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Chronic respiratory failure from end-stage disease 

Chronic respiratory failure from end-stage disease
Chapter:
Chronic respiratory failure from end-stage disease
Author(s):

Anna Spathis

, Helen E. Davies

, Sara Booth

, and Max Watson

DOI:
10.1093/med/9780199564033.003.002
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Subscriber: null; date: 23 October 2019

  • Definition [link]

  • Pathophysiology [link]

  • Clinical features [link]

  • Oxygen therapy in chronic respiratory failure [link]

  • Non-invasive ventilation in chronic respiratory failure [link]

Definition

Respiratory failure is defined as the presence of hypoxaemia (PaO2 <8kPa) with or without hypercapnia (PaCO2 ±6.0kPa). It is divided into two types:

  • Type I:

    • Hypoxaemia with normal or low CO2.

    • Typically a result of inadequate pulmonary gas exchange (raised alveolar-to-arterial, A-a, gradient).

  • Type II:

    • Hypoxaemia with an increased PaCO2.

    • Usually a consequence of hypoventilation ± V/Q mismatching.

    • Chronicity indicated by an elevated base excess and bicarbonate, to maintain normal serum pH (metabolic alkalosis due to renal compensation for high PaCO2).

Pathophysiology

Chronic respiratory failure can arise from an abnormality in any of the components of ventilatory control, including the central or peripheral nervous systems, respiratory muscle, chest wall, airways, or alveoli. It may be classified as:

  • Failure of ventilatory drive e.g. brainstem stroke, iatrogenic suppression (e.g. opioids).

  • Respiratory pump failure e.g. neuropathy, myopathy (see Chronic respiratory failure from end-stage disease Chapter 1 [link][link]).

  • Neuromuscular junction pathology.

  • Chest wall deformity/restriction e.g. scoliosis, obesity.

  • Obstructive lung pathology e.g. airways obstruction (COPD, chronic asthma), obliterative bronchiolitis.

  • Mixed e.g. obstructive sleep apnoea (OSA) combined with obesity-related hypoventilation; OSA in a patient with COPD; post-ITU (‘critical care’) neuromyopathy.

Determining the underlying cause(s) is fundamental to guiding optimal therapy.

Hypoxaemia is often the potent stimulus of respiratory drive for patients with chronic respiratory failure. Administration of high concentrations of supplemental oxygen can suppress this drive and result in acute respiratory acidosis (­­PaCO2) and decompensation of an otherwise stable state.

Clinical features

Chronic respiratory failure will often develop as a result of previously diagnosed disease after years of illness. An early appreciation of this risk can help to pre-empt difficult future management decisions. In patients who present de novo following good health, investigations and treatment must run concurrently to identify co-morbid and reversible causes of deterioration. The tests below must therefore be performed with this in mind and are indicated only when they would alter patients’ management.

Symptoms

  • Dyspnoea:

    • on exertion (although may be masked in patients with muscle weakness and limited mobility)

    • orthopnoea

    • dyspnoea whilst swimming (typically associated with diaphragmatic weakness).

  • Fatigue.

  • Reduced appetite.

  • Symptoms from chronic nocturnal hypoventilation:

    • excessive daytime sleepiness

    • headache/confusion on awakening

    • poor concentration

    • sleep disturbance/nightmares.

  • Anxiety.

  • Recurrent chest infections:

    • These occur often as a consequence of aspiration secondary to laryngeal and/or pharyngeal weakness.

  • Peripheral oedema:

    • Particularly in COPD, the effect of hypoxia may result in fluid retention (cor pulmonale).

Symptoms typically develop over a prolonged period of time, occasionally years. Given the insidious onset, clues are often missed or attributed to underlying disease progression. Concurrent, occasionally innocuous, illness may precipitate decompensation of long-standing respiratory failure. Acute respiratory failure with development of hypercapnia may result in confusion, reduced level of consciousness, or coma.

Examination

  • Signs of respiratory failure:

    • General: increased respiratory effort i.e. tachypnoea, prominent use of accessory respiratory muscles.

    • Hypoxia: central cyanosis, polycythaemia, fluid retention, cor pulmonale.

    • Hypercapnia: bounding pulse, tremor/flap, papilloedema, drowsiness, confusion.

  • Full neurological assessment may reveal signs of a known, or undiagnosed, neuromuscular condition e.g. fasciculation, muscle wasting, myotonia, and weakness.

  • Diaphragmatic weakness may be revealed by paradoxical thoraco-abdominal movement (inward movement of the abdominal wall during inspiration).

Investigations

Arterial blood gases

  • A raised PaCO2 (PaCO2 ±6.0kPa) is indicative of chronic type II respiratory failure.

  • An elevated base excess (±+2mmol/L) ± high bicarbonate (±28mmol/L) indicates chronicity of respiratory failure.

  • The alveolar to arterial (A-a) gradient is usually raised (±2–3kPa) when V/Q mismatch is present, i.e. abnormal lung parenchyma, but normal with underlying central or neuromyopathic disease.

Imaging

  • A CXR may show features of airway obstruction or a complication of the underlying disease e.g. pneumonia or pneumothorax.

  • CT/MRI brain imaging can reveal presence of an underlying stroke or tumour.

Pulmonary function tests

  • Reveal extent of airflow obstruction or restriction.

  • Determine vital capacity.

  • Assess diaphragm/respiratory muscle weakness e.g. discrepancy between lying and standing vital capacity.

Others

  • A sleep study may reveal features of obstructive sleep apnoea and nocturnal hypoxia e.g. in obesity-related hypoventilation.

  • An EMG should be considered if an underlying myopathy or MND is suspected. Subsequent muscle biopsy may be required.

  • Blood tests may provide useful information e.g. acetylcholine receptor antibodies detected in cases of suspected myasthenia gravis, or elevated creatine kinase concentrations in some myopathies.

Oxygen therapy in chronic respiratory failure

Most data supporting the use of oxygen in chronic respiratory failure stem from patients with COPD. There is little evidence guiding its application in other disease states, and the research base underpinning oxygen use in dyspnoea palliation is scanty (see Chronic respiratory failure from end-stage disease Chapter 5 [link][link]). No reliable factors predict which patients will benefit from oxygen therapy and medical management of all underlying conditions must be optimized prior to its consideration.

Types of oxygen therapy

Ambulatory oxygen

  • This is delivered by a portable, lightweight cylinder and used during exercise/daily activities.

  • Ambulatory oxygen may be considered for:

    • mobile patients on LTOT

    • patients who experience improvement in exercise tolerance ± dyspnoea with oxygen supplementation.

Short-burst oxygen therapy (SBOT)

  • SBOT involves intermittent use of oxygen at rest, prior to exertion, during exercise (ambulatory oxygen), or during recovery.

  • There is some evidence that use of oxygen during exercise can improve exercise capacity and breathlessness in patients with COPD. Systematic reviews of clinical trials suggest that oxygen at rest is not usually effective at relieving symptoms.

  • No factors predict which patients will benefit; therefore, individual therapeutic trials with clinical assessment of subjective gains may be appropriate.

  • This topic is considered in further detail in Chronic respiratory failure from end-stage disease Chapter 5 [link][link].

Long-term oxygen therapy (LTOT)

COPD patients

  • Landmark trials1,2 have shown that LTOT, administered for ≥15hrs/d (including when asleep), increases survival and quality of life in patients with hypoxaemic COPD. A greater benefit may be gained from application of oxygen for ±19hrs/d.

  • Further studies have demonstrated improvement in cardiovascular morbidity, sleep quality, secondary polycythaemia, neuropsychological and cognitive function, exercise capacity, sleep quality, and frequency of hospitalization.

  • Peripheral oedema due to cor pulmonale is reduced as reversal of hypoxaemia improves renal perfusion and increases salt/water excretion.

  • LTOT does not influence the decline in FEV1.

  • Current indications for LTOT in COPD patients:

    • PaO2 <7.3kPa breathing room air when clinically stable.

    • PaO2 ±7.3 kPa but <8kPa when clinically stable with one of: secondary polycythaemia; nocturnal hypoxaemia (SaO2 <90% for ±30% of the night); peripheral oedema; or pulmonary hypertension.

  • Assessment should comprise arterial blood gas (ABG) measurements on two occasions at least 4 weeks apart in patients who are receiving optimum medical management and whose COPD is stable (ideally ±6 weeks following an exacerbation).

  • Arterial hypoxaemia in COPD patients with a FEV1 ±40% or 1.5L suggests that there may be another cause (e.g. pulmonary emboli or nocturnal hypoventilation) and further investigations are appropriate.

Non-COPD patients

  • Evidence is limited. Use of LTOT in patients with chronic hypoxaemia related to other pulmonary or non-pulmonary conditions (i.e. interstitial lung disease, terminal cancer, or chronic heart failure) has not been shown to improve survival.

Practical applications

  • Nasal cannulae or a face mask may be used.

  • An oxygen flow rate of 2–4L/min is often initiated, but controlled concentration oxygen (24% or 28%) may be given via a mask.

  • Aim for an oxygen saturation 90–92% (PaO2 8–9kPa).

  • Check ABG on LTOT to assess for hypercapnia, especially if raised PaCO2 at baseline or if patient develops suggestive symptoms e.g. morning headache, daytime somnolence.

  • Although smoking is considered a contraindication to oxygen use, many patients continue to smoke. They must be warned about the flammability risks and probably negated benefit from treatment.

  • Oxygen concentrators are the most efficient source of LTOT and can deliver up to 10L/min of oxygen. Multiple concentrators may be joined using a Y-shaped adapter to allow a higher flow if required.

References

1. Nocturnal Oxygen Therapy Trial Group (1980) Continuous or nocturnal oxygen therapy in hypoxemic chronic obstructive lung disease: a clinical trial. Ann Intern Med; 93: 391–398.

2. Medical Research Council Working Party (1981) Long-term domiciliary oxygen therapy in chronic hypoxic cor pulmonale complicating chronic bronchitis and emphysema. Lancet; 1: 681–686.

Non-invasive ventilation in chronic respiratory failure

Non-invasive ventilation (NIV) has an important role in the management of patients with chronic hypercapnic respiratory failure. However, there are no data to suggest that prophylactic NIV is beneficial for patients at risk of developing chronic respiratory failure and it is not a substitute for invasive ventilation in patients for whom escalation of treatment, i.e. intubation, is appropriate.

Indications

Deciding when to start NIV will differ between patients. Potential clinical benefits, such as relief of morning headaches and reduced daytime sleepiness, should be balanced with patient wishes and ability to tolerate the intervention.

  • NIV should be considered in patients with symptomatic chronic hypercapnic respiratory failure, and/or evidence of nocturnal hypoventilation on overnight oximetry.

  • Common underlying conditions include:

    • neuromuscular weakness e.g. muscular dystrophies, myopathy

    • thoracic wall deformity

    • decompensated obstructive sleep apnoea

    • obesity hypoventilation syndrome.

  • Development of respiratory failure in MND/ALS occurs with advanced disease and often results in frightening dyspnoea (∼85% patients). NIV has been shown to improve survival and quality of life, and reduce sleep disruption (less REM sleep). It does not influence respiratory muscle weakness or disease progression.

  • The role of NIV in patients with severe COPD and chronic hypercapnic respiratory failure remains unclear. There are reports of it being used very near the end of life to palliate breathlessness when other measures are ineffective or cause adverse effects, or in order to ‘buy time’ to organize affairs or await the arrival of family (see box on [link]).

  • In patients with cystic fibrosis and progressive respiratory failure, nocturnal NIV may be required, to act as a ‘bridge’ to transplantation.

Contraindications

NIV is contraindicated or should be used with caution in the following situations. As always, the balance of potential benefits and burdens should be weighed up in each individual patient.

  • Inability to use mask: facial trauma/surgery/deformity.

  • Inability to protect the airway: moderate to severe bulbar impairment/impaired mental status/agitation/upper airway obstruction.

  • Excessive respiratory secretions.

  • Vomiting/recent oesophageal surgery or injury.

  • Haemodynamic instability e.g. cardiac arrhythmia.

  • Untreated pneumothorax.

  • Life-threatening refractory hypoxaemia.

Practical applications

Although NIV is usually administered nocturnally, control of daytime symptoms is seen. This is likely to be from a combined effect of relief of muscle fatigue, improved chest wall compliance, and reversal of nocturnal hypoventilation.

Ventilator

A portable non-invasive positive pressure ventilator (NIPPV) is used in most cases. If this is not tolerated a negative pressure ventilator (i.e. iron lung), abdominal ventilator, or rocking bed device may be tried.

Interface

Nasal masks are preferred by the majority of patients. Alternatives include oro-nasal masks or a mouthpiece.

Compliance

Patients may find it difficult to tolerate the ventilator, and a failure to respond clinically may reflect non-compliance. Equipment adjustments are often necessary i.e. ventilation settings, mask size or type, and strap tension. A humidifier can be added if mucosal dryness is troublesome. Most patients adapt within weeks and this is enhanced if symptomatic improvement has been noticed (often seen with ≥4hrs NIV use each night).

Monitoring

Patient compliance, symptom response, and features suggestive of hypercapnia should be noted. Repeat nocturnal studies for patients using NIV are usually required only if there is failure to improve or deterioration (with no obvious clinical precedent).

Withdrawal of NIV

Deterioration in respiratory function with increased dependency on ventilatory support (i.e. daytime NIV use) is inevitable in the majority of patients with neuromuscular disease who initiate NIV. Recurrence of previously controlled symptoms, i.e. morning headaches, and progression of the patient's underlying disease despite escalation of ventilatory support (i.e. higher inspiratory pressure settings) indicate insipient failure of ventilatory control. Preparation for this, at its instigation, is important. Good, early communication can avoid distress when clinical decline occurs.

A structured plan should be clearly documented prior to treatment, stating the patient's suitability for future invasive mechanical ventilation. This may be in the form of a statement of wishes or preferences, or an advance decision, and should be informed by medical opinion (see Chronic respiratory failure from end-stage disease Chapter 8 [link][link]).

All patients should be able to opt to discontinue supportive therapy at any point regardless of clinical status. Practical steps involved in the withdrawal of NIV are described in Chronic respiratory failure from end-stage disease Chapter 12 [link][link].

Mrs O was 37 years old and dying of lung cancer. She was a single parent, living alone with a 7-year-old daughter, Amy, and was divorced and estranged from her daughter's father. Her mother was alive and well and helped to care for Amy at times, although she also worked.
Mrs O had a respiratory infection requiring admission to hospital. She wanted to be ventilated, but as she had bony metastases and rib fracture this was not possible. However, she received NIV on the ward and made a partial recovery. She then quickly asked for and chaired a case conference, and organized care for her daughter in the event of her death. She also spent a weekend at home for Amy's birthday.
Shortly after returning to hospital she developed another infection and this time refused intervention. A paper detailing the discussion and decisions made at the case conference was put into a memory box for Amy, to show her how much her mother cared for her.