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Summary Background Severe infections kill more than 4·5 million children every year. Population-based data for severe infections in children requiring admission to intensive care units (ICUs) are scarce. We assessed changes in incidence and mortality of severe infections in critically ill children in Australia and New Zealand. Methods We did a retrospective multicentre cohort study of children requiring intensive care in Australia and New Zealand between 2002 and 2013, with data from the Australian and New Zealand Paediatric Intensive Care Registry. We included children younger than 16 years with invasive infection, sepsis, or septic shock. We assessed incidence and mortality in the ICU for 2002–07 versus 2008–13. Findings During the study period, 97 127 children were admitted to ICUs, 11 574 (11·9%) had severe infections, including 6688 (6·9%) with invasive infections, 2847 (2·9%) with sepsis, and 2039 (2·1%) with septic shock. Age-standardised incidence increased each year by an average of 0·56 cases per 100 000 children (95% CI 0·41–0·71) for invasive infections, 0·09 cases per 100 000 children (0·00–0·17) for sepsis, and 0·08 cases per 100 000 children (0·04–0·12) for septic shock. 260 (3·9%) of 6688 patients with invasive infection died, 159 (5·6%) of 2847 with sepsis died, and 346 (17·0%) of 2039 with septic shock died, compared with 2893 (3·0%) of all paediatric ICU admissions. Children admitted with invasive infections, sepsis, and septic shock accounted for 765 (26·4%) of 2893 paediatric deaths in ICUs. Comparing 2008–13 with 2002–07, risk-adjusted mortality decreased significantly for invasive infections (odds ratio 0·72, 95% CI 0·56–0·94; p=0·016), and for sepsis (0·66, 0·47–0·93; p=0·016), but not significantly for septic shock (0·79, 0·61–1·01; p=0·065). Interpretation Severe infections remain a major cause of mortality in paediatric ICUs, representing a major public health problem. Future studies should focus on patients with the highest risk of poor outcome, and assess the effectiveness of present sepsis interventions in children. Funding National Medical Health and Research Council, Australian Resuscitation Outcomes Consortium, Centre of Research Excellence (1029983).

Although suctioning is a standard airway maintenance procedure, there are significant associated risks, such as loss of lung volume due to high negative suction pressures. This study aims to assess the extent and duration of change in end-expiratory level (EEL) resulting from endotracheal tube (ETT) suction and to examine the relationship between EEL and regional lung ventilation in ventilated preterm infants with respiratory distress syndrome.A prospective observational clinical study of the effect of ETT suction on 20 non-muscle-relaxed preterm infants with respiratory distress syndrome (RDS) on conventional mechanical ventilation was conducted in a neonatal intensive care unit. Ventilation distribution was measured with regional impedance amplitudes and EEL using electrical impedance tomography.ETT suction resulted in a significant increase in EEL post-suction (P0.01). Regionally, anterior EEL decreased and posterior EEL increased post-suction, suggesting heterogeneity. Tidal volume was significantly lower in volume-guarantee ventilation compared with pressure-controlled ventilation (P = 0.04).ETT suction in non-muscle-relaxed and ventilated preterm infants with RDS results in significant lung volume increase that is maintained for at least 90 min. Regional differences in distribution of ventilation with ETT suction suggest that the behaviour of the lung is heterogeneous in nature.

Introduction Similarities in size, anatomy and physiology have supported the use of sheep to model a wide range of human diseases, including coagulopathy. However, coagulation studies involving sheep are limited by the absence of high quality data defining normal ovine coagulation and fibrinolysis. Materials and Methods Full blood examination, routine and specialised coagulation tests, rotational thromboelastometry and whole blood platelet aggregometry was performed on 50 healthy Samm & Border Leicester Cross ewes and compared to corresponding human ranges. Intraspecies breed and gender variability was investigated by comparison to a smaller population of 13 healthy Merino wethers. Results Ovine coagulation was similar to human according to routine coagulation methods (PT, aPTT, TCT, Fib(C)) and some specialised coagulation tests (vWF, AT, Plasmin Inh). Despite these similarities, ovine secondary haemostasis demonstrated substantial differences to that of human. Rapid initiation of the contact activation pathway, high levels of FVIII, low Protein C, greater overall clot firmness and a reduced capacity for clot lysis was documented in sheep. In addition, ADP and collagen agonists precipitated a reduced primary haemostatic response in sheep relative to human. Intraspecies differences in whole blood platelet aggregometry between the cohorts of sheep indicate the need for breed-specific normal ranges. Conclusions The application of a board spectrum of coagulation assays has enabled elucidation of the similarities as well as differences between ovine and human coagulation. The new knowledge generated from this study will guide the design of future translational coagulation studies in ovine models.

BACKGROUND: Respiratory support is a central component of the management of critically ill children. It can be delivered invasively via an endotracheal tube or non‐invasively via face mask, nasal mask, nasal cannula or oxygen hood/tent. Invasive ventilation can be damaging to the lungs, and the tendency to use non‐invasive forms is growing. However, non‐invasive delivery is often poorly tolerated by children. High‐flow nasal cannula (HFNC) oxygen delivery is a relatively new therapy that shows the potential to reduce the need for intubation and be better tolerated by children than other non‐invasive forms of support. HFNC therapy differs from other non‐invasive forms of treatment in that it delivers heated, humidified and blended air/oxygen via nasal cannula at rates > 2 L/kg/min. This allows the user to deliver high concentrations of oxygen and to potentially deliver continuous distending pressure; this treatment often is better tolerated by the child. OBJECTIVES: To determine whether HFNC therapy is more effective than other forms of non‐invasive therapy in paediatric patients who require respiratory support. SEARCH METHODS: We searched the Cochrane Central Register of Controlled Trials (CENTRAL) (2013, Issue 4); MEDLINE via PubMed (January 1966 to April 2013); EMBASE (January 1980 to April 2013); CINAHL (1982 to April 2013); and LILACS (1982 to April 2013). Abstracts from conference proceedings, theses and dissertations and bibliographical references to relevant studies were also searched. We applied no restriction on language. SELECTION CRITERIA: We planned to included randomized controlled trials (RCTs) and quas‐randomized trials comparing HFNC therapy with other forms of non‐invasive respiratory support for children. Non‐invasive support encompassed cot, hood or tent oxygen; low‐flow nasal cannulae (flow rates ≤ 2 L/min); and continuous positive airway pressure (CPAP) or bilevel positive airway pressure (BiPAP) delivered via facial or nasal mask/cannula. Treatment failure was defined by the need for additional respiratory support. We excluded children with a diagnosis of bronchiolitis. DATA COLLECTION AND ANALYSIS: Two review authors independently assessed all studies for selection and data extraction. We used standard methodological procedures expected by The Cochrane Collaboration. MAIN RESULTS: Our search yielded 922 records. A total of 109 relevant records were retrieved with reference to our search criteria. After duplicates and irrelevant studies were removed, 69 studies were further scrutinized. Of these, 11 studies involved children. No study matched our inclusion criteria. AUTHORS' CONCLUSIONS: Based on the results of this review, no evidence is available to allow determination of the safety or effectiveness of HFNC as a form of respiratory support in children.

The main physiological impact of high flow nasal cannula (HFNC) therapy is presumed to be a decrease in work of breathing (WOB). To assess this, diaphragmatic electrical activity and esophageal pressure changes were measured off then on HFNC delivered at 2 L/kg/min, in 14 infants with bronchiolitis and 14 cardiac infants. Electrical activity of the diaphragm (Edi) was measured using an Edi catheter with calculations of signal peak (EdiMAX ) and amplitude (EdiAMPL ). Pressure-rate and pressure-time products (PRP, PTP) were calculated from analyses of esophageal pressure. Changes in end-expiratory lung volume were measured using respiratory inductance plethysmography (RIPEEL ). The EdiMAX and EdiAMPL were significantly higher in infants with bronchiolitis than in cardiac infants (P 0.05). Within the bronchiolitis group, both were significantly reduced between HFNC states from 27.9 µV [20.4, 35.4] to 21.0 µV [14.8, 27.2] and from 25.1 µV [18.0, 32.2] to 19.2 µV [13.3, 25.1], respectively (mean, 95% CI, P 0.05). A less prominent offload of the diaphragm was observed in cardiac infants (P 0.05). WOB decreased in both groups with a significant reduction of PRP and PTP (P 0.05). RIPEEL increased significantly in bronchiolitis only (P 0.05). HFNC offloads the diaphragm and reduces the WOB in bronchiolitis. A similar effect was demonstrated in cardiac infants, a group without signs of airway-obstruction.

Optimal respiratory support for interhospital transport of critically ill children is challenging and has been scarcely investigated. High-flow nasal cannula (HFNC) therapy has emerged as a promising support mode in the paediatric intensive care unit (PICU), but no data are available on HFNC used during interhospital transport. We aimed to assess the safety of HFNC during retrievals of critically ill children and its impact on the need for invasive ventilation (IV).This was a retrospective, single-centre study of children under 2 years old transported by a specialized paediatric retrieval team to PICU. We compared IV rates before (2005-2008) and after introduction of HFNC therapy (2009-2012).A total of 793 infants were transported. The mean transport duration was 1.4 h (range 0.25-8), with a mean distance of 205 km (2-2,856). Before introduction of HFNC, 7 % (n = 23) were retrieved on non-invasive ventilation (NIV) and 49 % (n = 163) on IV. After introduction of HFNC, 33 % (n = 150) were retrieved on HFNC, 2 % (n = 10) on NIV, whereas IV decreased to 35 % (n = 162, p0.001). No patients retrieved on HFNC required intubation during retrieval, or developed pneumothorax or cardiac arrest. Using HFNC was associated with a significant reduction in IV initiated by the retrieval team (multivariate OR 0.51; 95 % CI 0.27-0.95; p = 0.032).We report on a major change of practice in transport of critically ill children in our retrieval system. HFNC therapy was increasingly used and was not inferior to low-flow oxygen or NIV. Randomized trials are needed to assess whether HFNC can reduce the need for IV in interhospital transport of critically ill children.

To obtain data on the safety and clinical impact of managing infants with bronchiolitis on the ward with high-flow nasal cannula (HFNC) treatment.A prospective pilot study was conducted of 61 infants aged12 months with bronchiolitis and oxygen requirement presenting to the emergency department. HFNC was commenced at 2 L/kg/min, and fraction of inspired oxygen was titrated to oxygen saturation94%. A standard-treatment group (n = 33) managed with standard low-flow subnasal oxygen during the same time period was retrospectively identified.Admission demographics, heart rate (HR) and respiratory rate (RR) were similar in test and standard-treatment groups. Responders and non-responders to HFNC were identified within 60 min of treatment. Non-responders to HFNC requiring paediatric intensive care unit (PICU) admission showed no change in HR and RR, whereas responders showed decreases in HR and RR (P0.02). Patients receiving HFNC were four times less likely to need PICU admission than the standard treatment group (OR 4.086, 95%CI 1.0-8.2; P = 0.043). No adverse events such as pneumothorax, bradycardia, bradypnoea, emergency intubation or cardiopulmonary resuscitation were observed. No patients admitted to the PICU required intubation.HFNC treatment in the paediatric ward is safe. Non-responders requiring PICU admission can be identified within the first hour of HFNC treatment by monitoring HR and RR. It is feasible to undertake a randomised controlled trial based on this pilot with the aim of decreasing PICU admissions.

Electrical impedance tomography (EIT) can determine ventilation and perfusion relationship. Most of the data obtained so far originates from experimental settings and in healthy subjects. The aim of this study was to demonstrate that EIT measures the perioperative changes in pulmonary blood flow after repair of a ventricular septum defect in children with haemodynamic relevant septal defects undergoing open heart surgery. In a 19 bed intensive care unit in a tertiary children's hospital ventilation and cardiac related impedance changes were measured using EIT before and after surgery in 18 spontaneously breathing patients. The EIT signals were either filtered for ventilation (ΔZV) or for cardiac (ΔZQ) related impedance changes. Impedance signals were then normalized (normΔZV, normΔZQ) for calculation of the global and regional impedance related ventilation perfusion relationship (normΔZV/normΔZQ). We observed a trend towards increased normΔZV in all lung regions, a significantly decreased normΔZQ in the global and anterior, but not the posterior lung region. The normΔZV/normΔZQ was significantly increased in the global and anterior lung region. Our study qualitatively validates our previously published modified EIT filtration technique in the clinical setting of young children with significant left-to-right shunt undergoing corrective open heart surgery, where perioperative assessment of the ventilation perfusion relation is of high clinical relevance.

Positioning is considered vital to the maintenance of good lung ventilation by optimizing oxygen transport and gas exchange in ventilated premature infants. Previous studies suggest that the prone position is advantageous; however, no data exist on regional ventilation distribution for this age group.To investigate the effect of body position on regional ventilation distribution in ventilated and nonventilated preterm infants using electrical impedance tomography.Randomized crossover study design.Neonatal ICU.A total of 24 ventilated preterm infants were compared with six spontaneously breathing preterm infants.Random assignment of the order of the positions supine, prone, and quarter prone.Ventilation distribution was measured with regional impedance amplitudes and global inhomogeneity indices using electrical impedance tomography. In the spontaneously breathing infants, regional impedance amplitudes were increased in the posterior compared with the anterior lung (p0.01) and in the right compared with the left lung (p = 0.03). No differences were found in the ventilated infants. Ventilation was more inhomogeneous in the ventilated compared with the healthy infants (p0.01). Assessment of temporal regional lung filling showed that the posterior lung filled earlier than the anterior lung in the spontaneously breathing infants (p0.02) whereas in the in the ventilated infants the right lung filled before the left lung (p0.01).In contrast to previous studies showing that ventilation is distributed to the nondependent lung in infants and children, this study shows that gravity has little effect on regional ventilation distribution.

Our understanding of regional filling of the lung and regional ventilation distribution is based on studies using stepwise inhalation of radiolabelled tracer gases, magnetic resonance imaging and positron emission tomography. We aimed to investigate whether these differences in ventilation distribution at different end-expiratory levels (EELs) and tidal volumes (V (T)s) held also true during tidal breathing. Electrical impedance tomography (EIT) measurements were performed in ten healthy adults in the right lateral position. Five different EELs with four different V (T)s at each EEL were tested in random order, resulting in 19 combinations. There were no measurements for the combination of the highest EEL/highest V (T). EEL and V (T) were controlled by visual feedback based on airflow. The fraction of ventilation directed to different slices of the lung (VENT(RL1)-VENT(RL8)) and the rate of the regional filling of each slice versus the total lung were analysed. With increasing EEL but normal tidal volume, ventilation was preferentially distributed to the dependent lung and the filling of the right and left lung was more homogeneous. With increasing V (T) and maintained normal EEL (FRC), ventilation was preferentially distributed to the dependent lung and regional filling became more inhomogeneous (p 0.05). We could demonstrate that regional and temporal ventilation distribution during tidal breathing was highly influenced by EEL and V (T).

1. Respiratory alkalosis accompanies the clinical syndrome of tetany, precipitates cardiac arrhythmias and predisposes to coronary vasoconstriction. Magnesium plays a critical role in the maintenance of membrane function, and magnesium depletion is often associated with cardiac arrhythmias or vasoconstriction. 2. As technology for detecting circulating ionized magnesium (the most interesting form with respect to physiological and biological properties) is now available in the form of new magnesium-selective electrodes, the effect of respiratory alkalosis induced by voluntary overbreathing for 30 min on circulating ionized magnesium was studied in eight healthy subjects. 3. The total plasma magnesium concentration was not modified by hyperventilation. On the contrary, hyperventilation was associated with a significant reduction in the ionized magnesium concentration of 0.05 (0.02–0.15) mmol/l (median and range) and in the free magnesium fraction of 0.06 (0.01–0.19). During hyperventilation the relative intravascular magnesium mass, calculated from changes in total plasma magnesium concentration and haematocrit, decreased significantly. 4. It is concluded that acute overbreathing reduces the circulating ionized magnesium concentration and the intravascular magnesium mass. It is therefore conceivable that extracellular magnesium deficiency is at least a subsidiary cause of the syndrome of tetany and the cardiac complications that are precipitated by hyperventilation.

The measurement of ventilation distribution is currently performed using inhaled tracer gases for multiple breath inhalation studies or imaging techniques to quantify spatial gas distribution. Most tracer gases used for these studies have properties different from that of air. The effect of gas density on regional ventilation distribution has not been studied. This study aimed to measure the effect of gas density on regional ventilation distribution. Methods Ventilation distribution was measured in seven rats using electrical impedance tomography (EIT) in supine, prone, left and right lateral positions while being mechanically ventilated with either air, heliox (30% oxygen, 70% helium) or sulfur hexafluoride (20% SF6, 20% oxygen, 60% air). The effect of gas density on regional ventilation distribution was assessed. Results Gas density did not impact on regional ventilation distribution. The non-dependent lung was better ventilated in all four body positions. Gas density had no further impact on regional filling characteristics. The filling characteristics followed an anatomical pattern with the anterior and left lung showing a greater impedance change during the initial phase of the inspiration. Conclusion It was shown that gas density did not impact on convection dependent ventilation distribution in rats measured with EIT.

To investigate whether ventilatory management using a temperature-corrected (pH-stat) or uncorrected (alpha-stat) blood gas analysis strategy improves brain tissue oxygen tension (PbrO(2)) in children prophylactically treated with moderate hypothermia for traumatic brain injury.Double crossover study conducted in the intensive care unit of a tertiary children's hospital. Nine children aged 3-14 years with severe traumatic brain injury were randomly allocated twice to a 6-hour period of either alpha- or pH-stat management while being kept hypothermic at 32.5°C.PbrO(2), intracranial pressure (ICP) and PbrO(2)/PaO(2).PbrO(2) was significantly higher during pH-stat management (alpha-stat, 23.2mmHg [95% CI, 22.4- 24.0mmHg] v pH-stat, 28.7mmHg [95% CI, 27.9- 29.5mmHg]; P0.001). PbrO(2)/PaO(2) was significantly higher during pH-stat (alpha-stat, 0.190 [95% CI, 0.187- 0.193] v pH-stat, 0.251 [95% CI, 0.246-0.259]; P0.05). ICP was non-significantly higher during pH-stat (alpha-stat, 8.8mmHg [95% CI, 8.1-9.5mmHg] v ph-stat,10.2mmHg [95% CI, 9.6-10.8]).PbrO(2) may be improved using a pH-stat blood gas management strategy in prophylactic hypothermia for paediatric patients with traumatic brain injury without any clinically relevant increase in ICP.

Background Hyperpolarised helium MRI (He3 MRI) is a new technique that enables imaging of the air distribution within the lungs. This allows accurate determination of the ventilation distribution in vivo. The technique has the disadvantages of requiring an expensive helium isotope, complex apparatus and moving the patient to a compatible MRI scanner. Electrical impedance tomography (EIT) a non-invasive bedside technique that allows constant monitoring of lung impedance, which is dependent on changes in air space capacity in the lung. We have used He3MRI measurements of ventilation distribution as the gold standard for assessment of EIT. Methods Seven rats were ventilated in supine, prone, left and right lateral position with 70% helium/30% oxygen for EIT measurements and pure helium for He3 MRI. The same ventilator and settings were used for both measurements. Image dimensions, geometric centre and global in homogeneity index were calculated. Results EIT images were smaller and of lower resolution and contained less anatomical detail than those from He3 MRI. However, both methods could measure positional induced changes in lung ventilation, as assessed by the geometric centre. The global in homogeneity index were comparable between the techniques. Conclusion EIT is a suitable technique for monitoring ventilation distribution and inhomgeneity as assessed by comparison with He3 MRI.

Rapid bedside determination of cerebral blood pressure autoregulation (AR) may improve clinical utility. We tested the hypothesis that cerebral Hb oxygenation (HbDiff) and cerebral Hb volume (HbTotal) measured by near-infrared spectroscopy (NIRS) would correlate with cerebral blood flow (CBF) after single dose phenylephrine (PE). Critically ill patients requiring artificial ventilation and arterial lines were eligible. During rapid blood pressure rise induced by i.v. PE bolus, ΔHbDiff and ΔHbTotal were calculated by subtracting values at baseline (normotension) from values at peak blood pressure elevation (hypertension). With the aid of NIRS and bolus injection of indocyanine green, relative measures of CBF, called blood flow index (BFI), were determined during normotension and during hypertension. BFI during hypertension was expressed as percentage from BFI during normotension (BFI%). Autoregulation indices (ARIs) were calculated by dividing BFI%, ΔHbDiff, and ΔHbTotal by the concomitant change in blood pressure. In 24 patients (11 newborns and 13 children), significant correlations between BFI% and ΔHbDiff (or ΔHbTotal) were found. In addition, the associations between Hb-based ARI and BFI%-based ARI were significant with correlation coefficients of 0.73 (or 0.72). Rapid determination of dynamic AR with the aid of cerebral Hb signals and PE bolus seems to be reliable.

To describe the change in ventilatory practice in a tertiary paediatric intensive care unit (PICU) in the 5-year period after the introduction of high-flow nasal prong (HFNP) therapy in infants

Recent studies have highlighted the need for careful titration of ventilatory support to minimise ventilator-induced lung injury. To achieve this, the measurement of both respiratory mechanics and gas distribution in the lung is required. Measurement of dynamic compliance during recruitment can identify an optimum positive end-expiratory level. Pressure-volume curves measure recruitable lung and characterise quasi-static compliance of the respiratory system. Intrapulmonary gas distribution and regional lung mechanics can be measured on a breath-by-breath basis using electrical impedance tomography.

Perfusion in healthy adults is gravity-dependent. Little is known about lung perfusion in the preterm infant. The aim of this study was to describe the regional distribution of blood volume within the thorax in preterm infants receiving synchronised volume-targeted mechanical ventilation (SIPPV + TTV) and to compare this to regional distribution of tidal ventilation using electrical impedance tomography (EIT). Stable supine ventilated preterm infants (7 days) and oxygen requirement. A total of 5,471 beats were analysed from 26 infants (78 recordings); mean (standard deviation (SD)) gestational age was 26 (2) weeks and mean (SD) postnatal age was 9 (10) days. The median (interquartile range) ΔZ c in the anterior half of the hemithorax was 1.41-fold (0.88–2.11) greater than that in the posterior half. The geometric centre of ΔZ c was located at 46.7% of the anterior-posterior thoracic distance, compared to a more centrally located ΔZ v (49.6%; p 7 days of age and not influenced by oxygen requirement. There are gravity dependent differences in the distribution of blood volume and ventilation in the ventilated preterm chest.

Purpose: To examine the impact of different endotracheal tube (ETT) suction techniques on regional end-expiratory lung volume (EELV) and tidal volume (VT) in an animal model of surfactant-deficient lung injury. Methods: Six 2-week old piglets were intubated (4.0 mm ETT), muscle-relaxed and ventilated, and lung injury was induced with repeated saline lavage. In each animal, open suction (OS) and two methods of closed suction (CS) were performed in random order using both 5 and 8 French gauge (FG) catheters. The pre-suction volume state of the lung was standardised on the inflation limb of the pressure-volume relationship. Regional EELV and VT expressed as a proportion of the impedance change at vital capacity (%ZVCroi) within the anterior and posterior halves of the chest were measured during and for 60 s after suction using electrical impedance tomography. Results: During suction, 5 FG CS resulted in preservation of EELV in the anterior (nondependent) and posterior(dependent) lung compared to the other permutations, but these only reached significance in the anterior regions (p\0.001 repeated-measures ANOVA). VT within the anterior, but not posterior lung was significantly greater during 5FG CS compared to 8 FG CS; the mean difference was 15.1 [95% CI 5.1, 25.1]%ZVCroi. Neither catheter size nor suction technique influenced post-suction regional EELV or VT compared to pre-suction values (repeated-measures ANOVA). Conclusions: ETT suction causes transient loss of EELV and VT throughout the lung. Catheter size exerts a greater influence than suction method, with CS only protecting against derecruitment when a small catheter is used, especially in the non-dependent lung.

In adults, ventilation is preferentially distributed towards the dependent lung. A reversal of the adult pattern has been observed in infants using radionuclide ventilation scanning. But these results have been obtained in infants and children with lung disease. In this study we investigate whether healthy infants have a similar reverse pattern of ventilation distribution.Measurement of regional ventilation distribution in healthy newborn infants during non-REM sleep in comparison to adults.Twenty-four healthy newborns and 13 adults were investigated with electrical impedance tomography (EIT) in supine and prone position. Regional ventilation distribution was assessed with profiles of relative impedance change. The phase lag between dependent and non-dependent ventilation was calculated as a measure of asynchronous ventilation.In newborns and adults the geometric center of ventilation was centrally located in the lung at 52.2 +/- 6.2% from anterior to posterior and at 50.5 +/- 14.7%, respectively. Using impedance profiles, ventilation was equally distributed to the dependent and non-dependent lung regions in newborns. Ventilation distribution in adults was similar. Phase lag characteristics of the impedance signal showed that infants had slower emptying of the dependent lung than adults.The speculated reverse pattern of regional ventilation distribution in healthy infants compared to adults could not be demonstrated. Gravity had little effect on ventilation distribution in both infants and adults measured in supine and prone position.

Introduction. The blue-ringed octopus (Hapalochlaena sp.) is a small animal, which can inject a toxin that produces a respiratory arrest within minutes. This envenomation is a rare occurrence with very few reported outcomes in children. Case report. A 4-year-old boy was bitten by a blue-ringed octopus (Hapalochlaena sp.) whilst playing at a popular beach in Queensland, Australia. Within ten minutes of the bite, he had vomited three times, lost the ability to stand and complained of blurred vision. An ambulance was called by the time he presented to the local emergency department (20 minutes after the bite) he had acute and progressive skeletal muscle weakness. He was intubated, ventilated, and transferred to a pediatric intensive care unit for specialized supportive care. He was ventilated for a total of 17 hours with spontaneous muscular activity returning at around 15 hours from envenomation. Discussion. If not treated appropriately the bite of this small and innocuous looking animal could have lead to death within minutes. Conclusion. This case report serves as a reminder of how appropriate treatment can ensure discharge from hospital with no long-term consequences. It also highlights the importance of education for beach goers and in particular parents to prevent exposure of tetrodotoxin to children.

A 14-year-old boy with catecholamine-induced polymorphic ventricular tachycardia was treated for hypoxic brain injury after a 25-minute ventricular tachycardia arrest. He had been treated by the local paediatric cardiology service with ?-blockers for syncopal events related to episodes of ventricular tachycardia. As standard inotropic support was contraindicated, he was treated for hypoxic brain injury, with targeting of brain tissue oxygen levels (PtO2) with vasopressin. He was extubated after 7 days and discharged home with an automatic implantable cardioverter defibrillator, with no neurological sequelae. PtO2 is a reliable and effective clinical assessment tool that can aid in the management of patients with significant cerebral injury. Vasopressin proved a valuable adjunct in treatment of hypoxic brain injury when inotropic agents were contraindicated.

Background Despite being the leading cause of death and disability in the paediatric population, traumatic brain injury (TBI) in this group is largely understudied. Clinical practice within the paediatric intensive care unit (PICU) has been based upon adult guidelines however children are significantly different in terms of mechanism, pathophysiology and consequence of injury. Aim To review TBI management in the PICU and gain insight into potential management strategies. Method To conduct this review, a literature search was conducted using MEDLINE, PUBMED and The Cochrane Library using the following key words; traumatic brain injury; paediatric; hypothermia. There were no date restrictions applied to ensure that past studies, whose principles remain current were not excluded. Results Three areas were identified from the literature search and will be discussed against current acknowledged treatment strategies: Prophylactic hypothermia, brain tissue oxygen tension monitoring and decompressive craniectomy. Conclusion Previous literature has failed to fully address paediatric specific management protocols and we therefore have little evidence-based guidance. This review has shown that there is an emerging and ongoing trend towards paediatric specific TBI research in particular the area of moderate prophylactic hypothermia (MPH).

Objective The purpose of lung recruitment manoeuvres is to open collapsed lung regions, improve gas exchange and optimise regional lung mechanics. This study investigates the efficacy of recruitment manoeuvres for improving regional ventilation distribution as characterised using electrical impedance tomography (EIT). Design, subjects, interventions A ventilated ovine smoke inhalation lung injury model was used. Respiratory mechanics and regional filling capacity of the lung were measured using EIT pre- and post- recruitment and compared to a control group. Measurements EIT, expressed as the time course relation of the regional versus the global impedance change, measured the regional filling capacities of the lung. Main results After smoke inhalation injury, the dependent lung showed a significantly larger area of collapse and a reduced filling capacity compared to the non-dependent lung. After recruitment the ventilated volume increased and the dependent lung showed improved respiratory mechanics, whereas the non-dependent lung was more likely to be hyper-inflated during tidal breathing. Conclusions Lung recruitment manoeuvres have a significant impact on regional lung mechanics and individual measurement of ventilation distribution using EIT may assist to improve ventilatory management. Electronic supplementary material The online version of this article (doi:10.1007/s00134-008-1324-0) contains supplementary material, which is available to authorized users.

OBJECTIVE: The mortality rate in paediatric intensive care units (PICU) has fallen over the last two decades. More advanced treatment is offered to children with life-threatening disease and there is substantial interest in knowing whether long term outcome and quality of life after intensive care are acceptable. SETTING: 12-bed paediatric and neonatal intensive care unit. INTERVENTION: Prospective follow-up study with telephone interview 1 and 2 years after discharge. METHODS: Four domains of quality of life (physical function, role function, social-emotional function and health problem) were recorded by calculating the health state classification (HSC) index. Outcome was classified good (HSC 1.0-0.7), moderate (HSC 0.69-0.3), poor (HSC 0.29-0) and very poor (HSC

BACKGROUND: High fractions of inspired oxygen (Fio2) result in resorption atelectasis shortly after their application. However, the impact of different levels of Fio2 and their interaction with positive end-expiratory pressure (PEEP) on functional residual capacity (FRC) and ventilation distribution is unknown in anesthetized children. We hypothesized that the use of a Fio2 of 1.0 results in a decrease of FRC and ventilation homogeneity compared with that of a Fio2 of 0.3, and that this decrease is prevented by PEEP of 6-cm H2O compared to a PEEP of 3-cm H2O. METHODS: Forty-six children (3–6 yr) without cardiopulmonary disease were randomly allocated to receive PEEP of 6-cm H2O (PEEP 6 group) during the entire study period or PEEP of 3-cm H2O (PEEP 3 group). The order of the Fio2 (0.3 or 1.0) was also randomized. A defined recruitment maneuver was performed after tracheal intubation and 5 min later the first measurement. This procedure was then repeated with the second Fio2 level. FRC and lung clearance index (LCI) were calculated by a blinded observer. RESULTS: While FRC (mean sd) was similar at both levels of Fio2 (0.3: 25.6 2.9 mL/kg vs 1.0: 25.6 2.8 mL/kg, P 0.189) in the PEEP 6 group, FRC decreased in the PEEP 3 group (0.3: 24.9 3.8 vs 1.0: 21.7 4.1, P 0.0001). Furthermore, with continuous PEEP of 6-cm H2O a similar LCI was observed at both levels of Fio2 (0.3: 6.45 0.4 vs 6.43 0.4, P 0.668) while LCI increased at the higher Fio2 in the PEEP 3 group (0.3: 6.5 0.5 vs 1.0: 7.7 1.2, P 0.0001). CONCLUSIONS: During the application of a very low PEEP of 3–cm H2O, FRC and ventilation distribution decreased significantly at an Fio2 of 1.0 compared with that at an Fio2 of 0.3. This decrease could be counterbalanced by the administration of PEEP of 6-cm H2O, indicating that a low level of PEEP is sufficient to maintain FRC and ventilation distribution regardless of the oxygen concentration.

Background Propofol is commonly used in children undergoing diagnostic interventions under anaesthesia or deep sedation. Because hypoxaemia is the most common cause of critical deterioration during anaesthesia and sedation, improved understanding of the effects of anaesthetics on pulmonary function is essential. The aim of this study was to determine the effect of different levels of propofol anaesthesia on functional residual capacity (FRC) and ventilation distribution. Methods In 20 children without cardiopulmonary disease mean age (sd) 49.75 (13.3) months and mean weight (sd) 17.5 (3.9)kg, anaesthesia was induced by a bolus of i.v. propofol 2mgkg−1 followed by an infusion of propofol 120µgkg−1min−1 (level I). Then, a bolus of propofol 1mgkg−1 was given followed by a propofol infusion at 240µgkg−1min−1 (level II). FRC and lung clearance index (LCI) were calculated at each level of anaesthesia using multibreath analysis. Results The FRC mean (sd) decreased from 20.7 (3.3)mlkg−1 at anaesthesia level I to 17.7 (3.9)mlkg−1 at level II (P < 0.0001). At the same time, mean (sd) LCI increased from 10.4 (1.1) to 11.9 (2.2) (P = 0.0038), whereas bispectral index score values decreased from mean (sd) 57.5 (7.2) to 35.5 (5.9) (P < 0.0001). Conclusions Propofol elicited a deeper level of anaesthesia that led to a significant decrease of the FRC whereas at the same time the LCI, an index for ventilation distribution, increased indicating an increased vulnerability to hypoxaemia

Predicting outcome and potential lung disease for any child suffering from severe respiratory failure in the paediatric intensive care unit is difficult. The causes of the acute respiratory failure are diverse and still not well understood. In simple terms, it may be concluded that high pressures and supplementary oxygen in the phase of acute respiratory failure increase the likelihood that complications and subsequent death may occur. As a simple rule of thumb, if the oxygenation index after intubation exceeds 15-20 and there follows prolonged mechanical ventilation, a poor outcome is likely.

Summary The most commonly observed severe lung injuries in early life are the respiratory distress syndrome in premature infants and the acute respiratory distress syndrome in children. Both diseases are characterised by alveolar instability, fluid filled airspace and some degree of airway obstruction. In the acute phase, collapsed alveoli can be reopened with positive end-expiratory pressure and lung recruitment. New insight into the physiology of lung recruitment suggests that the shape of the pressure–volume curve is defined by the change in rate of alveolar opening and closing. Reduced lung volumes and severe ventilation maldistribution are found in the acute phase but may persist during childhood. Any severe lung injury in this early phase of life can cause significant structural and functional damage to the developing lung. Follow-up studies of children with chronic lung disease have shown that the functional abnormalities will improve but may still be present in later childhood.

Smoke inhalation injuries are the leading cause of mortality from burn injury. Airway obstruction due to mucus plugging and bronchoconstriction can cause severe ventilation inhomogeneity and worsen hypoxia. Studies describing changes of viscoelastic characteristics of the lung after smoke inhalation are missing. We present results of a new smoke inhalation device in sheep and describe pathophysiological changes after smoke exposure. Fifteen female Merino ewes were anesthetized and intubated. Baseline data using electrical impedance tomography and multiple-breath inert-gas washout were obtained by measuring ventilation distribution, functional residual capacity, lung clearance index, dynamic compliance, and stress index. Ten sheep were exposed to standardized cotton smoke insufflations and five sheep to sham smoke insufflations. Measured carboxyhemoglobin before inhalation was 3.87 ± 0.28% and 5 min after smoke was 61.5 ± 2.1%, range 50–69.4% ( P < 0.001). Two hours after smoke functional residual capacity decreased from 1,773 ± 226 to 1,006 ± 129 ml and lung clearance index increased from 10.4 ± 0.4 to 14.2 ± 0.9. Dynamic compliance decreased from 56.6 ± 5.5 to 32.8 ± 3.2 ml/cmH2O. Stress index increased from 0.994 ± 0.009 to 1.081 ± 0.011 ( P < 0.01) (all means ± SE, P < 0.05). Electrical impedance tomography showed a shift of ventilation from the dependent to the independent lung after smoke exposure. No significant change was seen in the sham group. Smoke inhalation caused immediate onset in pulmonary dysfunction and significant ventilation inhomogeneity. The smoke inhalation device as presented may be useful for interventional studies.

Functional electrical impedance tomography (EIT) measures relative impedance change that occurs in the chest during a distinct observation period and an EIT image describing regional relative impedance change is generated. Analysis of such an EIT image may be erroneous because it is based on an impedance signal that has several components. Most of the change in relative impedance in the chest is caused by air movement but other physiological events such as cardiac activity change in end expiratory level or pressure swings originating from a ventilator circuit can influence the impedance signal. We obtained EIT images and signals in spontaneously breathing healthy adults, in extremely prematurely born infants on continuous positive airway pressure and in ventilated sheep on conventional mechanical or high frequency oscillatory ventilation (HFOV). Data were analyzed in the frequency domain and results presented after band pass filtering within the frequency range of the physiological event of interest. Band pass filtering of EIT data is necessary in premature infants and on HFOV to differentiate and eliminate relative impedance changes caused by physiological events other than the one of interest.

OBJECTIVE: To obtain optimal titration of positive end-expiratory pressure (PEEP) during mechanical ventilation with functional residual capacity and ventilation homogeneity measurements. DESIGN: Experimental human and animal study. INTERVENTIONS: Functional residual capacity and five indices of uneven ventilation (alveolar mean dilution number, mean dilution number, lung clearance index, mixing ratio, and pulmonary clearance delay) were investigated in 22 children aged 0 to 14 yrs with lung disease and in seven rabbits by using a sulfur-hexafluoride wash-out technique. The children and rabbits were exposed to three different levels of PEEP (0, 5, and 10 cm H(2)O for the children and 0, 3 and 6 cm H(2)O for the rabbits). RESULTS: Functional residual capacity of the children increased from 256.9 +/- 178.6 mL (0 PEEP) to 280.0 +/- 201.1 mL (5 PEEP) and to 302.2 +/- 160.4 mL (10 PEEP, p.001). Ventilation inhomogeneity decreased significantly in all children with increasing PEEP (p.05). The alveolar mean dilution number decreased from 2.00 +/- 0.29 (0 PEEP) to 1.82 +/- 0.37 (5 PEEP) and to 1.66 +/- 0.34 (10 PEEP), and pulmonary clearance delay decreased from 74.9 +/- 24.2% to 66.6 +/- 38.1% and to 63.9 +/- 24.2%, respectively. The reduction in ventilation inhomogeneity was associated with an improvement in Pao(2) from 101 +/- 42 mm Hg (0 PEEP) to 122 +/- 48 mm Hg (5 PEEP) and to 126 +/- 53 mm Hg (10 PEEP). Functional residual capacity of the rabbits increased from 54.1 +/- 18.7 mL at 0 PEEP to 72.3 +/- 23.4 mL at 3 PEEP and to 93.9 +/- 27.3 mL at 10 PEEP. Alveolar mean dilution number decreased from 2.93 +/- 0.1 (0 PEEP) to 2.20 +/- 0.29 (3 PEEP) and to 1.45 +/- 0.13 (6 PEEP). CONCLUSIONS: In children with lung disease receiving ventilatory support, optimal PEEP titration can be obtained by the measurement of the functional residual capacity and ventilation distribution by using a sulfur-hexafluoride wash-in-wash-out technique.

Background - Mechanically ventilated children are at risk of chronic de-recruitment with low tidal volume ventilation and acute de-recruitment with each disconnection from the circuit and application of suction. Lung recruitment manoeuvres have demonstrated gain in end expiratory levels (EEL) in both adult and experimental studies. Aim - To quantify the impact of two different methods of manipulating PEEP on EEL and regional gas distribution as measured by electrical impedance tomography (EIT) . Method - A randomised crossover clinical trial in 60 intubated and mechanically ventilated children in a PICU. Forty children underwent two methods of lung recruitment following endotracheal suctioning: a double baseline PEEP manoeuvre – held for two minutes and an incremental PEEP manoeuvre, each step held for one minute. Twenty children acted as controls. EIT measurements to quantify EEL were taken at baseline and at 15 minute intervals throughout the study period. Results - The Double PEEP manoeuvre showed significant and sustained improvement in global EEL from baseline up to 120 min (P < 0.01 ANOVA). Global EEL did not change with the Incremental PEEP manoeuvre or in the control group. The Double PEEP manoeuvre also demonstrated preferential ventilation distribution towards the dependent regions of the lung (P = 0.03 ANOVA). Nil adverse events were observed. Conclusion - Significant increases in EEL were achieved globally with a simple Double PEEP manoeuvre. The magnitude of the dependent ventilation also increased, suggesting genuine alveolar recruitment in dependent regions of the lung that was sustained for up to 120 min.

Genotype-phenotype association in cystic fibrosis (CF) is difficult because of heterogeneous disease expression. The genotype-phenotype correlation for the 3905insT mutation in comparison to ΔF508 was studied here.Thirty CF patients compound heterozygous for 3905insT were compared to clinical presentation of matched patients homozygous for ΔF508 (1960–1997). Sweat tests, age at diagnosis, at death and at onset ofPseudomonas aeruginosacolonization were analysed. Chrispin-Norman scores and pulmonary function forced expiratory volume in one second (FEV1) determined severity of lung disease. Twenty-five of the patients with 3905insT had ΔF508 as a second mutation and five had another rare mutation.At the age of 15 yrs, 60% of patients with 3905insT had an FEV1P. aeruginosacolonization was not different in the study groups. Sweat chloride concentrations were lower in patients homozygous for ΔF508 (105.63±15.3 mmol·L−1) than in patients with 3905insT (119.9±22.1 mmol·L−1) (pPatients compound heterozygous for 3905insT have similar high morbidity and mortality to patients homozygous for ΔF508.

Background: We propose a new approach to the measurement of small airway function as an alternative to recordings of maximal expiratory flow-volume (MEFV) curves. Objectives: A newly developed technique to record isoflow-volume (IFV) curves to be tested against maximal respiratory flow curves. Methods: An isoflow whistle (IFW; Iflopen®) measures the length of a constant expiration after full inspiration. The note of the whistle enables a subject to generate an even expiration, and the isoflow maintenance times at 1 l·s–1 (IFMT1) and 2 l·s–1 (IFMT2) are recorded. The accuracy and reproducibility of the IFV technique were evaluated in 17 healthy adults (age 17–55 years) and in 14 asthmatic children (age 6–14 years). Comparisons with standard lung function parameters, such as forced expiratory volume in 1 s (FEV1), maximal expiratory flow at 50% (MEF50) and 25% (MEF25) vital capacity and peak expiratory flow (PEF), obtained with a Wright® Peakflow Meter were undertaken in 102 healthy (aged 8–14 years) and 101 asthmatic children (aged 6–17 years). A bronchial challenge test was performed in 13 asthmatic children. Results: The expired volume measured by the IFW showed an acceptable agreement with that of a pneumotachograph (mean error of 4.32% for IFMT1 and 5.93% for IFMT2). In healthy and in asthmatic children, the correlations between FEV1 and IFMT1 or IFMT2 (r = 0.92 and 0.94, respectively) were found to be greater than that between FEV1 and PEF (r = 0.68). During bronchial challenge tests in 13 asthmatic children, the FEV1 decreased to 69% of baseline and IFMT1 to 58% of baseline. Conclusions: The IFV technique accurately measured airway obstruction and closely followed changes in standard parameters of the MEFV curve.

A sulfur hexafluoride (SF(6)) washin/washout technique was developed using an ultrasonic flowmeter to measure functional residual capacity (FRC) during mechanical ventilation. The ultrasonic flowmeter measures simultaneously flow and molar mass of the mainstream gas. Ventilation distribution was studied using moment ratios analysis (alveolar-based mean dilution number). Accuracy and precision of the measurement technique were tested in a mechanical lung model, and the method's sensitivity to changes of FRC was assessed in seven ventilated rabbits and six children. In the mechanical lung model with a volume range from 10 to 60 mL, the mean error of FRC measurement was 0.096 +/- 0.9 mL (range, 0-2 mL). In seven rabbits (mean body weight, 3.6 kg), measurements of FRC and alveolar-based mean dilution number were made at positive end-expiratory pressures (PEEP) of 0, 3, and 6 cm H(2)O. The mean coefficient of variation of 66 FRC-measurements was 5.5% (range, 0-15.3%). As the applied PEEP increased, mean FRC per kilogram body weight increased from 13.3 +/- 3.4 mL/kg (PEEP of 0 cm H(2)O) to 16.7 +/- 3.6 mL/kg (PEEP of 3 cm H(2)O) and to 20.8 +/- 4.3 mL/kg (PEEP of 6 cm H(2)O). Alveolar-based mean dilution number decreased accordingly from 1.94 +/- 0.42 (PEEP = 0; mean +/- SD), to 1.91 +/- 0.45 (PEEP = 3) and to 1.59 +/- 0.35 (PEEP = 6). In the six children, as applied PEEP increased, mean FRC per kilogram increased from 21.1 +/- 4.51 mL/kg (PEEP = 0), to 22.4 +/- 1.8 mL/kg (PEEP = 5) and 27.2 +/- 3.4 mL/kg (PEEP = 10). FRC measurement using the ultrasonic flowmeter is accurate and simple to use in ventilated and spontaneously breathing children.

Chronic recurrent multifocal osteomyelitis is a rare chronic inflammatory musculoskeletal process observed in children and young adults. Recently, the acronym SAPHO syndrome (for synovitis, acne, pustulosis, hyperostosis, osteitis) was coined to emphasise the association between osteo-articular inflammations and different skin abnormalities which are aseptic and filled with neutrophils. In adults, chronic recurrent multifocal osteomyelitis is now a classical manifestation of SAPHO syndrome. Chronic skin disorders were seen in eight of ten children on follow-up at the University Children's Hospitals in Bern and Zurich and in 61 of 260 paediatric cases reported in the literature. The different skin lesions were palmoplantar pustulosis (n = 40), non-palmoplantar pustulosis (n = 6), psoriasis vulgaris (n = 16) or severe acne (n = 4). More rarely Sweet syndrome (n = 2) or pyoderma gangrenosum (n = 1) were reported. Conclusion: The synovitis, acne, pustulosis, hyperostosis, osteitis syndrome is pertinent even in paediatrics since skin involvement is frequent.

A syndrome involving periodic fever, pharyngitis, adenitis and aphthous stomatitis is described in 8 children. Attacks are characterized by abrupt onset of fever and, in addition to the above symptoms, by malaise, headache and abdominal pain. Mild leukocytosis and elevation of the erythrocyte sedimentation rate are found in the laboratory. Patients exhibit normal growth and development and are otherwise healthy. PFAPA is clinically benign, with no long-term sequelae. Recognition and diagnosis of the syndrome eliminate the need for intensive work-up. The cause remains unknown. No evidence linking bacterial, viral, or fungal pathogens to this syndrome has been found. No patient has exhibited atypical lymphocytosis or neutropenia, and all patients had normal levels of immunoglobulin. All had received antibiotics early in the course of their illness but without effect. Cimetidine has been discussed in the literature as a possible treatment, but the results are controversial.

The value of interrupter resistance measurements has been questioned because these depend on equilibration between alveolar (PA) and mouth pressure (PAO), which may not occur during airway obstruction or in measurements in children. In order to determine whether airway geometry and its interaction with the lung volume can be obtained without complete pressure equilibration, the postocclusional oscillatory airway opening pressure transients PAO(t) after flow interruption were studied in comparison to airway resistance (RAW), lung volumes (TGV, VC) and MEF50 in 9 healthy children (7-14 y) and 5 adults (28-37 y) in both time and frequency domains. The frequency of pressure oscillations was correlated to TGV (p < 0.01). Its damping properties (d) were correlated to MEF50 (p < 0.005). Performing airflow interruptions in the same subject showed that d increased at low lung volumes. During bronchial challenge test, d significantly increased with carbachol and decreased with salbutamol, whereas the frequency decreased with carbachol and increased with salbutamol. Therefore, the analysis of postocclusional pressure oscillations can be used to assess relative changes in airway mechanics and its interaction with lung volume during bronchial challenge tests in patients such as children with poor cooperation.

The analysis of the postocclusional rapid oscillatory mouth pressure transients pao(t) after expiratory flow interruption during 100 ms features additional information to the conventional interrupter technique. The analysis focuses on the sudden oscillatory rise in pressure after flow interruption and the following damped oscillation. By calculating the first derivative of pao(t) ( = change in pressure), the frequency omega 0 and damping characteristic d of the pressure swings reflecting the inertive and elastic properties of the thoracopulmonary system can be computed. The interrelationship between omega 0 respectively d and different sizes of lung volume respectively characteristics of airway mechanics (airway resistance (Raw) and/or maximal expiratory flow at 50% vital capacity (MEF50)) was evaluated in 5 healthy adult subjects (28-37 y) and 10 healthy children (7-14 y). The measured frequency was statistically significantly related to lung volume (p < 0.05) and varied between 66 Hz in healthy adults and 91 Hz in children. The damping factor d increased with increasing airway resistance (n.s.) and decreasing MEF50 (p < 0.005). These findings add further arguments to the conjecture previously intimated that development of the viscoelastic properties of the lung are defined by characteristics of airway mechanics in close relationship to lung growth. In consequence, alterations in mechanical properties observed in diseased lungs have functionally closely be evaluated in relation to actual lung volumes (pulmonary hyperinflation, restrictive lung disease).