Normoxic Management during Cardiopulmonary Bypass Does Not Reduce Cerebral Mitochondrial Dysfunction in Neonatal Swine.

Optimal oxygen management during pediatric cardiopulmonary bypass (CPB) is unknown. We previously demonstrated an increase in cortical mitochondrial reactive oxygen species and decreased mitochondrial function after CPB using hyperoxic oxygen management. This study investigates whether controlled oxygenation (normoxia) during CPB reduces cortical mitochondrial dysfunction and oxidative injury. Ten neonatal swine underwent three hours of continuous CPB at 34 °C (flow > 100 mL/kg/min) via cervical cannulation targeting a partial pressure of arterial oxygen (PaO2) goal < 150 mmHg (normoxia, n = 5) or >300 mmHg (hyperoxia, n = 5). The animals underwent continuous hemodynamic monitoring and serial arterial blood sampling. Cortical microdialysate was serially sampled to quantify the glycerol concentration (represents neuronal injury) and lactate-to-pyruvate ratio (represents bioenergetic dysfunction). The cortical tissue was analyzed via high-resolution respirometry to quantify mitochondrial oxygen consumption and reactive oxygen species generation, and cortical oxidized protein carbonyl concentrations were quantified to assess for oxidative damage. Serum PaO2 was higher in hyperoxia animals throughout CPB (p < 0.001). There were no differences in cortical glycerol concentration between groups (p > 0.2). The cortical lactate-to-pyruvate ratio was modestly elevated in hyperoxia animals (p < 0.03) but the values were not clinically significant (<30). There were no differences in cortical mitochondrial respiration (p = 0.48), protein carbonyls (p = 0.74), or reactive oxygen species generation (p = 0.93) between groups. Controlled oxygenation during CPB does not significantly affect cortical mitochondrial function or oxidative injury in the acute setting. Further evaluation of the short and long-term effects of oxygen level titration during pediatric CPB on cortical tissue and other at-risk brain regions are needed, especially in the presence of cyanosis.

Indexed oxygen delivery during pediatric cardiopulmonary bypass is a modifiable risk factor for postoperative acute kidney injury.

BACKGROUND: Acute kidney injury after pediatric cardiac surgery is a common complication with few established modifiable risk factors. We sought to characterize whether indexed oxygen delivery during cardiopulmonary bypass was associated with postoperative acute kidney injury in a large pediatric cohort. METHODS: This was a retrospective analysis of patients under 1 year old undergoing cardiac surgery with cardiopulmonary bypass between January 1, 2013, and January 1, 2020. Receiver operating characteristic curves across values ranging from 260 to 400 mL/min/m2 were used to identify the indexed oxygen delivery most significantly associated with acute kidney injury risk. RESULTS: We included 980 patients with acute kidney injury occurring in 212 (21.2%). After adjusting for covariates associated with acute kidney injury, an indexed oxygen delivery threshold of 340 mL/min/m2 predicted acute kidney injury in STAT 4 and 5 neonates (area under the curve = 0.66, 95% CI = 0.60 - 0.72, sensitivity = 56.1%, specificity = 69.4%). An indexed oxygen delivery threshold of 400 mL/min/m2 predicted acute kidney injury in STAT 1-3 infants (area under the curve = 0.65, 95% CI = 0.58 - 0.72, sensitivity = 52.6%, specificity = 74.6%). CONCLUSION: Indexed oxygen delivery during cardiopulmonary bypass is a modifiable variable independently associated with postoperative acute kidney injury in specific pediatric populations. Strategies aimed at maintaining oxygen delivery greater than 340 mL/min/m2 in complex neonates and greater than 400 mL/min/m2 in infants may reduce the occurrence of postoperative acute kidney injury in the pediatric population.

Effects of circulatory arrest and cardiopulmonary bypass on cerebral autoregulation in neonatal swine.

BACKGROUND: Cerebral autoregulation mechanisms help maintain adequate cerebral blood flow (CBF) despite changes in cerebral perfusion pressure. Impairment of cerebral autoregulation, during and after cardiopulmonary bypass (CPB), may increase risk of neurologic injury in neonates undergoing surgery. In this study, alterations of cerebral autoregulation were assessed in a neonatal swine model probing four perfusion strategies. METHODS: Neonatal swine (n = 25) were randomized to continuous deep hypothermic cardiopulmonary bypass (DH-CPB, n = 7), deep hypothermic circulatory arrest (DHCA, n = 7), selective cerebral perfusion (SCP, n = 7) at deep hypothermia, or normothermic cardiopulmonary bypass (control, n = 4). The correlation coefficient (LDx) between laser Doppler measurements of CBF and mean arterial blood pressure was computed at initiation and conclusion of CPB. Alterations in cerebral autoregulation were assessed by the change between initial and final LDx measurements. RESULTS: Cerebral autoregulation became more impaired (LDx increased) in piglets that underwent DH-CPB (initial LDx: median 0.15, IQR [0.03, 0.26]; final: 0.45, [0.27, 0.74]; p = 0.02). LDx was not altered in those undergoing DHCA (p > 0.99) or SCP (p = 0.13). These differences were not explained by other risk factors. CONCLUSIONS: In a validated swine model of cardiac surgery, DH-CPB had a significant effect on cerebral autoregulation, whereas DHCA and SCP did not. IMPACT: Approximately half of the patients who survive neonatal heart surgery with cardiopulmonary bypass (CPB) experience neurodevelopmental delays. This preclinical investigation takes steps to elucidate and isolate potential perioperative risk factors of neurologic injury, such as impairment of cerebral autoregulation, associated with cardiac surgical procedures involving CPB. We demonstrate a method to characterize cerebral autoregulation during CPB pump flow changes in a neonatal swine model of cardiac surgery. Cerebral autoregulation was not altered in piglets that underwent deep hypothermic circulatory arrest (DHCA) or selective cerebral perfusion (SCP), but it was altered in piglets that underwent deep hypothermic CBP.

Comparison of three autotransfusion devices for utilization in the pediatric population.

INTRODUCTION: A device that may help attenuate the amount of homologous blood product given to pediatric cardiac surgical patients is the autotransfusion device. Three separate autotransfusion devices were selected for evaluation. The Sorin Xtra, Fresenius Continuous Autotransfusion System Plus (CATS*plus), and the Fresenius Continuous Autotransfusion System Smart (CATSmart) were evaluated based on the mechanical processes of each device, hematocrit value of the salvaged packed red cell product, time of processing, and the advantageous accessories with each device. METHODS: Each of the autotransfusion devices were used to collect salvageable blood from the surgical field as well as to process residual blood from the cardiopulmonary bypass circuit after decannulation. The cell salvage process was performed in accordance with the manufacturer's instructions for use and the recommended settings for processing and washing. The Sorin Xtra device had the 55 mL bowl set up for all cases, while the Fresenius continuous autotransfusion systems utilized the standard disposable for each device. RESULTS: Each cell salvage device was employed during 30 pediatric cardiac surgery procedures, and data for each device, was broken down into four groups based on patient weight (0-10, 10-20, 20-40, and >40 kg). For all patient sizes, the Sorin Xtra tended to produce the greatest volume of cell saver product (55-825 mL) as compared to the CATS*plus and CATSmart devices (7-550 mL and 0-860 mL, respectively). The Continuous Autotransfusion System Smart tended to produce the highest hematocrit product, ranging from 44 to 81%. DISCUSSION: Through this evaluation, it was determined the continuous autotransfusion systems provided the highest hematocrit with the lowest recovered packed red cell volume, while the Sorin Xtra packed red cell product showed to have a lower hematocrit with a larger packed red cell volume. Each device proved effective within our pediatric population.

Comparison of three infant venous reservoirs with vacuum-assisted venous drainage during varying levels of cardiotomy suction.

BACKGROUND: Vacuum-assisted venous drainage has gained widespread use within the pediatric perfusion community for use during cardiopulmonary bypass. It is questioned whether its efficiency may be compromised with application of excessive cardiotomy suction to the infant hard-shell venous reservoir. An in vitro simulation circuit was used to research this phenomenon. A comparison of three different infant hard-shell venous reservoirs also took place to determine if one reservoir type was more advantageous when handling cardiotomy suction. The reservoirs tested were the Maquet VHK 11000, Medtronic Affinity Pixie, and Terumo Capiox FX05. METHODS: The in vitro simulation circuit consisted of a 1 L reservoir bag that was cannulated at one access point with an Edwards Lifesciences 10Fr aortic cannula and the other access area with an Edwards Lifesciences 10Fr right angle venous cannula and 12Fr right angle venous cannula that were joined together. Key points of measurement and response variables were the pressures on the connection of the venous cannulas, inlet of the venous reservoir, and flow through the venous line. Vacuum was applied and manipulated with a Maquet VAVD Controller to settings of -20 mmHg, -30 mmHg, -40 mmHg, -50 mmHg, and -60 mmHg. Cardiotomy suction was added at settings of 1 LPM, 2 LPM, 3 LPM, and 4 LPM. Values from each response variable were monitored and recorded. These data were utilized to compare the reservoirs with a random coefficient model for each response variable. CONCLUSIONS: There is an adverse effect of excessive cardiotomy suction on the efficacy of vacuum-assisted venous drainage in infant hard-shell venous reservoirs. There is no significant difference between the VHK 11000, Pixie, and FX05 regarding their ability to handle this occurrence. An important discovery was that the FX05 showed a greater transfer of vacuum to the venous cannulas and reservoir inlet.

A single center's conversion from roller pump to centrifugal pump technology in extracorporeal membrane oxygenation.

OVERVIEW:: Recent advances in blood pump technology have led to an increased use of centrifugal pumps for prolonged extracorporeal membrane oxygenation (ECMO). Data from the Extracorporeal Life Support Organization confirms that many institutions have converted to centrifugal pumps after prior experience with roller pump technology. Centrifugal pump technology is more compact and may generate less heat and hemolysis than a conventional roller pump. Based on the potential advantages of centrifugal pumps, a decision was made institution-wide to convert to centrifugal pump technology in pediatric implementation of ECMO. Based on limited prior experience with centrifugal pumps, a multidisciplinary approach was used to implement this new technology. The new centrifugal pump (Sorin Revolution, Arvada, CO) was intended for ECMO support in the cardiac intensive care unit (CICU), the pediatric intensive care unit (PICU) and the neonatal intensive care unit (NICU). DESCRIPTION:: The perfusion team used their knowledge and expertise with centrifugal pumps to create the necessary teaching tools and interactive training sessions for the technical specialists who consisted primarily of registered nurses and respiratory therapists. The first phase consisted of educating all personnel involved in the care of the ECMO patient, followed by patient implementation in the CICU, followed by the PICU and NICU. CONCLUSION:: The institution-wide conversion took several months to complete and was well received among all disciplines in the CICU and PICU. The NICU personnel did use the centrifugal pump circuit, but decided to revert back to using the roller pump technology. A systematic transition from roller pump to centrifugal pump technology with a multidisciplinary team can ensure a safe and successful implementation.

Early Impairment of Cerebral Bioenergetics After Cardiopulmonary Bypass in Neonatal Swine.

Objectives: We previously demonstrated cerebral mitochondrial dysfunction in neonatal swine immediately following a period of full-flow cardiopulmonary bypass (CPB). The extent to which this dysfunction persists in the postoperative period and its correlation with other markers of cerebral bioenergetic failure and injury is unknown. We utilized a neonatal swine model to investigate the early evolution of mitochondrial function and cerebral bioenergetic failure after CPB. Methods: Twenty piglets (mean weight 4.4 ± 0.5 kg) underwent 3 h of CPB at 34 °C via cervical cannulation and were followed for 8, 12, 18, or 24 h (n = 5 per group). Markers of brain tissue damage (glycerol) and bioenergetic dysfunction (lactate to pyruvate ratio) were continuously measured in cerebral microdialysate samples. Control animals (n = 3, mean weight 4.1 ± 1.2 kg) did not undergo cannulation or CPB. Brain tissue was extracted immediately after euthanasia to obtain ex-vivo cortical mitochondrial respiration and frequency of cortical microglial nodules (indicative of cerebral microinfarctions) via neuropathology. Results: Both the lactate to pyruvate ratio (P < .0001) and glycerol levels (P = .01) increased in cerebral microdialysate within 8 h after CPB. At 24 h post-CPB, cortical mitochondrial respiration was significantly decreased compared with controls (P = .046). The presence of microglial nodules increased throughout the study period (24 h) (P = .01, R2 = 0.9). Conclusion: CPB results in impaired cerebral bioenergetics that persist for at least 24 h. During this period of bioenergetic impairment, there may be increased susceptibility to secondary injury related to alterations in metabolic delivery or demand, such as hypoglycemia, seizures, and decreased cerebral blood flow.

The use of novel diffuse optical spectroscopies for improved neuromonitoring during neonatal cardiac surgery requiring antegrade cerebral perfusion.

Background: Surgical procedures involving the aortic arch present unique challenges to maintaining cerebral perfusion, and optimal neuroprotective strategies to prevent neurological injury during such high-risk procedures are not completely understood. The use of antegrade cerebral perfusion (ACP) has gained favor as a neuroprotective strategy over deep hypothermic circulatory arrest (DHCA) due to the ability to selectively perfuse the brain. Despite this theoretical advantage over DHCA, there has not been conclusive evidence that ACP is superior to DHCA. One potential reason for this is the incomplete understanding of ideal ACP flow rates to prevent both ischemia from underflowing and hyperemia and cerebral edema from overflowing. Critically, there are no continuous, noninvasive measurements of cerebral blood flow (CBF) and cerebral oxygenation (StO2) to guide ACP flow rates and help develop standard clinical practices. The purpose of this study is to demonstrate the feasibility of using noninvasive, diffuse optical spectroscopy measurements of CBF and cerebral oxygenation during the conduct of ACP in human neonates undergoing the Norwood procedure. Methods: Four neonates prenatally diagnosed with hypoplastic left heart syndrome (HLHS) or a similar variant underwent the Norwood procedure with continuous intraoperative monitoring of CBF and cerebral oxygen saturation (StO2) using two non-invasive optical techniques, namely diffuse correlation spectroscopy (DCS) and frequency-domain diffuse optical spectroscopy (FD-DOS). Changes in CBF and StO2 due to ACP were calculated by comparing these parameters during a stable 5 min period of ACP to the last 5 min of full-body CPB immediately prior to ACP initiation. Flow rates for ACP were left to the discretion of the surgeon and ranged from 30 to 50 ml/kg/min, and all subjects were cooled to 18°C prior to initiation of ACP. Results: During ACP, the continuous optical monitoring demonstrated a median (IQR) percent change in CBF of -43.4% (38.6) and a median (IQR) absolute change in StO2 of -3.6% (12.3) compared to a baseline period during full-body cardiopulmonary bypass (CPB). The four subjects demonstrated varying responses in StO2 due to ACP. ACP flow rates of 30 and 40 ml/kg/min (n = 3) were associated with decreased CBF during ACP compared to full-body CPB. Conversely, one subject with a higher flow6Di rate of 50 ml/kg/min demonstrated increased CBF and StO2 during ACP. Conclusions: This feasibility study demonstrates that novel diffuse optical technologies can be utilized for improved neuromonitoring in neonates undergoing cardiac surgery where ACP is utilized. Future studies are needed to correlate these findings with neurological outcomes to inform best practices during ACP in these high-risk neonates.

Pediatric Extracorporeal Cardiopulmonary Resuscitation: Development of a Porcine Model and the Influence of Cardiopulmonary Resuscitation Duration on Brain Injury.

Background The primary objective was to develop a porcine model of prolonged (30 or 60 minutes) pediatric cardiopulmonary resuscitation (CPR) followed by 22- to 24-hour survival with extracorporeal life support, and secondarily to evaluate differences in neurologic injury. Methods and Results Ten-kilogram, 4-week-old female piglets were used. First, model development established the technique (n=8). Then, a pilot study was conducted (n=15). After 80% survival was achieved in the final 5 pilot animals, a proof-of-concept randomized study was completed (n=11). Shams (n=6) underwent anesthesia only. Severe neurological injury was determined by a composite score of mitochondrial function, neuropathology, and cerebral metabolism: scale of 0-6 (severe: >3). Among 15 piglets in the pilot study, overall survival was 10 (67%); of the final 5, overall survival was 4 (80%). Eleven piglets were then randomized to 60 (CPR60, n=5) or 30 minutes of CPR (CPR30, n=5); 1 animal was excluded from prerandomization for intra-abdominal hemorrhage (10/11, 91% survival). Three of 5 animals in the CPR60 group had severe neurological injury scores versus 1 of 5 in the CPR30 group (P=0.52). During ECMO, CPR60 animals had lower pH (CPR60: 7.4 [IQR 7.4-7.4] versus CPR30: 7.5 [IQR 7.4-7.5], P=0.022), higher lactate (CPR60: 6.8 [IQR 6.8-11] versus CPR30: 4.2 [IQR 4.1-4.3] mmol/L; P=0.012), and higher ICP (CPR60: 19.3 [IQR 11.7-29.3] versus CPR30: 7.9 [IQR 6.7-9.3] mm Hg; P=0.037). Both groups had greater mitochondrial injury than shams (CPR60: P<0.001; CPR30: P<0.001). CPR60 did not differ from CPR30 in mitochondrial respiration, neuropathology, or cerebral metabolism. Conclusions A pediatric porcine model of extracorporeal cardiopulmonary resuscitation after 60 and 30 minutes of CPR consistently resulted in 24-hour survival with more severe lactic acidosis in the 60-minute cohort.

Diffuse Optical Monitoring of Cerebral Hemodynamics and Oxygen Metabolism during and after Cardiopulmonary Bypass: Hematocrit Correction and Neurological Vulnerability.

Cardiopulmonary bypass (CPB) provides cerebral oxygenation and blood flow (CBF) during neonatal congenital heart surgery, but the impacts of CPB on brain oxygen supply and metabolic demands are generally unknown. To elucidate this physiology, we used diffuse correlation spectroscopy and frequency-domain diffuse optical spectroscopy to continuously measure CBF, oxygen extraction fraction (OEF), and oxygen metabolism (CMRO2) in 27 neonatal swine before, during, and up to 24 h after CPB. Concurrently, we sampled cerebral microdialysis biomarkers of metabolic distress (lactate-pyruvate ratio) and injury (glycerol). We applied a novel theoretical approach to correct for hematocrit variation during optical quantification of CBF in vivo. Without correction, a mean (95% CI) +53% (42, 63) increase in hematocrit resulted in a physiologically improbable +58% (27, 90) increase in CMRO2 relative to baseline at CPB initiation; following correction, CMRO2 did not differ from baseline at this timepoint. After CPB initiation, OEF increased but CBF and CMRO2 decreased with CPB time; these temporal trends persisted for 0-8 h following CPB and coincided with a 48% (7, 90) elevation of glycerol. The temporal trends and glycerol elevation resolved by 8-24 h. The hematocrit correction improved quantification of cerebral physiologic trends that precede and coincide with neurological injury following CPB.

Correlation of Cerebral Microdialysis with Non-Invasive Diffuse Optical Cerebral Hemodynamic Monitoring during Deep Hypothermic Cardiopulmonary Bypass.

Neonates undergoing cardiac surgery involving aortic arch reconstruction are at an increased risk for hypoxic-ischemic brain injury. Deep hypothermia is utilized to help mitigate this risk when periods of circulatory arrest are needed for surgical repair. Here, we investigate correlations between non-invasive optical neuromonitoring of cerebral hemodynamics, which has recently shown promise for the prediction of postoperative white matter injury in this patient population, and invasive cerebral microdialysis biomarkers. We compared cerebral tissue oxygen saturation (StO2), relative total hemoglobin concentration (rTHC), and relative cerebral blood flow (rCBF) measured by optics against the microdialysis biomarkers of metabolic stress and injury (lactate-pyruvate ratio (LPR) and glycerol) in neonatal swine models of deep hypothermic cardiopulmonary bypass (DHCPB), selective antegrade cerebral perfusion (SACP), and deep hypothermic circulatory arrest (DHCA). All three optical parameters were negatively correlated with LPR and glycerol in DHCA animals. Elevation of LPR was found to precede the elevation of glycerol by 30-60 min. From these data, thresholds for the detection of hypoxic-ischemia-associated cerebral metabolic distress and neurological injury are suggested. In total, this work provides insight into the timing and mechanisms of neurological injury following hypoxic-ischemia and reports a quantitative relationship between hypoxic-ischemia severity and neurological injury that may inform DHCA management.

Increased cerebral mitochondrial dysfunction and reactive oxygen species with cardiopulmonary bypass.

OBJECTIVES: Neurodevelopmental injury after cardiac surgery using cardiopulmonary bypass (CPB) for congenital heart defects is common, but the mechanism behind this injury is unclear. This study examines the impact of CPB on cerebral mitochondrial reactive oxygen species (ROS) generation and mitochondrial bioenergetics. METHODS: Twenty-three piglets (mean weight 4.2 ± 0.5 kg) were placed on CPB for either 1, 2, 3 or 4 h (n = 5 per group) or underwent anaesthesia without CPB (sham, n = 3). Microdialysis was used to measure metabolic markers of ischaemia. At the conclusion of CPB or 4 h of sham, brain tissue was harvested. Utilizing high-resolution respirometry, with simultaneous fluorometric analysis, mitochondrial respiration and ROS were measured. RESULTS: There were no significant differences in markers of ischaemia between sham and experimental groups. Sham animals had significantly higher mitochondrial respiration than experimental animals, including maximal oxidative phosphorylation capacity of complex I (OXPHOSCI) (3.25 ± 0.18 vs 4-h CPB: 1.68 ± 0.10, P < 0.001) and maximal phosphorylating respiration capacity via convergent input through complexes I and II (OXPHOSCI+CII) (7.40 ± 0.24 vs 4-h CPB: 3.91 ± 0.20, P < 0.0001). At 4-h, experimental animals had significantly higher ROS related to non-phosphorylating respiration through complexes I and II (ETSCI+CII) than shams (1.08 ± 0.13 vs 0.64 ± 0.04, P = 0.026). CONCLUSIONS: Even in the absence of local markers of ischaemia, CPB is associated with decreased mitochondrial respiration relative to shams irrespective of duration. Exposure to 4 h of CPB resulted in a significant increase in cerebral mitochondrial ROS formation compared to shorter durations. Further study is needed to improve the understanding of cerebral mitochondrial health and its effects on the pathophysiology of neurological injury following exposure to CPB.

An in vitro comparison of the ability of three commonly used pediatric cardiopulmonary bypass circuits to filter gaseous microemboli.

BACKGROUND: The purpose of this study was to compare the ability of three commonly used pediatric cardiopulmonary bypass (CPB) circuits to filter gaseous microemboli (GME) in an in vitro model. METHODS: Devices were tested at different levels of two specific independent variables: volume of air injected (1, 3, 5ml) and percentage of each oxygenator's rated flow (50%, 75%, 100%, 125%). The air-handling ability of each CPB circuit was determined by the Emboli Detection and Classification Quantifier (Luna Innovations Inc., Roanoke,VA). RESULTS: At all tested conditions, the FX-05 allowed a higher percentage of GME when compared to either one or both of the other two CPB circuits. When comparing oxygenators at similar absolute flow rates, the KIDS D100/D130 CPB circuit performed worse compared to the other two CPB circuits. CONCLUSIONS: The combination of the Baby RX-05 oxygenator and Capiox AF02 arterial line filter provides the highest level of protection from air emboli in an in vitro investigation.

Non-invasive optical neuromonitoring of the temperature-dependence of cerebral oxygen metabolism during deep hypothermic cardiopulmonary bypass in neonatal swine.

Management of deep hypothermic (DH) cardiopulmonary bypass (CPB), a critical neuroprotective strategy, currently relies on non-invasive temperature to guide cerebral metabolic suppression during complex cardiac surgery in neonates. Considerable inter-subject variability in temperature response and residual metabolism may contribute to the persisting risk for postoperative neurological injury. To characterize and mitigate this variability, we assess the sufficiency of conventional nasopharyngeal temperature (NPT) guidance, and in the process, validate combined non-invasive frequency-domain diffuse optical spectroscopy (FD-DOS) and diffuse correlation spectroscopy (DCS) for direct measurement of cerebral metabolic rate of oxygen (CMRO2). During CPB, n = 8 neonatal swine underwent cooling from normothermia to 18℃, sustained DH perfusion for 40 min, and then rewarming to simulate cardiac surgery. Continuous non-invasive and invasive measurements of intracranial temperature (ICT) and CMRO2 were acquired. Significant hysteresis (p < 0.001) between cooling and rewarming periods in the NPT versus ICT and NPT versus CMRO2 relationships were found. Resolution of this hysteresis in the ICT versus CMRO2 relationship identified a crucial insufficiency of conventional NPT guidance. Non-invasive CMRO2 temperature coefficients with respect to NPT (Q10 = 2.0) and ICT (Q10 = 2.5) are consistent with previous reports and provide further validation of FD-DOS/DCS CMRO2 monitoring during DH CPB to optimize management.

Cerebral mitochondrial dysfunction associated with deep hypothermic circulatory arrest in neonatal swine.

OBJECTIVES: Controversy remains regarding the use of deep hypothermic circulatory arrest (DHCA) in neonatal cardiac surgery. Alterations in cerebral mitochondrial bioenergetics are thought to contribute to ischaemia-reperfusion injury in DHCA. The purpose of this study was to compare cerebral mitochondrial bioenergetics for DHCA with deep hypothermic continuous perfusion using a neonatal swine model. METHODS: Twenty-four piglets (mean weight 3.8 kg) were placed on cardiopulmonary bypass (CPB): 10 underwent 40-min DHCA, following cooling to 18°C, 10 underwent 40 min DHCA and 10 remained at deep hypothermia for 40 min; animals were subsequently rewarmed to normothermia. 4 remained on normothermic CPB throughout. Fresh brain tissue was harvested while on CPB and assessed for mitochondrial respiration and reactive oxygen species generation. Cerebral microdialysis samples were collected throughout the analysis. RESULTS: DHCA animals had significantly decreased mitochondrial complex I respiration, maximal oxidative phosphorylation, respiratory control ratio and significantly increased mitochondrial reactive oxygen species (P < 0.05 for all). DHCA animals also had significantly increased cerebral microdialysis indicators of cerebral ischaemia (lactate/pyruvate ratio) and neuronal death (glycerol) during and after rewarming. CONCLUSIONS: DHCA is associated with disruption of mitochondrial bioenergetics compared with deep hypothermic continuous perfusion. Preserving mitochondrial health may mitigate brain injury in cardiac surgical patients. Further studies are needed to better understand the mechanisms of neurological injury in neonatal cardiac surgery and correlate mitochondrial dysfunction with neurological outcomes.

Evolution of membrane oxygenator technology for utilization during pediatric cardiopulmonary bypass.

The development of the membrane oxygenator for pediatric cardiopulmonary bypass has been an incorporation of ideology and technological advancements with contributions by many investigators throughout the past two centuries. With the pursuit of this technological achievement, the ability to care for mankind in the areas of cardiac surgery has been made possible. Heart disease can affect anyone within the general population, but one such segment that it can affect from inception includes children. Currently, congenital heart defects are the most common birth defects nationally and worldwide. A large meta-analysis study from 1930 to 2010 was conducted in review of published medical literature totaling 114 papers with a study population of 24,091,867 live births, and divulged a staggering incidence of congenital heart disease involving 164,396 subjects with diverse cardiac illnesses. The prevalence of these diseases increased from 0.6 per 1,000 live births from 1930-1934 to 9.1 per 1,000 live births after 1995. These data reveal an emphasis on a growing public health issue regarding congenital heart disease. This discovery displays a need for heightened awareness in the scientific and medical industrial community to accelerate investigative research on emerging cardiovascular devices in an effort to confront congenital anomalies. One such device that has evolved over the past several decades is the pediatric membrane oxygenator. The pediatric membrane oxygenator, in conjunction with the heart lung machine, assists in the repair of most congenital cardiac defects. Numerous children born with congenital heart disease with or without congestive heart failure have experienced improved clinical outcomes in quality of life, survival, and mortality as a result of the inclusion of this technology during their cardiac surgical procedure. The purpose of this review is to report a summary of the published medical and scientific literature related to development of the pediatric membrane oxygenator from its conceptual evolutionary stages to artificially supporting whole body perfusion in the modern pediatric cardiac surgical setting.

2004 survey of ECMO in the neonate after open heart surgery: circuitry and team roles.

Over the past 20 years, the bulk of the literature and texts published about extracorporeal membrane oxygenation (ECMO) has been written by physicians and nurses. The consensus of this body of printed information would suggest, among other things, that (1) despite significant advancements in extracorporeal technology, the standard ECMO circuit has remained fundamentally unchanged since originally described in 1982, and (2) perfusionists are nearly absent from the staffing algorithm at most centers. While these conclusions may be representative of the extracorporeal life support (ELSO) reporting centers, they may not be representative of the field as a whole. We hypothesized that the use of modern extracorporeal equipment and the involvement of perfusionists in ECMO patient care is largely underreported in previous studies. To study this hypothesis, we developed a standard survey instrument and queried perfusion teams from the hospitals listed on the American Society of Extra-Corporeal Technology Pediatric Registry. All centers were contacted by phone and were asked questions regarding their caseload, circuitry, and staffing algorithms. Data are reported as a percentage of respondents. ECMO is used as a method of mechanical support after neonatal open heart surgery in 94% of centers surveyed. For 60% of the centers, a silicone membrane oxygenator is used exclusively, whereas 40% of the centers have used a hollow fiber oxygenator (HFO), and of that group, 19% use a HFO routinely for neonatal post-cardiopulmonary bypass ECMO. Roller pumps are used exclusively at 65% of the centers, whereas centrifugal pumps are used routinely in 12%, and 23% have used both. Perfusionists are responsible for set-up/initiation (79%) and daily rounding/troubleshooting (71%), and provide around-the-clock bedside care (46%) at the surveyed centers. These data suggest that previously published ELSO-centric ECMO studies may significantly underestimate the contemporary application of modern technologies and the involvement of perfusionists.

A description of a prototype miniature extracorporeal membrane oxygenation circuit using current technologies in a sheep model.

In the United States, standardization of neonatal extracorporeal membrane oxygenation (ECMO) circuit was achieved during the 1980s. Since that time, the consoles and components of the ECMO circuit have remained fundamentally unchanged (bladder, rollerpump, silicone membrane oxygenator). Extracorporeal technology, however, has witnessed many significant advancements in components during the past two decades. These new technologies have characteristics that may improve outcomes when applied in the ECMO arena. Understanding how these technologies perform in long-term applications is necessary. Therefore, the purpose of this project is to evaluate the performance of a miniature ECMO circuit consisting of current generation technologies in an animal model. An ECMO circuit (prime volume 145 mL) was designed that included a hollow fiber oxygenator and a remote mounted centrifugal pump. All circuit tubing and components were surface coated. Three sheep (approx 13 kg) were placed on ECMO using standard neck cannulation techniques and maintained according to clinical protocols. Technical implementation, oxygenator function, and hematological parameters were accessed. Duration of ECMO was 20, 48, and 58 hours. There was no evidence of oxygenator failure, as measured by pressure drop and oxygen transfer, in any of the procedures. No plasma leak was observed in any oxygenators. Platelet count trended downward after 24 hours. Visual inspection after ECMO showed very little evidence of gross thrombosis. This ECMO circuit design departs dramatically from the typical North American systems. The use of this console and components facilitated a 70% reduction in priming volume over a traditional ECMO circuit. Further investigations should be conducted to determine if circuit miniaturization can reduce the morbidity associated with blood product consumption and the bloods contact with the artificial surfaces of the ECMO circuitry.

A novel method of measuring cardiac output in infants following extracorporeal procedures: preliminary validation in a swine model.

In infants, technologies for obtaining rapid, quantified measurements of cardiac output (CO) following weaning from cardiopulmonary bypass (CPB) or extracorporeal membrane oxygenation are not readily available. A new technique to measure CO based on ultrasound velocity dilution is described. It utilizes reusable probes placed on the extracorporeal circuit that permits convenient measurement of CO prior to decannulation. This report provides preliminary validation data in an animal model. Three Yorkshire pigs (11-14 kg) were fully heparinized and cannulated via the right common carotid artery (cannula advanced to the aortic arch) and right atrium. Both the venous and arterial lines were instrumented with ultrasonic probes connected to a computer-monitoring system. A 'stopcock bridge' between the arterial and venous cannulas provided the access for saline injection and a controlled AV-shunt. For comparison, a vascular flow probe was fitted directly to the pulmonary artery (PA) in both animals and, for the larger animal, a PA catheter was inserted to obtain standard thermodilution measurements. Linear regression analysis revealed a correlation between the CO by ultrasound dilution (CO UD) technique and the vascular probe and PA thermodilution techniques to be R2 =0.94 and 0.81. This pilot study demonstrated that the CO UD technique correlates to other benchmarks of CO measurements. This novel technology has specific application in the field of pediatric open heart surgery in that it would allow the surgeon to accurately and inexpensively measure the CO of neonatal and pediatric patients before and after surgical manipulation of the heart without the need for placement of additional catheters or probes.