaluated. Transfusion of platelets, fresh frozen plasma, and fibrinogen, defined as hemostasis-derived transfusion (HD transfusion), were determined. Patients with and without HD transfusion were compared to identify predictors. Measurements and Main ResultsAfter CPB, fibrinogen was reduced by 24.5% (interquartile range [IQR] 8.9-32.1) to 201 mg/dL (IQR 172-249), resulting in a reduction of FIBTEM A10 by 20% (1.8-33.3) to 8 mm (6-11). The platelet count decreased by a median of 47.2% (25.6-61.3) to 162 × 103/µL (119-215). However, the median fibrinogen concentration and platelet count remained within normal range. Neonates with abnormal ROTEM results were more likely to receive HD transfusions. The HD transfusions were more likely with lower preoperative FIBTEM maximum clot firmness values (p = 0.031), lower hemoglobin concentrations at termination of CPB (p = 0.02), and longer CPB duration (p = 0.017). Perioperative hemostasis without any HD transfusion was achieved in 64 neonates. ConclusionsGuidance from ROTEM analyses facilitates hemostasis management after neonatal CPB. Circuit miniaturization with transfusion-free CPB is associated with acceptable changes in ROTEM in most patients, and allows sufficient hemostasis without any HD transfusions in most patients.

The lower threshold of hypothermic oxygen delivery to prevent neonatal acute kidney injury.

Oxygen delivery during cardiopulmonary bypass (CPB) is closely related to postoperative acute kidney injury (AKI). The value of critical indexed oxygen delivery (DO2i) is a key indicator to reflect oxygen supply in cardiovascular surgery. However, the target DO2i value for neonates undergoing hypothermic CPB remains unclear. One hundred and twenty-six consecutive newborns (≤28 days) undergoing arterial switch operations were retrospectively divided into two groups according to AKI occurrence. Baseline characteristics, intraoperative variables, and clinical outcomes were collected. Multivariate logistic regression analysis and receiver-operating characteristic curve were performed to investigate the association between DO2i and AKI. Neonates in the no-AKI group (n = 67) had significantly higher nadir bypass flow and DO2i during the hypothermic phase compared with the AKI group (n = 59). AKI group had remarkably higher incidences of hepatic dysfunction and peritoneal dialysis requirement compared with newborns without AKI. Mixed venous oxygen saturation (SvO2) was comparable between the two groups. Base excess (BE)(P = 0.011) value during the hypothermic phase of the AKI group was higher than the no-AKI group. Multivariate analysis showed that hypothermic DO2i was negatively associated with AKI. The cut-off value of hypothermic DO2i was 269 mL min-1 m-2. The importance of hypothermic DO2i should be highlighted, even when SvO2 was satisfactory. A lower threshold of DO2i > 269 mL min-1 m-2 may help protect neonates from the risk of postoperative AKI. The key message of our article is that the lower threshold of DO2i > 269 mL min-1 m-2 may help protect neonates from the risk of AKI after on-pump hypothermic cardiovascular surgery. The critical DO2i value for neonates undergoing hypothermic CPB remains unclear, and our study may add new evidence for this matter based on the 6-year experience of our center. In this study, the lowest critical value of DO2i in neonatal hypothermic CPB is determined for the first time, which provides a reference for intra-CPB management strategy to improve the postoperative outcomes of newborns.

Plasma Proteolytic Cascade Activation and Control during Neonatal Cardiopulmonary Bypass Surgery

Introduction: As blood passes through the cardiopulmonary bypass (CPB) circuit, foreign surface exposure activates cells producing tissue factor expression and microparticles that induce procoagulant and pro-inflammatory responses. In the neonate, higher pump flow rates, longer bypass times and decreased levels of endogenous plasma proteins, make plasma proteolytic cascades vulnerable to uncontrolled activation. Changes in the plasma concentrations and structures of five plasma protease inhibitors regulating coagulation, inflammation, fibrinolysis and complement were examined in neonates undergoing CPB to understand how deregulation of proteolytic cascades may contribute to excessive bleeding, which continues to be a common problem in these patients.Methods: Blood samples were obtained at baseline (Draw 1), on CPB (Draw 2), following protamine (Draw 3) and in the intensive care unit (Draw 4). Plasma total protein and the concentrations of the serpins, antitrypsin, antithrombin, antiplasmin and C1-inhibitior, and the Kunitz inhibitor, tissue factor pathway inhibitor (TFPI) were measured. Serpin structures were examined using transverse urea gradient (TUG) gels. TFPI degradation was examined by SDS-PAGE. Excessive bleeding was defined by meeting one or more of the following: ≥ 84 mL/kg total chest tube output (CTO) in the first 24 hours, ≥ 7 mL/kg/hr CTO for ≥2 consecutive hours in the first 12 hours, or re-exploration in the first 24 hours for bleeding or tamponade.Results: Of 44 neonates, 16 (36%) were classified as bleeders. The total plasma protein concentration was 60% that of adults at Draw 1. Adult plasma transfusion increased total protein by 43%, 59% and 32% at Draws 2, 3 and 4. The concentration of each inhibitor changed over the course of surgery (p<0.001 for all). Antitrypsin, an inhibitor of inflammation, and C1-inhibitor, an inhibitor of complement, are acute phase proteins. C1-Inhibitor increased in neonates by 56% and 81% at Draws 2 and 3, returning to baseline at Draw 4. However, antitrypsin decreased 30% between Draws 1 and 2, and remained low at Draws 3 and 4, suggesting it is consumed during surgery. Antithrombin and antiplasmin inhibit coagulation and fibrinolysis, respectively. Changes in antithrombin concentration mirrored those of total protein, while antiplasmin remained stable or decreased, again suggesting consumption. TFPI inhibits coagulation. It is a heparin-releasable protein that increased 5-fold at Draw 2, and remained 4-fold and 3-fold elevated following protamine at Draws 3 and 4. Comparisons of neonates who bled with those who did not revealed that antithrombin was higher in those bleeding at Draw 2 (p=0.031). There was no difference between groups in other inhibitors. TUG gels produce a unique unfolding signature for each serpin and differentiate virgin, proteolytically cleaved, protease complexed and polymerized forms. TUG signatures revealed only virgin antitrypsin, C1-inhibitor and antiplasmin at all 4 draws. Heparin administration at Draw 2 produced antithrombin-FXa and antithrombin-thrombin complexes, as well as proteolytically cleaved forms of antithrombin. These were also variably present at Draws 3 and 4. Western blots for TFPI revealed the appearance of degraded forms at Draws 3 and 4 in some patients.Conclusions: C1-inhibitor concentration increased during surgery, consistent with it being an acute phase reactant. Changes in antithrombin concentration mirrored the conversion to adult plasma, while antitrypsin and antiplasmin decreased in concentration suggesting consumption and clearance. Structural analysis of serpins, other than antithrombin, revealed only the virgin form, indicating the absence of widespread, unregulated proteolysis by plasma proteolytic cascades. Antithrombin displayed complexed and cleaved forms following heparin administration, consistent with its role as an anticoagulant during surgery. TFPI increased 5-fold following heparin administration and remained 3-fold elevated at Draw 4. A portion of this elevation could be attributed to proteolytic degradation, but it is unclear why levels remained so high following protamine reversal. TFPI levels were not different between neonates who bled or not. In contrast, elevated antithrombin levels at Draw 2 were more common in neonates who bled, suggesting that administration of recombinant antithrombin may worsen bleeding in these patients. DisclosuresMast:Novo Nordisk: Research Funding.

The Characterization of Postoperative Mechanical Respiratory Requirement in Neonates and Infants Undergoing Cardiac Surgery on Cardiopulmonary Bypass in a Single Tertiary Institution

Although neonates and infants undergoing cardiac surgery on cardiopulmonary bypass (CPB) are at high risk of developing perioperative morbidity and mortality, including lung injury, the intraoperative profile of lung injury in this cohort is not well-described. Given that the postoperative course of patients in the pediatric cardiac surgical arena has become increasingly expedited, the objective of this study was to characterize the profiles of postoperative mechanical ventilatory support in neonates and infants undergoing cardiac surgery on CPB and to examine the characteristics of lung mechanics and lung injury in this patient population who are potentially amendable to early postoperative recovery in a single tertiary pediatric institution. A retrospective data analysis of neonates and infants who underwent cardiac surgery on cardiopulmonary bypass. A single-center, university teaching hospital. The study included 328 neonates and infants who underwent cardiac surgery on cardiopulmonary bypass. A subset of 128 patients were studied: 58 patients undergoing ventricular septal defect (VSD) repair, 36 patients undergoing complete atrioventricular canal (CAVC) repair, and 34 patients undergoing bidirectional Glenn (BDG) shunt surgery. Of the entire cohort, 3.7% experienced in-hospital mortality. Among all surgical procedures, VSD repair (17.7%) was the most common, followed by CAVC repair (11.0%) and BDG shunt surgery (10.4%). Of patients who underwent VSD repair, CAVC repair, and BDG shunt surgery, 65.5%, 41.7%, and 67.6% were off mechanical ventilatory support within 24 hours postoperatively, respectively. In all three of the surgical repairs, lung compliance decreased after CPB compared to pre-CPB phase. Sixty point three percent of patients with VSD repair and 77.8% of patients with CAVC repair showed a PaO2/FIO2 (P/F) ratio of <300 after CPB. Post- CPB P/F ratios of 120 for VSD patients and 100 for CAVC patients were considered as optimal cutoff values to highly predict prolonged (>24 hours) postoperative mechanical ventilatory support. A higher volume of transfused platelets also was associated with postoperative ventilatory support ≥24 hours in patients undergoing VSD repair, CAVC repair, and BDG shunt surgery. There was a high incidence of lung injury after CPB in neonates and infants, even in surgeries amendable for early recovery. Given that CPB-related factors (CPB duration, crossclamp time) and volume of transfused platelet were significantly associated with prolonged postoperative ventilatory support, the underlying cause of cardiac surgery-related lung injury can be multi-factorial.

Pediatric Extracorporeal Cardiopulmonary Resuscitation ELSO Guidelines.

Pediatric Extracorporeal Cardiopulmonary Resuscitation ELSO Guidelines.

Postoperative Improvement of Brain Maturation in Infants With Congenital Heart Disease

Children with severe congenital heart disease are at risk for neurodevelopmental impairments. We examined brain maturation in infants undergoing neonatal cardiopulmonary bypass surgery or hybrid procedure for hypoplastic left heart syndrome compared to controls. This is a prospective cohort study on term-born infants with congenital heart disease with cerebral MRI pre- and postoperatively. Healthy infants served as controls. Brain maturation was measured using a semiquantitative scoring system. The progress of brain maturation from the preoperative to postoperative MRI within patients was compared. Neurodevelopment was assessed at 1 year with the Bayley Scales of Infant and Toddler Development III. A total of 92 patients with congenital heart disease and 46 controls were studied. Median total maturation score in patients was 12 (interquartile range 10.6-13.0) preoperatively and 14 (12.0-15.0) postoperatively, in controls it was 14 (13.0-15.0). Median time interval between scans was 19 days (interquartile range 14-26). After correction for postmenstrual age at MRI, the pre- and postoperative maturation score was lower in patients compared to controls (preoperative P = 0.01, postoperative P = 0.03) and increased between pre- and postoperative assessment (P ≤ 0.001). Brain maturation scores did not correlate with neurodevelopmental outcome at 1 year, when corrected for socioeconomic status and postmenstrual age at MRI. This study confirms delayed brain maturation in children with congenital heart disease, and despite neonatal cardiac bypass surgery followed by postoperative intensive care medicine brain maturation is ongoing. We encourage further investigation in outcome prediction in this population, potentially by combining more advanced MRI measures with clinical methods.

Specific parameters of operation of the minimized system for cardioplegia in children. Bench test

It is very important to observe all the parameters of cardioplegia when protecting myocardium during cardiac surgery. To perform this task, it is necessary to have clear understanding of properties of the elements of the extracorporeal circuit of cardiopulmonary bypass. The objective : to develop a test model and using it to evaluate technical capabilities of blood cardioplegic system reducing the filling volume of the heat exchange chamber and the system supplying solution to the myocardium. Subjects and methods . A model of a neonatal cardiopulmonary bypass circuit was tested, it included an oxygenator and the cardioplegic system with a 7-ml heat exchange chamber; changes in the pressure and temperature in key nodes of the extracorporeal and cardioplegic circuits were assessed when the pump velocity, ambient temperature and fluid temperature in the main circuit were changed. Results . This modification provides a wide range of liquid volumetric velocities. Maintaining the selected variant of blood cardioplegia and safe pressure within the cardioplegic circuit is ensured at the perfusion rate of up to 350 ml/min. With normothermal circulation and air temperature in the operating room of 23°C, parameters of the cardioplegic circuit and solution delivery system allows maintaining the solution temperature within the range from 16 to 19°C. When the solution is cooled in a heat exchanger down to 4°C, the temperature of the final cardioplegic solution is maintained within 12-17°C; and with normothermal perfusion, air temperature in the operating room of 15°C and the solution temperature in the heat exchange chamber of 4°C, the temperature of the final cardioplegic solution can be within 6‒13°C. With perfusion in the mode of moderate hypothermia (32°C), air temperature in the operating room 15°C and temperature in the heat exchange chamber 4°C, the final cardioplegic solution can be delivered at the temperature from 5 to 9°C. Conclusions . The proposed test model allows investigating aimed to find out additional characteristics of the cardioplegic circuit. Ambient air temperature, cardioplegic pump velocity and main circuit fluid temperature are the main factors influencing the final cardioplegic solution temperature. When using the studied variant of the cardioplegic circuit assembly, the maintenance of the selected variant of blood cardioplegia and safe pressure inside the cardioplegic circuit are ensured at a perfusion rate of up to 350 ml/min.

Efficacy of Nitric Oxide Administration in Attenuating Ischemia/Reperfusion Injury During Neonatal Cardiopulmonary Bypass.

Nitric oxide (NO) plays several protective roles in ischemia/reperfusion (I/R) injury. Neonates undergoing the Norwood procedure are subject to develop I/R injury due to the immaturity of their organs and the potential need to interrupt or decrease systemic flow during surgery. We hypothesized that NO administration during cardiopulmonary bypass (CPB) ameliorates the I/R and could help the postoperative recovery after the Norwood procedure. Twenty-four neonates who underwent a Norwood procedure were enrolled in a prospective randomized blinded controlled trial to receive NO (12 patients) or placebo (12 patients) into the oxygenator of the CPB circuit during the Norwood procedure. Markers of I/R injury were collected at baseline (T0), after weaning from CPB before modified ultrafiltration (T1), after modified ultrafiltration (T2), and at 12 hours (T3) and 24 hours (T4) after surgery, and they were compared between both groups, as well as other postoperative clinical variables. There was no difference in age, weight, anatomical diagnosis, CPB, and aortic cross-clamp time between both groups. Troponin levels were lower in the study group at T1 (0.62 ± 58 ng/mL vs 0.87 ± 0.58 ng/mL, P = .31) and became significantly lower at T2 (0.36 ± 0.32 ng/mL vs 0.97 ± 0.48 ng/mL, P = .009).There were no significant differences between both groups for all other markers. Despite a lower troponin level, there was no difference in inotropic scores or ventricular function between both groups. Time to start diuresis, time to sternal closure and extubation, and intensive care unit and hospital stay were not different between both groups. Systemic administration of NO during the Norwood procedure has myocardial protective effects (lower Troponin levels) but we observed no effect on postoperative recovery. Larger sample size may be needed to show clinical differences.

Efficacy of Nitric Oxide Administration During Neonatal Cardiopulmonary Bypass.

This editorial accompanies an original research article by Dr Elzein and colleagues describing findings of a randomized, placebo-controlled trial of nitric oxide administration during cardiopulmonary bypass surgery in infants undergoing the Norwood procedure.

Surgical Considerations and Management Options in Premature and Very Low Birth Weight Infants With Complex Congenital Heart Disease

The purpose of this review is to provide a concise discussion regarding surgical management of infants born pre-term and/or of low birth weight with congenital heart disease (CHD). The following provides a summary of current available experiential data and treatment paradigms that remain in evolution for this high-risk subset of infants. The composite of these findings supports center- and patient-specific decision-making to define the optimal timing and technique utilized for the palliation and definitive surgical treatment of CHD across a spectrum of severity. The following establishes that infants born both pre-term and of low birth weight represent a high-risk surgical cohort with CHD. Despite this increased risk of both morbidity and mortality following surgical palliation or definitive anatomic correction, advancements in prenatal diagnostics, in postnatal resuscitation, and in the conduct of complex neonatal surgery and cardiopulmonary bypass now enable early intervention with improved outcomes and favorable long-term risk of need for re-intervention. Infants of low birth weight and those born pre-term represent a high-risk subset of patients with CHD. Advancements in both surgical technique and the advent of interventional therapies have introduced important considerations that have enabled earlier treatment in a subset of carefully selected patients. Further prospective, well-controlled data are needed to better define the multi-system effects of early surgical intervention in this high-risk patient population.

Deep Hypothermic Circulatory Arrest Activates Neural Precursor Cells in the Neonatal Brain

Use of antegrade cerebral perfusion (ACP) as an alternative neuroprotection strategy to deep hypothermic circulatory arrest (DHCA) in the setting of cardiopulmonary bypass in neonates has become a common approach, although the value of ACP over DHCA remains highly debated. This study investigated the disruption to neonatal brain homeostasis by DHCA and ACP. Neonatal pigs (7 days old) undergoing bypass were assigned to 4 groups: DHCA at 18°C and ACP at 18°, 25°, and 32° for 45 minutes (n= 6 per group). ACP was initiated through the innominate artery and maintained at 40 mL/kg/min. After bypass, all animals were maintained sedated and intubated for 24 hours before being euthanized. Brain subventricular zone tissues were analyzed for histologic injury by assessing apoptosis and neural homeostasis (Nestin). Histologic examination showed no significant ischemic/hypoxic neuronal death at any cooling temperature among the 4 treatment groups. However, we detected a significantly higher apoptotic rate in DHCA compared with ACP at 18°C (P= .003-.017) or 25°C (P= .012-.043), whereas apoptosis at 32°C was not different from DHCA. Of note, we identified increased Nestin expression in the DHCA group compared with all ACP groups (P range= .011-.041). Neonatal piglet ACP at 18° or 25°C provides adequate protection from increased brain cellular apoptosis. In contrast to ACP, however, DHCA induces brain Nestin expression, indicating activation of neural progenitor cells and the potential of altering neonatal neurodevelopmental progression. DHCA has potential to more profoundly disrupt neural homeostasis than does ACP.

Nitric Oxide During Cardiopulmonary Bypass in Neonates to Reduce Risk of Acute Kidney Injury

Nitric Oxide During Cardiopulmonary Bypass in Neonates to Reduce Risk of Acute Kidney Injury

Lower limit of adequate oxygen delivery for the maintenance of aerobic metabolism during cardiopulmonary bypass in neonates

BackgroundThe objective of cardiopulmonary bypass (CPB) is to maintain an adequate balance between oxygen delivery (Ḋo2) and consumption. The critical Ḋo2 is that at which consumption becomes supply dependent. This study aimed to identify the critical Ḋo2 in neonates, who have higher metabolic rates than adults. MethodsIn a retrospective cohort of neonates, Ḋo2 was calculated from CPB parameters recorded during aortic cross-clamping. High lactate concentration measured after aortic unclamping (lactOFF) was used to identify anaerobic metabolism. Data were analysed using mixed linear and proportional odds regression models. The relationship between Ḋo2 and temperature was analysed in a subgroup of patients with lactOFF <2.5 mM, thought to have had balanced oxygen delivery and consumption. The estimated regression coefficient was further used to adjust hypothetical Ḋo2 thresholds, and Ḋo2 excursions below the threshold were quantified as magnitude–durations. The lowest threshold that provided magnitude–durations and linked with an increase in lactOFF was used as the lowest suitable (critical) Ḋo2 at 37°C. ResultsOverall, 22 896 time points were analysed in 180 neonates. In 40 patients with lactOFF <2.5 mM, Ḋo2 varied by 22.87 (0.70) ml min−1 m−2 °C−1. When varying the Ḋo2 threshold between 340 and 380 ml min−1 m−2, excursions below the threshold were linked with incremental lactOFF. A 100 ml m−2 excursion below the 340 ml min−1 m−2Ḋo2 threshold increased the risk of a 1 mM increment in lactOFF by 22% (odds ratio: 1.22; 95% confidence interval: 1.02–1.45). ConclusionsIt was found that 340 ml min−1 m−2 is likely to represent the lowest suitable Ḋo2 required in neonates to maintain aerobic metabolism during normothermic CPB.

Recovery of cefazolin and clindamycin in in vitro pediatric CPB systems.

Cardiopulmonary bypass (CPB) is often necessary for congenital cardiac surgery, but CPB can alter drug pharmacokinetic parameters resulting in underdosing. Inadequate plasma levels of antibiotics could lead to postoperative infections with increased morbidity. The influence of pediatric CPB systems on cefazolin and clindamycin plasma levels is not known. We have measured plasma levels of cefazolin and clindamycin in in vitro pediatric CPB systems. We have tested three types of CPB systems. All systems were primed and spiked with clindamycin and cefazolin. Samples were taken at different time points to measure the recovery of cefazolin and clindamycin. Linear mixed model analyses were performed to assess if drug recovery was different between the type of CPB system and sampling time point. The experiments were conducted at a tertiary university hospital. 81 samples were analyzed. There was a significant difference in the recovery over time between CPB systems for cefazolin and clindamycin (P < .001). Cefazolin recovery after 180 minutes was 106% (95% CI: 91‐123) for neonatal, 99% (95% CI: 85‐115) for infant, and 77% (95% CI: 67‐89) for pediatric systems. Clindamycin recovery after 180 minutes was 143% (95% CI: 116‐177) for neonatal, 111% (95% CI: 89‐137) for infant, and 120% (95% CI: 97‐149) for pediatric systems. Clindamycin recovery after 180 minutes compared to the theoretical concentration was 0.4% for neonatal, 1.2% for infants, and 0.6% for pediatric systems. The recovery of cefazolin was high in the neonatal and infant CPB systems and moderate in the pediatric system. We found a large discrepancy between the theoretical and measured concentrations of clindamycin in all tested CPB systems.

Platelet Administration During Cardiopulmonary Bypass in Neonates: A Universal Therapy Applied in a Novel Way.

Advances in pharmaceuticals (eg, factor concentrates), laboratory testing (eg, rotational thromboelastometry), and processes (eg, transfusion protocols) have contributed to improved outcomes regarding transfusion in neonates undergoing surgical repair for congenital heart disease. A novel strategy, platelets administered during the rewarming phase of cardiopulmonary bypass, as a solution to improved hemostasis, was prospectively evaluated in 42 neonates. Improved intraoperative and postoperative hemostasis was observed in neonates given platelets during the rewarming phase of cardiopulmonary bypass.

Platelet Function Changes during Neonatal Cardiopulmonary Bypass Surgery: Mechanistic Basis and Lack of Correlation with Excessive Bleeding.

Thrombocytopenia and platelet dysfunction induced by extracorporeal blood circulation are thought to contribute to postsurgical bleeding complications in neonates undergoing cardiac surgery with cardiopulmonary bypass (CPB). In this study, we examined how changes in platelet function relate to changes in platelet count and to excessive bleeding in neonatal CPB surgery. Platelet counts and platelet P-selectin exposure in response to agonist stimulation were measured at four times before, during, and after CPB surgery in neonates with normal versus excessive levels of postsurgical bleeding. Relative to baseline, platelet counts were reduced in patients while on CPB, as was platelet activation by the thromboxane A2 analog U46619, thrombin receptor activating peptide (TRAP), and collagen-related peptide (CRP). Platelet activation by adenosine diphosphate (ADP) was instead reduced after platelet transfusion. We provide evidence that thrombocytopenia is a likely contributor to CPB-associated defects in platelet responsiveness to U46619 and TRAP, CPB-induced collagen receptor downregulation likely contributes to defective platelet responsiveness to CRP, and platelet transfusion may contribute to defective platelet responses to ADP. Platelet transfusion restored to baseline levels platelet counts and responsiveness to all agonists except ADP but did not prevent excessive bleeding in all patients. We conclude that platelet count and function defects are characteristic of neonatal CPB surgery and that platelet transfusion corrects these defects. However, since CPB-associated coagulopathy is multifactorial, platelet transfusion alone is insufficient to treat bleeding events in all patients. Therefore, platelet transfusion must be combined with treatment of other factors that contribute to the coagulopathy to prevent excessive bleeding.

In Vitro Recovery of Sufentanil, Midazolam, Propofol, and Methylprednisolone in Pediatric Cardiopulmonary Bypass Systems

To evaluate in vitro drug recovery in cardiopulmonary bypass (CPB) systems used for pediatric cardiac surgery. Observational in vitro study. Single-center university hospital. In vitro CPB systems used for pediatric cardiac surgery. Three full neonatal, infant, and pediatric CPB systems were primed according to hospital protocol and kept running for 6 hours. Midazolam, propofol, sufentanil, and methylprednisolone were added to the venous side of the systems in doses commonly used for induction of general anesthesia. Blood samples were taken from the postoxygenator side of the circuit immediately after injection of the drugs and after 2, 5, 7, 10, 30, 60, 180, and 300 minutes. Linear mixed model analyses were performed to assess the relationship between log-transformed drug concentration (dependent variable) and type of CPB system and sample time point (independent variables). The mean percentage of drug recovery after 60 and 180 minutes compared with T1 was 41.7% (95% confidence interval [CI] 35.9-47.4) and 23.0% (95% CI 9.2-36.8) for sufentanil, 87.3% (95% CI 64.9-109.7) and 82.0% (95% CI 64.6-99.4) for midazolam, 41.3% (95% CI 15.5-67.2) and 25.0% (95% CI 4.7-45.3) for propofol, and 119.3% (95% CI 101.89-136.78) and 162.0% (95% CI 114.09-209.91) for methylprednisolone, respectively. The present in vitro experiment with neonatal, infant, and pediatric CPB systems shows a variable recovery of routinely used drugs with significant differences between drugs, but not between system categories (with the exception of propofol). The decreased recovery of mainly sufentanil and propofol could lead to suboptimal dosing of patients during cardiac surgery with CPB.

Somatic and cerebral near infrared spectroscopy for the monitoring of perfusion during neonatal cardiopulmonary bypass.

The somatic-cerebral regional oxygen saturation (rSO2) gradient has the potential to reveal a low cardiac output state at an early stage, when systemic vascular resistance increases in order to maintain cerebral perfusion, and results in a drop in somatic rSO2. We hypothesized that during neonatal cardiopulmonary bypass (CPB), the somatic-cerebral rSO2 gradient can also signal poor perfusion, as assessed by an increase in lactate concentration. In a retrospective review of neonatal bypass records, we investigated the association between the somatic-cerebral rSO2 gradient and serial lactate measurements. The somatic-cerebral rSO2 gradient, i.e. the area between the somatic and cerebral rSO2, was calculated for each CPB time interval between 2 lactate measurements, using the trapezoidal method. The association between the somatic-cerebral rSO2 gradient and lactate variation was explored using a mixed model for repeated measurements adjusted for the CPB temperature across intervals. A total of 94 CPB intervals were analysed in 24 neonates, median age 6 days, median weight 3.1 kg. The median lactate variation per interval was +0.2 mmol l-1 (range -1.5 to +2.7), the median somatic-cerebral gradient was 0 (range -1229% min to +2049% min) and the median CPB temperature was 29.5°C (IQR 28.1-33.4). There was an independent association between the lactate increase and the somatic-cerebral rSO2 gradient (regression coefficient = -0.0006 ± 0.0002, P = 0.009). A decrease in the somatic-cerebral rSO2 gradient was associated with an increase in lactate concentration, suggesting that the somatic-cerebral rSO2 gradient is a useful monitoring tool for the adequacy of perfusion during neonatal CPB.

Postoperative brain volumes are associated with one-year neurodevelopmental outcome in children with severe congenital heart disease

Children with congenital heart disease (CHD) remain at risk for neurodevelopmental impairment despite improved perioperative care. Our prospective cohort study aimed to determine the relationship between perioperative brain volumes and neurodevelopmental outcome in neonates with severe CHD. Pre- and postoperative cerebral MRI was acquired in term born neonates with CHD undergoing neonatal cardiopulmonary bypass surgery. Brain volumes were measured using an atlas prior-based automated method. One-year neurodevelopmental outcome was assessed with the Bayley-III. CHD infants (n = 77) had lower pre- and postoperative total and regional brain volumes compared to controls (n = 44, all p < 0.01). CHD infants had poorer cognitive and motor outcome (p ≤ 0.0001) and a trend towards lower language composite score compared to controls (p = 0.06). Larger total and selected regional postoperative brain volumes were found to be associated with better cognitive and language outcomes (all p < 0.04) at one year. This association was independent of length of intensive care unit stay for total, cortical, temporal, frontal and cerebellar volumes. Therefore, reduced cerebral volume in CHD neonates undergoing bypass surgery may serve as a biomarker for impaired outcome.

Heart valve inspired and multi-stream aortic cannula: Novel designs for cardiopulmonary bypass improvement in neonates.

In a typical open-heart surgery, the blood flow through the aortic cannula is a critical element of the cardiopulmonary bypass (CPB) procedure. Especially for the neonatal and pediatric CPB flow conditions, the need for small hydraulic diameter and large blood flow results confined turbulent jet flow regimes that exacerbate blood damage and platelet activation. Simultaneously, the confined jet wake leads to complex stagnation and recirculating flows that cause considerable thrombosis, blood, and endothelial cell damage through the aorta. Thus, an ideal neonatal CPB cannula should be able to generate optimal jet expansion so that sufficient cerebral perfusion is achieved through the head-neck vessels to avoid postoperative neurological complications and developmental defects in children. To address these challenges, a formal bio-inspired design framework is conducted to reach the desired cannula function through novel analogous biological components, first-time in literature. Among the biological jet flow regimes studied, the ventricle filling-jet generated through the atrio-ventricle (AV) valves are found to be the most promising. Inspired from human AV valve shapes, 8 different novel cannula designs, considering the size constrains of neonatal and pediatric patients are built via high-accurate micro stereo-lithography. Using 2-dimensional time-resolved particle image velocimetry the turbulent jet wake characteristics are measured and compared. The proposed designs have exhibited a significant improvement as compared to standard circular cannula by around 30% reduction in maximum outflow velocity and more than 80% reduction in potential core length and spatial energy dissipation which results in a lower risk of cardiovascular and blood damage.