Source: saline instillation+nebs in I+V pts.pptx (24 slides) Author: Lauren Murphy (B6PT) Date: January 2024 Learning Level: 🟡 Intermediate through 🔴 Advanced
1. Learning Objectives
- To be confident with different types of nebulisers and their use
- To review current literature around nebulisers and saline instillation in PCCU intubated and ventilated (I+V) patients
- To develop clinical reasoning and understanding of saline instillation and nebulisers in the PCCU intubated patient
Aim
To work with other PCCUs across London to help standardise current practice across PCCU and ensure the team stays up to date with current literature regarding saline instillation and nebuliser usage in intubated and ventilated patients.
2. Overview of Common Nebulisers
🟢 Foundation / 🟡 Intermediate
| Category | Medications |
|---|---|
| Bronchodilators | Atrovent (ipratropium bromide), Salbutamol, Adrenaline |
| Mucolytics | Hypertonic Saline (3% and 7%), N-Acetylcysteine (NAC), DNase (dornase alfa) — can be given as nebuliser or instillation |
| Normal saline | 0.9% NaCl — can be instilled or nebulised |
| Other nebulisers | MgSO4 (if very wheezy), Adrenaline nebulisers |
3. Bronchodilators — Detailed Pharmacology
🟡 Intermediate
3.1 Atrovent (Ipratropium Bromide)
Classification: Antimuscarinic bronchodilator
Mechanism of action: Blocks muscarinic receptors found on the smooth muscle surrounding the airways, causing them to dilate.
Indications:
- Reversible airway obstruction
- Acute bronchospasm
- Asthma (severe and life threatening)
Pharmacokinetics:
- Maximal effect occurs 30-60 minutes after use (when inhaled)
- Duration of action: 3 to 6 hours
- Bronchodilation can usually be maintained with treatment 3 times a day
Cautions (when used by inhalation):
- Avoid spraying near eyes
- Cystic fibrosis patients require additional caution
- Bladder outflow obstruction
- Paradoxical bronchospasm
- Prostatic hyperplasia
- Susceptibility to angle-closure glaucoma
Preparation Note: If dilution of ipratropium bromide nebuliser solution is necessary, use only sterile sodium chloride 0.9%.
3.2 Salbutamol
Classification: Beta-2 agonist (selective)
Mechanism of action: Activates the beta-2 receptors on the muscles surrounding airways, causing relaxation of smooth muscle.
Indications:
- Exacerbation of reversible airways obstruction (including nocturnal asthma)
- Prophylaxis of allergen- or exercise-induced bronchospasm
Dosing (by inhalation of aerosol):
- Persistent symptoms: Child: 100-200 micrograms, up to 4 times a day
- Moderate and severe acute asthma: Child: 2-10 puffs, each puff inhaled separately, repeat every 10-20 minutes or when required. Give via large volume spacer (and close-fitting face mask in children under 3 years). Each puff is equivalent to 100 micrograms.
Important: The dose given by nebuliser is substantially higher than that given by inhaler.
Preparation Note: For nebulisation, dilute nebuliser solution with a suitable volume of sterile Sodium Chloride 0.9% solution according to nebuliser type and duration of administration. Salbutamol and ipratropium bromide solutions are compatible and can be mixed for nebulisation.
Cautions:
Hypokalaemia Warning: Potentially serious hypokalaemia may result from beta-2 agonist therapy. Particular caution is required in severe asthma or COPD, because this effect may be potentiated by concomitant treatment with theophylline and its derivatives, corticosteroids, diuretics, and by hypoxia.
Additional cautions for all beta-2-adrenoceptor agonists (selective):
- Arrhythmias
- Cardiovascular disease
- Diabetes (risk of hyperglycaemia and ketoacidosis, especially with intravenous use)
- Hypertension
- Hyperthyroidism
- Hypokalaemia
- Susceptibility to QT-interval prolongation
3.3 Adrenaline (Nebulised)
Classification: Non-selective adrenergic agonist (alpha and beta receptor stimulant)
Mechanism of action: Stimulates alpha and beta receptors in the sympathetic nervous system, inhibiting an enzyme in smooth muscle. Note: also increases HR and BP by increasing cardiac output.
4. Mucolytics — Detailed Pharmacology
🟡 Intermediate / 🔴 Advanced
Mucoactive substances act to increase the ability to expectorate sputum or to decrease mucus hypersecretion. Expectorants and mucolytics are examples of mucoactive substances.
4.1 Hypertonic Sodium Chloride Solution (3% / 6% / 7% HTS)
Mechanism of action: Increases the amount of sodium and chloride in airway surface liquid, thereby increasing the osmotic gradient and rehydrating the mucus layer.
Indications:
- Mobilise lower respiratory tract secretions in mucous consolidation (e.g. cystic fibrosis)
- Mild to moderate acute viral bronchiolitis in infants
Dosing (by inhalation of nebulised solution):
- Adult: 4 mL, 2-4 times a day
Adverse effects: Temporary irritation, such as coughing, hoarseness, or reversible bronchoconstriction may occur.
Clinical Tip: An inhaled bronchodilator can be used before treatment with hypertonic sodium chloride to reduce the risk of adverse effects.
Key Evidence:
- Improves lung function and quality of life in bronchiectasis
- Improves mucus clearance, airflow, and reduces rates of exacerbation in cystic fibrosis
Important: Hypertonic saline 7% should NOT be given via a vibrating mesh nebuliser.
4.2 N-Acetylcysteine (NAC)
Mechanism of action: Severs disulphide bonds that link mucin monomers to polymers and solubilises sputum. It is also an antioxidant and anti-inflammatory agent.
- Antioxidant effects are mediated by increased levels of intracellular reduced glutathione in the lungs and neutralising oxidant species
- Mucolytic action is attributed to its effect of reducing sulfhydryl moieties, leading to a disruption of disulphide bridges within the glycoprotein matrix of mucus
- This causes a reduction in the viscoelasticity of mucus, bringing levels closer to the optimal level, making it easier to transport along the airways
Role in mechanically ventilated patients: NAC has a role in reducing lung inflammation and dislodging mucus secretions in mechanically ventilated patients.
Caution: In vitro studies have demonstrated that NAC rapidly decreases mucus viscosity; however, it may increase the risk of bronchospasm due to its acidic pH (pH = 2.2). This risk may be mitigated by:
- Pre-treatment with a bronchodilator, OR
- Utilising a reduced concentration of NAC (10% as opposed to 20% concentration)
Reference: Sheffner et al., 1964; Henke and Ratjen, 2007
Evidence in neonates: NAC in pre-term neonates caused no benefits and increased airway resistance and bradycardias.
4.3 Dornase Alfa (DNase)
Classification: Genetically engineered version of a naturally occurring human enzyme.
Mechanism of action: Peptide mucolytic that cleaves extracellular deoxyribonucleic acid (DNA). Hydrolyses DNA polymer and reduces DNA length.
Licensed indication: Management of cystic fibrosis patients with a forced vital capacity (FVC) of greater than 40% of predicted to improve pulmonary function.
Dosing (by inhalation of nebulised solution):
- Child 5-17 years: 2500 units once daily, administered by jet nebuliser
Timing: Expert sources advise usually once daily at least 1 hour BEFORE physiotherapy.
5. Bronchiolitis — Context for Nebuliser Use
🟢 Foundation
5.1 Overview
- Inflammation of the bronchioles
- Viral infection (e.g. RSV)
- Affects children under 2 years old
- Presents with coryzal symptoms and poor feeding
- Patchy CXR changes
5.2 NICE Guidelines for Bronchiolitis
| Recommendation | Details |
|---|---|
| Physiotherapy | No physiotherapy unless significant co-morbidities or intubated |
| Treatment | Use oxygen therapy, CPAP and IV fluids |
| Suction | No indication for regular suction (unless respiratory distress) |
| Nebulisers | No indication for routine nebulisers |
| Prevention | May be offered Palivizumab vaccination against RSV (see updated note below) |
Updated (2026): Palivizumab is more accurately described as passive immunisation with a monoclonal antibody rather than a “vaccination”. From 2025, nirsevimab (a longer-acting, single-dose monoclonal antibody) has begun replacing palivizumab in NHS England, alongside the maternal RSV vaccine Abrysvo. See JCVI statement, 11 September 2023.
6. Literature Review: Mucolytics on PCCU
🔴 Advanced
6.1 Overview of Evidence Base
A review of 9 journal articles was conducted, including:
- Retrospective cohort studies
- Randomised controlled trials (RCTs)
- National cross-sectional surveys
- Systematic reviews
Studies examined nebulised and instilled mucolytics and 0.9% saline.
6.2 Hypertonic Saline Evidence
Study 1: Nebulised HTS in Children with Bronchiolitis on PICU (2019, Retrospective)
| Element | Detail |
|---|---|
| Participants | 104 children <2 years old admitted to PICU with bronchiolitis |
| Groups | 45 given 3% HTS (74% RSV+ve) vs 59 given none (70% RSV+ve) |
| Key results | No significant difference in disease severity, total duration of respiratory support, or length of hospital stay between the two groups |
| Conclusions | Study suggests shorter duration of respiratory support and LOS at PICU with use of nebulised HS in RSV bronchiolitis patients |
| Limitations | Retrospective study; no validated tool used to assess severity of bronchiolitis |
Study 2: Mucoactive Medications in Paediatric Airway Disease (2020, Review)
| Element | Detail |
|---|---|
| Participants | 427 children on PICU receiving ventilator support given either no saline or 0.225-0.9% HTS; 18 children on PICU receiving routine nebulisation with 3% HTS versus 0.9% saline |
| Key results | Non-blinded trial; no statistically significant differences in duration of mechanical ventilation, oxygen therapy, or PICU stay between groups. No differences for duration of mechanical ventilation or chest X-ray atelectasis score, or respiratory mechanics parameters before and after intervention |
| Conclusions | This review does not make any recommendations on routine mucoactive medication strategies for PICU patients possible. Merely reveals the need for further randomised trials |
| Limitations | Non-blinding of trials; small sample size; no explanation of characteristics or reason for PICU admission |
Study 3: HTS in Mechanically Ventilated Patients (from Mucus Clearance Review 2022)
| Element | Detail |
|---|---|
| Participants | 18 paediatric patients undergoing mechanical ventilation randomised to nebulised 3% HTS versus 0.9% saline four times daily until seven days or extubation (prophylactic) |
| Key results | Greater duration of mechanical ventilation among patients receiving HTS (Shein et al., 2016) |
| Note | Patients randomised to HTS group had markers of greater illness severity at baseline compared to NS group |
Study 4: HTS vs NS — No Significant Difference
| Element | Detail |
|---|---|
| Key findings | No statistically significant difference between HTS and normal saline in chest X-ray scores or oxygenation (Youness et al., 2012) |
6.3 DNase (Dornase Alfa) Evidence
Study 1: Intrapulmonary Drug Administration Review (2011, Comprehensive Review)
| Element | Detail |
|---|---|
| Key findings | DNase reduced ventilation days in children with congenital heart disease, and is effective in resolving atelectasis in children without CF who are I+V |
| Evidence quality | From other meta-analysis of RCTs or a high quality systematic review of case-control studies or a low grade RCT, but with high probability that the relationship is causal |
Study 2: DNase in Mechanically Ventilated Children with Bronchiolitis (2022, Retrospective Cohort)
| Element | Detail |
|---|---|
| Participants | 72 children intubated on PICU with confirmed bronchiolitis; 41 given DNase, 31 not given DNase |
| Key results | Children who received dornase alfa were intubated for an average of 33.04 hours longer than standard of care children. Children who received dornase alfa stayed in the PICU an average of 2.05 days longer than standard of care patients |
| Conclusions | Emphasises the need for an RCT. There is still no data to support the use of dornase alfa in this specific population |
| Limitations | Only utilising ICD codes; no assessment of baseline severity of bronchiolitis prior to administering DNase; utilising SpO2 instead of PaO2 goes against standards proposed by The Second Paediatric Acute Lung Injury Consensus Conference |
Study 3: DNase in the PICU — Literature and National Survey (2020)
| Element | Detail |
|---|---|
| Participants | Systematic review: one RCT; intratracheal DNase compared with normal saline twice daily in children after cardiac surgery (n=88) |
| Key results | No difference in reintubation rates (primary outcome); observed a reduction in duration of mechanical ventilation by approximately 1 day (52 vs 82 hours, 36% reduction, p<0.05) in favour of DNase |
| Conclusions | Insufficient evidence to recommend DNase as a routine treatment for airway mucus obstruction or atelectasis in critically ill children with non-CF diseases in the PICU |
| Limitations | Only one RCT found focusing on a very specific patient group; publication bias or threat to study validity based on financial support from manufacturer without prior study protocol registration |
Study 4: Mucus Clearance in Ventilated Patients (2022 Review — DNase arm)
| Element | Detail |
|---|---|
| Participants | One paediatric study: 100 infants undergoing mechanical ventilation following cardiac surgery randomised to dornase alfa and placebo. Regimen: 0.1-0.2 mg/kg twice daily from surgery until extubation (Riethmueller et al., 2006) |
| Key results | No statistically significant difference between groups, but a trend toward improvement in atelectasis scores in the dornase alfa group compared to HTS and NS groups |
| Additional study | Youness et al. (2012): 33 adult mechanically ventilated patients with new onset lobar/multilobar collapse randomised to 7% HTS, dornase alfa, or NS twice daily for 7 days. No difference in chest X-ray scores (primary outcome), but intervention group showed improved oxygenation and more extubation on treatment day 1 (Zitter et al., 2013) |
Updated (2026): The summary above understates the Riethmueller 2006 findings. The original paper (Pediatr Pulmonol. 2006;41(1):61-6. DOI: 10.1002/ppul.20298. PMID: 16265663) — titled “Recombinant human deoxyribonuclease shortens ventilation time in young, mechanically ventilated children” — enrolled 100 infants and reported lower incidence of atelectasis (6 vs 17), shorter median ventilation time (2.2 vs 3.4 days), and shorter median PICU stay (7 vs 8 days) in the dornase alfa group, with the ventilation time difference reaching statistical significance. The 2022 review summary characterising this only as “a trend” therefore understates the result. Note that Youness 2012 was an adult (not paediatric) study. The Zitter 2013 paper actually reported oxygenation improvement at day 5 (P=.03) rather than day 1.
Study 5: Combination HTS/DNase
| Element | Detail |
|---|---|
| Participants | Retrospective case-control cohort study: 7% HTS and dornase alfa in mechanically ventilated neonates with atelectasis unresponsive to conventional airway clearance. Both medications given twice daily |
| Key results | All treatment arms experienced greater improvement in atelectasis compared to control: 27% control, 70% HTS, 81% dornase alfa, 95% combination therapy |
6.4 N-Acetylcysteine (NAC) Evidence
Study 1: NAC in Pre-term Neonates (from 2011 Review)
| Element | Detail |
|---|---|
| Key findings | NAC in pre-term neonates caused no benefits and increased airway resistance and bradycardias |
| Evidence quality | From other meta-analysis of RCTs or a high quality systematic review of case-control studies |
Study 2: Mucus Clearance Review (2022 — NAC arm)
| Element | Detail |
|---|---|
| Participants | RCT of 40 mechanically ventilated patients. Nebulised NAC: 2 mL of 20% NAC diluted within 8 mL of normal saline administered three times daily for 1 day |
| Key results | Found lower mean secretion density and increased oxygen saturation but failed to demonstrate superiority in comparison to normal saline nebulisation (Masoompour et al., 2015) |
| Conclusions | Data supporting use of NAC as a mucolytic in the mechanically ventilated population is limited |
Study 3: Role of NAC in Secretion Clearance in Mechanically Ventilated Patients (2019)
| Element | Detail |
|---|---|
| Participants | RCT, 2018-2019. 50 patients enrolled (more males than females), aged 15-80 years, nebulised NAC in mechanically ventilated adults >24 hours. Intervention: NAC 2 mL with 8 mL normal saline TDS for 1 day. Control: 10 mL 0.9% saline TDS |
| Key results | No statistically significant differences between SpO2, FiO2, mortality, Ppeak, plateau pressure, or secretion density throughout time periods |
| Conclusions | NAC effective in secretion clearance but nil difference in outcomes compared to 0.9% saline |
| Limitations | Limited sample size; limited time period; started after 24 hours of intubation |
Study 4: Nebulised NAC on Respiratory Secretions — RCT (2015)
| Element | Detail |
|---|---|
| Participants | RCT on 10-bed adult ICU in Shiraz, 2012. 40 patients aged 15-90 years (mean age 59 in 21 females and 50 in 19 males), I+V >72 hours. Randomly allocated to control group (0.9% saline nebs TDS) or nebulised NAC |
| Dosing note | Pilot study used 3 mL NAC 20% with 3 mL normal saline — induced bronchospasm — therefore actual study dropped to NAC 2 mL with 8 mL normal saline TDS for 1 day |
| Key results | No adverse effects of NAC; nil difference in plateau or PIP; NAC significantly increased SpO2; mean secretion density lower in NAC group but did not differ significantly between time points |
| Conclusions | Nebulised NAC via ETT was not more effective than 0.9% saline nebulisers in reducing density of mucous plugs |
| Limitations | Unable to measure viscosity of secretions; short time period of 24 hours |
NAC Case Reports: Status Asthmaticus
From speaker notes (detailed clinical narrative):
- In a patient with status asthmaticus complicated by mucus impaction, pulmonary lavage was done twice in 24 hours using 30 mL of 20% NAC, 250 mL normal saline, 0.5 mL Bronkosol and 125 mg Solu-Medrol. After this procedure, a marked improvement was recorded and extubation was accomplished within 48 hours.
- A case series reports significant results in three patients with severe chronic bronchial asthma who underwent bronchoscopy and lavage, using NAC, Solu-Medrol and isoetharine in the irrigation fluid. These three patients improved dramatically following the lavage.
6.5 Summary of Mucus Clearance Review (2022) Limitations
“It is beneficial to use mucoactive therapies in combination with cough augmentation strategies, however more studies need robust validation and standardisation.”
“Complex mucus treated with potent mucolytics should be better explored for mucus plugging resulting in atelectasis and prolonged ventilatory failure.”
“This data suggests that there is reason to utilise mucolytic and expectorant therapies in patients requiring mechanical ventilation, especially in those with excessive secretions and approaching extubation. However, the available evidence in critically ill patients is based on anecdotal data and expert recommendations, rather than validated studies, which limits drawing a definitive conclusion for the standardisation of treatment regimens in critically ill patients.”
7. Main Aims of Respiratory Physiotherapy on PCCU
🟢 Foundation
- Removal of excess secretions
- Improve tidal volumes
- Improve gas exchange
- Reduce work of breathing (WOB)
8. Key Learning Points and Clinical Reasoning
🟡 Intermediate / 🔴 Advanced
8.1 Summary of Evidence
- Some positive results throughout the papers, specifically for DNase in selected populations
- Most limitations and conclusions summarise “more research needed” or have found “no major difference between interventions and control group”
8.2 Clinical Reasoning Framework for Nebuliser Selection
When considering nebuliser use during treatments, ask:
- Are they wheezy? Is there evidence of gas trapping on the ventilator?
- Are secretions too thick to clear with 0.9% saline instillation alone?
- If secretions are thick AND the patient is wheezy, what other options are available? Consider utilising NAC and DNase.
Key Message: “If you’re not sure… ASK! Peer support, senior support, chat through clinical reasoning. You can always try a treatment and if it is not as effective, try something else!“
9. Cross-References to Other Modules
- Deep suction (see 01-deep-suction.md): Suction is provided after each nebuliser episode in ventilated patients. Understanding suction technique, catheter sizing and pressure settings is essential when combining nebulisation with secretion clearance.
- Tracheostomy care (see 02-tracheostomy.md): Tracheostomy patients on PCCU may receive nebulised therapies via the tracheostomy circuit. Humidification and secretion management principles from tracheostomy care overlap directly with this module.
10. References
-
BNF and BNFc (NICE)
-
Otu, A., Langridge, P. and Denning, D.W. Nebulised N-Acetylcysteine for Unresponsive Bronchial Obstruction in Allergic Bronchopulmonary Aspergillosis: A Case Series and Review of the Literature.
-
Nebulised hypertonic saline in children with bronchiolitis admitted to the paediatric intensive care unit: A retrospective study. 2019.
-
Intrapulmonary drug administration in neonatal and paediatric critical care: a comprehensive review. 2011.
-
Rational use of mucoactive medications to treat pediatric airway disease. 2020.
-
Dornase alfa in mechanically ventilated children with bronchiolitis: A retrospective cohort study. 2022.
-
Use of dornase alfa in the paediatric intensive care unit: current literature and a national cross-sectional survey. 2020.
-
Mucus Clearance Strategies in Mechanically Ventilated Patients. 2022.
-
Role of N-Acetylcysteine in Clearance of Secretions in Mechanical Ventilated Patients. 2019.
-
Evaluation of the Effect of Nebulized N-Acetylcysteine on Respiratory Secretions in Mechanically Ventilated Patients: Randomized Clinical Trial. 2015.
-
The effects of N-acetylcysteine on lung alveolar epithelial cells infected with respiratory syncytial virus. 2023.
Additional References Cited in Speaker Notes
- Sheffner et al., 1964 (NAC viscosity and bronchospasm risk)
- Henke and Ratjen, 2007 (NAC concentration mitigation)
- Riethmueller et al., 2006 (DNase dosing post cardiac surgery)
- Youness et al., 2012 (HTS vs DNase vs NS)
- Zitter et al., 2013 (DNase and oxygenation outcomes)
- Shein et al., 2016 (HTS in mechanically ventilated paediatric patients)
- Masoompour et al., 2015 (NAC vs NS nebulisation)