Nebulized in-line endotracheal dornase alfa and albuterol administered to mechanically ventilated COVID-19 patients: a case series

Abstract Background Mechanically ventilated patients with COVID-19 have a mortality of 24–53%, in part due to distal mucopurulent secretions interfering with ventilation. DNA from neutrophil extracellular traps (NETs) contribute to the viscosity of mucopurulent secretions and NETs are found in the serum of COVID-19 patients. Dornase alfa is recombinant human DNase 1 and is used to digest DNA in mucoid sputum. Here, we report a single-center case series where dornase alfa was co-administered with albuterol through an in-line nebulizer system. Methods Demographic and clinical data were collected from the electronic medical records of five mechanically ventilated patients with COVID-19—including three requiring veno-venous extracorporeal membrane oxygenation—treated with nebulized in-line endotracheal dornase alfa and albuterol, between March 31 and April 24, 2020. Data on tolerability and response were analyzed. Results The fraction of inspired oxygen requirements was reduced for all five patients after initiating dornase alfa administration. All patients were successfully extubated, discharged from hospital and remain alive. No drug-associated toxicities were identified. Conclusions Results suggest that dornase alfa will be well-tolerated by patients with severe COVID-19. Clinical trials are required to formally test the dosing, safety, and efficacy of dornase alfa in COVID-19, and several have been recently registered.

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Nebulized in-line endotracheal dornase alfa and albuterol administered to mechanically ventilated COVID-19 patients: A case series

10.1101/2020.05.13.20087734 ◽

2020 ◽

Cited By ~ 1

Author(s):

Andrew G. Weber ◽

Alice S Chau ◽

Mikala Egeblad ◽

Betsy J Barnes ◽

Tobias Janowitz

Keyword(s):

Critically Ill ◽

Critically Ill Patients ◽

Case Series ◽

Mechanically Ventilated ◽

Mechanically Ventilated Patients ◽

Dornase Alfa ◽

Link Type ◽

Inflammatory Status ◽

Oxygen Requirements ◽

Ventilated Patients

Background Mechanically ventilated patients with coronavirus disease 2019 (COVID-19) have a mortality of 24-53%, in part due to distal mucopurulent secretions interfering with ventilation. Dornase alfa is recombinant human DNase 1 and digests DNA in mucoid sputum. Nebulized dornase alfa is FDA-approved for cystic fibrosis treatment. DNA from neutrophil extracellular traps (NETs) contributes to the viscosity of mucopurulent secretions. NETs are found in the serum of patients with severe COVID-19, and targeting NETs reduces mortality in animal models of acute respiratory distress syndrome (ARDS). Thus, dornase alfa may be beneficial to patients with severe COVID-19, acting as a mucolytic and targeting NETs. However, delivery of nebulized drugs can aerosolize SARS-CoV-2, which causes COVID-19, increasing the infection risk for staff. Here, we report a single center case series where dornase alfa was administered through an in-line nebulizer system to minimize risk of virus aerosolization. Methods Demographic, clinical data, and outcomes were collected from the electronic medical records of five mechanically ventilated patients with COVID-19, including three requiring veno-venous extracorporeal membrane oxygenation (VV-ECMO), treated with nebulized in-line endotracheal dornase alfa co-administered with albuterol (used to increase delivery to the alveoli), between March 31 and April 24, 2020. Data on tolerability and responses, including longitudinal values capturing respiratory function and inflammatory status, were analyzed. Results Following nebulized in-line administration of dornase alfa with albuterol, the fraction of inspired oxygen requirements was reduced for all five patients. All patients remain alive and two patients have been discharged from the intensive care unit. No drug associated toxicities were identified. Conclusions The results presented in this case series suggest that dornase alfa will be well-tolerated by critically ill patients with COVID-19. Clinical trials are required to formally test the dosing, safety, and efficacy of dornase alfa in COVID-19, and two have recently been registered (NCT04359654 and NCT04355364). With this case series, we hope to contribute to the development of management approaches for critically ill patients with COVID-19.

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Knobmanship: Dialing Up Understanding of VAE Triggers

Antimicrobial Stewardship & Healthcare Epidemiology ◽

10.1017/ash.2021.158 ◽

2021 ◽

Vol 1 (S1) ◽

pp. s80-s81

Author(s):

Kelly Cawcutt ◽

Mark Rupp ◽

Lauren Musil

Keyword(s):

Chart Review ◽

Clinical Care ◽

Trigger Points ◽

Mechanically Ventilated ◽

Mechanically Ventilated Patients ◽

Review Period ◽

Fraction Of Inspired Oxygen ◽

Provider Bias ◽

Inspired Oxygen ◽

Ventilated Patients

Background: Mechanical ventilation is a lifesaving therapy for critically ill patients. Hospitals perform surveillance for the NHSN for ventilator-associated events (VAE) by monitoring mechanically ventilated patients for metrics that are generally thought to be objective and preventable and that lead to poor patient outcomes. The VAE definition is met in a stepwise manner; initially, a ventilator-associated condition (VAC) is triggered with an increase in positive end-expiratory pressure (PEEP, >3 cm H2O) or fraction of inspired oxygen (FIO2, 0.20 or 20 points) after a period of stability or improvement on the ventilator. We believe that many reported VAEs could be avoided by provider and respiratory therapy attention to “knobmanship.” We define knobmanship as knowledge of the VAE definition and trigger points combined with appropriate clinical care for mechanically ventilated patients while avoiding unnecessary triggering of the VAE definition by avoiding small unneeded changes in PEEP or FIO2. Methods: We performed a chart review of 283 patients who had a reported VAE to the NHSN between January 1, 2019, and December 31, 2020. We collected data including type of VAE, VAE triggering criteria, and clinical course. Results: Of the 283 VAEs, 59 were triggered by a PEEP increase from 5 to 8 with stable or decreasing FIO2. Of the 59 VAEs, 33 were VACs, 18 were infection-related ventilator- associated complications (IVACs), and 8 were possible ventilator-associated pneumonia (PVAP). Most of these transient changes in PEEP were deemed clinically unnecessary. A 21% reduction of VAEs reported to the NSHN over the 2-year review period could have been avoided by knobmanship. Conclusions: The VAE definition may often be triggered by provider bias to the ventilator settings rather than what the patient’s clinical-condition requires. Attention to knobmanship may result in substantial decrease in reported VAE.Funding: NoDisclosures: None

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On the Transition from Control Modes to Spontaneous Modes during ECMO

Journal of Clinical Medicine ◽

10.3390/jcm10051001 ◽

2021 ◽

Vol 10 (5) ◽

pp. 1001

Author(s):

Krista Stephens ◽

Nathan Mitchell ◽

Sean Overton ◽

Joseph E. Tonna

Keyword(s):

Respiratory Rate ◽

Multivariate Regression ◽

Arterial Oxygen ◽

High Fidelity ◽

Positive End Expiratory Pressure ◽

Mechanically Ventilated ◽

Mechanically Ventilated Patients ◽

Fraction Of Inspired Oxygen ◽

Inspired Oxygen ◽

Ventilated Patients

The transition from control modes to spontaneous modes is ubiquitous for mechanically ventilated patients yet there is little data describing the changes and patterns that occur to breathing during this transition for patients on ECMO. We identified high fidelity data among a diverse cohort of 419 mechanically ventilated patients on ECMO. We examined every ventilator change, describing the differences in >30,000 sets of original ventilator observations, focused around the time of transition from control modes to spontaneous modes. We performed multivariate regression with mixed effects, clustered by patient, to examine changes in ventilator characteristics within patients, including a subset among patients with low compliance (<30 milliliters (mL)/centimeters water (cmH2O)). We found that during the transition to spontaneous modes among patients with low compliance, patients exhibited greater tidal volumes (471 mL (364,585) vs. 425 mL (320,527); p < 0.0001), higher respiratory rate (23 breaths per minute (bpm) (18,28) vs. 18 bpm (14,23); p = 0.003), greater mechanical power (elastic component) (0.08 mL/(cmH2O × minute) (0.05,0.12) vs. 0.05 mL/(cmH2O × minute) (0.02,0.09); p < 0.0001) (range 0 to 1.4), and lower positive end expiratory pressure (PEEP) (6 cmH2O (5,8) vs. 10 cmH2O (8,11); p < 0.0001). For patients on control modes, the combination of increased tidal volume and increased respiratory rate was temporally associated with significantly low partial pressure of arterial oxygen (PaO2)/fraction of inspired oxygen (FiO2) ratio (p < 0.0001). These changes in ventilator parameters warrant prospective study, as they may be associated with worsened lung injury.

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Association Between Peripheral Blood Oxygen Saturation (SpO2)/Fraction of Inspired Oxygen (FiO2) Ratio Time at Risk and Hospital Mortality in Mechanically Ventilated Patients

The Permanente Journal ◽

10.7812/tpp/19.113 ◽

2020 ◽

Cited By ~ 1

Keyword(s):

Hospital Mortality ◽

Oxygen Saturation ◽

Peripheral Blood ◽

Blood Oxygen ◽

Blood Oxygen Saturation ◽

Mechanically Ventilated ◽

Mechanically Ventilated Patients ◽

Fraction Of Inspired Oxygen ◽

Inspired Oxygen ◽

Ventilated Patients

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Immediate Effects of Acapella® on Dynamic Lung Compliance in Mechanically Ventilated Patients with Acute Respiratory Distress Syndrome: A Case Series

Indian Journal of Critical Care Medicine ◽

10.4103/ijccm.ijccm_157_17 ◽

2018 ◽

Vol 22 (2) ◽

pp. 100-102

Author(s):

Priya Sharma ◽

V Prem ◽

Sakshee Jain

Keyword(s):

Acute Respiratory Distress Syndrome ◽

Respiratory Distress Syndrome ◽

Respiratory Distress ◽

Distress Syndrome ◽

Case Series ◽

Lung Compliance ◽

Mechanically Ventilated ◽

Mechanically Ventilated Patients ◽

Dynamic Lung Compliance ◽

Ventilated Patients

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Bronchoscopic Cryotherapy for Acute Hypoxemic Respiratory Failure in Three Mechanically Ventilated Patients: A Case Series

Indian Journal of Critical Care Medicine ◽

10.5005/jp-journals-10071-23707 ◽

2021 ◽

Vol 25 (1) ◽

pp. 94-96

Author(s):

Mayank Mishra ◽

Sudheer Tale ◽

Soibam P Meitei ◽

Vipul Prakash ◽

Arjun Negi ◽

...

Keyword(s):

Respiratory Failure ◽

Case Series ◽

Hypoxemic Respiratory Failure ◽

Acute Hypoxemic Respiratory Failure ◽

Mechanically Ventilated ◽

Mechanically Ventilated Patients ◽

Ventilated Patients

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Factors associated with successful extubation following the use of systemic dexamethasone in ventilator dependent extremely preterm infants with bronchopulmonary dysplasia

10.22541/au.162428601.17874600/v1 ◽

2021 ◽

Author(s):

Kristin O'Connor ◽

Cameron Hurst ◽

Stacey Llewellyn ◽

Mark Davies

Keyword(s):

Bronchopulmonary Dysplasia ◽

Binary Logistic Regression ◽

Mechanically Ventilated ◽

Extremely Preterm ◽

Extremely Preterm Infants ◽

Average Fraction ◽

Fraction Of Inspired Oxygen ◽

Oxygen Requirements ◽

Inspired Oxygen ◽

Successful Extubation

Objectives The aim of our study was to identify, in mechanically ventilated neonates <30 weeks GA with clinical evidence of bronchopulmonary dysplasia (BPD), factors likely to be predictive of a first course of systemic dexamethasone leading to extubation within 14 days and remaining extubated for at least 7 days. Methods We studied a retrospective cohort of neonates (23+0-29+6 weeks GA), with evidence of BPD, prescribed their first course of systemic dexamethasone to aid in extubation from mechanical ventilation. The data collected only pertained to the first course of dexamethasone for any given neonate, with the primary outcome of interest of successful extubation within 14 days (i.e., extubated within 14 days of starting dexamethasone and remaining extubated for at least seven days). Binary logistic regression was employed. Results A total of 287 neonates were included. Each additional week of GA at birth led to a 1.53 increase in the odds of successful extubation (95% CI 1.122-2.096, p<0.01). Higher average fraction of inspired oxygen (FiO2) requirements in the preceding 24 hours resulted in a 0.94 decrease in the odds of successful extubation (p<0.05) and higher mean airway pressure (MAP) resulted in 0.76 decrease in odds of successful extubation (p<0.01). Conclusions Mechanically ventilated neonates born at <30 week GA, with evidence of BPD requiring dexamethasone to facilitate extubation, had a lower likelihood of successful extubation by day 14 if at the time of commencing steroids they were less mature at birth, had higher MAPs and higher oxygen requirements.

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