Testing the Prognostic Accuracy of the Updated Pediatric Sepsis Biomarker Risk Model

Background We previously derived and validated a risk model to estimate mortality probability in children with septic shock (PERSEVERE; PEdiatRic SEpsis biomarkEr Risk modEl). PERSEVERE uses five biomarkers and age to estimate mortality probability. After the initial derivation and validation of PERSEVERE, we combined the derivation and validation cohorts (n = 355) and updated PERSEVERE. An important step in the development of updated risk models is to test their accuracy using an independent test cohort. Objective To test the prognostic accuracy of the updated version PERSEVERE in an independent test cohort. Methods Study subjects were recruited from multiple pediatric intensive care units in the United States. Biomarkers were measured in 182 pediatric subjects with septic shock using serum samples obtained during the first 24 hours of presentation. The accuracy of PERSEVERE 28-day mortality risk estimate was tested using diagnostic test statistics, and the net reclassification improvement (NRI) was used to test whether PERSEVERE adds information to a physiology-based scoring system. Results Mortality in the test cohort was 13.2%. Using a risk cut-off of 2.5%, the sensitivity of PERSEVERE for mortality was 83% (95% CI 62–95), specificity was 75% (68–82), positive predictive value was 34% (22–47), and negative predictive value was 97% (91–99). The area under the receiver operating characteristic curve was 0.81 (0.70–0.92). The false positive subjects had a greater degree of organ failure burden and longer intensive care unit length of stay, compared to the true negative subjects. When adding PERSEVERE to a physiology-based scoring system, the net reclassification improvement was 0.91 (0.47–1.35; p<0.001). Conclusions The updated version of PERSEVERE estimates mortality probability reliably in a heterogeneous test cohort of children with septic shock and provides information over and above a physiology-based scoring system

Prospective clinical testing and experimental validation of the Pediatric Sepsis Biomarker Risk Model

Sepsis remains a major public health problem with no major therapeutic advances over the last several decades. The clinical and biological heterogeneity of sepsis have limited success of potential new therapies. Accordingly, there is considerable interest in developing a precision medicine approach to inform more rational development, testing, and targeting of new therapies. We previously developed the Pediatric Sepsis Biomarker Risk Model (PERSEVERE) to estimate mortality risk and proposed its use as a prognostic enrichment tool in sepsis clinical trials; prognostic enrichment selects patients based on mortality risk independent of treatment. Here, we show that PERSEVERE has excellent performance in a diverse cohort of children with septic shock with potential for use as a predictive enrichment strategy; predictive enrichment selects patients based on likely response to treatment. We demonstrate that the PERSEVERE biomarkers are reliably associated with mortality in mice challenged with experimental sepsis, thus providing an opportunity to test precision medicine strategies in the preclinical setting. Using this model, we tested two clinically feasible therapeutic strategies, guided by the PERSEVERE-based enrichment, and found that mice identified as high risk for mortality had a greater bacterial burden and could be rescued by higher doses of antibiotics. The association between higher pathogen burden and higher mortality risk was corroborated among critically ill children with septic shock. This bedside to bench to bedside approach provides proof of principle for PERSEVERE-guided application of precision medicine in sepsis

2019 International Consensus on Cardiopulmonary Resuscitation and Emergency Cardiovascular Care Science With Treatment Recommendations

The International Liaison Committee on Resuscitation has initiated a continuous review of new, peer-reviewed, published cardiopulmonary resuscitation science. This is the third annual summary of the International Liaison Committee on Resuscitation International Consensus on Cardiopulmonary Resuscitation and Emergency Cardiovascular Care Science With Treatment Recommendations. It addresses the most recent published resuscitation evidence reviewed by International Liaison Committee on Resuscitation Task Force science experts. This summary addresses the role of cardiac arrest centers and dispatcher-assisted cardiopulmonary resuscitation, the role of extracorporeal cardiopulmonary resuscitation in adults and children, vasopressors in adults, advanced airway interventions in adults and children, targeted temperature management in children after cardiac arrest, initial oxygen concentration during resuscitation of newborns, and interventions for presyncope by first aid providers. Members from 6 International Liaison Committee on Resuscitation task forces have assessed, discussed, and debated the certainty of the evidence on the basis of the Grading of Recommendations, Assessment, Development, and Evaluation criteria, and their statements include consensus treatment recommendations. Insights into the deliberations of the task forces are provided in the Justification and Evidence to Decision Framework Highlights sections. The task forces also listed priority knowledge gaps for further research

Cardiopulmonary Resuscitation in Interfacility Transport: An International Report Using the Ground Air Medical Quality in Transport (GAMUT) Database

Background. With the regionalization of specialty care, there is an increasing need for interfacility transport from local to regional hospitals. There are very limited data on rates of cardiopulmonary resuscitation (CPR) during medical transport and relationship between transport-specific factors, such as transport program type and need of CPR during transport of critically ill patients. We present the first, multicenter, international report of CPR during medical transport using the large Ground and Air Medical qUality Transport (GAMUT) database. Methods. We retrospectively reviewed the GAMUT database from January 2014 to March 2017 for CPR during transport. We determined the overall CPR rate and CPR rates for adult, pediatric, and neonatal transport programs. The rate of CPR per total transports was expressed as percentage, and then, Spearman’s rho nonparametric associations were determined between CPR and other quality metrics tracked in the GAMUT database. Examples include advanced airway presence, waveform capnography usage, average mobilization time from the start of referral until en route, 1st attempt intubation success rate, and DASH1A intubation success (definitive airway sans hypoxia/hypotension on 1st attempt). Data were analyzed using chi-square tests, and in the presence of overall significance, post hoc Bonferroni adjusted z tests were performed. Results. There were 72 programs that had at least one CPR event during the study period. The overall CPR rate was 0.42% (777 CPR episodes/184,272 patient contacts) from 115 programs reporting transport volume and CPR events from the GAMUT database during the study period. Adult, pediatric, and neonatal transport programs (n = 57, 40 and 16, respectively) had significantly different CPR rates (P<0.001) i.e., 0.68% (555/82,094), 0.18% (138/76,430), and 0.33% (73/21,823), respectively. Presence of an advanced airway and mobilization time was significantly associated with CPR episodes (P<0.001) (Rs = +0.41 and Rs  = −0.60, respectively). Other transport quality metrics such as waveform capnography, first attempt intubation, and DASH1A success rate were not significantly associated with CPR episodes. Conclusion. The overall CPR rate during medical transport is 0.42%. Adult, pediatric, and neonatal program types have significantly different overall rates of CPR. Presence of advanced airway and mobilization time had an association with the rate of CPR during transport

Risk Factors for Failed Tracheal Intubation in Pediatric and Neonatal Critical Care Specialty Transport.

Abstract Objective. Nearly 200,000 pediatric and neonatal transports occur in the United States each year with some patients requiring tracheal intubation. First-pass intubation rates in both pediatric and adult transport literature are variable as are the factors that influence intubation success. This study sought to determine risk factors for failed tracheal intubation in neonatal and pediatric transport. Methods. A retrospective chart review was performed over a 2.5-year period. Data were collected from a hospital-based neonatal/pediatric critical care transport team that transports 2,500 patients annually, serving 12,000 square miles. Patients were eligible if they were transported and tracheally intubated by the critical care transport team. Patients were categorized into two groups for data analysis: (1) no failed intubation attempts and (2) at least one failed intubation attempt. Data were tabulated using Epi Info Version 3.5.1 and analyzed using SPSSv17.0. Results. A total of 167 patients were eligible for enrollment and were cohorted by age (48% pediatric versus 52% neonatal). Neonates were more likely to require multiple attempts at intubation when compared to the pediatric population (69.6% versus 30.4%, p = 0.001). Use of benzodiazepines and neuromuscular blockade was associated with increased successful first attempt intubation rates (p = 0.001 and 0.008, respectively). Use of opiate premedication was not associated with first-attempt intubation success. The presence of comorbid condition(s) was associated with at least one failed intubation attempt (p = 0.006). Factors identified with increasing odds of at least one intubation failure included, neonatal patients (OR 3.01), tracheal tube size ≤ 2.5 mm (OR 3.78), use of an uncuffed tracheal tube (OR 6.85), and the presence of a comorbid conditions (OR 2.64). Conclusions. There were higher rates of tracheal intubation failure in transported neonates when compared to pediatric patients. This risk may be related to the lack of benzodiazepine and neuromuscular blocking agents used to facilitate intubation. The presence of a comorbid condition is associated with a higher risk of tracheal intubation failure.http://deepblue.lib.umich.edu/bitstream/2027.42/192990/2/Risk Factors for Failed Tracheal Intubation in Pediatric and Neonatal Critical Care Specialty Transport.pdfPublished versionDescription of Risk Factors for Failed Tracheal Intubation in Pediatric and Neonatal Critical Care Specialty Transport.pdf : Published versio

Decreasing handoff-related care failures in children\u27s hospitals

Bigham, M. T., Logsdon, T. R., Manicone, P. E., Landrigan, C. P., Hayes, L. W., Randall, K. H., . . . Sharek, P. J. (2014). Decreasing handoff-related care failures in children\u27s hospitals. Pediatrics, 134(2), e572-e579