Haemodynamic effects of prophylactic post-operative hydrocortisone following cardiopulmonary bypass in neonates undergoing cardiac surgery.

Multiple studies have endeavoured to define the role of steroids in paediatric congenital heart surgery; however, steroid utilisation remains haphazard. In September, 2017, our institution implemented a protocol requiring that all neonates undergoing cardiac surgery with the use of cardiopulmonary bypass receive a five-day post-operative hydrocortisone taper. This single-centre retrospective study was designed to test the hypothesis that routine post-operative hydrocortisone administration reduces the incidence of capillary leak syndrome, leads to favourable postoperative fluid balance, and less inotropic support in the early post-operative period. Data were gathered on all term neonates who underwent cardiac surgery with the use of bypass between September, 2015 and 2019. Subjects who were unable to separate from bypass, required long-term dialysis, or long-term mechanical ventilation were excluded. Seventy-five patients met eligibility criteria (non-hydrocortisone group = 52; hydrocortisone group = 23). For post-operative days 0-4, we did not observe a significant difference in net fluid balance or vasoactive inotropic score between study groups. Similarly, we saw no major difference in secondary clinical outcomes (post-operative duration of mechanical ventilation, ICU/hospital length of stay, and time from surgery to initiation of enteral feeds). In contrast to prior analyses, our study was unable to demonstrate a significant difference in net fluid balance or vasoactive inotropic score with the administration of a tapered post-operative hydrocortisone regimen. Similarly, we saw no effect on secondary clinical outcomes. Further long-term randomised control studies are necessary to validate the potential clinical benefit of utilising steroids in paediatric cardiac surgery, especially in the more fragile neonatal population.

Pediatric Extracorporeal Membrane Oxygenation Anticoagulation Protocol Associated with a Decrease in Complications.

Extracorporeal membrane oxygenation (ECMO) in pediatrics has rapidly progressed in recent years; however, there continues to be considerable variation in anticoagulation practices. In 2016, we implemented a standardized anticoagulation protocol in effort to reduce clotting and bleeding complications. A single-center retrospective analysis of pediatric patients requiring ECMO between 2014 and 2018 was performed. One hundred one ECMO cases in 94 pediatric patients met eligibility criteria (preprotocol = 64 cases; postprotocol = 37 cases). Demographics, ECMO parameters, complications, laboratories, and blood product requirements were analyzed for differences between the two groups. There was a significant decrease in the incidence of hematologic (p < 0.022), neurologic (p < 0.001), and renal complications (p < 0.001) in the postprotocol era. Incidence of bleeding, cardiac/pulmonary complications, and circuit changes were similar between the groups. The postprotocol group required fewer transfusions of red blood cells and cryoprecipitate. Additionally, platelet counts and fibrinogen levels were maintained higher in the postprotocol era. In conclusion, implementation of a standardized anticoagulation protocol was associated with improved anticoagulation parameters and a decrease in hematologic and neurologic complications, coagulopathy, renal injury, and blood product administration. We attribute these findings to transitioning to anti-Xa as a measure of heparinization and maintaining higher platelet counts.

Review of acute kidney injury and continuous renal replacement therapy in pediatric extracorporeal membrane oxygenation.

PURPOSE: To review the relevant literature of acute kidney injury (AKI) and continuous renal replacement therapy (CRRT) as it relates to pediatric extracorporeal membrane oxygenation (ECMO). METHODS: Available online relevant literature. RESULTS: ECMO is a therapeutic modality utilized to support patients with refractory respiratory and/or cardiac failure. AKI and fluid overload (FO) are frequently observed in this patient population. There are multiple modalities that can be utilized for AKI and FO which include the following: diuretics, in-line hemofiltration, and CRRT. There are multiple considerations when using CRRT with ECMO including access, CRRT flows, hemolysis, anticoagulation, and CRRT termination. CONCLUSION: While each ECMO center has its own set of equipment, experiences, and practices, it is imperative that the international ECMO community continues to work together to provide an evidence-based approach to address the morbidity and mortality associated with AKI and FO.

Outcomes of Pediatric Extracorporeal Cardiopulmonary Resuscitation: A Systematic Review and Meta-Analysis.

OBJECTIVE: The goal of this work is to provide insight into survival and neurologic outcomes of pediatric patients supported with extracorporeal cardiopulmonary resuscitation. DATA SOURCES: A systematic search of Embase, PubMed, Cochrane, Scopus, Google Scholar, and Web of Science was performed from January 1990 to May 2020. STUDY SELECTION: A comprehensive list of nonregistry studies with pediatric patients managed with extracorporeal cardiopulmonary resuscitation was included. DATA EXTRACTION: Study characteristics and outcome estimates were extracted from each article. DATA SYNTHESIS: Estimates were pooled using random-effects meta-analysis. Differences were estimated using subgroup meta-analysis and meta-regression. The Meta-analyses Of Observational Studies in Epidemiology guideline was followed and the certainty of evidence was assessed using Grading of Recommendations Assessment, Development and Evaluation system. Twenty-eight studies (1,348 patients) were included. There was a steady increase in extracorporeal cardiopulmonary resuscitation occurrence rate from the 1990s until 2020. There were 32, 338, and 1,094 patients' articles published between 1990 and 2000, 2001 and 2010, and 2010 and 2020, respectively. More than 70% were cannulated for a primary cardiac arrest. Pediatric extracorporeal cardiopulmonary resuscitation patients had a 46% (CI 95% = 43-48%; p < 0.01) overall survival rate. The rate of survival with favorable neurologic outcome was 30% (CI 95% = 27-33%; p < 0.01). CONCLUSIONS: The use of extracorporeal cardiopulmonary resuscitation is rapidly expanding, particularly for children with underlying cardiac disease. An overall survival of 46% and favorable neurologic outcomes add credence to this emerging therapy.

EEG is A Predictor of Neuroimaging Abnormalities in Pediatric Extracorporeal Membrane Oxygenation.

The goal of this project was to evaluate if severity of electroencephalogram (EEG) during or shortly after being placed on extracorporeal membrane oxygenation (ECMO) would correlate with neuroimaging abnormalities, and if that could be used as an early indicator of neurologic injury. This was a retrospective chart review spanning November 2009 to May 2018. Patients who had an EEG recording during ECMO or within 48 hours after being decannulated (early group) or within 3 months of being on ECMO (late group) were included if they also had ECMO-related neuroimaging. In the early EEG group, severity of the EEG findings of mild, moderate, and severe EEG correlated to mild, moderate, and severe neuroimaging scores. Patients on venoarterial (VA) ECMO were noted to have higher EEG and neuroimaging severity; this was statistically significant. There was no association in the late EEG group to neuroimaging abnormalities. Our study highlights that EEG severity can be an early predictor for neuroimaging abnormalities that can be identified by computed tomography (CT) and or magnetic resonance imaging (MRI). This can provide guidance for both the medical team and families, allowing for a better understanding of overall prognosis.

Quantitative Evaluation of a Mexican and a Ghanaian Tabernaemontana Species as Alternatives to Voacanga africana for the Production of Antiaddictive Ibogan Type Alkaloids.

In continuation of our efforts to provide quantitative information on antiaddictive ibogan type alkaloid-producing Tabernaemontana species, we used gas chromatography-mass spectrometry (GC/MS) to compare the alkaloid profiles of the barks and/or leaves of one Mexican and one African species - T. arborea and T. crassa, respectively, with the primary sources of commercially available semisynthetic ibogaine, Voacanga africana root and stem bark. The qualitative and quantitative similarities between T. arborea and V. africana barks consolidate previous reports regarding the potential of the former as a promising alternative source of voacangine and ibogaine. The results also suggest that T. crassa could be used to produce conopharyngine and ibogaline, two compounds with the same basic skeletal structure and possibly similar antiaddictive properties as ibogaine.

An analytical study of iboga alkaloids contained in Tabernanthe iboga-derived products offered by ibogaine treatment providers

Abstract Background Therapeutic properties of ibogaine in the treatment of addiction are attracting both clinicians and patients to its use. Since ibogaine is not an authorized medicine, the quality of these products is not always known, increasing the probability of adverse reactions. Objective This study collects different types of iboga-derived samples from treatment providers, vendors and online buyers to analyse their content. Methods Analysis of iboga products (n = 16) was performed using gas chromatography and mass spectrometry methods (GC/MS). Products included Iboga root bark, Total Alkaloids (TA), Purified Total Alkaloids (PTA HCl), ibogaine hydrochloride (ibogaine HCl) and one Voacanga africana root bark. Results The content of ibogaine was highly variable, ranging from 0.6% to 11.2% for products sold as iboga root bark, from 8.2% to 32.9% for products sold as TA, 73.7% for one sample sold as PTA and from 61.5% to 73.4% for products sold as ibogaine HCl. One sample did not show any iboga alkaloids. Other alkaloids and unknown substances were found in almost all samples. Discussion The purity of iboga products is highly variable. These results should be taken into consideration by suppliers and users, especially regarding correct dosing to avoid overdose, as well as potential interactions with other substances.

High Hemoglobin Is an Independent Risk Factor for the Development of Hemolysis During Pediatric Extracorporeal Life Support.

OBJECTIVE: To evaluate risk factors for hemolysis in pediatric extracorporeal life support. DESIGN: Retrospective, single-center study. SETTING: Pediatric intensive care unit. PATIENTS: Two hundred thirty-six children who received extracorporeal membrane oxygenation. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Risk factors for hemolysis were retrospectively analyzed from a single center in a total of 236 neonatal and pediatric patients who received extracorporeal membrane oxygenation support (ECMO). There was no difference in the incidence of hemolysis between centrifugal (127 patients) and roller head (109 patients) pump type or between venoarterial and venovenous ECMO. High hemoglobin (Hb) was found to be an independent risk factor for hemolysis in both pump types. The Hb level >12 g/dL was significant in the roller group and the Hb level >13 g/dL was significant in the centrifugal group for the development of hemolysis for the cumulative ECMO run. The presence of high Hb levels on any given day increased the risk of hemolysis for that day of the ECMO run regardless of ECMO pump type. Higher revolutions per minute (RPMs) and higher inlet pressures on any given day increased the risk for the development of hemolysis in the centrifugal pump. Lower inlet venous pressures and RPMs were not associated with hemolysis in the roller group. CONCLUSIONS: An Hb level greater than 13 g/dL was associated with an increased risk of hemolysis, and a high Hb on a given day was associated with a significantly higher risk of hemolysis on the same day. Higher RPMs and lower inlet venous pressures were associated with an increased risk of hemolysis in the centrifugal pump only.

Pediatric Extracorporeal Membrane Oxygenation.

Extracorporeal life support is a modified form of cardiopulmonary bypass. Experience in extracorporeal membrane oxygenation (ECMO) has come largely from the neonatal population. Most centers have transitioned the ECMO pumps from roller pumps to centrifugal technology. Modes of support include venovenous for respiratory support and venoarterial for cardiac support. "Awake" ECMO is the trend with extubation and tracheostomy on the rise. Fluid overload is common and managed with diuretics or hemofiltration. Nutrition is important and provided enterally or via total parenteral nutrition. Overall survival for pediatric cardiac and respiratory ECMO has remained at approximately 50% to 60%.

An International Survey on Ventilator Practices Among Extracorporeal Membrane Oxygenation Centers.

Although the optimal ventilation strategy is unknown for patients placed on extracorporeal support, there are increasing reports of extubation being used. Our objective was to describe the change in ventilation strategies and use of tracheostomy and bronchoscopy practices among extracorporeal membrane oxygenation (ECMO) centers across the world. A descriptive, cross-sectional 22 item survey of neonatal, pediatric, and adult ECMO centers was used to evaluate ventilator strategies, extubation, bronchoscopy, and tracheostomy practices. Extubation practices are increasing among all types of ECMO centers, representing 27% of all patients in pediatric centers, 41% of all patients in mixed centers, and 52% of all patients in adult centers. The most common mode of ventilation during ECMO is pressure control. There is a trend toward increased use of bilevel ventilation particularly for lung recruitment. Additionally, there is a trend toward increase in performance of bronchoscopy (pediatrics: 69%, mixed centers: 81%, adults: 76%) and tracheostomy. Among the centers performing tracheostomies, 45% reported the percutaneous method (pediatric: 31%, mixed: 46%, adult: 57%), 19% reported the open method (pediatric: 9%, mixed: 27%, adult: 24%), and 10% reported using both types of tracheostomies (pediatric: 2%, mixed: 8%, adult: 16%). Our study shows that ECMO centers are extubating their patients, performing tracheostomies and bronchoscopies on their patients more than in the previous years. There remains significant variation in ECMO ventilator strategies and management internationally. Future studies are needed to correlate these changes in practices to outcome benefits.

Elevated cranial ultrasound resistive indices are associated with improved neurodevelopmental outcomes one year after pediatric cardiac surgery: A single center pilot study.

OBJECTIVE: To determine if a non-invasive, repeatable test can be used to predict neurodevelopmental outcomes in patients with congenital heart disease. METHODS: This was a prospective study of pediatric patients less than two months of age undergoing congenital heart surgery at the Children's Health Children's Medical Center at Dallas. Multichannel near-infrared spectroscopy (NIRS) was utilized during the surgery, and ultrasound (US) resistive indices (RI) of the major cranial vessels were obtained prior to surgery, immediately post-operatively, and prior to discharge. Pearson's correlation, Fischer exact t test, and Fischer r to z transformation were used where appropriate. RESULTS: A total of 16 patients were enrolled. All had US data. Of the sixteen patients, two died prior to the neurodevelopmental testing, six did not return for the neurodevelopmental testing, and eight patients completed the neurodevelopmental testing. There were no significant correlations between the prior to surgery and prior to discharge US RI and neurodevelopmental outcomes. The immediate post-operative US RI demonstrated a strong positive correlation with standardized neurodevelopmental outcome measures. We were able to demonstrate qualitative differences using multichannel NIRS during surgery, but experienced significant technical difficulties implementing consistent monitoring. CONCLUSIONS: A higher resistive index in the major cerebral blood vessels following cardiac surgery in the neonatal period is associated with improved neurological outcomes one year after surgery. Obtaining an ultrasound with resistive indices of the major cerebral vessels prior to and after surgery may yield information that is predictive of neurodevelopmental outcomes.

Regional Cerebral Abnormalities Measured by Frequency-Domain Near-Infrared Spectroscopy in Pediatric Patients During Extracorporeal Membrane Oxygenation.

Extracorporeal membrane oxygenation (ECMO) is a form of advanced cardiorespiratory support provided to critically ill patients with severe respiratory or cardiovascular failure. While children undergoing ECMO therapy have significant risk for neurological morbidity, currently there is a lack of reliable bedside tool to detect the neurologic events for patients on ECMO. This study assessed the feasibility of frequency-domain near-infrared spectroscopy (NIRS) for detection of intracranial complications during ECMO therapy. The frequency-domain NIRS device measured the absorption coefficient (µa) and reduced scattering coefficient (µs') at six cranial positions from seven pediatric patients (0-16 years) during ECMO support and five healthy controls (2-14 years). Regional abnormalities in both absorption and scattering were identified among ECMO patients. A main finding in this study is that the abnormalities in scattering appear to be associated with lower-than-normal µs' values in regional areas of the brain. Because light scattering originates from the intracellular structures (such as nuclei and mitochondria), a reduction in scattering primarily reflects loss or decreased density of the brain matter. The results from this study indicate a potential to use the frequency-domain NIRS as a safe and complementary technology for detection of intracranial complications during ECMO therapy.

Drug hypersensitivity causing organizing eosinophilic pneumonia in a pediatric patient.

OBJECTIVE: To describe a relatively rare hypersentivity reaction with pulmonary manifestations in a pediatric patient. DATA SOURCES: Electronic medical records. STUDY SELECTION: Patient treatment in the pediatric critical care unit. DATA EXTRACTION AND SYNTHESIS: Electronic medical records. CONCLUSIONS: Eosinophilic pneumonias are rare in the pediatric population. Peripheral eosinophilia is not necessary to make the diagnosis. Bronchoalveolar lavage is the diagnostic study of choice. Lung biopsies are rarely needed to make the diagnosis. The treatment of choice is steroids. If steroids fail to improve the patient's condition, consider IVIG, and cyclosporine A.

Extraction studies of Tabernanthe iboga and Voacanga africana.

The root bark of Tabernanthe iboga contains ibogaine as its predominant alkaloid and has been an important source of it. Ibogaine is used experimentally to interrupt drug addiction and allow therapeutic intervention, but is currently unaffordable to doctors in less economically developed countries. To meet this need, an extraction of alkaloids from T. iboga root bark was optimized and simplified to use only diluted vinegar and ammonia, and was successfully applied to related alkaloids from Voacanga africana bark also. The alkaloids were converted to their hydrochlorides and purified, and the minor alkaloids were recovered.