Danielle Guffey

Relationship Between Chest Compression Rates and Outcomes From Cardiac Arrest

Background— Guidelines for cardiopulmonary resuscitation recommend a chest compression rate of at least 100 compressions per minute. Animal and human studies have reported that blood flow is greatest with chest compression rates near 120/min, but few have reported rates used during out-of-hospital (OOH) cardiopulmonary resuscitation or the relationship between rate and outcome. The purpose of this study was to describe chest compression rates used by emergency medical services providers to resuscitate patients with OOH cardiac arrest and to determine the relationship between chest compression rate and outcome. Methods and Results— Included were patients aged ≥20 years with OOH cardiac arrest treated by emergency medical services providers participating in the Resuscitation Outcomes Consortium. Data were abstracted from monitor-defibrillator recordings during cardiopulmonary resuscitation. Multiple logistic regression analysis assessed the association between chest compression rate and outcome. From December 2005 to May 2007, 3098 patients with OOH cardiac arrest were included in this study. Mean age was 67±16 years, and 8.6% survived to hospital discharge. Mean compression rate was 112±19/min. A curvilinear association between chest compression rate and return of spontaneous circulation was found in cubic spline models after multivariable adjustment (P=0.012). Return of spontaneous circulation rates peaked at a compression rate of ≈125/min and then declined. Chest compression rate was not significantly associated with survival to hospital discharge in multivariable categorical or cubic spline models. Conclusions— Chest compression rate was associated with return of spontaneous circulation but not with survival to hospital discharge in OOH cardiac arrest.

Chest compression rates and survival following out-of-hospital cardiac arrest.

Objective:Guidelines for cardiopulmonary resuscitation recommend a chest compression rate of at least 100 compressions/min. A recent clinical study reported optimal return of spontaneous circulation with rates between 100 and 120/min during cardiopulmonary resuscitation for out-of-hospital cardiac arrest. However, the relationship between compression rate and survival is still undetermined. Design:Prospective, observational study. Setting:Data is from the Resuscitation Outcomes Consortium Prehospital Resuscitation IMpedance threshold device and Early versus Delayed analysis clinical trial. Participants:Adults with out-of-hospital cardiac arrest treated by emergency medical service providers. Interventions:None. Measurements Main Results:Data were abstracted from monitor-defibrillator recordings for the first five minutes of emergency medical service cardiopulmonary resuscitation. Multiple logistic regression assessed odds ratio for survival by compression rate categories (<80, 80–99, 100–119, 120–139, ≥140), both unadjusted and adjusted for sex, age, witnessed status, attempted bystander cardiopulmonary resuscitation, location of arrest, chest compression fraction and depth, first rhythm, and study site. Compression rate data were available for 10,371 patients; 6,399 also had chest compression fraction and depth data. Age (mean ± SD) was 67 ± 16 years. Chest compression rate was 111 ± 19 per minute, compression fraction was 0.70 ± 0.17, and compression depth was 42 ± 12 mm. Circulation was restored in 34%; 9% survived to hospital discharge. After adjustment for covariates without chest compression depth and fraction (n = 10,371), a global test found no significant relationship between compression rate and survival (p = 0.19). However, after adjustment for covariates including chest compression depth and fraction (n = 6,399), the global test found a significant relationship between compression rate and survival (p = 0.02), with the reference group (100–119 compressions/min) having the greatest likelihood for survival. Conclusions:After adjustment for chest compression fraction and depth, compression rates between 100 and 120 per minute were associated with greatest survival to hospital discharge.

Comparing Intelligence Quotient Change After Treatment With Proton Versus Photon Radiation Therapy for Pediatric Brain Tumors

PURPOSE Compared with photon radiation (XRT), proton beam radiation therapy (PBRT) reduces dose to normal tissues, which may lead to better neurocognitive outcomes. We compared change in intelligence quotient (IQ) over time in pediatric patients with brain tumors treated with PBRT versus XRT. PATIENTS AND METHODS IQ scores were available for 150 patients (60 had received XRT, 90 had received PBRT). Linear mixed models examined change in IQ over time since radiation therapy (RT) by RT group, controlling for demographic/clinical characteristics. Craniospinal and focal RT subgroups were also examined. RESULTS In the PBRT group, no change in IQ over time was identified (P = .130), whereas in the XRT group, IQ declined by 1.1 points per year (P = .004). IQ slopes did not differ between groups (P = .509). IQ was lower in the XRT group (by 8.7 points) versus the PBRT group (P = .011). In the craniospinal subgroup, IQ remained stable in both the PBRT (P = .203) and XRT groups (P = .060), and IQ slopes did not differ (P = .890). IQ was lower in the XRT group (by 12.5 points) versus the PBRT group (P = .004). In the focal subgroup, IQ scores remained stable in the PBRT group (P = .401) but declined significantly in the XRT group by 1.57 points per year (P = .026). IQ slopes did not differ between groups (P = .342). CONCLUSION PBRT was not associated with IQ decline or impairment, yet IQ slopes did not differ between the PBRT and XRT groups. It remains unclear if PBRT results in clinically meaningful cognitive sparing that significantly exceeds that of modern XRT protocols. Additional long-term data are needed to fully understand the neurocognitive impact of PBRT in survivors of pediatric brain tumors.

Impact of prehospital mode of transport after severe injury: a multicenter evaluation from the Resuscitation Outcomes Consortium.

BACKGROUND: There is ongoing controversy about the relative effectiveness of air medical versus ground transportation for severely injured patients. In some systems, air medical crews may provide a higher level of care but may require longer transport times. We sought to evaluate the impact of mode of transport on outcome based on analysis of data from two randomized trials of prehospital hypertonic resuscitation. METHODS: Injured patients were enrolled based on prehospital evidence of hypovolemic shock (systolic blood pressure ⩽70 mm Hg or systolic blood pressure = 71–90 mm Hg with heart rate ≥108 bpm) or severe traumatic brain injury (TBI; Glasgow Coma Scale score ⩽8). Patient demographics, injury severity, and physiology were compared based on mode of transport. Multivariate logistic regression was used to determine the impact of mode of transport on 24-hour and 28-day survival for all patients and 6-month extended Glasgow Outcome Scale for patients with TBI, adjusting for differences in injury severity. RESULTS: Included were 2,049 patients, of which 703 (34%) were transported by air. Patients transported by air were more severely injured (mean Injury Severity Score, 30.3 vs. 22.8; p < 0.001), more likely to be in the TBI cohort (70% vs. 55.4%; p < 0.001), and more likely blunt mechanism (94.0% vs. 78.1%; p < 0.001). Patients transported by air had higher rates of prehospital intubation (81% vs. 36%; p < 0.001), received more intravenous fluids (mean 1.3 L vs. 0.8 L; p < 0.001), and had longer prehospital times (mean 76.1 minutes vs. 43.5 minutes; p < 0.001). Adjusted analysis revealed no significant impact of mode of transport on survival or 6-month neurologic outcome (air transport—28-day survival: odds ratio, 1.11; 95% confidence interval, 0.82–1.51; 6-month extended Glasgow Outcome Scale score ⩽4: odds ratio, 0.94; 95% confidence interval, 0.68–1.31). CONCLUSION: There was no difference in the adjusted clinical outcome according to mode of transport. However, air medical transported more severely injured patients with more advanced life support procedures and longer prehospital time. LEVEL OF EVIDENCE: III.

Post-discharge outcomes after resuscitation from out-of-hospital cardiac arrest: A ROC PRIMED substudy

IMPORTANCE Assessment of morbidity is an important component of evaluating interventions for patients with out-of-hospital cardiac arrest (OHCA). OBJECTIVE We evaluated among survivors of OHCA cognition, functional status, health-related quality of life and depression as functions of patient and emergency medical services (EMS) factors. DESIGN Prospective cohort sub-study of a randomized trial. SETTING The parent trial studied two comparisons in persons with non-traumatic OHCA treated by EMS personnel participating in the Resuscitation Outcomes Consortium. PARTICIPANTS Consenting survivors to discharge. MAIN OUTCOME MEASURES Telephone assessments up to 6 months after discharge included neurologic function (modified Rankin score, MRS), cognitive impairment (Adult Lifestyle and Function Mini Mental Status Examination, ALFI-MMSE), health-related quality of life (Health Utilities Index Mark 3, HUI3) and depression (Telephone Geriatric Depression Scale, T-GDS). RESULTS Of 15,794 patients enrolled in the parent trial, 729 (56% of survivors) consented. About 644 respondents (88% of consented) completed ≥ 1 assessment. Likelihood of assessment was associated with baseline characteristics and study site. Most respondents had MRS ≤ 3 (82.7%), no cognitive impairment (82.7% ALFI-MMSE ≥ 17), no severe impairment in health (71.6%, HUI3 ≥ 0.7) and no depression (90.1% T-GDS≤10). Outcomes did not differ by trial intervention or time from hospital discharge. CONCLUSIONS AND RELEVANCE The majority of patients in this large cohort who survived cardiac arrest and were interviewed had no, mild or moderate health impairment. Concern about poor quality of life is not a valid reason to abandon efforts to improve an EMS systems response to cardiac arrest.

Increased trauma center volume is associated with improved survival after severe injury: Results of a resuscitation outcomes consortium study

Objective:To investigate the relationship between trauma center volume and outcome. Background:The Resuscitation Outcomes Consortium is a network of 11 centers and 60 hospitals conducting emergency care research. For many procedures, high-volume centers demonstrate superior outcomes versus low-volume centers. This remains controversial for trauma center outcomes. Methods:This study was a secondary analysis of prospectively collected data from the Resuscitation Outcomes Consortium multicenter out-of-hospital Hypertonic Saline Trial in patients with Glasgow Coma Scale score of 8 or less (traumatic brain injury) or systolic blood pressure of 90 or less and pulse of 110 or more (shock). Regression analyses evaluated associations between trauma volume and the following outcomes: 24-hour mortality, 28-day mortality, ventilator-free days, Multiple Organ Dysfunction Scale incidence, worst Multiple Organ Dysfunction Scale score, and poor 6-month Glasgow Outcome Scale—Extended score. Results:A total of 2070 patients were evaluated: 1251 in the traumatic brain injury cohort and 819 in the shock cohort. Overall, 24-hour and 28-day mortality was 16% and 25%, respectively. For every increase of 500 trauma center admissions, there was a 7% decreased odds of 24-hour and 28-day mortality for all patients. As trauma center volume increased, nonorgan dysfunction complications increased, ventilator-free days increased, and worst Multiple Organ Dysfunction Scale score decreased. The associations with higher trauma center volume were similar for the traumatic brain injury cohort, including better neurologic outcomes at 6 months, but not for the shock cohort. Conclusions:Increased trauma center volume was associated with increased survival, more ventilator-free days, and less severe organ failure. Trauma system planning and implementation should avoid unnecessary duplication of services.

Hypoglycaemia and hyperglycaemia are associated with unfavourable outcome in infants with hypoxic ischaemic encephalopathy: a post hoc analysis of the CoolCap Study

Objective To investigate the association of neonatal hypoglycaemia and hyperglycaemia with outcomes in infants with hypoxic ischaemic encephalopathy (HIE). Design Post hoc analysis of the CoolCap Study. Setting 25 perinatal centres in the UK, the USA and New Zealand during 1999–2002. Patients 234 infants at ≥36 weeks’ gestation with moderate-to-severe HIE enrolled in the CoolCap Study. 214 (91%) infants had documented plasma glucose and follow-up outcome data. Intervention Infants were randomised to head cooling for 72 h starting within 6 h of birth, or standard care. Plasma glucose levels were measured at predetermined time intervals after randomisation. Main outcome measure The unfavourable primary outcome of the study was death and/or severe neurodevelopmental disability at 18 months. Hypoglycaemia (≤40 mg/dL, ≤2.2 mmol/L) and hyperglycaemia (>150 mg/dL, >8.3 mmol/L) during the first 12 h after randomisation were investigated for univariable and multivariable associations with unfavourable primary outcome. Results 121 (57%) infants had abnormal plasma glucose values within 12 h of randomisation. Unfavourable outcome was observed in 126 (60%) infants and was more common among subjects with hypoglycaemia (81%, p=0.004), hyperglycaemia (67%, p=0.01) and any glucose derangement within the first 12 h (67%, p=0.002) compared with normoglycaemic infants (48%) in univariable analysis. These associations remained significant after adjusting for birth weight, Apgar score, pH, Sarnat stage and hypothermia therapy. Conclusions Both hypoglycaemia and hyperglycaemia in infants with moderate-to-severe HIE were independently associated with unfavourable outcome. Future studies are needed to investigate the prognostic significance of these associations and their role as biomarkers of brain injury. Trial registration number (ClinicalTrials.gov NCT00383305).

Aspartate aminotransferase to platelet ratio and fibrosis-4 as biomarkers in biopsy-validated pediatric cystic fibrosis liver disease

Up to 10% of cystic fibrosis (CF) children develop cirrhosis by the first decade. We evaluated the utility of two simple biomarkers, aspartate aminotransferase to platelet ratio index (APRI) and FIB‐4, in predicting degree of fibrosis in pediatric CF liver disease (CFLD) validated by liver biopsy. In this retrospective, cross‐sectional study, 67 children with CFLD had dual‐pass liver biopsies and 104 age‐ and sex‐matched CF children without liver disease (CFnoLD) had serum to calculate APRI and FIB‐4 collected at enrollment. CFLD was defined as having two of the following: (1) hepatomegaly ± splenomegaly; (2) >6 months elevation of ALT (>1.5× upper limit of normal ULN); or (3) abnormal liver ultrasound findings. Biopsies were staged according to Metavir classification by two blinded pathologists. Receiver operating characteristic (ROC) analysis and continuation ratio logistic regression were performed to assess the predictability of these biomarkers to distinguish CFLD from CFnoLD and determine fibrosis stage‐specific cut‐off values. The AUC for APRI was better than FIB‐4 (0.75 vs. 0.60; P = 0.005) for predicting CFLD and severe CFLD (F3‐F4) (0.81). An APRI score >0.264 demonstrated a sensitivity (95% confidence interval [CI]) of 73.1% (60.9, 83.2) and specificity of 70.2% (60.4, 78.8) in predicting CFLD. A 50% increase in APRI was associated with a 2.4‐fold (95% CI: 1.7, 3.3) increased odds of having CFLD. APRI demonstrated full agreement with histology staging 37% of the time, but was within one stage 73% of the time. Only FIB‐4 predicted portal hypertension at diagnosis (area under the receiver operator characteristic curve [AUC] = 0.91; P < 0.001). Conclusion: This is the first liver biopsy‐validated study of APRI and FIB‐4 in pediatric CFLD. APRI appears superior to FIB‐4 in differentiating CFLD versus CFnoLD. APRI also exhibited a high AUC in predicting severe liver fibrosis with specific cutoffs for lower stages. (Hepatology 2015;62:1576–1583)

The Cognitive and Behavioral Phenotypes of Individuals with CHRNA7 Duplications.

Chromosome 15q11q13 is among the least stable regions in the genome due to its highly complex genomic architecture. Low copy repeat elements at 15q13.3 facilitate recurrent copy number variants (CNVs), with deletions established as pathogenic and CHRNA7 implicated as a candidate gene. However, the pathogenicity of duplications of CHRNA7 is unclear, as they are found in affected probands as well as in reportedly healthy parents and unaffected control individuals. We evaluated 18 children with microduplications involving CHRNA7, identified by clinical chromosome microarray analysis (CMA). Comprehensive phenotyping revealed high prevalence of developmental delay/intellectual disability, autism spectrum disorder, and attention deficit/hyperactivity disorder. As CHRNA7 duplications are the most common CNVs identified by clinical CMA, this study provides anticipatory guidance for those involved with care of affected individuals.

Circulating Aldosterone Levels and Disease Severity in Pulmonary Arterial Hypertension.

Objectives: It is not known whether aldosterone levels are associated with increased mortality in patients with pulmonary arterial hypertension (PAH). The primary goal of this study was to determine whether circulating aldosterone levels predict severity of PAH in terms of hemodynamic characteristics and mortality. Methods: Patients with stable PAH were enrolled at the Baylor PH program. The plasma levels of aldosterone and BNP were measured. Clinical, hemodynamic, and outcome data was collected by chart review. Mean follow up time from study enrollment was 39 ± 102 months. Cox proportional hazards model was used to assess time to death. Results: There were 125 PAH patients with plasma aldosterone levels. Median aldosterone level was 9.9 pg/ml (25th-75th percentile: 4.1 pg/ml, 27.1 pg/ml) and median brain natriuretic peptide (BNP) level was 67.5 pg/ml (25th- 75th percentile: 31 pg/ml, 225 pg/ml). Aldosterone levels were not significantly associated with BNP levels, six-minute walk distance, Borg dyspnea score, right ventricular systolic pressure, cardiac output and cardiac index. However, the association between aldosterone and right atrial pressure was dependent on mineralocorticoid receptor blocker treatment (Coef.=2.88, 95CI: 1.19, 4.56, p=0.001). By log-rank statistic there was no statistical difference between the survival of patients divided by median aldosterone level (p=0.914). However, there was a significant difference in patient survival between the BNP categories (p 180 pg/mL) had a shorter survival time. conclusions: The aldosterone level was not associated with increased mortality in PAH but was a marker of disease severity.