Esophageal Versus Rectal Temperature Monitoring During Whole-Body Therapeutic Hypothermia for Hypoxic-Ischemic Encephalopathy: Association with Short- and Long-Term Outcomes.

OBJECTIVE: To compare the short- and long-term outcomes of infants with hypoxic-ischemic encephalopathy (HIE) treated with whole-body therapeutic hypothermia (TH), monitored by esophageal vs rectal temperature. STUDY DESIGN: We conducted a secondary analysis of the multicenter High-Dose Erythropoietin for Asphyxia and Encephalopathy (HEAL) trial. All infants had moderate or severe HIE and were treated with whole-body TH. The primary outcome was death or neurodevelopmental impairment (NDI) at 22-36 months of age. Secondary outcomes included seizures, evidence of brain injury on magnetic resonance imaging, and complications of hypothermia. Logistic regression was used with adjustment for disease severity and site as clustering variable because cooling modality differed by site. RESULTS: Of the 500 infants who underwent TH, 294 (59%) and 206 (41%) had esophageal and rectal temperature monitoring, respectively. There were no differences in death or NDI, seizures, or evidence of injury on magnetic resonance imaging between the 2 groups. Infants treated with TH and rectal temperature monitoring had lower odds of overcooling (OR 0.52, 95% CI 0.34-0.80) and lower odds of hypotension (OR 0.57, 95% CI 0.39-0.84) compared with those with esophageal temperature monitoring. CONCLUSIONS: Although infants undergoing TH with esophageal monitoring were more likely to experience overcooling and hypotension, the rate of death or NDI was similar whether esophageal monitoring or rectal temperature monitoring was used. Further studies are needed to investigate whether esophageal temperature monitoring during TH is associated with an increased risk of overcooling and hypotension.

Association Between Urinary Biomarkers and CKD in Extremely Low Gestational Age Neonates.

RATIONALE & OBJECTIVE: Children born before 28 weeks' gestation are at increased risk of chronic kidney disease (CKD). Urine biomarkers may shed light on mechanistic pathways and improve the ability to forecast CKD. We evaluated whether urinary biomarkers in neonates of low gestational age (GA) are associated with a reduced estimated glomerular filtration rate (eGFR) over time. STUDY DESIGN: A cohort study of neonates with an exploratory case-control study of a subset of the cohort. SETTING & PARTICIPANTS: 327 neonates born at 24-27 weeks' gestation with 2-year eGFR data from the PENUT (Preterm Erythropoietin Neuroprotection Trial) and the REPaIReD (Recombinant Erythropoietin for Prevention of Infant Renal Disease) study. EXPOSURES: 11 urinary biomarkers measured at 27, 30, and 34 weeks' postmenstrual age for the primary cohort study and 10 additional biomarkers for the exploratory case-control study. OUTCOMES: eGFR<90mL/min/1.73m2 at 2 years corrected for GA. ANALYTICAL APPROACH: Linear mixed models to assess differences in biomarker values between neonates in whom CKD did and did not develop, accounting for multiple comparisons using Bonferroni-Holm correction in the cohort study only. Cohort analyses were adjusted for sex, GA, and body mass index. Cases were matched to controls on these variables in the case-control study. RESULTS: After adjusting for weeks of GA, urinary levels of α-glutathione-S-transferase (log difference, 0.27; 95% CI, 0.12-0.43), albumin (log difference, 0.13; 95% CI, 0.02-0.25), and cystatin C (log difference, 0.19; 95% CI, 0.04-0.34) were higher in those in whom CKD developed than in those in whom it did not. Urinary albumin and cystatin C levels did not remain significantly different after Bonferroni-Holm correction. In the exploratory case-control analysis, there were no differences in any biomarkers between cases and controls. LIMITATIONS: Early deaths and a high number of subjects without eGFR at 2 years corrected for GA. CONCLUSIONS: Measurement of urinary biomarkers may assist in monitoring neonates who are at risk for CKD. Additional studies are needed to confirm these findings. FUNDING: Grants from government (National Institutes of Health). TRIAL REGISTRATION: Registered at ClinicalTrials.gov with study number NCT01378273. PLAIN-LANGUAGE SUMMARY: Approximately 15 million neonates worldwide are born prematurely, and 2 million are born before 28 weeks' gestation. Many of these children go on to experience chronic kidney disease. Urine biomarkers may allow for early recognition of those at risk for the development of kidney disease. In this study of more than 300 children born before 28 weeks' gestational age, we found higher mean urinary levels of α-glutathione-S-transferase at 27, 30, and 34 weeks in children whose estimated glomerular filtration rate was<90mL/min/1.73m2 at 2 years compared with children whose estimated glomerular filtration rate was>90mL/min/1.73m2 at 2 years. Measurement of urinary biomarkers may assist in monitoring neonates who are at risk for chronic kidney disease. Additional studies are needed to confirm our findings.

Premature infants born <28 weeks with acute kidney injury have increased bronchopulmonary dysplasia rates.

BACKGROUND: Despite a growing understanding of bronchopulmonary dysplasia (BPD) and advances in management, BPD rates remain stable. There is mounting evidence that BPD may be due to a systemic insult, such as acute kidney injury (AKI). Our hypothesis was that severe AKI would be associated with BPD. METHODS: We conducted a secondary analysis of premature infants [24-27 weeks gestation] in the Recombinant Erythropoietin for Protection of Infant Renal Disease cohort (N = 885). We evaluated the composite outcome of Grade 2/3 BPD or death using generalized estimating equations. In an exploratory analysis, urinary biomarkers of angiogenesis (ANG1, ANG2, EPO, PIGF, TIE2, FGF, and VEGFA/D) were analyzed. RESULTS: 594 (67.1%) of infants had the primary composite outcome of Grade 2/3 BPD or death. Infants with AKI (aOR: 1.69, 95% CI: 1.16-2.46) and severe AKI (aOR: 2.05, 95% CI: 1.19-3.54). had increased risk of the composite outcome after multivariable adjustment Among 106 infants with urinary biomarkers assessed, three biomarkers (VEGFA, VEGFD, and TIE2) had AUC > 0.60 to predict BPD. CONCLUSIONS: Infants with AKI had a higher likelihood of developing BPD/death, with the strongest relationship seen in those with more severe AKI. Three urinary biomarkers of angiogenesis may have potential to predict BPD development. IMPACT: AKI is associated with lung disease in extremely premature infants, and urinary biomarkers may predict this relationship. Infants with AKI and severe AKI have higher odds of BPD or death. Three urinary angiogenesis biomarkers are altered in infants that develop BPD. These findings have the potential to drive future work to better understand the mechanistic pathways of BPD, setting the framework for future interventions to decrease BPD rates. A better understanding of the mechanisms of BPD development and the role of AKI would have clinical care, cost, and quality of life implications given the long-term effects of BPD.

Urine acute kidney injury biomarkers in extremely low gestational age neonates: a nested case control study of 21 candidate urine biomarkers.

BACKGROUND: Acute kidney injury (AKI) is common and is associated with poor clinical outcomes in premature neonates. Urine biomarkers hold the promise to improve our understanding and care of patients with kidney disease. Because kidney maturation and gender can impact urine biomarker values in extremely low gestational age neonates (ELGANs), careful control of gestational age (GA) and time is critical to any urine biomarker studies in neonates. METHODS: To improve our understanding of the potential use of urine biomarkers to detect AKI during the first postnatal weeks, we performed a nested case-control study to evaluate 21 candidate urine AKI biomarkers. Cases include 20 ELGANs with severe AKI. Each case was matched with 2 controls for the same GA week (rounded down to the nearest week), gender, and birth weight (BW) (± 50 g). RESULTS: Urine cystatin C, creatinine, ghrelin, fibroblast growth factor-23 (FGF23), tissue metalloproteinase 2 (TIMP2) and vascular endothelial growth factor A (VEGFa) concentrations were higher in ELGANs with early severe AKI compared to matched control subjects without AKI. Urine epidermal growth factor (EGF) and uromodulin (UMOD) concentrations are lower in cases than controls. Interleukin (IL)-15 was lower on day 1, but higher on day 8 in cases than controls; while VEGFa was lower on day 1, but higher on day 5 in cases than controls. CONCLUSION: Urine biomarkers hold the promise to improve our ability to reliably detect kidney injury. Interventional studies are needed to determine the biomarkers' ability to predict outcomes, enhance AKI phenotypes, and improve timely interventions which can prevent the sequalae of AKI in ELGANs. A higher resolution version of the Graphical abstract is available as Supplementary information.

Assessment of intensive care unit-free and ventilator-free days as alternative outcomes in the pragmatic airway resuscitation trial.

OBJECTIVE: We sought to evaluate the utility and validity of ICU-free days and ventilator-free days as candidate outcomes for OHCA trials. METHODS: We conducted a secondary analysis of the Pragmatic Airway Resuscitation Trial. We determined ICU-free (days alive and out of ICU during the first 30 days) and ventilator-free days (days alive and without mechanical ventilation). We determined ICU-free and ventilator-free day distributions and correlations with Modified Rankin Scale (MRS). We tested associations with trial interventions (laryngeal tube (LT), endotracheal intubation (ETI)) using continuous (t-test), non-parametric (Wilcoxon Rank-Sum test - WRS), count (negative binomial - NB) and survival models (Cox proportional hazards (CPH) and competing risks regression (CRR)). We conducted bootstrapped simulations to estimate statistical power. MAIN RESULTS: ICU-free days was skewed; median 0 days (IQR 0, 0), survivors only 24 (18, 27). Ventilator-free days was skewed; median 0 (IQR 0, 0) days, survivors only 27 (IQR 23, 28). ICU-free and ventilator-free days correlated with MRS (Spearman's ρ = -0.95 and -0.97). LT was associated with higher ICU-free days using t-test (p = 0.001), WRS (p = 0.003), CPH (p = 0.02) and CRR (p = 0.04), but not NB (p = 0.13). LT was associated with higher ventilator-free days using t-test (p = 0.001), WRS (p = 0.001) and CRR (p = 0.03), but not NB (p = 0.13) or CPH (p = 0.13). Simulations suggested that t-test and WRS would have had the greatest power to detect the observed ICU- and ventilator-free days differences. CONCLUSION: ICU-free and ventilator-free days correlated with MRS and differentiated trial interventions. ICU-free and ventilator-free days may have utility in the design of OHCA trials.

Prevalence and Risk Factors for Kidney Disease and Elevated BP in 2-Year-Old Children Born Extremely Premature.

BACKGROUND AND OBJECTIVES: Extremely low gestational age neonates born <28 weeks gestation are at risk for chronic disease. We sought to describe the prevalence of kidney outcomes by gestational age and determine risk factors for their development. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: The Recombinant Erythropoietin for Protection of Infant Renal Disease (REPAIReD) study examined kidney outcomes of extremely low gestational age neonates enrolled in the Preterm Epo NeuroProtection Trial (PENUT) study. Kidney function, urine albumin, and BP were measured at 2-year (24±2 months) corrected gestational age. We compared outcomes across gestational age categories and evaluated associations between kidney-related outcomes and neonatal and maternal characteristics. The primary outcome was eGFR <90 ml/min per 1.73 m2 (CKD); secondary outcomes were spot urine albumin-creatinine ratio ≥30 mg/g (albuminuria) and either systolic BP or diastolic BP >90th percentile for height, age, and sex. RESULTS: A total of 832 survived to 2 years, and 565 (68%) had at least one outcome measured. Overall, 297 (53%) had one abnormal kidney outcome; 61 (18%) had an eGFR <90 ml/min per 1.73 m2, 155 (36%) had albuminuria, 65 (22%) had elevated systolic BP, and 128 (44%) had elevated diastolic BP. Gestational age (odds ratio, 0.94; 95% confidence interval, 0.89 to 0.99), birth weight z-score (odds ratio, 0.92; 95% confidence interval, 0.85 to 0.98), and prenatal steroids (odds ratio, 1.23; 95% confidence interval, 1.08 to 1.39) were associated with an eGFR <90 ml/min per 1.73 m2. An elevated systolic BP was associated with indomethacin use (odds ratio, 1.18; 95% confidence interval, 1.04 to 1.33) and Black race (odds ratio, 1.19; 95% confidence interval, 1.01 to 1.39); elevated diastolic BP was associated with male sex (odds ratio, 1.29; 95% confidence interval, 1.12 to 1.49), severe AKI (odds ratio, 1.24; 95% confidence interval, 1.04 to 1.48), and indomethacin use (odds ratio, 1.16; 95% confidence interval, 1.01 to 1.33). CONCLUSIONS: Approximately 18% of extremely low gestational age neonates have CKD, 36% have albuminuria, 22% have an elevated systolic BP, and 44% have an elevated diastolic BP at 2 years of age. Gestational age, birthweight z-score, and prenatal steroids were associated with CKD. Male sex, Black race, indomethacin use, and severe AKI were associated with elevated BP. PODCAST: This article contains a podcast at https://www.asn-online.org/media/podcast/CJASN/2022_07_19_CJN15011121.mp3.

Airway strategy and ventilation rates in the pragmatic airway resuscitation trial.

BACKGROUND: We sought to describe ventilation rates during out-of-hospital cardiac arrest (OHCA) resuscitation and their associations with airway management strategy and outcomes. METHODS: We analyzed continuous end-tidal carbon dioxide capnography data from adult OHCA enrolled in the Pragmatic Airway Resuscitation Trial (PART). Using automated signal processing techniques, we determined continuous ventilation rates for consecutive 10-second epochs after airway insertion. We defined hypoventilation as a ventilation rate < 6 breaths/min. We defined hyperventilation as a ventilation rate > 12 breaths/min. We compared differences in total and percentage post-airway hyper- and hypoventilation between airway interventions (laryngeal tube (LT) vs. endotracheal intubation (ETI)). We also determined associations between hypo-/hyperventilation and OHCA outcomes (ROSC, 72-hour survival, hospital survival, hospital survival with favorable neurologic status). RESULTS: Adequate post-airway capnography were available for 1,010 (LT n = 714, ETI n = 296) of 3,004 patients. Median ventilation rates were: LT 8.0 (IQR 6.5-9.6) breaths/min, ETI 7.9 (6.5-9.7) breaths/min. Total duration and percentage of post-airway time with hypoventilation were similar between LT and ETI: median 1.8 vs. 1.7 minutes, p = 0.94; median 10.5% vs. 11.5%, p = 0.60. Total duration and percentage of post-airway time with hyperventilation were similar between LT and ETI: median 0.4 vs. 0.4 minutes, p = 0.91; median 2.1% vs. 1.9%, p = 0.99. Hypo- and hyperventilation exhibited limited associations with OHCA outcomes. CONCLUSION: In the PART Trial, EMS personnel delivered post-airway ventilations at rates satisfying international guidelines, with only limited hypo- or hyperventilation. Hypo- and hyperventilation durations did not differ between airway management strategy and exhibited uncertain associations with OCHA outcomes.

Chest radiography in children aged 2-59 months enrolled in the Innovative Treatments in Pneumonia (ITIP) project in Lilongwe Malawi: a secondary analysis.

BACKGROUND: Pneumonia is the leading infectious cause of death in children aged under 5 years in low- and middle-income countries (LMICs). World Health Organization (WHO) pneumonia diagnosis guidelines rely on non-specific clinical features. We explore chest radiography (CXR) findings among select children in the Innovative Treatments in Pneumonia (ITIP) project in Malawi in relation to clinical outcomes. METHODS: When clinically indicated, CXRs were obtained from ITIP-enrolled children aged 2 to 59 months with community-acquired pneumonia hospitalized with treatment failure or relapse. ITIP1 (fast-breathing pneumonia) and ITIP2 (chest-indrawing pneumonia) trials enrolled children with non-severe pneumonia while ITIP3 enrolled children excluded from ITIP1 and ITIP2 with severe pneumonia and/or selected comorbidities. A panel of trained pediatricians classified the CXRs using the standardized WHO CXR research methodology. We analyzed the relationship between CXR classifications, enrollee characteristics, and outcomes. RESULTS: Between March 2016 and June 2018, of 114 CXRs obtained, 83 met analysis criteria with 62.7% (52/83) classified as having significant pathology per WHO standardized interpretation. ITIP3 (92.3%; 12/13) children had a higher proportion of CXRs with significant pathology compared to ITIP1 (57.1%, 12/21) and ITIP2 (57.1%, 28/49) (p-value = 0.008). The predominant pathological CXR reading was "other infiltrates only" in ITIP1 (83.3%, 10/12) and ITIP2 (71.4%, 20/28), while in ITIP3 it was "primary endpoint pneumonia"(66.7%, 8/12,; p-value = 0.008). The percent of CXRs with significant pathology among children clinically cured (60.6%, 40/66) vs those not clinically cured (70.6%, 12/17) at Day 14 was not significantly different (p-value = 0.58). CONCLUSIONS: In this secondary analysis we observed that ITIP3 children with severe pneumonia and/or selected comorbidities had a higher frequency of CXRs with significant pathology, although these radiographic findings had limited relationship to Day 14 outcomes. The proportion of CXRs with "primary endpoint pneumonia" was low. These findings add to existing data that additional diagnostics and prognostics are important for improving the care of children with pneumonia in LMICs. TRIAL REGISTRATION: ITIP1, ITIP2, and ITIP3 were registered with ClinicalTrials.gov ( NCT02760420 , NCT02678195 , and NCT02960919 , respectively).

Gestational age, sex, and time affect urine biomarker concentrations in extremely low gestational age neonates.

BACKGROUND: Our understanding of the normative concentrations of urine biomarkers in premature neonates is limited. METHODS: We evaluated urine from 750 extremely low gestational age (GA) neonates without severe acute kidney injury (AKI) to determine how GA affects ten different urine biomarkers at birth and over the first 30 postnatal days. Then, we investigated if the urine biomarkers changed over time at 27, 30, and 34 weeks postmenstrual age (PMA). Next, we evaluated the impact of sex on urine biomarker concentrations at birth and over time. Finally, we evaluated if urine biomarkers were impacted by treatment with erythropoietin (Epo). RESULTS: We found that all ten biomarker concentrations differ at birth by GA and that some urine biomarker concentrations increase, while others decrease over time. At 27 weeks PMA, 7/10 urine biomarkers differed by GA. By 30 weeks PMA, 5/10 differed, and by 34 weeks PMA, only osteopontin differed by GA. About half of the biomarker concentrations differed by sex, and 4/10 showed different rates of change over time between males vs. females. We found no differences in urine biomarkers by treatment group. CONCLUSIONS: The temporal patterns, GA, and sex differences need to be considered in urine AKI biomarker analyses. IMPACT: Urine biomarker concentrations differ by GA at birth. Some urine biomarkers increase, while others decrease, over the first 30 postnatal days. Most urine biomarkers differ by GA at 27 weeks PMA, but are similar by 34 weeks PMA. Some urine biomarkers vary by sex in premature neonates. Urine biomarkers did not differ between neonates randomized to placebo vs. Epo.

The association of race with CPR quality following out-of-hospital cardiac arrest.

INTRODUCTION: Previous studies have shown racial disparities in outcomes after out-of-hospital cardiac arrest. Although several treatment factors may account for these differences, there is limited information regarding differences in CPR quality and its effect on survival in underrepresented racial populations. METHODS: We conducted a secondary analysis of data from patients enrolled in the Pragmatic Airway Resuscitation Trial (PART). We calculated compliance rates with AHA 2015 high quality CPR metrics as well as compliance to intended CPR strategy (30:2 or continuous chest compression) based on the protocol in place for the first responding EMS agency. The primary analysis used general estimating equations logistic regression to examine differences between black and white patients based on EMS-assessed race after adjustment for potential confounders. Sensitivity analyses examined differences using alternate race definitions. RESULTS: There were 3004 patients enrolled in PART of which 1734 had > 2 minutes of recorded CPR data and an EMS-assessed race (1003 white, 555 black, 176 other). Black patients had higher adjusted odds of compression rate compliance (OR: 1.36, 95% CI: 1.02-1.81) and lower adjusted odds of intended CPR strategy compliance (OR: 0.78, 95% CI: 0.63-0.98) compared to white patients. Of 974 transported to the hospital, there was no difference in compliance metric estimates based on ED-reported race. CONCLUSION: Compression rate compliance was higher in black patients however compliance with intended strategy was lower based on EMS-assessed race. The remaining metrics showed no difference suggesting that CPR quality differences are not important contributors to the observed outcome disparities by race.

Methodology and framework for the analysis of cardiopulmonary resuscitation quality in large and heterogeneous cardiac arrest datasets.

BACKGROUND: Out-of-hospital cardiac arrest (OHCA) data debriefing and clinical research often require the retrospective analysis of large datasets containing defibrillator files from different vendors and clinical annotations by the emergency medical services. AIM: To introduce and evaluate a methodology to automatically extract cardiopulmonary resuscitation (CPR) quality data in a uniform and systematic way from OHCA datasets from multiple heterogeneous sources. METHODS: A dataset of 2236 OHCA cases from multiple defibrillator models and manufacturers was analyzed. Chest compressions were automatically identified using the thoracic impedance and compression depth signals. Device event time-stamps and clinical annotations were used to set the start and end of the analysis interval, and to identify periods with spontaneous circulation. A manual audit of the automatic annotations was conducted and used as gold standard. Chest compression fraction (CCF), rate (CCR) and interruption ratio were computed as CPR quality variables. The unsigned error between the automated procedure and the gold standard was calculated. RESULTS: Full-episode median errors below 2% in CCF, 1 min-1 in CCR, and 1.5% in interruption ratio, were measured for all signals and devices. The proportion of cases with large errors (>10% in CCF and interruption ratio, and >10 min-1 in CCR) was below 10%. Errors were lower for shorter sub-intervals of interest, like the airway insertion interval. CONCLUSIONS: An automated methodology was validated to accurately compute CPR metrics in large and heterogeneous OHCA datasets. Automated processing of defibrillator files and the associated clinical annotations enables the aggregation and analysis of CPR data from multiple sources.

CPR compression strategy 30:2 is difficult to adhere to, but has better survival than continuous chest compressions when done correctly.

BACKGROUND: A large, randomized trial showed no significant difference in survival to discharge between cardiopulmonary resuscitation (CPR) strategies of 30 compressions with pause for 2 ventilations per cycle (30:2) and continuous chest compression with asynchronous ventilations (CCC). Data from the same trial suggested that adherence to the intended CPR strategy was associated with significantly greater survival. We sought to determine the adherence rate with intended strategy and then explore the association of adherence with survival to discharge in the Resuscitation Outcomes Consortium (ROC). METHODS: This secondary analysis of data from the ROC included three interventional trials and a prospective registry. We modified an automated software algorithm that classified care as 30:2 or CCC before intubation based on compression segment length (defined as the elapsed time from start of compressions to subsequent pause of ≥2 s), number of pauses per minute ≥2 s in length and chest compression fraction. Intended CPR strategy for individual agencies was based on study randomization (during trial phase) or local standard of care (during registry phase). We defined CPR delivered as adherent when its classification matched the intended strategy. We characterized adherence with intended strategy across trial and registry periods. We examined its association with survival to hospital discharge using multivariate logistic regression after adjustment for Utstein and other potential confounders. Effect modification with intended strategy was assessed through a multiplicative interaction term. RESULTS: Included were 26,810 adults with out of hospital cardiac arrest, of which 10,942 had an intended strategy of 30:2 and 15,868 an intended strategy of CCC. The automated algorithm classified 12,276 cases as CCC, 7037 as 30:2 and left 7497 as unclassified. Adherence to intended strategy was 54.4%; this differed by intended strategy (58.6% for CCC vs 48.3% for 30:2). Overall adherence was less during the registry phase as compared to during the trial phase(s). The association between adherence and survival was modified by treatment arm (CCC OR: 0.72, 95% CI: 0.64-0.81 vs 30:2 OR: 1.05, 95% CI: 0.90-1.22; interaction p-value<0.01) after adjustment for known confounders. CONCLUSION: For intended strategy CCC, survival was significantly lower, OR (95%CI) = 0.72 (0.64, 0.81), when adhered to while for intended strategy 30:2, survival was higher, OR (95%CI) = 1.05 (0.90, 1.22), when adhered to. Intended strategy of 30:2 had lower adherence rates than CCC possibly a result of being a more difficult strategy to administer.

Severe Acute Kidney Injury and Mortality in Extremely Low Gestational Age Neonates.

BACKGROUND AND OBJECTIVES: AKI is associated with poor short- and long-term outcomes. Questions remain about the frequency and timing of AKI, and whether AKI is a cause of death in extremely low gestational age neonates. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: The Recombinant Erythropoietin for Protection of Infant Kidney Disease Study examines the kidney outcomes of extremely low gestational age neonates enrolled in the Preterm Epo Neuroprotection study, a randomized, placebo-controlled trial of recombinant human erythropoietin. We included 900 of 941 patients enrolled in Preterm Epo Neuroprotection. Baseline characteristics were compared by primary exposure (severe AKI versus none/stage 1 AKI) using unadjusted logistic regression models. Cox regression models estimated the relationship between severe AKI and death after adjustment for potential confounders. Time-dependent AKI was modeled as a binary outcome and a categorical variable by stage of AKI. We fit Cox models using time-dependent AKI status lagged by <7 days before death. Landmark analyses examined the relationship of death with development of severe AKI. RESULTS: Severe AKI occurred in 168 of 900 (19%, 95% confidence interval, 17% to 20%) neonates, and stage 3 AKI occurred in 60 (7%, 95% confidence interval, 5% to 8%). Stage 3 AKI occurring 7 days before death (hazard ratio, 3.88; 95% confidence interval, 1.26 to 11.96), intraventricular hemorrhage (hazard ratio, 2.01; 95% confidence interval, 1.01 to 3.99) and sepsis (hazard ratio, 2.85; 95% confidence interval, 1.12 to 7.22) were all independently associated with death. Severe AKI occurring 7 days before death (hazard ratio, 2.21; 95% confidence interval, 0.92 to 5.26) was associated with death but not statistically significant. In a landmark analysis, after adjusting for potential confounders, late (after day 14 and before day 28) severe AKI was strongly associated with higher hazard of death (hazard ratio, 4.57; 95% confidence interval, 1.82 to 11.5). CONCLUSIONS: Severe AKI occurs frequently in extremely low gestational age neonates. Stage 3 AKI is associated with mortality, and this association is present 7 days before death.

Malawian children with fast-breathing pneumonia with and without comorbidities.

BACKGROUND: Due to high risk of mortality, children with comorbidities are typically excluded from trials evaluating pneumonia treatment. Understanding heterogeneity of outcomes among children with pneumonia and comorbidities is critical to ensuring appropriate treatment. METHODS: We explored whether the percentage of children with fast-breathing pneumonia cured at Day 14 was lower among those with selected comorbidities enrolled in a prospective observational study than among those enrolled in a concurrent randomized controlled trial evaluating treatment with amoxicillin in Lilongwe, Malawi. RESULTS: Among 79 children with fast-breathing pneumonia in the prospective observational cohort, 57 (72.2%) had HIV infection/exposure, 20 (25.3%) had malaria, 2 (2.5%) had severe acute malnutrition, and 17 (21.5%) had anemia. Treatment failure rate was slightly (not significantly) lower in children with comorbidities (4.1%, 3/73) compared to those without comorbidities (4.5%, 25/552) similarly treated. There was no significant difference in clinical cure rates by Day 14 (95.8% with vs 96.7% without comorbidity). CONCLUSIONS: Children with fast-breathing pneumonia excluded from a concurrent clinical trial due to comorbidities did not fare worse. Children at higher risk whose caregivers seek care early and who receive appropriate risk assessment (e.g., pulse oximetry, hemoglobin, HIV/malaria testing) and treatment, can achieve clinical cure by Day 14. TRIAL REGISTRATION: ClinicalTrials.gov NCT02960919 ; registered November 8, 2016.

Airway strategy and chest compression quality in the Pragmatic Airway Resuscitation Trial.

BACKGROUND: Chest compression (CC) quality is associated with improved out-of-hospital cardiopulmonary arrest (OHCA) outcomes. Airway management efforts may adversely influence CC quality. We sought to compare the effects of initial laryngeal tube (LT) and initial endotracheal intubation (ETI) airway management strategies upon chest compression fraction (CCF), rate and interruptions in the Pragmatic Airway Resuscitation Trial (PART). METHODS: We analyzed CPR process files collected from adult OHCA enrolled in PART. We used automated signal processing techniques and a graphical user interface to calculate CC quality measures and defined interruptions as pauses in chest compressions longer than 3 s. We determined CC fraction, rate and interruptions (number and total duration) for the entire resuscitation and compared differences between LT and ETI using t-tests. We repeated the analysis stratified by time before, during and after airway insertion as well as by successive 3-min time segments. We also compared CC quality between single vs. multiple airway insertion attempts, as well as between bag-valve-mask (BVM-only) vs. ETI or LT. RESULTS: Of 3004 patients enrolled in PART, CPR process data were available for 1996 (1001 LT, 995 ETI). Mean CPR analysis duration were: LT 22.6 ±â€¯10.8 min vs. ETI 25.3 ±â€¯11.3 min (p < 0.001). Mean CC fraction (LT 88% vs. ETI 87%, p = 0.05) and rate (LT 114 vs. ETI 114 compressions per minute (cpm), p = 0.59) were similar between LT and ETI. Median number of CC interruptions were: LT 11 vs. ETI 12 (p = 0.001). Total CC interruption duration was lower for LT than ETI (LT 160 vs. ETI 181 s, p = 0.002); this difference was larger before airway insertion (LT 56 vs. ETI 78 s, p < 0.001). There were no differences in CC quality when stratified by 3-min time epochs. CONCLUSION: In the PART trial, compared with ETI, LT was associated with shorter total CC interruption duration but not other CC quality measures. CC quality may be associated with OHCA airway management.

The Impact of Erythropoietin on Short- and Long-Term Kidney-Related Outcomes in Neonates of Extremely Low Gestational Age. Results of a Multicenter, Double-Blind, Placebo-Controlled Randomized Clinical Trial.

OBJECTIVE: To evaluate whether extremely low gestational age neonates (ELGANs) randomized to erythropoietin have better or worse kidney-related outcomes during hospitalization and at 22-26 months of corrected gestational age (cGA) compared with those randomized to placebo. STUDY DESIGN: We performed an ancillary study to a multicenter double-blind, placebo-controlled randomized clinical trial of erythropoietin in ELGANs. RESULTS: The prevalence of severe (stage 2 or 3) acute kidney injury (AKI) was 18.2%. We did not find a statistically significant difference between those randomized to erythropoietin vs placebo for in-hospital primary (severe AKI) or secondary outcomes (any AKI and serum creatinine/cystatin C values at days 0, 7, 9, and 14). At 22-26 months of cGA, 16% of the cohort had an estimated glomerular filtration rate (eGFR) <90 mL/min/1.73 m2, 35.8% had urine albumin/creatinine ratio >30 mg/g, 23% had a systolic blood pressure (SBP) >95th percentile for age, and 40% had a diastolic blood pressure (DBP) >95th percentile for age. SBP >90th percentile occurred less often among recipients of erythropoietin (P < .04). This association remained even after controlling for gestational age, site, and sibship (aOR 0.6; 95% CI 0.39-0.92). We did not find statistically significant differences between treatment groups in eGFR, albumin/creatinine ratio, rates of SBP >95th percentile, or DBP >90th or >95th percentiles at the 2 year follow-up visit. CONCLUSIONS: ELGANs have high rates of in-hospital AKI and kidney-related problems at 22-26 months of cGA. Recombinant erythropoietin may protect ELGANs against long-term elevated SBP but does not appear to protect from AKI, low eGFR, albuminuria, or elevated DBP at 22-26 months of cGA.

Software annotation of defibrillator files: Ready for prime time?

BACKGROUND: High-quality chest compressions are associated with improved outcomes after cardiac arrest. Defibrillators record important information about chest compressions during cardiopulmonary resuscitation (CPR) and can be used in quality-improvement programs. Defibrillator review software can automatically annotate files and measure chest compression metrics. However, evidence is limited regarding the accuracy of such measurements. OBJECTIVE: To compare chest compression fraction (CCF) and rate measurements made with software annotation vs. manual annotation vs. limited manual annotation of defibrillator files recorded during out-of-hospital cardiac arrest (OHCA) CPR. METHODS: This was a retrospective, observational study of 100 patients who had CPR for OHCA. We assessed chest compression bioimpedance waveforms from the time of initial CPR until defibrillator removal. A reviewer revised software annotations in two ways: completely manual annotations and limited manual annotations, which marked the beginning and end of CPR and ROSC, but not chest compressions. Measurements were compared for CCF and rate using intraclass correlation coefficient (ICC) analysis. RESULTS: Case mean rate showed no significant difference between the methods (108.1-108.6 compressions per minute) and ICC was excellent (>0.90). The case mean (±SD) CCF for software, manual, and limited manual annotation was 0.64 ±â€¯0.19, 0.86 ±â€¯0.07, and 0.81 ±â€¯0.10, respectively. The ICC for manual vs. limited manual annotation of CCF was 0.69 while for individual minute epochs it was 0.83. CONCLUSION: Software annotation performed very well for chest compression rate. For CCF, the difference between manual and software annotation measurements was clinically important, while manual vs. limited manual annotation were similar with an ICC that was good-to-excellent.

Airway insertion first pass success and patient outcomes in adult out-of-hospital cardiac arrest: The Pragmatic Airway Resuscitation Trial.

OBJECTIVE: While emphasized in clinical practice, the association between advanced airway insertion first-pass success (FPS) and patient outcomes is incompletely understood. We sought to determine the association of airway insertion FPS with adult out-of-hospital cardiac arrest (OHCA) outcomes in the Pragmatic Airway Resuscitation Trial (PART). METHODS: We performed a secondary analysis of PART, a multicenter clinical trial comparing LT and ETI upon adult OHCA outcomes. We defined FPS as successful LT insertion or ETI on the first attempt as reported by EMS personnel. We examined the outcomes return of spontaneous circulation (ROSC), 72-h survival, hospital survival, and hospital survival with favorable neurologic status (Modified Rankin Scale ≤3). Using multivariable GEE (generalized estimating equations), we determined the association between FPS and OHCA outcomes, adjusting for age, sex, witnessed arrest, bystander CPR, initial rhythm, and initial airway type. RESULTS: Of 3004 patients enrolled in the trial, 1423 received LT, 1227 received ETI, 354 received bag-valve-mask ventilation only. FPS was: LT 86.2% and ETI 46.7%. FPS was associated with increased ROSC (aOR 1.23; 95%CI: 1.07-1.41)), but not 72-h survival (1.22; 0.94-1.58), hospital survival (0.90; 0.68-1.19) or hospital survival with favorable neurologic status (0.66; 0.37-1.19). CONCLUSION: In adult OHCA, airway insertion FPS was associated with increased ROSC but not other OHCA outcomes. The influence of airway insertion FPS upon OHCA outcomes is unclear.

Prospective evaluation of airway management in pediatric out-of-hospital cardiac arrest.

OBJECTIVE: The objective of the study was to identify the association between airway management modality and time to the initial dose of epinephrine in pediatric out-of-hospital cardiac arrest (OHCA). METHODS: This was a prospective observational study conducted between April 2016 to April 2018. Ten Emergency Medical Services (EMS) agencies in 2 US metropolitan areas, which were part of the Resuscitation Outcomes Consortium research network, participated in the study. We included all EMS-treated OHCA patients less than 18 years of age during the study period. Study outcomes included time to the initial dose of epinephrine, airway management success rates, rescue techniques, and complications (e.g. pneumothorax, pneumonia). RESULTS: The study included a total of 155 patients, 67% were male, and 55% were less than age one. The airway management modality (TI, SGA, BMV) was not associated with the time to the intial dose of epinephrine in the adjusted analysis. Tracheal intubation (TI) was the most common airway management modality (47.1%) followed by bag-mask-ventilation (BMV) (40.7%), and supraglottic airways (SGA) (12.3%). Success was 65.7% for TI and 94.7% for SGA. We found a significant difference in the proportion of initial survivors diagnosed with pneumonia on chest X-ray between those with BMV (1/19) versus TI (13/21) p < 0.001. CONCLUSIONS: In this prospective study, the airway management modality was not associated with the time to the initial dose of epinephrine. Unexpectedly, pneumonia was significantly more common among children treated with TI compared to BMV. SGAs had high first-attempt success rates, while intubation success rates were low.