ABSTRACT
BACKGROUND: Patient- and proxy-reported outcomes (PROs) are an important indicator of healthcare quality and can be used to inform treatment. Despite the widescale use of PROs in adult cardiology, they are underutilised in paediatric cardiac care. This study describes a six-center feasibility and pilot experience implementing PROs in the paediatric and young adult ventricular assist device population. METHODS: The Advanced Cardiac Therapies Improving Outcomes Network (ACTION) is a collaborative learning network comprised of 55 centres focused on improving clinical outcomes and the patient/family experience for children with heart failure and those supported by ventricular assist devices. The development of ACTION's PRO programme via engagement with patient and parent stakeholders is described. Pilot feasibility, patient/parent and clinician feedback, and initial PRO findings of patients and families receiving paediatric ventricular assist support across six centres are detailed. RESULTS: Thirty of the thirty-five eligible patients (85.7%) were enrolled in the PRO programme during the pilot study period. Clinicians and participating patients/parents reported positive experiences with the PRO pilot programme. The most common symptoms reported by patients/parents in the first month post-implant period included limitations in activities, dressing change distress, and post-operative pain. Poor sleep, dressing change distress, sadness, and fatigue were the most common symptoms endorsed >30 days post-implant. Parental sadness and worry were notable throughout the entirety of the post-implant experience. CONCLUSIONS: This multi-center ACTION learning network-based PRO programme demonstrated initial success in this six-center pilot study experience and yields important next steps for larger-scale PRO collection, research, and clinical intervention.
Subject(s)
Heart-Assist Devices , Young Adult , Humans , Child , Pilot Projects , Feasibility Studies , Parents , Patient Reported Outcome MeasuresABSTRACT
We sought to characterize strokes in children with ventricular assist devices. Of 407 patients in the ACTION registry (4/1/18-5/3/2021), 45 (11%) experienced 52 strokes (45 ischemic and 7 hemorrhagic). Median time to stroke was 23.5 days and 19/52 (37%) occurred ≤ 10 days. Stroke rate was 0.09 and 0.63 strokes per patient-year for implantable continuous and paracorporeal devices, respectively. Patients with stroke were younger, more likely to have congenital heart disease and have been on extracorporeal membrane oxygenation at time of VAD. Based on these data, ACTION is now focused on decreasing strokes in these higher-risk patients with particular attention to the peri-implant period.
Subject(s)
Extracorporeal Membrane Oxygenation , Heart Failure , Heart-Assist Devices , Stroke , Child , Heart Failure/etiology , Heart-Assist Devices/adverse effects , Humans , Registries , Retrospective Studies , Stroke/epidemiology , Stroke/etiology , Stroke/prevention & control , Treatment OutcomeABSTRACT
OBJECTIVES: A growing number of children receive support from left ventricular assist devices (LVADs) in the outpatient setting. Unexpected complications of LVAD support occur that require emergent management, and no studies examine how pediatric LVAD patients present to the emergency department (ED). The goals of this study were (1) to describe frequency of visits, clinical characteristics, adverse events, and outcomes of LVAD-supported children treated in ED settings and (2) to evaluate for associations between specified patient outcomes and ED care location. METHODS: This was a retrospective cohort study of children in a single-center outpatient VAD program who presented to several EDs during a 10-year period. We defined adverse events according to the Advanced Cardiac Therapies Improving Outcomes Network registry guidelines. Secondary analysis evaluated for associations between specified patient outcomes (adverse events, hospitalizations, intensive care unit admissions) and ED care location (institutional vs other ED). RESULTS: Of 104 subjects with LVAD implantations during the study period, 30 (28.8%) transitioned to outpatient care. Among subjects in the outpatient VAD program, 24 (80%) of 30 had 54 visits to various EDs over 141.9 patient-months. The median age at time of ED visit was 13.5 years (range, 7.2-17.9 years). The median number of visits per subject was 1 (range, 0-6). The most common complaints on arrival to the ED were vomiting or abdominal pain (16.7%), fever (15.3%), and headache (13.9%). Seventeen adverse events occurred during 14 (25.9%) of 54 ED visits. The most common adverse events were major infection (33.3%) and right heart failure (16.7%). Hospital admission resulted from 41 (75.9%) of 54 ED visits, including 17 (41.5%) of 41 to a cardiovascular intensive care unit. Care at a nonspecialty ED was associated with a higher rate of hospitalization (93.8% vs 68.4%, P = 0.049). During the study period, 4 subjects (13.3%) died, including 1 patient on destination therapy, 1 with multisystem organ failure due to cardiogenic shock, and 2 with hemorrhagic stroke. No patient died while in the ED. CONCLUSIONS: Among subjects in a single outpatient pediatric VAD program presenting to the ED, the most common complaints were abdominal pain/vomiting, fever, and headache. The most common adverse events were major infection and right heart failure. Subjects had a high rate of ED utilization and hospital admission.
Subject(s)
Heart Failure , Heart-Assist Devices , Child , Emergency Service, Hospital , Heart Failure/epidemiology , Heart Failure/therapy , Heart-Assist Devices/adverse effects , Hospitalization , Humans , Retrospective StudiesABSTRACT
TRIAL DESIGN: Peripheral neuropathy is a commonly reported adverse effect of oxaliplatin treatment, representing a significant limitation which may require discontinuation of effective therapy. The present study investigated the neuroprotective potential of riluzole in patients undergoing oxaliplatin treatment in a randomised-controlled trial comparing riluzole and placebo-control. METHODS: Fifty-two patients (17 females, 58.1 ± 12.7 years) receiving oxaliplatin treatment were randomised into either a treatment (50 mg riluzole) or lactose placebo group. The primary outcome measure was the total neuropathy score-reduced (TNSr). Secondary outcome measures include nerve excitability measures, 9-hole pegboard and FACT-GOG NTX questionnaire. Patients were assessed at baseline, pre-cycle 10 or 12, 4-week and 12-week post-treatment. RESULTS: Both the treatment and placebo groups developed objective and patient reported evidence of neurotoxicity over the course of oxaliplatin treatment, although there were no significant differences across any parameters between the two groups. However, across follow-up assessments, the treatment group experienced greater neuropathy, represented by a higher TNSr score at 4-week post-chemotherapy of 8.3 ± 2.7 compared with 4.6 ± 3.6 (p = 0.032) which was sustained at 12-week post-treatment (p = 0.089). Similarly, patients in the treatment group reported worse symptoms with a FACT-GOG NTX score of 37.4 ± 10.2 compared with 43.3 ± 7.4 (p = 0.02) in the placebo group at 4-week post-treatment. CONCLUSION: This study is the first to provide an objective clinical investigation of riluzole in oxaliplatin-induced peripheral neuropathy employing both functional and neurophysiological measures. Although the recruitment target was not reached, the results do not show any benefit of riluzole in minimising neuropathy and may suggest that riluzole worsens neuropathy associated with oxaliplatin treatment.
Subject(s)
Neuroprotection/drug effects , Oxaliplatin/adverse effects , Peripheral Nervous System Diseases/chemically induced , Riluzole/therapeutic use , Adolescent , Adult , Aged , Aged, 80 and over , Female , Humans , Male , Middle Aged , Riluzole/pharmacology , Young AdultABSTRACT
BACKGROUND: The incidence of neurological complications related to ventricular assist devices (VAD) remains high and includes life-threatening conditions such as intracranial hemorrhage or ischemic stroke. Although no definitive management guidelines exist, operative interventions may be required for major neurological injuries. AIMS: This case series describes the perioperative management of children at a single center who underwent neurosurgical procedures for major intracranial bleeds or ischemic strokes while on VAD support. METHODS: A database review identified all pediatric VAD patients who underwent a neurosurgical procedure for an intracranial hemorrhage or ischemic stroke from April 2014 to January 2020. Data regarding patient characteristics, preoperative medical management, intraoperative anesthetic management, and postoperative outcomes were collected using retrospective chart review. RESULTS: Ninety VADs were implanted in 78 patients. Five neurosurgical interventions were performed: four for intracranial hemorrhages and one for an ischemic stroke. All four patients with hemorrhages were receiving anticoagulation at the time of their event and the three patients on warfarin received emergent reversal with prothrombin concentrate complex and vitamin K. Three patients also received pre-procedural platelet transfusions. Two of the five procedures were emergent bedside external ventricular drain placements, and three were surgical operations. All three patients who underwent operative procedures received invasive hemodynamic monitoring and were supported with a combination of inotropes and afterload reduction. One patient required a massive blood product transfusion. The two patients who underwent external ventricular drain placement had no further surgical interventions and died from the severity of their neurological injuries. All three patients who underwent operative procedures survived to transplantation and discharge home. CONCLUSIONS: Perioperative concerns for the anesthesiologist include VAD hemodynamic management, bleeding, VAD thrombosis, and prevention of secondary brain injury. A systematic, multidisciplinary approach to management is paramount to attain favorable outcomes.
Subject(s)
Heart-Assist Devices , Thrombosis , Child , Hemorrhage , Humans , Neurosurgical Procedures , Retrospective StudiesABSTRACT
With growing number of pediatric cases of COVID-19, a unique hyper-inflammatory syndrome, linked to SARS-CoV-2 infection, has emerged in children referred to as multisystem inflammatory syndrome in children (MIS-C). This Kawasaki Disease (KD)-like illness has been described across the world. This syndrome shares features of KD, toxic shock syndrome, and macrophage activation syndrome and is associated with significantly elevated inflammatory markers. Everyday there are new data emerging improving the care of these patients. The Advanced Cardiac Therapies Improving Outcomes Network (ACTION) is a collaborative network designed to improve the outcomes of pediatric patients with end-stage heart failure and involves centers from across North America. The committee gathered information concerning COVID-19 anticoagulation practices at various centers and harmonized the data to formulate a set of recommendations.
Subject(s)
COVID-19 , Mucocutaneous Lymph Node Syndrome , Child , Humans , Mucocutaneous Lymph Node Syndrome/complications , Mucocutaneous Lymph Node Syndrome/drug therapy , SARS-CoV-2 , Systemic Inflammatory Response SyndromeABSTRACT
BACKGROUND: Malnutrition is common in pediatric heart failure and is associated with mortality. The effect of VAD support on malnutrition in children is unknown. We sought to compare the prevalence and severity of malnutrition at HT in children on VAD support vs OMT to inform decisions regarding support strategies. METHODS: Retrospective chart review involving all patients <18 years who underwent HT at Stanford between 1/1/2011 and 3/1/2018. Malnutrition diagnosis and severity were defined by ASPEN guidelines using the lowest age-adjusted z-score for weight (WAZ), height (HAZ), and BMI (BMIZ) when the patient was euvolemic. Changes in z-scores from baseline to HT and across groups were analyzed. RESULTS: A total of 104 patients (52 in each group) were included. Among all patients, WAZ (-0.9 vs 0.3, P < 0.001) and BMIZ (0 vs 0.6, P < 0.001) improved while HAZ (-0.9 vs -0.9, P = 0.4) did not. Compared to children on OMT, children on VAD experienced greater increases in WAZ (0.8 vs 0.3, P < 0.001) and BMIZ (0.7 vs 0.2, P < 0.003) at HT. The prevalence of moderate-to-severe malnutrition decreased in VAD patients (40% to 19%, P < 0.001) and increased in OMT patients (37% to 46%, P < 0.001), leading to a lower prevalence of moderate-to-severe malnutrition at HT (19% vs 46%, P = 0.003). CONCLUSIONS: Malnutrition is common in pediatric HT candidates. Compared to children on OMT, children on VAD support had greater improvement in nutritional status while awaiting HT, and a lower prevalence of malnutrition at HT.
Subject(s)
Heart Failure/surgery , Heart Transplantation , Heart-Assist Devices , Malnutrition/prevention & control , Nutritional Status , Preoperative Care/methods , Adolescent , Child , Child, Preschool , Female , Follow-Up Studies , Heart Failure/complications , Humans , Infant , Infant, Newborn , Male , Malnutrition/diagnosis , Malnutrition/epidemiology , Malnutrition/etiology , Preoperative Period , Prevalence , Retrospective Studies , Severity of Illness Index , Treatment OutcomeABSTRACT
OBJECTIVES: This study's objective was to investigate compassionate ventricular assist device deactivation (VADdeact) in children from the perspective of the pediatric heart failure provider. BACKGROUND: Pediatric VAD use is a standard therapy for advanced heart failure. Serious adverse events may affect relative benefit of continued support, leading to consideration of VADdeact. Perspectives and practices regarding VADdeact have been studied in adults but not in children. METHODS: A web-based anonymous survey of clinicians for pediatric VAD patients (<18 years) was sent to list-serves for the ISHLT Pediatric Council, the International Consortium of Circulatory Assist Clinicians Pediatric Taskforce, and the Pediatric Cardiac Intensivist Society. RESULTS: A total of 106 respondents met inclusion criteria of caring for pediatric VAD patients. Annual VAD volume per clinician ranged from <4 (33%) to >9 (20%). Seventy percent of respondents had performed VADdeact of a child. Response varied to VADdeact requests by parent or patient and was influenced by professional degree and region of practice. Except for the scenario of intractable suffering, no consensus on VADdeact appropriateness was reported. Age of child thought capable of making informed requests for VADdeact varied by subspecialty. The majority of respondents (62%) do not feel fully informed of relevant legal issues; 84% reported that professional society supported guidelines for VADdeact in children had utility. CONCLUSION: There is limited consensus regarding indications for VADdeact in children reported by pediatric VAD provider survey respondents. Knowledge gaps related to legal issues are evident; therefore, professional guidelines and educational resources related to pediatric VADdeact are needed.
Subject(s)
Heart Failure/therapy , Heart-Assist Devices , Pediatrics/methods , Practice Patterns, Physicians' , Withholding Treatment/ethics , Withholding Treatment/statistics & numerical data , Adolescent , Attitude of Health Personnel , Canada , Child , Child, Preschool , Cross-Sectional Studies , Decision Making , Heart Transplantation , Humans , Informed Consent By Minors , International Cooperation , Internet , Nurses , Palliative Care/methods , Physicians , Surveys and Questionnaires , Treatment Outcome , United StatesABSTRACT
Pediatric ventricular assist device (VAD) implantation outcomes are increasingly promising for children with dilated cardiomyopathy and advanced decompensated heart failure (ADHF). VAD placement in patients with clinical features such as complex congenital cardiac anatomy, small body size, or major comorbidities remains problematic. These comorbidities have been traditionally prohibitive for VAD consideration leaving these children as a treatment-orphaned population. Here we describe the quality bundle surrounding these patients with ADHF considered high risk for VAD implantation at our institution. Over a 7-year period, a quality bundle aimed at the peri-operative care for children with high-risk features undergoing VAD implantation was incrementally implemented at a tertiary children's hospital. Patients were considered high risk if they were neonates (< 30 days), had single-ventricle physiology, non-dilated cardiomyopathy, biventricular dysfunction, or significant comorbidities. The quality improvement bundle evolved to include (1) structured team-based peri-operative evaluation, (2) weekly VAD rounds addressing post-operative device performance, (3) standardized anticoagulation strategies, and (4) a multidisciplinary system for management challenges. These measures aimed to improve communication, standardize management, allow for ongoing process improvement, and incorporate principles of a high-reliability organization. Between January 2010 and December 2017, 98 patients underwent VAD implantation, 48 (49%) of which had high-risk comorbidities and a resultant cohort survival-to-transplant rate of 65%. We report on the evolution of a quality improvement program to expand the scope of VAD implantation to patients with high-risk clinical profiles. This quality bundle can serve as a template for future large-scale collaborations to improve outcomes in these treatment-orphaned subgroups.
Subject(s)
Cardiomyopathy, Dilated/surgery , Heart Failure/surgery , Heart-Assist Devices/adverse effects , Adolescent , Anticoagulants/therapeutic use , Cardiomyopathy, Dilated/complications , Cardiomyopathy, Dilated/mortality , Child , Child, Preschool , Cohort Studies , Comorbidity , Female , Heart Failure/complications , Heart Failure/mortality , Humans , Infant , Male , Postoperative Period , Quality Improvement , Reproducibility of Results , Retrospective Studies , Risk Factors , Treatment OutcomeABSTRACT
INTRODUCTION: Given recent findings of subclinical sensory deficits in colorectal cancer patients before oxaliplatin treatment, in the current study we aimed to identify evidence of subclinical peripheral neuropathy on multimodal testing before chemotherapy commencement. METHODS: Clinical, functional, and neurophysiological assessments were undertaken in 93 colorectal cancer patients before chemotherapy. RESULTS: There was no neurophysiological evidence of neuropathy, with 92 of 93 sural sensory values within normative reference values for age and no significant abnormalities detected in nerve conduction or nerve excitability studies. Clinical neurological assessment revealed 75.9% of patients with no signs or symptoms, 10.3% with reduction in distal vibration or pinprick sensitivity, and 6.9% with reduction in ankle reflexes only. There was no difference in manual dexterity (using the 9-hole peg-board test) compared with normative data. DISCUSSION: The present study has established a low likelihood of significant distal symmetrical polyneuropathy in colorectal cancer patients before initiation of chemotherapy. Muscle Nerve 57: 615-621, 2018.
Subject(s)
Antineoplastic Agents/adverse effects , Colorectal Neoplasms/drug therapy , Neural Conduction , Oxaliplatin/adverse effects , Peripheral Nervous System Diseases/diagnosis , Sural Nerve/physiopathology , Adult , Aged , Colorectal Neoplasms/complications , Female , Humans , Male , Middle Aged , Peripheral Nervous System Diseases/chemically induced , Peripheral Nervous System Diseases/complications , Peripheral Nervous System Diseases/physiopathology , Refractory Period, Electrophysiological , Young AdultABSTRACT
Pump exchanges are frequently required in the Berlin Heart EXCOR VAD. We intended to describe the characteristics of pump deposits in a larger patient series and evaluate if changes in our exchange procedure over time have led to increased complications. We reviewed all EXCOR pump exchanges in our institution from July 2004 to October 2014. We gathered data on size and location of pump deposits and exchange procedures. EXCOR devices were implanted in 38 children. Support was LVAD only in 22, BiVAD in 13, and SVAD in 3 cases. Sixty-seven pumps were exchanged. The incidence of pump exchanges per month was higher for smaller pumps and for RVADs vs LVADs. Indications were visible pump deposit in 55, stroke without visible deposit in 5, incorporation of membrane oxygenator in 3, pump size change in 2, and sepsis in 1 case, respectively. Deposits were located in the outflow valve in 73%, inflow valve in 22%, pump body in 3%, and outflow cannula in 3%. EXCOR pumps are predominantly exchanged for deposits, which are most frequently located in the outflow valves. The procedure is now carried out without sedation at the bedside. No major complications were observed during exchanges.
Subject(s)
Device Removal/methods , Heart-Assist Devices/adverse effects , Postoperative Complications , Thrombosis/etiology , Child , Child, Preschool , Device Removal/statistics & numerical data , Female , Humans , Infant , Infant, Newborn , Male , Postoperative Complications/diagnosis , Postoperative Complications/surgery , Retrospective Studies , Stroke/etiology , Stroke/prevention & control , Thrombosis/diagnosis , Thrombosis/surgeryABSTRACT
OBJECTIVE: To describe the safety and efficacy of warfarin for patients with Kawasaki disease and giant coronary artery aneurysms (CAAs, ≥8 mm). Giant aneurysms are managed with combined anticoagulation and antiplatelet therapies, heightening risk of bleeding complications. STUDY DESIGN: We reviewed the time in therapeutic range; percentage of international normalization ratios (INRs) in range (%); bleeding events, clotting events; INRs ≥6; INRs ≥5 and <6; and INRs <1.5. RESULTS: In 9 patients (5 male), median age 14.4 years (range 7.1-22.8 years), INR testing was prescribed weekly to monthly and was done by home monitor (n = 5) or laboratory (n = 3) or combined (1). Median length of warfarin therapy was 7.2 years (2.3-13.3 years). Goal INR was 2.0-3.0 (n = 6) or 2.5-3.5 (n = 3), based on CAA size and history of CAA thrombosis. All patients were treated with aspirin; 1 was on dual antiplatelet therapy and warfarin. The median time in therapeutic range was 59% (37%-85%), and median percentage of INRs in range was 68% (52%-87%). INR >6 occurred in 3 patients (4 events); INRs ≥5 <6 in 7 patients (12 events); and INR <1.5 in 5 patients (28 events). The incidence of major bleeding events and clinically relevant nonmajor bleeding events were each 4.3 per 100 patient-years (95% CI 0.9-12.6). New asymptomatic coronary thrombosis was detected by imaging in 2 patients. CONCLUSIONS: Bleeding and clotting complications are common in patients with Kawasaki disease on warfarin and aspirin, with INRs in range only two-thirds of the time. Future studies should evaluate the use of direct oral anticoagulants in children as an alternative to warfarin.
Subject(s)
Anticoagulants/therapeutic use , Mucocutaneous Lymph Node Syndrome/drug therapy , Warfarin/therapeutic use , Adolescent , Anticoagulants/adverse effects , Child , Female , Hemorrhage/chemically induced , Hemorrhage/epidemiology , Humans , Incidence , International Normalized Ratio , Male , Retrospective Studies , Thrombosis/chemically induced , Thrombosis/epidemiology , Warfarin/adverse effects , Young AdultABSTRACT
Congenital heart disease is the leading cause of stroke in children. Warfarin therapy can be difficult to manage safely in this population because of its narrow therapeutic index, multiple drug and dietary interactions, small patient size, high-risk cardiac indications, and lack of data to support anticoagulation recommendations. We sought to describe our institution's effort to develop a dedicated cardiac anticoagulation service to address the special needs of this population and to review the literature. In 2009, in response to Joint Commission National Patient Safety Goals for Anticoagulation, Boston Children's Hospital created a dedicated pediatric Cardiac Anticoagulation Monitoring Program (CAMP). The primary purpose was to provide centralized management of outpatient anticoagulation to cardiac patients, to serve as a disease-specific resource to families and providers, and to devise strategies to evolve clinical care with rapidly emerging trends in anticoagulation care. Over 5 years the CAMP Service, staffed by a primary pediatric cardiology attending, a full-time nurse practitioner, and administrative assistant with dedicated support from pharmacy and nutrition, has enrolled over 240 patients ranging in age from 5 months to 55 years. The most common indications include a prosthetic valve (34 %), Fontan prophylaxis (20 %), atrial arrhythmias (11 %), cardiomyopathy (10 %), Kawasaki disease (7 %), and a ventricular assist device (2 %). A patient-centered multi-disciplinary cardiac anticoagulation clinic was created in 2012. Overall program international normalized ratio (INR) time in therapeutic range (TTR) is favorable at 67 % (81 % with a 0.2 margin) and has improved steadily over 5 years. Pediatric-specific guidelines for VKOR1 and CYP2C9 pharmacogenomics testing, procedural bridging with enoxaparin, novel anticoagulant use, and quality metrics have been developed. Program satisfaction is rated highly among families and providers. A dedicated pediatric cardiac anticoagulation program offers a safe and effective strategy to standardize anticoagulation care for pediatric cardiology patients, is associated with high patient and provider satisfaction, and is capable of evolving care strategies with emerging trends in anticoagulation.
Subject(s)
Anticoagulants/therapeutic use , Blood Coagulation/drug effects , Heart Defects, Congenital/complications , Primary Health Care/methods , Primary Health Care/statistics & numerical data , Warfarin/therapeutic use , Adolescent , Adult , Anticoagulants/administration & dosage , Boston , Child , Child, Preschool , Female , Heart Defects, Congenital/physiopathology , Humans , Infant , International Normalized Ratio , Male , Middle Aged , Primary Health Care/organization & administration , Warfarin/administration & dosage , Young AdultABSTRACT
Riluzole, a benzothiazole derivative, has been shown to be effective in prolonging survival in amyotrophic lateral sclerosis. The mechanisms by which riluzole exerts neuroprotective effects in amyotrophic lateral sclerosis remains to be fully elucidated, although inhibition of glutamatergic transmission and modulation of Na+ channel function have been proposed. In an attempt to determine the mechanisms by which riluzole exerts neuroprotective effects, in particular to dissect the relative contributions of inhibition of glutamatergic transmission and Na+ channel modulation, the present study utilized a combination of cortical and peripheral axonal excitability approaches to monitor changes in excitability and function in patients with amyotrophic lateral sclerosis. Cortical assessment was undertaken by utilising the threshold tracking transcranial magnetic stimulation (TMS) technique and combined with peripheral axonal excitability studies in 25 patients with amyotrophic lateral sclerosis. Studies were performed at baseline and repeated when patients were receiving riluzole 100 mg/day. At the time of second testing all patients were tolerating the medication well. Motor evoked potential and compound muscle action potential responses were recorded over the abductor pollicis brevis muscle. At baseline, features of cortical hyperexcitability were evident in patients with amyotrophic lateral sclerosis, indicated by marked reduction in short interval intracortical inhibition (P < 0.001) and cortical silent period duration (P < 0.001), as well as an increase in the motor evoked potential amplitude (P < 0.01). Riluzole therapy partially normalized cortical excitability by significantly increasing short interval intracortical inhibition (short interval intracortical inhibitionbaseline 0.5 ± 1.8%; short interval intracortical inhibitionON riluzole 7.9 ± 1.7%, P < 0.01). In contrast, riluzole did not exert any modulating effect on cortical silent period duration (P = 0.45) or motor evoked potential amplitude (P = 0.31). In terms of peripheral nerve function, axonal excitability studies established that, relative to control subjects, patients with amyotrophic lateral sclerosis had significant increases in depolarizing threshold electrotonus [amyotrophic lateral sclerosisbaseline TEd (90-100 ms) 49.1 ± 1.8%; controlsTEd (90-100 ms) 45.2 ± 0.6%, P < 0.01] and superexcitability (amyotrophic lateral sclerosisbaseline 30.1 ± 2.3%; control subjects 23.4 ± 1.0%, P < 0.01) at baseline. Following institution of riluzole therapy there was a significant reduction in superexcitability (amyotrophic lateral sclerosisbaseline 30.1 ± 2.3%; amyotrophic lateral sclerosisON riluzole 27.3 ± 2.3%, P < 0.05) and refractoriness at 2 ms (amyotrophic lateral sclerosisbaseline 98.7 ± 10.7%; amyotrophic lateral sclerosisON riluzole 67.8 ± 9.3%, P < 0.001). In conclusion, the present study has established that riluzole exerts effects on both central and peripheral nerve function, interpreted as partial normalization of cortical hyperexcitability and reduction of transient Na+ conductances. Taken together, these findings suggest that the neuroprotective effects of riluzole in amyotrophic lateral sclerosis are complex, with evidence of independent effects across both compartments of the nervous system.
Subject(s)
Amyotrophic Lateral Sclerosis/drug therapy , Amyotrophic Lateral Sclerosis/physiopathology , Motor Cortex/physiology , Neuroprotective Agents/therapeutic use , Peripheral Nerves/physiology , Riluzole/therapeutic use , Adult , Aged , Cohort Studies , Evoked Potentials, Motor/drug effects , Evoked Potentials, Motor/physiology , Female , Follow-Up Studies , Humans , Longitudinal Studies , Male , Middle Aged , Motor Cortex/drug effects , Peripheral Nerves/drug effects , Treatment OutcomeABSTRACT
Patients supported on ventricular assist devices (VADs) benefit from rehabilitation while awaiting heart transplantation to recover from surgery, prevent deconditioning, and, in most cases, optimize transplant candidacy. With bleeding and neurological dysfunction as the most common VAD complications, the importance of rehabilitation dramatically increases when a patient on a VAD also suffers from a neurological injury. The rehabilitation needs for cardiac conditioning and neurological reeducation are not the same. Patients with severe neurological deficits require intense rehabilitation that often includes base-of-support challenges, usage of bolsters and balls, partial weight-bearing treadmill training, and assumption of various body positions in prone, kneeling, or quadruped for neuromotor reeducation. However, some devices are more conducive to rehabilitation than others. For children supported by the CentriMag in particular, rehabilitation is challenged by short cannula tubing, an external motor, a large interface, and an intensive care unit (ICU) admission. We report a safe and successful physical therapy course of a pediatric stroke patient with a diagnosis of Ebstein's anomaly supported by a CentriMag right VAD (RVAD) while awaiting heart transplant in the ICU.
ABSTRACT
Mechanical circulatory support (MCS), including ventricular assist device (VAD) support, is a leading cause of stroke in children; however, existing pediatric stroke recommendations do not apply to many pediatric VAD patients. We sought to develop a multidisciplinary pathway to improve timely and effective acute stroke care and examine the early performance of the pathway in expediting stroke care. Stakeholders from pediatric heart failure, cardiac intensive care, neurology, interventional radiology, neuroradiology, neurosurgery, pharmacy, and adult VAD care convened at Stanford University in August 2017 to discuss the challenges of providing high-quality acute stroke care to children on VAD support, and to develop multidisciplinary acute stroke pathways. Stakeholders identified multiple barriers to providing timely acute stroke care to pediatric VAD patients. These include delayed recognition of stroke, and lack of clarity related to the optimal imaging technique, when to emergently reverse antithrombotic therapy (AT), pediatric indications for thrombectomy and cranial decompression, and strategies to avoid unnecessary serial CTS. Four stroke pathways were created including evaluation and management of the pediatric patient with (1) an acute neurologic change before an imaging diagnosis; (2) an arterial ischemic stroke (AIS); (3) an intracerebral hemorrhage (ICH); and (4) a subdural hematoma (SDH). With the implementation of the stroke pathway, the median time-to-first-CT image decreased by 43 minutes from 66 to 23 minutes ( P < 0.001) while the proportion with a CT within 30 minutes increased from 0% to 67% ( P < 0.001). Despite a variety of challenges, multidisciplinary consensus can be achieved on a rapid stroke management pathway for children on VAD support that addresses important barriers to timely stroke care. Although too few stoke events occurred to differentiate clinical outcomes, the time-to-first-CT image was significantly shorter after pathway implementation.
Subject(s)
Heart Failure , Heart Transplantation , Heart-Assist Devices , Stroke , Adult , Humans , Child , Heart-Assist Devices/adverse effects , Treatment Outcome , Stroke/surgery , Stroke/etiology , Heart Failure/surgery , Heart Transplantation/adverse effects , Retrospective StudiesABSTRACT
Stroke, thromboembolism, and bleeding are the most recognized complications associated with pediatric ventricular assist devices (VADs) and the leading cause of death and disability on VAD support. Recently, newer antithrombotic strategies like bivalirudin have emerged that appear to be associated with a reduction in the neurologic event rates, especially for smaller pediatric-specific VADs like the Berlin Heart and PediMag/CentriMag systems where the risk of stroke is the highest. While contemporary antithrombotic therapies have likely contributed to lowering adverse event rates, we speculate that clotting and bleeding adverse events may have dropped because of a variety of other seemingly small changes to antithrombotic management that are independent of the antithrombotic agents used. This view is supported by recent reports documenting low stroke rates with anticoagulants other than bivalirudin, a drug that may have a wider therapeutic window but is not available in all locations throughout the world. The primary purpose of this report is 1) to summarize contemporary antithrombotic regimens used for smaller pediatric VADs today associated with low event rates in the United States and abroad and () to review 10 practical lessons learned and pitfalls to avoid that we believe to be important to reducing bleeding and clotting events based on our collective experience managing pediatric VADs over the past 20 years irrespective of the antithrombotic agents used.
Subject(s)
Heart Failure , Heart-Assist Devices , Stroke , Thromboembolism , Child , Humans , Fibrinolytic Agents/adverse effects , Heart Failure/therapy , Heart-Assist Devices/adverse effects , Hemorrhage/chemically induced , Hemorrhage/prevention & control , Hemorrhage/complications , Stroke/etiology , Thromboembolism/etiology , Thromboembolism/prevention & control , Treatment Outcome , United StatesABSTRACT
Children on ventricular assist device (VAD) support can present several unique challenges, including small patient size, univentricular or biventricular congenital heart disease (1V- or 2V-CHD) and need for biventricular VAD (BiVAD) support. While cardiac catheterization can provide valuable information, it is an invasive procedure with inherent risks. We sought to evaluate the safety of catheterization in pediatric patients on VAD support. We performed a retrospective review of patients on VAD support who underwent catheterization at Lucile Packard Children's Hospital between January 1, 2014 and September 1, 2019. Using definitions adapted from Pedimacs, adverse events (AEs) after catheterization were identified, including arrhythmia; major bleeding or acute kidney injury within 24 hours; respiratory failure persisting at 24 hours; and stroke, pericardial effusion, device malfunction, bacteremia or death within 7 days. AEs were categorized as related or unrelated to catheterization. Sixty procedures were performed on 39 patients. Underlying diagnoses were dilated cardiomyopathy (48%), 1V-CHD (35%), 2V-CHD (8%), and other (8%). Devices were implantable continuous flow (72%), paracorporeal pulsatile (18%) and paracorporeal continuous flow (10%). Catheterizations were performed on patients in the ICU (60%), on inotropic support (42%), with deteriorating clinical status (37%) and on BiVAD support (12%). There were 9 AEs possibly related to catheterization including 6 episodes of respiratory failure, 2 major bleeding events, and 1 procedural arrhythmia. AE occurrence was associated with ICU status ( P = 0.01), BiVAD support ( P = 0.04) and procedural indication to evaluate worsening clinical status ( P = 0.04). Despite high medical acuity, catheterization can be performed with an acceptable AE profile in children on VAD support.
Subject(s)
Heart Failure , Heart-Assist Devices , Respiratory Insufficiency , Cardiac Catheterization/adverse effects , Child , Heart Failure/diagnosis , Heart Failure/surgery , Heart-Assist Devices/adverse effects , Humans , Retrospective Studies , Treatment OutcomeABSTRACT
CONTEXT: Compassionate deactivation (CD) of ventricular assist device (VAD) support is a recognized option for children when the burden of therapy outweighs the benefits. OBJECTIVES: To describe the prevalence, indications, and outcomes of CD of children supported by VADs at the end of life. METHODS: Review of cases of CD at our institution between 2011 and 2020. To distinguish CD from other situations where VAD support is discontinued, patients were excluded from the study if they died during resuscitation (including extracorporeal membrane oxygenation), experienced brain or circulatory death prior to deactivation, or experienced a non-survivable brain injury likely to result in imminent death regardless of VAD status. RESULTS: Of 24 deaths on VAD, 14 (58%) were CD. Median age was 5.7 (interquartile range (IQR) 0.6, 11.6) years; 6 (43%) had congenital heart disease; 4 (29%) were on a device that can be used outside of the hospital. CD occurred after 40 (IQR: 26, 75) days of support; none while active transplant candidates. CD discussions were initiated by the caregiver in 6 (43%) cases, with the remainder initiated by a medical provider. Reasons for CD were multifactorial, including end-organ injury, infection, and stroke. CD occurred with endotracheal extubation and/or discontinuation of inotropes in 12 (86%) cases, and death occurred within 10 (IQR: 4, 23) minutes of CD. CONCLUSION: CD is the mode of death in more than half of our VAD non-survivors and is pursued for reasons primarily related to noncardiac events. Caregivers and providers both initiate CD discussions. Ventilatory and inotropic support is often withdrawn at time of CD with ensuing death.
Subject(s)
Heart Defects, Congenital , Heart Failure , Heart-Assist Devices , Child , Child, Preschool , Heart Failure/therapy , Heart Ventricles , Humans , Infant , Retrospective Studies , Treatment OutcomeABSTRACT
BACKGROUND: The Berlin Heart EXCOR Pediatric (EXCOR) ventricular assist device (VAD) was introduced in North America nearly 2 decades ago. The EXCOR was approved under Humanitarian Device Exemption status in 2011 and received post-market approval (PMA) in 2017 from Food and Drug Administration. Since the initial approval, the field of pediatric mechanical circulatory support has changed, specifically with regard to available devices, anticoagulation strategies, and the types of patients supported. This report summarizes the outcomes of patients supported with EXCOR from the Advanced Cardiac Therapies Improving Outcomes Network (ACTION) registry. These data were part of the PMA surveillance study (PSS) required by the Food and Drug Administration. METHODS: ACTION is a learning collaborative of over 40 pediatric heart failure programs worldwide, which collects data for all VAD implantations as one of its initiatives. All patients in North America with EXCOR implants reported to ACTION from 2018 to 2020 (nâ¯=â¯72) who had met an outcome were included in the EXCOR PSS group. This was compared with a historical, previously reported Berlin Heart EXCOR study group (Berlin Heart study [BHS] group, nâ¯=â¯320, 2007â2014). RESULTS: Patients in the PSS group were younger, were smaller in weight/body surface area, were more likely to have congenital heart disease, and were less likely to receive a bi-VAD than those in the BHS group. Patients in the PSS group were less likely to be in Interagency Registry for Mechanically Assisted Circulatory Support Profile 1 and were supported for a longer duration. The primary anticoagulation therapy for 92% of patients in the PSS group was bivalirudin. Success, defined as being transplanted, being weaned for recovery, or being alive on a device at 180 days after implantation, was 86% in the PSS group compared with 76% in the BHS group. Incidence of stroke was reduced by 44% and the frequency of pump exchange by 40% in the PSS group compared with those in the BHS group. Similarly, all other adverse events, including major bleeding, were reduced in the PSS group. CONCLUSIONS: The PSS data, collected through ACTION, highlight the improvement in outcomes for patients supported with EXCOR compared with the outcomes in a historical cohort. These findings may be the result of changes in patient care practices over time and collaborative learning.