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Supplemental Digital Content is available in the text., Background and Purpose: Blinded outcome assessment in trials with prospective randomized open blinded end point design is challenging. Unblinding can result in misclassified outcomes and biased treatment effect estimates. An outcome adjudication committee assures blinded outcome assessment, but the added value for trials with prospective randomized open blinded end point design and subjective outcomes is unknown. We aimed to assess the degree of misclassification of modified Rankin Scale (mRS) scores by a central assessor and its impact on treatment effect estimates in a stroke trial with prospective randomized open blinded end point design. Methods: We used data from the MR CLEAN (Multicenter Randomized Clinical Trial of Endovascular Treatment for Acute Ischemic Stroke in the Netherlands). The primary outcome was the mRS at 90 days. Standardized, algorithm-based telephone interviews to assess the mRS were conducted from a central location by an experienced research nurse, unaware but not formally blinded to treatment allocation (central assessor). Masked reports of these interviews were adjudicated by a blinded outcome committee. Misclassification was defined as an incorrect classification of the mRS by the central assessor. The effect of endovascular treatment on the mRS was assessed with multivariable ordinal logistic regression. Results: In MR CLEAN, 53/500 (10.6%) of the mRS scores were misclassified. The degree and direction of misclassification did not differ between treatment arms (P=0.59). Benefit of endovascular treatment was shown on the mRS when scored by the central assessor (adjusted common odds ratio, 1.60 [95% CI, 1.16–2.21]) and the outcome adjudication committee (adjusted common odds ratio, 1.67 [95% CI, 1.21–2.20]). Conclusions: Misclassification by the central assessor was small, randomly distributed over treatment arms, and did not affect treatment effect estimates. This study suggests that the added value of a blinded outcome adjudication committee is limited in a stroke trial with prospective randomized open blinded end point design applying standardized, algorithm-based outcome assessment by a central assessor, who is unaware but not formally blinded to treatment allocation. Registration: URL: https://www.isrctn.com; Unique identifier: ISRCTN10888758.

BackgroundRecurrent delivery of tidal mechanical energy (ME) inflicts ventilator-induced lung injury (VILI) when stress and strain exceed the limits of tissue tolerance. Mechanical power (MP) is the mathematical description of the ME delivered to the respiratory system over time. It is unknown how ME relates to underlying lung pathology and outcome in mechanically ventilated children. We therefore tested the hypothesis that ME per breath with tidal volume (Vt) normalized to bodyweight correlates with underlying lung pathology and to study the effect of resistance on the ME dissipated to the lung.MethodsWe analyzed routinely collected demographic, physiological, and laboratory data from deeply sedated and/or paralyzed children ResultsData of 312 patients with a median age of 7.8 (1.7–44.2) months was analyzed. Age (p p p ConclusionsME better related to underlying lung pathology and patient outcome than MP. The delivery of generated energy to the lung was not dependent on ETT size during PC ventilation. Further studies are needed to identify injurious MErs thresholds in ventilated children.

Background and Purpose: Endovascular treatment for acute ischemic stroke has been proven clinically effective, but evidence of the cost-effectiveness based on real-world data is scarce. The aim of this study was to assess whether endovascular therapy plus usual care is cost-effective in comparison to usual care alone in acute ischemic stroke patients. Methods: An economic evaluation was performed from a societal perspective with a 2-year time horizon. Empirical data on health outcomes and the use of resources following endovascular treatment were gathered parallel to the MR CLEAN trial (Multicenter Randomized Clinical Trial of Endovascular Treatment for Acute Ischemic Stroke in the Netherlands) and its 2-year follow-up study. Incremental cost-effectiveness ratios were calculated as the extra costs per additional patient with functional independence (modified Rankin Scale score 0–2) and the extra cost per quality-adjusted life year gained. Results: The mean costs per patient in the intervention group were $126 494 versus $143 331 in the control group (mean difference, −$16 839 [95% CI, −$38 113 to $5456]). Compared with patients in the control group, more patients in the intervention group achieved functional independence, 37.2% versus 23.9% (absolute difference, 13.3% [95% CI, 4.0%–22.0%]) and they generated more quality-adjusted life years, 0.99 versus 0.83 (mean difference of 0.16 [95% CI, 0.04–0.29]). Endovascular treatment dominated standard treatment with $18 233 saved per extra patient with a good outcome and $105 869 saved per additional quality-adjusted life year. Conclusions: Endovascular treatment added to usual care is clinically effective, and cost saving in comparison to usual care alone in patients with acute ischemic stroke. Registration: URL: https://www.trialregister.nl/trial/695 ; Unique identifier: NL695. URL: https://www.isrctn.com ; Unique identifier: ISRCTN10888758.

Non-invasive ventilation (NIV) is increasingly used in the supportive treatment of acute respiratory failure in children in the pediatric intensive care unit (PICU). However, finding an optimal fitting commercial available NIV face mask is one of the major challenges in daily practice, in particular for young children and those with specific facial features. Large air leaks and pressure-related skin injury due to suboptimal fit are important complications associated with NIV failure. Here, we describe a case of a 4-year old boy with cardiofaciocutaneous syndrome and rhinovirus-associated hypoxic acute respiratory failure who was successfully supported with NIV delivered by a simple anesthetic mask connected to a headgear by an in-house developed and 3D printed adaptor. This case is an example of the clinical challenge related to pediatric NIV masks in the PICU, but also shows the potential of alternative NIV interfaces e.g., by using a widely available and relatively cheap simple anesthetic mask. Further personalized strategies (e.g., by using 3D scanning and printing techniques) that optimize NIV mask fitting in children are warranted.

BACKGROUND: High-frequency oscillatory ventilation (HFOV) is a common but unproven management strategy in paediatric critical care. Oscillator settings have been traditionally guided by patient age and/or weight rather than by lung mechanics, thereby potentially negating any beneficial effects. We have adopted an open-lung HFOV strategy based on a corner frequency approach using an initial incremental-decremental mean airway pressure titration manoeuvre, a high frequency (8-15 Hz), and high power to initially target a proximal pressure amplitude (∆Pproximal) of 70-90 cm H2O, irrespective of age or weight.METHODS: We reviewed prospectively collected data on patients RESULTS: Data from 115 non-cardiac patients were analysed, of whom 53 had moderate-to-severe paediatric acute respiratory distress syndrome (PARDS). Sixteen patients (13.9%) died. Frequencies≥ 8 Hz and high ∆Pproximal were achieved in all patients irrespective of age or PARDS severity. Patients with severe PARDS showed the greatest improvement in oxygenation. pH and PaCO2 normalized in all patients. Haemodynamic parameters, cumulative amount of fluid challenges, and daily fluid balance did not deteriorate after transitioning to HFOV in any age or PARDS severity group. We observed a transient increase neuromuscular blocking agent use after switching to HFOV, but there was no increase in the daily cumulative amount of continuous midazolam or morphine in any age or PARDS severity group. No patients experienced clinically apparent barotrauma.CONCLUSIONS: This is the first study reporting the feasibility of an alternative, individualized, physiology-based open-lung HFOV strategy targeting high F and high ∆Pproximal. No adverse effects were observed with this strategy. Our findings warrant further systematic evaluation.

BackgroundTitration of the continuous distending pressure during a staircase incremental–decremental pressure lung volume optimization maneuver in children on high-frequency oscillatory ventilation is traditionally driven by oxygenation and hemodynamic responses, although validity of these metrics has not been confirmed.MethodsRespiratory inductance plethysmography values were used construct pressure–volume loops during the lung volume optimization maneuver. The maneuver outcome was evaluated by three independent investigators and labeled positive if there was an increase in respiratory inductance plethysmography values at the end of the incremental phase. Metrics for oxygenation (SpO2, FiO2), proximal pressure amplitude, tidal volume and transcutaneous measured pCO2(ptcCO2) obtained during the incremental phase were compared between outcome maneuvers labeled positive and negative to calculate sensitivity, specificity, and the area under the receiver operating characteristic curve. Ventilation efficacy was assessed during and after the maneuver by measuring arterial pH and PaCO2. Hemodynamic responses during and after the maneuver were quantified by analyzing heart rate, mean arterial blood pressure and arterial lactate.Results41/54 patients (75.9%) had a positive maneuver albeit that changes in respiratory inductance plethysmography values were very heterogeneous. During the incremental phase of the maneuver, metrics for oxygenation and tidal volume showed good sensitivity (> 80%) but poor sensitivity. The sensitivity of the SpO2/FiO2ratio increased to 92.7% one hour after the maneuver. The proximal pressure amplitude showed poor sensitivity during the maneuver, whereas tidal volume showed good sensitivity but poor specificity. PaCO2decreased and pH increased in patients with a positive and negative maneuver outcome. No new barotrauma or hemodynamic instability (increase in age-adjusted heart rate, decrease in age-adjusted mean arterial blood pressure or lactate > 2.0 mmol/L) occurred as a result of the maneuver.ConclusionsAbsence of improvements in oxygenation during a lung volume optimization maneuver did not indicate that there were no increases in lung volume quantified using respiratory inductance plethysmography. Increases in SpO2/FiO2one hour after the maneuver may suggest ongoing lung volume recruitment. Ventilation was not impaired and there was no new barotrauma or hemodynamic instability. The heterogeneous responses in lung volume changes underscore the need for monitoring tools during high-frequency oscillatory ventilation.

Supplemental Digital Content is available in the text., Background and Purpose— The modified Rankin Scale (mRS) at 3 months is the most commonly used primary outcome measure in stroke treatment trials, but it lacks specificity and requires long-term follow-up interviews, which consume time and resources. An alternative may be the National Institutes of Health Stroke Scale (NIHSS), early after stroke. Our aim was to evaluate whether the NIHSS assessed within 1 week after treatment could serve as a primary outcome measure for trials of acute treatment for ischemic stroke. Methods— We used data from 2 randomized controlled trials of endovascular treatment for ischemic stroke: the positive MR CLEAN (Multicenter Randomized Clinical Trial of Endovascular Treatment for Acute Ischemic Stroke in the Netherlands; N=500) and the neutral IMS (Interventional Management of Stroke) III trial (N=656). We used a causal mediation model, with linear and ordinal logistic regression adjusted for confounders, to evaluate the NIHSS 24 hours and 5 to 7 days after endovascular treatment as primary outcome measures (instead of the mRS at 3 months) in both trials. Patients who had died before the NIHSS was assessed received the maximum score of 42. NIHSS+1 was then log10-transformed. Results— In both trials, there was a significant correlation between the NIHSS at 24 hours and 5 to 7 days and the mRS. In MR CLEAN, we found a significant effect of endovascular treatment on the mRS and on the NIHSS at 24 hours and 5 to 7 days. After adjustment for NIHSS at 24 hours and 5 to 7 days, the effect of endovascular treatment on the mRS decreased from common odds ratio 1.68 (95% CI, 1.22–2.32) to respectively 1.36 (95% CI, 0.97–1.91) and 1.24 (95% CI, 0.87–1.79), indicating that treatment effect on the mRS is in large part mediated by the NIHSS. In the IMS III trial there was no treatment effect on the NIHSS at 24 hours and 5 to 7 days, corresponding with the absence of a treatment effect on the mRS. Conclusions— The NIHSS within 1 week satisfies the requirements for a surrogate end point and may be used as a primary outcome measure in trials of acute treatment for ischemic stroke, particularly in phase II(b) trials. This could reduce stroke-outcome assessment to its essentials (ie, neurological deficit), and reduce trial duration and costs. Whether and under which conditions it could be used in phase III trials requires a debate in the field with all parties. Clinical Trial Registration— URL: http://www.isrctn.com. Unique identifier: ISRCTN10888758; https://www.clinicaltrials.gov. Unique identifier: NCT00359424.

The number of children on commercial aircrafts is rising steeply and poses a need for their treating physicians to be aware of the physiologic effects and risks of air travel. The most important risk factors while flying are a decrease in partial oxygen pressure, expansion of trapped air volume, low cabin humidity, immobility, recirculation of air and limited options for medical emergencies. Because on-board medical emergencies mostly concern exacerbations of chronic disease, the medical history, stability of current disease and previous flight experience should be assessed before flight. If necessary, hypoxia altitude simulation testing can be performed to simulate the effects of in-flight hypoxia. Although the literature on paediatric safety of air travel is sparse, recommendations for many different situations can be given. Conclusion: We present an overview of the most up to date recommendations to ensure the safety of children during flight. What is Known: • Around 65% of on-board medical emergencies are complications of underlying disease.• In children, the three most common emergencies during flight concern respiratory, neurological and infectious disease. What is New: • Although studies are scarce, some advices to ensure safe air travel can be given for most underlying medical conditions in children, based on physiology, studies in adults and expert opinions.• In former preterm infants without chronic lung disease, hypoxia altitude simulation testing to rule out in-flight desaturation is not recommended. Electronic supplementary material The online version of this article (10.1007/s00431-018-3119-9) contains supplementary material, which is available to authorized users.

Background and Purpose— High blood pressure (BP) is associated with poor outcome and the occurrence of symptomatic intracranial hemorrhage in acute ischemic stroke. Whether BP influences the benefit or safety of intra-arterial treatment (IAT) is not known. We aimed to assess the relation of BP with functional outcome, occurrence of symptomatic intracranial hemorrhage and effect of IAT. Methods— This is a post hoc analysis of the MR CLEAN (Multicenter Randomized Clinical Trial of Endovascular Treatment of Acute Ischemic Stroke in the Netherlands). BP was measured at baseline, before IAT or stroke unit admission. We estimated the association of baseline BP with the score on the modified Rankin Scale at 90 days and safety parameters with ordinal and logistic regression analysis. Effect of BP on the effect of IAT was tested with multiplicative interaction terms. Results— Systolic BP (SBP) had the best correlation with functional outcome. This correlation was U-shaped; both low and high baseline SBP were associated with poor functional outcome. Higher SBP was associated with symptomatic intracranial hemorrhage (adjusted odds ratio, 1.25 for every 10 mm Hg higher SBP [95% confidence interval, 1.09–1.44]). Between SBP and IAT, there was no interaction for functional outcome, symptomatic intracranial hemorrhage, or other safety parameters; the absolute benefit of IAT was evident for the whole SBP range. The same was found for diastolic BP. Conclusions— BP does not affect the benefit or safety of IAT in patients with acute ischemic stroke caused by proximal intracranial vessel occlusion. Our data provide no arguments to withhold or delay IAT based on BP. Clinical Trial Registration— URL: http://www.isrctn.com . Unique identifier: ISRCTN10888758.

Background and Purpose— A high clot burden score (CBS) is associated with favorable outcome after intravenous treatment for acute ischemic stroke. The added benefit of intra-arterial treatment might be less in these patients. The aim of this exploratory post hoc analysis was to assess the relation of CBS with neurological improvement and endovascular treatment effect. Methods— For 499 of 500 patients in the MR CLEAN study (Multicenter Randomized Clinical Trial of Endovascular Treatment for Acute Ischemic Stroke in the Netherlands), the CBS was determined. Ordinal logistic regression models with and without main baseline prognostic variables were used to assess the association between CBS (continuous or dichotomized at CBS of 6) and a shift toward better outcome on the modified Rankin Scale. The model without main baseline prognostic variables only included treatment allocation and CBS. Models with and without a multiplicative interaction term of CBS and treatment were compared using the χ 2 test to assess treatment effect modification by CBS. Results— Higher CBS was associated with a shift toward better outcome on the modified Rankin Scale; adjusted common odds ratio per point CBS was 1.12 (95% confidence interval, 1.04–1.20]. Dichotomized CBS had an adjusted common odds ratio of 1.67 (95% confidence interval, 1.12–2.51). Both effect estimates were slightly attenuated by adding baseline prognostic variables. The addition of the interaction terms did not significantly improve the fit of the models. There was a small and insignificant increase of intra-arterial treatment efficacy in the high CBS group. Conclusions— A higher CBS is associated with improved outcome and may be used as a prognostic marker. We found no evidence that CBS modifies the effect of intra-arterial treatment. Clinical Trial Registration— URL: http://www.trialregister.nl . Unique identifier: NTR1804. URL: http://www.controlled-trials.com . Unique identifier: ISRCTN10888758.

Background The advent of the immunomodulatory imide drugs (IMiDs) lenalidomide and thalidomide for the treatment of patients with plasma cell myeloma (PCM), has contributed to more than a doubling of the overall survival of these individuals. As a result, PCM patients join survivors of other malignancies such as breast and prostate cancer with a relatively new clinical problem – second primary malignancies (SPMs) – many of which are a result of the treatment of the initial cancer. PCM patients have a statistically significant increased risk for acute myeloid leukemia (AML) and Kaposi sarcoma. IMiD treatment has also been associated with an increased risk of myelodysplastic syndrome (MDS), AML, and squamous cell carcinoma of the skin. However, within these overlapping groups, acute lymphoblastic leukemia (ALL) is much less common. Case presentation Herein, we describe an elderly man with PCM and a 14-year cumulative history of IMiD therapy who developed persistent pancytopenia and was diagnosed with B-cell acute lymphoblastic leukemia (B-ALL). He joins a group of 17 other patients documented in the literature who have followed a similar sequence of events starting with worsening cytopenias while on IMiD maintenance for PCM. These PCM patients were diagnosed with B-ALL after a median time of 36 months after starting IMiD therapy and at a median age of 61.5 years old. Conclusions PCM patients with subsequent B-ALL have a poorer prognosis than their de novo B-ALL counterparts, however, the very low prevalence rate of subsequent B-ALL and high efficacy of IMiD maintenance therapy in PCM should not alter physicians’ current practice. Instead, there should be a low threshold for bone marrow biopsy for unexplained cytopenias.

Background CT perfusion (CTP) and diffusion or perfusion MRI might assist patient selection for endovascular thrombectomy. We aimed to establish whether imaging assessments of irreversibly injured ischaemic core and potentially salvageable penumbra volumes were associated with functional outcome and whether they interacted with the treatment effect of endovascular thrombectomy on functional outcome.Methods In this systematic review and meta-analysis, the HERMES collaboration pooled patient-level data from all randomised controlled trials that compared endovascular thrombectomy (predominantly using stent retrievers) with standard medical therapy in patients with anterior circulation ischaemic stroke, published in PubMed from Jan 1,2010, to May 31, 2017. The primary endpoint was functional outcome, assessed by the modified Rankin Scale (mRS) at 90 days after stroke. Ischaemic core was estimated, before treatment with either endovascular thrombectomy or standard medical therapy, by CTP as relative cerebral blood flow less than 30% of normal brain blood flow or by MRI as an apparent diffusion coefficient less than 620 mu m(2)/s. Critically hypoperfused tissue was estimated as the volume of tissue with a CTP time to maximum longer than 6 s. Mismatch volume (ie, the estimated penumbral volume) was calculated as critically hypoperfused tissue volume minus ischaemic core volume. The association of ischaemic core and penumbral volumes with 90-day mRS score was analysed with multivariable logistic regression (functional independence, defined as mRS score 0-2) and ordinal logistic regression (functional improvement by at least one mRS category) in all patients and in a subset of those with more than 50% endovascular reperfusion, adjusted for baseline prognostic variables. The meta-analysis was prospectively designed by the HERMES executive committee, but not registered.Findings We identified seven studies with 1764 patients, all of which were included in the meta-analysis. CTP was available and assessable for 591 (34%) patients and diffusion MRI for 309 (18%) patients. Functional independence was worse in patients who had CTP versus those who had diffusion MRI, after adjustment for ischaemic core volume (odds ratio [OR] 0.47 [95% CI 0.30-0.72], p=0.0007), so the imaging modalities were not pooled. Increasing ischaemic core volume was associated with reduced likelihood of functional independence (CTP OR 0.77 [0.69-0.86] per 10 mL, p(interaction)=0.29; diffusion MRI OR 0.87 [0.81-0.94] per 10 mL, p(interaction)=0.94). Mismatch volume, examined only in the CTP group because of the small numbers of patients who had perfusion MRI, was not associated with either functional independence or functional improvement. In patients with CTP with more than 50% endovascular reperfusion (n=186), age, ischaemic core volume, and imaging-to-reperfusion time were independently associated with functional improvement. Risk of bias between studies was generally low.Interpretation Estimated ischaemic core volume was independently associated with functional independence and functional improvement but did not modify the treatment benefit of endovascular thrombectomy over standard medical therapy for improved functional outcome. Combining ischaemic core volume with age and expected imagingto-reperfusion time will improve assessment of prognosis and might inform endovascular thrombectomy treatment decisions. Copyright (C) 2018 Elsevier Ltd. All rights reserved.

Despite representing 30% to 40% of newly diagnosed cases of adult non-Hodgkin lymphoma, diffuse large B-cell lymphoma (DLBCL) rarely presents (1) in the leukemic phase (2) with dysregulation of the TP53 tumor suppressor gene and (3) an elevated serum lactic acid level. In this case report and literature review, we highlight this unfortunate triad of poor prognostic features associated with an aggressive and fatal clinical course in a 53-year-old man with recrudescent DLBCL. A leukemic presentation of de novo or relapsed DLBCL is rare and may be related to differential expressions of adhesion molecules on cell surfaces. In addition, TP53 gene mutations are present in approximately 20% to 25% of DLBCL cases and foreshadow worse clinical outcomes. Finally, an elevated serum lactic acid level in DLBCL that is not clearly associated with sepsis syndrome is a poor prognostic factor for survival and manifests as type B lactic acidosis through the Warburg effect.

Objectives: We validated the automatic nucleated RBC (nRBC) count on a Sysmex XE-5000 hematology analyzer (Sysmex Corporation, Kobe, Japan) and then evaluated the frequency of nRBCs in our patient population. Methods: We correlated automated nRBC enumeration by the Sysmex XE-5000 hematology analyzer on 463 peripheral blood (PB) samples with the manual nRBC count. Results from 360,504 consecutive blood samples were reviewed to determine the frequency of nRBCs in various patient populations in our hospital. Results: There was a strong correlation between the automated and manual nRBC count (Pearson’s r = 0.97). Frequency of nRBCs varied in different patient populations and was significantly higher in the presence of other morphology flags or abnormal CBC parameters. Low-level nRBCs (0.2%-1.3%) were detected in 0.5% of samples with otherwise normal parameters. Conclusions: The automated method offers many advantages for high-throughput laboratories, including faster turnaround time, labor savings, and high reliability. Automated nRBC measurement allowed us to recognize a group of individuals who have low-level circulating nRBCs with otherwise normal CBC parameters. Nucleated RBC levels below 1.5% as detected by the automated count may be present in patients without increased erythropoiesis or a pathologic bone marrow process.

Background and Purpose— Recent randomized trials have proven the benefit of intra-arterial treatment (IAT) with retrievable stents in acute ischemic stroke. Patients with poor or absent collaterals (preexistent anastomoses to maintain blood flow in case of a primary vessel occlusion) may gain less clinical benefit from IAT. In this post hoc analysis, we aimed to assess whether the effect of IAT was modified by collateral status on baseline computed tomographic angiography in the Multicenter Randomized Clinical Trial of Endovascular Treatment of Acute Ischemic Stroke in the Netherlands (MR CLEAN). Methods— MR CLEAN was a multicenter, randomized trial of IAT versus no IAT. Primary outcome was the modified Rankin Scale at 90 days. The primary effect parameter was the adjusted common odds ratio for a shift in direction of a better outcome on the modified Rankin Scale. Collaterals were graded from 0 (absent) to 3 (good). We used multivariable ordinal logistic regression analysis with interaction terms to estimate treatment effect modification by collateral status. Results— We found a significant modification of treatment effect by collaterals ( P =0.038). The strongest benefit (adjusted common odds ratio 3.2 [95% confidence intervals 1.7–6.2]) was found in patients with good collaterals (grade 3). The adjusted common odds ratio was 1.6 [95% confidence intervals 1.0–2.7] for moderate collaterals (grade 2), 1.2 [95% confidence intervals 0.7–2.3] for poor collaterals (grade 1), and 1.0 [95% confidence intervals 0.1–8.7] for patients with absent collaterals (grade 0). Conclusions— In MR CLEAN, baseline computed tomographic angiography collateral status modified the treatment effect. The benefit of IAT was greatest in patients with good collaterals on baseline computed tomographic angiography. Treatment benefit appeared less and may be absent in patients with absent or poor collaterals. Clinical Trial Registration— URL: http://www.trialregister.nl and http://www.controlled-trials.com . Unique identifier: (NTR)1804 and ISRCTN10888758, respectively.

OBJECTIVE: We aim to describe current clinical practice, the past decade of experience and factors related to improved outcomes for pediatric patients receiving high-frequency oscillatory ventilation. We have also modeled predictive factors that could help stratify mortality risk and guide future high-frequency oscillatory ventilation practice. DESIGN: Multicenter retrospective, observational questionnaire study. SETTING: Seven PICUs. PATIENTS: Demographic, disease factor, and ventilatory and outcome data were collected, and 328 patients from 2009 to 2010 were included in this analysis. INTERVENTIONS: None. MEASUREMENT AND MAIN RESULTS: Patients were classified into six cohorts based on underlying diagnosis. We used univariate analysis to identify factors associated with mortality risk and multivariate logistic regression to identify independent predictors of mortality risk. An oxygenation index greater than 35 and immunocompromise exhibited the greatest predictive power (p < 0.0001) for increased mortality risk, and respiratory syncytial virus was associated with lowest mortality risk (p = 0.003). Differences in mortality risk as a function of oxygenation index were highly dependent on primary underlying condition. A trend toward an increase in oscillator amplitude and frequency was observed when compared with historical data. CONCLUSIONS: Given the number of centers and subjects included in the database, these findings provide a robust description of current practice regarding the use of high-frequency oscillatory ventilation for pediatric hypoxic respiratory failure. Patients with severe hypoxic respiratory failure and immunocompromise had the highest mortality risk, and those with respiratory syncytial virus had the lowest. A means of identifying the risk of 30-day mortality for subjects can be obtained by identifying the underlying disease and oxygenation index on conventional ventilation preceding the initiation of high-frequency oscillatory ventilation.

BACKGROUND: General anaesthesia (GA) during endovascular thrombectomy has been associated with worse patient outcomes in observational studies compared with patients treated without GA. We assessed functional outcome in ischaemic stroke patients with large vessel anterior circulation occlusion undergoing endovascular thrombectomy under GA, versus thrombectomy not under GA (with or without sedation) versus standard care (ie, no thrombectomy), stratified by the use of GA versus standard care.METHODS: For this meta-analysis, patient-level data were pooled from all patients included in randomised trials in PuMed published between Jan 1, 2010, and May 31, 2017, that compared endovascular thrombectomy predominantly done with stent retrievers with standard care in anterior circulation ischaemic stroke patients (HERMES Collaboration). The primary outcome was functional outcome assessed by ordinal analysis of the modified Rankin scale (mRS) at 90 days in the GA and non-GA subgroups of patients treated with endovascular therapy versus those patients treated with standard care, adjusted for baseline prognostic variables. To account for between-trial variance we used mixed-effects modelling with a random effect for trials incorporated in all models. Bias was assessed using the Cochrane method. The meta-analysis was prospectively designed, but not registered.FINDINGS: Seven trials were identified by our search; of 1764 patients included in these trials, 871 were allocated to endovascular thrombectomy and 893 were assigned standard care. After exclusion of 74 patients (72 did not undergo the procedure and two had missing data on anaesthetic strategy), 236 (30%) of 797 patients who had endovascular procedures were treated under GA. At baseline, patients receiving GA were younger and had a shorter delay between stroke onset and randomisation but they had similar pre-treatment clinical severity compared with patients who did not have GA. Endovascular thrombectomy improved functional outcome at 3 months both in patients who had GA (adjusted common odds ratio (cOR) 1·52, 95% CI 1·09-2·11, p=0·014) and in those who did not have GA (adjusted cOR 2·33, 95% CI 1·75-3·10, pINTERPRETATION: Worse outcomes after endovascular thrombectomy were associated with GA, after adjustment for baseline prognostic variables. These data support avoidance of GA whenever possible. The procedure did, however, remain effective versus standard care in patients treated under GA, indicating that treatment should not be withheld in those who require anaesthesia for medical reasons.FUNDING: Medtronic.

Objective: To determine whether tidal volume is associated with mortality in critically ill, mechanically ventilated children.Data Sources: MEDLINE, EM BASE, and CINAHL databases from inception until July 2013 and bibliographies of included studies without language restrictions.Study Selection: Randomized clinical trials and observational studies reporting mortality in mechanically ventilated PICU patients.Data Extraction: Two authors independently selected studies and extracted data on study methodology, quality, and patient outcomes. Meta-analyses were performed using the Mantel-Haenszel random-effects model. Heterogeneity was quantified using P. Study quality was assessed using the Newcastle-Ottawa Score for cohort studies.Data Synthesis: Out of 142 citations, seven studies met the inclusion criteria, and additional two articles were identified from references of the found articles. One was excluded. These eight studies included 1,756 patients. Mortality rates ranged from 13% to 42%. There was no association between tidal volume and mortality when tidal volume was dichotomized at 7, 8, 10, or 12 mL/kg. Comparing patients ventilated with tidal volume less than 7 mL/kg and greater than 10 mL/kg or greater than 12 mL/kg and tidal volume less than 8 mL/kg and greater than 10 mL/kg or greater than 12 mL/kg also showed no association between tidal volume and mortality. Limiting the analysis to patients with acute lung injury/acute respiratory distress syndrome did not change these results. Heterogeneity was observed in all pooled analyses.Conclusions: A relationship between tidal volume and mortality in mechanically ventilated children could not be identified, irrespective of the severity of disease. The significant heterogeneity observed in the pooled analyses necessitates future studies in well-defined patient populations to understand the effects of tidal volume on patient outcome.

The Dutch Encapsulating Peritoneal Sclerosis (EPS) Registry was started in 2009. Cases were identified by contacting all Dutch nephrologists twice yearly. The predefined criteria for EPS allowed for inclusion of patients with diagnosed and suspected EPS. Cases registered between January 2009 and January 2015 were analyzed with follow-up until September 2015. Fifty-three EPS cases were identified, of which 28.3% were post-transplantation EPS cases. Fourteen patients were initially categorized as suspected EPS, of whom 13 developed EPS. A remarkable 6-fold decrease in the yearly incidence of EPS was observed, from 0.85% in 2009 to 0.14% in 2014. This decrease could not be explained by a decrease in the number of PD patients or average duration of PD treatment in this period. Two-year survival of EPS patients was 52%. The use of tamoxifen and surgical interventions increased significantly over the years. Tamoxifen-treated cases showed a trend to better patient survival and post-transplantation EPS had a significantly favorable outcome. In conclusion, the incidence of EPS has declined significantly in the Netherlands from 2009 to 2014.

Much of the common practice in paediatric mechanical ventilation is based on personal experiences and what paediatric critical care practitioners have adopted from adult and neonatal experience. This presents a barrier to planning and interpretation of clinical trials on the use of specific and targeted interventions. We aim to establish a European consensus guideline on mechanical ventilation of critically children.MethodsThe European Society for Paediatric and Neonatal Intensive Care initiated a consensus conference of international European experts in paediatric mechanical ventilation to provide recommendations using the Research and Development/University of California, Los Angeles, appropriateness method. An electronic literature search in PubMed and EMBASE was performed using a combination of medical subject heading terms and text words related to mechanical ventilation and disease-specific terms.ResultsThe Paediatric Mechanical Ventilation Consensus Conference (PEMVECC) consisted of a panel of 15 experts who developed and voted on 152 recommendations related to the following topics: (1) general recommendations, (2) monitoring, (3) targets of oxygenation and ventilation, (4) supportive measures, (5) weaning and extubation readiness, (6) normal lungs, (7) obstructive diseases, (8) restrictive diseases, (9) mixed diseases, (10) chronically ventilated patients, (11) cardiac patients and (12) lung hypoplasia syndromes. There were 142 (93.4%) recommendations with ?strong agreement?. The final iteration of the recommendations had none with equipoise or disagreement.ConclusionsThese recommendations should help to harmonise the approach to paediatric mechanical ventilation and can be proposed as a standard-of-care applicable in daily clinical practice and clinical research.; Une grande partie de la pratique courante en ventilation mécanique pédiatrique est basée sur des expériences personnelles et ce que les praticiens en soins intensifs pédiatriques ont adopté à partir de l'expérience adulte et néonatale.

Objective: To describe the frequency and type of patient-ventilator asynchrony in mechanically ventilated children by analyzing ventilator flow and pressure signals.Design: Prospective observational study.Setting: Tertiary PICU in a university hospital.Patients: Mechanically ventilated children between 0 and 18 years old and who were able to initiate and maintain spontaneous breathing were eligible for inclusion. Patients with congenital or acquired neuromuscular disorders, those with congenital or acquired central nervous system disorders, and those who were unable to initiate and maintain spontaneous breathing from any other cause were excluded.Interventions: None.Measurements and Main Results: All patients were ventilated in a time-cycled, pressure-limited mode with flow triggering set at 1.0 L/min by using the Evita XL (Drager, Lubeck, Germany). Patient-ventilator asynchrony was identified by a random 30-minute continuous recording and an offline analysis of the flow and pressure signals. Patient-ventilator asynchrony was categorized and labeled into four different groups: 1) trigger asynchrony (i.e., insensitive trigger, double triggering, autotriggering, or trigger delay), 2) flow asynchrony, 3) termination asynchrony (i.e., delayed or premature termination), and 4) expiratory asynchrony. Flow and pressure signals were recorded in 45 patients for 30 minutes. A total number of 57,651 breaths were analyzed. Patient-ventilator asynchrony occurred in 19,175 breaths (33%), and it was seen in every patient. Ineffective triggering was the most predominant type of asynchrony (68%), followed by delayed termination (19%), double triggering (4%), and premature termination (3%). Patient-ventilator asynchrony significantly increased with lower levels of peak inspiratory pressure, positive end-expiratory pressure, and set frequency.Conclusions: Patient-ventilator asynchrony is extremely common in mechanically ventilated children, and the predominant cause is ineffective triggering.

Introduction Thrombus density may be a predictor for acute ischemic stroke treatment success. However, only limited data on observer variability for thrombus density measurements exist. This study assesses the variability and bias of four common thrombus density measurement methods by expert and non-expert observers. Methods For 132 consecutive patients with acute ischemic stroke, three experts and two trained observers determined thrombus density by placing three standardized regions of interest (ROIs) in the thrombus and corresponding contralateral arterial segment. Subsequently, absolute and relative thrombus densities were determined using either one or three ROIs. Intraclass correlation coefficient (ICC) was determined, and Bland–Altman analysis was performed to evaluate interobserver and intermethod agreement. Accuracy of the trained observer was evaluated with a reference expert observer using the same statistical analysis. Results The highest interobserver agreement was obtained for absolute thrombus measurements using three ROIs (ICCs ranging from 0.54 to 0.91). In general, interobserver agreement was lower for relative measurements, and for using one instead of three ROIs. Interobserver agreement of trained non-experts and experts was similar. Accuracy of the trained observer measurements was comparable to the expert interobserver agreement and was better for absolute measurements and with three ROIs. The agreement between the one ROI and three ROI methods was good. Conclusion Absolute thrombus density measurement has superior interobserver agreement compared to relative density measurement. Interobserver variation is smaller when multiple ROIs are used. Trained non-expert observers can accurately and reproducibly assess absolute thrombus densities using three ROIs. Electronic supplementary material The online version of this article (doi:10.1007/s00234-015-1607-4) contains supplementary material, which is available to authorized users.

Contains fulltext : 168317.PDF (Publisher’s version ) (Open Access) BACKGROUND AND PURPOSE: In acute ischemic stroke (AIS) management, CT-based thrombus density has been associated with treatment success. However, currently used thrombus measurements are prone to inter-observer variability and oversimplify the heterogeneous thrombus composition. Our aim was first to introduce an automated method to assess the entire thrombus density and then to compare the measured entire thrombus density with respect to current standard manual measurements. MATERIALS AND METHOD: In 135 AIS patients, the density distribution of the entire thrombus was determined. Density distributions were described using medians, interquartile ranges (IQR), kurtosis, and skewedness. Differences between the median of entire thrombus measurements and commonly applied manual measurements using 3 regions of interest were determined using linear regression. RESULTS: Density distributions varied considerably with medians ranging from 20.0 to 62.8 HU and IQRs ranging from 9.3 to 55.8 HU. The average median of the thrombus density distributions (43.5 +/- 10.2 HU) was lower than the manual assessment (49.6 +/- 8.0 HU) (p

Neuromuscular blockade (NMB) has been shown to improve outcome in acute respiratory distress syndrome (ARDS) in adults, challenging maintaining spontaneous breathing when there is severe lung injury. We tested in a prospective physiological study the hypothesis that continuous administration of NMB agents in mechanically ventilated children with severe acute hypoxemic respiratory failure (AHRF) improves the oxygenation index without a redistribution of tidal volume V T toward non-dependent lung zones. Oxygenation index, PaO2/FiO2 ratio, lung mechanics (plateau pressure, mean airway pressure, respiratory system compliance and resistance), hemodynamics (heart rate, central venous and arterial blood pressures), oxygenation [oxygenation index (OI), PaO2/FiO2 and SpO2/FiO2], ventilation (physiological dead space-to-V T ratio) and electrical impedance tomography measured changes in end-expiratory lung volume (EELV), and V T distribution was measured before and 15 min after the start of continuous infusion of rocuronium 1 mg/kg. Patients were ventilated in a time-cycled, pressure-limited mode with pre-set V T. All ventilator settings were not changed during the study. Twenty-two patients were studied (N = 18 met the criteria for pediatric ARDS). Median age (25–75 interquartile range) was 15 (7.8–77.5) weeks. Pulmonary pathology was present in 77.3%. The median lung injury score was 9 (8–10). The overall median CoV and regional lung filling characteristics were not affected by NMB, indicating no ventilation shift toward the non-dependent lung zones. Regional analysis showed a homogeneous time course of lung inflation during inspiration, indicating no tendency to atelectasis after the introduction of NMB. NMB decreased the mean airway pressure (p = 0.039) and OI (p = 0.039) in all patients. There were no significant changes in lung mechanics, hemodynamics and EELV. Subgroup analysis showed that OI decreased (p = 0.01) and PaO2/FiO2 increased (p = 0.02) in patients with moderate or severe PARDS. NMB resulted in an improved oxygenation index in pediatric patients with AHRF. Distribution of V T and regional lung filling characteristics were not affected.

Background and Purpose— Preclinical studies showed that thrombi can be permeable and may, therefore, allow for residual blood flow in occluded arteries of patients having acute ischemic stroke. This perviousness may increase tissue oxygenation, improve thrombus dissolution, and augment intra-arterial treatment success. We hypothesize that the combination of computed tomographic angiography and noncontrast computed tomography imaging allows measurement of contrast agent penetrating a permeable thrombus, and it is associated with improved outcome. Methods— Thrombus and contralateral artery attenuations in noncontrast computed tomography and computed tomographic angiography images were measured in 184 Multicenter Randomized Clinical trial of Endovascular treatment of acute ischemic stroke in the Netherlands (MR CLEAN) patients with thin-slice images. Two quantitative estimators of the thrombus permeability were introduced: computed tomographic angiography attenuation increase (Δ) and thrombus void fraction (ε). Patients were dichotomized as having a pervious or impervious thrombus and associated with outcome, recanalization, and final infarct volume. Results— Patients with Δ≥10.9 HU (n=81 [44%]) and ε≥6.5% (n=77 [42%]) were classified as having a pervious thrombus. These patients were 3.2 (95% confidence interval, 1.7–6.4) times more likely to have a favorable outcome, and 2.5 (95% confidence interval, 1.3–4.8) times more likely to recanalyze, for Δ based classification, and similarly for ε. These odds ratios were independent from intravenous or intra-arterial treatment. Final infarct volume was negatively correlated with both perviousness estimates (correlation coefficient, −0.39 for Δ and −0.40 for ε). Conclusions— This study shows that simultaneous measurement of thrombus attenuation in noncontrast computed tomography and computed tomographic angiography allows for quantification of thrombus perviousness. Thrombus perviousness is strongly associated with improved functional outcome, smaller final infarct volume, and higher recanalization rate.

Mechanical ventilation using low tidal volumes has become universally accepted to prevent ventilator-induced lung injury. High-frequency oscillatory ventilation (HFOV) allows pulmonary gas exchange using very small tidal volume (1-2 mL/kg) with concomitant decreased risk of atelectrauma. However, its use in pediatric critical care varies between only 3% and 30% of all ventilated children. This might be explained by the fact that the beneficial effect of HFOV on patient outcome has not been ascertained. Alternatively, in contrast with present recommendations, one can ask if HFOV has been employed in its most optimal fashion related especially to the indications for and timing of HFOV, as well as to using the best oscillator settings. The first was addressed in one small randomized study showing that early use of HFOV, instead of rescue use, was associated with improved survival. From a physiologic perspective, the oscillator settings could be refined. Lung volume is the main determinant of oxygenation in diffuse alveolar disease, suggesting using an open-lung strategy by recruitment maneuvers, although this is in practice not custom. Using such an approach, the patient can be oscillated on the deflation limb of the pressure-volume (P-V) curve, allowing less pressure required to maintain a certain amount of lung volume. Gas exchange is determined by the frequency and the oscillatory power setting, controlling the magnitude of the membrane displacement. Experimental work as well as preliminary human data have shown that it is possible to achieve the smallest tidal volume with concomitant adequate gas exchange when oscillating at high frequency and high fixed power setting. Future studies are needed to validate these novel approaches and to evaluate their effect on patient outcome.

Initial diagnosis of submucosal gastrointestinal stromal tumors (GISTs) is often made from material obtained by endoscopic ultrasound–guided fine-needle aspiration (EUS-FNA). Although 95% of GISTs are positive for KIT by immunohistochemical analysis on surgical specimens, we have observed several cases of GIST that were negative for KIT on the cell block but subsequently positive on the surgical resection. DOG1 has been found to be a specific and sensitive marker for GISTs on surgical material. We compared KIT and DOG1 staining in 52 GIST cell blocks and in 44 cell blocks of other intra-abdominal spindle cell neoplasms. We found that DOG1 was the more sensitive marker, with positivity in all 52 GIST cell blocks. KIT was positive in 46 (88%) of the GIST cases, with sensitivity dependent on the FNA method. Both markers were highly specific: KIT was negative in all 44 non-GIST cases, whereas DOG1 showed weak positivity in only 1 leiomyosarcoma.

Objectives: Transfusion of red blood cells is increasingly linked with adverse outcomes in critically ill children. We tested the hypothesis that leukocyte-depleted red blood cell transfusions were independently associated with increased development of bloodstream infections, ventilator-associated pneumonias, or urinary tract infections.Design: Historical, descriptive cohort study.Setting: Single-center, mixed medical-surgical, closed nine-bed pediatric intensive care unit of a tertiary university hospital.Patients: All childrenInterventions: None.Results: One thousand one hundred twenty-three patients were admitted, of whom 503 (44.8%) were admitted for >48 hrs. Sixty-five (12.9%) had a nosocomial infection (incidence 19.3 per 1,000 pediatric intensive care unit admissions per year). Patients with a nosocomial infection were significantly more often male (72.3% vs. 27.7%, p = .033), had a higher Pediatric Risk of Mortality II score (median 19.1 [range, 6-44] vs. 18.0 [range, 2-39], p = .023), were more often ventilated (95.4% vs. 80.1%, p = .003), and received more often red blood cell transfusions (55.4% vs. 40.2%, p = .021). Multivariate logistic regression analysis showed that male gender (odds ratio, 2.07; 95% confidence interval, 1.14-3.76), presence of an indwelling central venous catheter (odds ratio, 2.41; 95% confidence interval, 1.29-4.48), and simultaneous use of more than one type of antimicrobial drug were independently associated with the development of nosocomial infections. Red blood cell transfusion was discarded as a predictor.Conclusions: Transfusion of leukocyte-depleted red blood cells was not independently associated with the development of nosocomial infections in a heterogeneous group of critically ill children. (Pediatr Crit Care Med 2011; 12:519-524)

Background: Maintenance of spontaneous breathing is advocated in mechanical ventilation. This study evaluates the effect of spontaneous breathing on regional lung characteristics during high-frequency oscillatory (HFO) ventilation in an animal model of mild lung injury. Methods: Lung injury was induced by lavage with normal saline in eight pigs (weight range 47–64 kg). HFO ventilation was applied, in runs of 30 min on paralyzed animals or on spontaneous breathing animals with a continuous fresh gas flow (CF) or a custom-made demand flow (DF) system. Electrical impedance tomography (EIT) was used to assess lung aeration and ventilation and the occurrence of hyperinflation. Results: End expiratory lung volume (EELV) decreased in all different HFO modalities. HFO, with spontaneous breathing maintained, showed preservation in lung volume in the dependent lung regions compared with paralyzed conditions. Comparing DF with paralyzed conditions, the center of ventilation was located at 50% and 51% (median, left and right lung) from anterior to posterior and at 45% and 46% respectively, Po0.05. Polynomial coefficients using a continuous flow were 0.02 (range 0.35 to 0.32) and 0.01 ( 0.17 to 0.23) for CF and DF, respectively, P 5 0.01. Conclusions: This animal study demonstrates that spontaneous breathing during HFO ventilation preserves lung volume, and when combined with DF, improves ventilation of the dependent lung areas. No significant hyperinflation occurred on account of spontaneous breathing. These results underline the importance of maintaining spontaneous breathing during HFO ventilation and support efforts to optimize HFO ventilators to facilitate patients’ spontaneous breathing.

Importance: It is uncertain whether therapeutic reperfusion with endovascular treatment yields more or less brain edema. Objective: To elucidate the association between reperfusion and brain edema. The secondary objectives were to evaluate whether brain edema could partially be responsible for worse outcomes in patients with later reperfusion or lower Alberta Stroke Program Early Computed Tomography Score. Design, Setting, and Participants: This was a post hoc analysis of the Multicenter Randomized Clinical Trial of Endovascular Treatment for Acute Ischemic Stroke in the Netherlands (MR CLEAN), which was a prospective, randomized, multicenter clinical trial of endovascular treatment compared with conventional care of patients with acute anterior circulation ischemic stroke. Of 502 patients enrolled from December 2010 to June 2014, 2 patients declined to participate. Additionally, exclusion criteria were absence of follow-up imaging or presence of parenchymal hematoma, resulting in 462 patients included in this study. Brain edema was assessed retrospectively, from December 10, 2016, to July 24, 2017, by measuring midline shift (MLS) in all available follow-up scans. Observers were blinded to clinical data. Main Outcomes and Measures: Midline shift was assessed as present or absent and as a continuous variable. Reperfusion status was assessed by the modified thrombolysis in cerebral infarction score in the endovascular treatment arm. The modified arterial occlusive lesion score was used to evaluate the recanalization status in both arms. The modified Rankin scale score at 90 days was used for functional outcome. Results: Of 462 patients, the mean (SD) age was 65 (11) years, and 41.8% (n = 193) were women. Successful reperfusion and recanalization were associated with a reduced likelihood of having MLS (adjusted common odds ratio, 0.25; 95% CI, 0.12-0.53; P

Summary Aim To describe the safety and efficacy of HFOV as a rescue therapy for lung haemorrhage. Methods We conducted a retrospective case study of nine children. Lung haemorrhage was defined as large amounts of blood-stained effluent not attributable to a cardiovascular malformation or trauma, with bilateral opacities on chest X-ray. HFOV was started when conventional ventilation was ineffective in controlling the haemorrhage resulting in hypoxaemia or hypercarbia. A strategy was used aiming at tamponading transudation of oedema and decreasing blood flow from ruptured vessels. Results Seven infants improved significantly on HFOV. Two infants died, both showing an increasing oxygenation index. Conclusions HFOV therapy can be life-saving in massive lung haemorrhage in children, using a strategy with high pressures to tamponade transudation of haemorrhagic oedema, and to decrease blood flow from ruptured arterioles by reducing blood flow and increasing intrathoracic pressure. Similar to previous trials, an increasing oxygenation index was a sign of imminent death.

OBJECTIVE: To test the hypothesis that RBC transfusion in critically ill children is independently associated with increased mortality and morbidity.DESIGN: Retrospective, descriptive epidemiologic cohort study.SETTING: Single-center experience of a nine-bed pediatric intensive care unit (PICU) facility.PATIENTS: Critically ill children without ongoing active blood loss aged 0[Symbol: see text]months to 18[Symbol: see text]years, excluding prematurely born infants or patients after cardiothoracic surgery, and patients with chronic anemia.INTERVENTIONS: None.MEASUREMENTS AND RESULTS: Data of 295 consecutive patients was studied. Of these patients, 13.4% had a Hb concentration less than 9.6 g/dl. Sixty-seven (22.7%) of all patients were transfused, 39 only once. Transfused patients had a higher mortality (16.4 vs. 2.6%, p < 0.001). Mortality seemed related to the number of transfusion (p = 0.002) rather than the pre-transfusion Hb concentration (p = 0.10). Transfused patients required prolonged ventilatory support (11.1 +/- 1.8 vs. +/- 0.3 days, p < 0.001), infusion of vaso-active agents (8.2 +/- 1.8 vs. 2.8 +/- 0.6 days, p < 0.001) and PICU stay (13.0 +/- 1.8 vs. 3.2 +/- 0.2 days, p < 0.001). After multivariate analysis adjusting for age, PIM probability of death, mean TISS-28 score during the first 48 h, post-operative admission, diagnosis of sepsis or trauma or malignancy, pre-transfusion Hb concentration, and RBC transfusion remained independently associated with mortality and morbidity.CONCLUSIONS: RBC transfusion in critically ill children is independently associated with increased mortality and prolonged duration of mechanical ventilation, prolonged infusion of vaso-active agents and prolonged PICU stay.

Background and objective: This study was performed to assess the accuracy of respiratory inductive plethysmographic (RIP) estimated lung volume changes at varying positive end-expiratory pressures (PEEP) during different degrees of acute respiratory failure. Methods: Measurements of inspiratory tidal volume were validated in eight piglets during constant volume ventilation at incremental and decremental PEEP levels and with increasing severity of pulmonary injury. RIP accuracy was assessed with calibration from the healthy state, from the disease state as the measurement error was assessed, and at various PEEP levels. Results: Best results (bias 3%, precision 7%) were obtained in healthy animals. RIP accuracy decreased with progressing degrees of acute respiratory failure and was PEEP dependent, unless RIP was calibrated again. When calibration was performed in the disease state as the measurement error was assessed, bias was reduced but precision did not improve (bias - 2%, precision 9%). Conclusions: RIP accuracy is within the accuracy range found in monitoring devices currently in clinical use. Most reliable results with RIP are obtained when measurements are preceded by calibration in pulmonary conditions that are comparable to the measurement period. When RIP calibration is not possible, fixed weighting of the RIP signals with species and subject size adequate factors is an alternative. Measurement errors should be taken into account with interpretation of small volume changes.

To assess the value of monitoring abdominal and rib cage tidal displacement as an indicator of optimal mean airway pressure (Paw) during high-frequency oscillatory ventilation (HFOV).Prospective observational study in a university research laboratory.Eight piglets weighing 12.0+/-0.5 kg, surfactant depleted by lung lavage.Compliance of the respiratory system (C(rs)) was calculated from a quasistatic pressure volume loop. After initiation of HFOV lung volume was recruited by increasing Paw to 40 cmH(2)O. Then mean Paw was decreased in steps until PaO(2)/FIO(2) was below 100 mmHg. Proximal pressure amplitude remained constant.Abdominal and rib cage tidal displacement was determined using respiratory inductive plethysmography. During HFOV there was maximum in tidal volume (Vt) in seven of eight piglets. At maximal mean Paw abdominal and rib cage displacement were in phase. Phase difference between abdominal and rib cage displacement increased to a maximum of 178+/-28 degrees at minimum mean Paw. A minimum in abdominal displacement and a maximum of Vt was found near the optimal mean Paw, defined as the lowest mean Paw where shunt fraction is below 0.1.During HFOV abdominal and rib cage displacement displayed mean Paw dependent asynchrony. Maximal Vt and minimal abdominal displacement coincided with optimal C(rs), oxygenation, and ventilation, suggesting potential clinical relevance of monitoring Vt and abdominal displacement during HFOV.

To study the value of objective pressure-volume characteristics for predicting optimal airway pressures and the development of atelectasis and overstretching during a structured lung volume recruitment procedure with subsequent reduction in airway pressures. We used a mathematical model of a lung with adjustable characteristics of acute respiratory distress syndrome (ARDS) characteristics. Simulations were performed in five grades of ARDS in the presence of pure alveolar or combined alveolar-small airway closure as well complete or incomplete lung volume recruitability. For each simulation optimal end-expiratory pressure was determined. A static pressure-volume curve was constructed and objective characteristics of this curve calculated. The predictive value of these characteristics for end-expiratory atelectasis, overstretching, and optimal end-expiratory pressure was assessed. Simultaneous alveolar recruitment and overstretching during inflation were more pronounced than alveolar derecruitment and overstretching during deflation. End-expiratory pressure needed to prevent significant alveolar collapse in severe ARDS resulted in maximal safe tidal volumes that may be insufficient for adequate ventilation using conventional mechanical ventilatory modes. Plateau pressures well below the “upper corner point” (airway pressure where compliance decreases) resulted in significant alveolar overstretching. A recruitment maneuver followed by subsequent reduction in airway pressure limits end-expiratory atelectasis, overstretching, and pressure. None of the objective characteristics of the pressure-volume curve was predictive for end-expiratory atelectasis, overstretching, or optimal airway pressure.

Background: A study was undertaken to evaluate the efficacy of dexamethasone in patients mechanically ventilated for lower respiratory infection caused by respiratory syncytial virus (RSV-LRTI). Methods: In a multicentre randomised controlled trial patients were randomised to receive either intravenous dexamethasone (0.15 mg/kg 6 hourly for 48 hours) or placebo. End points were the duration of mechanical ventilation, length of stay (LOS) in the pediatric intensive care unit (PICU) and in hospital, and the duration of supplemental oxygen administration. Results: Thirty seven patients received dexamethasone and 45 received placebo. There was no significant difference in any of the end points between the two groups. In a post hoc analysis patients were stratified into those with mild gas exchange anomalies ( PaO2/FiO(2) > 200 mm Hg and/or mean airway pressure 10 cm H2O, pneumonia group). In the 39 patients with bronchiolitis the duration of mechanical ventilation was 4.3 days shorter in the dexamethasone group than in the placebo group (4.9 v 9.2 days, 95% CI - 7.8 to - 0.8, p= 0.02) and the duration of supplemental oxygen was 3.6 days shorter (7.7 v 11.3 days, 95% CI - 8.0 to - 0.1, p= 0.048). No differences in end points were found in the pneumonia group. Conclusions: Dexamethasone had no beneficial effect in patients mechanically ventilated for RSV-LRTI but was found to have a beneficial effect in patients with bronchiolitis

Objective: To assess the risk of ventilator-associated pneumo- nia (VAP) and the incidence of upper airway colonisation related to the use of stress ulcer prophylaxis in critical- ly ill children. Design: Retrospective study. Setting: Paediatric intensive care unit (PICU) of a tertiary care centre. Patients: All children who were mechanically ventilated for more than 48 h. Interventions: None. Results: A total of 54 patients were given ranitidine, 53 patients were given sucralfate and 48 patients were given no stress ulcer prophylaxis. Thirteen (8.4%) patients developed VAP: 6 (11.1%) patients in the raniti- dine group, 4 (7.5%) in the sucral- fate group and 3 (6.2%) in the group without prophylaxis. The rate of up- per airway colonisation with Gram negative bacilli was 25.9% (14/54) in the ranitidine group, 22.6% (12/53) in the sucralfate group and 37.5% (18/48) in the group without prophylaxis. The differences among the groups were not significant. Conclusions: In contrast to findings in adults, we found that, in children, sucralfate does not decrease the inci- dence of VAP or the incidence of up- per airway colonisation with Gram negative bacilli as compared to ra- nitidine or no stress ulcer prophyl- axis. However, the small sample size and study design substantially limit our conclusions.

In a randomized, prospective, multicenter study, we compared the safety, efficacy, and metabolic effects of a 7.5% icodextrin solution (Extraneal) with a 2.27% glucose solution for long dwell exchanges in patients undergoing automated peritoneal dialysis. Thirty-nine stable patients on automated peritoneal dialysis were randomized to receive either icodextrin (n = 20) or glucose 2.27% solution (n = 19). The study included a 2-week baseline period followed by a 12-week icodextrin treatment phase and a 2-week follow-up period when switching back to glucose. The average net ultrafiltration during the long dwell period was 278 +/- 43 mL/d for the icodextrin group and -138 +/- 81 mL/d for the control group (P < 0.001). The higher ultrafiltration volume with icodextrin was associated with higher creatinine (2.59 +/- 0.09 mL/min versus 2.16 +/- 0.11 mL/min) and urea (2.67 +/- 0.09 mL/min versus 2.28 +/- 0.12 mL/min) peritoneal clearances for the long dwell (both P < 0.001). Ultrafiltration rate per mass of carbohydrate absorbed was +5.2 +/- 1.2 microL/min/g in the icodextrin group and -5.5 +/- 2.8 microL/min/g in the glucose group (P < 0.001). In the icodextrin group, there was a decrease in serum sodium and chloride compared with baseline (P < 0.01). Total dialysate sodium removal increased in the icodextrin group from 226.7 mEq to 269.6 mEq (week 12, P < 0.001). Serum alpha-amylase activity decreased from 103 U/L to 16 U/L (P < 0.001). The total icodextrin plasma levels reached a steady-state concentration of 6,187 +/- 399 mg/L after 1 week of treatment. Urine volume and residual renal function were not specifically affected by icodextrin compared with glucose. None of the laboratory changes resulted in any reported clinically meaningful side effect. Icodextrin produced increased, sustained ultrafiltration during the long dwell period, increasing (convective) peritoneal clearance and sodium removal in automated peritoneal dialysis patients.

To assess the feasibility, stability and predictability of pCO2 measurement (PetCO2) using a main stream capnograph in a high frequency oscillatory ventilation circuit. A commercially available capnograph was mounted into a high frequency oscillatory ventilator patient circuit, adjustable CO2 flow was introduced into an artificial lung and the output of the CO2 sensor assessed under varying ventilator settings. Influence of oxygen content, pressures, heat and moisture were recorded. A linear relationship between CO2 flow rate and PetCO2 was found. Varying ventilator settings influenced the measurements, but the results for PetCO2 remained within a range of 1.5 mmHg above or under then mean measurement value. Measurements remained stable despite humidification, heat, pressure amplitudes or mean airway pressure changes. From this bench test, we conclude it is feasible to measure PetCO2 using a main stream capnograph during high frequency oscillatory conditions, these measurements were stable during the experiment. Changes in CO2 production or output can be detected. The system may prove to be of clinical value, but further in vivo measurements are warranted.

Background: High-frequency oscillatory ventilation (HFOV) is a ventilatory mode using small tidal volumes with low phasic pressures at supraphysiological frequencies. Beyond the neonatal period there are distinct lung diseases for which HFOV is used. Data of 35 children who deteriorated on conventional ventilation were retrospectively analysed in two tertiary pediatric intensive care units. Methods: Depending on the underlying pulmonary pathophysiology, three strategies were employed. First, the ‘open-lung’ strategy designed to rapidly recruit and maintain optimal lung volume in DAD ( n =27) and pulmonary hemorrhage ( n =5). Second, the ‘low-volume’ strategy in persistent air leak ( n =1) where, after an initial identical approach, mean airway pressure (MAP) is reduced until the air leak ceases. Third, the ‘open-airway’ strategy in obstructive airway disease ( n =5) where MAP is used to recruit and stent the airways. Results: Seven patients died, two due to respiratory failure. Three patients developed an air leak. Nine patients developed chronic lung disease. There was a significant decrease of the oxygenation index (OI) in the survivors. In the two patients who died of respiratory failure, the OI increased. Conclusion: If certain conditions are met, HFOV appears a safe and effective mode of ventilation in pediatric respiratory failure.

Objective: To study the effect of dexamethasone on postextubation stridor (PS) incidence and reintubation rate due to PS in a high-risk paediatric intensive care population. Patients and methods: All children aged between 4 wk and 6 y, who were intubated for at least 24 h and extubated between August 1999 and May 2002, were retrospectively included (n=60). Medical records of the included patients were studied; records of patients treated with dexamethasone prior to and following extubation (n=23) were compared with control patients who had not received prophylactic medication (n=37). Results: Nine patients in the control group developed significant postextubation stridor, necessitating nebulized epinephrine or glucocorticosteroids. In six of these children, reintubation as a result of postextubation stridor was indicated. None of the patients treated with dexamethasone developed severe postextubation stridor or required reintubation. Conclusions: The risk of postextubation stridor is relatively high in the group of children aged between 4 wk and 6 y with intubation exceeding 24 h. We found dexamethasone to be effective in preventing reintubation due to postextubation stridor in this paediatric high-risk group.

Background: A small percentage of patients who undergo surgical correction of a chest wall deformity will have results so unsatisfactory that a second procedure, the so-called "re-do", will be required. Conclusions: The literature contains very little information regarding the technique and results of these procedures. Based on experience with 18 "re-do" procedures, the authors believe that recurrent deformities should be surgically corrected. Although this is a somewhat diverse group based on age at the first and second procedure, type of original operative procedure, and interval between the procedures, the operative approach is standard, and the results are predictable.

Objective. The objective of this study is to determine the accuracy andprecision of chemiluminescence and electrochemical nitric oxide (NO)measurements and accuracy of NO dosage with electronic mass flow controllers(MFC) versus rotameters during NO inhalational therapy. Methods. NO flow wasdelivered to a high frequency oscillator and mixed with ventilator flow. NOand NO2 concentrations were measured simultaneously with astandard chemiluminescence analyzer and a modified electrochemical analyzer.Dosage accuracy was assessed with gas flows adjusted with either MFC’sor rotameters. Accuracy of both analyzers was validated with both NO andventilator flow regulated with a MFC. Results. In dry air, without pulsatilepressure, MFC controlled NO and ventilator flow resulted in an accuracyexpressed as the ratio of calculated concentration to measured concentration(RCM) of 0.995 (CI: 0.983–0.988) when measured with chemiluminescence.When the ventilator rotameter was used instead of a MFC, RCM was 0.856 (CI:0.835–0.877). With a rotameter for both NO and ventilator flow, RCMincreased to 1.175 (CI: 0.793–1.740) with an increase of confidenceinterval limits. Chemiluminescence was sensitive to humidification of theventilatory gases (p < 0.05), slightly sensitive to the addition ofoxygen and to pulsatile pressure (not significant). RCM obtained with themodified electrochemical analyzer was in close agreement withchemiluminescence RCM, although 95% CI were wider withelectrochemical analysis. Conclusions. During high frequency oscillatoryventilation (HFOV), standard rotameter flow control of both NO andventilator flow results in unpredictable NO concentrations that would beclinically unacceptable. When one MFC was used for NO flow control, withventilator flow controlled with a rotameter, this resulted in moderatedosage accuracy. To achieve a still higher accuracy, MFC flow control forboth NO and ventilator flow is indicated. During HFOV, standardchemiluminescence analyzers cannot be considered to be the gold standard fordetermination of the NO concentration delivered. Measurement of NOconcentration may not be mandatory for determination of inhaled NO doseduring HFOV, but may be used to monitor for unsafe or unwanted events.

The use of high-frequency oscillatory ventilation(HFOV) in pulmonary conditions with increasedairway resistance and prolonged time constants,such as small airway disease (SAD), remains con-troversial, in particular if an underlying airwayabnormality like tracheobronchomalacia is present.This is based upon the assumption that with thismode of ventilation the risk of dynamic air trappingis increased.