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INTRODUCTION: The frequency of extracorporeal membrane oxygenation in pediatric patients continues to increase, especially in patients with complex congenital heart disease. Providing adequate anticoagulation is necessary for patients on extracorporeal membrane oxygenation and is achieved with adequate heparin administration. Antithrombin is administered to potentiate heparin's effects. However, the efficacy of antithrombin supplementation is unclear and a clear clinical benefit has not been established. We present a large retrospective study examining the effects of antithrombin on pediatric patients receiving extracorporeal membrane oxygenation. METHODS: Data for this study were obtained from the Pediatric Health Information System and Pediatric Health Information System+ databases from 2004 to 2015. Pediatric patients receiving extracorporeal membrane oxygenation with a congenital heart disease diagnosis were included and divided into groups that did or did not utilize antithrombin. For all admissions, the following were captured: age of admission, gender, year of admission, length of stay, billed charges, inpatient mortality, the presence of specific congenital malformations of the heart, specific cardiac surgeries, and comorbidities. RESULTS: A total of 9,193 admissions were included and 865 (9.4%) utilized antithrombin. Between groups, there were significantly different frequencies of co-morbidities, cardiac lesion types and antithrombin usage over the study period. There were significantly lower odds in the antithrombin group of venous thrombosis. Antithrombin was not significantly associated with hemorrhage; however, antithrombin was associated with increased inpatient mortality and a decrease in length of stay and billed charges. CONCLUSION: Antithrombin administration is associated with increased mortality, a shorter length of stay, and decreased billing cost. Recently, antithrombin usage has been decreasing-potentially due to the reported lack of clinical benefit. Together, these results reinforce that antithrombin may not be indicated for all pediatric extracorporeal membrane oxygenation patients.
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Antitrombinas , Oxigenación por Membrana Extracorpórea , Anticoagulantes , Niño , Heparina , Humanos , Lactante , Estudios RetrospectivosRESUMEN
INTRODUCTION: For CHD patients undergoing corrective surgery utilising cardiopulmonary bypass, post-operative inhaled nitric oxide has been administered to alleviate pulmonary hypertension. We performed a systematic review and meta-analyses to determine the effect of inhaled nitric oxide on haemodynamics, gas exchange, and hospitalisation characteristics in children immediately after cardiopulmonary bypass. MATERIALS AND METHODS: A systematic review of the literature was performed to identify full-text manuscripts in English. PubMed, EMBASE, and the Cochrane databases were queried. Once manuscripts were identified for inclusion, a list of all the endpoints in each manuscript was created. Endpoints with data present from two or more studies were then kept for pooled analyses. All endpoints included were continuous variables and so mean and standard deviation were utilised as the effect data for comparison. RESULTS: A total of eight studies were deemed appropriate for inclusion. There were significant differences with decreases in mean pulmonary artery pressure of -6.82 mmHg, left atrial pressure of -1.16 mmHg, arteriovenous oxygen difference of -1.63, arterial carbon dioxide concentration of -2.41 mmHg, mechanical ventilation duration of -8.56 hours, and length of cardiac ICU stay duration of -0.91 days. All significant variables achieved p < 0.001. CONCLUSION: Inhaled nitric oxide in children immediately after cardiopulmonary bypass decreases mean pulmonary artery pressure significantly and decreases the arterial carbon dioxide concentration significantly without significantly altering other haemodynamic parameters. This results in a statistically shorter duration of mechanical ventilation and cardiac ICU length of stay without altering overall hospital length of stay.
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Procedimientos Quirúrgicos Cardíacos , Hipertensión Pulmonar , Administración por Inhalación , Puente Cardiopulmonar , Niño , Hemodinámica , Humanos , Hipertensión Pulmonar/tratamiento farmacológico , Óxido Nítrico/uso terapéuticoRESUMEN
INTRODUCTION: Cardiopulmonary bypass (CPB) is known to cause a systemic inflammatory and immune response. OBJECTIVE: An in-vitro model of cardiotomy suction was designed to quantify the effects of incrementally increased air-blood exposure on leucocyte marker CD11b and cytokine activation in two common anticoagulants, heparin and citrate. METHODS: Fresh human blood was exposed to increasing amounts of air flow for ten minutes. Leucocyte and cytokine levels were measured prior to and after ten minutes of air flow. Cytokine levels were also measured after air exposure when incubated for 24 hours at 37oC. RESULTS: Leucocyte activation, measured by CD11b, was elevated between baseline and air flow rates up to 50 mL/min. After 10 minutes of air exposure, no measured cytokine levels were elevated. After 24 hours of incubation, cytokine levels of TNFα, IL-10, IL-6, and IL-8 were elevated. However, only IL-8 was significantly elevated in citrated blood, but not in heparinized blood, when compared to baseline samples that were also incubated for 24 hours. CONCLUSION: This study investigates CD11b levels in response to an air stimulus in blood that was anticoagulated with citrate or heparin. Exposure to an air stimulus activates leucocytes. Activation of CD11b was less when using heparin as an anticoagulant compared to citrate. Cytokine activation occurs with air stimulation, but levels do not immediately rise, indicating that time is required to generate free cytokines.
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Puente Cardiopulmonar/métodos , Citocinas/metabolismo , Leucocitos/metabolismo , Succión/métodos , HumanosRESUMEN
INTRODUCTION: Adults with congenital heart disease (ACHD) represent a population with unique health-care needs. Many patients require cardiac surgery, with some requiring postoperative extracorporeal membrane oxygenation (ECMO). This study aimed to identify the risk factors for the need of postoperative ECMO and characterize the impact of ECMO on admission characteristics. METHODS: Data from the 2005-2012 iterations of the Nationwide Inpatient Sample were used. ACHD admissions over 18 years with a documented cardiac surgery were included. Univariate analysis was conducted to compare the characteristics between those requiring ECMO and those who did not. Regression analysis was done to identify the independent risk factors associated with ECMO and to determine the impact of ECMO on length, cost, and mortality of the admission. RESULTS: A total of 186,829 admissions were included. Of these, 446 (0.2%) admissions required ECMO. Those with acute kidney injury, double-outlet right ventricle, or total anomalous pulmonary venous connection were more likely to require ECMO. ECMO was also significantly more utilized in patients undergoing septal defect repair, complete repair of tetralogy of Fallot, atrial switch, and heart transplant. The use of ECMO significantly increased length, cost, and mortality of stay. Overall mortality was 62.6% in the ECMO group. CONCLUSION: ECMO is only needed in a small proportion of postoperative ACHD patients. The use of ECMO significantly increases cost, length of stay and mortality in these patients. Improved identification of postoperative ACHD patients who are more likely to survive ECMO may facilitate improved survival and decreased resource utilization.
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A novel electrochemically controlled release method for nitric oxide (NO) (based on electrochemical reduction of nitrite ions) is combined with an amperometric oxygen sensor within a dual lumen catheter configuration for the continuous in vivo sensing of the partial pressure of oxygen (PO2) in blood. The on-demand electrochemical NO generation/release method is shown to be fully compatible with amperometric PO2 sensing. The performance of the sensors is evaluated in rabbit veins and pig arteries for 7 and 21 h, respectively. Overall, the NO releasing sensors measure both venous and arterial PO2 values more accurately with an average deviation of -2 ± 11% and good correlation (R(2) = 0.97) with in vitro blood measurements, whereas the corresponding control sensors without NO release show an average deviation of -31 ± 28% and poor correlation (R(2) = 0.43) at time points >4 h after implantation in veins and >6 h in arteries. The NO releasing sensors induce less thrombus formation on the catheter surface in both veins and arteries (p < 0.05). This electrochemical NO generation/release method could offer a new and attractive means to improve the biocompatibility and performance of implantable chemical sensors.
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Técnicas Biosensibles/métodos , Monitoreo Fisiológico/métodos , Óxido Nítrico/química , Oxígeno/análisis , Animales , Electroquímica/tendencias , Óxido Nítrico/sangre , Conejos , PorcinosRESUMEN
BACKGROUND: In Southern Italy and, specifically, in the region of Campania, many surveys show that the average of students with reading difficulties is much higher than in northern Italy and abroad. On the other hand, specific learning disorders (SLDs) in Campania are much less certified. Since there are no etiological reasons that can explain this apparent inconsistency, an objective of this cross-sectional study was to evaluate the extent of reading/writing difficulties in students from a province of Campania and then to assess the ability of teachers to identify such difficulties in their students. METHODS: Of a total of 241 enrolled students, 155 (64.31%), including 73 from primary school and 82 from secondary school, belonging to 5 schools in the province of Salerno (Italy), took part in the survey. Students' reading and writing skills were assessed through standardized tests. The tests results were then compared with teacher judgments and context-related variables. RESULTS: At the reading test, 28.7% of primary school and 13.4% of lower secondary school students fell below the 5th percentile for age. Results of the writing test were even more significant: almost half of the students of both levels of education performed below the 5th percentile. Teacher judgments showed higher agreement with standardized assessments in primary (88%, K of Cohen=0.68) than in secondary school (78%, K=0.23). CONCLUSIONS: Reading and writing difficulties were common in our sample. While reading skills tended to improve with age, writing difficulties apparently persisted to some extent in third and sixth-grade classes. The accuracy of teacher judgments on reading skills is relatively high, but teachers seem to hardly report reading difficulties "requiring attention." Although less "severe" than others, such difficulties should be considered, mainly because of their potential developmental trajectories.
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Dislexia , Lectura , Humanos , Estudios Transversales , Dislexia/diagnóstico , Dislexia/epidemiología , Estudiantes , Escritura , NiñoRESUMEN
INTRODUCTION: Few studies have focused on the long-term effects of the COVID-19 pandemic on mental health. The objective of our work was to evaluate the changes in emotional and behavioral symptoms in patients with neuropsychiatric disorders and the impact on parenting stress 1 year after the first national lockdown. METHODS: We enrolled 369 patients aged 1.5-18 years of age referred to the Child and Adolescent Neuropsychiatry Unit of the University Hospital of Salerno (Italy) by their parents. We asked their parents to complete two standardized questionnaires for the assessment of emotional/behavioral symptoms (Child Behavior CheckList, CBCL) and parental stress (Parenting Stress Index, PSI) prior to the pandemic (Time 0), during the first national lockdown (Time 1) and after 1 year (Time 2), and we monitored the changes in symptoms over time. RESULTS: After 1 year from the start of the first national lockdown, we found a significant increase of internalizing problems, anxiety, depression, somatization, and social and oppositional-defiant problems in older children (6-18 years), and a significant increase of somatization, anxiety problems, and sleep problems in younger children (1.5-5 years). We also observed a significant relationship between emotional/behavioral symptoms and parental stress. CONCLUSION: Our study showed that parental stress levels increased compared to the pre-pandemic months and continues to persist over time, while internalizing symptoms of children and adolescents showed a significant worsening during 1 year follow-up from the first COVID-19 lockdown.
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COVID-19 , Humanos , Niño , Adolescente , Lactante , Preescolar , Pandemias , Estudios de Seguimiento , Control de Enfermedades Transmisibles , Responsabilidad Parental/psicologíaRESUMEN
(1) Background: The aim of our study was to evaluate parental stress after 6 and 12 months of a ketogenic diet, considering demographic and clinical variables (epilepsy type, epilepsy duration, seizure number, antiseizure medications, comorbidities, efficacy, and adverse events). (2) Methods: We consecutively enrolled 36 children aged between 3 and 10 years who had been diagnosed with various types of drug-resistant epilepsy and who were in therapy with a ketogenic diet for better seizure control. A standardized neuropsychological questionnaire (Parenting Stress Index-PSI) was administered to the parents evaluating parental stress at baseline (T0), after 6 (T1) months, and after 12 months (T2). (3) Results: After 6 and 12 months of dietary treatment, Parental Distress and Total Stress mean scores were statistically significantly increased. Post hoc analysis showed no significant changes in the scores between T0 and T1, although there was a significant increase between T1 and T2. We did not find statistically significant relationships between parental stress and the other variables considered. (4) Conclusions: The ketogenic diet can be challenging for parents and can affect the perception of parental stress, especially in the long term. Parents may feel inadequate in their role; therefore, they should be helped and encouraged through additional supports in order to maximize the adherence to diet therapy.
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Dieta Cetogénica , Epilepsia , Humanos , Niño , Preescolar , Dieta Cetogénica/efectos adversos , Resultado del Tratamiento , Convulsiones , PadresRESUMEN
Tuberous sclerosis complex (TSC) is a rare multisystem genetic disorder characterized by benign tumor growth in multiple organs, including the brain, kidneys, heart, eyes, lungs, and skin. Pathogenesis stems from mutations in either the TSC1 or TSC2 gene, which encode the proteins hamartin and tuberin, respectively. These proteins form a complex that inhibits the mTOR pathway, a critical regulator of cell growth and proliferation. Disruption of the tuberin-hamartin complex leads to overactivation of mTOR signaling and uncontrolled cell growth, resulting in hamartoma formation. Neurological manifestations are common in TSC, with epilepsy developing in up to 90% of patients. Seizures tend to be refractory to medical treatment with anti-seizure medications. Infantile spasms and focal seizures are the predominant seizure types, often arising in early childhood. Drug-resistant epilepsy contributes significantly to morbidity and mortality. This review provides a comprehensive overview of the current state of knowledge regarding the pathogenesis, clinical manifestations, and treatment approaches for epilepsy and other neurological features of TSC. While narrative reviews on TSC exist, this review uniquely synthesizes key advancements across the areas of TSC neuropathology, conventional and emerging pharmacological therapies, and targeted treatments. The review is narrative in nature, without any date restrictions, and summarizes the most relevant literature on the neurological aspects and management of TSC. By consolidating the current understanding of TSC neurobiology and evidence-based treatment strategies, this review provides an invaluable reference that highlights progress made while also emphasizing areas requiring further research to optimize care and outcomes for TSC patients.
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(1) Background: The principal aim of our research was to explore the relationship between digital devices use and fine motor skills in children aged three to six years and to explore the effect of some socio-demographic factors. (2) Methods: we enrolled 185 children aged between three to six years. The parents of all the participants fulfilled a questionnaire to explore the digital device use, and their children performed a standardized test to assess fine motor skills (APCM-2). We performed the Spearman correlation test to explore the relationship between different variables. (3) Results: the children spent an average of 3.08 ± 2.30 h/day on digital devices. We did not find a significant association between the time of use of digital devices and fine motor skills (p = 0.640; r = -0.036). The youngest children experienced digital tools earlier than older ones (p < 0.001; r = 0.424) and they were also the ones who used digital tools more time afterwards (p = 0.012; -0.202). The children who had working parents spent more time on digital devices (p = 0.028; r = 0.164/p = 0.037; r = 0.154) and used digital devices earlier (p = 0.023; r = 0.171). (4) Conclusions: This data suggest that it would be useful to monitor the use of digital tools, especially in the very first years of life. Future studies are needed to further explore this topic.
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Objectives: The aim of our study was to evaluate the effectiveness and tolerability of perampanel (PER) as first add-on and as second line monotherapy in subjects with childhood absence epilepsy. Methods: Our sample consisted of 20 patients with childhood absence epilepsy, aged between 8 and 10, already in therapy with a first antiseizure medication with incomplete seizure control. PER was added as first add-on in a dose ranging from 3 to 8 mg/die with 1- 2 mg/week increments. The patients that were seizure-free were shifted to a PER monotherapy. All patients underwent a standardized neuropsychological evaluation in order to assess non-verbal intelligence and executive functions before adding PER and after 6 months of drug therapy. All parents completed two questionnaires, in order to assess the emotional-behavioral problems and parental stress. Results: 15/20 patients responded to add-on PER and were seizure-free, in 3/20 patients we observed a reduction of seizure frequency <50%, and in the 2 remaining patients the add-on therapy with PER did not lead to a reduction in seizures frequency from baseline. The patients who were seizure-free were switched to PER monotherapy. 9/15 patients remained seizure-free in monotherapy with PER. In the first month of therapy with PER 2/20 patients (10%) reported mild, transient side effects of irritability, headache and dizziness, which did not lead to discontinuation of therapy. Adjunctive treatment with PER did not negatively affect non-verbal intelligence, executive functions, emotional/behavioral symptoms of children and parental stress levels. Significance: Our clinical experience in real life showed that PER appears to be effective in the control of absence seizures in childhood absence epilepsy, with a favorable tolerability profile. PER would seem effective on absence seizures even in monotherapy. Further studies with larger samples, longer follow-up and controlled vs. placebo (or other first choice antiseizure medications) are needed to confirm our data.
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Alpha-thalassemia X-linked intellectual disability syndrome (ATRX) is a rare genetic condition caused by mutations in the ATRX gene characterized by distinctive dysmorphic features, alpha thalassemia, mild-to-profound intellectual disability, and epilepsy, reported in nearly 30% of the patients. To date, different types of seizures are reported in patients with ATRX syndrome including either clonic, tonic, myoclonic seizures or myoclonic absences. However, an accurate analysis of electroencephalographic features is lacking in literature. We report on the epileptic and electroencephalographic phenotype of seven unpublished patients with ATRX syndrome, highlighting the presence of a peculiar EEG pattern characterized by diffuse background slowing with superimposed low voltage fast activity. Likewise, we also review the available literature on this topic.
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Epilepsia , Discapacidad Intelectual , Discapacidad Intelectual Ligada al Cromosoma X , Talasemia alfa , Electroencefalografía , Humanos , Discapacidad Intelectual/diagnóstico , Discapacidad Intelectual/genética , Discapacidad Intelectual Ligada al Cromosoma X/diagnóstico , Discapacidad Intelectual Ligada al Cromosoma X/genética , Convulsiones/diagnóstico , Convulsiones/etiología , Proteína Nuclear Ligada al Cromosoma X/genética , Talasemia alfa/complicaciones , Talasemia alfa/diagnóstico , Talasemia alfa/genéticaRESUMEN
GRIN2A encodes for the 2A subunit of N-methyl-D-aspartate receptors. Pathogenic variants in GRIN2A have been associated with a wide spectrum of neurodevelopmental disorders ranging from speech disorders and/or self-limiting epilepsy (childhood epilepsy with centrotemporal spikes) to severe and disabling phenotypes (atypical childhood epilepsy with centrotemporal spikes, epileptic encephalopathy with continuous spike-wave during sleep, Landau-Kleffner syndrome and infantile-onset epileptic encephalopathy). Here we describe a family with two affected sisters with atypical childhood epilepsy with centrotemporal spikes and their mildly affected mother carrying a novel N-terminal null variant in GRIN2A gene. These familial cases corroborate previous studies showing that loss-of-function GRIN2A variants are associated with milder phenotypes, possibly due to haploinsufficiency.
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Epilepsia , Síndrome de Landau-Kleffner , Niño , Electroencefalografía , Epilepsia/genética , Humanos , Síndrome de Landau-Kleffner/genética , Mutación , Fenotipo , Receptores de N-Metil-D-Aspartato/genéticaRESUMEN
Background We previously reported that resuscitation delivering electrical shocks guided by real-time ventricular fibrillation amplitude spectral area (AMSA) enabled return of spontaneous circulation (ROSC) with fewer shocks, resulting in less myocardial dysfunction. We now hypothesized that AMSA could also guide delivery of epinephrine, expecting further outcome improvement consequent to less electrical and adrenergic burdens. Methods and Results A swine model of ventricular fibrillation was used to compare after 10 minutes of untreated ventricular fibrillation a guidelines-driven (n=8) resuscitation protocol, delivering shocks every 2 minutes and epinephrine every 4 minutes, with an AMSA-driven shocks (n=8) protocol, delivering epinephrine every 4 minutes, and with an AMSA-driven shocks and epinephrine (ADSE; n=8) protocol. For guidelines-driven, AMSA-driven shocks, and ADSE protocols, the time to ROSC (mean±SD) was 569±164, 410±111, and 400±80 seconds (P=0.045); the number of shocks (mean±SD) was 5±2, 3±1, and 3±2 (P=0.024) with ADSE fewer than guidelines-driven (P=0.03); and the doses of epinephrine (median [interquartile range]) were 2.0 (1.3-3.0), 1.0 (1.0-2.8), and 1.0 (0.3-3.0) (P=0.419). The ROSC rate was similar, yet survival after ROSC favored AMSA-driven protocols (guidelines-driven, 3/6; AMSA-driven shocks, 6/6; and ADSE, 7/7; P=0.019 by log-rank test). Left ventricular function and survival after ROSC correlated inversely with electrical burden (ie, cumulative unsuccessful shocks, J/kg; P=0.020 and P=0.046) and adrenergic burden (ie, total epinephrine doses, mg/kg; P=0.042 and P=0.002). Conclusions Despite similar ROSC rates achieved with all 3 protocols, AMSA-driven shocks and ADSE resulted in less postresuscitation myocardial dysfunction and better survival, attributed to attaining ROSC with less electrical and adrenergic myocardial burdens.
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Terapia Electroconvulsiva , Epinefrina , Fibrilación Ventricular , Adrenérgicos/metabolismo , Animales , Modelos Animales de Enfermedad , Terapia Electroconvulsiva/métodos , Epinefrina/uso terapéutico , Miocardio/metabolismo , Análisis de Supervivencia , Porcinos , Fibrilación Ventricular/terapiaRESUMEN
The left pulmonary artery arising from the ascending aorta is an infrequent finding. It may be found isolated or with intracardiac anomalies. We present a new case of the left pulmonary artery arising from the ascending aorta and pool these findings with those of previously reported cases. Associated cardiac, extracardiac, and syndromic findings are discussed along with the implications of these in the evaluation and management of this condition.
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INTRODUCTION: This study aimed to determine factors associated with the need for extracorporeal membrane oxygenation (ECMO) in children with congenital heart disease (CHD) during admission for cardiac surgery (CS). A secondary aim was to determine how ECMO impacted length, cost, and mortality of the admission. METHODS: Data from the Kids' Inpatient Database (KIDS) were utilized. Admissions with CHD under 18 years of age with cardiac surgery were included. Need for ECMO in these admissions was then identified. Univariate analysis was conducted to compare characteristics between admissions with and without ECMO. Regression analyses were conducted to determine what factors were independently associated with ECMO and whether ECMO independently impacted admission characteristics. RESULTS: A total of 46,176 admissions with CHD and CS were included in the final analysis. Of these, 798 (1.7%) required ECMO. Median age of ECMO admissions was 0.5 years. The following were associated with ECMO: decreased age, heart failure, acute kidney injury, arrhythmia, double outlet right ventricle, atrioventricular septal defect, transposition, Ebstein anomaly, hypoplastic left heart syndrome, common arterial trunk, tetralogy of Fallot, coronary anomaly, valvuloplasty, repair of total anomalous pulmonary venous connection, arterial switch, RV to PA conduit placement, and heart transplant (p < 0.01). ECMO independently increased length of stay by 17.8 days, cost of stay by approximately $415,917, and inpatient mortality 22-fold. CONCLUSION: Only a small proportion of CHD patients undergoing CS require ECMO, although these patients require increased resource utilization and have high mortality. Specific cardiac lesions, cardiac surgeries, and comorbidities are associated with increased need for ECMO.
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BACKGROUND: The ventricular fibrillation amplitude spectral area (AMSA) predicts whether an electrical shock could terminate ventricular fibrillation and prompt return of spontaneous circulation. We hypothesized that AMSA can guide more precise timing for effective shock delivery during cardiopulmonary resuscitation. METHODS AND RESULTS: Three shock delivery protocols were compared in 12 pigs each after electrically induced ventricular fibrillation, with the duration of untreated ventricular fibrillation evenly stratified into 6, 9, and 12 minutes: AMSA-Driven (AD), guided by an AMSA algorithm; Guidelines-Driven (GD), according to cardiopulmonary resuscitation guidelines; and Guidelines-Driven/AMSA-Enabled (GDAE), as per GD but allowing earlier shocks upon exceeding an AMSA threshold. Shocks delivered using the AD, GD, and GDAE protocols were 21, 40, and 62, with GDAE delivering only 2 AMSA-enabled shocks. The corresponding 240-minute survival was 8/12, 6/12, and 2/12 (log-rank test, P=0.035) with AD exceeding GDAE (P=0.026). The time to first shock (seconds) was (median [Q1-Q3]) 272 (161-356), 124 (124-125), and 125 (124-125) (P<0.001) with AD exceeding GD and GDAE (P<0.05); the average coronary perfusion pressure before first shock (mm Hg) was 16 (9-30), 10 (6-12), and 3 (-1 to 9) (P=0.002) with AD exceeding GDAE (P<0.05); and AMSA preceding the first shock (mV·Hz, mean±SD) was 13.3±2.2, 9.0±1.6, and 8.6±2.0 (P<0.001) with AD exceeding GD and GDAE (P<0.001). The AD protocol delivered fewer unsuccessful shocks (ie, less shock burden) yielding less postresuscitation myocardial dysfunction and higher 240-minute survival. CONCLUSIONS: The AD protocol improved the time precision for shock delivery, resulting in less shock burden and less postresuscitation myocardial dysfunction, potentially improving survival compared with time-fixed, guidelines-driven, shock delivery protocols.