Interhospital Transport of Critically Ill Children to PICUs in the United Kingdom and Republic of Ireland: Analysis of an International Dataset.

OBJECTIVES: International data on characteristics and outcomes of children transported from general hospitals to PICUs are scarce. We aimed to 1) describe the development of a common transport dataset in the United Kingdom and Ireland and 2) analyze transport data from a recent 2-year period. DESIGN: Retrospective analysis of prospectively collected data. SETTING: Specialist pediatric critical care transport teams and PICUs in the United Kingdom and Ireland. PATIENTS: Critically ill children less than 16 years old transported by pediatric critical care transport teams to PICUs in the United Kingdom and Ireland. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: A common transport dataset was developed as part of the Paediatric Intensive Care Audit Network, and standardized data were collected from all PICUs and pediatric critical care transport teams from 2012. Anonymized data on transports (and linked PICU admissions) from a 2-year period (2014-2015) were analyzed to describe patient and transport characteristics, and in uni- and multivariate analyses, to study the association between key transport factors and PICU mortality. A total of 8,167 records were analyzed. Transported children were severely ill (median predicted mortality risk 4.4%) with around half being infants (4,226/8,167; 51.7%) and nearly half presenting with respiratory illnesses (3,619/8,167; 44.3%). The majority of transports were led by physicians (78.4%; consultants: 3,059/8,167, fellows: 3,344/8,167). The median time for a pediatric critical care transport team to arrive at the patient's bedside from referral was 85 minutes (interquartile range, 58-135 min). Adverse events occurred in 369 transports (4.5%). There were considerable variations in how transports were organized and delivered across pediatric critical care transport teams. In multivariate analyses, consultant team leader and transport from an intensive care area were associated with PICU mortality (p = 0.006). CONCLUSIONS: Variations exist in United Kingdom and Ireland services for critically ill children needing interhospital transport. Future studies should assess the impact of these variations on long-term patient outcomes taking into account treatment provided prior to transport.

Development of an Intelligent Spacer Data Logger System.

BACKGROUND: Although delivery of drugs from pressurized metered dose inhalers (pMDIs) via spacer devices is widespread it cannot be assumed that patients take their medication as prescribed or use their spacer appropriately. We developed a Spacer Data Logger device to record patient adherence and whether patients had shaken the pMDI, actuated it soon after shaking, and inhaled a sufficient volume from it. METHODS: We report an assessment of the Spacer Data Logger to measure and record that the pMDI was adequately shaken, the time to actuation, and the volume "inhaled" from the spacer up to 26 seconds after actuation. The effect of a delay in actuation following shaking on the dose available for inhalation from the spacer and the effect of a delay in extraction of aerosol from the spacer were assessed using different strengths of beclomethasone dipropionate (50 and 100 µg) and fluticasone propionate (50, 125 and 250 µg). RESULTS: The volumes measured by the Spacer Data Logger were in close agreement with the reference volumes of four simulated breathing patterns. A delay between shaking and actuating the pMDI resulted in a significant increase in the dose available for inhalation after only 4 seconds for the 50 and 250 µg strengths of fluticasone propionate pMDIs (p = 0.004 and p < 0.001, respectively). A delay between actuation of the drug into the spacer and "inhalation" of aerosol from the spacer also resulted in a steady decline in the dose available from the spacer (p < 0.0001). CONCLUSIONS: These results confirmed the importance of using the pMDI spacer correctly by actuating directly after shaking and inhaling the aerosol from the spacer as soon after actuation as possible to optimize the dose available for inhalation. The Spacer Data Logger should be a useful tool to determine adherence to and "optimum" use of pMDI spacers in patients with asthma and chronic obstructive pulmonary disease (COPD).

Nebulisation of corticosteroid suspensions and solutions with a beta(2) agonist.

The aim of this study was to determine the output of salbutamol nebulised in combination with either flunisolide or beclometasone dipropionate (BDP) from two different nebulisers under simulated breathing conditions. The BimboNeb and Nebula nebulisers were used to nebulise 3.0 mL of the two drug mixtures (salbutamol, 5000 microg plus either flunisolide, 600 microg, or BDP, 800 microg). Particle size was determined by inertial impaction. Total outputs of all drugs from both nebulisers were measured using a sinus flow pump under simulated paediatric and adult breathing patterns. The mass median aerodynamic diameter (MMAD) of BDP particles from the mixture was 6.34 mum using the BimboNeb and 5.34 mum using the Nebula. Values for salbutamol in this mixture were 3.93 and 3.32 microm, respectively. The MMAD of flunisolide particles from the BimboNeb and Nebula were 3.74 and 3.65 microm, respectively, while for salbutamol were 3.79 and 3.74 microm, respectively. With the simulated adult breathing pattern, all drug outputs from both mixtures were greater from the BimboNeb than from the Nebula after 5 and 10 min' nebulisation. Drug delivery from the BimboNeb, but not the Nebula, was affected by the simulated breathing pattern. Outputs with the BimboNeb were lower with the paediatric breathing pattern than with the adult pattern. In the majority of cases, nebulising for 10 min produced significantly greater drug output than after 5 min. For the Nebula, outputs were generally similar at 5 and 10 min, irrespective of the breathing pattern. These results highlight the need to assess the amount of aerosolised drug available when drugs are combined, when different nebulisers are used and when they are used with patients of different ages.

Altitude-related cough.

Cough is a troublesome condition which affects many visitors to high altitude. Traditionally it has been attributed to the inspiration of the cold, dry air which characterizes the high altitude environment. This aetiology was brought into question by observations and experiments in long duration hypobaric chamber studies in which cough still occurred despite controlled temperature and humidity. Anecdotally however, exercise, possibly via the associated increase in ventilation, does appear to precipitate cough at altitude. It is likely that the term, altitude-related cough, covers a number of conditions and aetiologies. These aetiologies are discussed and include water loss from the respiratory tract; high altitude pulmonary oedema; acute mountain sickness; bronchoconstriction; respiratory tract infections; vasomotor rhinitis and post-nasal drip; and alterations in the central control of respiration. We hypothesize that there are two forms of altitude-related cough: a cough which may occur at relatively low altitudes and which is related to exercise and persists despite descent and a cough which does not occur at altitudes below 5000-6000 m and which improves rapidly with descent to lower altitude. The treatment of altitude-related cough is symptomatic and frequently ineffective. Further work is required to understand the nature and aetiology of the cough which occurs at high altitude before effective therapies can be developed.

Enhanced delivery of nebulised salbutamol during non-invasive ventilation.

Non-invasive ventilation (NIV) is used to treat acute respiratory failure. Nebulised drugs can be delivered concurrently with NIV or during breaks from ventilatory support. We hypothesised that the amount of nebulised salbutamol inhaled when delivered via bi-level ventilation would be no different to the amount available directly from the same nebuliser. A standard bi-level ventilation circuit was attached to a lung model simulating adult respiration. Drug delivery was compared when salbutamol (5 mg) was nebulised at different positions in the circuit and separately, with no ventilator. The amount of salbutamol contained in various particle size fractions was also determined. Nebuliser position within the NIV circuit was critically important for drug delivery. Optimal delivery of salbutamol occurred with the expiration port between the facemask and nebuliser (647+/-67 micro g). This was significantly better than nebulisation without the ventilator (424+/-61 micro g; P < 0.01). Delivery when the nebuliser was positioned between the facemask and expiration port was 544+/-85 micro g. The amount of salbutamol contained in particles < 5 micro m was significantly increased when the nebuliser was used in conjunction with bi-level ventilation (576+/-60 micro g vs 300+/-43 micro g, P < 0.001). We conclude that nebulised bronchodilator therapy, using a Cirrus jet nebuliser, during bi-level ventilation increases respirable particles likely to be inhaled when the nebuliser is optimally positioned within the circuit.

Effect of device inhalational resistance on the three-dimensional configuration of the upper airway.

Entrainment and de-aggregation of aerosol particles from dry powder inhalers (DPIs) is achieved by a forceful inhalation from the device by the patient and by the airflow resistance built into the device. The aerodynamic shear stress imposed by the upper airway also plays an important role in the de-aggregation process. In this study the effect of device airflow resistance on the upper airway shape is determined. Seven healthy subjects inhaled via a test inhaler of different resistances (0.2 x 10(5) to 2.2 x 10(5) N(0.5).s.m(-4)) while the upper airway was imaged using magnetic resonance imaging. Decreasing the test inhaler resistance led to an increase in the cross-sectional areas of the upper airway at the oral cavity, oropharynx and larynx, while the cross-sectional areas of the upper trachea remained rather constant. The mean volume of the upper airway also increased from 72 (22) cm3 (mean (SD)) to 101 (25) cm3 by decreasing device airflow resistance from 2.2 x 10(5) to 0.2 x 10(5) N(0.5).s.m(-4). In conclusion, this study shows a significant variation in the shape of the upper airway during inhalation via devices with different resistances. This may aid understanding of drug deposition in the lungs from DPIs.

Dynamic change of the upper airway during inhalation via aerosol delivery devices.

Although it is likely that the upper airway is a major factor in the large inter- and intra-subject variation in deposition of inhaled drug aerosols in the lung, data on the configuration of the upper airway during inhalation is sparse. We have developed a unique method, using magnetic resonance imaging, to reconstruct the upper airway in three dimensions during inhalation from aerosol devices used to deliver medication to patients with asthma, chronic obstructive pulmonary disease, and cystic fibrosis. Ten healthy adults were imaged while inhaling from a pressurized metered dose inhaler (pMDI), a spacer used with pMDI (spacer), and a high-resistance dry powder inhaler, the Turbuhaler (DPI). The mean cross-sectional area of the oropharyngeal region was significantly larger (Wilcoxon's signed-rank test with Bonferroni correction, p < 0.0167) when the DPI (281 [143] mm2, mean [SD]) was used compared to the spacer (205 [32] mm2, p = 0.016) or pMDI (152 [48] mm2, p = 0.013). Considerable variations in the cross-sectional areas of the oral cavity, oropharynx, and larynx were seen when compared to the upper trachea. The main cause for this was the varying position of the tongue during inhalation via the devices. Although differences were observed when comparing the total volume of the upper airway during inhalation via the DPI (70 [17] cm3) to the pMDI (56 [20] cm3, p = 0.037) or spacer (59 [12] cm3, p = 0.022), these did not reach significance. This study shows that there are very significant variations in the configuration of the upper airway when different devices are used for inhalation. These changes are likely to be produced by a number of factors, including tongue position, device airflow resistance, and patient effort.

The future of nebulization.

Currently available nebulizers are inefficient, bulky, noisy, and take longer to use than other inhalation devices. Use of nebulizers is increasingly confined to patients who cannot use other devices or who require therapies not available in another form. In the future, nebulizers will be smaller and more efficient. "Smart" nebulizers that can monitor patient use and provide feedback to the patient and the caregiver will be developed. Critical study will be needed to determine whether these innovations improve patient compliance with therapy. Nebulizers will also be refined for delivering complex molecules for both pulmonary and systemic disease. One example is in the use of gene therapy, in which issues such as the best gene vector are unresolved. Nebulizing these complex molecules without damaging them may be difficult, and nebulizers of the future will have to be more efficient to avoid wasting expensive drugs. For the delivery of widely used, less expensive medications, such as some bronchodilators, these innovations will not be cost-effective, so cheaper, less efficient nebulizers will continue to be used.