A Pumpless Microfluidic Neonatal Lung Assist Device for Support of Preterm Neonates in Respiratory Distress.

Premature neonates suffer from respiratory morbidity as their lungs are immature, and current supportive treatment such as mechanical ventilation or extracorporeal membrane oxygenation causes iatrogenic injuries. A non-invasive and biomimetic concept known as the "artificial placenta" (AP) would be beneficial to overcome complications associated with the current respiratory support of preterm infants. Here, a pumpless oxygenator connected to the systemic circulation supports the lung function to relieve respiratory distress. In this paper, the first successful operation of a microfluidic, artificial placenta type neonatal lung assist device (LAD) on a newborn piglet model, which is the closest representation of preterm human infants, is demonstrated. This LAD has high oxygenation capability in both pure oxygen and room air as the sweep gas. The respiratory distress that the newborn piglet is put under during experimentation, repeatedly and over a significant duration of time, is able to be relieved. These findings indicate that this LAD has a potential application as a biomimetic artificial placenta to support the respiratory needs of preterm neonates.

An integrated array of microfluidic oxygenators as a neonatal lung assist device: in vitro characterization and in vivo demonstration.

A miniaturized oxygenator device that is perfused like an artificial placenta via the umbilical vessels may have significant potential to save the lives of newborns with respiratory insufficiency. Recently we presented the concept of an integrated modular lung assist device (LAD) that consists of stacked microfluidic single oxygenator units (SOUs) and demonstrated the technical details and operation of SOU prototypes. In this article, we present a LAD prototype that is designed to accommodate the different needs of term and preterm infants by permitting changing of the number of parallel-stacked microfluidic SOUs according to the actual body weight. The SOUs are made of polydimethylsiloxane, arranged in parallel, and connected though 3D-printed polymeric interconnects to form the LAD. The flow characteristics and the gas exchange properties were tested in vitro using human blood. We found that the pressure drop of the LAD increased linearly with flow rate. Gas exchange rates of 2.4-3.8 µL/min/cm(2) (0.3-0.5 mL/kg/min) and 6.4-10.1 µL/min/cm(2) (0.8-1.3 mL/kg/min) for O2 and CO2 , respectively, were achieved. We also investigated protein adsorption to provide preliminary information on the need for application of anticoagulant coating of LAD materials. Albumin adsorption, as measured by gold staining, showed that surface uptake was evenly distributed and occurred at the monolayer level (>0.2 µg/cm(2) ). Finally, we also tested the LAD under in vivo conditions using a newborn piglet model (body weight 1.65-2.0 kg). First, the effect of an arteriovenous bypass via a carotid artery-to-jugular vein shortcut on heart rate and blood pressure was investigated. Heart rate and mean arterial blood pressure remained stable for extracorporeal flow rates of up to 61 mL/kg/min (101 mL/min). Next, the LAD was connected to umbilical vessels (maximum flow rate of 24 mL/min [10.4 mL/kg/min]), and O2 gas exchange was measured under hypoxic conditions (Fi O2 = 0.15) and was found to be 3.0 µL/min/cm(2) . These results are encouraging and support the feasibility of an artificial placental design for an LAD.

Airway pressure release ventilation: a neonatal case series and review of current practice.

BACKGROUND: The use of airway pressure release ventilation (APRV) in very low birth weight infants is limited. OBJECTIVE: To report the authors' institutional experience and to review the current literature regarding the use of APRV in pediatric populations. METHODS: Neonates <1500 g ventilated using APRV from 2005 to 2006 at McMaster Children's Hospital (Hamilton, Ontario) were retrospectively reviewed. Publications describing APRV in children from 1987 to 2011 were reviewed. RESULTS: Five infants, 24 to 28 weeks' gestational age, were ventilated using APRV. Indications for APRV were refractory hypoxemia (n=3), ventilatory dyssynchrony (n=1) and minimizing sedatives (n=1). All infants appeared to tolerate APRV well with no recorded adverse events. Current pediatric evidence regarding APRV is primarily observational. Published experience reveals that APRV settings in pediatrics often approximate those used in adults, thus deviating from the original guidelines recommended in children. Clinical outcomes, such as oxygenation, ventilation and sedation requirements, are inconsistent. CONCLUSIONS: APRV is primarily used as a rescue ventilation mode in children. Neonatal evidence is limited; however, the present study indicates that APRV is feasible in very low birth weight infants. There are unique considerations when applying this mode in small infants. Further research is necessary to confirm whether APRV is a safe and effective ventilation strategy in this population.

The use of the Laerdal infant resuscitator results in the delivery of high oxygen fractions in the absence of a blender.

BACKGROUND: High oxygen increases morbidity and mortality. Current guidelines in Neonatal Resuscitation Programme (NRP) state if self-inflating bags are used with an input FiO2 of 1.0 without an oxygen reservoir a delivered safe FiO2 of approximately 0.40 is achieved. This conflicts with manufacturer findings (Laerdal infant resuscitator (LIR)). We assessed FiO2 delivery by the LIR, varying oxygen reservoir (OR) use, ventilation and input flowrates. METHODS: A test lung was connected to the LIR and oxygen analyzer. FiO2 delivery was measured under these four conditions: LIR plus OR and FiO2 1.0 or FiO2 0.40; LIR minus OR and FiO2 of 1.0 and 0.40. Variations of ventilation patterns in random order, assessed tidal volumes (from 20 and 40mL), ventilation rates (from 30, 40 and 60breaths/min), and input flowrates (from 1, 3, 5, 8, and 10Lpm). A wash-out period of 1min of ventilation was followed by measure of FiO2 during manual ventilation. RESULTS: The measured FiO2 with the LIR delivered the same source FiO2 under all experimental conditions for flowrates of 5Lpm and greater; irrespective of the OR presence or absence. At flowrates of 1 and 3Lpm, FiO2 was lower, with and without the reservoir, but the reservoir was visibly identified as not filled. CONCLUSION: Our findings support the manufacturers performance specification that high input FiO2 results in high delivered FiO2 with/without an OR. These results dispute the 2006 NRP guidelines that state "in the absence of a reservoir (oxygen) the delivered oxygen is reduced to about 40%".

Positive end-expiratory pressure above lower inflection point minimizes influx of activated neutrophils into lung.

OBJECTIVES: To compare the effects of low vs. high tidal volume (Vt) with three positive end-expiratory pressure (PEEP) strategies on activated neutrophil influx into the lung. DESIGN: Prospective, randomized controlled animal study. SETTING: Animal laboratory in a university hospital. SUBJECTS: Newborn piglets. INTERVENTIONS: Surfactant-depleted piglets were randomized in littermate pairs; to PEEP of either 0 (zero end-expiratory pressure [ZEEP]; n = 6), 8 cm H2O (PEEP 8; n = 5), or 1 cm H2O above the lower inflection point (LIP) (PEEP>LIP; n = 6). Within each pair piglets were randomized to a low VT (5-7 mL/kg) or high VT strategy (17-19 mL/kg). After 4 hrs of mechanical ventilation, 18-fluorodeoxyglucose (18FDG) was injected and positron emission tomography scanning was performed. MEASUREMENTS AND MAIN RESULTS: VT and PEEP changes on influx constants of 18FDG were assessed by analysis of variance. A within-litter comparison of Vt was nonsignificant (p = .50). A between-litter comparison, ordered in linear trend rank, from ZEEP, to PEEP 8, to PEEP>LIP, showed a strong effect of PEEP on influx constant (p = .019). CONCLUSIONS: PEEP set above the LIP on the inspiratory limb of the pressure-volume curve affords a stronger lung protection than VT strategy.

PEEP--a "cheap" and effective lung protection.

Mechanical ventilation is a complex therapy with several different parameters which can be altered. In preterm and term infants, more attention has been paid to the levels of peak inspiratory pressure than to the positive end-expiratory pressure (PEEP). An awareness that lung protection can be conferred by an appropriate level of PEEP has increasingly stimulated a renewed interest in achieving the "best PEEP" strategy. We review the history of the introduction of PEEP therapy, some of the early demonstrations of its potential for mischief, the evidence on what levels of PEEP are appropriate in infants, some data concerning the lung-protective value of PEEP and finally some recent efforts at defining measures to determine the so-called "best PEEP". Some of this work has been performed in adults with the acute respiratory distress syndrome. In newborns, we are regrettably forced to conclude that there is, for the immediate present, no easy substitute for sensible clinical observations coupled with a judicious and cautious adjustment of PEEP. We anticipate that a more logical application of PEEP with individualisation of therapy, based on a pressure-volume relationship, will in future enable targeted tests of PEEP as a lung-protection strategy.