Epoprostenol Delivered via High Flow Nasal Cannula for ICU Subjects with Severe Hypoxemia Comorbid with Pulmonary Hypertension or Right Heart Dysfunction

Li, Jie; Harnois, Lauren; Markos, Bethelhem; Roberts, Keith M; Homoud, Salma Al; Liu, Jing; Mirza, Sara; Vines, David

doi:10.3390/pharmaceutics11060281

Cited by 26 publications

(35 citation statements)

References 30 publications

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“…Due to its short half-life, iEPO is continuously delivered for extended periods of time (usually > 24 h), which becomes a challenge for spontaneous breathing patients, as conventional aerosol therapy via mouthpiece or mask for a long duration is uncomfortable and impossible to maintain [4]. Transnasal pulmonary delivery of iEPO via high-flow nasal cannula (HFNC) provides a feasible route, which has been shown to deliver sufficient dose to elicit a clinical response [8,9].…”

Section: Introductionmentioning

confidence: 99%

The Clinical Impact of Flow Titration on Epoprostenol Delivery via High Flow Nasal Cannula for ICU Patients with Pulmonary Hypertension or Right Ventricular Dysfunction: A Retrospective Cohort Comparison Study

Gurnani

Roberts

et al. 2020

JCM

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1) Background: inhaled epoprostenol (iEPO) delivered via high-flow nasal cannula (HFNC) has been reported to be effective for pulmonary hypertension and right ventricular dysfunction. In vitro studies have identified HFNC gas flow as a key factor in trans-nasal aerosol delivery efficiency; however, little evidence is available on the clinical impact of flow titration on trans-nasal aerosol delivery. At our institution, iEPO via HFNC was initiated in 2015 and the concept of flow titration during iEPO via HFNC has been gradually accepted and carried out by clinicians in the recent years.(2) Methods: a retrospective review of the electronic medical records for all adult patients who received iEPO via HFNC in a tertiary teaching hospital. Pre-and post-iEPO responses were reported for patients whose HFNC flow was titrated or maintained constant during iEPO delivery. Positive response to iEPO was defined as the reduction of mean pulmonary arterial pressure (mPAP) > 10% for pulmonary hypertension patients or the improvement of oxygenation [pulse oximetry (SpO 2 )/fraction of inhaled oxygen (F I O 2 )] > 20%. The number of responders to iEPO was compared between groups with titrated vs constant flow. (3) Results: 51 patients who used iEPO to treat pulmonary hypertension and/or right ventricular dysfunction were reviewed. Following iEPO administration via HFNC, mPAP decreased (43.6 ± 11.7 vs. 36.3 ± 9.7 mmHg, p < 0.001). Among the 51 patients, 24 had concomitant refractory hypoxemia, their oxygenation (SpO 2 /F I O 2 ) improved after iEPO delivery (127.8 ± 45.7 vs. 157.6 ± 62.2, p < 0.001). During iEPO initiation, gas flow was titrated in 25 patients and the remaining 26 patients used constant flow. The percentage of patients in the flow titration group who met the criteria for a positive response was higher compared to the group with constant flow (85.7% vs. 50%, p = 0.035). Pre-vs post-iEPO responses were significant in the flow titration group included improvement in cardiac output (p = 0.050), cardiac index (p = 0.021) and F I O 2 reduction (p = 0.016). These improvements in hemodynamics and F I O 2 were not observed in the constant flow group. (4) Conclusion: in patients with pulmonary hypertension and/or right ventricular dysfunction, trans-nasal iEPO decreased pulmonary arterial pressure. It also improved oxygenation in patients with combined refractory hypoxemia. These improvements were more evident in patients whose gas flow was titrated during iEPO initiation than those patients using constant flow.

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Section: Introductionmentioning

confidence: 99%

The Clinical Impact of Flow Titration on Epoprostenol Delivery via High Flow Nasal Cannula for ICU Patients with Pulmonary Hypertension or Right Ventricular Dysfunction: A Retrospective Cohort Comparison Study

Gurnani

Roberts

et al. 2020

JCM

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“…In recent years, aerosol delivery via high-flow nasal cannula (HFNC) has become a popular measure to deliver aerosol therapy [1][2][3][4][5][6][7][8], particularly for patients who are using HFNC concurrently [1][2][3][4][5]. At regular flow setting, trans-nasal albuterol delivery for stable patients with chronic obstructive airway diseases has been shown to elicit similar response as conventional nebulization treatment [6][7][8], such as small volume jet nebulizer via mask/mouthpiece or metered dose inhaler with spacer.…”

Section: Introductionmentioning

confidence: 99%

“…Due to its features of no additional gas and little to no residual volume, vibrating mesh nebulizer (VMN) has been commonly utilized in trans-nasal aerosol delivery [1][2][3][4][5][7][8][9]. However, the currently available commercial product of VMN generates aerosol continuously.…”

Section: Introductionmentioning

confidence: 99%

In vitro comparison between inspiration synchronized and continuous vibrating mesh nebulizer during trans-nasal aerosol delivery

Fink

2020

ICMx

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Background: Compared to continuous vibrating mesh nebulizer (VMN), inspiration synchronized VMN has shown increased inhaled dose during noninvasive ventilation; however, its use during aerosol delivery via high-flow nasal cannula (HFNC) is still unknown. Methods: An adult manikin was connected to a dual-chamber model lung, which was driven by a critical care ventilator to simulate spontaneous breathing. A HFNC system was utilized with temperature at 37°C while gas flow at 5, 10, 20, 40, and 60 L/min. Inspiration synchronized and continuous aerosol generation were compared at different positions (at the inlet of humidifier vs close to patient). One milliliter of albuterol (2.5 mg/mL) was used in each run (n = 3). Collection filter was placed at the trachea and was removed after each run. Drug was eluted from the filter and assayed with UV spectrophotometry (276 nm). Results: When nebulizer was placed close to patient, inhaled dose was higher with inspiration synchronized than continuous aerosol generation at all gas flows (p = 0.05) except at 5 L/min. When placed at the inlet of humidifier, compared to continuous, inspiration synchronized aerosol generated higher inhaled dose with gas flow set below 50% of patient inspiratory flow [23.9 (20.6, 28.3)% vs 18.1 (16.7, 19.6)%, p < 0.001], but lower inhaled dose with gas flow set above 50% of patient inspiratory flow [3.5 (2.2, 9.3)% vs 9.9 (8.2, 16.4)%, p = 0.001]. Regardless of breathing pattern, continuous aerosol delivered greater inhaled dose with nebulizer placed at humidifier than close to patient at all gas flows except at 5 L/min. Conclusion: When the HFNC gas flow was set higher than 50% of patient inspiratory flow, no significant advantage was found in inspiration synchronized over continuous aerosol. However, inspiration synchronized aerosol generated 30% more inhaled dose than continuous with gas flow set below 50% of patient inspiratory flow, regardless of nebulizer placement. Continuous nebulizer needs to be placed at the inlet of humidifier.

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“…Primary clinical strategies to administer albuterol via HFNC include: (a) the unit dose of 1 to 3 mL placed in nebulizer reservoir generated aerosol continuously until all of the medication is nebulized over a period of 3 to 9 minutes (Figure A). If needed, frequently repeated unit doses at short intervals may be used to deliver higher dose; and (b) continuous feed of albuterol using an infusion pump to control the medication delivery rate to VMN . When the feed tube set is primed, with the pump and nebulizer turned on, the formulation is pumped into the nebulizer reservoir and gradually accumulates, till when it is sufficient for drug to establish a path to contact the mesh.…”

Section: Introductionmentioning

confidence: 99%

“…If needed, frequently repeated unit doses at short intervals may be used to deliver higher dose; and (b) continuous feed of albuterol using an infusion pump to control the medication delivery rate to VMN. 17 When the feed tube set is primed, with the pump and nebulizer turned on, the formulation is pumped into the nebulizer reservoir and gradually accumulates, till when it is sufficient for drug to establish a path to contact the mesh. The formulation reaching the mesh is generated as an aerosol, leaving the mesh dry until the next drop reaches the mesh, resulting in intervals between aerosol generation ( Figure 1B,C).…”

Section: Introductionmentioning

confidence: 99%

In vitro comparison of unit dose vs infusion pump administration of albuterol via high‐flow nasal cannula in toddlers

Fink

2019

Pediatric Pulmonology

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Objectives Transnasal pulmonary aerosol delivery using high‐flow nasal cannula (HFNC) devices has become a popular route of aerosol administration in toddlers. Clinically, albuterol is administered using an infusion pump or unit doses. However, little evidence is available to compare the two administration strategies. Methods A toddler manikin (15 kg) with appropriate anatomic airway was connected with collecting filter to a simulator of distressed breathing. HFNC device with mesh nebulizer placed at the inlet of a humidifier at 37°C, with the gas flow set at 25 and 3.75 L/min. Five milligrams of albuterol was delivered in all experiments. With infusion pump administration, albuterol concentrations of 5 and 1 mg/mL were delivered at 4 and 20 mL/hr for 15 minutes. With unit dose administration, 1 mL (5 mg/mL) and 2 mL (2.5 mg/mL) of albuterol were nebulized. Additional tests with mouth open and nebulizers via mask were using 5 mg/1 mL for mesh nebulizer and 5 mg/3 mL for jet nebulizer (n = 3). The drug was eluted from the filter and assayed with UV spectrophotometry (276 nm). Results The inhaled dose was higher with unit dose than infusion pump administration with gas flows of 25 L/min (2.66 ± 0.38 vs 1.16 ± 0.28%; P = .004) and 3.75 L/min (10.51 ± 1.29 vs 8.58 ± 0.68%; P = .025). During unit dose administration, compared with closed‐mouth breathing, open‐mouth breathing generated a higher inhaled dose at 3.75 L/min and lower inhaled dose at 25 L/min. Compared to the nebulizers via mask with both open and closed‐mouth breathing, nebulization via HFNC at 3.75 L/min generated greater inhaled dose, while HFNC at 25 L/min generated lower inhaled dose. Conclusions During transnasal aerosol delivery, the inhaled dose was higher with medication administrated using unit dose than using an infusion pump.

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Epoprostenol Delivered via High Flow Nasal Cannula for ICU Subjects with Severe Hypoxemia Comorbid with Pulmonary Hypertension or Right Heart Dysfunction

Cited by 26 publications

References 30 publications

The Clinical Impact of Flow Titration on Epoprostenol Delivery via High Flow Nasal Cannula for ICU Patients with Pulmonary Hypertension or Right Ventricular Dysfunction: A Retrospective Cohort Comparison Study

The Clinical Impact of Flow Titration on Epoprostenol Delivery via High Flow Nasal Cannula for ICU Patients with Pulmonary Hypertension or Right Ventricular Dysfunction: A Retrospective Cohort Comparison Study

In vitro comparison between inspiration synchronized and continuous vibrating mesh nebulizer during trans-nasal aerosol delivery

In vitro comparison of unit dose vs infusion pump administration of albuterol via high‐flow nasal cannula in toddlers

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