High-Frequency Percussive Ventilation in Cystic Fibrosis Patients With Acute Respiratory Failure: A Case Series

Acute respiratory failure in cystic fibrosis carries a high risk of mortality. The optimal mode of mechanical ventilation (MV) in this population is not well established. In this case series, we identified patients with cystic fibrosis who were ventilated with high-frequency percussive ventilation (HFPV) at our institution and describe their characteristics and outcomes. The use of high-frequency percussive ventilation has been sparsely described in the literature. This case series could serve as hypothesis-generating for future research.


Introduction
Acute respiratory failure in cystic fibrosis (CF) carries a significant risk of morbidity and mortality [1]. The short and long-term outcomes are significantly worse when mechanical ventilation (MV) is needed. The optimal ventilation mode for this patient population is unknown. The benefits of chest physiotherapy and airway clearance in CF are well known [2]. This becomes of utmost importance during respiratory failure. However, once on MV, the conventional means of airway clearance are generally of limited effectiveness as patients are generally sedated and unable to complete the necessary maneuvers to facilitate effective airway clearance. Thus, on MV, accumulation of inspissated infected sputum can lead to further compromise and worsening respiratory failure. High-frequency percussive ventilation (HFPV) is a time-cycled, pressurelimited mode of percussive ventilation that delivers subphysiologic tidal volumes at rates that can exceed 500 breaths per minute. In other pulmonary diseases with airway debris, HFPV is employed as the percussive airflow facilitates secretion mobilization and clearance after endotracheal intubation takes place [3]. While this approach has not been studied in CF, the use of HFPV in thermal inhalation injuries has consistently shown less incidence of ventilator-associated pneumonia (VAP), improved oxygenation and ventilation, and possibly improved mortality [3][4][5].
We reviewed the available literature and could only find a single case report of using HFPV in a cystic fibrosis pediatric patient [6]. Given poor outcomes on conventional MV and mechanistic plausibility supporting HFPV, we have been using this mode of ventilation at our institution with our adult CF population. We aim to describe our experience with this case series.

Materials And Methods
The institutional review board approval for data collection was obtained before any data gathering. The medical record Epic (Epic Systems, Verona, USA) was queried using HERON (Healthcare Enterprise Repository for Ontological Narration) software (University of Kansas Medical Center, Kansas City, USA) with appropriate ICD-9/ICD-10 codes to identify patients who had cystic fibrosis and required mechanical ventilation using high-frequency percussive ventilation. A list of 12 patient encounters was identified. This was cross-referenced and confirmed with our departmental CF registry. Patients' charts were individually checked to confirm cystic fibrosis diagnosis (defined by sweat chloride > 60 mmol/L or two known CFcausing mutations) and identify those who were ventilated using HFPV. One patient was excluded due to lung transplant status and one patient had two encounters that are reported separately. The identified patients were hospitalized between April 2010 to May 2019 and data was collected in September 2020. Baseline forced expiratory volume in the first second (FEV1) was defined as the most recent FEV1 measured at an office visit prior to admission in a stable condition and post-hospital FEV1 was defined as the FEV1 measured at the first office visit post-hospitalization.

FIGURE 1: Comparison of survivors and non-survivors
Their median prior-to-admission baseline FEV1 was 1.41 L (33.5% of predicted) with a median follow-up FEV1 of 1.33 L (32% of predicted) (Figure 2). All the patients in this cohort had documented improved airway clearance by the ICU team after implementing HFPV without documented complications. However, this finding was limited to subjective observation and was not quantified by a standard method.

Discussion
High-frequency percussive ventilation is a subtype of high-frequency ventilation. It is a time-cycled and pressure-limited ventilator that delivers small tidal volumes using inspiratory and expiratory oscillations. The ventilator is called Volumetric Diffusive Respiration Unit (VDR-4) and comes with a Phasitron (Percussionnaire, Sandpoint, USA). This is an inspiratory and expiratory valve that is driven by a highpressure and high-frequency gas supply superimposed on conventional pressure-controlled cycles [7].
There are multiple mechanisms that contribute to gas exchange during HFPV. Aside from the direct bulk flow that is observed with conventional ventilation, HFPV creates an asymmetric velocity profile with a laminar flow pattern in which gas in the center of the airway advances inward and gas outside the center flows in a retrospect fashion [8]. This flow pattern along with the continuous pulsatory percussive waves, aid the lysis and mobilization of inspissated viscous secretions in cystic fibrosis patients [9].
While it is possible to use conventional mechanical ventilation with intermittent intrapulmonary percussive pressure, HFPV offers the potential advantage of continuous secretions mobilization and minute-to-minute airway clearance for CF patients. This is especially beneficial when cough reflexes are suppressed with sedation and when mucous production is at a peak with active infection.
In this case series, we report the outcomes of 10 cystic fibrosis patients (11 hospital encounters) in whom HFPV was used during invasive MV. While small, this CF cohort does appear to represent the adult CF ICU patient in terms of initial diagnosis, the severity of illness, and age. All of the patients were admitted with primary respiratory and CF-related diagnoses. All of the MV indications were directly related to primary respiratory failure. As expected, the median baseline FEV1 of 29% does suggest advanced CF lung disease and poor lung function at baseline.
The in-hospital mortality in this case series is five out of 11 patients, which is consistent with a recent national cross-sectional study where Siuba et al found a mortality rate of 44.5% for cystic fibrosis patients requiring MV [1]. The modes of ventilation were not defined in that study, but our numbers would at least suggest mortality outcomes consistent with the national trend. Respiratory therapy documentation and physician progress notes all noted significant improvement in airway clearance (secretion mobilization via endotracheal tube) after HFPV implementation, but this finding was not uniformly quantified by a standard method and could be prone to bias. However, it is consistent with the authors' experience and with non-CF trials on HFPV, especially in thermal inhalation injuries. In addition, the HFPV offers an added advantage of using lower peak airway pressures and decreases the risk of dynamic hyperinflation by using smaller tidal volumes. None of the patients in our cohort suffered from pneumothorax or ventilator-related complications.

Conclusions
High-frequency percussive ventilation appears to be safe, has the potential to augment airway clearance,