Perinatal morbidity among women with a previous caesarean delivery (PRISMA trial): a cluster-randomised trial.

BACKGROUND: Women with a previous caesarean delivery face a difficult choice in their next pregnancy: planning another caesarean or attempting vaginal delivery, both of which are associated with potential maternal and perinatal complications. This trial aimed to assess whether a multifaceted intervention, which promoted person-centred decision making and best practices, would reduce the risk of major perinatal morbidity among women with one previous caesarean delivery. METHODS: We conducted an open, multicentre, cluster-randomised, controlled trial of a multifaceted 2-year intervention in 40 hospitals in Quebec among women with one previous caesarean delivery, in which hospitals were the units of randomisation and women the units of analysis. Randomisation was stratified according to level of care, using blocked randomisation. Hospitals were randomly assigned (1:1) to the intervention group (implementation of best practices and provision of tools that aimed to support decision making about mode of delivery, including an estimation of the probability of vaginal delivery and an ultrasound estimation of the risk of uterine rupture), or the control group (no intervention). The primary outcome was a composite risk of major perinatal morbidity. This trial was registered with ISRCTN, ISRCTN15346559. FINDINGS: 21 281 eligible women delivered during the study period, from April 1, 2016 to Dec 13, 2019 (10 514 in the intervention group and 10 767 in the control group). None were lost to follow-up. There was a significant reduction in the rate of major perinatal morbidity from the baseline period to the intervention period in the intervention group as compared with the control group (adjusted odds ratio [OR] for incremental change over time, 0·72 [95% CI 0·52-0·99]; p=0·042; adjusted risk difference -1·2% [95% CI -2·0 to -0·1]). Major maternal morbidity was significantly reduced in the intervention group as compared with the control group (adjusted OR 0·54 [95% CI 0·33-0·89]; p=0·016). Minor perinatal and maternal morbidity, caesarean delivery, and uterine rupture rates did not differ significantly between groups. INTERPRETATION: A multifaceted intervention supporting women in their choice of mode of delivery and promoting best practices resulted in a significant reduction in rates of major perinatal and maternal morbidity, without an increase in the rate of caesarean or uterine rupture. FUNDING: Canadian Institutes of Health Research (CIHR, MOP-142448).

Discharge Directly Home From the PICU: A Retrospective Cohort Study.

OBJECTIVE: Healthcare constraints with decreasing bed availability cause strain in acute care units, and patients are more frequently being discharged directly home. Our objective was to describe the population, predictors, and explore PICU readmission rates of patients discharged directly home from PICU, compared with those discharge to the hospital ward, then home. DESIGN: An observational cohort study. SETTING: Children admitted to the PICU of CHU Sainte-Justine, between January 2014 and 2020. PATIENTS: Patients less than 18 years old, who survived their PICU stay, and were discharged directly home or to an inpatient ward. Patients discharged directly home were compared with patients discharged to the ward using descriptive statistics. Logistic regression was used to identify factors associated with home discharge. Propensity scores were used to compare PICU readmission rates in patients discharged directly home to those discharged to the ward. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Among the 5,531 admissions included, 594 (10.7%) were discharged directly home from the PICU. Patients who were more severe ill (odds ratio [OR], 0.93; 95% CI, 0.90-0.97), had invasive ventilation (OR, 0.70; 95% CI, 0.53-0.92), or had vasoactive agents (OR, 0.70; 95% CI, 0.53-0.92) were less likely to be discharged directly home. Diagnoses associated with discharge directly home were acute intoxication, postoperative ear-nose-throat care, and shock states. There was no difference in the rate of readmission to PICU at 2 (relative risk [RR], 0.20 [95% CI, 0.02-1.71]) and 28 days (RR, 1.20 [95% CI, 0.61-3.36]) between propensity matched patients discharged to the ward for 2 or less days, compared with those discharged directly home. CONCLUSION: Discharge directly home from the PICU is increasing locally. The population includes less severely ill patients with rapidly resolving diagnoses. Rates of PICU readmission between patients discharged directly home from the PICU versus to ward are similar, but safety of the practice requires ongoing evaluation.

Association between leukoreduced red blood cell transfusions and hospital-acquired infections in critically ill children: A secondary analysis of the TRIPICU study.

BACKGROUND AND OBJECTIVES: Hospital-acquired infections (HAIs) are an important problem in critically ill children. Studies show associations between the transfusion of non-leukoreduced red blood cell units (RBC) and increased HAI incidence rates (IRs). We hypothesize that transfusing pre-storage leukoreduced RBC is also associated with increased HAI IR. We aim to evaluate the associations between (1) a leukoreduced RBC restrictive transfusion strategy and HAI IR, (2) leukoreduced RBC transfusions and HAI IR, and (3) the number or volume of leukoreduced RBC transfusions and HAI IR in critically ill children. MATERIALS AND METHODS: This post hoc secondary analysis of the "Transfusion Requirement in Paediatric Intensive Care Units" (TRIPICU) randomized controlled trial (637 patients) used quasi-Poisson multivariable regression models to estimate HAI incidence rate ratios (IRRs) and 95% confidence intervals (CI). RESULTS: A restrictive transfusion strategy yielded an IRR of 0.88 (95% CI 0.67, 1.16). The association between transfusing leukoreduced RBCs (IRR 1.25; 95% CI 0.73, 2.13) and HAI IR was not statistically significant. However, we observed significant associations between patients who received >20 cc/kg volume of leukoreduced RBC transfusions (IRR 2.14; 95% CI 1.15, 3.99) and ≥3 leukoreduced RBC transfusions (IRR 2.40; 95% CI 1.15, 4.99) and HAI IR. CONCLUSION: Exposing critically ill children to >20 cc/kg or ≥3 leukoreduced RBC transfusions were associated with higher HAI IR, suggesting dose-response patterns.

Is Busulfan Clearance Different in Patients With Sickle Cell Disease? Let's Clear Up That Case With Some Controls.

In busulfan-based conditioning regimen for hematopoietic stem cell transplantation in children, accurate a priori determination of the first dose is important because of its narrow therapeutic window. Sickle cell disease (SCD) influences pharmacokinetics of the commonly used drugs by affecting organs responsible for drug metabolism and elimination. This pharmacokinetics study assesses the influence of SCD on the metabolic pathway of busulfan that is mainly metabolized in the liver. In this retrospective cross-sectional case-control study, 16 patients with SCD were matched to 50 patients without SCD on known busulfan clearance's covariates (glutathione-S-transferase alpha1 polymorphisms, age, weight). Clearance of the first dose of busulfan was not significantly different independently of genetic or anthropometric factors in patients with or without SCD.

Association between the length of storage of transfused leukoreduced red blood cell units and hospital-acquired infections in critically ill children: A secondary analysis of the TRIPICU study.

OBJECTIVE: Evaluate the association between leukoreduced red blood cell (RBC) storage length and hospital-acquired infection (HAI) incidence rate in critically ill children. BACKGROUND: RBC transfusions are common in critically ill children. Despite their benefits, observational studies suggest an association between them and HAIs. One possible mechanism for increased HAI is transfusion-related immunomodulation due to bioactive substances' release as transfused blood ages. METHODS: In this secondary analysis of the 'Transfusion Requirement in Paediatric Intensive Care Units' (TRIPICU) study, we analysed a subset of 257 participants that received only one pre-storage leukoreduced RBC transfusion. RBC storage length was classified as 1) transfusion of 'fresh' RBCs (≤10 days), 2) transfusion of 'stored' RBCs (21-34 days), and 3) transfusion of 'long-stored' RBCs (≥35 days). All were compared to a 'golden' period (11-20 days), representing the time between 'fresh' and 'stored'. We used quasi-Poisson multivariable regression models to estimate the HAI incidence rate ratio (IRR) and corresponding 95% confidence interval (CI). RESULTS: We found that the association between the length of storage time of leukoreduced RBCs and HAIs was not significant in the 'fresh' group (IRR 1.23; 95% CI 0.55, 2.78) and the 'stored' group (IRR 1.61; 95% CI 0.63, 4.13) when compared to the 'golden' period. However, we observed a statistically significant association between the 'long-stored' group and an increase in the HAI incidence rate (IRR 3.66; 95% CI 1.22, 10.98). CONCLUSION: Transfusion of leukoreduced RBC units stored for ≥35 days is associated with increased HAI incidence rate in haemodynamically stable, critically ill children.

Clinical relevance of membrane attack complex deposition in children with IgA nephropathy and Henoch-Schönlein purpura.

BACKGROUND: IgA nephropathy (IgAN) and Henoch-Schönlein purpura are common glomerular disorders in children sharing the same histopathologic pattern of IgA deposits within the mesangium, even if their physiopathology may be different. Repeated exposure to pathogens induces the production of abnormal IgA1. The immune complex deposition in the renal mesangium in IgAN or potentially in small vessels in Henoch-Schönlein purpura induces complement activation via the alternative and lectin pathways. Recent studies suggest that levels of membrane attack complex (MAC) in the urine might be a useful indicator of renal injury. Because of the emerging availability of therapies that selectively block complement activation, the aim of the present study is to investigate whether MAC immunostaining might be a useful marker of IgA-mediated renal injury. METHODS: We conducted immunohistochemistry analysis of the MAC on renal biopsies from 67 pediatric patients with IgAN and Henoch-Schönlein purpura. We classified their renal biopsies according to the Oxford classification, retrieved symptoms, biological parameters, treatment, and follow-up. RESULTS: We found MAC expression was significantly related to impaired renal function and patients whose clinical course required therapy. MAC deposits tend to be more abundant in patients with decreased glomerular filtration rate (p = 0.02), patients with proteinuria > 0.750 g/day/1.73 m2, and with nephrotic syndrome. No correlation with histological alterations was observed. CONCLUSIONS: We conclude that MAC deposition could be a useful additional indicator of renal injury in patients with IgAN and Henoch-Schönlein purpura, independent of other indicators.

A cluster-randomized trial to reduce caesarean delivery rates in Quebec: cost-effectiveness analysis.

BACKGROUND: Widespread increases in caesarean section (CS) rates have sparked concerns about risks to mothers and infants and rising healthcare costs. A multicentre, two-arm, cluster-randomized trial in Quebec, Canada assessed whether an audit and feedback intervention targeting health professionals would reduce CS rates for pregnant women compared to usual care, and concluded that it reduced CS rates without adverse effects on maternal or neonatal health. The effect was statistically significant but clinically small. We assessed cost-effectiveness to inform scale-up decisions. METHODS: A prospective economic evaluation was undertaken using individual patient data from the Quality of Care, Obstetrics Risk Management, and Mode of Delivery (QUARISMA) trial (April 2008 to October 2011). Analyses took a healthcare payer perspective. The time horizon captured hospital-based costs and clinical events for mothers and neonates from labour onset to 3 months postpartum. Resource use was identified and measured from patient charts and valued using standardized government sources. We estimated the changes in CS rates and costs for the intervention group (versus controls) between the baseline and post-intervention periods. We examined heterogeneity between clinical subgroups of high-risk versus low-risk pregnancies and estimated the joint uncertainty in cost-effectiveness over 20,000 trial simulations. We decomposed costs to identify drivers of change. RESULTS: The intervention group experienced per-patient reductions of 0.005 CS (95% confidence interval (CI): -0.015 to 0.004, P = 0.09) and $180 (95% CI: -$277 to - $83, P < 0.001). Women with low-risk pregnancies experienced statistically significant reductions in CS rates and costs; changes for the high-risk subgroup were not significant. The intervention was "dominant" (effective in reducing CS and less costly than usual care) in 86.08% of simulations. It reduced costs in 99.99% of simulations. Cost reductions were driven by lower rates of neonatal complications in the intervention group (-$190, 95% CI: -$255 to - $125, P < 0.001). Given 88,000 annual provincial births, a similar intervention could save $15.8 million (range: $7.3 to $24.4 million) in Quebec annually. CONCLUSIONS: From a healthcare payer perspective, a multifaceted intervention involving audits and feedback resulted in a small reduction in caesarean deliveries and important cost savings. Cost reductions are consistent with improved quality of care in intervention group hospitals. TRIAL REGISTRATION: International Clinical Trials Registry Platform, ISRCTN95086407 . Registered on 23 October 2007.

Determinants of red blood cell transfusion in pediatric trauma patients admitted to the intensive care unit.

BACKGROUND: There are no well-designed prospective studies evaluating transfusion practices in pediatric trauma. We sought to describe red blood cell (RBC) transfusion practices in trauma patients who were admitted to a pediatric intensive care unit (PICU). STUDY DESIGN AND METHODS: This study is a post-hoc analysis of a prospective, 6-month observational study in 30 PICUs. We studied a total of 580 patients aged less than 18 years who had been admitted to a PICU for more than 48 hours, including 95 who were trauma patients. RESULTS: Trauma patients more frequently received transfusion before PICU admission (p < 0.001), were older (p < 0.0001), and more frequently were mechanically ventilated (p = 0.05). In the PICU, trauma patients received more transfusions (55% vs. 37%; p < 0.001), although admission hemoglobin levels were similar in both groups (p = 0.86). The mean (± standard deviation) pretransfusion hemoglobin level in the PICU was 9.0 ± 2.4 g/dL for trauma patients compared with 8.3 ± 2.4 g/dL for nontrauma patients (p = 0.09). Among the trauma patients, transfusion was associated with younger age, higher Pediatric Logistic Organ Regression scores, mechanical ventilation, bleeding, and transfusion before PICU admission. Multivariate regression demonstrated that receiving an RBC transfusion before admission was strongly associated with receiving a blood transfusion in the PICU (p = 0.008). CONCLUSION: Trauma patients are at high risk for receiving an RBC transfusion both before and during their PICU stay, despite a similar transfusion threshold compared with nontrauma patients. Transfusion before PICU admission is a strong determinant, suggesting ongoing bleeding that will require re-transfusion. Further studies are needed to evaluate whether a restrictive transfusion strategy can safely be considered in these patients.

Revisiting Pathological Criteria for Earlier Diagnosis of Coeliac Disease.

OBJECTIVES: The diagnosis of coeliac disease (CD) remains sometimes difficult because the histological criteria are not fully met. The aim of this study was to refine histological diagnostic criteria of CD. METHODS: One hundred seventy-five duodenal bulb D1 (n = 79) and duodenal D2 (n = 96) biopsies of 96 patients with CD (58 girls, mean age 7 years), 135 normal D2 biopsies (69 girls, mean age 12 years), and 64 D2 biopsies of other digestive disorders (DDs) (39 girls, mean age 13 years) obtained from children during a period of 4 years were reviewed. RESULTS: Interobserver agreement was greater for the classification of Corazza-Villanacci than for Marsh-Oberhuber (κ = 0.812 vs κ = 0.409, respectively). Between 40 and 70 intraepithelial lymphocytes (IELs) per 100 epithelial cells (ECs), 32% of patients were CD, whereas 50% had other DD. Above 70 IELs per 100 EC, 53% were CD, and only 6% had other DD. In CD, IELs were significantly located above EC nuclei compared with other DD, (12 IELs/100 EC vs 2 IELs/100 EC, respectively). In 21% of CD cases, D2 were normal and the diagnosis could only be made on D1. Finally, 6% of CD cases showed isolated increase of IELs in D1 without architectural modification. CONCLUSIONS: D1 allowed diagnosis of CD in 21% of cases and IEL >70 per 100 EC correlated strongly with CD. Between 40 and 70 IELs per 100 EC, CD is very likely but other DD must be considered. Finally, the preferential localisation of IELs above EC nuclei favours CD, and increased IEL in D1 may be the sole abnormality.

Platelet Transfusions in Pediatric Intensive Care.

OBJECTIVES: To characterize the determinants of platelet transfusion in a PICU and determine whether there exists an association between platelet transfusion and adverse outcomes. DESIGN: Prospective observational single center study, combined with a self-administered survey. SETTING: PICU of Sainte-Justine Hospital, a university-affiliated tertiary care institution. PATIENTS: All children admitted to the PICU from April 2009 to April 2010. INTERVENTION: None. MEASUREMENTS AND MAIN RESULTS: Among 842 consecutive PICU admissions, 60 patients (7.1%) received at least one platelet transfusion while in PICU. In the univariate analysis, significant determinants for platelet transfusion were admission Pediatric Risk of Mortality Score greater than 10 (odds ratio, 6.80; 95% CI, 2.5-18.3; p < 0.01) and Pediatric Logistic Organ Dysfunction scores greater than 20 (odds ratio, 26.9; 95% CI, 8.88-81.5; p < 0.01), history of malignancy (odds ratio, 5.08; 95% CI, 2.43-10.68; p < 0.01), thrombocytopenia (platelet count, < 50 × 10/L or < 50,000/mm) (odds ratio, 141; 95% CI, 50.4-394.5; p < 0.01), use of heparin (odds ratio, 3.03; 95% CI, 1.40-6.37; p < 0.01), shock (odds ratio, 5.73; 95% CI, 2.85-11.5; p < 0.01), and multiple organ dysfunction syndrome (odds ratio, 10.41; 95% CI, 5.89-10.40; p < 0.01). In the multivariate analysis, platelet count less than 50 × 10/L (odds ratio, 138; 95% CI, 42.6-449; p < 0.01) and age less than 12 months (odds ratio, 3.06; 95% CI, 1.03-9.10; p = 0.02) remained statistically significant determinants. The attending physicians were asked why they gave a platelet transfusion; the most frequent justification was prophylactic platelet transfusion in presence of thrombocytopenia with an average pretransfusion platelet count of 32 ± 27 × 10/L (median, 21), followed by active bleeding with an average pretransfusion platelet count of 76 ± 39 × 10/L (median, 72). Platelet transfusions were associated with the subsequent development of multiple organ dysfunction syndrome (odds ratio, 2.53; 95% CI, 1.18-5.43; p = 0.03) and mortality (odds ratio, 10.1; 95% CI, 4.48-22.7; p < 0.01). CONCLUSIONS: Among children, 7.1% received at least one platelet transfusion while in PICU. Thrombocytopenia and active bleeding were significant determinants of platelet transfusion. Platelet transfusions were associated with the development of multiple organ dysfunction syndrome and increased mortality.

Clonidine as a First-Line Sedative Agent After Neonatal Cardiac Surgery: Retrospective Cohort Study.

OBJECTIVES: To determine the cardiovascular tolerance of clonidine used as a first-line sedative after cardiac surgery in small infants. DESIGN: Retrospective chart review. SETTING: A tertiary and quaternary referral cardiac PICU. PATIENTS: All infants younger than 2 months who received a clonidine infusion for sedation after cardiac surgery from October 2011 to July 2013. INTERVENTIONS: None. MEASUREMENT AND MAIN RESULTS: Heart rate, blood pressure, central venous and left atrial pressure, vasoactive inotropic score, volume of fluid bolus, and lactate and central mixed venous saturation were assessed. Preinfusion values were compared with postinfusion values. Of 224 potentially eligible patients, only 23 infants met inclusion criteria, as most patients only received high doses of morphine and some received midazolam instead of clonidine. Clonidine administration was started at a median of 12 hours after surgery (Q1-Q3, 5-23), and infusion rate was 0.5-2 µg/kg/hr for a median duration of 30 hours (Q1-Q3, 12-54). Heart rate decreased (maximal mean decrease: 12% [149 beats/min (SD, 17) to 131 beats/min (SD, 17)]; p < 0.0001). Apart from a transient and limited drop in diastolic blood pressure of 13% (maximal mean decrease: from 42.8 mm Hg [SD, 5.9] to 37.1 mm Hg [SD, 4.0]; p = 0.018), all other cardiovascular variables were stable or improved. A contemporaneous cohort of patients who received midazolam, did so sooner after surgery, stayed longer in the PICU and showed less favorable hemodynamics. CONCLUSIONS: IV clonidine as sedative added to morphine in selected patients seems hemodynamically safe. The observed decrease in heart rate and diastolic blood pressure seems of minimal clinical importance as all other hemodynamic variables remained stable or improved. The safety of clonidine given early after cardiac surgery as alternative to midazolam merits further study.

Red Blood Cell Transfusion in the Postoperative Care of Pediatric Cardiac Surgery: Survey on Stated Practice.

The optimal red blood cell transfusion threshold for postoperative pediatric cardiac surgery patients is unknown. This study describes the stated red blood cell transfusion practice of physicians who treat postoperative pediatric cardiac surgery patients in intensive care units. A scenario-based survey was sent to physicians involved in postoperative intensive care of pediatric cardiac surgery patients in all Canadian centers that perform such surgery. Respondents reported their red blood cell transfusion practice in four postoperative scenarios: acyanotic or cyanotic cardiac lesion, in a neonate or an infant. In part A of each scenario, the patient was critically ill, but stabilized; in part B, the patient became unstable. Response rate was 58 % (71 of 123), with 45 respondents indicating direct involvement in postoperative intensive care. There was a wide variability in stated transfusion threshold, ranging from <7.0-14.0 g/dL for stabilized cases. There was no significant difference between neonates and infants in stated transfusion threshold. The mean hemoglobin level below which respondents would transfuse a stabilized patient was 9 g/dL for acyanotic and 11.2 g/dL for cyanotic patients, a statistically significant difference (2.2 ± 0.9 g/dL, p < 0.001). All clinical determinants of instability significantly increased transfusion threshold. Hemodynamic instability increased transfusion threshold by 2.3 ± 1.3 g/dL in acyanotic patients and by 1.3 ± 1.1 g/dL in cyanotic patients. Cyanotic lesion and clinical instability, but not patient age, increased stated red blood cell transfusion threshold. Significant variation in reported red blood cell transfusion practice exists among physicians treating pediatric patients in intensive care following cardiac surgery.

Compression stockings to prevent post-thrombotic syndrome: a randomised placebo-controlled trial.

BACKGROUND: Post-thrombotic syndrome (PTS) is a common and burdensome complication of deep venous thrombosis (DVT). Previous trials suggesting benefit of elastic compression stockings (ECS) to prevent PTS were small, single-centre studies without placebo control. We aimed to assess the efficacy of ECS, compared with placebo stockings, for the prevention of PTS. METHODS: We did a multicentre randomised placebo-controlled trial of active versus placebo ECS used for 2 years to prevent PTS after a first proximal DVT in centres in Canada and the USA. Patients were randomly assigned to study groups with a web-based randomisation system. Patients presenting with a first symptomatic, proximal DVT were potentially eligible to participate. They were excluded if the use of compression stockings was contraindicated, they had an expected lifespan of less than 6 months, geographical inaccessibility precluded return for follow-up visits, they were unable to apply stockings, or they received thrombolytic therapy for the initial treatment of acute DVT. The primary outcome was PTS diagnosed at 6 months or later using Ginsberg's criteria (leg pain and swelling of ≥1 month duration). We used a modified intention to treat Cox regression analysis, supplemented by a prespecified per-protocol analysis of patients who reported frequent use of their allocated treatment. This study is registered with ClinicalTrials.gov, number NCT00143598, and Current Controlled Trials, number ISRCTN71334751. FINDINGS: From 2004 to 2010, 410 patients were randomly assigned to receive active ECS and 396 placebo ECS. The cumulative incidence of PTS was 14·2% in active ECS versus 12·7% in placebo ECS (hazard ratio adjusted for centre 1·13, 95% CI 0·73-1·76; p=0·58). Results were similar in a prespecified per-protocol analysis of patients who reported frequent use of stockings. INTERPRETATION: ECS did not prevent PTS after a first proximal DVT, hence our findings do not support routine wearing of ECS after DVT. FUNDING: Canadian Institutes of Health Research.

ABO Group as a Thrombotic Risk Factor in Children With Acute Lymphoblastic Leukemia: A Retrospective Study of 523 Patients.

Children with acute lymphoblastic leukemia (ALL) are at high risk of thrombotic complications, resulting from multiple risk factors (malignancy, chemotherapy, central venous access devices, and inherent host characteristics). Non-O blood groups have been associated with an increased risk of venous thromboembolism (VTE) in adults, with a compounding effect in the presence of thrombophilia or cancer. We hypothesized that among children with ALL receiving a standardized protocol, there would be an increased risk of thrombotic events in non-O compared with O blood group patients. In a retrospective study of 523 children with ALL from June 1995 to April 2013, there were 56 (10.7%) thromboembolic events. Patients with VTE were compared with the whole cohort, based on blood group, age, sex, leukemia phenotype, and clinical risk category. Among children with VTE, 42 (75%) had non-O and 14 (25%) had O blood group, compared with 302 (57.7%) non-O and 221 (42.3%) O blood groups in the cohort. Non-O blood group was confirmed as an independent risk factor for VTE in multivariate analysis. This is the first study to report a significant association between non-O blood groups and VTE in children with cancer.

Heliox inhalation therapy for bronchiolitis in infants.

BACKGROUND: Bronchiolitis is the leading cause of hospitalisation among infants in high-income countries. Acute viral bronchiolitis is associated with airway obstruction and turbulent gas flow. Heliox, a mixture of oxygen and the inert gas helium, may improve gas flow through high-resistance airways and decrease the work of breathing. In this review, we selected trials that objectively assessed the effect of the addition of heliox to standard medical care for acute bronchiolitis. OBJECTIVES: To assess heliox inhalation therapy in addition to standard medical care for acute bronchiolitis in infants with respiratory distress, as measured by clinical endpoints (in particular the rate of endotracheal intubation, the rate of emergency department discharge, the length of treatment for respiratory distress) and pulmonary function testing (mainly clinical respiratory scores). SEARCH METHODS: We searched CENTRAL (2015, Issue 2), MEDLINE (1966 to March week 3, 2015), EMBASE (1974 to March 2015), LILACS (1982 to March 2015) and the National Institutes of Health (NIH) website (May 2009). SELECTION CRITERIA: Randomised controlled trials (RCTs) and quasi-RCTs of heliox in infants with acute bronchiolitis. DATA COLLECTION AND ANALYSIS: Two review authors independently extracted data and assessed trial quality. MAIN RESULTS: We included seven trials involving 447 infants younger than two years with respiratory distress secondary to viral bronchiolitis. All children were recruited from a paediatric intensive care unit (PICU; 378 infants), except in one trial (emergency department; 69 infants). All children were younger than two (under nine months in two trials and under three months in one trial). Positive tests for respiratory syncytial virus (RSV) were required for inclusion in five trials. The two other trials were carried out in the bronchiolitis seasons. Seven different protocols were used for inhalation therapy with heliox.When heliox was used in the PICU, we observed no significant reduction in the rate of intubation: risk ratio (RR) 2.73 (95% confidence interval (CI) 0.96 to 7.75, four trials, 408 infants, low quality evidence). When heliox inhalation was used in the emergency department, we observed no increase in the rate of discharge: RR 0.51 (95% CI 0.17 to 1.55, one trial, 69 infants, moderate quality evidence).There was no decrease in the length of treatment for respiratory distress: mean difference (MD) -0.19 days (95% CI -0.56 to 0.19, two trials, 320 infants, moderate quality evidence). However, in the subgroup of infants who were started on nasal continuous positive airway pressure (nCPAP) right from the start, because of severe respiratory distress, heliox therapy reduced the length of treatment: MD -0.76 days (95% CI -1.45 to -0.08, one trial, 21 infants, low quality evidence). No adverse events related to heliox inhalation were reported.We found that infants treated with heliox inhalation had a significantly lower mean clinical respiratory score in the first hour after starting treatment when compared to those treated with air or oxygen inhalation: MD -1.04 (95% CI -1.60 to -0.48, four trials, 138 infants, moderate quality evidence). This outcome had statistical heterogeneity, which remained even after removing the study using a standard high-concentration reservoir mask. Several factors may explain this heterogeneity, including first the limited number of patients in each trial, and the wide differences in the baseline severity of disease between studies, with the modified Wood Clinical Asthma Score (m-WCAS) in infants treated with heliox ranging from less than two to more than seven. AUTHORS' CONCLUSIONS: Current evidence suggests that the addition of heliox therapy may significantly reduce a clinical score evaluating respiratory distress in the first hour after starting treatment in infants with acute RSV bronchiolitis. We noticed this beneficial effect regardless of which heliox inhalation protocol was used. Nevertheless, there was no reduction in the rate of intubation, in the rate of emergency department discharge, or in the length of treatment for respiratory distress. Heliox could reduce the length of treatment in infants requiring CPAP for severe respiratory distress. Further studies with homogeneous logistics in their heliox application are needed. Inclusion criteria must include a clinical severity score that reflects severe respiratory distress to avoid inclusion of children with mild bronchiolitis who may not benefit from heliox inhalation. Such studies would provide the necessary information as to the appropriate place for heliox in the therapeutic schedule for severe bronchiolitis.

Clinical Outcomes Associated With RBC Transfusions in Critically Ill Children: A 1-Year Prospective Study.

OBJECTIVE: To identify the potential complications associated with RBC transfusions. DESIGN: Prospective observational study. SETTING: PICU in a tertiary children's hospital. PATIENTS: All children consecutively admitted to our PICU during a 1-year period. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Data were abstracted from medical charts prospectively. Outcomes possibly attributable to RBC transfusions were looked for daily. In transfused cases, it was considered that an outcome was associated with a transfusion only if it was observed after the first RBC transfusion. During the 1-year study period, 913 consecutive admissions were documented, 842 of which were included. Among them, 144 (17%) were transfused at least once. When comparing transfused cases with nontransfused cases, the odds ratio for new or progressive multiple organ dysfunction syndrome was 5.14 (95% CI, 3.28-8.06; p < 0.001). This association remained statistically significant in the multivariable analysis (odds ratio, 3.85; 95% CI, 2.38-6.24; p < 0.001). Transfused cases were ventilated longer than nontransfused cases (14.1 ± 32.6 vs 4.3 ± 9.6 d, p < 0.001), even after adjustment in a Cox model. The PICU length of stay was significantly increased for transfused cases (12.4 ± 26.2 vs 4.9 ± 10.2 d, p < 0.001), even after controlling for potential confounders. The paired analysis for comparison of pretransfusion and posttransfusion values showed that the arterial partial pressure in oxygen was significantly reduced within the 6 hours after the first RBC transfusion (mean difference, 25.6 torr, 95% CI, 5.7-45.4; p = 0.029). The paired analysis also showed an increased proportion of renal replacement therapy. CONCLUSIONS: RBC transfusions in critically ill children were associated with prolonged mechanical ventilation and prolonged PICU stay. The risk of new or progressive multiple organ dysfunction syndrome was also increased in some transfused children. Furthermore, our study questions the ability of stored RBCs to improve oxygenation in critically ill children. Practitioners should take into account these data when prescribing an RBC transfusion to PICU patients.

Respiratory Dysfunction Associated With RBC Transfusion in Critically Ill Children: A Prospective Cohort Study.

OBJECTIVE: Respiratory complications associated with RBC transfusions may be underestimated in PICUs because current definitions exclude patients with preexisting respiratory dysfunction. This study aims to determine the prevalence and characterize the risk factors and outcomes of new or progressive respiratory dysfunction observed after RBC transfusion in critically ill children. DESIGN: Prospective cohort study of all children admitted over a 1-year period. SETTING: A multidisciplinary PICU in a tertiary pediatric university hospital. PATIENTS: Patients who received a RBC transfusion while in PICU. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Two independent adjudicators established the diagnosis of respiratory dysfunction. A respiratory dysfunction associated with transfusion was considered new if it appeared after the first RBC transfusion in PICU. A progressive respiratory dysfunction associated with transfusion was diagnosed if the respiratory dysfunction was present before the transfusion and the PaO2/FIO2 or the SpO2/FIO2 ratio dropped by at least 20% thereafter. Among 842 children admitted into the PICU, 136 received at least one RBC transfusion and were analyzed. Fifty-eight cases of respiratory dysfunction associated with transfusion (43% of transfused patients) were detected, including nine new respiratory dysfunction associated with transfusion (7%) and 49 progressive respiratory dysfunction associated with transfusion (36%). Higher severity of illness, multiple organ dysfunction syndrome prior to transfusion, and volume (mL/kg) of RBC transfusion were independently associated with respiratory dysfunction associated with transfusion. A dose-response relationship was observed between transfusion volume (mL/kg) and the prevalence of respiratory dysfunction associated with transfusion. Patients with respiratory dysfunction associated with transfusion had more progressive multiple organ dysfunction and less ventilation-free and PICU-free days at day 28. CONCLUSIONS: Development of respiratory dysfunction associated with transfusion is frequent in PICU and occurs mainly in patients with prior respiratory dysfunction, who would not be identified using current definitions for transfusion-associated complications. A cause-effect relationship cannot be confirmed. However, the high prevalence and the serious adverse outcomes associated with respiratory dysfunction associated with transfusion suggest that this complication should be further studied.

Red blood cell transfusion in critically ill children (CME).

BACKGROUND: Red blood cell (RBC) transfusions are common in the pediatric intensive care unit (PICU). However, there are no recent data on transfusion practices in the PICU. Our objective was to determine transfusion practice in the PICU, to compare this practice with that observed 10 years earlier, and to estimate the compliance to the recommendation of a large randomized clinical trial, the Transfusion Requirements in Pediatric Intensive Care Unit (TRIPICU) study. STUDY DESIGN AND METHODS: This was a single-center prospective observational study over a 1-year period. Information was abstracted from medical charts. Determinants of transfusion were searched for daily until the first transfusion in transfused cases or until PICU discharge in nontransfused cases. The justifications for transfusions were assessed using a questionnaire. RESULTS: Of 913 consecutive admissions, 842 were included. At least one RBC transfusion was given in 144 patients (17.1%). The mean hemoglobin (Hb) level before the first transfusion was 77.3 ± 27.2 g/L. The determinants of a first transfusion event retained in the multivariate analysis were young age (<12 months), congenital cardiopathy, lowest Hb level of not more than 70 g/L, severity of illness, and some organ dysfunctions. The three most frequently quoted justifications for RBC transfusion were a low Hb level, intent to improve oxygen delivery, and hemodynamic instability. The main recommendation of the TRIPICU study was applied in 96.4% of the first transfusion events. CONCLUSIONS: RBC transfusions are frequent in the PICU. Young age, congenital heart disease, low Hb level, severity of illness, and some organ dysfunctions are significant determinants of RBC transfusions in the PICU. Most first transfusion events were prescribed according to recent recommendations.

Impact of maternal HIV-1 viremia on lymphocyte subsets among HIV-exposed uninfected infants: protective mechanism or immunodeficiency.

BACKGROUND: Reports of increased morbidity and mortality from infectious diseases among HIV Exposed Uninfected (HEU) infants have raised concern about a possible underlying immunodeficiency among them. The objective of this study was to assess the immunological profile of HEU infants born to mothers exhibiting different levels of HIV-1 viremia at the time of delivery. METHODS: Study subjects were enrolled in the Centre maternel et infantile sur le SIDA (CMIS) mother-child cohort between 1997 and 2010 (n =585). Infant CD4+ T cell, CD8+ T cell and CD19+ B cell counts were assessed at 2 and 6 months of age, and compared among HEU infants in groups defined by maternal viral load (VL) at the time of delivery (VL < 50 copies/ml, VL 50-1000 copies/ml, and VL > 1000 copies/ml) in a multivariable analysis. RESULTS: At 2 months of age, infants born to mothers with VL > 1000 copies/ml had lower CD4+ T cell counts compared to those born to mothers with VL < 50 copies/ml at the time of delivery (44.3% versus 48.3%, p = 0.007, and 2884 vs. 2432 cells/mm3, p = 0.02). These differences remained significant after adjusting for maternal and infant antiretroviral drug use, gender, race and gestational age, and persisted at 6 months of age. There were no differences in CD8+ T cell count or absolute CD19+ B cell count between groups, though higher CD19+ B cell percentage was seen among infants born to mothers with VL > 1000 copies/ml. CONCLUSIONS: These results suggest that exposure to high levels of HIV-1 viremia in utero, even in the absence of perinatal transmission, may affect the infant's developing immune system. While further work needs to be done to confirm these findings, they reinforce the need for optimal treatment of HIV infected pregnant women, and careful follow-up of HEU infants.

Survey on stated transfusion practices in PICUs*.

OBJECTIVES: To analyze the RBC transfusion practice patterns among pediatric intensivists in light of the new evidence advocating for a restrictive transfusion strategy. DESIGN: Self-administered questionnaire. SETTING: PICUs. SUBJECTS: Intensivists and fellows in pediatric critical care medicine. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Scenario-based survey carried out among North American and European intensivists, working in tertiary-care PICUs. Respondents were asked to report their decisions with regard to RBC transfusion in stable critically ill children with bronchiolitis, septic shock, trauma, or tetralogy of Fallot repair scenarios. Answers were compared with those of a similar scenario-based survey administered to pediatric intensivists in 1997. Ninety-seven respondents were retained for the study, the majority from the United States, Canada, and France. In 2010, respondents reported that the mean (± SD) transfusion threshold was a hemoglobin level of 7.7 ± 1.0 g/dL for bronchiolitis, 8.1 ± 1.2 g/dL for trauma, 9.1 ± 1.2 g/dL for a tetralogy of Fallot repair, and 9.2 ± 1.0 g/dL for septic shock. For all clinical scenarios, there was a trend toward a more restrictive transfusion approach (a threshold ≤ 7 g/dL) in 2010 compared with 1997: a restrictive strategy was adopted by 55.7% of respondents in 2010 versus 37.0% in 1997 (p = 0.01) with the scenario of bronchiolitis, 8.3% versus 3.4% (p = 0.16) with septic shock, 38.1% versus 9.0% (p < 0.001) with trauma, and 16.0% versus 7.9% (p = 0.10) with tetralogy of Fallot repair. CONCLUSIONS: Stated transfusion practice patterns of pediatric intensivists appear to be evolving toward a more restrictive approach two and a half years after the publication of the Transfusion Requirement in PICU trial. Incomplete implementation of new knowledge with regard to the safety of a restrictive transfusion approach in stable PICU patients is perplexing and requires further studies.