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

Abstract

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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“…3 a and b) should be utilized. For patients who cannot tolerate a mouthpiece or require medication administered over a prolonged period of time, such as continuous bronchodilator for asthmatic patients [ 63 ] or inhaled epoprostenol for patients with pulmonary hypertension or hypoxemia [ 64 , 65 ], in-line placement of a nebulizer with HFNC setup is recommended. This setup has two advantages: (1) more comfortable and better tolerated when compared to a mask or mouthpiece [ 63 ] and (2) a surgical mask to reduce the aerosol dispersion distance or aerosol mass concentration can be placed on the patient [ 53 , 56 ].…”

Year in Review 2019: High-Flow Nasal Cannula Oxygen Therapy for Adult Subjects

“…In their study, the investigators reported that 1.5 mg albuterol delivered via HFNC at 15-20 L/min elicited similar bronchodilation effects as 400 mg albuterol via pressurized metered-dose inhaler and spacer. 66 For patients who need to inhale aerosolized medication continuously for long periods of time (ie, > 2 h), such as inhaled albuterol for those with severe asthma 67 or inhaled epoprostenol for patients with pulmonary hypertension, 68,69,70 traditional aerosol delivery such as jet nebulizer via mask/mouthpiece is challenging. Continuous transnasal aerosol delivery via HFNC offers a feasible solution to reduce the inconvenience and discomfort associated with traditional aerosol delivery setups.…”

“…68,69 Titrating flow to be lower than subject inspiratory flow was found to generate more evident responses of inhaled epoprostenol than using constant flow. 70 However, the evidence to support the use of continuous aerosol delivery via HFNC is still weak due to the retrospective nature and small sample size of these studies. Also, the overall safety of delivering pulmonary vasodilators via the nasal route warrants more investigation.…”

A narrative review on trans-nasal pulmonary aerosol delivery

“…In two small retrospective studies, adult patients with pulmonary hypertension and refractory hypoxemia improved oxygenation after inhaling epoprostenol via HFNC at an average gas flow of 40 L/min [ 13 , 14 ]. Mean pulmonary arterial pressure was reduced more effectively by titrating HFNC gas flow based on individual response to inhaled epoprostenol at the bedside compared with a constant HFNC flow [ 15 ]. Future prospective studies with larger sample size are needed to validate these findings.…”

“…However, findings on the gas flow to patient’s inspiratory flow ratio [ 29 , 30 ] should remind clinicians to titrate gas flow settings when employing HFNC for aerosol delivery, especially for drugs such as inhaled epoprostenol that produce immediate clinical responses. In support of this recommendation, a retrospective study in patients with pulmonary hypertension and hypoxemia found that titration of gas flow at the bedside led to a better response to inhaled epoprostenol via HFNC compared with application of a constant gas flow [ 15 ].…”