• The viscoelastic properties of purulent airway secretions are largely due to the presence of highly polymerized DNA broken down by neutrophils (DNA content is proportional to the neutrophil content of mucus)

• Recombinant human rhDNase (Pulmozyme^®) liquefies mucus in vitro within minutes and may be effective in re-establishing patency of airways occluded by severe mucus plugs (e.g. asthma and bronchiolitis and plastic bronchitis) ^1,2

• Dornase alfa (Pulmozyme®) is licensed for the management of CF patients. Evidence in non CF patients is limited to small numbers but practice has shown benefit.

Suspected airway plugs (either segmental or widespread) resulting in increased ventilator requirements and hypoventilation despite high ventilator pressures (peak airway pressure >28 cm H₂O). Do not use CO₂ levels as an indication for dornase alfa.

Dornase alfa should be only used after conventional attempts to clear the mucus plugs have failed or are clinically contraindicated. This includes: -

1. Airway clearance techniques (ACT) with positioning, hyperinflation techniques, saline lavage, manual techniques, cough augmentation and suctioning

2. Mucolytics including the use of 7% sodium chloride (saline) nebulisation and carbocisteine

3. Mechanical ventilation with muscle relaxation and a strategy to minimize air trapping (slow rate, minimal auto PEEP)

• Dornase alfa 2.5mg (2500units) 2.5ml as nebulised solution via nebuliser.

• Maximum dose of 5mg.

• Nebulised dornase alfa should be administered at least one hour prior to ACT to allow maximal dispersal and action of the enzyme.

• A further dose can be prescribed if required. It has been used at a frequency of 6-8 hourly. If no benefit, then discontinue use. Short term use only. Dornase alfa for this indication is to be prescribed only whilst patient is on ICU.

• If patients are unable to be ventilated appropriately to receive nebulised drug, consider direct endotracheal instillation.

• Dissolve 2.5mg (2.5ml) vial of dornase alfa with 7.5ml sodium chloride 0.9%. (Total volume of 10ml=concentration of 0.25mg/ml)

• Ensure patient is muscle relaxed, well sedated and adequately oxygenated.

• Directly instil the prepared dornase alfa solution via the endotracheal tube using a nasogastric tube or suction catheter, or direct bronchoscopy by the ICU doctor.

In order for dornase alfa, administered directly via endotracheal tube, to be maximally dispersed:

• Postural drainage, manual-hyperinflation plus manual techniques should be used (2-3minutes/lobe).

• Ideally, the manual technique employed would be chest wall vibrations but where this is clinically contraindicated, chest wall percussion could be utilised.

• Place the patient back on the ventilator and adjust the pressures to achieve adequate ventilation. If tolerated, the patient to be left with worst affected lobe dependent.

• Avoid endotracheal suctioning for 30mins where possible (to allow the enzyme time to have maximum effect).

• After this 30-minute period, ACT and endotracheal suction can be employed as clinically indicated.

Using the Critical Care/On-call Physiotherapist

The critical care physiotherapist is available between 08:30 – 16:00 or the on-call physiotherapist is available via Switchboard between 16:00 – 08:30.

Ideally, the physiotherapist should be involved to ensure optimal ACT is utilised, so consider the timing of the drug administration and of contacting the physiotherapist in order to ensure their ability to attend the patient in a timely fashion.

Please be aware that whilst the on-call physiotherapist is competent to provide manual techniques to a mechanically ventilated patient they may not be experienced in critical care.

• Dornase alfa may cause a temporary deterioration in oxygenation.

• Pulmonary haemorrhage may occasionally occur (maybe related to high airway proteases released) following neutrophil degranulation.

• Dornase alfa does not provoke bronchospasm (unlike nebulised acetylcysteine).

1. Claudius C, Perner A and Moller M. Nebulised dornase alfa versus placebo or hypertonic saline in adult critically ill patients: a systematic review of randomised clinical trials with meta-analysis and trial sequential analysis. Systematic Reviews 2015 Available from https://systematicreviewsjournal.biomedcentral.com/articles/10.1186/s13643-015-0142-z

2. Durward et al Critical Care Medicine 2000; 28:560-562

3. AARC Clinical Practice Guideline (2015) Effectiveness of Pharmacological Airway Clearance Therapies in Hospitalised Patients https://www.aarc.org/wp-content/uploads/2014/08/pharm_cpg.pdf

4. Zitter J, Maldijian P, Brimacombe M and Fenelly K. Inhaled Dornase alfa as a non-invasive treatment of atelectasis in mechanically ventilated patients. Journal of Critical Care. 2013 28, 218.

This guideline has been registered with the Trust. However, clinical guidelines are guidelines only. The interpretation and application of clinical guidelines will remain the responsibility of the individual clinician. If in doubt, contact a senior colleague or expert. Caution is advised when using guidelines after the review date.

This guideline is for use in Frimley Health NHS Foundation Trust hospitals only. Any use outside this location will not be supported by the Trust and will be at the risk of the individual using it.

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