To determine the association between preintubation respiratory support and outcomes in patients with acute respiratory failure and to determine the impact of immunocompromised (IC) diagnoses on ...outcomes after adjustment for illness severity.
Retrospective multicenter cohort study.
Eighty-two centers in the Virtual Pediatric Systems database.
Children 1 month to 17 years old intubated in the PICU who received invasive mechanical ventilation (IMV) for greater than or equal to 24 hours.
None.
High-flow nasal cannula (HFNC) or noninvasive positive-pressure ventilation (NIPPV) or both were used prior to intubation in 1,825 (34%) of 5,348 PICU intubations across 82 centers. When stratified by IC status, 50% of patients had no IC diagnosis, whereas 41% were IC without prior hematopoietic cell transplant (HCT) and 9% had prior HCT. Compared with patients intubated without prior support, preintubation exposure to HFNC (adjusted odds ratio aOR, 1.33; 95% CI, 1.10-1.62) or NIPPV (aOR, 1.44; 95% CI, 1.20-1.74) was associated with increased odds of PICU mortality. Within subgroups of IC status, preintubation respiratory support was associated with increased odds of PICU mortality in IC patients (HFNC: aOR, 1.50; 95% CI, 1.11-2.03; NIPPV: aOR, 1.76; 95% CI, 1.31-2.35) and HCT patients (HFNC: aOR, 1.75; 95% CI, 1.07-2.86; NIPPV: aOR, 1.85; 95% CI, 1.12-3.02) compared with IC/HCT patients intubated without prior respiratory support. Preintubation exposure to HFNC/NIPPV was not associated with mortality in patients without an IC diagnosis. Duration of HFNC/NIPPV greater than 6 hours was associated with increased mortality in IC HCT patients (HFNC: aOR, 2.41; 95% CI, 1.05-5.55; NIPPV: aOR, 2.53; 95% CI, 1.04-6.15) and patients compared HCT patients with less than 6-hour HFNC/NIPPV exposure. After adjustment for patient and center characteristics, both preintubation HFNC/NIPPV use (median, 15%; range, 0-63%) and PICU mortality varied by center.
In IC pediatric patients, preintubation exposure to HFNC and/or NIPPV is associated with increased odds of PICU mortality, independent of illness severity. Longer duration of exposure to HFNC/NIPPV prior to IMV is associated with increased mortality in HCT patients.
Major Adverse Kidney Events in Pediatric Sepsis Weiss, Scott L; Balamuth, Fran; Thurm, Cary W ...
Clinical journal of the American Society of Nephrology,
05/2019, Letnik:
14, Številka:
5
Journal Article
Recenzirano
Odprti dostop
Major adverse kidney events, a composite of death, new kidney replacement therapy, or persistent kidney dysfunction, is a potential patient-centered outcome for clinical trials in sepsis-associated ...kidney injury. We sought to determine the incidence of major adverse kidney events within 30 days and validate this end point in pediatric sepsis.
We conducted a retrospective observational study using the Pediatric Health Information Systems Plus database of patients >6 months to <18 years old with a diagnosis of severe sepsis/septic shock; orders for bacterial blood culture, antibiotics, and at least one fluid bolus on hospital day 0/1; and known hospital disposition between January 2007 and December 2011. The primary outcome was incidence of major adverse kidney events within 30 days. Major adverse kidney events within 30 days were validated against all-cause mortality at hospital discharge, hospital length of stay, total hospital costs, hospital readmission within 30 days and 1 year, and lowest eGFR between 3 months and 1 year after discharge. We reported incidence of major adverse kidney events within 30 days with 95% confidence intervals using robust SEM and used multivariable logistic regression to test the association of major adverse kidney events within 30 days with hospital costs and mortality.
Of 1685 admissions, incidence of major adverse kidney events within 30 days was 9.6% (95% confidence interval, 8.1% to 11.0%), including 4.5% (95% confidence interval, 3.5% to 5.4%) death, 1.7% (95% confidence interval, 1.1% to 2.3%) kidney replacement therapy, and 5.8% (95% confidence interval, 4.7% to 6.9%) persistent kidney dysfunction. Patients with versus without major adverse kidney events within 30 days had higher all-cause mortality at hospital discharge (28% versus 1%;
<0.001), higher total hospital costs ($61,188; interquartile range, $21,272-140,356 versus $28,107; interquartile range, $13,056-72,697;
<0.001), and higher proportion with eGFR<60 ml/min per 1.73 m
between 3 months and 1 year after discharge (19% versus 4%;
=0.001). Major adverse kidney events within 30 days was not associated with length of stay or readmissions.
In children with sepsis, major adverse kidney events within 30 days are common, feasible to measure, and a promising end point for future clinical trials.
A method to identify pediatric sepsis episodes that is not affected by changing diagnosis and claims-based coding practices does not exist. We derived and validated a surveillance algorithm to ...identify pediatric sepsis using routine clinical data and applied the algorithm to study longitudinal trends in sepsis epidemiology.
Retrospective observational study.
Single academic children's hospital.
All emergency and hospital encounters from January 2011 to January 2019, excluding neonatal ICU and cardiac center.
Sepsis episodes identified by a surveillance algorithm using clinical data to identify infection and concurrent organ dysfunction.
None.
A surveillance algorithm was derived and validated in separate cohorts with suspected sepsis after clinician-adjudication of final sepsis diagnosis. We then applied the surveillance algorithm to determine longitudinal trends in incidence and mortality of pediatric sepsis over 8 years. Among 93,987 hospital encounters and 1,065 episodes of suspected sepsis in the derivation period, the surveillance algorithm yielded sensitivity 78% (95% CI, 72-84%), specificity 76% (95% CI, 74-79%), positive predictive value 41% (95% CI, 36-46%), and negative predictive value 94% (95% CI, 92-96%). In the validation period, the surveillance algorithm yielded sensitivity 84% (95% CI, 77-92%), specificity of 65% (95% CI, 59-70%), positive predictive value 43% (95% CI, 35-50%), and negative predictive value 93% (95% CI, 90-97%). Notably, most "false-positives" were deemed clinically relevant sepsis cases after manual review. The hospital-wide incidence of sepsis was 0.69% (95% CI, 0.67-0.71%), and the inpatient incidence was 2.8% (95% CI, 2.7-2.9%). Risk-adjusted sepsis incidence, without bias from changing diagnosis or coding practices, increased over time (adjusted incidence rate ratio per year 1.07; 95% CI, 1.06-1.08; p < 0.001). Mortality was 6.7% and did not change over time (adjusted odds ratio per year 0.98; 95% CI, 0.93-1.03; p = 0.38).
An algorithm using routine clinical data provided an objective, efficient, and reliable method for pediatric sepsis surveillance. An increased sepsis incidence and stable mortality, free from influence of changes in diagnosis or billing practices, were evident.
Renal dysfunction is associated with poor outcomes in critically ill children.
To evaluate the current evidence for criteria defining renal dysfunction in critically ill children and association with ...adverse outcomes. To develop contemporary consensus criteria for renal dysfunction in critically ill children.
PubMed and Embase were searched from January 1992 to January 2020.
Included studies evaluated critically ill children with renal dysfunction, performance characteristics of assessment tools for renal dysfunction, and outcomes related to mortality, functional status, or organ-specific or other patient-centered outcomes. Studies with adults or premature infants (≤36 weeks' gestational age), animal studies, reviews, case series, and studies not published in English with inability to determine eligibility criteria were excluded.
Data were extracted from included studies into a standard data extraction form by task force members.
The systematic review supported the following criteria for renal dysfunction: (1) urine output <0.5 mL/kg per hour for ≥6 hours and serum creatinine increase of 1.5 to 1.9 times baseline or ≥0.3 mg/dL, or (2) urine output <0.5 mL/kg per hour for ≥12 hours, or (3) serum creatinine increase ≥2 times baseline, or (4) estimated glomerular filtration rate <35 mL/minute/1.73 m2, or (5) initiation of renal replacement therapy, or (6) fluid overload ≥20%. Data also support criteria for persistent renal dysfunction and for high risk of renal dysfunction.
All included studies were observational and many were retrospective.
We present consensus criteria for renal dysfunction in critically ill children.
Immune effector cell (IEC) therapies offer durable and sustained remissions in significant numbers of patients with hematological cancers. While these unique immunotherapies have improved outcomes ...for pediatric and adult patients in a number of disease states, as ‘living drugs,’ their toxicity profiles, including cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS), differ markedly from conventional cancer therapeutics. At the time of article preparation, the US Food and Drug Administration (FDA) has approved tisagenlecleucel, axicabtagene ciloleucel, and brexucabtagene autoleucel, all of which are IEC therapies based on genetically modified T cells engineered to express chimeric antigen receptors (CARs), and additional products are expected to reach marketing authorization soon and to enter clinical development in due course. As IEC therapies, especially CAR T cell therapies, enter more widespread clinical use, there is a need for clear, cohesive recommendations on toxicity management, motivating the Society for Immunotherapy of Cancer (SITC) to convene an expert panel to develop a clinical practice guideline. The panel discussed the recognition and management of common toxicities in the context of IEC treatment, including baseline laboratory parameters for monitoring, timing to onset, and pharmacological interventions, ultimately forming evidence- and consensus-based recommendations to assist medical professionals in decision-making and to improve outcomes for patients.
Most children with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection have mild or minimal disease, with a small proportion developing severe disease or multisystem inflammatory ...syndrome in children (MIS-C). Complement-mediated thrombotic microangiopathy (TMA) has been associated with SARS-CoV-2 infection in adults but has not been studied in the pediatric population. We hypothesized that complement activation plays an important role in SARS-CoV-2 infection in children and sought to understand if TMA was present in these patients. We enrolled 50 hospitalized pediatric patients with acute SARS-CoV-2 infection (n = 21, minimal coronavirus disease 2019 COVID-19; n = 11, severe COVID-19) or MIS-C (n = 18). As a biomarker of complement activation and TMA, soluble C5b9 (sC5b9, normal 247 ng/mL) was measured in plasma, and elevations were found in patients with minimal disease (median, 392 ng/mL; interquartile range IQR, 244-622 ng/mL), severe disease (median, 646 ng/mL; IQR, 203-728 ng/mL), and MIS-C (median, 630 ng/mL; IQR, 359-932 ng/mL) compared with 26 healthy control subjects (median, 57 ng/mL; IQR, 9-163 ng/mL; P < .001). Higher sC5b9 levels were associated with higher serum creatinine (P = .01) but not age. Of the 19 patients for whom complete clinical criteria were available, 17 (89%) met criteria for TMA. A high proportion of tested children with SARS-CoV-2 infection had evidence of complement activation and met clinical and diagnostic criteria for TMA. Future studies are needed to determine if hospitalized children with SARS-CoV-2 should be screened for TMA, if TMA-directed management is helpful, and if there are any short- or long-term clinical consequences of complement activation and endothelial damage in children with COVID-19 or MIS-C.
•sC5b9 plasma levels are elevated in children with SARS-CoV-2 infection, even if they have minimal symptoms of COVID-19.•A high proportion of children with SARS-CoV-2 infection met clinical criteria for TMA.
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Abstract Sepsis-associated cardiac arrest is a relatively common occurrence with especially poor outcomes. Of the greater than 200,000 in-hospital cardiac arrests that occur in the United States ...annually, between 30,000 and 60,000 occur in patients with underlying sepsis. These patients are less likely to survive than cardiac arrest victims without sepsis. In this review, we discuss the epidemiology of sepsis-associated in-hospital cardiac arrest in adults and children, the relevant physiology responsible for its pathogenesis and poor outcomes, and potential therapeutic interventions based on this pathophysiology. We postulate that persistence of sepsis pathophysiology during and after cardiac arrest is responsible for these poor outcomes. This includes derangements of vascular tone and intravascular volume status; myocardial dysfunction; hypoxemia, acidemia, and other metabolic derangements; and pulmonary hypertension. Potential interventions that specifically target this pathophysiology before, during, and after cardiac arrest may augment standard cardiopulmonary resuscitation and post-resuscitation care for patients with sepsis and septic shock.
OBJECTIVES:To compare the performance of three methods of identifying children with severe sepsis and septic shock from the Virtual Pediatric Systems database to prospective screening using consensus ...criteria.
DESIGN:Observational cohort study.
SETTING:Single-center PICU.
PATIENTS:Children admitted to the PICU in the period between March 1, 2012, and March 31, 2014.
INTERVENTIONS:None.
MEASUREMENTS AND MAIN RESULTS:During the study period, all PICU patients were prospectively screened daily for sepsis, and those meeting consensus criteria for severe sepsis or septic shock on manual chart review were entered into the sepsis registry. Of 7,459 patients admitted to the PICU during the study period, 401 met consensus criteria for severe sepsis or septic shock (reference standard cohort). Within Virtual Pediatric Systems, patients identified using “Martin” (n = 970; κ = 0.43; positive predictive value = 34%; F1 = 0.48) and “Angus” International Classification of Diseases, 9th Edition, Clinical Modification codes (n = 1387; κ = 0.28; positive predictive value = 22%; F1 = 0.34) showed limited agreement with the reference standard cohort. By comparison, explicit International Classification of Diseases, 9th Edition, Clinical Modification codes for severe sepsis (995.92) and septic shock (785.52) identified a smaller, more accurate cohort of children (n = 515; κ = 0.61; positive predictive value = 57%; F1 = 0.64). PICU mortality was 8% in the reference standard cohort and the cohort identified by explicit codes; age, illness severity scores, and resource utilization did not differ between groups. Analysis of discrepancies between the reference standard and Virtual Pediatric Systems explicit codes revealed that prospective screening missed 66 patients with severe sepsis or septic shock. After including these patients in the reference standard cohort as an exploratory analysis, agreement between the cohort of patients identified by Virtual Pediatric Systems explicit codes and the reference standard cohort improved (κ = 0.73; positive predictive value = 70%; F1 = 0.75).
CONCLUSIONS:Children with severe sepsis and septic shock are best identified in the Virtual Pediatric Systems database using explicit diagnosis codes for severe sepsis and septic shock. The accuracy of these codes and level of clinical detail available in the Virtual Pediatric Systems database allow for sophisticated epidemiologic studies of pediatric severe sepsis and septic shock in this large, multicenter database.
Background
Studies in critically ill adults demonstrate associations between serum renin concentrations (a proposed surrogate for renin–angiotensin–aldosterone system dysregulation) and poor ...outcomes, but data in critically ill children are lacking. We assessed serum renin + prorenin concentrations in children with septic shock to determine their predictive ability for acute kidney injury (AKI) and mortality.
Methods
We conducted a secondary analysis of a multicenter observational study of children aged 1 week to 18 years admitted to 14 pediatric intensive care units (PICUs) with septic shock and residual serum available for renin + prorenin measurement. Primary outcomes were development of severe persistent AKI (≥ KDIGO stage 2 for ≥ 48 h) in the first week and 28-day mortality.
Results
Among 233 patients, day 1 median renin + prorenin concentration was 3436 pg/ml (IQR 1452–6567). Forty-two (18%) developed severe persistent AKI and 32 (14%) died. Day 1 serum renin + prorenin predicted severe persistent AKI with an AUROC of 0.75 (95% CI 0.66–0.84,
p
< 0.0001; optimal cutoff 6769 pg/ml) and mortality with an AUROC of 0.79 (95% CI 0.69–0.89,
p
< 0.0001; optimal cutoff 6521 pg/ml). Day 3/day 1 (D3:D1) renin + prorenin ratio had an AUROC of 0.73 (95% CI 0.63–0.84,
p
< 0.001) for mortality. On multivariable regression, day 1 renin + prorenin > optimal cutoff retained associations with severe persistent AKI (aOR 6.8, 95% CI 3.0–15.8,
p
< 0.001) and mortality (aOR 6.9, 95% CI 2.2–20.9,
p
< 0.001). Similarly, D3:D1 renin + prorenin > optimal cutoff was associated with mortality (aOR 7.6, 95% CI 2.5–23.4,
p
< 0.001).
Conclusions
Children with septic shock have very elevated serum renin + prorenin concentrations on PICU admission, and these concentrations, as well as their trend over the first 72 h, predict severe persistent AKI and mortality.
Graphical abstract
A higher resolution version of the Graphical abstract is available as
Supplementary information
Objectives
The objective was to compare the effectiveness of physician judgment and an electronic algorithmic alert to identify pediatric patients with severe sepsis/septic shock in a pediatric ...emergency department (ED).
Methods
This was an observational cohort study of patients older than 56 days with fever or hypothermia. All patients were evaluated for potential sepsis in real time by the ED clinical team. An electronic algorithmic alert was retrospectively applied to identify patients with potential sepsis independent of physician judgment. The primary outcome was the proportion of patients correctly identified with severe sepsis/septic shock defined by consensus criteria. Test characteristics were determined and receiver operating characteristic (ROC) curves were compared.
Results
Of 19,524 eligible patient visits, 88 patients developed consensus‐confirmed severe sepsis or septic shock. Physician judgment identified 159 and the algorithmic alert identified 3,301 patients with potential sepsis. Physician judgment had sensitivity of 72.7% (95% confidence interval CI = 72.1% to 73.4%) and specificity of 99.5% (95% CI = 99.4% to 99.6%); the algorithmic alert had sensitivity of 92.1% (95% CI = 91.7% to 92.4%) and specificity of 83.4% (95% CI = 82.9% to 83.9%) for severe sepsis/septic shock. There was no significant difference in the area under the ROC curve for physician judgment (0.86, 95% CI = 0.81 to 0.91) or the algorithm (0.88, 95% CI = 0.85 to 0.91; p = 0.54). A combination method using either positive physician judgment or an algorithmic alert improved sensitivity to 96.6% and specificity to 83.3%. A sequential approach, in which positive identification by the algorithmic alert was then confirmed by physician judgment, achieved 68.2% sensitivity and 99.6% specificity. Positive and negative predictive values for physician judgment versus algorithmic alert were 40.3% versus 2.5% and 99.88% versus 99.96%, respectively.
Conclusions
The electronic algorithmic alert was more sensitive but less specific than physician judgment for recognition of pediatric severe sepsis and septic shock. These findings can help to guide institutions in selecting pediatric sepsis recognition methods based on institutional needs and priorities.