Diagnostic Errors in Pediatric Critical Care: A Systematic Review.

OBJECTIVES: To summarize the literature on prevalence, impact, and contributing factors related to diagnostic error in the PICU. DATA SOURCES: Search of PubMed, EMBASE, and the Cochrane Library up to December 2019. STUDY SELECTION: Studies on diagnostic error and the diagnostic process in pediatric critical care were included. Non-English studies with no translation, case reports/series, studies providing no information on diagnostic error, studies focused on non-PICU populations, and studies focused on a single condition/disease or a single diagnostic test/tool were excluded. DATA EXTRACTION: Data on research design, objectives, study sample, and results pertaining to the prevalence, impact, and factors associated with diagnostic error were abstracted from each study. DATA SYNTHESIS: Using independent tiered review, 396 abstracts were screened, and 17 studies (14 full-text, 3 abstracts) were ultimately included. Fifteen of 17 studies (88%) had an observational research design. Autopsy studies (autopsy rates were 20-47%) showed a 10-23% rate of missed major diagnoses; 5-16% of autopsy-discovered diagnostic errors had a potential adverse impact on survival and would have changed management. Retrospective record reviews reported varying rates of diagnostic error from 8% in a general PICU population to 12% among unexpected critical admissions and 21-25% of patients discussed at PICU morbidity and mortality conferences. Cardiovascular, infectious, congenital, and neurologic conditions were most commonly misdiagnosed. Systems factors (40-67%), cognitive factors (20-3%), and both systems and cognitive factors (40%) were associated with diagnostic error. Limited information was available on the impact of misdiagnosis. CONCLUSIONS: Knowledge of diagnostic errors in the PICU is limited. Future work to understand diagnostic errors should involve a balanced focus between studying the diagnosis of individual diseases and uncovering common system- and process-related determinants of diagnostic error.

Consensus Recommendations for Blood Culture Use in Critically Ill Children Using a Modified Delphi Approach.

OBJECTIVES: Blood cultures are fundamental in evaluating for sepsis, but excessive cultures can lead to false-positive results and unnecessary antibiotics. Our objective was to create consensus recommendations focusing on when to safely avoid blood cultures in PICU patients. DESIGN: A panel of 29 multidisciplinary experts engaged in a two-part modified Delphi process. Round 1 consisted of a literature summary and an electronic survey sent to invited participants. In the survey, participants rated a series of recommendations about when to avoid blood cultures on five-point Likert scale. Consensus was achieved for the recommendation(s) if 75% of respondents chose a score of 4 or 5, and these were included in the final recommendations. Any recommendations that did not meet these a priori criteria for consensus were discussed during the in-person expert panel review (Round 2). Round 2 was facilitated by an independent expert in consensus methodology. After a review of the survey results, comments from round 1, and group discussion, the panelists voted on these recommendations in real-time. SETTING: Experts' institutions; in-person discussion in Baltimore, MD. SUBJECTS: Experts in pediatric critical care, infectious diseases, nephrology, oncology, and laboratory medicine. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Of the 27 original recommendations, 18 met criteria for achieving consensus in Round 1; some were modified for clarity or condensed from multiple into single recommendations during Round 2. The remaining nine recommendations were discussed and modified until consensus was achieved during Round 2, which had 26 real-time voting participants. The final document contains 19 recommendations. CONCLUSIONS: Using a modified Delphi process, we created consensus recommendations on when to avoid blood cultures and prevent overuse in the PICU. These recommendations are a critical step in disseminating diagnostic stewardship on a wider scale in critically ill children.

Practices, Perceptions, and Attitudes in the Evaluation of Critically Ill Children for Bacteremia: A National Survey.

OBJECTIVES: Sending blood cultures in children at low risk of bacteremia can contribute to a cascade of unnecessary antibiotic exposure, adverse effects, and increased costs. We aimed to describe practice variation, clinician beliefs, and attitudes about blood culture testing in critically ill children. DESIGN: Cross-sectional electronic survey. SETTING: Fifteen PICUs enrolled in the Blood Culture Improvement Guidelines and Diagnostic Stewardship for Antibiotic Reduction in Critically Ill Children collaborative, an investigation of blood culture use in critically ill children in the United States. SUBJECTS: PICU clinicians (bedside nurses, resident physicians, fellow physicians, nurse practitioners, physician assistants, and attending physicians). INTERVENTIONS: None. MEASUREMENT AND MAIN RESULTS: Survey items explored typical blood culture practices, attitudes and beliefs about cultures, and potential barriers to changing culture use in a PICU setting. Fifteen of 15 sites participated, with 347 total responses, 15-45 responses per site, and an overall median response rate of 57%. We summarized median proportions and interquartile ranges of respondents who reported certain practices or beliefs: 86% (73-91%) report that cultures are ordered reflexively; 71% (61-77%) do not examine patients before ordering cultures; 90% (86-94%) obtain cultures for any new fever in PICU patients; 33% (19-61%) do not obtain peripheral cultures when an indwelling catheter is in place; and 64% (36-81%) sample multiple (vs single) lumens of central venous catheters for new fever. When asked about barriers to reducing unnecessary cultures, 80% (73-90%) noted fear of missing sepsis. Certain practices (culture source and indication) varied by clinician type. Obtaining surveillance cultures and routinely culturing all possible sources (each lumen of indwelling catheters and peripheral specimens) are positively correlated with baseline blood culture rates. CONCLUSIONS: There is variation in blood culture practices in the PICU. Fear and reflexive habits are common drivers of cultures. These practices may contribute to over-testing for bacteremia. Further investigation of how to optimize blood culture use is warranted.

How good is our diagnostic intuition? Clinician prediction of bacteremia in critically ill children.

BACKGROUND: Clinical intuition and nonanalytic reasoning play a major role in clinical hypothesis generation; however, clinicians' intuition about whether a critically ill child is bacteremic has not been explored. We endeavored to assess pediatric critical care clinicians' ability to predict bacteremia and to evaluate what affected the accuracy of those predictions. METHODS: We conducted a retrospective review of clinicians' responses to a sepsis screening tool ("Early Sepsis Detection Tool" or "ESDT") over 6 months. The ESDT was completed during the initial evaluation of a possible sepsis episode. If a culture was ordered, they were asked to predict if the culture would be positive or negative. Culture results were compared to predictions for each episode as well as vital signs and laboratory data from the preceding 24 h. RESULTS: From January to July 2017, 266 ESDTs were completed. Of the 135 blood culture episodes, 15% of cultures were positive. Clinicians correctly predicted patients with bacteremia in 82% of cases, but the positive predictive value was just 28% as there was a tendency to overestimate the presence of bacteremia. The negative predictive value was 96%. The presence of bandemia, thrombocytopenia, and abnormal CRP were associated with increased likelihood of correct positive prediction. CONCLUSIONS: Clinicians are accurate in predicting critically ill children whose blood cultures, obtained for symptoms of sepsis, will be negative. Clinicians frequently overestimate the presence of bacteremia. The combination of evidence-based practice guidelines and bedside judgment should be leveraged to optimize diagnosis of bacteremia.

Transforming the Morbidity and Mortality Conference to Promote Safety and Quality in a PICU.

OBJECTIVE: Determine the effectiveness of a structured systems-oriented morbidity and mortality conference in improving the process of reviewing and responding to adverse events in a PICU. DESIGN: Prospective time series analysis before and after implementation of a systems-oriented morbidity and mortality conference. SETTING: Single tertiary referral PICU in Baltimore, MD. PATIENTS: Thirty-three patients discussed before and 31 patients after implementation of a systems-oriented morbidity and mortality conference over a total of 20 morbidity and mortality conferences, from April 2013 to March 2014. INTERVENTIONS: Systems-oriented morbidity and mortality conference incorporating elements of medical incident analysis. MEASUREMENTS AND MAIN RESULTS: There was a significant increase in meeting attendance (mean, 12 vs 31 attendees per morbidity and mortality conference; p < 0.001) after the systems-oriented morbidity and mortality conference was instituted. There was no significant difference in the mean number of cases suggested (4.2 vs 4.6) or discussed (3.3 vs 3.1) per morbidity and mortality conference. There was also no significant difference in the mean number of adverse events identified per morbidity and mortality conference (3.4 vs 4.3). However, there was an increase in the proportion of cases discussed using a standard case review tool, but this did not reach statistical significance (27% vs 45%; p = 0.231). Nevertheless, we observed a significant increase in the mean number of quality improvement interventions suggested (2.4 vs 5.6; p < 0.001) and implemented (1.7 vs 4.4; p < 0.001) per morbidity and mortality conference. All adverse event categories identified had corresponding interventions suggested after the systems-oriented morbidity and mortality conference was instituted compared with before (80% vs 100%). Intervention-to-adverse event ratios per category were also higher (mean, 0.6 vs 1.5). CONCLUSIONS: A structured systems-oriented PICU morbidity and mortality conference incorporating elements of medical incident analysis improves the process of reviewing and responding to adverse events by significantly increasing quality improvement interventions suggested and implemented. Future work would involve testing locally adapted versions of the systems-oriented morbidity and mortality conference in multiple inpatient settings.

Hemoglobin thresholds for transfusion in pediatric patients at a large academic health center.

BACKGROUND: Although prior studies support the use of a hemoglobin (Hb) transfusion trigger of 7 to 8 g/dL for most hospitalized adults, there are few studies in pediatric populations. We therefore investigated transfusion practices and Hb triggers in hospitalized children. STUDY DESIGN AND METHODS: We performed a historical cohort study comparing transfusion practices in hospitalized children by service within a single academic institution. Blood utilization data from transfused patients (n = 3370) were obtained from electronic records over 4 years. Hb triggers and posttransfusion Hb levels were defined as the lowest and last Hb measured during hospital stay, respectively, in transfused patients. The mean and percentile distribution for Hb triggers were compared to the evidence-based restrictive transfusion threshold of 7 g/dL. RESULTS: Mean Hb triggers were above the restrictive trigger (7 g/dL) for eight of 12 pediatric services. Among all of the services, there were significant differences between the mean Hb triggers (>2.5 g/dL, p<0.0001) and between the posttransfusion Hb levels (>3 g/dL, p < 0.0001). The variation between the 10th and 90th percentiles for triggers (up to 4 g/dL, p < 0.0001) and posttransfusion Hb levels (up to 6 g/dL, p < 0.0001) were significant. Depending on the service, between 25 and 90% of transfused patients had Hb triggers higher than the restrictive range. CONCLUSIONS: Red blood cell (RBC) transfusion therapy varies significantly in hospitalized children with mean Hb triggers above a restrictive threshold for most services. Our findings suggest that transfusions may be overused and that implementing a restrictive transfusion strategy could decrease the use of RBC transfusions, thereby reducing the associated risks and costs.

Diagnostic Errors in a PICU: Insights From the Morbidity and Mortality Conference.

OBJECTIVES: To describe diagnostic errors identified among patients discussed at a PICU morbidity and mortality conference in terms of Goldman classification, medical category, severity, preventability, contributing factors, and occurrence in the diagnostic process. DESIGN: Retrospective record review of morbidity and mortality conference agendas, patient charts, and autopsy reports. SETTING: Single tertiary referral PICU in Baltimore, MD. PATIENTS: Ninety-six patients discussed at the PICU morbidity and mortality conference from November 2011 to December 2012. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Eighty-nine of 96 patients (93%) discussed at the PICU morbidity and mortality conference had at least one identified safety event. A total of 377 safety events were identified. Twenty patients (21%) had identified misdiagnoses, comprising 5.3% of all safety events. Out of 20 total diagnostic errors identified, 35% were discovered at autopsy while 55% were reported primarily through the morbidity and mortality conference. Almost all diagnostic errors (95%) could have had an impact on patient survival or safety. Forty percent of errors did not cause actual patient harm, but 25% were severe enough to have potentially contributed to death (40% no harm vs 35% some harm vs 25% possibly contributed to death). Half of the diagnostic errors (50%) were rated as preventable. There were slightly more system-related factors (40%) solely contributing to diagnostic errors compared with cognitive factors (20%); however, 35% had both system and cognitive factors playing a role. Most errors involved vascular (35%) followed by neurologic (30%) events. CONCLUSIONS: Diagnostic errors in the PICU are not uncommon and potentially cause patient harm. Most appear to be preventable by targeting both cognitive- and system-related contributing factors. Prospective studies are needed to further determine how and why diagnostic errors occur in the PICU and what interventions would likely be effective for prevention.

The morbidity and mortality conference in PICUs in the United States: a national survey.

OBJECTIVE: Determine how many morbidity and mortality conferences in PICUs across the United States conform to key elements of medical incident analysis. DESIGN: Web-based cross-sectional survey open from March to September 2013. SETTING: Seventy-five PICUs with regular morbidity and mortality conferences in the United States identified by cross-referencing publicly available databases. PARTICIPANTS: Multidisciplinary PICU staff who attend the PICU morbidity and mortality conference. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Eighty-four identified PICUs of 206 PICUs contacted had at least one respondent, with a 40.8% PICU-level response rate. The PICUs had a mean of three respondents (SD, 2.5; range, 1-13), with 45 of 84 (54%) having greater than one respondent. There were 305 total respondents to the survey, of which 220 of 300 (73%) self-identified as attending physicians and 47 of 300 (16%) as fellows. Four PICUs with only one respondent were excluded due to poor question response rates. Forty-nine of eighty-three PICUs (59%) had fellowship training programs. Five of eighty-three PICUs (6%) had no regular morbidity and mortality conference. Among 75 PICUs with regular morbidity and mortality conferences, morbidity and mortality conference process and structure characteristics varied widely. Among PICUs with greater than one respondent, when asked about morbidity and mortality conference conformity to each of the three key elements of medical incident analysis, 62-68% had intra-PICU disagreement among respondents. Fifteen of thirty-seven PICUs with greater than one respondent (41%) had intra-PICU disagreement on all three key elements. CONCLUSIONS: Morbidity and mortality conferences varied widely in structure and process across PICUs in the United States. There was marked disagreement as to whether the morbidity and mortality conference conforms to key elements of medical incident analysis, which might itself be revealing a lack of morbidity and mortality conference structure and consistency. Future research is needed to identify barriers to the use of the morbidity and mortality conference as a patient safety improvement tool and to test strategies for effective implementation linked to improved patient outcomes.

Application of Participatory Ergonomics to the Dissemination of a Quality Improvement Program for Optimizing Blood Culture Use.

BACKGROUND: Blood cultures are overused in pediatric ICUs (PICUs), which may lead to unnecessary antibiotic use and antibiotic resistance. Using a participatory ergonomics (PE) approach, the authors disseminated a quality improvement (QI) program for optimizing blood culture use in PICUs to a national 14-hospital collaborative. The objective of this study was to evaluate the dissemination process and its impact on blood culture reduction. METHODS: The PE approach emphasized three key principles (stakeholder participation, application of human factors and ergonomics knowledge and tools, and cross-site collaboration) with a six-step dissemination process. Data on interactions between sites and the coordinating team and site experiences with the dissemination process were collected using site diaries and semiannual surveys with local QI teams, respectively, and correlated with the site-specific change in blood culture rates. RESULTS: Overall, participating sites were able to successfully implement the program and reduced their blood culture rates from 149.4 blood cultures per 1,000 patient-days/month before implementation to 100.5 blood cultures per 1,000 patient-days/month after implementation, corresponding to a 32.7% relative reduction (p < 0.001). Variations in the dissemination process, as well as in local interventions and implementation strategies, were observed across sites. Site-specific changes in blood culture rates were weakly negatively correlated with the number of preintervention interactions with the coordinating team (p = 0.057) but not correlated with their experiences with the six domains of the dissemination process or their interventions. CONCLUSIONS: The authors applied a PE approach to disseminate a QI program for optimizing PICU blood culture use to a multisite collaborative. Working with local stakeholders, participating sites tailored their interventions and implementation processes and achieved the goal of reducing blood culture use.

Real-time forecasting of pediatric intensive care unit length of stay using computerized provider orders.

OBJECTIVE: To develop a model to produce real-time, updated forecasts of patients' intensive care unit length of stay using naturally generated provider orders. The model was designed to be integrated within a computerized decision support system to improve patient flow management. DESIGN: Retrospective cohort study. SETTING: Twenty-six bed pediatric intensive care unit within an urban, academic children's hospital using a computerized order entry system. PATIENTS: A total of 2,178 consecutive pediatric intensive care unit admissions during a 16-month time period. MEASUREMENTS AND MAIN RESULTS: We obtained unit length of stay measurements, time-stamped provider orders, age, admission source, and readmission status. A joint discrete-time logistic regression model was developed to produce probabilistic length of stay forecasts from continuously updated provider orders. Accuracy was assessed by comparing forecasted expected discharge time with observed discharge time, rank probability scoring, and calibration curves. Cross-validation procedures were conducted. The distribution of length of stay was heavily right-skewed with a mean of 3.5 days (95% confidence interval 0.3-19.1). Provider orders were predictive of length of stay in real-time accurately forecasting discharge within a 12-hr window: 46% for patients within 1 day of discharge, 34% for patients within 2 days of discharge, and 27% for patients within 3 days of discharge. The forecast model incorporating predictive orders demonstrated significant improvements in accuracy compared with forecasts based solely on empirical and temporal information. Seventeen predictive orders were found, grouped by medication, ventilation, laboratory, diet, activity, foreign body, and extracorporeal membrane oxygenation. CONCLUSIONS: Provider orders reflect dynamic changes in patients' conditions, making them useful for real-time length of stay prediction and patient flow management. Patients' length of stay represent a major source of variability in intensive care unit resource utilization and if accurately predicted and communicated, may lead to proactive bed management with more efficient patient flow.

A qualitative study of expert and team cognition on complex patients in the pediatric intensive care unit.

OBJECTIVES: To understand expert and team cognition of complex patients in the pediatric intensive care unit through the use of cognitive task analysis. DESIGN: Qualitative study with semistructured interviews. SETTING: Academic medical center pediatric intensive care unit. PARTICIPANTS: Physicians, nurses, and nurse practitioners. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Semistructured interviews were conducted with members of the critical care team involved with the care of seven complex patients. Interviews were transcribed and themes were identified based on grounded theory and further divided into categories. A focus group of critical care team members further refined and validated the findings. From the interviews, 177 verbal fragments were sorted into 11 themes. Four broad thematic categories were identified and a cognitive framework for the care of complex patients was formulated. We found that at the center of this framework, critical care teams attempt to create and share mental models of their patients. These mental models serve as the framework for delivery of longitudinal care across handovers and shift changes. The analysis revealed that this process is limited by a number of factors such that team members utilize a variety of techniques to overcome these limitations and develop more complete and shared mental models. CONCLUSIONS: An inadequately developed or inadequately shared mental model is a substantial cognitive limitation for expert and team cognition in the complex environment of the pediatric intensive care unit. Providers utilize techniques that may avoid or decrease the variable interpretations of patient condition that would otherwise impair mental model formation and sharing. Future studies should be designed to enhance mental model formation and communication in the pediatric intensive care unit and other environments that deal with complex patients.

A Research Agenda for Diagnostic Excellence in Critical Care Medicine.

Diagnosing critically ill patients in the intensive care unit is difficult. As a result, diagnostic errors in the intensive care unit are common and have been shown to cause harm. Research to improve diagnosis in critical care medicine has accelerated in past years. However, much work remains to fully elucidate the diagnostic process in critical care. To achieve diagnostic excellence, interdisciplinary research is needed, adopting a balanced strategy of continued biomedical discovery while addressing the complex care delivery systems underpinning the diagnosis of critical illness.

Association of Diagnostic Stewardship for Blood Cultures in Critically Ill Children With Culture Rates, Antibiotic Use, and Patient Outcomes: Results of the Bright STAR Collaborative.

Importance: Blood culture overuse in the pediatric intensive care unit (PICU) can lead to unnecessary antibiotic use and contribute to antibiotic resistance. Optimizing blood culture practices through diagnostic stewardship may reduce unnecessary blood cultures and antibiotics. Objective: To evaluate the association of a 14-site multidisciplinary PICU blood culture collaborative with culture rates, antibiotic use, and patient outcomes. Design, Setting, and Participants: This prospective quality improvement (QI) collaborative involved 14 PICUs across the United States from 2017 to 2020 for the Bright STAR (Testing Stewardship for Antibiotic Reduction) collaborative. Data were collected from each participating PICU and from the Children's Hospital Association Pediatric Health Information System for prespecified primary and secondary outcomes. Exposures: A local QI program focusing on blood culture practices in the PICU (facilitated by a larger QI collaborative). Main Outcomes and Measures: The primary outcome was blood culture rates (per 1000 patient-days/mo). Secondary outcomes included broad-spectrum antibiotic use (total days of therapy and new initiations of broad-spectrum antibiotics ≥3 days after PICU admission) and PICU rates of central line-associated bloodstream infection (CLABSI), Clostridioides difficile infection, mortality, readmission, length of stay, sepsis, and severe sepsis/septic shock. Results: Across the 14 PICUs, the blood culture rate was 149.4 per 1000 patient-days/mo preimplementation and 100.5 per 1000 patient-days/mo postimplementation, for a 33% relative reduction (95% CI, 26%-39%). Comparing the periods before and after implementation, the rate of broad-spectrum antibiotic use decreased from 506 days to 440 days per 1000 patient-days/mo, respectively, a 13% relative reduction (95% CI, 7%-19%). The broad-spectrum antibiotic initiation rate decreased from 58.1 to 53.6 initiations/1000 patient-days/mo, an 8% relative reduction (95% CI, 4%-11%). Rates of CLABSI decreased from 1.8 to 1.1 per 1000 central venous line days/mo, a 36% relative reduction (95% CI, 20%-49%). Mortality, length of stay, readmission, sepsis, and severe sepsis/septic shock were similar before and after implementation. Conclusions and Relevance: Multidisciplinary diagnostic stewardship interventions can reduce blood culture and antibiotic use in the PICU. Future work will determine optimal strategies for wider-scale dissemination of diagnostic stewardship in this setting while monitoring patient safety and balancing measures.