Oliver Karam

Association between length of storage of transfused red blood cells and multiple organ dysfunction syndrome in pediatric intensive care patients

BACKGROUND: The objective was to determine if there is an association between red blood cell (RBC) storage time and development of new or progressive multiple organ dysfunction syndrome (MODS) in critically ill children.

Association between length of storage of red blood cell units and outcome of critically ill children: a prospective observational study

IntroductionTransfusion is a common treatment in pediatric intensive care units (PICUs). Studies in adults suggest that prolonged storage of red blood cell units is associated with worse clinical outcome. No prospective study has been conducted in children. Our objectives were to assess the clinical impact of the length of storage of red blood cell units on clinical outcome of critically ill children.MethodsProspective, observational study conducted in 30 North American centers, in consecutive patients aged <18 years with a stay ≥ 48 hours in a PICU. The primary outcome measure was the incidence of multiple organ dysfunction syndrome after transfusion. The secondary outcomes were 28-day mortality and PICU length of stay. Odds ratios were adjusted for gender, age, number of organ dysfunctions at admission, total number of transfusions, and total dose of transfusion, using a multiple logistic regression model.ResultsThe median length of storage was 14 days in 296 patients with documented length of storage. For patients receiving blood stored ≥ 14 days, the adjusted odds ratio for an increased incidence of multiple organ dysfunction syndrome was 1.87 (95% CI 1.04;3.27, P = 0.03). There was also a significant difference in the total PICU length of stay (adjusted median difference +3.7 days, P < 0.001) and no significant change in mortality.ConclusionsIn critically ill children, transfusion of red blood cell units stored for ≥ 14 days is independently associated with an increased occurrence of multiple organ dysfunction syndrome and prolonged PICU stay.

Red blood cell transfusion thresholds in pediatric patients with sepsis.

Objectives: In children with severe sepsis or septic shock, the optimal red blood cell transfusion threshold is unknown. We analyzed the subgroup of patients with sepsis and transfusion requirements in a pediatric intensive care unit study to determine the impact of a restrictive vs. liberal transfusion strategy on clinical outcome. Design: Subgroup analysis of a prospective, multicenter, randomized, controlled trial. Setting: Multicenter pediatric critical care units. Patients: Stabilized critically ill children (mean systemic arterial pressure >2 sd below normal mean for age and cardiovascular support not increased for at least 2 hrs before enrollment) with a hemoglobin ≤9.5 g/dL within 7 days after pediatric critical care unit admission. Interventions: One hundred thirty-seven stabilized critically ill children with sepsis were randomized to receive red blood cell transfusion if their hemoglobin decreased to either <7.0 g/dL (restrictive group) or 9.5 g/dL (liberal group). Measurements and Main Results: In the restrictive group (69 patients), 30 patients did not receive any red blood cell transfusion, whereas only one patient in the liberal group (68 patients) never underwent transfusion (p < .01). No clinically significant differences were found for the occurrence of new or progressive multiple organ dysfunction syndrome (18.8% vs. 19.1%; p = .97), for pediatric critical care unit length of stay (p = .74), or for pediatric critical care unit mortality (p = .44) in the restrictive vs. liberal group. Conclusions: In this subgroup analysis of children with stable sepsis, we found no evidence that a restrictive red cell transfusion strategy, as compared to a liberal one, increased the rate of new or progressive multiple organ dysfunction syndromes. Furthermore, a restrictive transfusion threshold significantly reduced exposure to blood products. Our data suggest that a hemoglobin level of 7.0 g/dL may be safe stabilized for children with sepsis, but further studies are required to support this recommendation.

Length of storage and in vitro immunomodulation induced by prestorage leukoreduced red blood cells

BACKGROUND: The relationship between length of storage of red blood cell (RBC) units and biochemical changes has been well studied, but little is known about the progression of cellular immunomodulative properties in blood recipients. This study aims to quantify in vitro T‐cell activation and cytokine release by white blood cells, after incubation with supernatants from leukoreduced RBCs.

Patient-ventilator asynchrony during noninvasive pressure support ventilation and neurally adjusted ventilatory assist in infants and children.

Objectives: To document the prevalence of asynchrony events during noninvasive ventilation in pressure support in infants and in children and to compare the results with neurally adjusted ventilatory assist. Design: Prospective randomized cross-over study in children undergoing noninvasive ventilation. Setting: The study was performed in a PICU. Patients: From 4 weeks to 5 years. Interventions: Two consecutive ventilation periods (pressure support and neurally adjusted ventilatory assist) were applied in random order. During pressure support (PS), three levels of expiratory trigger (ETS) setting were compared: initial ETS (PSinit), and ETS value decreased and increased by 15%. Of the three sessions, the period allowing for the lowest number of asynchrony events was defined as PSbest. Neurally adjusted ventilator assist level was adjusted to match the maximum airway pressure during PSinit. Positive end-expiratory pressure was the same during pressure support and neurally adjusted ventilator assist. Asynchrony events, trigger delay, and cycling-off delay were quantified for each period. Results: Six infants and children were studied. Trigger delay was lower with neurally adjusted ventilator assist versus PSinit and PSbest (61 ms [56–79] vs 149 ms [134–180] and 146 ms [101–162]; p = 0.001 and 0.02, respectively). Inspiratory time in excess showed a trend to be shorter during pressure support versus neurally adjusted ventilator assist. Main asynchrony events during PSinit were autotriggering (4.8/min [1.7–12]), ineffective efforts (9.9/min [1.7–18]), and premature cycling (6.3/min [3.2–18.7]). Premature cycling (3.4/min [1.1–7.7]) was less frequent during PSbest versus PSinit (p = 0.059). The asynchrony index was significantly lower during PSbest versus PSinit (40% [28–65] vs 65.5% [42–76], p < 0.001). With neurally adjusted ventilator assist, all types of asynchronies except double triggering were reduced. The asynchrony index was lower with neurally adjusted ventilator assist (2.3% [0.7–5] vs PSinit and PSbest, p < 0.05 for both comparisons). Conclusion: Asynchrony events are frequent during noninvasive ventilation with pressure support in infants and in children despite adjusting the cycling-off criterion. Compared with pressure support, neurally adjusted ventilator assist allows improving patient–ventilator synchrony by reducing trigger delay and the number of asynchrony events. Further studies should determine the clinical impact of these findings.

Association between plasma transfusions and clinical outcome in critically ill children: a prospective observational study

Plasma transfusions are commonly used in adult and paediatric intensive care units. Recent data suggest an association between plasma transfusions and worse clinical outcome in adult trauma patients. To date, no prospective paediatric study has addressed this issue. Our objective was to prospectively analyse the association between plasma transfusions and clinical outcome of critically ill children.

Optimizing patient-ventilator synchrony during invasive ventilator assist in children and infants remains a difficult task

Objectives: To document and compare the prevalence of asynchrony events during invasive-assisted mechanical ventilation in pressure support mode and in neurally adjusted ventilatory assist in children. Design: Prospective, randomized, and crossover study. Setting: Pediatric and Neonatal Intensive Care Unit, University Hospital of Geneva, Switzerland. Patients: Intubated and mechanically ventilated children, between 4 weeks and 5 years old. Interventions: Two consecutive ventilation periods (pressure support and neurally adjusted ventilatory assist) were applied in random order. During pressure support, three levels of expiratory trigger setting were compared: expiratory trigger setting as set by the clinician in charge (PSinit), followed by a 10% (in absolute values) increase and decrease of the clinician’s expiratory trigger setting. The pressure support session with the least number of asynchrony events was defined as PSbest. Therefore, three periods were compared: PSinit, PSbest, and neurally adjusted ventilatory assist. Asynchrony events, trigger delay, and inspiratory time in excess were quantified for each of them. Measurements and Main Results: Data from 19 children were analyzed. Main asynchrony events during PSinit were autotriggering (3.6 events/min [0.7–8.2]), ineffective efforts (1.2/min [0.6–5]), and premature cycling (3.5/min [1.3–4.9]). Their number was significantly reduced with PSbest: autotriggering 1.6/min (0.2–4.9), ineffective efforts 0.7/min (0–2.6), and premature cycling 2/min (0.1–3.1), p < 0.005 for each comparison. The median asynchrony index (total number of asynchronies/triggered and not triggered breaths ×100) was significantly different between PSinit and PSbest: 37.3% [19–47%] and 29% [24–43%], respectively, p < 0.005). With neurally adjusted ventilatory assist, all types of asynchrony events except double-triggering and inspiratory time in excess were significantly reduced resulting in an asynchrony index of 3.8% (2.4–15%) (p < 0.005 compared to PSbest). Conclusions: Asynchrony events are frequent during pressure support in children despite adjusting the cycling off criteria. Neurally adjusted ventilatory assist allowed for an almost ten-fold reduction in asynchrony events. Further studies should determine the clinical impact of these findings.

Blunt Abdominal Trauma in Children: A Score to Predict the Absence of Organ Injury

OBJECTIVES To evaluate the initial workup and design a score that would allow ruling out significant intra-abdominal organ injuries following blunt abdominal traumas (BAT). STUDY DESIGN Data were collected prospectively from 147 consecutive patients admitted for BAT in a tertiary care hospital, over a 30-month period. RESULTS Statistical significance of various parameters (trauma mechanism, clinical examination, laboratory tests, and ultrasound findings) were analyzed in relation to intra-abdominal injuries. The 10 parameters with the best negative predictive values (NPV) were then used to build a score (BATiC). The following points were attributed for these items: abnormal abdominal Doppler ultrasound (4 points), abdominal pain (2 points), peritoneal irritation (2 points), hemodynamic instability (2 points), aspartate aminotransferase >60 IU/L (2 points), alanine aminotransferase >25 IU/L (2 points), white blood cell count >9.5 g/L (1 point), LDH >330 IU/L (1 point), lipase >30 IU/L (1 point), and creatinine >50 microg/L (1 point). A score of < or = 7 has a NPV of 97% and includes 67% of the studied population. CONCLUSIONS These results suggest that in hemodynamically stable patients with a normal abdominal Doppler ultrasound and a BATiC score of < or = 7, intra-abdominal lesions are very unlikely, and systematic CT scan or hospital admission may be avoided.

Indications and Effects of Plasma Transfusions in Critically Ill Children

RATIONALE Plasma transfusions are frequently prescribed for critically ill children, although their indications lack a strong evidence base. Plasma transfusions are largely driven by physician conceptions of need, and these are poorly documented in pediatric intensive care patients. OBJECTIVES To identify patient characteristics and to characterize indications leading to plasma transfusions in critically ill children, and to assess the effect of plasma transfusions on coagulation tests. METHODS Point-prevalence study in 101 pediatric intensive care units in 21 countries, on 6 predefined weeks. All critically ill children admitted to a participating unit were included if they received at least one plasma transfusion. MEASUREMENTS AND MAIN RESULTS During the 6 study weeks, 13,192 children were eligible. Among these, 443 (3.4%) received at least one plasma transfusion and were included. The primary indications for plasma transfusion were critical bleeding in 22.3%, minor bleeding in 21.2%, planned surgery or procedure in 11.7%, and high risk of postoperative bleeding in 10.6%. No bleeding or planned procedures were reported in 34.1%. Before plasma transfusion, the median international normalized ratio (INR) and activated partial thromboplastin time (aPTT) values were 1.5 and 48, respectively. After plasma transfusion, the median INR and aPTT changes were -0.2 and -5, respectively. Plasma transfusion significantly improved INR only in patients with a baseline INR greater than 2.5. CONCLUSIONS One-third of transfused patients were not bleeding and had no planned procedure. In addition, in most patients, coagulation tests are not sensitive to increases in coagulation factors resulting from plasma transfusion. Studies assessing appropriate plasma transfusion strategies are urgently needed.

Unilateral focal polymicrogyria in a patient with classical Aarskog–Scott syndrome due to a novel missense mutation in an evolutionary conserved RhoGEF domain of the faciogenital dysplasia gene FGD1†

Faciogenital dysplasia or Aarskog–Scott syndrome (AAS) is an X‐linked disorder characterized by craniofacial, skeletal, and urogenital malformations and short stature. Mutations in the only known causative gene FGD1 are found in about one‐fifth of the cases with the clinical diagnosis of AAS. FGD1 is a guanine nucleotide exchange factor (GEF) that specifically activates the Rho GTPase Cdc42 via its RhoGEF domain. The Cdc42 pathway is involved in skeletal formation and multiple aspects of neuronal development. We describe a boy with typical AAS and, in addition, unilateral focal polymicrogyria (PMG), a feature hitherto unreported in AAS. Sequencing of the FGD1 gene in the index case and his mother revealed the presence of a novel mutation (1396A>G; M466V), located in the evolutionary conserved α‐helix 4 of the RhoGEF domain. M466V was not found in healthy family members, in >300 healthy controls and AAS patients, and has not been reported in the literature or mutation databases to date, indicating that this novel missense mutation causes AAS, and possibly PMG. Brain cortex malformations such as PMG could be initiated by mutations in the evolutionary conserved RhoGEF domain of FGD1, by perturbing the signaling via Rho GTPases such as Cdc42 known to cause brain malformation.