Association of MRI Brain Injury With Outcome After Pediatric Out-of-Hospital Cardiac Arrest.
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ABSTRACT: Objective
To determine the association between the extent of diffusion restriction and T2/fluid-attenuated inversion recovery (FLAIR) injury on brain MRI and outcomes after pediatric out-of-hospital cardiac arrest (OHCA).Methods
Diffusion restriction and T2/FLAIR injury were described according to the pediatric MRI modification of the Alberta Stroke Program Early Computed Tomography Score (modsASPECTS) for children from 2005 to 2013 who had an MRI within 14 days of OHCA. The primary outcome was unfavorable neurologic outcome defined as ≥1 change in Pediatric Cerebral Performance Category (PCPC) from baseline resulting in a hospital discharge PCPC score 3, 4, 5, or 6. Patients with unfavorable outcomes were further categorized into alive with PCPC 3-5, dead due to withdrawal of life-sustaining therapies for poor neurologic prognosis (WLST-neuro), or dead by neurologic criteria.Results
We evaluated MRI scans from 77 patients (median age 2.21 [interquartile range 0.44, 13.07] years) performed 4 (2, 6) days postarrest. Patients with unfavorable outcomes had more extensive diffusion restriction (median 7 [4, 10.3] vs 0 [0, 0] regions, p < 0.001) and T2/FLAIR injury (5.5 [2.3, 8.2] vs 0 [0, 0.75] regions, p < 0.001) compared to patients with favorable outcomes. Area under the receiver operating characteristic curve for the extent of diffusion restriction and unfavorable outcome was 0.96 (95% confidence interval [CI] 0.91, 0.99) and 0.92 (95% CI 0.85, 0.97) for T2/FLAIR injury. There was no difference in extent of diffusion restriction between patients who were alive with an unfavorable outcome and patients who died from WLST-neuro (p = 0.11).Conclusions
More extensive diffusion restriction and T2/FLAIR injury on the modsASPECTS score within the first 14 days after pediatric cardiac arrest was associated with unfavorable outcomes at hospital discharge.
SUBMITTER: Kirschen MP
PROVIDER: S-EPMC7884994 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:To analyze functional performance measures collected prospectively during the conduct of a clinical trial that enrolled children (up to age 18 yr old), resuscitated after out-of-hospital cardiac arrest, who were at high risk of poor outcomes.Children with Glasgow Motor Scale score less than 5, within 6 hours of resuscitation, were enrolled in a clinical trial that compared two targeted temperature management interventions (THAPCA-OH, NCT00878644). The primary outcome, 12-month survival with Vineland Adaptive Behavior Scale, second edition, score greater or equal to 70, did not differ between groups.Thirty-eight North American PICUs.Two hundred ninety-five children were enrolled; 270 of 295 had baseline Vineland Adaptive Behavior Scale, second edition, scores greater or equal to 70; 87 of 270 survived 1 year.Targeted temperatures were 33.0°C and 36.8°C for hypothermia and normothermia groups.Baseline measures included Vineland Adaptive Behavior Scale, second edition, Pediatric Cerebral Performance Category, and Pediatric Overall Performance Category. Pediatric Cerebral Performance Category and Pediatric Overall Performance Category were rescored at hospital discharges; all three were scored at 3 and 12 months. In survivors with baseline Vineland Adaptive Behavior Scale, second edition scores greater or equal to 70, we evaluated relationships of hospital discharge Pediatric Cerebral Performance Category with 3- and 12-month scores and between 3- and 12-month Vineland Adaptive Behavior Scale, second edition, scores. Hospital discharge Pediatric Cerebral Performance Category scores strongly predicted 3- and 12-month Pediatric Cerebral Performance Category (r = 0.82 and 0.79; p < 0.0001) and Vineland Adaptive Behavior Scale, second edition, scores (r = -0.81 and -0.77; p < 0.0001). Three-month Vineland Adaptive Behavior Scale, second edition, scores strongly predicted 12-month performance (r = 0.95; p < 0.0001). Hypothermia treatment did not alter these relationships.In comatose children, with Glasgow Motor Scale score less than 5 in the initial hours after out-of-hospital cardiac arrest resuscitation, function scores at hospital discharge and at 3 months predicted 12-month performance well in the majority of survivors.
| S-EPMC5129173 | biostudies-literature
Project description:ImportanceMany children with return of spontaneous circulation (ROSC) following cardiac arrest (CA) experience acute kidney injury (AKI). The impact of therapeutic hypothermia on the epidemiology of post-CA AKI in children has not been fully investigated.ObjectiveThe study aims were to: 1) describe the prevalence of severe AKI in comatose children following out-of-hospital CA (OHCA), 2) identify risk factors for severe AKI, 3) evaluate the impact of therapeutic hypothermia on the prevalence of severe AKI, and 4) evaluate the association of severe AKI with survival and functional outcomes.DesignA post hoc secondary analysis of data from the Therapeutic Hypothermia after Pediatric Cardiac Arrest Out-of-Hospital (THAPCA-OH) trial.SettingThirty-six pediatric intensive care units in the United States and Canada.ParticipantsOf 282 eligible subjects with an initial creatinine obtained within 24 h of randomization, 148 were randomized to therapeutic hypothermia and 134 were randomized to therapeutic normothermia.Main outcomes and measuresPrimary outcome was prevalence of severe AKI, as defined by stage 2 and 3 Kidney Disease Improving Global Outcomes (KDIGO) consensus definition; secondary outcome was survival with a favorable neurobehavioral outcome. For this study, risk factors and outcomes were compared between those with/without severe AKI.ResultsOf the 282 subjects enrolled, 180 (64%) developed AKI of which 117 (41% of all enrolled) developed severe AKI. Multivariable modeling found younger age, longer duration of chest compressions, higher lactate level at time of temperature intervention and higher number of vasoactive agents through day 1 of intervention associated with severe AKI. There was no difference in severe AKI between therapeutic hypothermia (39.9%) and therapeutic normothermia (43.3%) groups (p = 0.629). Survival was lower in those with severe AKI at 28 days (21% vs no severe AKI 49%, p < 0.001) and 12 months (21% vs no severe AKI 42%, p < 0.001). One year survival with favorable functional outcome was lower in those with severe AKI.Conclusions and relevanceSevere AKI occurs frequently in children with ROSC after OHCA, especially in younger children and those with higher initial lactates and hemodynamic support. Severe AKI was associated with worse survival and functional outcome. Therapeutic hypothermia did not reduce the incidence of severe AKI.
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Project description:To investigate relationships between cardiac arrest characteristics and survival and neurobehavioral outcome among children recruited to the Therapeutic Hypothermia after Pediatric Cardiac Arrest Out-of-Hospital trial.Secondary analysis of Therapeutic Hypothermia after Pediatric Cardiac Arrest Out-of-Hospital trial data.Thirty-six PICUs in the United States and Canada.All children (n = 295) had chest compressions for greater than or equal to 2 minutes, were comatose, and required mechanical ventilation after return of circulation.Neurobehavioral function was assessed using the Vineland Adaptive Behavior Scales, Second Edition at baseline (reflecting prearrest status) and 12 months postarrest. U.S. norms for Vineland Adaptive Behavior Scales, Second Edition scores are 100 (mean) ± 15 (SD). Higher scores indicate better functioning. Outcomes included 12-month survival and 12-month survival with Vineland Adaptive Behavior Scales, Second Edition greater than or equal to 70.Cardiac etiology of arrest, initial arrest rhythm of ventricular fibrillation/tachycardia, shorter duration of chest compressions, compressions not required at hospital arrival, fewer epinephrine doses, and witnessed arrest were associated with greater 12-month survival and 12-month survival with Vineland Adaptive Behavior Scales, Second Edition greater than or equal to 70. Weekend arrest was associated with lower 12-month survival. Body habitus was associated with 12-month survival with Vineland Adaptive Behavior Scales, Second Edition greater than or equal to 70; underweight children had better outcomes, and obese children had worse outcomes. On multivariate analysis, acute life threatening event/sudden unexpected infant death, chest compressions more than 30 minutes, and weekend arrest were associated with lower 12-month survival; witnessed arrest was associated with greater 12-month survival. Acute life threatening event/sudden unexpected infant death, other respiratory causes of arrest except drowning, other/unknown causes of arrest, and compressions more than 30 minutes were associated with lower 12-month survival with Vineland Adaptive Behavior Scales, Second Edition greater than or equal to 70.Many factors are associated with survival and neurobehavioral outcome among children who are comatose and require mechanical ventilation after out-of-hospital cardiac arrest. These factors may be useful for identifying children at risk for poor outcomes, and for improving prevention and resuscitation strategies.
| S-EPMC5138073 | biostudies-literature
Project description:PurposeThe majority of unconscious patients after cardiac arrest (CA) do not fulfill guideline criteria for a likely poor outcome, their prognosis is considered "indeterminate". We compared brain injury markers in blood for prediction of good outcome and for identifying false positive predictions of poor outcome as recommended by guidelines.MethodsRetrospective analysis of prospectively collected serum samples at 24, 48 and 72 h post arrest within the Target Temperature Management after out-of-hospital cardiac arrest (TTM)-trial. Clinically available markers neuron-specific enolase (NSE) and S100B, and novel markers neurofilament light chain (NFL), total tau, ubiquitin carboxy-terminal hydrolase L1 (UCH-L1) and glial fibrillary acidic protein (GFAP) were analysed. Normal levels with a priori cutoffs specified by reference laboratories or defined from literature were used to predict good outcome (no to moderate disability, Cerebral Performance Category scale 1-2) at 6 months.ResultsSeven hundred and seventeen patients were included. Normal NFL, tau and GFAP had the highest sensitivities (97.2-98% of poor outcome patients had abnormal serum levels) and NPV (normal levels predicted good outcome in 87-95% of patients). Normal S100B and NSE predicted good outcome with NPV 76-82.2%. Normal NSE correctly identified 67/190 (35.3%) patients with good outcome among those classified as "indeterminate outcome" by guidelines. Five patients with single pathological prognostic findings despite normal biomarkers had good outcome.ConclusionLow levels of brain injury markers in blood are associated with good neurological outcome after CA. Incorporating biomarkers into neuroprognostication may help prevent premature withdrawal of life-sustaining therapy.
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Project description:Background: Early prognostication is a major challenge after out-of-hospital cardiac arrest (OHCA). Aims: We hypothesized that a genome-wide analysis of blood gene expression could offer new prognostic tools and lines of research. Methods: Sixty-nine patients were enrolled from an ancillary study of the clinical trial NCT00999583 that tested the effect of erythropoietin (EPO) after OHCA. Blood samples were collected in comatose survivors of OHCA at hospital admission and 1 and 3 days after resuscitation. Gene expression profiles were analyzed (Illumina HumanHT-12 V4 BeadChip; >34,000 genes). Patients were classified into two categories representing neurologically favorable outcome (Cerebral Performance Category [CPC] = 1-2) vs unfavorable outcome (CPC>2) at Day 60 after OHCA. Differential and functional enrichment analyses were performed to compare transcriptomic profiles between these two categories. Results: Among the 69 enrolled patients, 33 and 36 patients were treated or not by EPO, respectively. Among them, 42% had a favorable neurological outcome in both groups. EPO did not affect the transcriptomic response at Day-0 and 1 after OHCA. In contrast, 76 transcripts differed at Day-0 between patients with unfavorable vs favorable neurological outcome. This signature persisted at Day-1 after OHCA. Functional enrichment analysis revealed a down-regulation of adaptive immunity with concomitant up-regulation of innate immunity and inflammation in patients with unfavorable vs favorable neurological outcome. The transcription of many genes of the HLA family was decreased in patients with unfavorable vs favorable neurological outcome. Concomitantly, neutrophil activation and inflammation were observed. Up-stream regulators analysis showed the implication of numerous factors involved in cell cycle and damages. A logistic regression including a set of genes allowed a reliable prediction of the clinical outcomes (Specificity=88%; Hit Rate=83%). Conclusions: A transcriptomic signature involving a counterbalance between adaptive and innate immune responses is able to predict neurological outcome very early after hospital admission after OHCA. This deserves confirmation in a larger population.
2019-03-21 | E-MTAB-7699 | biostudies-arrayexpress
Project description:Bedside detection and early treatment of lasting cerebral ischemia may improve outcome after out-of-hospital cardiac arrest (OHCA). This feasibility study explores the possibilities to use microdialysis (MD) for continuous monitoring of cerebral energy metabolism by analyzing the draining cerebral venous blood. Eighteen comatose patients were continuously monitored with jugular bulb and radial artery (reference) MD following resuscitation. Median time from cardiac arrest to MD was 300 min (IQR 230-390) with median monitoring time 60 h (IQR 40-81). The lactate/pyruvate ratio in cerebral venous blood was increased during the first 20 h after OHCA, and significant differences in time-averaged mean MD metabolites between jugular venous and artery measurements, were documented (p < 0.02). In patients with unfavorable outcome (72%), cerebral venous lactate and pyruvate levels remained elevated during the study period. In conclusion, the study indicates that jugular bulb microdialysis (JBM) is feasible and safe. Biochemical signs of lasting ischemia and mitochondrial dysfunction are frequent and associated with unfavorable outcome. The technique may be used in comatose OHCA patients to monitor biochemical variables reflecting ongoing brain damage and support individualized treatment early after resuscitation.
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Project description:BACKGROUND:Metabolic acidosis is frequently observed as a consequence of global ischemia-reperfusion after out-of-hospital cardiac arrest (OHCA). We aimed to identify risk factors and assess the impact of metabolic acidosis on outcome after OHCA. METHODS:We included all consecutive OHCA patients admitted between 2007 and 2012. Using admission data, metabolic acidosis was defined by a positive base deficit and was categorized by quartiles. Main outcome was survival at ICU discharge. Factors associated with acidosis severity and with main outcome were evaluated by linear and logistic regressions, respectively. RESULTS:A total of 826 patients (68.3% male, median age 61 years) were included in the analysis. Median base deficit was 8.8 [5.3, 13.2] mEq/l. Male gender (p = 0.002), resuscitation duration (p < 0.001), initial shockable rhythm (p < 0.001) and post-resuscitation shock (p < 0.001) were associated with an increased level of acidosis. ICU mortality rate increased across base deficit quartiles (39.1, 59.2, 76.3 and 88.3%, p for trend < 0.001), and base deficit was independently associated with ICU mortality (p < 0.001). The proportion of CPC 1 patients among ICU survivors was similar across base deficit quartiles (72.8, 67.1, 70.5 and 62.5%, p = 0.21), and 7.3% of patients with a base deficit higher than 13.2 mEq/l survived to ICU discharge with complete neurological recovery. CONCLUSION:Severe metabolic acidosis is frequent in OHCA patients and is associated with poorer outcome, in particular due to refractory shock. However, we observed that about 7% of patients with a very severe metabolic acidosis survived to ICU discharge with complete neurological recovery.
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Project description:Background: The optimal timing for transporting pediatric patients with out-of-hospital cardiac arrest (OHCA) who do not achieve return of spontaneous circulation (ROSC) is unclear. Therefore, we assessed the association between resuscitation time on the scene and 1-month survival. Methods and Results: Data from the All-Japan Utstein Registry from 2013 through 2015 for 3,756 pediatric OHCA patients (age <18 years) who did not achieve ROSC prior to departing the scene were analyzed. Overall, the proportion of 1-month survival for on-scene resuscitation time <5, 5-9, 10-14, and ≥15 min was 13.6% (104/767), 10.2% (170/1,666), 8.6% (75/870), and 4.0% (18/453), respectively. Among specific age groups, the proportion of 1-month survival for on-scene resuscitation time of <5, 5-9, 10-14, and ≥15 min was 12.6% (54/429), 8.7% (59/680), 8.6% (23/267), and 6.8% (8/118), respectively, for patients aged 0 years; 16.4% (38/232), 11.0% (52/473), 11.9% (23/194), and 7.1% (6/85), respectively, for those aged 1-7 years; and 11.3% (12/106), 11.5% (59/513), 7.1% (29/409), and 1.6% (4/250), respectively, for those aged 8-17 years. Conclusions: Longer on-scene resuscitation was associated with decreased chance of 1-month survival among pediatric OHCA patients without ROSC. For patients aged <8 years, earlier departure from the scene, within 5 min, may increase the chances of 1-month survival. Conversely, for patients aged ≥8 years, continuing on-scene resuscitation for up to 10 min would be reasonable.
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Project description:Post-resuscitation care after out-of-hospital cardiac arrest (OHCA) is challenging due to the threat of organ failure and difficult prognostication. Our aim was to examine whether urine biomarkers could give an early prediction of acute kidney injury (AKI) and outcome.This was a prospective observational study of comatose OHCA patients at Oslo University Hospital Ullevål, Norway. Risk factors were clinical parameters and biomarkers measured in spot urine (cystatin C, neutrophil gelatinase-associated lipocalin (NGAL) and the product of tissue inhibitor of metalloproteinase 2 (TIMP-2) and insulin-like growth factor-binding protein 7 (IGFBP7)) at admission and day 3. Outcome variables were AKI within 3 days using the Kidney Disease Improving Global Outcomes definition, 6-month mortality, and poor neurological outcome (PNO) defined as cerebral performance category 3-5.Among 195 included patients (85 % males, mean age 60 years), 88 (45 %) died, 96 (49 %) had PNO, and 88 (45 %) developed AKI. In univariate analysis, increased urine cystatin C and NGAL concentration sampled at admission and day 3 were independent risk factors for AKI, mortality and PNO. Increased urine TIMP-2?×?IGFBP7 levels was associated with AKI only at admission. In multivariate analyses combining clinical parameters and biomarker concentrations, the area under the receiver operating characteristics curve (AuROC) with 95 % confidence interval (CI) were 0.774 (0.700-0.848), 0.812 (0.751-0.873), and 0.819 (0.759-0.878) for AKI, mortality and PNO, respectively.In comatose OHCA patients, urine levels of cystatin C and NGAL at admission and day 3 were independent risk factors for AKI, 6-month mortality and PNO.Clinicaltrials.gov NCT01239420 . Registered 10 November 2010.
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Project description:Hypotension after cardiac arrest could aggravate prolonged hypoxic ischemic encephalopathy. The association of circulatory shock at hospital admission with outcome after cardiac arrest has not been well studied. The objective of this study was to investigate the independent association of circulatory shock at hospital admission with neurologic outcome, and to evaluate whether cardiovascular comorbidities interact with circulatory shock. 4004 adult patients with out-of-hospital cardiac arrest enrolled in the International Cardiac Arrest Registry 2006-2017 were included in analysis. Circulatory shock was defined as a systolic blood pressure below 90 mmHg and/or medical or mechanical supportive measures to maintain adequate perfusion during hospital admission. Primary outcome was cerebral performance category (CPC) dichotomized as good, (CPC 1-2) versus poor (CPC 3-5) outcome at hospital discharge. 38% of included patients were in circulatory shock at hospital admission, 32% had good neurologic outcome at hospital discharge. The adjusted odds ratio for good neurologic outcome in patients without preexisting cardiovascular disease with circulatory shock at hospital admission was 0.60 [0.46-0.79]. No significant interaction was detected with preexisting comorbidities in the main analysis. We conclude that circulatory shock at hospital admission after out-of-hospital cardiac arrest is independently associated with poor neurologic outcome.
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