Jet nebulization of prostaglandin E1 during neonatal mechanical ventilation: Stability, emitted dose and aerosol particle size

Sood, Beena G.; Peterson, Jennifer; Malian, Monica; Galli, Robert; Geisor-Walter, Maria; McKinnon, Jon; Sharp, Jody; Maddipati, Krishna Rao

doi:10.1016/j.phrs.2007.09.017

Cited by 16 publications

(19 citation statements)

References 38 publications

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“…Both PGE 1 and Gd-DTPA are water-soluble compounds. We have previously reported the physicochemical properties of PGE 1 and the aerosol particle size distribution (6). In this report, we have used aerosolized Gd-DTPA as a paramagnetic contrast agent.…”

Section: Discussionmentioning

confidence: 99%

“…We have previously described the safety and feasibility of inhaled PGE 1 (IPGE 1 ) in NHRF in a phase I/II unblinded clinical trial (5). We have also reported the stability and emitted dose of IPGE 1 following jet nebulization in a neonatal ventilator circuit and predicted primarily alveolar deposition based on the aerosol particle size distribution (6). Alveolar deposition is important for optimal drug effect.…”

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confidence: 99%

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Aerosol Delivery in Ventilated Newborn Pigs: An MRI Evaluation

et al. 2008

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Pulmonary deposition of inhaled drugs in ventilated neonates has not been studied in vivo. The objective of this study was to evaluate pulmonary delivery of gadopentetate dimeglumine (Gd-DTPA) following nebulization in ventilated piglets using magnetic resonance imaging. Seven ventilated piglets (5 Ϯ 2 d old, weight 1.8 Ϯ 0.5 kg) were scanned in the Bruker/Siemens 4T magnetic resonance scanner using T1 weighted spin-echo sequence. Aerosols of Gd-DTPA were generated continuously using the MiniHeart jet nebulizer. Breath-hold coronal images were obtained before and every 10 min during aerosolized Gd-DTPA for 90 min. Signal intensity (SI) changes over the lungs, kidneys, liver, skeletal muscle, and heart were evaluated. A significant increase in SI was observed in the lungs, kidney, and liver at 10, 20, and 40 min respectively after start of aerosol. At the end of 90 min, the SI increased by 95%, 101%, and 426% over the right lung, left lung, and kidney, respectively. A much smaller increase in SI was observed over the liver. In conclusion, we have demonstrated effective pulmonary aerosol delivery within 10 min of contrast nebulization in ventilated piglets. Contrast visualization in the kidneys within 20 min of aerosol initiation reflects alveolar absorption, glomerular filtration and renal concentration. (Pediatr Res 64: 159-164, 2008)

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Section: Discussionmentioning

confidence: 99%

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Aerosol Delivery in Ventilated Newborn Pigs: An MRI Evaluation

et al. 2008

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“…In contrast, Alzahrani et al 26 demonstrated that albuterol delivery during HFOV was significantly greater than that during conventional ventilation using an adult cast model. Using a low-flow jet nebulizer with aerosolized prostaglanding E1 placed in the inspiratory limb of a of neonatal ventilator circuit, Sood et al 27 reported drug delivery efficiency of 32%-40% of the nominal dose during conventional ventilation and only 0.1% during HFOV. A potential issue with their model is that they collected drug as condensate at the end of the ETT deposited in a closed bottle.…”

Section: Discussionmentioning

confidence: 99%

Iloprost Drug Delivery during Infant Conventional and High‐Frequency Oscillatory Ventilation

et al. 2016

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Iloprost is a selective pulmonary vasodilator approved for inhalation by the Food and Drug Administration. Iloprost has been increasingly used in the management of critically ill neonates with hypoxic lung disease. This in vitro study was designed to test the hypothesis that aerosol drug delivery could be effectively administered to infants with both conventional ventilation and high-frequency oscillatory ventilation (HFOV). A neonatal test lung model configured with newborn lung mechanics was ventilated with a conventional ventilator and an HFOV with standard settings. A vibrating-mesh nebulizer was placed (1) proximal to the patient airway in the inspiratory limb between the humidifier probe and patient wye (conventional) as well as between the vent circuit and the endotracheal tube (ETT) for HFOV and (2) between the ventilator and humidifier (distal). Iloprost was nebulized in three separate runs using three new nebulizers in each of the circuit locations. A collecting filter was placed at the distal end of the ETT for each trial. Iloprost was quantified using highperformance liquid chromatography. The percentage of nominal dose delivered was greater with the nebulizer placed proximal to the airway for conventional ventilation (10.74% ± 2%) and HFOV (29% ± 2%) than with it placed in the distal position (2.96% ± 0.2% vs. 0.96% ± 0.8%, respectively; P < 0.05). Drug delivery in proximal position was nearly threefold greater during HFOV than during conventional ventilation. In conclusion, iloprost drug delivery was best achieved when the nebulizer was placed proximal to the patient airway during neonatal mechanical ventilation. Drug delivery appears to be more efficient during HFOV than during conventional ventilation.Keywords: neonatal ventilation, pediatric aerosol delivery, high-frequency ventilation, inhaled pulmonary vasodilation, infant hypoxic lung disease. Iloprost (Ventavis; Actelion Pharmaceuticals US) is a stable prostacyclin analog used in the treatment of pulmonary hypertension. It is pharmacologically similar to epoprostenol, with vasodilatory, vascular remodeling, and platelet inhibitory properties, but it is a more stable compound, with an elimination half-life of 20-30 minutes. 1The longer half-life than that of other prostacyclin formulations allows the drug to be delivered with less frequency. Iloprost was the first prostacyclin designed specifically for aerosolization and approved for inhalation in ambulatory adults with primary pulmonary hypertension using the I-neb AAD system (Philips Respironics, Netherlands), a vibrating-mesh smart nebulizer. The design of the I-neb precludes its use in a closed ventilator circuit. While researchers have described a strategy for aerosol delivery during adult mechanical ventilation, none have applied such strategies for use with iloprost in infants. 2 Iloprost inhalation has been reported to be of some benefit in the management of critically ill neonates and infants with hypoxic lung disease and pulmonary hypertension.3-17 Many neonates with sever...

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“…In an in vitro study, we have demonstrated that the emitted dose of IPGE 1 following jet nebulization in a neonatal ventilator circuit was 32-40% (26). In the present study, we used a high dose of IPGE 1 , 1200 ng/kg/min, corresponding to a total dose of ~3,500 μg of PGE 1 administered over 24 h. Compared to doses known to reduce pulmonary hypertension in patients (8-300 ng/kg/min), this represents a high dose (7)(8)(9)20,28,36).…”

Section: Discussionmentioning

confidence: 99%

“…Compared to PGI 2 , PGE 1 has a shorter half-life, lower pH (6.3 versus 10.5), bronchodilator action, anti-proliferative and anti-inflammatory effects on the alveolar, interstitial and vascular spaces of the lung (8,(22)(23)(24)(25). We have described the emitted dose, stability and aerosol particle size distribution of inhaled PGE 1 in a neonatal ventilator circuit and demonstrated effective pulmonary delivery using magnetic resonance imaging in a ventilated piglet model (26,27). We have also reported the feasibility, safety and effective delivery of inhaled PGE 1 (IPGE 1 ) when administered for a maximum duration of three hours in a phase I-II study in term/nearterm neonates with NHRF (28,29).…”

Section: Introductionmentioning

confidence: 99%

Toxicity of prolonged high dose inhaled PGE1 in ventilated neonatal pigs

Sood

Dawe

Maddipati

et al. 2008

Pulmonary Pharmacology & Therapeutics

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Objective-To study the toxicity of inhaled PGE 1 (IPGE 1 ) in healthy ventilated piglets.Methods-Mechanically ventilated anesthetized piglets received either high dose IPGE 1 (IPGE 1 group) or nebulized saline (control group) continuously for 24 hours. Cardio-respiratory parameters, complete blood counts and serum electrolytes were monitored. Lung histology was evaluated by a masked pathologist for the severity (minimal, moderate, and severe) and extent (focal, multifocal, and diffuse) of histologic injury.Results-Ten neonatal pigs were instrumented. Four received nebulized saline and six received high dose IPGE 1 . There was no evidence of adverse cardio-respiratory effects, bronchial irritation or hypernatremia related to IPGE 1 . Diffuse/multifocal alveolar edema and focal polymorphonuclear infiltration was observed in both the control and IPGE 1 groups suggesting that alveolar alterations may be secondary to effects of mechanical ventilation. The most distinct histomorphological abnormalities observed in the IPGE 1 animals were focal ulceration, flattening of the bronchial epithelium and loss of cilia of moderate to severe degree in the trachea and bronchi.Conclusion-In healthy piglets, inhalation of high dose IPGE 1 was not associated with adverse cardiorespiratory effects, bronchial irritation, or hypernatremia and produced minimal signs of pulmonary toxicity even after 24 hours. Prolonged inhalation of high dose PGE 1 therefore appears safe in newborn piglets.

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Jet nebulization of prostaglandin E1 during neonatal mechanical ventilation: Stability, emitted dose and aerosol particle size

Cited by 16 publications

References 38 publications

Aerosol Delivery in Ventilated Newborn Pigs: An MRI Evaluation

Aerosol Delivery in Ventilated Newborn Pigs: An MRI Evaluation

Iloprost Drug Delivery during Infant Conventional and High‐Frequency Oscillatory Ventilation

Toxicity of prolonged high dose inhaled PGE1 in ventilated neonatal pigs

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