Extracorporeal membrane oxygenation is often used in children with single-ventricle anomalies. We aimed to describe extracorporeal membrane oxygenation use in single-ventricle patients to test the ...hypothesis that despite increasing prevalence, mortality has not improved and overall burden measure by hospital charges and length of stay have increased.
Retrospective analysis of the Healthcare Cost and Utilization Project Kids' Inpatient Database was performed with sample weighting to generate national estimates.
Pediatric patients (age ≤ 20) with a diagnosis of single ventricle heart disease requiring extracorporeal membrane oxygenation support from 2000 to 2009.
None.
Seven hundred one children (95% CI, 559-943) with single ventricle were supported with extracorporeal membrane oxygenation in the reporting period. Mortality was 57% and did not improve over time (2000 = 52%, 2003 = 63%, 2006 = 57%, and 2009 = 55%; p = 0.66). Single-ventricle patients who required extracorporeal membrane oxygenation were more likely to have had a cardiac procedure (90% vs 46%; p < 0.001), a diagnosis of arrhythmia (22% vs 13%; p < 0.001), cerebrovascular or neurologic insult (9% vs 1%; p < 0.001), heart failure (24% vs 12%; p < 0.001), acute renal failure (28% vs 3%; p < 0.001), or sepsis (28% vs 8%; p < 0.001). By multivariable analysis, acute renal failure was a risk factor for mortality (adjusted odds ratio, 3.12; 95% CI, 1.95-4.98; p < 0.001). The length of stay for single-ventricle patients with extracorporeal membrane oxygenation increased from 25.2 days in 2000 to 55.6 days in 2009 (p < 0.001). Total inflation-adjusted charges increased from $358,021 (95% CI, $278,658-439,765) in 2000 to $732,349 (95% CI, $671,781-792,917) in 2009 (p < 0.001).
Extracorporeal membrane oxygenation support is uncommon with single-ventricle admissions occurring in 2.3% of all hospitalizations. Among those patients, the mortality rate was 57% with no change over time. Acute renal failure was an independent risk factor for mortality during hospitalization. In addition, length of stay for these patients increased and hospital charges doubled. Further studies are needed to determine suitability and cost-effectiveness of extracorporeal membrane oxygenation in single-ventricle patients.
Patients with single ventricle (SV) heart defects have two primary surgical options for superior cavopulmonary connection (SCPC): bidirectional Glenn (BDG) and hemi-Fontan (HF). Outcomes based on ...type of SCPC have not been assessed in a multi-center cohort. This retrospective cohort study uses the Single Ventricle Reconstruction (SVR) Trial public use dataset. Infants who survived to SCPC were evaluated through 1 year of age, based on type of SCPC. The primary outcome was transplant-free survival at 1 year. The cohort included 343 patients undergoing SCPC across 15 centers in North America; 250 (73%) underwent the BDG. There was no difference between the groups in pre-SCPC clinical characteristics. Cardiopulmonary bypass times were longer 99 min (IQR 76, 126) vs 81 min (IQR 59, 116),
p
< 0.001 and use of deep hypothermic circulatory arrest (DHCA) more prevalent (51% vs 19%,
p
< 0.001) with HF. Patients who underwent HF had a higher likelihood of experiencing more than one post-operative complication (54% vs 41%,
p
= 0.05). There were no other differences including the rate of post-operative interventional cardiac catheterizations, length of stay, or survival at discharge, and there was no difference in transplant-free survival out to 1 year of age. Mortality after SCPC is low and there is no difference in mortality at 1 year of age based on type of SCPC. Differences in support time and post-operative complications support the preferential use of the BDG, but additional longitudinal follow-up is necessary to understand whether these differences have implications for long-term outcomes.
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OBVAL, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
To identify medications administered to pediatric patients on extracorporeal membrane oxygenation and to review the available pharmacokinetics and pharmacodynamics literature for the most commonly ...administered medications.
Retrospective single-center study.
ICUs at Children's Hospital of Philadelphia.
Pediatric patients supported by extracorporeal membrane oxygenation between October 1, 2014, and September 30, 2018.
None.
Drug exposure was described according to age group (< 1 mo, 1 mo to < 2 yr, 2 to < 12 yr, and > 12 yr) and ICU (cardiac, neonatal, pediatric). The association of drug exposure with patient's characteristics was examined using one-way analysis of variance for categorical variables and linear regression for continuous variables. All pharmacokinetics and pharmacodynamics literature for the 50 most commonly administered medications on extracorporeal membrane oxygenation was reviewed, with inclusion of studies that reported dosing regimens in conjunction with pharmacokinetics or pharmacodynamics data. A total of 179 different medications were administered to 254 children. Cumulative drug exposure increased with the duration of extracorporeal membrane oxygenation from a median (interquartile) of 10 drugs (6-14) at 1 week to 31 drugs (21-45) at 5 weeks following cannulation. There were significant differences in total drug exposure between age groups and ICUs. With exclusion of in vitro studies, published literature was available to support the use of 40% (20/50) of the most commonly administered medications. Dosing guidance was available for 20% (10/50) of medications and was primarily based on simulations and retrospective studies focusing on neonates and infants.
This study highlights specific needs for future pharmacokinetics and pharmacodynamics studies. Dosing guidelines are essential to optimize the care of critically ill children supported by extracorporeal membrane oxygenation.
Historically, our center has primarily used deep hypothermic circulatory arrest, but in recent years some surgeons have selectively used regional cerebral perfusion as an alternative. We aimed to ...compare the incidence of postoperative electroencephalographic seizure incidence in neonates undergoing surgery with regional cerebral perfusion and deep hypothermic circulatory arrest.
A retrospective analysis was performed in neonates who underwent surgery between 2012 and 2022 with either deep hypothermic circulatory arrest or regional cerebral perfusion with routine postoperative continuous electroencephalography monitoring for 48 hours. Propensity matching was performed to compare postoperative seizure risk between the 2 groups.
Among 1136 neonates undergoing cardiac surgery with cardiopulmonary bypass, regional cerebral perfusion was performed in 99 (8.7%) and deep hypothermic circulatory arrest in 604 (53%). The median duration of regional cerebral perfusion was 49 minutes (interquartile range, 38-68) and deep hypothermic circulatory arrest was 41 minutes (interquartile range, 31-49). The regional cerebral perfusion group had significantly longer total support, cardiopulmonary bypass, and aortic crossclamp times. Overall seizure incidence was 11% (N = 76) and 13% (N = 35) in the most recent era (2019-2022). The unadjusted seizure incidence was similar in neonates undergoing regional cerebral perfusion (N = 12, 12%) and deep hypothermic circulatory arrest (N = 64, 11%). After propensity matching, the seizure incidence was similar in neonates undergoing regional cerebral perfusion (N = 12, 12%) and deep hypothermic circulatory arrest (N = 37, 12%) (odds ratio, 0.97; 95% CI, 0.55-1.71;
92).
In this contemporary single-center experience, the incorporation of regional cerebral perfusion did not result in a change in seizure incidence in comparison with deep hypothermic circulatory arrest. However, unmeasured confounders may have impacted these findings. Further studies are needed to determine the impact, if any, of regional cerebral perfusion on postoperative seizure incidence.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Importance Cardiopulmonary resuscitation (CPR) duration is associated with cardiac arrest survival. Objectives To describe characteristics associated with CPR duration among hospitalized children ...without return of circulation (ROC) (patient-level analysis) and determine whether hospital median CPR duration in patients without ROC is associated with survival (hospital-level analysis). Design, Setting, and Participants This retrospective cohort study of patients undergoing pediatric in-hospital CPR between January 1, 2000, and December 31, 2021, used data from the Get With the Guidelines–Resuscitation registry. Children receiving chest compressions for at least 2 minutes and/or defibrillation were included in the patient-level analysis. For the hospital-level analysis, sites with at least 20 total events and at least 5 events without ROC were included. Data were analyzed from December 1, 2022, to November 15, 2023. Exposures For the patient-level analysis, the exposure was CPR duration in patients without ROC. For the hospital-level analysis, the exposure was quartile of median CPR duration in events without ROC at each hospital. Main Outcomes and Measures For the patient-level analysis, outcomes were patient and event factors, including race and ethnicity and event location; we used a multivariable hierarchical linear regression model to assess factors associated with CPR duration in patients without ROC. For the hospital-level analysis, the main outcome was survival to discharge among all site events; we used a random intercept multivariable hierarchical logistic regression model to examine the association between hospital quartile of CPR duration and survival to discharge. Results Of 13 899 events, 3859 patients did not have ROC (median age, 7 months IQR, 0 months to 7 years; 2175 boys 56%). Among event nonsurvivors, median CPR duration was longer in those with initial rhythms of bradycardia with poor perfusion (8.37 95% CI, 5.70-11.03 minutes; P < .001), pulseless electrical activity (8.22 95% CI, 5.44-11.00 minutes; P < .001), and pulseless ventricular tachycardia (6.17 95% CI, 0.09-12.26 minutes; P = .047) (vs asystole). Shorter median CPR duration was associated with neonates compared with older children (−4.86 95% CI, −8.88 to −0.84 minutes; P = .02), emergency department compared with pediatric intensive car7 e unit location (−4.02 95% CI, −7.48 to −0.57 minutes; P = .02), and members of racial or ethnic minority groups compared with White patients (−3.67 95% CI, −6.18 to −1.17; P = .004). Among all CPR events, the adjusted odds of survival to discharge differed based on hospital quartile of median CPR duration among events without ROC; compared with quartile 1 (15.0-25.9 minutes), the adjusted odds ratio for quartile 2 (26.0-29.4 minutes) was 1.22 (95% CI, 1.09-1.36; P < .001); for quartile 3 (29.5-32.9 minutes), 1.23 (95% CI, 1.08-1.39; P = .002); and for quartile 4 (33.0-53.0 minutes), 1.04 (95% CI, 0.91-1.19; P = .58). Conclusions and Relevance In this retrospective cohort study of pediatric in-hospital CPR, several factors, including age and event location, were associated with CPR duration in event nonsurvivors. The odds of survival to discharge were lower for patients at hospitals with the shortest and longest median CPR durations among events without ROC. Further studies are needed to determine the optimal duration of CPR during pediatric in-hospital cardiac arrest and to provide training guidelines for resuscitation teams to eliminate disparities in resuscitation care.
Although advances in cardiopulmonary resuscitation have improved survival from cardiac arrest (CA), neurologic injury persists and impaired mitochondrial bioenergetics may be critical for targeted ...neuroresuscitation. The authors sought to determine if excellent cardiopulmonary resuscitation and postresuscitation care and good traditional survival rates result in persistently disordered cerebral mitochondrial bioenergetics in a porcine pediatric model of asphyxia-associated ventricular fibrillation CA.
After 7 minutes of asphyxia, followed by ventricular fibrillation, 5 female 1-month-old swine (4 sham) received blood pressure-targeted care: titration of compression depth to systolic blood pressure of 90 mm Hg and vasopressor administration to a coronary perfusion pressure >20 mm Hg. All animals received protocol-based vasopressor support after return of spontaneous circulation for 4 hours before they were killed. The primary outcome was integrated mitochondrial electron transport system (ETS) function. CA animals displayed significantly decreased maximal, coupled oxidative phosphorylating respiration (OXPHOSCI + CII) in cortex (P<0.02) and hippocampus (P<0.02), as well as decreased phosphorylation and coupling efficiency (cortex, P<0.05; hippocampus, P<0.05). Complex I- and complex II-driven respiration were both significantly decreased after CA (cortex: OXPHOSCI P<0.01, ETSCII P<0.05; hippocampus: OXPHOSCI P<0.03, ETSCII P<0.01). In the hippocampus, there was a significant decrease in maximal uncoupled, nonphosphorylating respiration (ETSCI + CII), as well as a 30% reduction in citrate synthase activity (P<0.04).
Mitochondria in both the cortex and hippocampus displayed significant alterations in respiratory function after CA despite excellent cardiopulmonary resuscitation and postresuscitation care in asphyxia-associated ventricular fibrillation CA. Analysis of integrated ETS function identifies mitochondrial bioenergetic failure as a target for goal-directed neuroresuscitation after CA. IACUC Protocol: IAC 13-001023.
For stroke and spinal cord injury, folic acid supplementation has been shown to enhance neurodevelopment and to provide neuroprotection. We hypothesized that folic acid would reduce brain injury and ...improve neurological outcome in a neonatal piglet model of traumatic brain injury (TBI), using 4 experimental groups of 3- to 5-day-old female piglets. Two groups were intubated, anesthetized and had moderate brain injury induced by rapid axial head rotation without impact. One group of injured (Inj) animals received folic acid (Fol; 80 μg/kg) by intraperitoneal (IP) injection 15 min following injury, and then daily for 6 days (Inj + Fol; n = 7). The second group of injured animals received an IP injection of saline (Sal) at the same time points (Inj + Sal; n = 8). Two uninjured (Uninj) control groups (Uninj + Fol, n = 8; Uninj + Sal, n = 7) were intubated, anesthetized and received folic acid (80 μg/kg) or saline by IP injection at the same time points as the injured animals following a sham procedure. Animals underwent neurobehavioral and cognitive testing on days 1 and 4 following injury to assess behavior, memory, learning and problem solving. Serum folic acid and homocysteine levels were collected prior to injury and again before euthanasia. The piglets were euthanized 6 days following injury, and their brains were perfusion fixed for histological analysis. Folic acid levels were significantly higher in both Fol groups on day 6. Homocysteine levels were not affected by treatment. On day 1 following injury, the Inj + Fol group showed significantly more exploratory interest, and better motor function, learning and problem solving compared to the Inj + Sal group. Inj + Fol animals had a significantly lower cognitive composite dysfunction score compared to all other groups on day 1. These functional improvements were not seen on day 4 following injury. Axonal injury measured by β-amyloid precursor protein staining 6 days after injury was not affected by treatment. These results suggest that folic acid may enhance early functional recovery in this piglet model of pediatric head injury. This is the first study to describe the application of complex functional testing to assess an intervention outcome in a swine model of TBI.
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