1. enrolled in another clinical trial that is unapproved for co-enrolment 2. heparin allergy or heparin-induced thrombocytopaenia 3. aptt \> 100 seconds 4. platelet count \< 50 x 109 per l 5. pulmonary bleeding, which is frank bleeding in the trachea, bronchi or lungs with repeated haemoptysis or requiring repeated suctioning 6. uncontrolled bleeding 7. pregnant or suspected pregnancy (urine or serum hcg will be recorded) 8. receiving or about to commence ecmo or hfov 9. myopathy, spinal cord injury, or nerve injury or disease with a likely prolonged incapacity to breathe independently e.g. guillain-barre syndrome 10. usually receives home oxygen 11. dependent on others for personal care due to physical or cognitive decline (pre-morbid status) 12. death is imminent or inevitable within 24 hours 13. the clinical team would not be able to set up the study nebuliser and ventilator circuit as required including with active humidification 14. clinician objection. 15. the use or anticipated use of nebulised tobramycin during this clinical episode 16. any other specific contraindication to anticoagulation including prophylactic anticoagulation not otherwise listed here 17. relapse in clinical condition in patient that had fully weaned from advanced respiratory support 18. any systemic anticoagulation other than prophylactic anticoagulation

1. enrolled in another clinical trial that is unapproved for co-enrolment 2. heparin allergy or heparin-induced thrombocytopaenia 3. aptt \> 100 seconds 4. platelet count \< 50 x 109 per l 5. pulmonary bleeding, which is frank bleeding in the trachea, bronchi or lungs with repeated haemoptysis or requiring repeated suctioning 6. uncontrolled bleeding 7. pregnant or suspected pregnancy (urine or serum hcg will be recorded) 8. receiving or about to commence ecmo or hfov 9. myopathy, spinal cord injury, or nerve injury or disease with a likely prolonged incapacity to breathe independently e.g. guillain-barre syndrome 10. usually receives home oxygen 11. dependent on others for personal care due to physical or cognitive decline (pre-morbid status) 12. death is imminent or inevitable within 24 hours 13. the clinical team would not be able to set up the study nebuliser and ventilator circuit as required including with active humidification 14. clinician objection. 15. the use or anticipated use of nebulised tobramycin during this clinical episode 16. any other specific contraindication to anticoagulation including prophylactic anticoagulation not otherwise listed here 17. relapse in clinical condition in patient that had fully weaned from advanced respiratory support 18. any systemic anticoagulation other than prophylactic anticoagulation

enrolled in another clinical trial that is unapproved for co-enrolment heparin allergy or heparin-induced thrombocytopaenia aptt > 100 seconds platelet count < 50 x 109 per l pulmonary bleeding, which is frank bleeding in the trachea, bronchi or lungs with repeated haemoptysis or requiring repeated suctioning uncontrolled bleeding pregnant or suspected pregnancy (urine or serum hcg will be recorded) receiving or about to commence ecmo or hfov myopathy, spinal cord injury, or nerve injury or disease with a likely prolonged incapacity to breathe independently e.g. guillain-barre syndrome usually receives home oxygen dependent on others for personal care due to physical or cognitive decline (pre-morbid status) death is imminent or inevitable within 24 hours the clinical team would not be able to set up the study nebuliser and ventilator circuit as required including with active humidification clinician objection. the use or anticipated use of nebulised tobramycin during this clinical episode any other specific contraindication to anticoagulation including prophylactic anticoagulation not otherwise listed here relapse in clinical condition in patient that had fully weaned from advanced respiratory support any systemic anticoagulation other than prophylactic anticoagulation

enrolled in another clinical trial that is unapproved for co-enrolment heparin allergy or heparin-induced thrombocytopaenia aptt > 100 seconds platelet count < 50 x 109 per l pulmonary bleeding, which is frank bleeding in the trachea, bronchi or lungs with repeated haemoptysis or requiring repeated suctioning uncontrolled bleeding pregnant or suspected pregnancy (urine or serum hcg will be recorded) receiving or about to commence ecmo or hfov myopathy, spinal cord injury, or nerve injury or disease with a likely prolonged incapacity to breathe independently e.g. guillain-barre syndrome usually receives home oxygen dependent on others for personal care due to physical or cognitive decline (pre-morbid status) death is imminent or inevitable within 24 hours the clinical team would not be able to set up the study nebuliser and ventilator circuit as required including with active humidification clinician objection. the use or anticipated use of nebulised tobramycin during this clinical episode any other specific contraindication to anticoagulation including prophylactic anticoagulation not otherwise listed here relapse in clinical condition in patient that had fully weaned from advanced respiratory support any systemic anticoagulation other than prophylactic anticoagulation

1. enrolled in another clinical trial that is unapproved for co-enrolment 2. heparin allergy or heparin-induced thrombocytopaenia 3. aptt > 100 seconds 4. platelet count < 50 x 109 per l 5. pulmonary bleeding, which is frank bleeding in the trachea, bronchi or lungs with repeated haemoptysis or requiring repeated suctioning 6. uncontrolled bleeding 7. pregnant or suspected pregnancy (urine or serum hcg will be recorded) 8. receiving or about to commence ecmo or hfov 9. myopathy, spinal cord injury, or nerve injury or disease with a likely prolonged incapacity to breathe independently e.g. guillain-barre syndrome 10. usually receives home oxygen 11. dependent on others for personal care due to physical or cognitive decline (pre-morbid status) 12. death is imminent or inevitable within 24 hours 13. the clinical team would not be able to set up the study nebuliser and ventilator circuit as required including with active humidification 14. clinician objection. 15. the use or anticipated use of nebulised tobramycin during this clinical episode 16. any other specific contraindication to anticoagulation including prophylactic anticoagulation not otherwise listed here 17. relapse in clinical condition in patient that had fully weaned from advanced respiratory support 18. any systemic anticoagulation other than prophylactic anticoagulation

1. enrolled in another clinical trial that is unapproved for co-enrolment 2. heparin allergy or heparin-induced thrombocytopaenia 3. aptt > 100 seconds 4. platelet count < 50 x 109 per l 5. pulmonary bleeding, which is frank bleeding in the trachea, bronchi or lungs with repeated haemoptysis or requiring repeated suctioning 6. uncontrolled bleeding 7. pregnant or suspected pregnancy (urine or serum hcg will be recorded) 8. receiving or about to commence ecmo or hfov 9. myopathy, spinal cord injury, or nerve injury or disease with a likely prolonged incapacity to breathe independently e.g. guillain-barre syndrome 10. usually receives home oxygen 11. dependent on others for personal care due to physical or cognitive decline (pre-morbid status) 12. death is imminent or inevitable within 24 hours 13. the clinical team would not be able to set up the study nebuliser and ventilator circuit as required including with active humidification 14. clinician objection. 15. the use or anticipated use of nebulised tobramycin during this clinical episode 16. any other specific contraindication to anticoagulation including prophylactic anticoagulation not otherwise listed here 17. relapse in clinical condition in patient that had fully weaned from advanced respiratory support 18. any systemic anticoagulation other than prophylactic anticoagulation

1. enrolled in another clinical trial that is unapproved for co-enrolment 2. heparin allergy or heparin-induced thrombocytopaenia 3. aptt > 120 seconds and this is not due to anticoagulant therapy 4. platelet count < 20 x 109 per l 5. pulmonary bleeding, which is frank bleeding in the trachea, bronchi or lungs with repeated haemoptysis or requiring repeated suctioning 6. uncontrolled bleeding 7. pregnant or suspected pregnancy (urine or serum hcg will be recorded) 8. receiving or about to commence ecmo or hfov 9. myopathy, spinal cord injury, or nerve injury or disease with a likely prolonged incapacity to breathe independently e.g. guillain-barre syndrome 10. usually receives home oxygen 11. dependent on others for personal care due to physical or cognitive decline 12. death is imminent or inevitable within 24 hours 13. the clinical team would not be able to set up the study nebuliser and ventilator circuit as required including with active humidification 14. clinician objection. 15. the use or anticipated use of nebulised tobramycin during this clinical episode

1. enrolled in another clinical trial that is unapproved for co-enrolment 2. heparin allergy or heparin-induced thrombocytopaenia 3. aptt > 120 seconds and this is not due to anticoagulant therapy 4. platelet count < 20 x 109 per l 5. pulmonary bleeding, which is frank bleeding in the trachea, bronchi or lungs with repeated haemoptysis or requiring repeated suctioning 6. uncontrolled bleeding 7. pregnant or suspected pregnancy (urine or serum hcg will be recorded) 8. receiving or about to commence ecmo or hfov 9. myopathy, spinal cord injury, or nerve injury or disease with a likely prolonged incapacity to breathe independently e.g. guillain-barre syndrome 10. usually receives home oxygen 11. dependent on others for personal care due to physical or cognitive decline 12. death is imminent or inevitable within 24 hours 13. the clinical team would not be able to set up the study nebuliser and ventilator circuit as required including with active humidification 14. clinician objection. 15. the use or anticipated use of nebulised tobramycin during this clinical episode