Feasibility of bubble non-invasive positive pressure ventilation, a first-in-human study.

PURPOSE: Infant respiratory distress is  a significant cause of mortality globally. Bubble continuous positive airway pressure (CPAP) is a simple and effective therapy, but sicker infants may require additional support such as non-invasive positive-pressure ventilation (NIPPV). We investigated the feasibility of a simple, low-cost, non-electric bubble NIPPV device. METHODS: In this cross-over feasibility study, seven newborns with moderate respiratory distress (Downes score ≥ 3), weight > 1500 g and gestational age > 32 weeks were randomized to  4 h of treatment with bubble CPAP (5-8 cm H2O) vs. bubble NIPPV (Phigh 8-10 cm H2O/Plow 5-8 cm H2O) followed by 4 h of the alternate treatment. Treatment order (CPAP vs. NIPPV) was randomized. Outcome measures included hourly vital signs, Downes score and O2 saturation. Adverse events including pneumothorax, nasal septal necrosis, necrotizing enterocolitis and death before discharge were also recorded. RESULTS: It took nurses 39 (7.3) s to assemble the bubble NIPPV device. Patients had similar vital signs and Downes scores on both treatments; median (IQR) values on bubble CPAP vs. bubble NIPPV were: heart rate 140 (134.5, 144), 140 (134.5, 144); respiratory rate 70 (56, 80), 65 (58, 82), Downes score 4 (3, 5.75), 4 (3, 5), O2 96 (94, 98), 97 (96, 98). All newborns survived to discharge and there were no adverse events. . CONCLUSIONS: A simple, low-cost, non-electric method of providing NIPPV for newborns with respiratory distress is feasible in limited resource settings. Randomized-controlled trials comparing bubble CPAP and bubble NIPPV are justified.

Bubble bilevel ventilation facilitates gas exchange in anesthetized rabbits.

BACKGROUND: Bubble continuous positive airway pressure is an established therapy for infants in respiratory distress. In resource-limited settings, few treatment options exist for infants requiring further respiratory support. A bubble bilevel device has been developed to provide nonelectric, time-cycled, pressure-limited respiratory support. We compared the efficacy of bubble bilevel ventilation with conventional mechanical ventilation in sedated rabbits. METHODS: Six adult rabbits under inhaled isoflurane general anesthesia were ventilated by alternating intervals of conventional and bubble bilevel ventilation for three 10-15-min periods. During each period, interval arterial blood gas (ABG) measurements were obtained after at least 10 min on the respective mode of ventilation. RESULTS: The bubble bilevel system was able to deliver the following pressures: 20/7, 15/5, 12/5, 8/5 cm H2O. The estimated differences in arterial blood gas values on bubble bilevel vs. ventilator were as follows (normalized values): pH 7.41 vs. 7.40, pCO2 37.7 vs. 40, pO2 97.6 vs. 80. In addition, the bubble bilevel ventilation delivered consistent pressure waveforms without interruption for over 60 min on two rabbits. CONCLUSION: This study demonstrates promising in vivo results on the efficacy of a novel bubble bilevel device, which may prove useful for infants in respiratory distress. IMPACT: Given the lack of personnel, funds or infrastructure to provide neonatal mechanical ventilation in resource-limited settings, additional low-cost, low-tech treatments are necessary to save infant lives. Bubble bilevel ventilation reliably delivers two levels of airway pressure to anesthetized rabbits resulting in normalization of blood gases comparable to those achieved on a traditional ventilator. If proven effective, simple technologies like this device have the potential to significantly impact neonatal mortality due to respiratory distress globally.

Development and performance testing of the low-cost, 3D-printed, smartphone-compatible 'Tansen Videolaryngoscope' vs. Pentax-AWS videolaryngoscope vs. direct Macintosh laryngoscope: A manikin study.

BACKGROUND: While videolaryngoscopes help in the management of difficult airways, they remain too expensive for those with limited resources. We have developed a robust, re-usable, low-cost videolaryngoscope at United Mission Hospital Tansen, Nepal, by combining a smartphone-compatible endoscope capable of capturing still and video images with a three dimensional-printed, channelled, hyperangulated blade. The computer-aided design file for the videolaryngoscope blade was emailed and printed in London before evaluation of its performance on a difficult airway manikin. OBJECTIVE: To benchmark the intubation performance of the Tansen Videolaryngoscope (TVL) in a 'difficult airway' manikin (SimMan3G, tongue fully inflated, neck stiff), against a commercially available videolaryngoscope and a conventional Macintosh laryngoscope. DESIGN: A manikin study. SETTING AND PARTICIPANTS: Forty-three experienced videolaryngoscope users in two London teaching hospitals. INTERVENTION AND OUTCOME: Primary outcome: Intubation success rate. SECONDARY OUTCOMES: grade of laryngeal view, median time to intubation and intubator-rated 'ease of use'. RESULTS: Our device was equivalent to Pentax-AWS and superior to Macintosh laryngoscope (TVL vs. Pentax-AWS vs. Macintosh) in overall intubation success rate (88 vs. 98 vs. 67%, P < 0.05); grade of view (median Cormack-Lehane grade 1 vs. 1 vs. 3, P < 0.01); median time to intubation (17.5 vs. 15.5 vs. 27 s, P < 0.01). In subjective 'ease of use' scores, Pentax-AWS was superior to the TVL, which was superior to Macintosh laryngoscope (Likert-type 1 to 5 scale: 4 vs. 4 vs. 1, P < 0.00001). CONCLUSION: In this manikin simulation of a difficult airway, the 'TVL' was superior to the Macintosh laryngoscope, and noninferior to the Pentax-AWS videolaryngoscope in intubation success rate, grade of laryngeal view and time to intubation. Participants found the Pentax device easier to use, and their feedback has given us valuable insights for improving our device. The TVL is well suited to settings in which resources are limited, being inexpensive, simple and re-usable.

Bench Testing of a Bubble Noninvasive Ventilation Device in an Infant Lung Simulator.

BACKGROUND: Infant respiratory distress remains a significant problem worldwide, leading to more than one million neonatal deaths each year. The cost, maintenance, energy, and personnel required to implement ventilators have proven to be a barrier in many resource-limited settings. To address these barriers, a nonelectric bubble noninvasive positive pressure ventilation (NIV) device was developed. This study aims to benchmark the performance of this bubble NIV device against commercially available ventilators. METHODS: The delivered pressure waveforms and tidal volumes of the bubble NIV device were compared with those of 2 conventional ventilators (ie, Dräger Evita Infinity V500 and Hamilton G5) at the following pressure settings: 8/5, 12/5, and 15/5 cm H2O. To simulate the lung mechanics of an infant in respiratory distress, tests were conducted on the IngMar ASL 5000 Test Lung simulator. Resistance was set at 100 cm H2O/L/s, and compliance was tested at 0.5, 1.0, and 2.0 mL/cm H2O to simulate 3 different patients. RESULTS: The delivered pressure waveforms and compliance curves of the bubble NIV device are similar to those of the Hamilton and Dräger ventilators. The mean ± SD differences between delivered versus set pressure gradient (ie, the difference between the high delivered pressure and the low delivered pressure) for each treatment modality across the various values of compliance were -2 ± 8% for the bubble NIV device, 3 ± 4% for the Dräger ventilator, and 7 ± 10% for the Hamilton ventilator. CONCLUSIONS: The similarity of pressure waveforms and delivered tidal volumes in this simulated clinical scenario suggest that the bubble NIV device may provide comparable efficacy compared with traditional ventilator treatment for a range of patients. This may provide clinicians in resource-limited settings with an additional, simple, nonelectric treatment modality for the management of infant respiratory distress.

Reproducing Patient-Specific Hemodynamics in the Blalock-Taussig Circulation Using a Flexible Multi-Domain Simulation Framework: Applications for Optimal Shunt Design.

For babies born with hypoplastic left heart syndrome, several open-heart surgeries are required. During Stage I, a Norwood procedure is performed to construct an appropriate circulation to both the systemic and the pulmonary arteries. The pulmonary arteries receive flow from the systemic circulation, often using a Blalock-Taussig (BT) shunt between the innominate artery and the right pulmonary artery. This procedure causes significantly disturbed flow in the pulmonary arteries. In this study, we use computational hemodynamic simulations to demonstrate its capacity for examining the properties of the flow through and near the BT shunt. Initially, we construct a computational model which produces blood flow and pressure measurements matching the clinical magnetic resonance imaging (MRI) and catheterization data. Achieving this required us to determine the level of BT shunt occlusion; because the occlusion is below the MRI resolution, this information is difficult to recover without the aid of computational simulations. We determined that the shunt had undergone an effective diameter reduction of 22% since the time of surgery. Using the resulting geometric model, we show that we can computationally reproduce the clinical data. We, then, replace the BT shunt with a hypothetical alternative shunt design with a flare at the distal end. Investigation of the impact of the shunt design reveals that the flare can increase pulmonary pressure by as much as 7% and flow by as much as 9% in the main pulmonary branches, which may be beneficial to the pulmonary circulation.

The interdomain region of dengue NS5 protein that binds to the viral helicase NS3 contains independently functional importin beta 1 and importin alpha/beta-recognized nuclear localization signals.

Dengue virus NS5 protein is a multifunctional RNA-dependent RNA polymerase that is essential for virus replication. We have shown previously that the 37- amino acid interdomain spacer sequence (residues (369)X(2)KKX(14)KKKX(11)RKX(3)405) of Dengue2 NS5 contains a functional nuclear localization signal (NLS). In this study, beta-galactosidase fusion proteins carrying point mutations of the positively charged residues or truncations of the interdomain linker region (residues 369-389 or residues 386-405) were analyzed for nuclear import and importin binding activities to show that the N-terminal part of the linker region (residues 369-389, a/bNLS) is critical for nuclear localization and is recognized with high affinity by the conventional NLS-binding importin alpha/beta heterodimeric nuclear import receptor. We also show that the importin beta-binding site (residues 320-368, bNLS) adjacent to the a/bNLS, previously identified by yeast two-hybrid analysis, is functional as an NLS, recognized with high affinity by importin beta, and able to target beta-galactosidase to the nucleus. Intriguingly, the bNLS is highly conserved among Dengue and related flaviviruses, implying a general role for the region and importin beta in the infectious cycle.