The Association of Corticosteroids and Pediatric Sepsis Biomarker Risk Model (PERSEVERE)-II Biomarker Risk Stratification With Mortality in Pediatric Septic Shock.

OBJECTIVES: Mortality risk stratification may identify a subset of children who benefit from or are harmed by corticosteroid administration. The Pediatric Sepsis Biomarker Risk Model (PERSEVERE)-II score is a biomarker-based mortality risk stratification tool for pediatric sepsis. Our objective was to assess the association of corticosteroid administration with 28-day mortality within different levels of baseline mortality risk (PERSEVERE-II) in a cohort of children with septic shock. DESIGN: We performed a secondary analysis using prospectively collected data (January 2015 to December 2018). SETTING: PICUs in 13 tertiary care, academic centers in the United States. PATIENTS: Children with septic shock. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: We assessed the association of corticosteroid administration within PERSEVERE-II risk score categories and 28-day mortality, ICU-free days, and maximum failed organs in children with septic shock. We analyzed a total of 461 patients (215 with corticosteroids exposure, 246 without corticosteroid exposure) with an average age of 7.1 years (interquartile range, 2.2-13.6 yr). In the subgroup of patients with a high PERSEVERE-II score, corticosteroid administration was associated with an increased adjusted risk of 28-day mortality (odds ratio [OR] 4.10 [95% CI 1.70-9.86]; p = 0.002), but not in the low risk group (OR 0.20 [95% CI 0.02-1.73]; p = 0.15). A significant interaction between PERSEVERE-II score and corticosteroids was seen for both secondary outcomes complicated course ( p = 0.01) and maximum failed organs ( p < 0.001). Corticosteroid exposure was associated with fewer ICU-free days ( p < 0.0001). CONCLUSIONS: In our multicenter observational study, corticosteroid administration was associated with increased mortality in a subgroup of children with a high PERSEVERE-II risk score.

Diagnostic test accuracy for cessation of circulation during death determination: a systematic review.

PURPOSE: To synthesize the available evidence comparing noninvasive methods of measuring the cessation of circulation in patients who are potential organ donors undergoing death determination by circulatory criteria (DCC) with the current accepted standard of invasive arterial blood pressure (IAP) monitoring. SOURCE: We searched (from inception until 27 April 2021) MEDLINE, Embase, Web of Science, and the Cochrane Central Register of Controlled Trials. We screened citations and manuscripts independently and in duplicate for eligible studies that compared noninvasive methodologies assessing circulation in patients who were monitored around a period of cessation of circulation. We performed risk of bias assessment, data abstraction, and quality assessment using Grading of Recommendations, Assessment, Development, and Evaluation in duplicate and independently. We presented findings narratively. PRINCIPAL FINDINGS: We included 21 eligible studies (N = 1,177 patients). Meta-analysis was not possible because of study heterogeneity. We identified low quality evidence from four indirect studies (n = 89) showing pulse palpation is less sensitive and specific than IAP (reported sensitivity range, 0.76-0.90; specificity, 0.41-0.79). Isoelectric electrocardiogram (ECG) had excellent specificity for death (two studies; 0% [0/510]), but likely increases the average time to death determination (moderate quality evidence). We are uncertain whether point-of-care ultrasound (POCUS) pulse check, cerebral near-infrared spectroscopy (NIRS), or POCUS cardiac motion assessment are accurate tests for the determination of circulatory cessation (very low-quality evidence). CONCLUSION: There is insufficient evidence that ECG, POCUS pulse check, cerebral NIRS, or POCUS cardiac motion assessment are superior or equivalent to IAP for DCC in the setting of organ donation. Isoelectric ECG is specific but can increase the time needed to determine death. Point-of-care ultrasound techniques are emerging therapies with promising initial data but are limited by indirectness and imprecision. STUDY REGISTRATION: PROSPERO (CRD42021258936); first submitted 16 June 2021.

RéSUMé: OBJECTIF: Synthétiser les données probantes disponibles comparant les méthodes non invasives de mesure de l'arrêt de la circulation chez les patients qui sont des donneurs d'organes potentiels soumis à une détermination du décès selon des critères circulatoires (DCC) avec la norme actuellement acceptée de surveillance invasive de la tension artérielle (TA). SOURCES: Nous avons mené des recherches dans les bases de données MEDLINE, EMBASE, Web of Science et le registre Cochrane des essais contrôlés de leur création jusqu'au 27 avril 2021. Nous avons examiné les citations et les manuscrits de manière indépendante et en double pour en tirer les études éligibles qui comparaient des méthodologies non invasives d'évaluation de la circulation chez les patients qui étaient sous surveillance avant, pendant et après une période d'arrêt de la circulation. Nous avons réalisé l'évaluation du risque de biais, l'extraction des données et l'évaluation de la qualité en nous fondant sur la méthodologie GRADE (Grading of Recommendations, Assessment, Development, and Evaluation) en double et de manière indépendante. Nous présentons les résultats de façon narrative. CONSTATATIONS PRINCIPALES: Nous avons inclus 21 études éligibles (N = 1177 patients). Une méta-analyse n'a pas été possible en raison de l'hétérogénéité des études. Nous avons identifié des données de faible qualité issues de quatre études indirectes (n = 89) montrant que la palpation du pouls est moins sensible et spécifique que la mesure invasive de la TA (plage de sensibilité rapportée, 0,76-0,90; spécificité, 0,41-0,79). L'électrocardiogramme (ECG) isoélectrique avait une excellente spécificité pour le décès (deux études; 0 % [0/510]), mais augmente probablement le délai moyen avant la détermination du décès (données probantes de qualité modérée). Nous ne savons pas si la vérification du pouls par échographie ciblée (POCUS), la spectroscopie proche infrarouge (SPIR) cérébrale ou l'évaluation ciblée (POCUS) des mouvements cardiaques sont des examens précis pour la détermination de l'arrêt circulatoire (données probantes de très faible qualité). CONCLUSION: Il n'y a pas suffisamment de données probantes pour affirmer que l'ECG, la vérification ciblée du pouls, la SPIR cérébrale ou l'évaluation ciblée des mouvements cardiaques sont supérieurs ou équivalents à la mesure invasive de la TA pour un DCC dans le cadre du don d'organes. L'ECG isoélectrique est spécifique, mais peut augmenter le délai nécessaire avant de déterminer le décès. Les techniques d'échographie ciblée sont des thérapies émergentes avec des données initiales prometteuses, mais elles sont limitées par leur caractère indirect et l'imprécision de l'examen. ENREGISTREMENT DE L'éTUDE: PROSPERO (CRD42021258936); soumis pour la première fois le 16 juin 2021.

A brain-based definition of death and criteria for its determination after arrest of circulation or neurologic function in Canada: a 2023 clinical practice guideline.

This 2023 Clinical Practice Guideline provides the biomedical definition of death based on permanent cessation of brain function that applies to all persons, as well as recommendations for death determination by circulatory criteria for potential organ donors and death determination by neurologic criteria for all mechanically ventilated patients regardless of organ donation potential. This Guideline is endorsed by the Canadian Critical Care Society, the Canadian Medical Association, the Canadian Association of Critical Care Nurses, Canadian Anesthesiologists' Society, the Canadian Neurological Sciences Federation (representing the Canadian Neurological Society, Canadian Neurosurgical Society, Canadian Society of Clinical Neurophysiologists, Canadian Association of Child Neurology, Canadian Society of Neuroradiology, and Canadian Stroke Consortium), Canadian Blood Services, the Canadian Donation and Transplantation Research Program, the Canadian Association of Emergency Physicians, the Nurse Practitioners Association of Canada, and the Canadian Cardiovascular Critical Care Society.

RéSUMé: Ces Lignes directrices de pratique clinique 2023 Lignes directrices de pratique clinique dicale du décès basée sur l'arrêt permanent de la fonction cérébrale qui s'applique à toute personne, ainsi que des recommandations pour la détermination du décès par des critères circulatoires pour des donneurs d'organes potentiels et des recommandations pour la détermination du décès par des critères neurologiques pour tous les patients sous ventilation mécanique, indépendamment de leur potentiel de donneur d'organes. Les présentes Lignes directrices sont approuvées par la Société canadienne de soins intensifs, l'Association médicale canadienne, l'Association canadienne des infirmiers/infirmières en soins intensifs, la Société canadienne des anesthésiologistes, la Fédération des sciences neurologiques du Canada (représentant la Société canadienne de neurologie, la Société canadienne de neurochirurgie, la Société canadienne de neurophysiologie clinique, l'Association canadienne de neurologie pédiatrique, la Société canadienne de neuroradiologie et le Consortium neurovasculaire canadien), la Société canadienne du sang, le Programme de recherche en don et transplantation du Canada, l'Association canadienne des médecins d'urgence, l'Association des infirmières et infirmiers praticiens du Canada, et la Société canadienne de soins intensifs cardiovasculaires (CANCARE) et la Société canadienne de pédiatrie.

Diagnostic Potential of Coagulation-Related Biomarkers for Sepsis in the Emergency Department: Protocol for a Pilot Observational Cohort Study.

BACKGROUND: Between 75% and 80% of patients with sepsis arrive in the hospital through the emergency department. Early diagnosis is important to alter patient prognosis, but currently, there is no reliable biomarker. The innate immune response links inflammation and coagulation. Several coagulation -related biomarkers are associated with poor prognosis in the ICU. The role of coagulation biomarkers to aid in early sepsis diagnosis has not previously been investigated. The objective of our study is to determine the individual or combined accuracy of coagulation and inflammation biomarkers with standard biochemical tests to diagnose adult septic patients presenting to the emergency department. METHODS: in the Emergency Department is a prospective, observational cohort study with a target enrolment of 250 suspected septic patients from two Canadian emergency departments. The emergency physicians will enroll patients with suspected sepsis. Blood samples will be collected at two time points (initial presentation and 4 hr following). Patients will be adjudicated into septic, infected, or not infected status in accordance with the Sepsis-3 definitions. Patient demographics, cultures, diagnosis, and biomarkers will be reported using descriptive statistics. Optimal cut off values with sensitivity and specificity for each biomarker will be determined using C-statistics to distinguish between septic and nonseptic patients. Stepwise multiple logistic regression analysis with exclusion of nonsignificant covariates from the final model will be used to establish a panel of biomarkers. CONCLUSIONS: Our protocol describes the processes and methods for a pragmatic observational biomarker study in the emergency department. This study will seek to determine the potential diagnostic importance of early coagulation abnormalities to identify additional tools for sepsis diagnosis.