Use of dornase alfa in the paediatric intensive care unit: current literature and a national cross-sectional survey

Abstract

Objectives Airway mucus obstruction is a major challenge in children admitted to the paediatric intensive care unit (PICU). We aimed to evaluate the evidence and contemporary use of the mucolytic medication dornase alfa for non-cystic fibrosis conditions in the PICU. Methods (1) We performed a systematic review with searches in PubMed, EMBASE, and the Cochrane Library. Study selection: for quality assessment and data synthesis, we included only randomised controlled trials (RCTs) that compared dornase alfa to standard care or placebo in critically-ill paediatric patients (<18 years of age) in the PICU. However, non-randomised controlled studies and case series are also discussed. Data extraction: data were extracted independently by multiple reviewers using data extraction forms. The primary outcome was duration of mechanical ventilation. Data synthesis: The GRADE approach was used for quality assessment. No meta-analysis could be performed. (2) A national cross-sectional survey among all seven PICUs in the Netherlands was also performed. ResultsThe systematic review yielded only one RCT, comparing dornase alfa with normal saline in children after cardiac surgery. In this study, dornase alfa led to a reduction in duration of mechanical ventilation by approximately 1 day (36% reduction). In addition, we found nine retrospective observational and case studies. The survey revealed high current use of dornase alfa in Dutch PICUs: 42% of the respondents reported prescribing dornase alfa at least once every week. Only 4% of the respondents reported having access to a local PICU dornase alfa protocol. Conclusions The off-label use of dornase alfa in the PICU is frequent without strong evidence or local protocols, highlighting the need for further research on the effectiveness of this mucolytic agent.*More detailed information on the RCT of Riethmueller 2006 is reported in the main results and online supplemental tables 1 and 2. CF, cystic fibrosis; FiO 2 , fraction of inspired oxygen; MV, mechanical ventilation; pCO 2 , partial pressure of carbon dioxide; PICU, paediatric intensive care unit; pO 2 , partial pressure of oxygen; RCT, randomised controlled trial; RSV, respiratory syncytial virus.

Identifying and Understanding Risk Factors for Instability and Adverse Events Associated With Chest Physiotherapy in Ventilated Children

“…The response rate of 61% was lower than anticipated, particularly when compared to a physiotherapy survey in adult intensive care, which reported a 72% response rate (Van der Lee et al, 2017). However, surveys involving professionals on PICU appear to have lower response rates (46-65%) (den Hollander et al, 2020, Kumar et al, 2014, Snoek and Brierley, 2015. The lower response rate in this study was attributed to data collection taking place during the COVID19 pandemic, where PICUs within the UK were re-purposed and health professionals re-deployed.…”

“…DNase was used by 86% (6/7) of PICUs in the Netherlands (den Hollander et al, 2020). This national survey focused exclusively on DNase practice, and reported it was most frequently prescribed for bronchiolitis, neuromuscular disease, and pneumonia.…”

Human Recombinant DNase I (Pulmozyme®) Inhibits Lung Metastases in Murine Metastatic B16 Melanoma Model That Correlates with Restoration of the DNase Activity and the Decrease SINE/LINE and c-Myc Fragments in Blood Cell-Free DNA

“…In addition, the level of specific DNA fragments in the pool of cfDNA playing a role in carcinogenesis, such as SINE and LINE elements and the c-Myc oncogene, was determined. Pulmozyme ® is successfully used to treat cystic fibrosis, and attempts have been made to use Pulmozyme ® for the treatment of specific viral lung infections, pleural effusion, emphysema and autoimmune diseases [ 5 , 7 , 37 ]. However, Pulmozyme ® has never been used as an antimetastatic agent.…”

“…It has a very low toxicity due to its short half-life and poor systemic absorption [ 6 ]. Today, dornase alfa in the form of the commercially available medication Pulmozyme ® is recommended for the therapy of cystic fibrosis, especially for children, as well as for pleural effusion and emphysema [ 7 ]. Dornase alfa was found to degrade (fDNA)integrated in neutrophil extracellular traps (NETs), which are formed under various infectious and autoimmune diseases [ 8 ].…”