Secretion management in neuromuscular diseases.

Secretions in the airways are continuously produced by the goblet cells and the glands located beneath the mucosa – approx. 10 mL per day. Secretions play an important role in defense against inhaled pathogens and, due to their physical properties, bind inhaled foreign particles. These can then be removed from the airways either through the process of mucociliary clearance or, as an alternative, by coughing. 

An increase in airway secretions can have various causes: 

• Acute or chronic inflammation of the mucous membrane in the lower airways (viral, bacterial, or irritation from foreign objects such as tracheal tubes)
• (Recurrent) aspiration of saliva or food particles, particularly in cases of underlying swallowing disorders
• Increased secretion viscosity, for example due to insufficient airway humidification or as a result of abnormalities in secretion composition (e.g. cystic fibrosis)

Coughing is a complex process that requires the coordinated action of many muscle groups, including the laryngeal muscles and the muscles of inhalation and exhalation. An effective cough is initiated by a deep inhalation (typically up to 80% of vital capacity, with a minimum of 1.5 liters), followed by closure of the vocal cords (glottis) while simultaneously contracting the expiratory muscles (primarily the abdominal muscles), and then active opening of the glottis while maintaining contraction of the abdominal muscles.

Secretions become a problem for those affected when they

• either form in excessive quantities (as is the case with infections)
• build up in the deep airways, for example through aspiration of saliva or food particles, or
• if they cannot be removed from the airways through natural processes because of a weak cough reflex.

 The latter two conditions are especially prevalent in the case of neuromuscular diseases (NMD): the disease can weaken the inspiratory musculature, preventing the affected person from being able to breathe deeply enough to cough. The expiratory musculature, and especially the abdominal musculature, is also needed for an effective cough – if this can no longer vigorously compress the air in the chest with a closed glottis, it can critically reduce the peak cough flow. 

Additionally, the situation of the person affected is exacerbated if the pharyngeal and throat muscles are also affected, resulting in swallowing difficulties.

Several problems may arise as a result of a weak cough: 

• Shifting of airways resulting in reduced ventilation of parts of the lungs and the development of an oxygen deficit (hypoxemia)
• Increased breathing effort due to narrowing of the airways
• Increased risk of infection of the airways due to increased bacterial proliferation
• Failure of noninvasive ventilation Need for tracheotomy with consecutive invasive outpatient ventilation
• Need for renewed intubation after initially successful extubation in intensive care

The situations above call for intensive secretion management to be able to effectively remove the secretions from the airways. In addition to pharmacological secretion clearance (especially highly concentrated saline solutions for inhalation), there are five principles for secretion management (according to Schönhofer et al., Leitlinie Prolongiertes Weaning [Guideline on Prolonged Weaning], 2019): 

• Increasing intrathoracic volume before the cough effort
• Increasing the maximum expiratory airflow from the airways
• Oscillatory therapy to liquefy secretions
• Increasing expiratory volume
• Mechanical suctioning(blind endotracheal or via bronchoscopy)

For patients with neuromuscular disorders, the primary non-invasive measures suitable for out-of-hospital care are techniques that increase intrathoracic volume and enhance both maximal expiratory flow and expiratory volume.

Works by John Bach (Bach et al., 2004) have shown that the normal peak cough flow that forces secretions out of the airways is greater than 360 l/min. Values under 270 l/min also generally suffice in stable condition without an infection, but decompensation often occurs due to increased secretion collection. With values under 160 l/min which cannot be improved noninvasively with the measures mentioned below, after a short observation time most of the examined patients with motor neuron disease (amyotrophic later sclerosis, ALS) died or received a tracheotomy within 8 weeks.

The consequences of this are: 

• in patients with NMD the peak cough flow should be measured regularly (in the lung function or with a peak flow meter)
• at values below 270 l/min: initiation of non-invasive secretion management (see below)
• at values below 160 L/min that do not respond to non-invasive secretion management: discussion of either tracheotomy or palliative care

1. “Air stacking” refers to increasing intrathoracic volume before a cough, and is suitable for patients with neuromuscular disease who primarily have inspiratory muscle weakness with reduced vital capacity. Using a manual resuscitation bag or temporary pressure increase with non-invasive ventilation (LIAM function: Lung Insufflation Assist Maneuver), intrathoracic volume is ideally raised above 1.5 liters, allowing sufficient peak cough flow to be generated through compression of the expiratory muscles. Alternatively, some patients with neuromuscular disorders are able to perform glossopharyngeal breathing (also known as “frog breathing”), which allows them to increase intrathoracic air volume by swallowing air directly into the trachea.
2. Manually assisted coughing is a physiotherapeutic technique in which, following a deep inspiration or an air-stacking maneuver, compression applied either to the epigastrium or the lateral ribcage at the start of the cough increases peak cough flow by several liters per minute. Precise coordination between the deep inhalation and the execution of the maneuver at the onset of the cough is essential.
3. Machine-assisted coughing (Mechanical Insufflator-Exsufflator, MI-E) most closely replicates a normal cough (ATS, 2004). It consists of a mechanical inflation maneuver with positive pressure, delivered via a mask, mouthpiece, or even an endotracheal tube or tracheostomy tube, followed by an abrupt switch to negative pressure, which actively draws air out of the lower airways – either directly into the interface or into the pharynx, where it can be suctioned off.

According to current recommendations, studies from countries such as Spain, the UK, and France indicate that sufficiently high inspiratory and expiratory pressures are necessary when using the MI-E – pressures of 45-50 mbar for both inhalation and exhalation are recommended for patients with neuromuscular disorders. If patients cannot tolerate these pressure levels, lower pressures can be used, as long as they are still effective in clearing the secretions from the airways. A normal cough consists of an inhalation of approximately 2 cm, followed by a short expectoration phase. If the patient is able to actively breathe along with the device, the inspiratory and expiratory times should be set as follows: inspiration 2-3 seconds, expiration 1 second. 

If the patient is not able to actively participate, e.g. in the case of tracheotomized patients, the expiratory phase should be at least as long as the inspiratory phase. This is because the high inspiratory pressures – as well as the high flows that result – initially push the secretions toward the periphery, making a longer expiratory phase necessary to push them out of the lower airways.

The various MI-E devices available on the market differ in the performance of their turbines, as well as in the use of tubing systems of different lengths and internal diameters. For further details, refer to the work of A. Schütz (Pneumologie, 2017) and N. Terzi (Respir Care, 2023). 

From the author’s perspective, the consequence of this is that switching from one MI-E device to another, as is sometimes required by health insurance providers, is not possible without re-evaluating effectiveness and individual settings.

High-frequency oscillations (10-15 Hz) are often successfully used in physiotherapy for secretion clearance; however, each treatment typically lasts at least 10 minutes, which is far longer than the duration used with an MI-E. Several publications by Sanchez (Sanchez, 2020) found no improvement in 

• Increase in cough peak flow
• Reduction in hospitalizations, improvement in survival in patients with neuromuscular disorders. 

As such, a general recommendation on the use of oscillations cannot be made at present – it is an individual decision, taking the following points into consideration:

• Setting lower inspiratory and expiratory pressures to avoid hyperventilation
• Avoiding insufficiently delivered inspiratory volumes and inadequate expiratory flows
• Treatment duration: at least 5 minutes per session, 4-6 times daily, to achieve a total daily treatment time of 20-30 minutes

This question can clearly be answered with “no.” In recent years, assessment of the inspiratory and expiratory flow curves of modern MI-E devices has shown that problems can occur in the upper airways in particular due to the high inspiratory and expiratory flows: 

• Paradoxical adduction of the vocal cords with (sub)total glottic closure
• Epiglottis folding down with (partial) closure of the laryngeal inlet during inspiration
• (Near) collapse of the hypopharynx during the expiratory phase 

In all of these cases, the applied inspiratory volumes or achieved expiratory flows may be ineffective. In the case of an invasive ventilation access, these problems are not expected because the upper airways are bypassed. 

For further information, especially on curve analysis, see the references listed below (Andersen, 2021; Chatwin, 2024).

All measures to improve secretion management in patients with neuromuscular disorders should be guided by the “oximetry feedback protocol” (Bach, 2004), developed by J. Bach: 

Patients with neuromuscular disorders usually do not have an accompanying lung disease, so oxygen saturation measured by pulse oximetry on room air is generally above 95%. A drop in this saturation in NMD patients can have various causes, most commonly mucus retention in the airways or an increase in carbon dioxide partial pressure. 

Therefore, if oxygen saturation drops, effective secretion management should be initiated first, and in cases of ventilator dependence, (non-)invasive ventilation with room air should be applied. If this does not normalize oxygen saturation, conditions such as pneumonia, pulmonary embolism, or heart failure could be at hand – so a medical evaluation should then be conducted.

Peak cough flow should be measured regularly in all patients with neuromuscular disease who may have involvement of the inspiratory or expiratory muscles, in addition to monitoring of lung function and blood gases. If the value falls below 270 L/min, initiation of specific secretion management is indicated to prevent hospitalizations and often subsequent invasive ventilation, and to improve the patients’ survival prognosis.