Failed Extubation in Neonates After Cardiac Surgery: A Single-Center, Retrospective Study.

OBJECTIVES: To describe factors associated with failed extubation (FE) in neonates following cardiovascular surgery, and the relationship with clinical outcomes. DESIGN: Retrospective cohort study. SETTING: Twenty-bed pediatric cardiac ICU (PCICU) in an academic tertiary care children's hospital. PATIENTS: Neonates admitted to the PCICU following cardiac surgery between July 2015 and June 2018. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Patients who experienced FE were compared with patients who were successfully extubated. Variables associated with FE ( p < 0.05) from univariate analysis were considered for inclusion in multivariable logistic regression. Univariate associations of FE with clinical outcomes were also examined. Of 240 patients, 40 (17%) experienced FE. Univariate analyses revealed associations of FE with upper airway (UA) abnormality (25% vs 8%, p = 0.003) and delayed sternal closure (50% vs 24%, p = 0.001). There were weaker associations of FE with hypoplastic left heart syndrome (25% vs 13%, p = 0.04), postoperative ventilation greater than 7 days (33% vs 15%, p = 0.01), Society of Thoracic Surgeons-European Association for Cardio-Thoracic Surgery (STAT) category 5 operations (38% vs 21%, p = 0.02), and respiratory rate during spontaneous breathing trial (median 42 vs 37 breaths/min, p = 0.01). In multivariable analysis, UA abnormalities (adjusted odds ratio [AOR] 3.5; 95% CI, 1.4-9.0), postoperative ventilation greater than 7 days (AOR 2.3; 95% CI, 1.0-5.2), and STAT category 5 operations (AOR 2.4; 95% CI, 1.1-5.2) were independently associated with FE. FE was also associated with unplanned reoperation/reintervention during hospital course (38% vs 22%, p = 0.04), longer hospitalization (median 29 vs 16.5 d, p < 0.0001), and in-hospital mortality (13% vs 3%, p = 0.02). CONCLUSIONS: FE in neonates occurs relatively commonly following cardiac surgery and is associated with adverse clinical outcomes. Additional data are needed to further optimize periextubation decision-making in patients with multiple clinical factors associated with FE.

Methods to Enhance Causal Inference for Assessing Impact of Clinical Informatics Platform Implementation.

BACKGROUND: Hospitals are increasingly likely to implement clinical informatics tools to improve quality of care, necessitating rigorous approaches to evaluate effectiveness. We leveraged a multi-institutional data repository and applied causal inference methods to assess implementation of a commercial data visualization software in our pediatric cardiac intensive care unit. METHODS: Natural experiment in the University of Michigan (UM) Cardiac Intensive Care Unit pre and postimplementation of data visualization software analyzed within the Pediatric Cardiac Critical Care Consortium clinical registry; we identified N=21 control hospitals that contributed contemporaneous registry data during the study period. We used the platform during multiple daily rounds to visualize clinical data trends. We evaluated outcomes-case-mix adjusted postoperative mortality, cardiac arrest and unplanned readmission rates, and postoperative length of stay-most likely impacted by this change. There were no quality improvement initiatives focused specifically on these outcomes nor any organizational changes at UM in either era. We performed a difference-in-differences analysis to compare changes in UM outcomes to those at control hospitals across the pre versus postimplementation eras. RESULTS: We compared 1436 pre versus 779 postimplementation admissions at UM to 19 854 (pre) versus 14 160 (post) at controls. Admission characteristics were similar between eras. Postimplementation at UM we observed relative reductions in cardiac arrests among medical admissions, unplanned readmissions, and postoperative length of stay by -14%, -41%, and -18%, respectively. The difference-in-differences estimate for each outcome was statistically significant (P<0.05), suggesting the difference in outcomes at UM pre versus postimplementation is statistically significantly different from control hospitals during the same time. CONCLUSIONS: Clinical registries provide opportunities to thoroughly evaluate implementation of new informatics tools at single institutions. Borrowing strength from multi-institutional data and drawing ideas from causal inference, our analysis solidified greater belief in the effectiveness of this software across our institution.

Functional Status Change Among Infants, Children, and Adolescents Following Extracorporeal Life Support: a Multicenter Report.

In our retrospective multicenter study of patients 0 to 18 years of age who survived extracorporeal life support (ECLS) between January 2010 and December 2018, we sought to characterize the functional status scale (FSS) of ECLS survivors, determine the change in FSS from admission to discharge, and examine risk factors associated with development of new morbidity and unfavorable outcome. During the study period, there were 1,325 ECLS runs, 746 (56%) survived to hospital discharge. Pediatric patients accounted for 56%. Most common ECLS indication was respiratory failure (47%). ECLS support was nearly evenly split between veno-arterial and veno-venous (51% vs . 49%). Median duration of ECLS in survivors was 5.5 days. Forty percent of survivors had new morbidity, and 16% had an unfavorable outcome. In a logistic regression, African American patients (OR 1.68, p = 0.01), longer duration of ECLS (OR 1.002, p = 0.004), mechanical (OR 1.79, p = 0.002), and renal (OR 1.64, p = 0.015) complications had higher odds of new morbidity. Other races (Pacific Islanders, and Native Americans) (OR 2.89, p = 0.013), longer duration of ECLS (OR 1.002, p = 0.002), and mechanical complications (OR 1.67, p = 0.026) had higher odds of unfavorable outcomes. In conclusion, in our multi-center 9-year ECLS experience, 56% survived, 40% developed new morbidity, and 84% had favorable outcome. Future studies with larger populations could help identify modifiable risk factors that could help guide clinicians in this fragile patient population.

Prediction of extubation failure in the paediatric cardiac ICU using machine learning and high-frequency physiologic data.

BACKGROUND: Cardiac intensivists frequently assess patient readiness to wean off mechanical ventilation with an extubation readiness trial despite it being no more effective than clinician judgement alone. We evaluated the utility of high-frequency physiologic data and machine learning for improving the prediction of extubation failure in children with cardiovascular disease. METHODS: This was a retrospective analysis of clinical registry data and streamed physiologic extubation readiness trial data from one paediatric cardiac ICU (12/2016-3/2018). We analysed patients' final extubation readiness trial. Machine learning methods (classification and regression tree, Boosting, Random Forest) were performed using clinical/demographic data, physiologic data, and both datasets. Extubation failure was defined as reintubation within 48 hrs. Classifier performance was assessed on prediction accuracy and area under the receiver operating characteristic curve. RESULTS: Of 178 episodes, 11.2% (N = 20) failed extubation. Using clinical/demographic data, our machine learning methods identified variables such as age, weight, height, and ventilation duration as being important in predicting extubation failure. Best classifier performance with this data was Boosting (prediction accuracy: 0.88; area under the receiver operating characteristic curve: 0.74). Using physiologic data, our machine learning methods found oxygen saturation extremes and descriptors of dynamic compliance, central venous pressure, and heart/respiratory rate to be of importance. The best classifier in this setting was Random Forest (prediction accuracy: 0.89; area under the receiver operating characteristic curve: 0.75). Combining both datasets produced classifiers highlighting the importance of physiologic variables in determining extubation failure, though predictive performance was not improved. CONCLUSION: Physiologic variables not routinely scrutinised during extubation readiness trials were identified as potential extubation failure predictors. Larger analyses are necessary to investigate whether these markers can improve clinical decision-making.

In Vivo Porcine Aged Deep Vein Thrombosis Model for Testing Ultrasound-based Thrombolysis Techniques.

As blood clots age, many thrombolytic techniques become less effective. To fully evaluate these techniques for potential clinical use, a large animal aged-clot model is needed. Previous minimally invasive attempts to allow clots to age in an in vivo large animal model were unsuccessful because of the clot clearance associated with relatively high level of cardiac health of readily available research pigs. Prior models have thus subsequently used invasive surgical techniques with the associated morbidity, animal stress and cost. We propose a method for forming sub-acute venous blood clots in an in-vivo porcine model. The age of the clots can be controlled and varied. By using an intravenous scaffold to anchor the clot to the vessel wall during the aging process, we can show that sub-acute clots can consistently be formed with a minimally invasive, percutaneous approach. The clot formed in this study remained intact for at least 1 wk in all subjects. Therefore, we established a new minimally invasive, large animal aged-clot model for evaluation of thrombolytic techniques.

Predicting and Surviving Prolonged Critical Illness After Congenital Heart Surgery.

OBJECTIVES: Prolonged critical illness after congenital heart surgery disproportionately harms patients and the healthcare system, yet much remains unknown. We aimed to define prolonged critical illness, delineate between nonmodifiable and potentially preventable predictors of prolonged critical illness and prolonged critical illness mortality, and understand the interhospital variation in prolonged critical illness. DESIGN: Observational analysis. SETTING: Pediatric Cardiac Critical Care Consortium clinical registry. PATIENTS: All patients, stratified into neonates (≤28 d) and nonneonates (29 d to 18 yr), admitted to the pediatric cardiac ICU after congenital heart surgery at Pediatric Cardiac Critical Care Consortium hospitals. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: There were 2,419 neonates and 10,687 nonneonates from 22 hospitals. The prolonged critical illness cutoff (90th percentile length of stay) was greater than or equal to 35 and greater than or equal to 10 days for neonates and nonneonates, respectively. Cardiac ICU prolonged critical illness mortality was 24% in neonates and 8% in nonneonates (vs 5% and 0.4%, respectively, in nonprolonged critical illness patients). Multivariable logistic regression identified 10 neonatal and 19 nonneonatal prolonged critical illness predictors within strata and eight predictors of mortality. Only mechanical ventilation days and acute renal failure requiring renal replacement therapy predicted prolonged critical illness and prolonged critical illness mortality in both strata. Approximately 40% of the prolonged critical illness predictors were nonmodifiable (preoperative/patient and operative factors), whereas only one of eight prolonged critical illness mortality predictors was nonmodifiable. The remainders were potentially preventable (postoperative critical care delivery variables and complications). Case-mix-adjusted prolonged critical illness rates were compared across hospitals; six hospitals each had lower- and higher-than-expected prolonged critical illness frequency. CONCLUSIONS: Although many prolonged critical illness predictors are nonmodifiable, we identified several predictors to target for improvement. Furthermore, we observed that complications and prolonged critical care therapy drive prolonged critical illness mortality. Wide variation of prolonged critical illness frequency suggests that identifying practices at hospitals with lower-than-expected prolonged critical illness could lead to broader quality improvement initiatives.

Ex Vivo Heart Perfusion for 72 Hours Using Plasma Cross Circulation.

Preservation of a donor heart for transplantation is limited to 6-8 hours. Based on our demonstration of 12 hour perfusion with plasma cross circulation, this study aimed to evaluate ex vivo heart perfusion (EVHP) for up to 72 hours using cross plasma circulation (XC-plasma) from a live, awake paracorporeal sheep (PCS). Six ovine hearts were perfused for 72 hours using plasma cross circulation at a rate of 1 L/min with a live, awake PCS. Controls were seven perfused hearts without cross circulation. Experiments were electively ended at 72 hours, and epinephrine (0.1 mg) was delivered to demonstrate hormonal responsiveness. All controls failed at 6-10 hours. All six hearts perfused for 72 hours maintained normal heart function, metabolism, and responsiveness to epinephrine. Blood gases, electrolytes, and lactate levels were normal and stable throughout the study. All hearts appeared suitable for transplantation. We have demonstrated successful normothermic EVHP for 72 hours.

Three-dimensional US Fractional Moving Blood Volume: Validation of Renal Perfusion Quantification.

Background Three-dimensional (3D) fractional moving blood volume (FMBV) derived from 3D power Doppler US has been proposed for noninvasive approximation of perfusion. However, 3D FMBV has never been applied in animals against a ground truth. Purpose To determine the correlation between 3D FMBV and the reference standard of fluorescent microspheres (FMS) for measurement of renal perfusion in a porcine model. Materials and Methods From February 2017 to September 2017, adult pigs were administered FMS before and after measurement of renal 3D FMBV at baseline (100%) and approximately 75%, 50%, and 25% flow levels by using US machines from two different vendors. The 3D power Doppler US volumes were converted and segmented, and correlations between FMS and 3D FMBV were made with simple linear regression (r2). Similarity and reproducibility of manual segmentation were determined with the Dice similarity coefficient and 3D FMBV reproducibility (intraclass correlation coefficient [ICC]). Results Thirteen pigs were studied with 33 flow measurements. Kidney volume (mean Dice similarity coefficient ± standard deviation, 0.89 ± 0.01) and renal segmentation (coefficient of variation = 12.6%; ICC = 0.86) were consistent. The 3D FMBV calculations had high reproducibility (ICC = 0.97; 95% confidence interval: 0.96, 0.98). The 3D FMBV per-pig correlation showed excellent correlation for US machines from both vendors (mean r2 = 0.96 [range, 0.92-1.0] and 0.93 [range, 0.78-1.0], respectively). The correlation between 3D FMBV and perfusion measured with microspheres was high for both US machines (r2 = 0.80 [P < .001] and 0.70 [P < .001], respectively). Conclusion The strong correlation between three-dimensional (3D) fractional moving blood volume (FMBV) and fluorescent microspheres indicates that 3D FMBV shows excellent correlation to perfusion and good reproducibility. © RSNA, 2019 Online supplemental material is available for this article. See also the editorial by Morrell et al in this issue.

Current monitoring and innovative predictive modeling to improve care in the pediatric cardiac intensive care unit.

The objectives of this review are (I) to describe the challenges associated with monitoring patients in the pediatric cardiac intensive care unit (PCICU) and (II) to discuss the use of innovative statistical and artificial intelligence (AI) software programs to attempt to predict significant clinical events. Patients cared for in the PCICU are clinically fragile and at risk for fatal decompensation. Current monitoring modalities are often ineffective, sometimes inaccurate, and fail to detect a deteriorating clinical status in a timely manner. Predictive models created by AI and machine learning may lead to earlier detection of patients at risk for clinical decompensation and thereby improve care for critically ill pediatric cardiac patients.

Ultrasonic Cavitation-Enabled Treatment for Therapy of Hypertrophic Cardiomyopathy: Proof of Principle.

Ultrasound myocardial cavitation-enabled treatment was applied to the SS-16BN rat model of hypertrophic cardiomyopathy for proof of the principle underlying myocardial reduction therapy. A focused ultrasound transducer was targeted using 10-MHz imaging (10 S, GE Vivid 7) to the left ventricular wall of anesthetized rats in a warmed water bath. Pulse bursts of 4-MPa peak rarefactional pressure amplitude were intermittently triggered 1:8 heartbeats during a 10-min infusion of a microbubble suspension. Methylprednisolone was given to reduce initial inflammation, and Losartan was given to reduce fibrosis in the healing tissue. At 28 d post therapy, myocardial cavitation-enabled treatment significantly reduced the targeted wall thickness by 16.2% (p <0.01) relative to shams, with myocardial strain rate and endocardial displacement reduced by 34% and 29%, respectively, which are sufficient for therapeutic treatment. Premature electrocardiogram complexes and plasma troponin measurements were found to identify optimal and suboptimal treatment cohorts and would aid in achieving the desired impact. With clinical translation, myocardial cavitation-enabled treatment should fill the need for a new non-invasive hypertrophic cardiomyopathy therapy option.

Functional Status Change Among Children With Extracorporeal Membrane Oxygenation to Support Cardiopulmonary Resuscitation in a Pediatric Cardiac ICU: A Single Institution Report.

OBJECTIVES: The purpose of this study is to describe the functional status of survivors from extracorporeal cardiopulmonary resuscitation instituted during in-hospital cardiac arrest using the Functional Status Scale. We aimed to determine risk factors leading to the development of new morbidity and unfavorable functional outcomes. DESIGN: This was a single-center retrospective chart review abstracting patient characteristics/demographic data, duration of cardiopulmonary resuscitation, duration of extracorporeal membrane oxygenation support, as well as maximum lactate levels within 2 hours before and after extracorporeal cardiopulmonary resuscitation. Cardiac arrest was defined as the administration of chest compressions for a nonperfusing cardiac rhythm. Extracorporeal cardiopulmonary resuscitation was defined by instituting extracorporeal membrane oxygenation during active chest compressions. Functional Status Scale scores were calculated at admission and on hospital discharge for patients who survived. SETTING: Patients admitted in the pediatric cardiac ICU at C.S. Mott Children's Hospital from January 1, 2005, to December 31, 2015. PATIENTS: Children less than 18 years who underwent extracorporeal cardiopulmonary resuscitation. INTERVENTIONS: Not applicable. MEASUREMENTS AND MAIN RESULTS: Of 608 extracorporeal membrane oxygenation events during the study period, 80 were extracorporeal cardiopulmonary resuscitation (14%). There were 40 female patients (50%). Median age was 40 days (interquartile range, 9-342 d). Survival to hospital discharge was 48% (38/80). Median Functional Status Scale score at admission was 6 (interquartile range, 6-6) and at hospital discharge 9 (interquartile range, 8-11). Out of 38 survivors, 19 (50%) had a change of Functional Status Scale score greater than or equal to 3, that is consistent with new morbidity, and 26 (68%) had favorable functional outcomes with a change in Functional Status Scale score of less than 5. CONCLUSIONS: This is the first extracorporeal cardiopulmonary resuscitation report to examine changes in Functional Status Scale from admission (baseline) to discharge as a measure of overall functional outcome. Half of surviving patients (19/38) had new morbidity, while 68% (26/38) had favorable outcomes. Lactate levels, duration of cardiopulmonary resuscitation, and duration of extracorporeal membrane oxygenation were not found to be risk factors for the development of new morbidity and poor functional outcomes. Functional Status Scale may be used as a metric to monitor improvement of extracorporeal cardiopulmonary resuscitation outcomes and help guide research initiatives to decrease morbidity in this patient population.

Incidence of Fever and Positive Bacterial Cultures in Neonates Receiving Prostaglandin.

Prostaglandin E (PGE1) is necessary to maintain ductus arteriosus patency in many newborns with congenital heart disease. Because PGE1 therapy commonly leads to fever, and given this population's fragile state, a complete sepsis workup is often performed in febrile, but otherwise asymptomatic, patients. This practice of liberal evaluation with bacterial cultures, empiric antibiotic treatment, and delays in essential surgical intervention may result in poor resource utilization and lead to increased iatrogenic morbidity. This study sought to determine the incidence of fever and culture-positive infection in patients receiving PGE1, and identify diagnostic variables that predict culture-positive infection. The study included a single-center retrospective review of all neonates receiving PGE1 between 2011 and 2014. Logistic regression and receiver operator characteristic analysis were used to identify significant predictors of positive bacterial cultures. Among 435 neonates, 175 (40%) had fevers (≥ 38.3 °C) while concurrently receiving PGE1, but only 9 (2%) had culture-positive infection and 1 (< 1%) had culture-positive bacteremia. Among 558 cultures collected, only 16 (3%) had bacterial growth. Multivariable analysis revealed age (p = 0.049, AUC 0.604), hospital length of stay (p = 0.002, AUC 0.764) and hypoxemia (p = 0.044, AUC 0.727) as the only significant predictors of positive cultures. Fever (p = 0.998, AUC 0.424) was not a significant predictor. In conclusion, given that fever occurs frequently in neonates receiving PGE1 and it is a very non-specific marker and not a predictor of positive cultures, the common practice of complete sepsis workup should be re-examined in febrile patients at low risk of bacterial illness.

Multiple ultrasound cavitation-enabled treatments for myocardial reduction.

BACKGROUND: Ultrasound myocardial cavitation enabled treatment (MCET) is an image-guided method for tissue reduction. In this study, a strategy of fractionated (multiple) treatments was tested for efficacy. METHODS: Dahl SS rats were anesthetized and prepared for treatment with a focused ultrasound transducer in a warm water bath. Aiming at the anterior left ventricular wall was facilitated by imaging with a 10 MHz phased array (10S, GE Vivid 7, GE Vingmed Ultrasound, Horten, Norway). MCET was accomplished at 1.5 MHz by pulse bursts of 4 MPa peak rarefactional pressure amplitude, which were intermittently triggered 1:8 from the ECG during infusion of a microbubble suspension for cavitation nucleation. Test groups were sham, a 200 s treatment, three 200 s treatments a week apart, and a 600 s treatment. Treatment outcome was observed by plasma troponin after 4 h, echocardiographic monitoring and histology at 6 wk. RESULTS: The impacts of the fractionated treatments summed to approximately the same as the long treatment; e. g. the troponin result was 10.5 ± 3.2 for 200 s, 22.7 ± 5.4 (p < 0.001) for the summed fractionated treatments and 29.9 ± 6.4 for 600 s (p = 0.06 relative to the summed fractionated). While wall thickness was not reduced for the fractionated treatment, tissue strain was reduced by 35% in the target area relative sham (p < 0.001). CONCLUSION: The ability to fractionate treatment may be advantageous for optimizing patient outcome relative to all-or nothing therapy by surgical myectomy or alcohol ablation.

Non-Invasive Thrombolysis Using Microtripsy in a Porcine Deep Vein Thrombosis Model.

Histotripsy is a non-invasive therapeutic technique that uses ultrasound generated from outside the body to create controlled cavitation in targeted tissue, and fractionates it into acellular debris. We have developed a new histotripsy approach, termed microtripsy, to improve targeting accuracy and to avoid collateral tissue damage. This in vivo study evaluates the safety and efficacy of microtripsy for non-invasive thrombolysis in a porcine deep vein thrombosis model. Acute thrombi were formed in left femoral veins of pigs (∼35 kg) by occluding the vessel using two balloon catheters and infusing with thrombin. Guided by real-time ultrasound imaging, microtripsy thrombolysis treatment was conducted in 14 pigs; 10 pigs were euthanized on the same day (acute) and 4 at 2 wk (subacute). To evaluate vessel damage, 30-min free-flow treatment in the right femoral vein (no thrombus) was also conducted in 8 acute pigs. Blood flow was successfully restored or significantly increased after treatment in 13 of the 14 pigs. The flow channels re-opened by microtripsy had a diameter up to 64% of the vessel diameter (∼6 mm). The average treatment time was 16 min per centimeter-long thrombus. Only mild intravascular hemolysis was induced during microtripsy thrombolysis. No damage was observed on vessel walls after 2 wk of recovery, venous valves were preserved, and there was no sign of pulmonary embolism. The results of this study indicate that microtripsy has the potential to be a safe and effective treatment for deep vein thrombosis in a porcine model.

Normothermic Ex Vivo Heart Perfusion: Effects of Live Animal Blood and Plasma Cross Circulation.

Prolonged normothermic ex vivo heart perfusion could transform cardiac transplantation. To help identify perfusate components that might enable long-term perfusion, we evaluated the effects of cross-circulated whole blood and cross-circulated plasma from a live paracorporeal animal on donor porcine hearts preserved via normothermic ex vivo heart perfusion. Standard perfusion (SP; n = 40) utilized red blood cell/plasma perfusate and Langendorff technique for a goal of 12 hours. Cross-circulation groups used a similar circuit with the addition of cross-circulated venous whole blood (XC-blood; n = 6) or cross-circulated filtered plasma (XC-plasma; n = 7) between a live paracorporeal pig under anesthesia and the perfusate reservoir. Data included oxygen metabolism, vascular resistance, lactate production, left ventricular function, myocardial electrical impedance, and histopathologic injury score. All cross-circulation hearts were successfully perfused for 12 hours, compared with 22 of 40 SP hearts (55%; p = 0.002). Both cross-circulation groups demonstrated higher oxygen consumption and vascular resistance than standard hearts from hours 3-12. No significant differences were seen between XC-blood and XC-plasma hearts in any variable, including left ventricular dP/dT after 12 hours (1478 ± 700 mm Hg/s vs. 872 ± 500; p = 0.17). We conclude that cross circulation of whole blood or plasma from a live animal improves preservation of function of perfused hearts, and cross-circulated plasma performs similarly to cross-circulated whole blood.

Extracorporeal Life Support as a Rescue Measure for Managing Life-Threatening Arrythmia and Brugada Syndrome.

We describe the use of extracorporeal cardiopulmonary resuscitation (E-CPR) to transiently stabilize a 3-month-old patient who presented with ventricular tachyarrhythmias leading to spontaneous cardiac arrest. The patient required 4 days of extracorporeal life support (ECLS) where he was diagnosed with probable Brugada syndrome (BS). The patient was discharged home in stable condition after implantable cardioverter defibrillator placement. This case highlights the importance of early transfer to extracorporeal membrane oxygenation (ECMO) center in the setting of unexplained cardiac arrhythmia in a pediatric patient. BS is an autosomal dominant genetic disorder with variable expression characterized by abnormal findings on electrocardiogram (ECG) in conjunction with an increased risk of ventricular tachyarrhythmias and sudden cardiac arrest (SCA). Early management is critical and early consideration to transfer to an institution where extracorporeal life support (ECLS/ECMO) is present to support the patient while further diagnostic work up is in progress is lifesaving.

Histotripsy Thrombolysis on Retracted Clots.

Retracted blood clots have been previously recognized to be more resistant to drug-based thrombolysis methods, even with ultrasound and microbubble enhancements. Microtripsy, a new histotripsy approach, has been investigated as a non-invasive, drug-free and image-guided method that uses ultrasound to break up clots with improved treatment accuracy and a lower risk of vessel damage compared with the traditional histotripsy thrombolysis approach. Unlike drug-mediated thrombolysis, which is dependent on the permeation of the thrombolytic agents into the clot, microtripsy controls acoustic cavitation to fractionate clots. We hypothesize that microtripsy thrombolysis is effective on retracted clots and that the treatment efficacy can be enhanced using strategies incorporating electronic focal steering. To test our hypothesis, retracted clots were prepared in vitro and the mechanical properties were quantitatively characterized. Microtripsy thrombolysis was applied on the retracted clots in an in vitro flow model using three different strategies: single-focus, electronically-steered multi-focus and dual-pass multi-focus. Results show that microtripsy was used to successfully generate a flow channel through the retracted clot and the flow was restored. The multi-focus and the dual-pass treatments incorporating the electronic focal steering significantly increased the recanalized flow channel size compared to the single-focus treatments. The dual-pass treatments achieved a restored flow rate up to 324 mL/min without cavitation contacting the vessel wall. The clot debris particles generated from microtripsy thrombolysis remained within the safe range. The results of this study show the potential of microtripsy thrombolysis for retracted clot recanalization with the enhancement of electronic focal steering.

Achieving 12 Hour Normothermic Ex Situ Heart Perfusion: An Experience of 40 Porcine Hearts.

Although total body perfusion with extracorporeal life support (ECLS) can be maintained for weeks, individual organ perfusion beyond 12 hours has yet to be achieved clinically. Normothermic ex situ heart perfusion (ESHP) offers the potential for prolonged cardiac preservation. We developed an ESHP system to study the effect of perfusate variables on organ preservation, with the ultimate goal of extending organ perfusion for ≥24 hours. Forty porcine hearts were perfused for a target of 12 hours. Hearts that maintained electromechanical activity and had a <3× increase in vascular resistance were considered successful preservations. Perfusion variables, metabolic byproducts, and histopathology were monitored and sampled to identify factors associated with preservation failure. Twenty-two of 40 hearts were successfully preserved at 12 hours. Successful 12 hour experiments demonstrated lower potassium (4.3 ± 0.8 vs. 5.0 ± 1.2 mmol/L; p = 0.018) and lactate (3.5 ± 2.8 vs. 4.5 ± 2.9 mmol/L; p = 0.139) levels, and histopathology revealed less tissue damage (p = 0.003) and less weight gain (p = 0.072). Results of these early experiments suggest prolonged ESHP is feasible, and that elevated lactate and potassium levels are associated with organ failure. Further studies are necessary to identify the ideal perfusate for normothermic ESHP.

Hyperoxia Is Associated With Poor Outcomes in Pediatric Cardiac Patients Supported on Venoarterial Extracorporeal Membrane Oxygenation.

OBJECTIVES: Patients who require venoarterial extracorporeal membrane oxygenation because of cardiac failure frequently have supranormal blood oxygen tensions (hyperoxia). Recent studies have suggested worse outcomes in patients with hyperoxia after resuscitation from cardiac or respiratory arrests, presumably because of oxidative stress. There are limited data regarding the effect of hyperoxia on outcomes in pediatric patients on venoarterial extracorporeal membrane oxygenation. DESIGN: Retrospective chart review. SETTING: Pediatric cardiothoracic ICU. PATIENTS: Cardiac surgery patients less than 1 year old requiring venoarterial extracorporeal membrane oxygenation in the postoperative period from 2007 to 2013. MEASUREMENTS AND MAIN RESULTS: In 93 infants (median time on extracorporeal membrane oxygenation, 5 d), mortality at 30 days post surgery (primary outcome) was 38%. Using a receiver operating characteristic curve, a mean PaO2 of 193 mm Hg in the first 48 hours of extracorporeal membrane oxygenation was determined to have good discriminatory ability with regard to 30-day mortality. Univariate analysis identified a mean PaO2 greater than 193 mm Hg (p = 0.001), longer cardiopulmonary bypass times (p = 0.09), longer duration of extracorporeal membrane oxygenation (p < 0.0001), and higher extracorporeal membrane oxygenation pump flows (p = 0.052) as possible risk factors for 30-day mortality. In multivariable analysis controlling for the variables listed above, a mean PaO2 greater than 193 mm Hg remained an independent risk factor for mortality (p = 0.03). In addition, a mean PaO2 greater than 193 mm Hg was associated with the need for renal dialysis (p = 0.02) but not with neurologic injury (p = 0.41) during the hospitalization. CONCLUSIONS: In infants with congenital heart disease who are placed on venoarterial extracorporeal membrane oxygenation postoperatively, hyperoxia (defined as a mean PaO2 > 193 mm Hg in the first 48 hr of extracorporeal membrane oxygenation) was an independent risk factor for 30-day mortality after surgery. Future studies are needed to delineate the causative or associative role of hyperoxia with outcomes, especially in children with baseline cyanosis who may be more susceptible to the effects of oxidative stress.