1. Motor neuron diseases: Spinal muscular atrophy (SMA), amyotrophic lateral sclerosis (ALS)
2. Peripheral neuropathies: Guillain–Barré syndrome (GBS), chronic inflammatory demyelinating polyneuropathy (CIDP), critical illness polyneuropathy
3. Disorders of neuromuscular junction: Myasthenia gravis (MG)
4. Myopathies
4.1 Progressive muscular dystrophies: Duchenne muscular dystrophy (DMD), facioscapulohumeral muscular dystrophy (FSHD), limb-girdle muscular dystrophies (LGMD), myotonic dystrophies
4.2 Congenital myopathies (e.g., central core diseases, myotubular myopathy, nemaline myopathy, myofibrillar myopathies)
4.3 Congenital muscular dystrophies (e.g., merosin-deficient CMD)
4.4 Metabolic myopathies (Mitochondrial myopathies, glycogen storage diseases)
Once patients with NMDs develop respiratory failure, noninvasive mechanical ventilation (NIV) combined with techniques of manually or mechanically assisted coughing are the main therapeutic interventions to support their respiratory function [5–10]. This chapter reviews the pathophysiological mechanisms responsible for respiratory failure in patients with slowly progressive NMDs (e.g., amyotrophic lateral sclerosis (ALS), spinal muscular atrophy (SMA), Duchenne muscular dystrophy (DMD)) and the issues concerning their respiratory care during ARF. We do not consider rapidly progressive NMDs (e.g., Guillain-Barré syndrome and myasthenic crises) because there is currently insufficient data to support the extensive use of NIV in these patients, and clinical issues arising from their rapid clinical evolution deserve separate remarks.
32.2 Mechanisms Underlying Respiratory Failure in NMDs
Patients with NMDs can develop respiratory failure because of an imbalance between respiratory load and muscle strength, resulting in ineffective alveolar ventilation and hypercapnia. The main determinant of this process is the respiratory muscles’ weakness [3]. In addition, patients with slowly progressive NMD have a chronically elevated respiratory load, which leads to increased work of breathing [11–13]. The main contributions to the increased mechanical load are as follows:
1.
2.
Stiffening of the chest wall, caused by muscle atrophy, osteoporosis, and in some cases extra-articular contractures and intra-articular adhesions, progressing to the irreversible degeneration of the joint cartilage of the rib cage [14]
As the NMD progresses, nocturnal respiratory dysfunction becomes evident and can result in hypercapnia that is initially limited to sleep. With the progression of the NMD, hypoventilation becomes chronic, resulting in daytime hypercapnia. Additionally, weakness of expiratory muscle leads to inadequate clearance of airway secretions.
Patients with NMD may require intensive care because of the progressive respiratory muscle dysfunction. Their admission to the intensive care unit (ICU) is usually prompted by precipitating factors (Table 32.2). In particular, ARF usually occurs in NMD patients as a consequence of otherwise benign upper respiratory tract infections [15–17] or as a result of more severe respiratory complications, such as pneumonia, aspiration, atelectasis, and pneumothorax [18, 19]. During these events, the inspiratory muscles’ strength cannot compensate for the increased respiratory load, resulting in impaired alveolar ventilation. Moreover, weakness of expiratory and bulbar muscle causes ineffective coughing and airway mucus accumulation that further increases the work of breathing, leading to respiratory distress [15–17, 20].
Table 32.2
Causes of acute exacerbations of chronic respiratory failure in children with NMD
Upper respiratory tracts infections |
Pneumonia |
Atelectasis |
Aspiration |
Pneumothorax |
Cardiac failure |
Tracheal hemorrhage (patients with tracheostomy) |
Acute gastric distension (patients under mechanical ventilation) |
Abuse of sedative drugs |
Postoperative respiratory failure |
Pulmonary embolism |
Patients with NMD usually experience mild to moderate bulbar dysfunction, with the exception of patients diagnosed with type 1 SMA and ALS, who may develop a severe glottis functional impairment. Bulbar muscle weakness (facial, oropharyngeal, and laryngeal muscles) can affect the ability to swallow, leading to a risk of aspiration.
Additionally, several myopathies (DMD, limb-girdle muscular dystrophies, myotonic dystrophies, myofibrillar myopathies, mitochondrial myopathies, and glycogen storage diseases) are associated with cardiac dysfunctions (dilated cardiomyopathy and/or abnormalities of the conduction system) [21, 22], which may also contribute to the development of ARF [23].
In NMD patients with compromised respiratory function, anesthetic agents may further decrease respiratory muscles strength and can exacerbate hypoventilation, airway secretions retention, aspiration, and obstructive and central apneas [5, 7, 24]. These conditions may lead to nosocomial infections, prolonged intubation, tracheotomy, and eventually death. Therefore, in all patients with NMDs, preoperative pulmonary evaluation is strongly recommended to assess the risk of respiratory complications and when respiratory function measurements and/or sleep studies are abnormal, NIV and assisted cough techniques may be indicated [5, 7, 24].
32.3 Diagnostic Process
The early identification of precipitants to intensive care admission (Table 32.2) is essential because they are more amenable to therapy than the NMD itself [10, 18, 25–28]. The overall diagnostic process is summarized below [10].
History: rule out abuse of sedative drugs, aspiration, and anticipatory care plan (i.e., a do not intubate order)
Physical examination: rule out signs and symptoms of:
Heart failure (pulmonary crackles, peripheral edema, elevated jugular venous pressure, pleural effusion, hepatic congestion)
Clinical signs of pneumonia, aspiration, or atelectasis
Pneumothorax
Lab tests:
Serum B-natriuretic peptide and D-dimer (good negative predictive values for heart failure and pulmonary embolism)
Blood and sputum culture with Gram stain if pneumonia is suspected
Imaging:
Electrocardiogram to rule out arrhythmias and conduction defects
Chest X-ray to rule out cardiomegaly, pulmonary congestion, new pulmonary infiltrate, and pneumothorax (mandatory computed tomography (CT) scan in case of suspected pneumothorax and non-conclusive chest X-ray)
Echocardiogram to evaluate ventricular function if heart failure is suspected
It is important to note that pneumothorax is a rare but serious and life-threatening complication in NMD patients. Conventional chest X-ray has poor sensitivity for the detection of pneumothoraces and thoracic CT may be required [18]
32.4 Respiratory Management
Respiratory management of NMD patients includes invasive or noninvasive mechanical ventilation, assisted coughing techniques, and the extubation process.
32.4.1 Mechanical Ventilation
NIV combined with mechanically assisted coughing is an established standard technique in patients with NMDs without severe bulbar impairment who require mechanical ventilation (MV) for ARF. This strategy may represent an effective life-support measure and a good alternative to invasive MV, either as an outpatient or in the ICU [16, 17, 26–29]. Mechanical ventilation should be considered in NMD patients with acute exacerbation who have at least one of the following issues: (1) dyspnea, as referred by the patient; (2) lethargy; and (3) acute respiratory acidosis (i.e., arterial pH below 7.35 with PaCO2 greater than 45 mmHg) [27]. Most of these patients benefit from NIV. For patients already using nocturnal NIV, daytime NIV may be required during acute exacerbations [34, 35].
NIV is contraindicated in patients with severe inability to swallow; uncontrollable airway secretions; life-threatening hypoxemia; severely impaired mental status; hemodynamic instability; recent facial, upper airway, or upper gastrointestinal tract surgery; or bowel obstruction [26, 27, 36, 37].
Invasive ventilation should be considered if, despite 6–12 h of NIV with optimal ventilator settings, it proves impossible to reduce dyspnea or lethargy, to decrease the respiratory rate, or to improve blood gas exchange (i.e., refractory arterial pH below 7.30 or below the value on admission or failure to maintain a PaO2 > 65 mmHg with a FIO2 ≥ 0.6) [27, 36].
Hospital admission can be disruptive for these patients [38], who can often be successfully managed at home by experienced and well-trained family members [30]. Bach and colleagues [16, 17, 29, 39] described a regimen for managing acute on chronic neuromuscular respiratory failure at home. The patients received a 24-h NIV during the exacerbation periods. Oxygen saturation of room air was monitored continuously and when it fell below 95 %, secretions were aggressively removed using MI-E (mechanical insufflation-exsufflation) until oxygen saturation returned to the 95 % range. Although controlled studies establishing the efficacy of this approach are lacking, the authors reported a dramatic reduction in the need for hospitalization and a prolongation of life expectancy. Vianello et al. [40] showed that “hospital at home” for NMD patients with respiratory tract infection for whom hospital admission had been recommended after medical assessment is an effective alternative to hospital admission. They treated these patients according to the following treatment protocol:
District nurses visited the subjects mornings and afternoons until recovery from exacerbation. The nurse assessed the subject’s adherence and response to treatment and could request a pulmonology visit if clinical progress was unsatisfactory.
A pulmonologist visited the subjects each morning for the first 3 days, and thereafter at the discretion of the district nurses or subject’s general practitioner, to assess the response to therapy and eventually introduce changes.
Subject telephone access to the pulmonologists was ensured.
The subjects’ general practitioners were informed of the subjects being randomized to the hospital-at-home program.
Standard antibiotic therapy was used, following guidelines for the management of acute bronchitis or community-acquired pneumonia.
The ventilator was readjusted to obtain a tidal volume of 10–12 ml/kg and a breathing frequency of <25 breaths/min and to maintain SpO2 ≥ 95 %. NIV was initially delivered continuously, except for 30–60 min periods of “rest” to allow the subject to receive liquid dietary supplements, drink water, and speak. After the first 24–48 h, if clinical conditions and blood gas exchange were satisfactory, the application of NIV was interrupted by progressively longer intervals of spontaneous breathing. In all cases, nocturnal ventilation via nasal mask was continued until the end of the follow-up period.
Manually and mechanically assisted cough were provided whenever SpO2 decreased, the ventilator peak inspiratory pressure increased, or the subject had a respiratory deterioration or sense of retained secretions. Assisted cough treatments were usually repeated until one or more of the following factors were observed: improving dyspnea, reduction in breathing frequency, sputum elimination, or increased SpO2. Manually and mechanically assisted cough were administered for the first 3 days of the home-care protocol by a respiratory therapist who visited the subjects each morning, and by nonprofessional caregivers (i.e., the subject’s home care attendant or a family member) trained in the application of the device. Subsequently, assisted cough was independently administered by home caregivers.
Hospital-at-home subjects received pulse oximeter monitoring, and their caregivers were instructed to perform assisted coughing, NIV, or both as needed to return SpO2 ≥ 95 %.
If home management fails, patients must be hospitalized and they should be managed in an ICU, where a cough machine and NIV should be applied aggressively. NIV and assisted coughing techniques have become a standard therapy for the treatment of acute on chronic neuromuscular respiratory failure also in the critical care setting [26–28, 30, 36, 37]. The increased utilization of NIV has been driven in large part by the need to reduce patient discomfort and to avoid sedation and complications of invasive MV [41].
In particular, Vianello and colleagues [27] demonstrated that in the NIV group compared with the invasive MV group, intrahospital mortality (14 % vs 57 %), treatment failure (29 % vs 79 %), and duration of ICU stay (13.6 ± 9.7 vs 47.1 ± 51.9 days) were lower. Interestingly, superimposed or unresolved pneumonia with septic shock was absent in individuals receiving nasal intermittent positive pressure ventilation (NIPPV). These complications represented the cause of failure in 6 of the 11 subjects unsuccessfully treated via translaryngeal tube. In addition, the results of another prospective cohort study evaluating only NMD patients treated with a noninvasive approach (NIV and MI-E) showed a low mortality rate (8.3 %) and a short hospital stay (12.05 ± 7.03 days) [26].
Moreover, Servera et al. [26] treated 24 consecutive episodes of ARF in 17 patients with neuromuscular disease using NIV and mechanical coughing aids. They showed that noninvasive management was successful in averting death and endotracheal intubation in 79.2 % of the acute episodes.
The role of NIV as a reliable alternative to intubation is indirectly supported by two clinical studies conducted in patients with NMDs treated with invasive MV for ARF [38, 42]. In these studies, the mortality rate was 29 % and 32.8 %, respectively. Moreover, Bradley and colleagues [38] reported a median weaning time period before being discharged to the community of 10 weeks among survivors.
Patient selection remains crucial for the success of this ventilatory strategy. Bulbar dysfunction increases the patient’s risk for aspiration, hampers the elimination of airway secretions, and increases resistance to airflow [26, 41, 43]. Therefore, it can decrease the possibilities of successful use of NIV and MI-E [44]. In addition, patient training in NIV and assisted coughing before hospitalization is important to the success of this therapeutic approach [45].
In conclusion, there are only few prospective studies concerning the management of patients with NMDs presenting acute on chronic respiratory failure [26–28]. This is probably because it is methodologically difficult to recruit patients with NMDs presenting with ARF [41]. These trials and other retrospective studies [16, 17, 29, 31–33, 39, 44, 46] reported the successful use of NIV in improving gas exchange abnormalities and avoiding intubation in this group of patients. Therefore, a noninvasive approach (e.g., NIPPV combined with assisted coughing) is always preferred where feasible. If it fails or is contraindicated (e.g., because of severe bulbar impairment), patients can require endotracheal intubation as a short-term measure.
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