Formal Ethics Consultation in Extracorporeal Membrane Oxygenation Patients: A Single-Center Retrospective Cohort of a Quaternary Pediatric Hospital.

OBJECTIVE: To examine characteristics associated with formal ethics consultation (EC) referral in pediatric extracorporeal membrane oxygenation (ECMO) cases, and document ethical issues presented. DESIGN: Retrospective cohort study using mixed methods. SETTING: Single-center quaternary pediatric hospital. PATIENTS: Patients supported on ECMO (January 2012 to December 2021). INTERVENTIONS: We compared clinical variables among ECMO patients according to the presence of EC. We defined optimal cutoffs for EC based on run duration, ICU length of stay (LOS), and sum of procedures or complications. To identify independent explanatory variables for EC, we used a forward stepwise selection multivariable logistic regression model. EC records were thematically characterized into ethical issues. MEASUREMENTS AND MAIN RESULTS: Of 601 ECMO patients and 225 patients with EC in 10 years, 27 ECMO patients received EC (4.5% of ECMO patients, 12% of all ECs). On univariate analysis, use of EC vs. not was associated with multiple ECMO runs, more complications/procedures, longer ICU LOS and ECMO duration, cardiac admissions, decannulation outcome, and higher mortality. Cutoffs for EC were ICU LOS >52 days, run duration >160 hours, and >6 complications/procedures. Independent associations with EC included these three cutoffs and older age. The model showed good discrimination (area under the curve 0.88 [0.83, 0.93]) and fit. The most common primary ethical issues were related to end-of-life, ECMO discontinuation, and treatment decision-making. Moral distress was cited in 22 of 27 cases (82%). CONCLUSION: EC was used in 4.5% of our pediatric ECMO cases, with most ethical issues related to end-of-life care or ECMO discontinuation. Older age, longer ICU LOS, prolonged runs, and multiple procedures/complications were associated with greater odds for EC requests. These data highlight our single-center experience of ECMO-associated ethical dilemmas. Historical referral patterns may guide a supported decision-making framework. Future work will need to include quality improvement projects for timely EC, with evaluation of impacts on relevant endpoints.

Tracheostomy Timing During Pediatric Cardiac Intensive Care: Single Referral Center Retrospective Cohort.

OBJECTIVES: To describe associations between the timing of tracheostomy and patient characteristics or outcomes in the cardiac ICU (CICU). DESIGN: Single-institution retrospective cohort study. SETTING: Freestanding academic children's hospital. PATIENTS: CICU patients with tracheostomy placed between July 1, 2011, and July 1, 2020. INTERVENTIONS: We compared patient characteristics and outcomes between early and late tracheostomy based on the duration of positive pressure ventilation (PPV) before tracheostomy placement, fitting a receiver operating characteristic curve for current survival to define a cutoff. MEASUREMENTS AND MAIN RESULTS: Sixty-one patients underwent tracheostomy placement (0.5% of CICU admissions). Median age was 7.8 months. Eighteen patients (30%) had single ventricle physiology and 13 patients (21%) had pulmonary vein stenosis (PVS). Primary indications for tracheostomy were pulmonary/lower airway (41%), upper airway obstruction (UAO) (31%), cardiac (15%), neuromuscular (4%), or neurologic (4%). In-hospital mortality was 26% with 41% survival at the current follow-up (median 7.8 [interquartile range, IQR 2.6-30.0] mo). Late tracheostomy was defined as greater than or equal to 7 weeks of PPV which was equivalent to the median PPV duration pre-tracheostomy. Patients with late tracheostomy were more likely to be younger, have single ventricle physiology, and have greater respiratory severity. Patients with early tracheostomy were more likely to have UAO or genetic comorbidities. In multivariable analysis, late tracheostomy was associated with 4.2 times greater mortality (95% CI, 1.9-9.0). PVS was associated with higher mortality (adjusted hazard ratio [HR] 5.2; 95% CI, 2.5-10.9). UAO was associated with lower mortality (adjusted HR 0.2; 95% CI, 0.1-0.5). Late tracheostomy was also associated with greater cumulative opioid exposure. CONCLUSIONS: CICU patients who underwent tracheostomy had high in-hospital and longer-term mortality rates. Tracheostomy timing decisions are influenced by indication, disease, genetic comorbidities, illness severity, and age. Earlier tracheostomy was associated with lower sedative use and improved adjusted survival. Tracheostomy placement is a complex decision demanding individualized consideration of risk-benefit profiles and thoughtful family counseling.

"Death as the One Great Certainty": ethical implications of children with irreversible cardiorespiratory failure and dependence on extracorporeal membrane oxygenation.

Introduction: Advances in medical technology have led to both clinical and philosophical challenges in defining death. Highly publicized cases have occurred when families or communities challenge a determination of death by the irreversible cessation of neurologic function (brain death). Parallels can be drawn in cases where an irreversible cessation of cardiopulmonary function exists, in which cases patients are supported by extracorporeal cardiopulmonary support, such as extracorporeal membrane oxygenation (ECMO). Analysis: Two cases and an ethical analysis are presented which compare and contrast contested neurologic determinations of death and refusal to accept the irreversibility of an imminent death by cardiopulmonary standards. Ambiguities in the Uniform Determination of Death Act are highlighted, as it can be clear, when supported by ECMO, that a patient could have suffered the irreversible cessation of cardiopulmonary function yet still be alive (e.g., responsive and interactive). Parallel challenges with communication with families around the limits of medical technology are discussed. Discussion: Cases that lead to conflict around the removal of technology considered not clinically beneficial are likely to increase. Reframing our goals when death is inevitable is important for both families and the medical team. Building relationships and trust between all parties will help families and teams navigate these situations. All parties may require support for moral distress. Suggested approaches are discussed.

Extracorporeal Membrane Oxygenation Candidacy Decisions: An Argument for a Process-Based Longitudinal Approach.

Are all children extracorporeal membrane oxygenation (ECMO) candidates? Navigating ECMO decisions represents an enormous challenge in pediatric critical care. ECMO cannulation should not be a default option as it will not confer benefit for "all" critically ill children; however, "all" children deserve well-considered decisions surrounding their ECMO candidacy. The complexity of the decision demands a systematic, "well-reasoned" and "dynamic" approach. Due to clinical urgency, this standard cannot always be met prior to initiation of ECMO. We challenge the paradigm of "candidacy" as a singular decision that must be defined prior to ECMO initiation. Rather, the determination as to whether ECMO is in the patient's best interest is applicable regardless of cannulation status. The priority should be on collaborative, interdisciplinary decision-making processes aligned with principles of transparency, relevant reasoning, accountability, review, and appeal. To ensure a robust process, it should not be temporally constrained by cannulation status. We advocate that this approach will decrease both the risk of not initiating ECMO in a patient who will benefit and the risk of prolonged, nonbeneficial support. We conclude that to ensure fair decisions are made in a patient's best interest, organizations should develop procedurally fair processes for ECMO decision-making that are not tied to a particular time point and are revisited along the management trajectory.

Decision-Making, Ethics, and End-of-Life Care in Pediatric Extracorporeal Membrane Oxygenation: A Comprehensive Narrative Review.

OBJECTIVES: Pediatric extracorporeal membrane oxygenation is associated with significant morbidity and mortality. We sought to summarize literature on communication and decision-making, end-of-life care, and ethical issues to identify recommended approaches and highlight knowledge gaps. DATA SOURCES: PubMed, Embase, Web of Science, and Cochrane Library. STUDY SELECTION: We reviewed published articles (1972-2020) which examined three pediatric extracorporeal membrane oxygenation domains: 1) decision-making or communication between clinicians and patients/families, 2) ethical issues, or 3) end-of-life care. DATA EXTRACTION: Two reviewers independently assessed eligibility using Preferred Reporting Items for Systematic Reviews and Meta-Analyses methodology. DATA SYNTHESIS: Of 2,581 publications screened, we identified one systematic review and 35 descriptive studies. No practical guides exist for communication and decision-making in pediatric extracorporeal membrane oxygenation. Conversation principles and parent/clinician perspectives are described. Ethical issues related to consent, initiation, discontinuation, resource allocation, and research. No patient-level synthesis of ethical issues or end-of-life care in pediatric extracorporeal membrane oxygenation was identified. CONCLUSIONS: Despite numerous ethical issues reported surrounding pediatric extracorporeal membrane oxygenation, we found limited patient-level research and no practical guides for communicating with families or managing extracorporeal membrane oxygenation discontinuation.

Lights, camera, path splitter: a new approach for truly simultaneous dual optical mapping of the heart with a single camera.

BACKGROUND: Optical mapping of transmembrane voltage and intracellular calcium is a powerful tool for investigating cardiac physiology and pathophysiology. However, simultaneous dual mapping of two fluorescent probes remains technically challenging. We introduce a novel, easy-to-use approach that requires a path splitter, single camera and excitation light to simultaneously acquire voltage and calcium signals from whole heart preparations, which can be applied to other physiological models - including neurons and isolated cardiomyocytes. RESULTS: Complementary probes were selected that could be excited with a single wavelength light source. Langendorff-perfused hearts (rat, swine) were stained and imaged using a sCMOS camera outfitted with an optical path splitter to simultaneously acquire two emission fields at high spatial and temporal resolution. Voltage (RH237) and calcium (Rhod2) signals were acquired concurrently on a single sensor, resulting in two 384 × 256 images at 814 frames per second. At this frame rate, the signal-to-noise ratio was 47 (RH237) and 85 (Rhod2). Imaging experiments were performed on small rodent hearts, as well as larger pig hearts with sufficient optical signals. In separate experiments, each dye was used independently to assess crosstalk and demonstrate signal specificity. Additionally, the effect of ryanodine on myocardial calcium transients was validated - with no measurable effect on the amplitude of optical action potentials. To demonstrate spatial resolution, ventricular tachycardia was induced - resulting in the novel finding that spatially discordant calcium alternans can be present in different regions of the heart, even when electrical alternans remain concordant. The described system excels in providing a wide field of view and high spatiotemporal resolution for a variety of cardiac preparations. CONCLUSIONS: We report the first multiparametric mapping system that simultaneously acquires calcium and voltage signals from cardiac preparations, using a path splitter, single camera and excitation light. This approach eliminates the need for multiple cameras, excitation light patterning or frame interleaving. These features can aid in the adoption of dual mapping technology by the broader cardiovascular research community, and decrease the barrier of entry into panoramic heart imaging, as it reduces the number of required cameras.

Plasticizer Interaction With the Heart: Chemicals Used in Plastic Medical Devices Can Interfere With Cardiac Electrophysiology.

BACKGROUND: Phthalates are used as plasticizers in the manufacturing of flexible, plastic medical products. Patients can be subjected to high phthalate exposure through contact with plastic medical devices. We aimed to investigate the cardiac safety and biocompatibility of mono-2-ethylhexyl phthalate (MEHP), a phthalate with documented exposure in intensive care patients. METHODS: Optical mapping of transmembrane voltage and pacing studies were performed on isolated, Langendorff-perfused rat hearts to assess cardiac electrophysiology after MEHP exposure compared with controls. MEHP dose was chosen based on reported blood concentrations after an exchange transfusion procedure. RESULTS: Thirty-minute exposure to MEHP increased the atrioventricular node (147 versus 107 ms) and ventricular (117 versus 77.5 ms) effective refractory periods, compared with controls. Optical mapping revealed prolonged action potential duration at slower pacing cycle lengths, akin to reverse use dependence. The plateau phase of the action potential duration restitution curve steepened and became monophasic in MEHP-exposed hearts (0.18 versus 0.06 slope). Action potential duration lengthening occurred during late-phase repolarization resulting in triangulation (70.3 versus 56.6 ms). MEHP exposure also slowed epicardial conduction velocity (35 versus 60 cm/s), which may be partly explained by inhibition of Nav1.5 (874 and 231 µmol/L half-maximal inhibitory concentration, fast and late sodium current). CONCLUSIONS: This study highlights the impact of acute MEHP exposure, using a clinically relevant dose, on cardiac electrophysiology in the intact heart. Heightened clinical exposure to plasticized medical products may have cardiac safety implications-given that action potential triangulation and electrical restitution modifications are a risk factor for early after depolarizations and cardiac arrhythmias.

Myocardial Strain Using Cardiac MR Feature Tracking and Speckle Tracking Echocardiography in Duchenne Muscular Dystrophy Patients.

Duchenne muscular dystrophy (DMD) is an inherited X-linked disorder with an incidence of 1 in 3500 male births, and cardiomyopathy is becoming the leading cause of death. While Cardiac MRI (CMR) and late gadolinium enhancement (LGE) are important tools in recognizing myocardial involvement, myocardial strain imaging may demonstrate early changes and allow patients to avoid gadolinium contrast. We performed CMR feature tracking (FT) and echo-based speckle tracking (STE) strain measures on DMD patients and age/sex matched controls who had received a CMR with contrast and transthoracic echocardiogram. Data were collected for longitudinal strain in the apical four-chamber view and circumferential strain in the mid-papillary parasternal short axis. Segmental wall analysis was performed and compared with the presence of LGE. Data were analyzed using student's t tests or one-way ANOVA adjusting for multiple comparisons. We measured 24 subjects with DMD and 8 controls. Thirteen of 24 DMD subjects were LGE positive only in the lateral segments in short-axis views. Average circumferential strain (CS) measured by FT was significantly decreased in DMD compared to controls (- 18.8 ± 6.1 vs. - 25.5 ± 3.2; p < 0.001) and showed significant differences in the anterolateral, inferolateral, and inferior segments. Average CS by STE trended towards significance (p = 0.06) but showed significance in only the inferior segment. FT showed significant differences in the inferolateral segment between LGE positive (- 15.5 ± 9.0) and LGE negative (- 18.2 ± 8.3) in DMD subjects compared to controls (- 28.6 ± 7.3; p ≤ 0.04). FT also showed significant differences between anteroseptal and inferolateral segments within LGE-positive (p < 0.003) and LGE-negative (p < 0.03) DMD subjects while STE did not. There were no significant differences in longitudinal strain measures. CMR-FT-derived myocardial strain was able to demonstrate differences between subjects with DMD and controls not detected by STE. FT was also able to demonstrate differences in LGE-positive and LGE-negative segments within patients with DMD. FT may be able to predict LGE-positive segments in DMD without the use of gadolinium contrast.