Melania M. Bembea

Pediatric Acute Respiratory Distress Syndrome: Consensus Recommendations From the Pediatric Acute Lung Injury Consensus Conference

OBJECTIVE To describe the final recommendations of the Pediatric Acute Lung Injury Consensus Conference. DESIGN Consensus conference of experts in pediatric acute lung injury. SETTING Not applicable. SUBJECTS PICU patients with evidence of acute lung injury or acute respiratory distress syndrome. INTERVENTIONS None. METHODS A panel of 27 experts met over the course of 2 years to develop a taxonomy to define pediatric acute respiratory distress syndrome and to make recommendations regarding treatment and research priorities. When published, data were lacking a modified Delphi approach emphasizing strong professional agreement was used. MEASUREMENTS AND MAIN RESULTS A panel of 27 experts met over the course of 2 years to develop a taxonomy to define pediatric acute respiratory distress syndrome and to make recommendations regarding treatment and research priorities. When published data were lacking a modified Delphi approach emphasizing strong professional agreement was used. The Pediatric Acute Lung Injury Consensus Conference experts developed and voted on a total of 151 recommendations addressing the following topics related to pediatric acute respiratory distress syndrome: 1) Definition, prevalence, and epidemiology; 2) Pathophysiology, comorbidities, and severity; 3) Ventilatory support; 4) Pulmonary-specific ancillary treatment; 5) Nonpulmonary treatment; 6) Monitoring; 7) Noninvasive support and ventilation; 8) Extracorporeal support; and 9) Morbidity and long-term outcomes. There were 132 recommendations with strong agreement and 19 recommendations with weak agreement. Once restated, the final iteration of the recommendations had none with equipoise or disagreement. CONCLUSIONS The Consensus Conference developed pediatric-specific definitions for acute respiratory distress syndrome and recommendations regarding treatment and future research priorities. These are intended to promote optimization and consistency of care for children with pediatric acute respiratory distress syndrome and identify areas of uncertainty requiring further investigation.

Variability in anticoagulation management of patients on extracorporeal membrane oxygenation: an international survey

Objective: The objective of this study was to determine current practices of anticoagulation in patients on extracorporeal membrane oxygenation. Design: Internet-based cross-sectional survey distributed between November 2010 and May 2011. Setting: Extracorporeal Life Support Organization-registered extracorporeal membrane oxygenation centers internationally. Participants: Extracorporeal membrane oxy genation medical directors and coordinators. Interventions: None. Measurements and Main Results: There were 121 responses from extracorporeal membrane oxy genation medical directors and coordinators at 187 Extracorporeal Life Support Organization centers with access to the survey. Eighty-four of 117 (72%) respondents reported having a written institutional extracorporeal membrane oxy genation protocol for both anticoagulation and blood product management at their institutions. Sixty-nine of 117 (59%) respondents reported use of tip-to-tip or partially heparin-bonded circuits. Unfractionated heparin was used at all centers; only 8% of respondents indicated use of alternative anticoagulation medications in the six months prior to the survey. The preferred method of anticoagulation monitoring was the serial measurement of activated clotting time, as reported by 97% of respondents. In this survey, 82% of respondents reported antithrombin III testing, 65% reported anti-factor Xa testing, and 43% reported use of thromboelastography during extracorporeal membrane oxy genation. Goal ranges for these three tests and interventions triggered by out-of-range values were found to be variable. Conclusions: Extracorporeal membrane oxy genation anticoagulation management policies vary widely by center. The majority of extracorporeal membrane oxy genation programs employ activated clotting time as the preferred anticoagulation monitoring tool. The coagulation system is also monitored using more specific markers such as antithrombin III, anti-factor Xa, and thromboelastography by a large number of centers. Future research is needed to elucidate optimal anticoagulation management and improve outcomes.

Glial fibrillary acidic protein as a brain injury biomarker in children undergoing extracorporeal membrane oxygenation

Objective: To determine whether, in children, plasma glial fibrillary acidic protein is associated with brain injury during extracorporeal membrane oxygenation and with mortality. Design: Prospective, observational study. Setting: Pediatric intensive care unit in an urban tertiary care academic center. Patients: Neonatal and pediatric patients on extracorporeal membrane oxygenation (n = 22). Interventions: Serial blood sampling for glial fibrillary acidic protein measurements. Measurements and Main Results: Prospective patients age 1 day to 18 yrs who required extracorporeal membrane oxygenation from April 2008 to August 2009 were studied. Glial fibrillary acidic protein was measured using an electrochemiluminescent immunoassay developed at Johns Hopkins. Control samples were collected from 99 healthy children (0.5–16 yrs) and 59 neonatal intensive care unit infants without neurologic injury. In controls, the median glial fibrillary acidic protein concentration was 0.055 ng/mL (interquartile range, 0–0.092 ng/mL) and the 95th percentile of glial fibrillary acidic protein was 0.436 ng/mL. In patients on extracorporeal membrane oxygenation, plasma glial fibrillary acidic protein was measured at 6, 12, and every 24 hrs after cannulation. We enrolled 22 children who underwent extracorporeal membrane oxygenation. Median age was 7 days (interquartile range, 2 days to 9 yrs), and primary extracorporeal membrane oxygenation indication was: cardiac failure, six of 22 (27.3%); respiratory failure, 12 of 22 (54.5%); extracorporeal cardiopulmonary resuscitation, three of 22 (13.6%); and sepsis, one of 22 (4.6%). Seven of 22 (32%) patients developed acute neurologic injury (intracranial hemorrhage, brain death, or cerebral edema diagnosed by imaging). Fifteen of 22 (68%) survived to hospital discharge. In the extracorporeal membrane oxygenation group, peak glial fibrillary acidic protein levels were higher in children with brain injury than those without (median, 5.9 vs. 0.09 ng/mL, p = .04) and in nonsurvivors compared with survivors to discharge (median, 5.9 vs. 0.09 ng/mL, p = .04). The odds ratio for brain injury for glial fibrillary acidic protein >0.436 ng/mL vs. normal was 11.5 (95% confidence interval, 1.3–98.3) and the odds ratio for mortality was 13.6 (95% confidence interval, 1.7–108.5). Conclusions: High glial fibrillary acidic protein during extracorporeal membrane oxygenation is significantly associated with acute brain injury and death. Brain injury biomarkers may aid in outcome prediction and neurologic monitoring of patients on extracorporeal membrane oxygenation to improve outcomes and benchmark new therapies.

Anticoagulation monitoring during pediatric extracorporeal membrane oxygenation.

The best method of monitoring anticoagulation during extracorporeal membrane oxygenation (ECMO) is unknown. We conducted a prospective observational study in a tertiary pediatric intensive care unit. Antifactor Xa, antithrombin (AT), and factor VIII activity (FVIII) were measured in blood samples collected at 6, 12, and every 24 hours, respectively, of ECMO. We enrolled 34 children who underwent 35 ECMO runs from April 2008 to September 2010. Activated clotting time (ACT) and heparin doses were higher, whereas antifactor Xa levels were lower in neonates compared to infants/children. Median antifactor Xa was 0.4 IU/ml, median AT was 60%, and median FVIII was 67%. Heparin infusion rate, antifactor Xa, and antithrombin (AT) increased, FVIII was stable, and ACT decreased with each day on ECMO. ACT had poor agreement with antifactor Xa (42%). AT was inversely correlated with ACT (r = –0.33), even after adjusting for heparin dose, and positively correlated with antifactor Xa (r = 0.57). This study emphasizes the age differences as well as the variability over days of coagulation monitoring assays during ECMO. ACT is poorly correlated with antifactor Xa and AT modifies the relationship between ACT and the heparin dose, indicating that results should be interpreted with caution when managing anticoagulation on ECMO. Additional studies are warranted to determine optimal ECMO anticoagulation monitoring.

A multicenter outcomes analysis of children with severe viral respiratory infection due to human metapneumovirus.

Objective: To investigate the impact of human metapneumovirus on morbidity and mortality outcomes in children with severe viral respiratory infection. Design: Retrospective cohort study. Setting: ICU, either PICU or cardiac ICU, at three urban academic tertiary care children’s hospitals. Patients: All patients admitted to an ICU with laboratory-confirmed human metapneumovirus infection between January 2010 and June 2011. Interventions: We captured demographic and clinical data and analyzed associated morbidity and mortality outcomes. Measurements and Main Results: There were 111 patients with laboratory-confirmed human metapneumovirus admitted to an ICU at one of the three participating institutions during the period of study. The median hospital length of stay was 7 days (interquartile range 4–18 days) and median ICU length of stay was 4 days (interquartile range 1–10 days). Ten patients (9%) did not survive to discharge. Predisposing factors associated with increased mortality included female gender (p = 0.002), presence of a chronic medical condition (p = 0.04), and hospital acquisition of human metapneumovirus infection (p = 0.006). Adjusting for female gender, chronic medical conditions, hospital acquisition of infection and severity of illness score, logistic regression analysis demonstrated that female gender, hospital acquisition of infection, and chronic medical conditions each independently increased the odds of mortality (odds ratios 14.8, 10.7, and 12.7, respectively). Conclusions: Analysis of our results suggests that there is substantial morbidity and mortality associated with severe viral respiratory infection due to human metapneumovirus in children. Female gender, hospital acquisition of human metapneumovirus infection, and presence of chronic medical conditions each independently increases mortality. The burden of illness from human metapneumovirus on the ICU in terms of resource utilization may be considerable.

Temperature patterns in the early postresuscitation period after pediatric inhospital cardiac arrest.

Objective: To describe the prevalence of postarrest hyperthermia among children during the first 24 hrs after inhospital cardiac arrest and to determine the association of persistent postarrest hyperthermia with neurologic outcome and death before hospital discharge. Design: Multicenter, national registry of inhospital cardiopulmonary resuscitation. Setting: A total of 196 hospitals reporting to the American Heart Associations National Registry of Cardiopulmonary Resuscitation from January 1, 2005 to December 31, 2007. Patients: A total of 547 pediatric patients who suffered inhospital pulseless cardiac arrests reported to the National Registry of Cardiopulmonary Resuscitation, who survived resuscitative efforts and who had the maximum and the minimum temperature in the first 24 hrs postresuscitation reported to the National Registry of Cardiopulmonary Resuscitation. Interventions: None. Measurements and Main Results: Among 547 children with pulseless cardiac arrests, 238 (43.5%) had at least one temperature of ≥38°C, and 30 (5.5%) had “persistent hyperthermia” (i.e., both the minimum and the maximum temperature of ≥38°C) during the first 24 hrs postarrest. After adjusting for potential confounders by multivariate logistic regression, persistent hyperthermia in the first 24 hrs postarrest was associated with unfavorable neurologic outcome (adjusted odds ratio, 2.7; 95% confidence interval, 1.1–6.7), but not with death before hospital discharge (adjusted odds ratio, 1.2; 95% confidence interval, 0.4–3.4). Conclusions: Despite current guidelines to avoid postarrest hyperthermia, a temperature of ≥38°C occurred commonly among children in the first 24 hrs postarrest. Persistent postarrest hyperthermia was associated with unfavorable neurologic outcomes, even after controlling for potential confounding factors.

Pediatric Extracorporeal Life Support Organization Registry International Report 2016

The purpose of this report is to describe the international growth, outcomes, complications, and technology used in pediatric extracorporeal life support (ECLS) from 2009 to 2015 as reported by participating centers in the Extracorporeal Life Support Organization (ELSO). To date, there are 59,969 children who have received ECLS in the ELSO Registry; among those, 21,907 received ECLS since 2009 with an overall survival to hospital discharge rate of 61%. In 2009, 2,409 ECLS cases were performed at 157 centers. By 2015, that number grew to 2,992 cases in 227 centers, reflecting a 24% increase in patients and 55% growth in centers. ECLS delivered to neonates (0–28 days) for respiratory support was the largest subcategory of ECLS among children <18-years old. Overall, 48% of ECLS was delivered for respiratory support and 52% was for cardiac support or extracorporeal life support to support cardiopulmonary resuscitation (ECPR). During the study period, over half of children were supported on ECLS with centrifugal pumps (51%) and polymethylpentene oxygenators (52%). Adverse events including neurologic events were common during ECLS, a fact that underscores the opportunity and need to promote quality improvement work.

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.

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.

Physiologic monitoring of CPR quality during adult cardiac arrest: A propensity-matched cohort study

AIM The American Heart Association (AHA) recommends monitoring cardiopulmonary resuscitation (CPR) quality using end tidal carbon dioxide (ETCO2) or invasive hemodynamic data. The objective of this study was to evaluate the association between clinician-reported physiologic monitoring of CPR quality and patient outcomes. METHODS Prospective observational study of index adult in-hospital CPR events using the AHAs Get With The Guidelines - Resuscitation Registry. Physiologic monitoring was defined using specific database questions regarding use of either ETCO2 or arterial diastolic blood pressure (DBP) to monitor CPR quality. Logistic regression was used to evaluate the association between physiologic monitoring and outcomes in a propensity score matched cohort. RESULTS In the matched cohort, (monitored n=3032; not monitored n=6064), physiologic monitoring of CPR quality was associated with a higher rate of return of spontaneous circulation (ROSC; OR 1.22, CI95 1.04-1.43, p=0.017) compared to no monitoring. Survival to hospital discharge (OR 1.04, CI95 0.91-1.18, p=0.57) and survival with favorable neurological outcome (OR 0.97, CI95 0.75-1.26, p=0.83) were not different between groups. Of index events with only ETCO2 monitoring indicated (n=803), an ETCO2 >10mmHg during CPR was reported in 520 (65%), and associated with improved survival to hospital discharge (OR 2.41, CI95 1.35-4.30, p=0.003), and survival with favorable neurological outcome (OR 2.31, CI95 1.31-4.09, p=0.004) compared to ETCO2 ≤10mmHg. CONCLUSION Clinician-reported use of either ETCO2 or DBP to monitor CPR quality was associated with improved ROSC. An ETCO2 >10mmHg during CPR was associated with a higher rate of survival compared to events with ETCO2 ≤10mmHg.