Intermittent intravenous paracetamol versus continuous morphine in infants undergoing cardiothoracic surgery: a multi-center randomized controlled trial.

BACKGROUND: To determine whether intermittent intravenous (IV) paracetamol as primary analgesic would significantly reduce morphine consumption in children aged 0-3 years after cardiac surgery with cardiopulmonary bypass. METHODS: Multi-center, randomized, double-blinded, controlled trial in four level-3 Pediatric Intensive Care Units (PICU) in the Netherlands and Belgium. Inclusion period; March 2016-July 2020. Children aged 0-3 years, undergoing cardiac surgery with cardiopulmonary bypass were eligible. Patients were randomized to continuous morphine or intermittent IV paracetamol as primary analgesic after a loading dose of 100 mcg/kg morphine was administered at the end of surgery. Rescue morphine was given if numeric rating scale (NRS) pain scores exceeded predetermined cutoff values. Primary outcome was median weight-adjusted cumulative morphine dose in mcg/kg in the first 48 h postoperative. For the comparison of the primary outcome between groups, the nonparametric Van Elteren test with stratification by center was used. For comparison of the proportion of patients with one or more NRS pain scores of 4 and higher between the two groups, a non-inferiority analysis was performed using a non-inferiority margin of 20%. RESULTS: In total, 828 were screened and finally 208 patients were included; parents of 315 patients did not give consent and 305 were excluded for various reasons. Fourteen of the enrolled 208 children were withdrawn from the study before start of study medication leaving 194 patients for final analysis. One hundred and two patients received intermittent IV paracetamol, 106 received continuous morphine. The median weight-adjusted cumulative morphine consumption in the first 48 h postoperative in the IV paracetamol group was 5 times lower (79%) than that in the morphine group (median, 145.0 (IQR, 115.0-432.5) mcg/kg vs 692.6 (IQR, 532.7-856.1) mcg/kg; P < 0.001). The rescue morphine consumption was similar between the groups (p = 0.38). Non-inferiority of IV paracetamol administration in terms of NRS pain scores was proven; difference in proportion - 3.1% (95% CI - 16.6-10.3%). CONCLUSIONS: In children aged 0-3 years undergoing cardiac surgery, use of intermittent IV paracetamol reduces the median weight-adjusted cumulative morphine consumption in the first 48 h after surgery by 79% with equal pain relief showing equipoise for IV paracetamol as primary analgesic. Trial Registration Clinicaltrials.gov, Identifier: NCT05853263; EudraCT Number: 2015-001835-20.

Fresh Frozen Plasma Versus Solvent Detergent Plasma for Cardiopulmonary Bypass Priming in Neonates and Infants Undergoing Cardiac Surgery: A Retrospective Cohort Study.

OBJECTIVE: Compared with fresh frozen plasma (FFP), Omniplasma has been attributed to an increased coagulation potential and an increased fibrinolytic potential. This study aimed to compare Omniplasma and FFP used for cardiopulmonary bypass (CPB) priming regarding the incidence of postoperative thrombotic or hemorrhagic complications and outcomes in pediatric patients undergoing cardiac surgery. DESIGN: A retrospective observational cohort study SETTING: This single-center study was performed at the University Medical Center Groningen. PARTICIPANT: All pediatric patients up to 10 kg undergoing cardiac surgery with CPB. INTERVENTIONS: Procedures in which FFP was used for CPB priming were compared with those in which Omniplasma was used. MEASUREMENTS AND MAIN RESULTS: The primary outcome parameter was a composite endpoint consisting of the following: (1) pediatric intensive care unit (PICU) mortality, (2) thromboembolic complications, and (3) hemorrhagic complications during PICU stay. The authors included 143 procedures in the analyses, 90 (63%) in the FFP group and 53 (37%) in the Omniplasma group. The occurrence of the combined primary endpoint (FFP 20% v Omniplasma 11%, p = 0.18) and its components did not differ between the used CPB priming agent). Omniplasma for CPB priming was associated with decreased unfractionated heparin administration per kg bodyweight (585 IU v 510 IU, p = 0.03), higher preoperative and postoperative activated clotting times (ACT) discrepancy (90% v 94%, p = 0.03), a lower postoperative ACT value (125 v 118 seconds, p = 0.01), and less red blood cell transfusion per kilogram bodyweight (78 v 55 mL, p = 0.02). However, none of the variables differed statistically significantly in the multivariate logistic regression analyses. CONCLUSIONS: The authors did not find an association between the plasma used for CPB priming and thromboembolic and hemorrhagic complications and death in neonates and infants undergoing cardiac surgery. Omniplasma seems to be safe to use in this population.

Hemodynamic Effects of a High-Frequency Oscillatory Ventilation Open-Lung Strategy in Critically Ill Children With Acquired or Congenital Cardiac Disease.

OBJECTIVES: To study the hemodynamic consequences of an open-lung high-frequency oscillatory ventilation (HFOV) strategy in patients with an underlying cardiac anomaly with or without intracardiac shunt or primary pulmonary hypertension with severe lung injury. DESIGN: Secondary analysis of prospectively collected data. SETTING: Medical-surgical PICU. PATIENTS: Children less than 18 years old with cardiac anomalies (± intracardiac shunt) or primary pulmonary hypertension. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Data from 52 subjects were analyzed, of whom 39 of 52 with cardiac anomaly (23/39 with intracardiac shunt) and 13 of 52 with primary pulmonary hypertension. Fourteen patients were admitted postoperatively, and 26 patients were admitted with acute respiratory failure. Five subjects (9.6%) were canulated for ECMO (of whom four for worsening respiratory status). Ten patients (19.2%) died during PICU stay. Median conventional mechanical ventilation settings prior to HFOV were peak inspiratory pressure 30 cm H 2 O (27-33 cm H 2 O), positive end-expiratory pressure 8 cm H 2 O (6-10 cm H 2 O), and F io2 0.72 (0.56-0.94). After transitioning to HFOV, there was no negative effect on mean arterial blood pressure, central venous pressure, or arterial lactate. Heart rate decreased significantly over time ( p < 0.0001), without group differences. The percentage of subjects receiving a fluid bolus decreased over time ( p = 0.003), especially in those with primary pulmonary hypertension ( p = 0.0155) and without intracardiac shunt ( p = 0.0328). There were no significant differences in the cumulative number of daily boluses over time. Vasoactive Infusion Score did not increase over time. Pa co2 decreased ( p < 0.0002) and arterial pH significantly improved ( p < 0.0001) over time in the whole cohort. Neuromuscular blocking agents were used in all subjects switched to HFOV. Daily cumulative sedative doses were unchanged, and no clinically apparent barotrauma was found. CONCLUSIONS: No negative hemodynamic consequences occurred with an individualized, physiology-based open-lung HFOV approach in patients with cardiac anomalies or primary pulmonary hypertension suffering from severe lung injury.

Characteristics and Outcome of Children with Wilms Tumor Requiring Intensive Care Admission in First Line Therapy.

Survival rates are excellent for children with Wilms tumor (WT), yet tumor and treatment-related complications may require pediatric intensive care unit (PICU) admission. We assessed the frequency, clinical characteristics, and outcome of children with WT requiring PICU admissions in a multicenter, retrospective study in the Netherlands. Admission reasons of unplanned PICU admissions were described in relation to treatment phase. Unplanned PICU admissions were compared to a control group of no or planned PICU admissions, with regard to patient characteristics and short and long term outcomes. In a multicenter cohort of 175 children with an underlying WT, 50 unplanned PICU admissions were registered in 33 patients. Reasons for admission were diverse and varied per treatment phase. Younger age at diagnosis, intensive chemotherapy regimens, and bilateral tumor surgery were observed in children with unplanned PICU admission versus the other WT patients. Three children required renal replacement therapy, two of which continued dialysis after PICU discharge (both with bilateral disease). Two children died during their PICU stay. During follow-up, hypertension and chronic kidney disease (18.2 vs. 4.2% and 15.2 vs. 0.7%) were more frequently observed in unplanned PICU admitted patients compared to the other patients. No significant differences in cardiac morbidity, relapse, or progression were observed. Almost 20% of children with WT required unplanned PICU admission, with young age and treatment intensity as potential risk factors. Hypertension and renal impairment were frequently observed in these patients, warranting special attention at presentation and during treatment and follow-up.

Paediatric Acute Respiratory Distress Syndrome Neuromuscular Blockade study (PAN-study): a phase IV randomised controlled trial of early neuromuscular blockade in moderate-to-severe paediatric acute respiratory distress syndrome.

BACKGROUND: Paediatric acute respiratory distress syndrome (PARDS) is a manifestation of severe, life-threatening lung injury necessitating mechanical ventilation with mortality rates ranging up to 40-50%. Neuromuscular blockade agents (NMBAs) may be considered to prevent patient self-inflicted lung injury in PARDS patients, but two trials in adults with severe ARDS yielded conflicting results. To date, randomised controlled trials (RCT) examining the effectiveness and efficacy of NMBAs for PARDS are lacking. We hypothesise that using NMBAs for 48 h in paediatric patients younger than 5 years of age with early moderate-to-severe PARDS will lead to at least a 20% reduction in cumulative respiratory morbidity score 12 months after discharge from the paediatric intensive care unit (PICU). METHODS: This is a phase IV, multicentre, randomised, double-blind, placebo-controlled trial performed in level-3 PICUs in the Netherlands. Eligible for inclusion are children younger than 5 years of age requiring invasive mechanical ventilation with positive end-expiratory pressure (PEEP) ≥ 5 cm H2O for moderate-to-severe PARDS occurring within the first 96 h of PICU admission. Patients are randomised to continuous infusion of rocuronium bromide or placebo for 48 h. The primary endpoint is the cumulative respiratory morbidity score 12 months after PICU discharge, adjusted for confounding by age, gestational age, family history of asthma and/or allergy, season in which questionnaire was filled out, day-care and parental smoking. Secondary outcomes include respiratory mechanics, oxygenation and ventilation metrics, pulmonary and systemic inflammation markers, prevalence of critical illness polyneuropathy and myopathy and metrics for patient outcome including ventilator free days at day 28, length of PICU and hospital stay, and mortality DISCUSSION: This is the first paediatric trial evaluating the effects of muscular paralysis in moderate-to-severe PARDS. The proposed study addresses a huge research gap identified by the Paediatric Acute Lung Injury Consensus Collaborative by evaluating practical needs regarding the treatment of PARDS. Paediatric critical care practitioners are inclined to use interventions such as NMBAs in the most critically ill. This liberal use must be weighed against potential side effects. The proposed study will provide much needed scientific support in the decision-making to start NMBAs in moderate-to-severe PARDS. TRIAL REGISTRATION: ClinicalTrials.gov NCT02902055 . Registered on September 15, 2016.

Mechanical power in pediatric acute respiratory distress syndrome: a PARDIE study.

BACKGROUND: Mechanical power is a composite variable for energy transmitted to the respiratory system over time that may better capture risk for ventilator-induced lung injury than individual ventilator management components. We sought to evaluate if mechanical ventilation management with a high mechanical power is associated with fewer ventilator-free days (VFD) in children with pediatric acute respiratory distress syndrome (PARDS). METHODS: Retrospective analysis of a prospective observational international cohort study. RESULTS: There were 306 children from 55 pediatric intensive care units included. High mechanical power was associated with younger age, higher oxygenation index, a comorbid condition of bronchopulmonary dysplasia, higher tidal volume, higher delta pressure (peak inspiratory pressure-positive end-expiratory pressure), and higher respiratory rate. Higher mechanical power was associated with fewer 28-day VFD after controlling for confounding variables (per 0.1 J·min-1·Kg-1 Subdistribution Hazard Ratio (SHR) 0.93 (0.87, 0.98), p = 0.013). Higher mechanical power was not associated with higher intensive care unit mortality in multivariable analysis in the entire cohort (per 0.1 J·min-1·Kg-1 OR 1.12 [0.94, 1.32], p = 0.20). But was associated with higher mortality when excluding children who died due to neurologic reasons (per 0.1 J·min-1·Kg-1 OR 1.22 [1.01, 1.46], p = 0.036). In subgroup analyses by age, the association between higher mechanical power and fewer 28-day VFD remained only in children < 2-years-old (per 0.1 J·min-1·Kg-1 SHR 0.89 (0.82, 0.96), p = 0.005). Younger children were managed with lower tidal volume, higher delta pressure, higher respiratory rate, lower positive end-expiratory pressure, and higher PCO2 than older children. No individual ventilator management component mediated the effect of mechanical power on 28-day VFD. CONCLUSIONS: Higher mechanical power is associated with fewer 28-day VFDs in children with PARDS. This association is strongest in children < 2-years-old in whom there are notable differences in mechanical ventilation management. While further validation is needed, these data highlight that ventilator management is associated with outcome in children with PARDS, and there may be subgroups of children with higher potential benefit from strategies to improve lung-protective ventilation. TAKE HOME MESSAGE: Higher mechanical power is associated with fewer 28-day ventilator-free days in children with pediatric acute respiratory distress syndrome. This association is strongest in children <2-years-old in whom there are notable differences in mechanical ventilation management.

Additional work of breathing from trigger errors in mechanically ventilated children.

BACKGROUND: Patient-ventilator asynchrony is associated with increased morbidity and mortality. A direct causative relationship between Patient-ventilator asynchrony and adverse clinical outcome have yet to be demonstrated. It is hypothesized that during trigger errors excessive pleural pressure swings are generated, contributing to increased work-of-breathing and self-inflicted lung injury. The objective of this study was to determine the additional work-of-breathing and pleural pressure swings caused by trigger errors in mechanically ventilated children. METHODS: Prospective observational study in a tertiary paediatric intensive care unit in an university hospital. Patients ventilated > 24 h and < 18 years old were studied. Patients underwent a 5-min recording of the ventilator flow-time, pressure-time and oesophageal pressure-time scalar. Pressure-time-product calculations were made as a proxy for work-of-breathing. Oesophageal pressure swings, as a surrogate for pleural pressure swings, during trigger errors were determined. RESULTS: Nine-hundred-and-fifty-nine trigger errors in 28 patients were identified. The additional work-of-breathing caused by trigger errors showed great variability among patients. The more asynchronous breaths were present the higher the work-of-breathing of these breaths. A higher spontaneous breath rate led to a lower amount of trigger errors. Patient-ventilator asynchrony was not associated with prolonged duration of mechanical ventilation or paediatric intensive care stay. CONCLUSIONS: The additional work-of-breathing caused by trigger errors in ventilated children can take up to 30-40% of the total work-of-breathing. Trigger errors were less common in patients breathing spontaneously and those able to generate higher pressure-time-product and pressure swings. TRIAL REGISTRATION: Not applicable.

Onset of brain injury in infants with prenatally diagnosed congenital heart disease.

BACKGROUND: The exact onset of brain injury in infants with congenital heart disease (CHD) is unknown. Our aim was, therefore, to assess the association between prenatal Doppler flow patterns, postnatal cerebral oxygenation and short-term neurological outcome. METHODS: Prenatally, we measured pulsatility indices of the middle cerebral (MCA-PI) and umbilical artery (UA-PI) and calculated cerebroplacental ratio (CPR). After birth, cerebral oxygen saturation (rcSO2) and fractional tissue oxygen extraction (FTOE) were assessed during the first 3 days after birth, and during and for 24 hours after every surgical procedure within the first 3 months after birth. Neurological outcome was determined preoperatively and at 3 months of age by assessing general movements and calculating the Motor Optimality Score (MOS). RESULTS: Thirty-six infants were included. MOS at 3 months was associated with MCA-PI (rho 0.41, P = 0.04), UA-PI (rho -0.39, P = 0.047, and CPR (rho 0.50, P = 0.01). Infants with abnormal MOS had lower MCA-PI (P = 0.02) and CPR (P = 0.01) and higher UA-PI at the last measurement (P = 0.03) before birth. In infants with abnormal MOS, rcSO2 tended to be lower during the first 3 days after birth, and FTOE was significantly higher on the second day after birth (P = 0.04). Intraoperative and postoperative rcSO2 and FTOE were not associated with short-term neurological outcome. CONCLUSION: In infants with prenatally diagnosed CHD, the prenatal period may play an important role in developmental outcome. Additional research is needed to clarify the relationship between preoperative, intra-operative and postoperative cerebral oxygenation and developmental outcome in infants with prenatally diagnosed CHD.

Epidemiology and Outcome of Critically Ill Pediatric Cancer and Hematopoietic Stem Cell Transplant Patients Requiring Continuous Renal Replacement Therapy: A Retrospective Nationwide Cohort Study.

OBJECTIVE: Acute kidney injury requiring continuous renal replacement therapy is a serious treatment-related complication in pediatric cancer and hematopoietic stem cell transplant patients. The purpose of this study was to assess epidemiology and outcome of these patients requiring continuous renal replacement therapy in the PICU. DESIGN: A nationwide, multicenter, retrospective, observational study. SETTING: Eight PICUs of a tertiary care hospitals in the Netherlands. PATIENTS: Pediatric cancer and hematopoietic stem cell transplant patients (cancer and noncancer) who received continuous renal replacement therapy from January 2006 to July 2017 in the Netherlands. INTERVENTIONS: None. MEASUREMENT AND MAIN RESULTS: Of 1,927 PICU admissions of pediatric cancer and hematopoietic stem cell transplant patients, 68 of 70 evaluable patients who received continuous renal replacement therapy were included. Raw PICU mortality was 11.2% (216/1,972 admissions). PICU mortality of patients requiring continuous renal replacement therapy was 54.4% (37/68 patients). Fluid overload (odds ratio, 1.08; 95% CI, 1.01-1.17) and need for inotropic support (odds ratio, 6.53; 95% CI, 1.86-23.08) at the start of continuous renal replacement therapy were associated with PICU mortality. Serum creatinine levels increased above 150% of baseline 3 days before the start of continuous renal replacement therapy. Urine production did not reach the critical limit of oliguria. In contrast, body weight (fluid overload) increased already 5 days prior to continuous renal replacement therapy initiation. CONCLUSIONS: PICU mortality of pediatric cancer and hematopoietic stem cell transplant patients requiring continuous renal replacement therapy is sadly high. Fluid overload at the initiation of continuous renal replacement therapy is the most important and earliest predictor of PICU mortality. Our results suggest that the most commonly used criteria of acute kidney injury, that is, serum creatinine and urine production, are not useful as a trigger to initiate continuous renal replacement therapy. This highlights the urgent need for prospective studies to generate recommendations for effective therapeutic interventions at an early phase in this specific patient population.

The effect of pressure support on imposed work of breathing during paediatric extubation readiness testing.

BACKGROUND: Paediatric critical care practitioners often make use of pressure support (PS) to overcome the perceived imposed work of breathing (WOBimp) during an extubation readiness test (ERT). However, no paediatric data are available that shows the necessity of adding of pressure support during such tests. We sought to measure the WOBimp during an ERT with and without added pressure support and to study its clinical correlate. This was a prospective study in spontaneously breathing ventilated children < 18 years undergoing ERT. Using tracheal manometry, WOBimp was calculated by integrating the difference between positive end-expiratory pressure (PEEP) and tracheal pressure (Ptrach) over the measured expiratory tidal volume (VTe) under two paired conditions: continuous positive airway pressure (CPAP) with and without PS. Patients with post-extubation upper airway obstruction were excluded. RESULTS: A total of 112 patients were studied. Median PS during the ERT was 10 cmH2O. WOBimp was significantly higher without PS (median 0.27, IQR 0.20-0.50 J/L) than with added PS (median 0.00, IQR 0.00-0.11 J/L). Although there were statistically significant changes in spontaneous breath rate [32 (23-42) vs. 37 (27-46) breaths/min, p < 0.001] and higher ET-CO2 [5.90 (5.38-6.65) vs. 6.23 (5.55-6.94) kPa, p < 0.001] and expiratory Vt decreased [7.72 (6.66-8.97) vs. 7.08 (5.82-8.08) mL/kg, p < 0.001] in the absence of PS, these changes appeared clinically irrelevant since the Comfort B score remained unaffected [12 (10-13) vs. 12 (10-13), P = 0.987]. Multivariable analysis showed that changes in WOBimp occurred independent of endotracheal tube size. CONCLUSIONS: Withholding PS during ERT does not lead to clinically relevant increases in WOBimp, irrespective of endotracheal tube size.

Consensus Recommendations for RBC Transfusion Practice in Critically Ill Children From the Pediatric Critical Care Transfusion and Anemia Expertise Initiative.

OBJECTIVES: To date, there are no published guidelines to direct RBC transfusion decision-making specifically for critically ill children. We present the recommendations from the Pediatric Critical Care Transfusion and Anemia Expertise Initiative. DESIGN: Consensus conference series of multidisciplinary, international experts in RBC transfusion management of critically ill children. SETTING: Not applicable. INTERVENTION: None. SUBJECTS: Children with, or children at risk for, critical illness who receive or are at risk for receiving a RBC transfusion. METHODS: A panel of 38 content and four methodology experts met over the course of 2 years to develop evidence-based, and when evidence lacking, expert consensus-based recommendations regarding decision-making for RBC transfusion management and research priorities for transfusion in critically ill children. The experts focused on nine specific populations of critically ill children: general, respiratory failure, nonhemorrhagic shock, nonlife-threatening bleeding or hemorrhagic shock, acute brain injury, acquired/congenital heart disease, sickle cell/oncology/transplant, extracorporeal membrane oxygenation/ventricular assist/ renal replacement support, and alternative processing. Data to formulate evidence-based and expert consensus recommendations were selected based on searches of PubMed, EMBASE, and Cochrane Library from 1980 to May 2017. Agreement was obtained using the Research and Development/UCLA Appropriateness Method. Results were summarized using the Grading of Recommendations Assessment, Development, and Evaluation method. MEASUREMENTS AND RESULTS: The Transfusion and Anemia Expertise Initiative consensus conference developed and reached consensus on a total of 102 recommendations (57 clinical [20 evidence based, 37 expert consensus], 45 research recommendations). All final recommendations met agreement, defined a priori as greater than 80%. A decision tree to aid clinicians was created based on the clinical recommendations. CONCLUSIONS: The Transfusion and Anemia Expertise Initiative recommendations provide important clinical guidance and applicable tools to avoid unnecessary RBC transfusions. Research recommendations identify areas of focus for future investigation to improve outcomes and safety for RBC transfusion.

Intravenous morphine versus intravenous paracetamol after cardiac surgery in neonates and infants: a study protocol for a randomized controlled trial.

BACKGROUND: Morphine is worldwide the analgesic of first choice after cardiac surgery in children. Morphine has unwanted hemodynamic and respiratory side effects. Therefore, post-cardiac surgery patients may potentially benefit from a non-opioid drug for pain relief. A previous study has shown that intravenous (IV) paracetamol is effective and opioid-sparing in children after major non-cardiac surgery. The aim of the study is to test the hypothesis that intermittent IV paracetamol administration in children after cardiac surgery will result in a reduction of at least 30% of the cumulative morphine requirement. METHODS: This is a prospective, multi-center, randomized controlled trial at four level-3 pediatric intensive care units (ICUs) in the Netherlands and Belgium. Children who are 0-36 months old will be randomly assigned to receive either intermittent IV paracetamol or continuous IV morphine up to 48 h post-operatively. Morphine will be available as rescue medication for both groups. Validated pain and sedation assessment tools will be used to monitor patients. The sample size (n = 208, 104 per arm) was calculated in order to detect a 30% reduction in morphine dose; two-sided significance level was 5% and power was 95%. DISCUSSION: This study will focus on the reduction, or replacement, of morphine by IV paracetamol in children (0-36 months old) after cardiac surgery. The results of this study will form the basis of a new pain management algorithm and will be implemented at the participating ICUs, resulting in an evidence-based guideline on post-operative pain after cardiac surgery in infants who are 0-36 months old. TRIAL REGISTRATION: Dutch Trial Registry ( www.trialregister.nl ): NTR5448 on September 1, 2015. Institutional review board approval (MEC2015-646), current protocol version: July 3, 2017.

Infants with severe respiratory syncytial virus needed less ventilator time with nasal continuous airways pressure then invasive mechanical ventilation.

AIM: Nasal continuous positive airway pressure (NCPAP) has been proposed as an early first-line support for infants with severe respiratory syncytial virus (RSV) infection. We hypothesised that infants <6 months with severe RSV would require shorter ventilator support on NCPAP than invasive mechanical ventilation (IMV). METHODS: Retrospective cohort analysis of infants admitted to two paediatric intensive care units, one primarily using NCPAP and one exclusively using IMV, between January 2008 and February 2010. RESULTS: We studied 133 (NCPAP n = 89, IMV n = 46) consecutively admitted infants. On admission, disease severity [i.e. Paediatric RISk of Mortality (PRISM) II score (NCPAP 5.1 ± 2.8 vs. IMV 12.2 ± 6.0, p < 0.001) and SpO2 /Fi O2 ratio (NCPAP 309 ± 81 vs. IMV 135 ± 98, p < 0.001)] was higher in the IMV group. NCPAP remained independently associated with shorter ventilatory support (hazard ratio 2.3, 95% CI 1.1-4.7, p = 0.022) after adjusting for PRISM II score, PCO2 , SpO2 /Fi O2 ratio, bronchopulmonary dysplasia and occurrence of clinically suspected secondary bacterial pneumonia. CONCLUSION: Nasal continuous positive airway pressure was independently associated with a shorter duration of ventilatory support. Differences in baseline disease severity mandate a randomised trial before the routine use of NCPAP can be recommended.

Transfusion of leukocyte-depleted RBCs is independently associated with increased morbidity after pediatric cardiac surgery.

OBJECTIVE: To test the hypothesis that transfusion of leukocyte-depleted RBC preparations within the first 48 hours of PICU stay was independently associated with prolonged duration of mechanical ventilation, irrespective of surgery type and disease severity. DESIGN: Retrospective, observational study. SETTING: Single-center PICU in The Netherlands. PATIENTS: Children less than 18 years consecutively admitted after pediatric cardiac surgery between February 2007 and February 2010. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Data from 335 patients were used for analysis of whom 86 (25.7%) were transfused during the first 48 hours of PICU stay. Duration of mechanical ventilation (115 ± 19 hours vs. 25 ± 4 hours, p < 0.001) was longer among transfused patients. Ventilator-associated pneumonia (10.5% vs. 1.6%, odds ratio 7.2; 95% confidence interval 1.92-32.47; p < 0.001) was more frequent among transfused patients. New acute kidney injury after 48 hours of PICU admission (23.9% vs. 15.4%, p = 0.18) and mortality were comparable (2.3% vs. 4%, p = 0.16). The number of discrete transfusion events was significantly correlated with the duration of mechanical ventilation (Spearman's rho 0.617, p < 0.001). Transfusion remained independently associated with prolonged duration of mechanical ventilation after adjusting for confounders using Cox proportional hazards regression analysis. CONCLUSIONS: Transfusion of leukocyte-depleted RBCs within the first 48 hours of PICU stay after cardiac surgery is independently associated with prolonged duration of mechanical ventilation.

[Does CT scan for blunt abdominal trauma in children amount to a lot of radiation for little yield?]. / CT-scan bij stomp buiktrauma bij kinderen: veel stralen en weinig opbrengst?

Blunt abdominal trauma in children occurs fairly frequently. Although computed tomography scanning is considered by many to be the gold standard, in children who are hemodynamically stable, CT images do not usually result in new perspectives that lead to changes in treatment management. However, the burden of radiation for the child is considerable. CT scanning for blunt abdominal trauma should therefore be avoided in children who are hemodynamically stable. Novel algorithms, using parameters from the patient's history, physical examination, and possibly ultrasound and laboratory tests, seem to be sufficient for ruling out intra-abdominal injury in more than 95% of cases.

Early myocardial dysfunction is not caused by mitochondrial abnormalities in a rat model of peritonitis.

BACKGROUND: Patients with complicated intra-abdominal infections are prone to develop multiple organ failure, including myocardial dysfunction. We hypothesized that early dysfunction during sepsis is associated with inflammation, mitochondrial injury, impaired mitochondrial function, and activation of mitochondrial biogenesis. MATERIALS AND METHODS: Rats received lipopolysaccharide (LPS, n = 11) intraperitoneally. Healthy rats (n = 6) served as controls. Myocardial function was measured ex vivo in an isolated Langendorff-perfused heart set-up. Myocardial vascular cell adhesion molecule-1 (VCAM-1) expression was determined by immunofluorescence microscopy. Cytochrome c release and cytochrome c oxidase (COX IV) activity were measured by immunohistochemistry and enzyme histochemistry, respectively. Protein expression of tumor necrosis factor-α (TNF-α), B-cell lymphoma (Bcl)-2, peroxisome proliferator activated receptor γ cofactor 1α (PGC-1α), and mitochondrial transcription factor A (TFAM) were analyzed by Western blot technique. Mitochondria were studied by electron microscopy. RESULTS: Two hours after LPS injection, developed pressure had decreased and after 4 h myocardial contractility (+dP/dt) and relaxation (-dP/dt) also had decreased. TNF-α protein expression was increased after 2 h and returned to normal at 4 h, whereas after 4 h VCAM-1 expression was higher in LPS-treated animals. At 2 h a substrate-dependent increase in COXIV-activity was seen, but no mitochondrial damage occurred as cytochrome c release, COX IV activity and Bcl-2, PGC-1α or TFAM expression were not changed. Electron microscopy did not reveal differences in myocardial mitochondrial characteristics between LPS-treated and control rats. CONCLUSIONS: Early myocardial dysfunction in sepsis is associated with myocardial inflammation but not with mitochondrial injury, impaired mitochondrial function, or activated mitochondrial biogenesis.

High-frequency oscillatory ventilation and pediatric cardiac surgery: yes, we can!

In the previous issue of Critical Care, Bojan and colleagues reported their experiences with high-frequency oscillatory ventilation (HFOV) after pediatric cardiac surgery. A total of 120 patients were treated with HFOV on the day of surgery, thus excluding rescue HFOV use. The main finding of the authors was that the duration of mechanical ventilation was significantly shorter in patients in whom HFOV was initiated on the day of surgery. Especially interesting about this work is that the authors used HFOV when there was evidence of pulmonary hypertension or right ventricular (RV) failure in their patients. This is an interesting approach as it is often assumed that high intra-thoracic pressures increase RV afterload and thus may enhance RV dysfunction. The findings of Bojan and colleagues may be explained by the fact that they were able to decrease the pulmonary vascular resistance by finding a proper balance between atelectasis and overdistension of the lung. It can be argued that it is possible to do so by applying positive end-expiratory pressure. But, at the same time, this may coincide with the delivery of high inspiratory pressures (>30 cm H2O). As HFOV is, in fact, a continuous positive airway pressure system, its advantage is that it is possible to maintain sufficient lung volume without large injurious pressure swings. Although the observations by Bojan and colleagues need to be confirmed in a prospective randomized trial, they have provided arguments not to rule out the early use of HFOV in pediatric cardiac surgery patients.

Red blood cell transfusion in critically ill children is independently associated with increased mortality.

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.

Prediction of duration of hospitalization in respiratory syncytial virus infection.

Identification of variables that predict duration of RSV-associated hospitalization may be useful in the identification of preventive and therapeutic strategies. A recently published prediction model (Michigan model) for the duration of hospitalization in RSV infection demonstrated good discrimination between children with and without an increased likelihood of a hospital stay >or= 7 days, based on variables such as log weight, congenital heart disease, failure to thrive, premature birth, bronchopulmonary dysplasia, other pulmonary diseases, miscellaneous conditions, early mechanical ventilation, and early ribavirin treatment (receiver operating characteristic (ROC) area, 0.89). Validation of this model is of particular interest for Europe, since the mean duration of hospitalization in The Netherlands is approximately twice that in the USA. The objective of the current study was 1) to validate the Michigan model for RSV hospitalized patients in a large university hospital in The Netherlands, and 2) to develop our own prediction model for a prolonged hospital stay. Data from 177 children younger than 12 months of age admitted with confirmed RSV infection to the Sophia Children's Hospital Rotterdam between 1992-1995, were used for valiation of the Michigan model and derivation of the Rotterdam model. Mean duration of hospitalization for the Rotterdam database was 10.3 (+/-6.3) days, with a median of 9 days; 138 (78%) patients had a hospital stay >or= 7 days. The Michigan model performed poorly when applied to the Rotterdam database, with an ROC area of 0.65 (95% CI, 0.57-0.73). The Rotterdam prediction model (hospital stay >or= 9 days, the median in our database) considered weight and need for oxygen supplementation. The ROC area was 0.65 (95% CI, 0.57-0.73). When using data from patients for the 1995-1996 season, the ROC area was 0.52 (95% CI, 0.34-0.72). The Michigan and the Rotterdam models failed to identify a considerable number of patients who had a prolonged hospital stay, with a low false-positive rate. We conclude that neither the Michigan, nor the Rotterdam model reliably predicted the duration of hospitalization based on demographic and clinical variables.