Marisa Tucci

Hypothermia Therapy After Pediatric Cardiac Arrest

Background— Hypothermia therapy improves mortality and functional outcome after cardiac arrest and birth asphyxia in adults and newborns. The effect of hypothermia therapy in infants and children with cardiac arrest is unknown. Methods and Results— A 2-year, retrospective, 5-center study was conducted, and 222 patients with cardiac arrest were identified. Seventy-nine (35.6%) of these patients met eligibility criteria for the study (age >40 weeks postconception and <18 years, cardiac arrest >3 minutes in duration, survival for ≥12 hours after return of circulation, and no birth asphyxia). Twenty-nine (36.7%) of these 79 patients received hypothermia therapy and were cooled to 33.7±1.3°C for 20.8±11.9 hours. Hypothermia therapy was associated with higher mortality (P=0.009), greater duration of cardiac arrest (P=0.005), more resuscitative interventions (P<0.001), higher postresuscitation lactate levels (P<0.001), and use of extracorporeal membrane oxygenation (P<0.001). When adjustment was made for duration of cardiac arrest, use of extracorporeal membrane oxygenation, and propensity scores by use of a logistic regression model, no statistically significant differences in mortality were found (P=0.502) between patients treated with hypothermia therapy and those treated with normothermia. Also, no differences in hypothermia-related adverse events were found between groups. Conclusions— Hypothermia therapy was used in resuscitation scenarios that are associated with greater risk of poor outcome. In an adjusted analysis, the effectiveness of hypothermia therapy was neither supported nor refuted. A randomized controlled trial is needed to rigorously evaluate the benefits and harms of hypothermia therapy after pediatric cardiac arrest.

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.

Comparison of two red-cell transfusion strategies after pediatric cardiac surgery: a subgroup analysis.

Objective: To determine the impact of a restrictive vs. a liberal transfusion strategy on new or progressive multiple organ dysfunction syndrome in children post cardiac surgery. The optimal transfusion threshold after cardiac surgery in children is unknown. Design: Randomized, controlled trial. Setting: Tertiary pediatric intensive care units. Patients: Participants are a subgroup of pediatric patients post cardiac surgery from the TRIPICU (Transfusion Requirements in Pediatric Intensive Care Units) study. Exclusion criteria specific to the cardiac surgery subgroup included: age <28 days and patients remaining cyanotic. Intervention: Critically ill children with a hemoglobin ≤95 g/L within 7 days of pediatric intensive care unit admission were randomized to receive prestorage leukocyte-reduced red-cell transfusion if their hemoglobin dropped either <70 g/L (restrictive) or 95 g/L (liberal). Measurements and Main Results: Postoperative cardiac patients (n = 125) from seven centers were enrolled. The restrictive (n = 63) and liberal (n = 62) groups were similar at baseline in age (mean ± standard deviation = 31.4 ± 38.1 mos vs. 26.4 ± 39.1 mos), surgical procedure, severity of illness (Pediatric Risk of Mortality score = 3.4 ± 3.2 vs. 3.2 ± 3.2), multiple organ dysfunction syndrome (46% vs. 44%), mechanical ventilation (62% vs. 60%), and hemoglobin (83 vs. 80 g/L). Mean hemoglobin remained 21 g/L lower in the restrictive group after randomization. No significant difference was found in new or progressive multiple organ dysfunction syndrome (primary outcome) in the restrictive group vs. liberal group (12.7% vs. 6.5%; p = .36), pediatric intensive care unit length of stay (7.0 ± 5.0 days vs. 7.4 ± 6.4 days) or 28-day mortality (3.2% vs. 3.2%). Conclusion: In this subgroup analysis of cardiac surgery patients, a restrictive red-cell transfusion strategy, as compared with a liberal one, was not associated with any significant difference in new or progressive multiple organ dysfunction syndrome, but this evidence is not definitive.

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 threshold in postsurgical pediatric intensive care patients: a randomized clinical trial.

Background:The optimal transfusion threshold after surgery in children is unknown. We analyzed the general surgery subgroup of the TRIPICU (Transfusion Requirements in Pediatric Intensive Care Units) study to determine the impact of a restrictive versus a liberal transfusion strategy on new or progressive multiple organ dysfunction syndrome (MODS). Methods:The TRIPICU study, a prospective randomized controlled trial conducted in 17 centers, enrolled a total of 648 critically ill children with a hemoglobin equal to or below 9.5 g/dL within 7 days of pediatric intensive care unit (PICU) admission to receive prestorage leukocyte-reduced red-cell transfusion if their hemoglobin dropped below either 7.0 g/dL (restrictive) or 9.5 g/dL (liberal). A subgroup of 124 postoperative patients (60 randomized to restrictive and 64 to the liberal group) were analyzed. This study was registered at http://www.controlled-trials.com and carries the following ID ISRCTN37246456. Results:Participants in the restrictive and liberal groups were similar at randomization in age (restrictive vs. liberal: 53.5 ± 51.8 vs. 73.7 ± 61.8 months), severity of illness (pediatric risk of mortality [PRISM] score: 3.5 ± 4.0 vs. 4.4 ± 4.0), MODS (35% vs. 29%), need for mechanical ventilation (77% vs. 74%), and hemoglobin level (7.7 ± 1.1 vs. 7.9 ± 1.0 g/dL). The mean hemoglobin level remained 2.3 g/dL lower in the restrictive group after randomization. No significant differences were found for new or progressive MODS (8% vs. 9%; P = 0.83) or for 28-day mortality (2% vs. 2%; P = 0.96) in the restrictive versus liberal group. However, there was a statistically significant difference between groups for PICU length of stay (7.7 ± 6.6 days for the restrictive group vs. 11.6 ± 10.2 days for the liberal group; P = 0.03). Conclusions:In this subgroup analysis of pediatric general surgery patients, we found no conclusive evidence that a restrictive red-cell transfusion strategy, as compared with a liberal one, increased the rate of new or progressive MODS or mortality.

Prolonged neural expiratory time induced by mechanical ventilation in infants.

Mechanical ventilation may interfere with the spontaneous breathing pattern in infants because they have strong reflexes that play a large role in the control of breathing. This study aimed to answer the following questions: does a ventilator-assisted breath 1) reduce neural inspiratory time, 2) reduce the amplitude of the diaphragm electrical activity, and 3) prolong neural expiration, within the delivered breath? In 14 infants recovering from acute respiratory failure (mean age and weight were 2.3 ± 1.3 mo and 3.95 ± 0.82 kg, respectively), we measured 1) the electrical activity of the diaphragm with a multiple-array esophageal electrode, and 2) airway opening pressure, while patients breathed on synchronized intermittent mandatory ventilation (mean rate, 11.2 ± 6.5 breaths/min). We compared neural inspiratory and expiratory times for the mandatory breaths and for the spontaneous breaths immediately preceding and following the mandatory breath. Although neural inspiratory time was not different between mandatory and spontaneous breaths, neural expiratory time was significantly increased (p < 0.001) for the mandatory breaths (953 ± 449 ms) compared with the premandatory and postmandatory spontaneous breaths (607 ± 268 ms and 560 ± 227 ms, respectively). Delivery of the mandatory breath resulted in a reduction in neural respiratory frequency by 28.6 ± 6.4% from the spontaneous premandatory frequency. The magnitude of inspiratory electrical activity of the diaphragm was similar for all three breath conditions. For the mandatory breaths, ventilatory assist persisted for 507 ± 169 ms after the end of neural inspiratory time. Infant–ventilator asynchrony (both inspiratory and expiratory asynchrony) was present in every mandatory breath and constituted 53.4 ± 26.2% of the total breath duration.

Diaphragm Electrical Activity During Expiration in Mechanically Ventilated Infants

The presence of diaphragm electrical activity (EAdi) during expiration is believed to be involved in the maintenance of end-expiratory lung volume (EELV) and has never been studied in intubated and mechanically ventilated infants. The aim of this study was to quantify the amplitude of diaphragm electrical activity present during expiration in mechanically ventilated infants and to measure the impact of removing positive end-expiratory pressure (PEEP) on this activity. We studied the EAdi in 16 ready-to-be weaned intubated infants who were breathing on their prescribed ventilator and PEEP settings. In all 16 patients, 5 min of data were collected on the prescribed ventilator settings. In a subset of eight patients, the PEEP was briefly reduced to zero PEEP (ZEEP). EAdi was recorded with miniaturized sensors placed on a conventional nasogastric feeding tube. Airway pressure (Paw) was also measured. For each spontaneous breath, we identified the neural inspiration and neural expiration. Neural expiration was divided into quartiles (Q1, Q2, Q3, and Q4), and the amplitude of EAdi calculated for each Q1–Q4 represented 95 ± 29%, 31 ± 15%, 15 ± 8%, and 12 ± 7%, respectively, of the inspiratory EAdi amplitude. EAdi for Q3–Q4 significantly increased during ZEEP, and decreased after reapplication of PEEP. These findings confirm that the diaphragm remains partially active during expiration in intubated and mechanically ventilated infants and that removal of PEEP affects this tonic activity. This could have potential implications on the management of PEEP in intubated infants.

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.

Survey of transfusion policies at US and Canadian children's hospitals in 2008 and 2009.

BACKGROUND: Previous surveys have reported variation in transfusion practice or policies in specific pediatric populations. Our objective was to determine the current transfusion policies in US and Canadian childrens hospitals for both neonatal and pediatric general populations.

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.