A REVIEW OF DORNASE ALFA USE FOR SUSPECTED AIRWAY PLUGS Joanne Hood Paediatric Pharmacist Evelina Children’s Hospital Guys and St Thomas Foundation Trust

Introduction Recombinant human Dornase (DNase): genetically engineered mucolytic agent Licensed for use in Cystic Fibrosis patients There is limited information of use DNase outside CF Since 2002 DNase used on PICU in children with suspected airway plugs secondary to acute severe asthma refactory to treatment Recent Use of DNase within PICU and other ward areas increased Purulent secretions contain very high concentrations of extracellular DNA, a viscous polyanion released by degenerating leucocytes, which accumulate in response to infection. In vitro, dornase alfa hydrolyses DNA in sputum and greatly reduces the viscoelasticity of cystic fibrosis sputum.

Objectives -Assess the use of Dornase Alfa on PICU against current formulary guidelines -Identify usage in other paediatric ward areas

Formulary Guidelines Dornase Alpha Suspected airway plugs* Endotracheally (ETT) 1ml/kg (maximum 20ml) of reconstituted solution Physio immediately performed to affected lobe *Paediatric intensive care unit (PICU) only -patients should be ventilated with high ventilatory pressures (Peak Airway Pressure (PAP) >28cm/H2O)

Methods Patients prescribed rhDNase from April 2006-07 were retrospectively identified from pharmacy dispensing records Data was collected from medical notes including; - Indication of rhDNase - Dose Route of administration Ward location Time to physiotherapy

Results-PICU N= 20 patients, median age 5.5 years PICU, N= 9 patients (45%): 2 patients met formulary guidelines Measure Results Indication -100% mucous plugs secondary to; 44% (4/9) refractory acute severe asthma 33% (3/9) lower respiratory chest infect 11% (1/9) sickle cell chest crisis 11% (1/9) plastic bronchitis Route 66% (6/9) patients were ventilated (ETT) Dose All received recommended dose Physiotherapy 33% (3/9) sessions within recommended time 22% (2/9) of times were not stated clearly

Results-Other ward areas 55% (11/20) patients were outside PICU Measure Results Indication -100% mucous plugs secondary to; 45% (5/11) acute severe asthma 18% (2/11) viral wheeze 18% (2/11) lower respiratory chest infections 9% (1/11) RSV +ve Bronchiolitis 9% (1/11) plastic bronchitis Route 100% (11/11) received nebulised rhDNase Dose 100% (11/11) received recommended CF dose Physiotherapy 0% (0/11) were within the recommended time 36% (4/11) of times were not stated clearly

Discussion Indication -100% mucous plugging secondary causes variable -Current practice is based on limited evidence for use of DNase via ETT in ventilated patients with acute severe asthma, secondary to mucous plugs -Extrapolated success to other indications with no clinical evidence- small studies have shown it doesn’t work -Limited information for chronic use in plastic bronchitis Dose -No information re efficacy of reconstitution -CF patients may have different pharmacokinetics to non CF patients

Discussion cont… Route -?safety of ETT -?efficacy of nebulised dose Physiotherapy -In Cystic Fibrosis patients DNase is nebulised, the recommended time to physiotherapy is one hour post inhalation -No evidence to suggest best time for physiotherapy post ETT administration or for non CF patients-15 minutes seems the natural timing -Change of documentation method lead to unclear results

Conclusions Current use of rhDNase does not reflect the formulary recommendations RhDNase is an expensive therapy, our small clinical experience on PICU so far is encouraging There are still many unclear areas regarding safety and efficacy of this drug Further research is needed in order to provide safe and cost effective treatment The guidelines need to be reviewed to reflect future research findings

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Acknowledgements and References Thank you to all the ECH paediatric pharmacists, especially Sara Arenas Lopez. Steve Colthurst, Senior Physiotherapist PICU, and Andrew Durward, Senior consultant PICU, for all your help and advice References Patel A, Harrison E, Durward A et al. Intratracheal recombinant human deoxyribonuclease in acute life-threatening asthma refractory to conventional treatment, Br J Anaesth 2000;84:505-7 Guy’s and St Thomas’, King’s College and University of Lewisham Hospitals, Paediatric Formulary, seventh edition, GSTFT, London, 2005