Incidence of late vitamin K deficiency bleeding in newborns in the Netherlands in 2005: evaluation of the current guideline

Vitamin K prophylaxis is recommended to prevent the hazard of haemorrhage caused by vitamin K deficiency in newborns. The present Dutch guideline recommends 1 mg of vitamin K1 orally at birth, followed by a daily dose of 25 μg of vitamin K1 from 1 to 13 weeks of age for breastfed infants. Since the introduction of this prophylaxis, the incidence of vitamin K deficiency bleeding (VKDB) has decreased; however, late VKDB is still reported. From 1 January to 31 December 2005, a nationwide active surveillance was performed by the Netherlands Paediatric Surveillance Unit (NSCK) to study the current incidence and aetiology of late VKDB in infants. Six cases could be validated as late VKDB: all were breastfed, one fatal idiopathic intracranial haemorrhage at the age of 5 weeks and five bleedings secondary to an underlying cholestatic liver disease between the age of 3 and 7 weeks. The total incidence of late VKDB and idiopathic late VKDB was calculated to be 3.2 (95% CI: 1.2–6.9) and 0.5 (95% CI: 0–2.9) per 100,000 live births, respectively. With the current Dutch guideline, idiopathic late VKDB is rare but late VKDB secondary to cholestasis still occurs in breastfed infants. Doubling the daily dose of vitamin K1 to 50 μg, as is comparable to formula-feeding, may possibly prevent VKDB in this group. Further research, however, is needed to prove this hypothesis

Bench-to-bedside review: Hypercapnic acidosis in lung injury - from 'permissive' to 'therapeutic'

Modern ventilation strategies for patients with acute lung injury and acute respiratory distress syndrome frequently result in hypercapnic acidosis (HCA), which is regarded as an acceptable side effect ('permissive hypercapnia'). Multiple experimental studies have demonstrated advantageous effects of HCA in several lung injury models. To date, however, human trials studying the effect of carbon dioxide per se on outcome in patients with lung injury have not been performed. While significant concerns regarding HCA remain, in particular the possible unfavorable effects on bacterial killing and the inhibition of pulmonary epithelial wound repair, the potential for HCA in attenuating lung injury is promising. The underlying mechanisms by which HCA exerts its protective effects are complex, but dampening of the inflammatory response seems to play a pivotal role. After briefly summarizing the physiological effects of HCA, a critical analysis of the available evidence on the potential beneficial effects of therapeutic HCA from in vitro, ex vivo and in vivo lung injury models and from human studies will be reviewed. In addition, the potential concerns in the clinical setting will be outlined

No association between thickening fraction of the diaphragm and extubation success in ventilated children

Introduction: In mechanically ventilated adults, thickening fraction of diaphragm (dTF) measured by ultrasound is used to predict extubation success. Whether dTF can also predict extubation success in children is unclear. Aim: To investigate the association between dTF and extubation success in children. Second, to assess diaphragm thickness during ventilation and the correlation between dTF, diaphragm thickness (Tdi), age and body surface. Method: Prospective observational cohort study in children aged 0–18 years old with expected invasive ventilation for &gt;48 h. Ultrasound was performed on day 1 after intubation (baseline), day 4, day 7, day 10, at pre-extubation, and within 24 h after extubation. Primary outcome was the association between dTF pre-extubation and extubation success. Secondary outcome measures were Tdi end-inspiratory and Tdi end-expiratory and atrophy defined as &lt;10% decrease of Tdi end-expiratory versus baseline at pre-extubation. Correlations were calculated with Spearman correlation coefficients. Inter-rater reliability was calculated with intraclass correlation (ICC). Results: Fifty-three patients, with median age 3.0 months (IQR 0.1–66.0) and median duration of invasive ventilation of 114.0 h (IQR 55.5–193.5), were enrolled. Median dTF before extubation with Pressure Support 10 above 5 cmH2O was 15.2% (IQR 9.7–19.3). Extubation failure occurred in six children, three of whom were re-intubated and three then received non-invasive ventilation. There was no significant association between dTF and extubation success; OR 0.33 (95% CI; 0.06–1.86). Diaphragmatic atrophy was observed in 17/53 cases, in three of extubation failure occurred. Children in the extubation failure group were younger: 2.0 months (IQR 0.81–183.0) vs. 3.0 months (IQR 0.10–48.0); p = 0.045. At baseline, pre-extubation and post-extubation there was no significant correlation between age and BSA on the one hand and dTF, Tdi- insp and Tdi-exp on the other hand. The ICC representing the level of inter-rater reliability between the two examiners performing the ultrasounds was 0.994 (95% CI 0.970–0.999). The ICC of the inter-rater reliability between the raters in 36 paired assessments was 0.983 (95% CI 0.974–0.990). Conclusion: There was no significant association between thickening fraction of the diaphragm and extubation success in ventilated children.</p

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 H(2)O 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.govNCT02902055. Registered on September 15, 2016

Intracranial bleeding due to vitamin K deficiency: advantages of using a pediatric intensive care registry

Item does not contain fulltextAIM: To determine the incidence of late intracranial vitamin K deficiency bleeding (VKDB) in The Netherlands using the Dutch Pediatric Intensive Care Evaluation (PICE) registry. METHODS: The PICE registry was used to identify all infants who were admitted to a Dutch pediatric intensive care unit (PICU) with intracranial bleeding between 1 January 2004 and 31 December 2007. Cases of confirmed late intracranial VKDB were used to calculate the incidence for each year. To estimate the completeness of ascertainment of the PICE registry, data from 2005 were compared with general surveillance data from that year. RESULTS: In the 4-year study period, 16/64 (25%) of the infants admitted with intracranial bleeding had late intracranial VKDB, resulting in an overall incidence of 2.1/100,000 live births (95% confidence interval 1.2-3.5). The single-year incidence varied markedly between 0.5 and 3.3 per 100,000 live births. All five ascertained cases in 2005 were identified using the PICE registry, while general surveillance identified only three. CONCLUSIONS: The PICE registry allows ongoing monitoring of the incidence of late intracranial VKDB and appears to be associated with a higher rate of completeness than general surveillance. We propose the use of pediatric intensive care registries to assess the efficacy of national vitamin K prophylactic regimens

The impact of critical illness on the expiratory muscles and the diaphragm assessed by ultrasound in mechanical ventilated children

Background: Critical illness has detrimental effects on the diaphragm, but the impact of critical illness on other major muscles of the respiratory pump has been largely neglected. This study aimed to determine the impact of critical illness on the most important muscles of the respiratory muscle pump, especially on the expiratory muscles in children during mechanical ventilation. In addition, the correlation between changes in thickness of the expiratory muscles and the diaphragm was assessed. Methods: This longitudinal observational cohort study performed at a tertiary pediatric intensive care unit included 34 mechanical ventilated children (> 1 month– 10%) in 44% of the children. Diaphragm and expiratory muscle thickness increased (> 10%) in 26% and 20% of the children, respectively. No correlation was found between contractile activity of the muscles and the development of atrophy. Furthermore, no correlation was found between changes in thickness of the diaphragm and the expiratory muscles (P = 0.537). Decrease in expiratory muscle thickness was significantly higher in patients failing extubation compared to successful extubation (− 34% vs − 4%, P = 0.014). Conclusions: Changes in diaphragm and expiratory muscles thickness develop rapidly after the initiation of mechanical ventilation. Changes in thickness of the diaphragm and expiratory muscles were not significantly correlated. These data provide a unique insight in the effects of critical illness on the respiratory muscle pump in children

Reference values of diaphragmatic dimensions in healthy children aged 0–8 years

Diaphragmatic thickness (Tdi) and diaphragm thickening fraction (dTF) are widely used parameters in ultrasound studies of the diaphragm in mechanically ventilated children, but normal values for healthy children are scarce. We determined reference values of Tdi and dTF using ultrasound in healthy children aged 0–8 years old and assessed their reproducibility. In a prospective, observational cohort, Tdi and dTF were measured on ultrasound images across four age groups comprising at least 30 children per group: group 1 (0–6 months), group 2 (7 months-1 year), group 3 (2–4 years) and group 4 (5–8 years). Ultrasound images of 137 healthy children were included. Mean Tdi at inspiration was 2.07 (SD 0.40), 2.09 (SD 0.40), 1.69 (SD 0.30) and 1.72 (SD 0.30) mm for groups 1, 2, 3 and 4, respectively. Mean Tdi at expiration was 1.64 (SD 0.30), 1.67 (SD 0.30), 1.38 (SD 0.20) and 1.42 (SD 0.20) mm for groups 1, 2, 3 and 4, respectively. Mean Tdi at inspiration and mean Tdi at expiration for groups 1 and 2 were significantly greater than those for groups 3 and 4 (both p < 0.001). Mean dTF was 25.4% (SD 10.4), 25.2% (SD 8.3), 22.8% (SD 10.9) and 21.3% (SD 7.1) for group 1, 2, 3 and 4, respectively. The intraclass correlation coefficients (ICC) representing the level of inter-rater reliability between two examiners performing the ultrasounds was 0.996 (95% CI 0.982–0.999). ICC of the inter-rater reliability between the raters in 11 paired assessments was 0.989 (95% CI 0.973–0.995). Conclusion: Ultrasound measurements of Tdi and dTF were highly reproducible in healthy children aged 0–8 years. Trial registration: ClinicalTrials.gov identifier (NCT number): NCT04589910.What is Known:• Diaphragmatic thickness and diaphragm thickening fraction are widely used parameters in ultrasound studies of the diaphragm in mechanically ventilated children, but normal values for healthy children to compare these with are scarce.What is New:• We determined normal values of diaphragmatic thickness and diaphragm thickening fraction using ultrasound in 137 healthy children aged 0–8 years old. The diaphragmatic thickness of infants up to 1 year old was significantly greater than that of children from 2 to 8 years old. Diaphragmatic thickness decreased with an increase in body surface area. These normal values in healthy children can be used to assess changes in respiratory muscle thickness in mechanically ventilated children

Early restrictive fluid resuscitation has no clinical advantage in experimental severe pediatric acute respiratory distress syndrome

Intravenous fluids are widely used to treat circulatory deterioration in pediatric acute respiratory distress syndrome (PARDS). However, the accumulation of fluids in the first days of PARDS is associated with adverse outcome. As such, early fluid restriction may prove beneficial, yet the effects of such a fluid strategy on the cardiopulmonary physiology in PARDS are unclear. In this study, we compared the effect of a restrictive with a liberal fluid strategy on a hemodynamic response and the formation of pulmonary edema in an animal model of PARDS. Sixteen mechanically ventilated lambs (2-6 wk) received oleic acid infusion to induce PARDS and were randomized to a restrictive or liberal fluid strategy during a 6-h period of mechanical ventilation. Transpulmonary thermodilution determined extravascular lung water (EVLW) and cardiac output (CO). Postmortem lung wet-to-dry weight ratios were obtained by gravimetry. Restricting fluids significantly reduced fluid intake but increased the use of vasopressors among animals with PARDS. Arterial blood pressure was similar between groups, yet CO declined significantly in animals receiving restrictive fluids (P = 0.005). There was no difference in EVLW over time (P = 0.111) and lung wet-to-dry weight ratio [6.1, interquartile range (IQR) = 6.0-7.3 vs. 7.1, IQR = 6.6-9.4, restrictive vs. liberal, P = 0.725] between fluid strategies. Both fluid strategies stabilized blood pressure in this model, yet early fluid restriction abated CO. Early fluid restriction did not limit the formation of pulmonary edema; therefore, this study suggests that in the early phase of PARDS, a restrictive fluid strategy is not beneficial in terms of immediate cardiopulmonary effects