Hypoplastic left heart syndrome

Hypoplastic left heart syndrome(HLHS) refers to the abnormal development of the left-sided cardiac structures, resulting in obstruction to blood flow from the left ventricular outflow tract. In addition, the syndrome includes underdevelopment of the left ventricle, aorta, and aortic arch, as well as mitral atresia or stenosis. HLHS has been reported to occur in approximately 0.016 to 0.036% of all live births. Newborn infants with the condition generally are born at full term and initially appear healthy. As the arterial duct closes, the systemic perfusion becomes decreased, resulting in hypoxemia, acidosis, and shock. Usually, no heart murmur, or a non-specific heart murmur, may be detected. The second heart sound is loud and single because of aortic atresia. Often the liver is enlarged secondary to congestive heart failure. The embryologic cause of the disease, as in the case of most congenital cardiac defects, is not fully known. The most useful diagnostic modality is the echocardiogram. The syndrome can be diagnosed by fetal echocardiography between 18 and 22 weeks of gestation. Differential diagnosis includes other left-sided obstructive lesions where the systemic circulation is dependent on ductal flow (critical aortic stenosis, coarctation of the aorta, interrupted aortic arch). Children with the syndrome require surgery as neonates, as they have duct-dependent systemic circulation. Currently, there are two major modalities, primary cardiac transplantation or a series of staged functionally univentricular palliations. The treatment chosen is dependent on the preference of the institution, its experience, and also preference. Although survival following initial surgical intervention has improved significantly over the last 20 years, significant mortality and morbidity are present for both surgical strategies. As a result pediatric cardiologists continue to be challenged by discussions with families regarding initial decision relative to treatment, and long-term prognosis as information on long-term survival and quality of life for those born with the syndrome is limited

Nanoemulsions for drug delivery through different routes

Utilising nanoemulsions as vehicles for carrying active pharmaceutical ingredients is emerging as a promising approach for the latters’ targeted delivery. For drug molecules to be clinically effective, their administration by a route, which provides a proper channel for them to reach their target, is of prime importance. Further, they also need to be suitably protected in the biological milieu till they are delivered to the required site of action. Nanoemulsions with a mean droplet diameter of about 20-200 nm are extremely versatile in this regard. Due to their characteristic size and properties, which includes kinetic stability, they are very effective in enveloping and/or solubilising the drugs and successfully chaperoning them towards suitable targets. They also cause the drugs to be released  in controlled and sustained modes, thereby reducing drug toxicity and dumping. Additionally, depending on the physiochemical properties of the drugs, nanoemulsions can be structurally engineered to maximize their solubilisation as per the required route of delivery, which is heavily dependent on the drug structure. Effective targeting can be achieved by incorporating suitable homing molecules on their surface, which in turn  recognize and bind to specific receptors on the target molecules. This review focuses on the different routes by which drug loaded  nanoemulsions can be administered, thus throwing light on the versatility of these vehicles for therapeutic and other related applications

Extracorporeal Cardiopulmonary Resuscitation

ECMO, or extracorporeal membrane oxygenation, is an advanced life support technique that provides cardiac and pulmonary support similar to cardiopulmonary bypass. ECPR (extracorporeal cardiopulmonary resuscitation) is the rapid deployment of VA-ECMO when conventional cardiopulmonary resuscitation fails to provide return of spontaneous circulation. Evidence in the literature is sparse, but with expanding reported applications, ECPR has shown promise to improve outcomes of cardiac arrest. ECPR is superior to conventional CPR for both survival and neurologic outcomes. ECPR has been successfully used to manage arrests secondary to cardiac and non-cardiac causes. Arrests secondary to primary cardiac causes have the best overall outcome. Other determinants of outcomes of ECPR include duration of low flow state and on-ECMO complications. A narrow list of ECPR contraindications exists, and includes severe neurologic injury and irreversible primary disease process. Various complications can occur with ECPR, and include mechanical, cardiovascular, pulmonary, hematologic, renal, and neurologic complications. Neurologic complications are the most serious, and significantly affect mortality or quality of life. ECPR is a nascent field, and substantial work remains to be done to optimize its application. Given the small number of patients at each institutional level, this is a field ripe for collaborative work and rewarding results

Pulmonary function after modified venovenous ultrafiltration in infants: A prospective, randomized trial

AbstractObjective: We sought to examine the effects of modified venovenous ultrafiltration after cardiopulmonary bypass on pulmonary compliance in infants. Methods: We prospectively enrolled 38 infants undergoing their first operation for congenital heart disease. Infants were randomized to receive 20 minutes of modified ultrafiltration after bypass or control. Static and dynamic compliance was measured after induction of anesthesia, before and immediately after filtration in the operating theater, 1 hour after return to the pediatric intensive care unit, and 24 hours after the operation. Length of time on the ventilator, inotropic requirements, and length of stay in the intensive care unit were recorded. Results: Modified ultrafiltration produced a significant immediate improvement in dynamic (pre-ultrafiltration 2.5 ± 1.9 mL/cm H2O to post-ultrafiltration 2.9 ± 2.7 mL/cm H2O, P = .03) and static (pre-ultrafiltration 2.1 ± 0.9 mL/cm H2O to post-ultrafiltration 2.9 ± 2.1 mL/cm H2O, P = .04) compliance. However, there was no significant difference in the change in dynamic (P = .3) or static (P = .7) compliance in the ultrafiltration and control groups when compared before the operation, after the operation, and at 24 hours. There was no significant difference in the time to extubation between patients and control subjects (140 ± 91 hours vs 90 ± 58 hours) or the length of intensive care unit stay (10.0 ± 9.1 days vs 7.4 ± 5.7 days). Conclusions: Modified ultrafiltration produces an improvement in pulmonary compliance after bypass in infants. However, these improvements are not sustained past the immediate post-ultrafiltration period and do not lead to a decreased length of intubation or intensive care unit stay. (J Thorac Cardiovasc Surg 2000; 119:501-7

Characterizing peritoneal dialysis catheter use in pediatric patients after cardiac surgery

ObjectiveChildren who undergo cardiac surgery are at high risk for renal insufficiency and abdominal compartment syndrome. Peritoneal dialysis catheter (PDC) implantation is used in this population for abdominal decompression and access for dialysis. However, there is no consensus regarding PDC use, and the practice varies widely. This study was undertaken to assess associated factors, outcomes, and variability in the use of PDC in patients who have undergone cardiac surgery.MethodsThe cohort was obtained from the Kids' Inpatient Database, years 2006 and 2009. Patients who underwent cardiac surgery were included and the subset that underwent PDC implantation during the same hospitalization was identified. Univariable and multivariable analyses assessed factors associated with PDC and survival.ResultsA cohort of 28,259 patients underwent cardiac surgery, of whom 558 (2%) had PDCs placed. In the PDC group, 39.1% (n = 218) had acute renal failure whereas 3.5% or patients (n = 974) in the non-PDC group had acute renal failure. Among patients receiving PDC, mortality was 20.3% (n = 113; vs 3.4% overall mortality, n = 955). Excluding patients with acute renal failure, mortality remained 12% (n = 41) for the PDC group. Factors associated significantly with PDC placement in the overall cohort were younger age, greater surgical complexity, nonelective admission, hospital region, use of cardiopulmonary bypass, and acute renal failure.ConclusionsPatients receiving PDC after cardiac surgery had 20% mortality, which remained 12% after excluding patients with acute renal failure. Given the variability in PDC use and poor outcomes, further research is needed to assess the possible benefit of earlier intervention for peritoneal access in this high-risk cohort

Mild postoperative acute kidney injury and outcomes after surgery for congenital heart disease

ObjectiveThe effect of mild acute kidney injury (AKI) on outcomes after heart surgery in children is unclear. We sought to characterize the epidemiology of mild AKI associated with surgery for congenital heart disease (CHS-AKI) in children.MethodsWe conducted a single-center, retrospective cohort study of 693 patients (aged 6 days-18 years) who underwent heart surgery in 2009. The prevalence of AKI within 72 hours of surgery was determined using the 3-stage Acute Kidney Injury Network criteria. Factors associated with both hospital length of stay and AKI were used in a proportional hazards model to test the association of stage 1 AKI with hospital length of stay.ResultsThe median age of the patients was 11.5 months (interquartile range, 3-54 months). Eighteen percent of the cohort had single ventricle heart disease and 54% underwent RACHS-1 category 3 or higher surgery. The prevalence of stages 1, 2, and 3 AKI in this cohort was 11% (n = 77), 3% (n = 19), and 1% (n = 8), respectively. Factors independently associated with AKI were prematurity, single ventricle physiology, peak postoperative lactic acid concentration, cardiopulmonary bypass time, and a history of heart surgery. Stage 2 or greater CHS-AKI was associated with hospital length of stay (adjusted hazard ratio [AHR], 0.53; 95% confidence interval [CI], 0.33-0.87; P = .01), but stage 1 was not (AHR, 0.85; 95% CI, 0.66-1.10; P = .22).ConclusionsAKI occurs after surgery for congenital heart disease but may be less common than previously reported. Although moderate to severe CHS-AKI is independently associated with prolonged recovery after heart surgery, mild disease does not appear to be

Neural networks to predict radiographic brain injury in pediatric patients treated with Extracorporeal Membrane Oxygenation

Brain injury is a significant source of morbidity and mortality for pediatric patients treated with Extracorporeal Membrane Oxygenation (ECMO). Our objective was to utilize neural networks to predict radiographic evidence of brain injury in pediatric ECMO-supported patients and identify specific variables that can be explored for future research. Data from 174 ECMO-supported patients were collected up to 24 h prior to, and for the duration of, the ECMO course. Thirty-five variables were collected, including physiological data, markers of end-organ perfusion, acid-base homeostasis, vasoactive infusions, markers of coagulation, and ECMO-machine factors. The primary outcome was the presence of radiologic evidence of moderate to severe brain injury as established by brain CT or MRI. This information was analyzed by a neural network, and results were compared to a logistic regression model as well as clinician judgement. The neural network model was able to predict brain injury with an Area Under the Curve (AUC) of 0.76, 73% sensitivity, and 80% specificity. Logistic regression had 62% sensitivity and 61% specificity. Clinician judgment had 39% sensitivity and 69% specificity. Sequential feature group masking demonstrated a relatively greater contribution of physiological data and minor contribution of coagulation factors to the model\u27s performance. These findings lay the foundation for further areas of research directions

Extracorporeal membrane oxygenation support after the Fontan operation

ObjectiveExtracorporeal membrane oxygenation has been used to support children with cardiac failure after the Fontan operation. Mortality is high, and causes of mortality remain unclear. We evaluated the in-hospital mortality and factors associated with mortality in these patients.MethodsExtracorporeal Life Support Organization registry data on patients requiring extracorporeal membrane oxygenation after the Fontan operation from 1987 to 2009 were retrospectively analyzed. Demographics and extracorporeal membrane oxygenation data were compared for survivors and nonsurvivors. A multivariable logistic regression model was used to identify factors associated with mortality.ResultsOf 230 patients, 81 (35%) survived to hospital discharge. Cardiopulmonary resuscitation was more frequent (34% vs 17%, P = .04), and median fraction of inspired oxygen concentration was higher (1 [confidence interval, 0.9–1.0] vs 0.9 [confidence interval, 0.8–1.0], P = .03) before extracorporeal membrane oxygenation in nonsurvivors compared with survivors. Extracorporeal membrane oxygenation duration and incidence of complications, including surgical bleeding, neurologic injury, renal failure, inotrope use on extracorporeal membrane oxygenation, and bloodstream infection, were higher in nonsurvivors compared with survivors (P < .05 for all). In a multivariable model, neurologic injury (odds ratio, 5.18; 95% confidence interval, 1.97–13.61), surgical bleeding (odds ratio, 2.36; 95% confidence interval, 1.22–4.56), and renal failure (odds ratio, 2.81; 95% confidence interval, 1.41–5.59) increased mortality. Extracorporeal membrane oxygenation duration of more than 65 hours to 119 hours (odds ratio, 0.33; 95% confidence interval, 0.14–0.76) was associated with decreased mortality.ConclusionsCardiac failure requiring extracorporeal membrane oxygenation after the Fontan operation is associated with high mortality. Complications during extracorporeal membrane oxygenation support increase mortality odds. Prompt correction of surgical bleeding when possible may improve survival

Cardiovascular Dysfunction Criteria in Critically Ill Children: The PODIUM Consensus Conference

CONTEXT Cardiovascular dysfunction is associated with poor outcomes in critically ill children. OBJECTIVE We aim to derive an evidence-informed, consensus-based definition of cardiovascular dysfunction in critically ill children. DATA SOURCES Electronic searches of PubMed and Embase were conducted from January 1992 to January 2020 using medical subject heading terms and text words to define concepts of cardiovascular dysfunction, pediatric critical illness, and outcomes of interest. STUDY SELECTION Studies were included if they evaluated critically ill children with cardiovascular dysfunction and assessment and/or scoring tools to screen for cardiovascular dysfunction and assessed mortality, functional status, organ-specific, or other patient-centered outcomes. Studies of adults, premature infants (≤36 weeks gestational age), animals, reviews and/or commentaries, case series (sample size ≤10), and non-English-language studies were excluded. Studies of children with cyanotic congenital heart disease or cardiovascular dysfunction after cardiopulmonary bypass were excluded. DATA EXTRACTION Data were abstracted from each eligible study into a standard data extraction form, along with risk-of-bias assessment by a task force member. RESULTS Cardiovascular dysfunction was defined by 9 elements, including 4 which indicate severe cardiovascular dysfunction. Cardiopulmonary arrest (>5 minutes) or mechanical circulatory support independently define severe cardiovascular dysfunction, whereas tachycardia, hypotension, vasoactive-inotropic score, lactate, troponin I, central venous oxygen saturation, and echocardiographic estimation of left ventricular ejection fraction were included in any combination. There was expert agreement (>80%) on the definition. LIMITATIONS All included studies were observational and many were retrospective. CONCLUSIONS The Pediatric Organ Dysfunction Information Update Mandate panel propose this evidence-informed definition of cardiovascular dysfunction

Survival and Clinical Course at Fontan After Stage One Palliation With Either a Modified Blalock-Taussig Shunt or a Right Ventricle to Pulmonary Artery Conduit

ObjectivesWe sought to determine whether the type of shunt used at stage one palliation (S1P) affected the survival and the perioperative course through Fontan completion.BackgroundAlthough improved surgical and interstage survival have been demonstrated with the use of the right ventricle to pulmonary artery (RV-PA) conduit compared with a modified Blalock-Taussig shunt (BTS) at S1P, it is unknown whether this effect will be observed in long-term follow-up.MethodsAll patients who underwent a S1P during 2002 and 2003 (n = 80) at our institution were included for analysis. Patients were followed until death or June 1, 2007. Perioperative variables at Fontan completion were recorded.ResultsFor the entire cohort, cumulative survival for those who underwent a RV-PA conduit (n = 34) was 79.4% at 3 years compared with 65.8% in the modified BTS group (n = 46) (log-rank = 0.31). At Fontan (n = 44), when compared with those who had received a modified BTS, those who had a RV-PA conduit placed at S1P had no difference in the median duration of ventilation (21 h [range 10 to 96 h] vs. 26.5 h [range 7 to 204 h], p = 0.09) or hospital stay (9 days [range 5 to 29 days] vs. 10 days [range 6 to 48 days], p = 0.89), although length of stay in the intensive care unit was shorter (2 days [range 0 to 6 days] vs. 4 days [range 1 to 25 days], p = 0.01). Sixty-seven percent of the RV-PA conduit group had at least one PA intervention 3 years after S1P compared with 42.8% in the modified BTS group (log-rank = 0.11).ConclusionsNonstatistically significant trends toward improved cumulative survival and increased PA interventions were demonstrated in patients who had a RV-PA conduit placed at S1P. Longitudinal follow-up of larger groups of randomized patients is required to determine the influence of the RV-PA conduit on long-term outcomes