Operational Definitions Related to Pediatric Ventilator Liberation.

BACKGROUND: Common, operational definitions are crucial to assess interventions and outcomes related to pediatric mechanical ventilation. These definitions can reduce unnecessary variability among research and quality improvement efforts, to ensure findings are generalizable, and can be pooled to establish best practices. RESEARCH QUESTION: Can we establish operational definitions for key elements related to pediatric ventilator liberation using a combination of detailed literature review and consensus-based approaches? STUDY DESIGN AND METHODS: A panel of 26 international experts in pediatric ventilator liberation, two methodologists, and two librarians conducted systematic reviews on eight topic areas related to pediatric ventilator liberation. Through a series of virtual meetings, we established draft definitions that were voted upon using an anonymous web-based process. Definitions were revised by incorporating extracted data gathered during the systematic review and discussed in another consensus meeting. A second round of voting was conducted to confirm the final definitions. RESULTS: In eight topic areas identified by the experts, 16 preliminary definitions were established. Based on initial discussion and the first round of voting, modifications were suggested for 11 of the 16 definitions. There was significant variability in how these items were defined in the literature reviewed. The final round of voting achieved ≥ 80% agreement for all 16 definitions in the following areas: what constitutes respiratory support (invasive mechanical ventilation and noninvasive respiratory support), liberation and failed attempts to liberate from invasive mechanical ventilation, liberation from respiratory support, duration of noninvasive respiratory support, total duration of invasive mechanical ventilation, spontaneous breathing trials, extubation readiness testing, 28 ventilator-free days, and planned vs rescue use of post-extubation noninvasive respiratory support. INTERPRETATION: We propose that these consensus-based definitions for elements of pediatric ventilator liberation, informed by evidence, be used for future quality improvement initiatives and research studies to improve generalizability and facilitate comparison.

Executive Summary: International Clinical Practice Guidelines for Pediatric Ventilator Liberation, A Pediatric Acute Lung Injury and Sepsis Investigators (PALISI) Network Document.

Rationale: Pediatric-specific ventilator liberation guidelines are lacking despite the many studies exploring elements of extubation readiness testing. The lack of clinical practice guidelines has led to significant and unnecessary variation in methods used to assess pediatric patients' readiness for extubation. Methods: Twenty-six international experts comprised a multiprofessional panel to establish pediatrics-specific ventilator liberation clinical practice guidelines, focusing on acutely hospitalized children receiving invasive mechanical ventilation for more than 24 hours. Eleven key questions were identified and first prioritized using the Modified Convergence of Opinion on Recommendations and Evidence. A systematic review was conducted for questions that did not meet an a priori threshold of ⩾80% agreement, with Grading of Recommendations, Assessment, Development, and Evaluation methodologies applied to develop the guidelines. The panel evaluated the evidence and drafted and voted on the recommendations. Measurements and Main Results: Three questions related to systematic screening using an extubation readiness testing bundle and a spontaneous breathing trial as part of the bundle met Modified Convergence of Opinion on Recommendations criteria of ⩾80% agreement. For the remaining eight questions, five systematic reviews yielded 12 recommendations related to the methods and duration of spontaneous breathing trials, measures of respiratory muscle strength, assessment of risk of postextubation upper airway obstruction and its prevention, use of postextubation noninvasive respiratory support, and sedation. Most recommendations were conditional and based on low to very low certainty of evidence. Conclusions: This clinical practice guideline provides a conceptual framework with evidence-based recommendations for best practices related to pediatric ventilator liberation.

Interaction of Critical Care Practitioners With a Decision Support Tool for Weaning Mechanical Ventilation in Children.

BACKGROUND: There is evidence that ventilator weaning protocols provide benefit to children receiving mechanical ventilation, but many protocols do not include explicit instructions for decreasing ventilator support from maximal settings. We evaluated care provider opinions on ventilator weaning recommendations made by a computerized decision support tool. METHODS: Recommendations for ventilator adjustment were generated using a computerized decision support tool based on the ARDSNet protocol using data from children with acute hypoxemic respiratory failure admitted to the pediatric ICU (PICU). Attending physicians, fellows, nurse practitioners, and respiratory therapists (RTs) caring for these patients answered a brief survey to assess whether recommendations were reasonable and whether the practitioner believed they could be implemented. RESULTS: RTs completed 99 surveys and ICU providers completed 96 surveys based on data from 10 patients. RTs and ICU providers found 63.9% and 65.3% of recommendations reasonable, respectively. There were 5 instances of disagreement between RTs and ICU providers. The percent of recommendations that RTs thought could be implemented was 29.9%, whereas this figure for ICU providers was 26.3%, with 4 instances of disagreement. Free-text responses indicated that many RTs and ICU providers were concerned about disrupting current patient stability and low tidal volumes. CONCLUSIONS: On initial evaluation, the decision support tool did not appear to be highly acceptable to RTs and ICU providers in our setting because recommendations were rarely implemented. In addition, acceptability did not increase over time as patients generally improved. Most respondents preferred to make no ventilator changes and felt the recommendations were too aggressive. The notable barrier to use was a perception of potential patient instability with weaning.

Physiologic Effects of 3 Different Neonatal Volume-Targeted Ventilation Modes in Surfactant-Deficient Juvenile Rabbits.

BACKGROUND: Different brands of volume-targeted modes may vary the location of tidal volume (VT) monitoring and whether peak inspiratory pressure is adjusted based on inspiratory, expiratory, or leak-compensated VT. These variables may result in different levels of support provided to patients, especially when an endotracheal tube (ETT) leak is present. We hypothesized that there would be no differences in gas exchange, triggering, or work of breathing between volume-targeted modes of 3 different brands of equipment in a surfactant-deficient, spontaneously breathing animal model with and without an ETT leak. METHODS: Twelve rabbits (mean ± SD 1.61 ± 0.20 kg) were sedated, anesthetized, intubated, lavaged with 0.9% saline solution, and randomized in a crossover design so that each animal was supported by 3 different volume-targeted modes at identical settings with and without an ETT leak. After 30 min, arterial blood gas, VT, and esophageal and airway pressure were recorded for each condition, and pressure-rate product and percentage of successfully triggered breaths were calculated. RESULTS: Gas exchange and the pressure-rate product were not different between the ventilators in the absence of an ETT leak. When an ETT leak was introduced, volume-guarantee modes allowed a higher percentage of triggered breaths and peak inspiratory pressure, which resulted in higher minute ventilation, pH, and lower PaCO2 than the pressure-regulated volume control mode (P < .05). CONCLUSIONS: When a moderate ETT leak was present, volume-targeted modes that used proximal VT monitoring and triggering with adaptive leak compensation capabilities appeared more effective in providing ventilation support than did a ventilator that used measurements obtained from the back at the ventilator and does not have leak compensation.

C septicum Complicating Hemolytic Uremic Syndrome: Survival Without Surgical Intervention.

Clostridium septicum is an anaerobic bacterium that causes rapidly progressive myonecrosis, bacteremia, and central nervous system infection. It has been reported as a complication of Escherichia coli hemolytic uremic syndrome (HUS) in 8 children worldwide; 5 children died, and the 3 reported survivors had surgically treated disease. We present 3 cases of C septicum complicating HUS in children, including the first 2 reported cases of survival without surgical intervention. All patients presented with classic cases of HUS with initial clinical improvement followed by deterioration. Patient 1 had rising fever, tachycardia, and severe abdominal pain 24 hours after admission. She developed large multifocal intraparenchymal cerebral hemorrhages and died 12 hours later. Autopsy revealed C septicum intestinal necrosis, myonecrosis, and encephalitis. Patient 2 had new fever, increasing leukocytosis, and severe abdominal pain on hospital day 4. She was diagnosed with C septicum bacteremia and treated with metronidazole, meropenem, and clindamycin. Patient 3 had new fever and increasing leukocytosis on hospital day 3; blood cultures grew C septicum, and she was treated with penicillin. Patients 2 and 3 improved rapidly and did not require surgery. C septicum is a potential co-infection with E coli It thrives in the anaerobic environment of E coli-damaged intestinal mucosa and translocates to cause systemic infection. Fever, tachycardia, a rising white blood cell count, and abdominal pain out of proportion to examination are key findings for which physicians should be vigilant. Timely evaluation by anaerobic blood culture and early initiation of antibiotics are necessary to prevent fatalities.

Argument against the Routine Use of Steroids for Pediatric Acute Respiratory Distress Syndrome.

Steroids have a plausible mechanism of action of reducing severity of lung disease in acute respiratory distress syndrome (ARDS) but have failed to show consistent benefits in patient-centered outcomes. Many studies have confounding from the likely presence of ventilator-induced lung injury and steroids may have shown benefit because administration minimized ongoing inflammation incited by injurious ventilator settings. If steroids have benefit, it is likely for specific populations that fall within the heterogeneous diagnosis of ARDS. Those pediatric patients with concurrent active asthma or reactive airway disease of prematurity, in addition to ARDS, are the most common group likely to derive benefit from steroids, but are poorly studied. With the information currently available, it does not appear that the typical adult or pediatric patient with ARDS derives benefit from steroids and steroids should not be given on a routine basis.

Systematic Review and Meta-Analysis of End-Tidal Carbon Dioxide Values Associated With Return of Spontaneous Circulation During Cardiopulmonary Resuscitation.

OBJECTIVE: End-tidal carbon dioxide (ETCO(2)) measurements during cardiopulmonary resuscitation (CPR) reflect variable cardiac output over time, and low values have been associated with decreased survival. The goals of this review are to confirm and quantify this relationship and to determine the mean ETCO(2) value among patients with return of spontaneous circulation (ROSC) as an initial step toward determining an appropriate target for intervention during resuscitation in the absence of prospective data. DATA SOURCES AND STUDY SELECTION: The PubMed database was searched for the key words "end-tidal carbon dioxide" or "capnometry" or "capnography" and "resuscitation" or "return of spontaneous circulation." Randomized controlled trials, cohort studies, or case-control studies that reported ETCO(2) values for participants with and without ROSC were included. DATA EXTRACTION AND SYNTHESIS: Twenty-seven studies met the inclusion criteria for qualitative synthesis. Twenty studies were included in determination of average ETCO(2) values. The mean ETCO(2) in participants with ROSC was 25.8 ± 9.8 mm Hg versus 13.1 ± 8.2 mm Hg (P = .001) in those without ROSC. Nineteen studies were included in a meta-analysis. The mean difference in ETCO(2) was 12.7 mm Hg (95% confidence interval: 10.3-15.1) between participants with and without ROSC (P < .001). The mean difference in ETCO(2) was not modified by the receipt of sodium bicarbonate, uncontrolled minute ventilation, or era of resuscitation guidelines. The overall quality of data by Grades of Recommendations, Assessment, Development and Evaluation criteria is very low, but no prospective data are currently available. CONCLUSIONS: Participants with ROSC after CPR have statistically higher levels of ETCO(2). The average ETCO(2) level of 25 mm Hg in participants with ROSC is notably higher than the threshold of 10 to 20 mm Hg to improve delivery of chest compressions. The ETCO(2) goals during resuscitation may be higher than previously suggested and further investigation into appropriate targets during resuscitation is needed to diminish morbidity and mortality after cardiorespiratory arrest.

Effects of maternal antenatal glucocorticoid treatment on apoptosis in the ovine fetal cerebral cortex.

We examined the effects of single and multiple maternal glucocorticoid courses on apoptosis in the cerebral cortices of ovine fetuses (CC). Ewes received single dexamethasone or placebo courses at 104-106 or 133-135 days or multiple courses between 76-78 and 104-106 days gestation. In the single-course groups, ewes received four 6 mg dexamethasone or placebo injections every 12 hr for 48 hr. Multiple-course groups received the same treatment once per week for 5 weeks. Neuronal and nonneuronal apoptotic cell numbers per square millimeter were determined with TUNEL and NeuN staining and with caspase-3 enzyme activity on CC tissues harvested at 106-108 (70%) or 135-137 (90%) days of gestation. Apoptotic cell numbers and caspase-3 activity were 50% lower (P < 0.02) after single placebo courses at 90% than 70% gestation; 90% of apoptotic cells were (P < 0.01) nonneuronal at both ages. Nonneuronal apoptotic cells and caspase-3 activity were 40% and 20% lower (P < 0.02) after single dexamethasone than placebo courses at 70%, but not 90%, gestation. Caspase-3 activity was 20% lower (P < 0.01) after multiple dexamethasone than placebo courses, but apoptotic cell number did not differ. We conclude that nonneuronal apoptosis represents the major form of apoptosis in the CC at both 70% and 90% of gestation. Apoptosis in nonneuronal cells decreases with maturity and after a single course of dexamethasone at 70%, but not at 90%, gestation and not after multiple courses at 70% gestation. We speculate that a single course of glucocorticoids exerts maturational changes on the rate of apoptosis in the cerebral cortex of preterm ovine fetuses.

Technical feasibility and precision of radiostereometric analysis as an outcome measure in canine cemented total hip replacement.

Radiostereometric analysis (RSA) is an analytical technique in which biplanar radiographs are used to quantify the migration of implants in vivo. RSA is now considered the benchmark for quantifying implant migration in clinical studies of total joint replacement, yet its use in preclinical animal models has not been widely reported. The same attributes that make RSA appealing as an analytical method in humans (i.e., high precision and accuracy, noninvasiveness, objectivity) also make it a promising option for animal studies. The specific aims of this study were to determine the technical feasibility and analytical precision of RSA in a canine model of cemented total hip replacement. The precision of RSA was assessed in (1) a Plexiglas phantom, (2) a canine Sawbone model, and (3) a pilot series of dogs implanted with cemented canine THR implants. In vitro precision values, calculated as the 95% confidence limits for the error between duplicate RSA examinations, ranged from 4.3 to 17.9 microm for translation and from 0.01 degrees to 0.22 degrees for rotation. In vivo precision values ranged from 16.2 to 41.1 microm for translation and 0.17 degrees to 0.44 degrees for rotation. As is the case in humans, RSA appears to provide an order-of-magnitude improvement in technical precision as compared to plain film X-ray. RSA can therefore be considered a practical and potentially valuable noninvasive outcome measure for assessing implant function in canine cemented THR.