A novel method for monitoring abdominal compliance to optimize insufflation pressure during laparoscopy.

BACKGROUND: Abdominal compliance describes the ease of expansion of the abdominal cavity. Several studies highlighted the importance of monitoring abdominal compliance (Cab) during the creation of laparoscopic workspace to individualize the insufflation pressure. The lack of validated clinical monitoring tools for abdominal compliance prevents accurate tailoring of insufflation pressure. Oscillometry, also known as the forced oscillation technique (FOT), is currently used to measure respiratory mechanics and has the potential to be adapted for monitoring abdominal compliance. This study aimed to define, develop and evaluate a novel approach which can monitor abdominal compliance during laparoscopy using endoscopic oscillometry. MATERIALS AND METHODS: Endoscopic oscillometry was evaluated in a porcine model for laparoscopy. A custom-built insufflator was developed for applying an oscillatory pressure signal superimposed onto a mean intra-abdominal pressure. This insufflator was used to measure the abdominal compliance at insufflation pressures ranging from 5 to 20 hPa (3.75 to 15 mmHg). The measurements were compared to the static abdominal compliance, which was measured simultaneously with computed tomography imaging. RESULTS: Endoscopic oscillometry recordings and CT images were obtained in 10 subjects, resulting in 76 measurement pairs for analysis. The measured dynamic Cab ranged between 0.0216 and 0.261 L/hPa while the static Cab based on the CT imaging ranged between 0.0318 and 0.364 L/hPa. The correlation showed a polynomial relation and the adjusted R-squared was 97.1%. CONCLUSIONS: Endoscopic oscillometry can be used to monitor changes in abdominal compliance during laparoscopic surgery, which was demonstrated in this study with a comparison with CT imaging in a porcine laparoscopy model. Use of this technology to personalize the insufflation pressure could reduce the risk of applying excessive pressure and limit the drawbacks of insufflation.

Aerosol drug delivery to spontaneously-breathing preterm neonates: lessons learned.

Delivery of medications to preterm neonates receiving non-invasive ventilation (NIV) represents one of the most challenging scenarios for aerosol medicine. This challenge is highlighted by the undersized anatomy and the complex (patho)physiological characteristics of the lungs in such infants. Key physiological restraints include low lung volumes, low compliance, and irregular respiratory rates, which significantly reduce lung deposition. Such factors are inherent to premature birth and thus can be regarded to as the intrinsic factors that affect lung deposition. However, there are a number of extrinsic factors that also impact lung deposition: such factors include the choice of aerosol generator and its configuration within the ventilation circuit, the drug formulation, the aerosol particle size distribution, the choice of NIV type, and the patient interface between the delivery system and the patient. Together, these extrinsic factors provide an opportunity to optimize the lung deposition of therapeutic aerosols and, ultimately, the efficacy of the therapy.In this review, we first provide a comprehensive characterization of both the intrinsic and extrinsic factors affecting lung deposition in premature infants, followed by a revision of the clinical attempts to deliver therapeutic aerosols to premature neonates during NIV, which are almost exclusively related to the non-invasive delivery of surfactant aerosols. In this review, we provide clues to the interpretation of existing experimental and clinical data on neonatal aerosol delivery and we also describe a frame of measurable variables and available tools, including in vitro and in vivo models, that should be considered when developing a drug for inhalation in this important but under-served patient population.

Effect of nocturnal EPAP titration to abolish tidal expiratory flow limitation in COPD patients with chronic hypercapnia: a randomized, cross-over pilot study.

BACKGROUND: Tidal expiratory flow limitation (EFLT) promotes intrinsic PEEP (PEEPi) in patients with chronic obstructive pulmonary disease (COPD). Applying non-invasive ventilation (NIV) with an expiratory positive airway pressure (EPAP) matching PEEPi improves gas exchange, reduces work of breathing and ineffective efforts. We aimed to evaluate the effects of a novel NIV mode that continuously adjusts EPAP to the minimum level that abolishes EFLT. METHODS: This prospective, cross-over, open-label study randomized patients to one night of fixed-EPAP and one night of EFLT-abolishing-EPAP. The primary outcome was transcutaneous carbon dioxide pressure (PtcCO2). Secondary outcomes were: peripheral oxygen saturation (SpO2), frequency of ineffective efforts, breathing patterns and oscillatory mechanics. RESULTS: We screened 36 patients and included 12 in the analysis (age 72 ± 8 years, FEV1 38 ± 14%Pred). The median EPAP did not differ between the EFLT-abolishing-EPAP and the fixed-EPAP night (median (IQR) = 7.0 (6.0, 8.8) cmH2O during night vs 7.5 (6.5, 10.5) cmH2O, p = 0.365). We found no differences in mean PtcCO2 (44.9 (41.6, 57.2) mmHg vs 54.5 (51.1, 59.0), p = 0.365), the percentage of night time with PtcCO2 > 45 mm Hg was lower (62(8,100)% vs 98(94,100)%, p = 0.031) and ineffective efforts were fewer (126(93,205) vs 261(205,351) events/hour, p = 0.003) during the EFLT-abolishing-EPAP than during the fixed-EPAP night. We found no differences in oxygen saturation and lung mechanics between nights. CONCLUSION: An adaptive ventilation mode targeted to abolish EFLT has the potential to reduce hypercapnia and ineffective efforts in stable COPD patients receiving nocturnal NIV. TRIAL REGISTRATION: ClicalTrials.gov, NCT04497090. Registered 29 July 2020-Retrospectively registered, https://clinicaltrials.gov/ct2/show/NCT04497090 .

A novel delivery system for supraglottic atomization allows increased lung deposition rates of pulmonary surfactant in newborn piglets.

BACKGROUND: Earlier attempts to deliver effective lung doses of surfactant by aerosolization were unsuccessful, mostly because of technical shortcomings. We aimed at quantifying the lung deposition of poractant alfa with a new supraglottic delivery system for surfactant atomization in an experimental neonatal model. METHODS: The method involved six sedated 1-day-old piglets lying in the lateral decubitus, spontaneously breathing on nasal-mask continuous positive airway pressure (nCPAP). A pharyngeal cannula housing a multi-channel air-blasting atomization catheter was placed through the mouth with its tip above the glottis entrance. In all, 200 mg kg-1 of a 99mTc-surfactant mixture was atomized through the catheter synchronously with inspiration. Six intubated control piglets received an equal amount of intratracheally instilled 99mTc-surfactant mixture. The percentage of the 99mTc-surfactant mixture deposited in the lungs was estimated by scintigraphy. RESULTS: Median (range) deposition in the lungs was 40% (24-68%) after atomization and 87% (55-95%) after instillation (p < 0.001). Overall, almost 80% of the deposited surfactant was in the dependent lung. Effective atomization time (atomizer on) was 28 (17-52) min, yielding an output rate of 0.1-0.2 mL min-1. CONCLUSIONS: Without endotracheal intubation, in spontaneously breathing newborn piglets, this new supraglottic atomizer delivery system attained a median lung deposition of 40% of the nominal dose of surfactant.

Supraglottic Atomization of Surfactant in Spontaneously Breathing Lambs Receiving Continuous Positive Airway Pressure.

OBJECTIVES: To determine the short-term tolerance, efficacy, and lung deposition of supraglottic atomized surfactant in spontaneously breathing lambs receiving continuous positive airway pressure. DESIGN: Prospective, randomized animal study. SETTING: Animal research laboratory. SUBJECTS: Twenty-two preterm lambs on continuous positive airway pressure (132 ± 1 d gestational age). INTERVENTIONS: Animals receiving continuous positive airway pressure via binasal prongs at 8 cm H2O were randomized to receive atomized surfactant at approximately 60-minute of life (atom; n = 15) or not (control; n = 7). The atom group received 200 mg/kg of poractant alfa (Curosurf; Chiesi Farmaceutici SpA, Parma, Italy) over 45 minutes via a novel atomizer located in the upper pharynx that synchronized surfactant delivery with the inspiratory phase. MEASUREMENTS AND MAIN RESULTS: Arterial blood gas, regional distribution of tidal ventilation (electrical impedance tomography), and carotid blood flow were recorded every 15 minutes until 90 minutes after stabilizing on continuous positive airway pressure. Gas exchange, respiratory rate, and hemodynamic variables, including carotid blood flow, remained stable during surfactant treatment. There was a significant improvement in arterial alveolar ratio after surfactant delivery in the atom group (p < 0.05; Sidak posttests), while there was no difference in PaCO2. Electrical impedance tomography data showed a more uniform pattern of ventilation in the atom group. In the atom group, the median (interquartile range) deposition of surfactant in the lung was 32% (22-43%) of the delivered dose, with an even distribution between the right and the left lungs. CONCLUSIONS: In our model of spontaneously breathing lambs receiving CPAP, supraglottic atomization of Curosurf via a novel device was safe, improved oxygenation and ventilation homogeneity compared with CPAP only, and provided a relatively large lung deposition suggesting clinical utility.

Intratracheal atomized surfactant provides similar outcomes as bolus surfactant in preterm lambs with respiratory distress syndrome.

BACKGROUND: Aerosolization of exogenous surfactant remains a challenge. This study is aimed to evaluate the efficacy of atomized poractant alfa (Curosurf) administered with a novel atomizer in preterm lambs with respiratory distress syndrome. METHODS: Twenty anaesthetized lambs, 127 ± 1 d gestational age, (mean ± SD) were instrumented before birth and randomized to receive either (i) positive pressure ventilation without surfactant (Control group), (ii) 200 mg/kg of bolus instilled surfactant (Bolus group) at 10 min of life or (iii) 200 mg/kg of atomized surfactant (Atomizer group) over 60 min from 10 min of life. All lambs were ventilated for 180 min with a standardized protocol. Lung mechanics, regional lung compliance (electrical impedance tomography), and carotid blood flow (CBF) were measured with arterial blood gas analysis. RESULTS: Dynamic compliance and oxygenation responses were similar in the Bolus and Atomizer groups, and both better than Control by 180 min (all P < 0.05; two-way ANOVA). Both surfactant groups demonstrated more homogeneous regional lung compliance throughout the study period. There were no differences in CBFConclusion:In a preterm lamb model, atomized surfactant resulted in similar gas exchange and mechanics as bolus administration. This study suggests evaluation of supraglottic atomization with this system when noninvasive support is warranted.

Preclinical Assessment of Nebulized Surfactant Delivered through Neonatal High Flow Nasal Cannula Respiratory Support.

High-flow nasal cannula (HFNC) is a non-invasive respiratory support (NRS) modality to treat premature infants with respiratory distress syndrome (RDS). The delivery of nebulized surfactant during NRS would represent a truly non-invasive method of surfactant administration and could reduce NRS failure rates. However, the delivery efficiency of nebulized surfactant during HFNC has not been evaluated in vitro or in animal models of respiratory distress. We, therefore, performed first a benchmark study to compare the surfactant lung dose delivered by commercially available neonatal nasal cannulas (NCs) and HFNC circuits commonly used in neonatal intensive care units. Then, the pulmonary effect of nebulized surfactant delivered via HFNC was investigated in spontaneously breathing rabbits with induced respiratory distress. The benchmark study revealed the surfactant lung dose to be relatively low for both types of NCs tested (Westmed NCs 0.5 ± 0.45%; Fisher & Paykel NCs 1.8 ± 1.9% of a nominal dose of 200 mg/kg of Poractant alfa). The modest lung doses achieved in the benchmark study are compatible with the lack of the effect of nebulized surfactant in vivo (400 mg/kg), where arterial oxygenation and lung mechanics did not improve and were significantly worse than the intratracheal instillation of surfactant. The results from the present study indicate a relatively low lung surfactant dose and negligible effect on pulmonary function in terms of arterial oxygenation and lung mechanics. This negligible effect can, for the greater part, be explained by the high impaction of aerosol particles in the ventilation circuit and upper airways due to the high air flows used during HFNC.

A Compartment-Based Mathematical Model for Studying Convective Aerosol Transport in Newborns Receiving Nebulized Drugs during Noninvasive Respiratory Support.

Nebulization could be a valuable solution to administer drugs to neonates receiving noninvasive respiratory support. Small and irregular tidal volumes and air leaks at the patient interface, which are specific characteristics of this patient population and are primarily responsible for the low doses delivered to the lung (DDL) found in this application, have not been thoroughly addressed in in vitro and in vivo studies for quantifying DDL. Therefore, we propose a compartment-based mathematical model able to describe convective aerosol transport mechanisms to complement the existing deposition models. Our model encompasses a mechanical ventilator, a nebulizer, and the patient; the model considers the gas flowing between compartments, including air leaks at the patient-ventilator interface. Aerosol particles are suspended in the gas flow and homogeneously distributed. The impact of breathing pattern variability, volume of the nebulizer, and leaks level on DDL is assessed in representative conditions. The main finding of this study is that convective mechanisms associated to air leaks and breathing patterns with tidal volumes smaller than the nebulizer dramatically reduce the DDL (up to 70%). This study provides a possible explanation to the inconsistent results of drug aerosolization in clinical studies and may provide guidance to improve nebulizer design and clinical procedures.

In Vitro Performance of an Investigational Vibrating-Membrane Nebulizer with Surfactant under Simulated, Non-Invasive Neonatal Ventilation Conditions: Influence of Continuous Positive Airway Pressure Interface and Nebulizer Positioning on the Lung Dose.

Non-invasive delivery of nebulized surfactant has been a long-pursued goal in neonatology. Our aim was to evaluate the performance of an investigational vibrating-membrane nebulizer in a realistic non-invasive neonatal ventilation circuit with different configurations. Surfactant (aerosols were generated with a nebulizer in a set-up composed of a continuous positive airway pressure (CPAP) generator with a humidifier, a cast of the upper airway of a preterm infant (PrINT), and a breath simulator with a neonatal breathing pattern. The lung dose (LD), defined as the amount of surfactant collected in a filter placed at the distal end of the PrINT cast, was determined after placing the nebulizer at different locations of the circuit and using either infant nasal mask or nasal prongs as CPAP interfaces. The LD after delivering a range of nominal surfactant doses (100-600 mg/kg) was also investigated. Surfactant aerosol particle size distribution was determined by laser diffraction. Irrespective of the CPAP interface used, about 14% of the nominal dose (200 mg/kg) reached the LD filter. However, placing the nebulizer between the Y-piece and the CPAP interface significantly increased the LD compared with placing it 7 cm before the Y-piece, in the inspiratory limb. (14% ± 2.8 vs. 2.3% ± 0.8, nominal dose of 200 mg/kg). The customized eFlow Neos showed a constant aerosol generation rate and a mass median diameter of 2.7 µm after delivering high surfactant doses (600 mg/kg). The customized eFlow Neos nebulizer showed a constant performance even after nebulizing high doses of undiluted surfactant. Placing the nebulizer between the Y-piece and the CPAP interface achieves the highest LD under non-invasive ventilation conditions.

Extended Pharmacopeial Characterization of Surfactant Aerosols Generated by a Customized eFlow Neos Nebulizer Delivered through Neonatal Nasal Prongs.

The delivery of nebulized medications to preterm infants during Non-Invasive Ventilation (NIV) remains an unmet clinical need. In this regard, the effective delivery of nebulized surfactant has been particularly investigated in preclinical and clinical studies. In this work, we investigated the feasibility of delivering nebulized surfactant through various commercially available nasal prong types. We first performed a compendial characterization of surfactant aerosols generated by the eFlow Neos nebulizer, customized to be used in neonates, determining the amount of surfactant delivered by the device as well as the aerodynamic characteristics of surfactant aerosols. Additionally, we extended the compendial characterization by testing the effect of different nasal prong types on the estimated lung dose using a realistic Continuous Positive Airway Pressure (CPAP) circuit that included a cast of the upper airways of a preterm neonate. The compendial characterization of surfactant aerosols delivered through different nasal prongs achieved relatively high delivered surfactant doses (in the range 63-74% of the nominal dose), with aerodynamic characteristics displaying mass median aerodynamic diameters ranging between 2.52 and 2.81 µm. Nevertheless, when using a representative in vitro setup mimicking NIV in a clinical setting, significant differences were observed in terms of the estimated lung dose accounting for up to two-fold differences (from 10% to 20% estimated lung deposition of the nominal dose) depending on the chosen nasal prong type. Considering that surfactant lung deposition rates are correlated with therapeutic efficacy, this study points out the relevance of choosing the appropriate NIV interface to maximize the lung dose of nebulized medications.

Automatic tailoring of the lowest PEEP to abolish tidal expiratory flow limitation in seated and supine COPD patients.

RATIONALE: In COPD patients, the development of tidal expiratory flow limitation (EFLT) results in intrinsic positive end-expiratory pressure (PEEPi), leading to increased work of breathing and worsening patient-ventilator interaction. An external PEEP can mitigate these consequences, but how to optimize its value it is still unknown. OBJECTIVE: To measure the minimum PEEP able to abolish EFLT by a new automatic non-invasive ventilation (NIV) mode in stable hypercapnic COPD patients in the seated and supine positions. METHODS: Twenty-six hypercapnic COPD patients (mean±SD: FEV1%pred = 39.2 ±â€¯16.1, FEV1/FVC%pred = 46.3 ±â€¯16.3%) were studied while receiving NIV during two consecutive 15-min periods, with patients studied seated in the first and supine in the second. A ventilator able to identify EFLT breath-by-breath by using the forced oscillation technique optimized in real-time PEEP to the lowest pressure able to abolish EFLT (PEEPO). RESULTS: The ventilator was always able to identify a PEEPO. Its values were highly variable among patients and increased from median(iqr) 4.0 (0.03) (range: 4.0-8.3cmH2O) to 6 (6.1) cmH2O (range: 4.0-15.7 cmH2O) when patients moved from the seated to the supine position, respectively. PEEPO in supine position did not correlate to any spirometric or anthropometric variable. CONCLUSIONS: PEEPO in COPD patients is highly variable and increases in supine position. It is not predicted by spirometric nor anthropometric variables, but had a considerable variability among the patients. We suggest that PEEPo may be used as a phenotyping variable in COPD patients.

Forced Oscillation Technique and Small Airway Involvement in Chronic Hypersensitivity Pneumonitis.

OBJECTIVE: Hypersensitivity pneumonitis (HP) is an interstitial lung disease caused by the inhalation of specific organic antigens or low-molecular weight substances in genetically susceptible individuals. Although small airway involvement is prominent in patients with chronic HP, conventional pulmonary function tests (PFTs) are relatively insensitive to identify it. Thus, the authors aimed to evaluate resistance (R5) and reactance (X5) values at 5Hz on inspiration, expiration, and whole breath, as well as small airway resistance (R5-19) values using a forced oscillation technique (FOT) in patients with chronic HP, and their responses after bronchodilator. In addition, R5 and X5 values according to the presence or absence of mosaic attenuation on computed tomography (CT) were compared. METHODS: PFTs with plethysmography, diffusing capacity of the lungs for carbon monoxide (DLCO) and FOT measurements were performed pre-bronchodilator and post-bronchodilator. High-resolution CT was performed at the same visit, and classified according to the presence or absence of mosaic attenuation. R5 and X5 values were then compared according to the presence or absence of mosaic attenuation on CT. RESULTS: Twenty-eight patients with chronic HP (57.1% female; mean age, 56±11.5 years; mean forced vital capacity 57±17% predicted) were evaluated. All patients had low X5 values, reflecting lower lung compliance, and only three (8%) demonstrated elevated R5 (whole-breath) values. No patients exhibited bronchodilator response in R5, X5 and R5-19 values. In patients who exhibited greater extension of mosaic attenuation (n=11), R5 and X5 values could not discriminate those with a greater presence of these areas on CT. CONCLUSIONS: The results suggest that FOT does not help to additionally characterise concomitant small airway involvement in patients with chronic fibrotic HP who demonstrate restrictive ventilatory pattern in conventional PFTs. Nevertheless, FOT appeared to better characterise decreased lung compliance due to fibrosis through X5. Bronchodilator therapy did not appear to induce an acute response in chronic HP patients with restrictive disease. The precise role of FOT in subacute HP and obstructive chronic HP, therefore, must be evaluated.

Accuracy of oscillatory pressure measured by mechanical ventilators during high frequency oscillatory ventilation in newborns.

BACKGROUND: Oscillatory pressure (ΔP) measurement during high frequency oscillatory ventilation (HFOV) is technically challenging and influenced by all the components of the measurement system. OBJECTIVES: To evaluate the differences between the ΔP delivered at the inlet of the endotracheal tube and those displayed by commercial neonatal mechanical ventilators and monitoring devices and to characterize how the ventilator circuit and the flowmeter proximal to the patient affect these differences. METHODS: Six devices were evaluated while ventilating three mechanical analogues representing the newborn respiratory system in different disease states. ΔP measured at different points of the ventilator circuit were compared. RESULTS: ΔP accuracy is highly variable and decreases with increasing oscillation frequency and amplitude, independently of the mean airway pressure. At 15 Hz, a ΔP displayed by ventilators of 40 cmH2 O resulted in a ΔP effectively delivered at the tracheal tube ranging from 22 to 49 cmH2 O, depending on the ventilator model, the ventilator circuit, and the patient condition. At these settings, the errors exclusively due to the ventilator circuit and the presence of the flowmeter ranged from 6 to 9 cmH2 O and from 1 to 6 cmH2 O, respectively. CONCLUSIONS: The ventilator model, the breathing circuit, the flowmeter, and the patient condition severely impacts ΔP measurement accuracy during HFOV, leading to highly variable performances. This prevents the possibility of using the ΔP required to normalize gas exchange as an indicator of patients' condition, complicates comparison of ventilators performances, and adds a significant element of complexity in clinical management of HFOV.

Break-dance: an unusual cause of hammer syndrome.

We report the case of a young break-dancer presenting with hammer syndrome. This syndrome has been correlated with many professional and recreational activities but this is, to our knowledge, the first description of hammer syndrome caused by break-dancing. The etiology, diagnosis and treatment modalities of this rare syndrome are considered.