29 - Haematological symptoms | Oxford Textbook of Palliative Care for Children (Liben, Oxford Textbook of Palliative Care for Children)

Editors: Goldman, Ann; Hain, Richard; Liben, Stephen

Title: Oxford Textbook of Palliative Care for Children, 1st Edition

> Table of Contents > Section 3 - Symptom care > 27 - Respiratory symptoms

Respiratory symptoms

Stephen Liben

Richard Hain

Ann Goldman

Introduction

A major goal of palliative care is to alleviate symptoms that cause suffering. Suffering may stem from conditions or events that threaten the integrity of a person as a complex psychological and social entity [1]. However, suffering is not simply related to the severity of unrelieved physical symptoms. It is also experienced by whole persons and can occur in relation to any aspect of their physical, psychological, social, or spiritual personhood. A sense of loss of meaning and purpose, helplessness, hopelessness, endlessness, and lack of control are major causes of suffering [2].

Respiratory symptoms require management when they are the cause of distress or discomfort to the child. At the same time there are therapeutic interventions that may serve to both alleviate one kind of suffering while imposing another, for example mechanical ventilation may alleviate some aspects of breathlessness but also result in the need for suctioning, frequent infections, and potentially life-threatening complications. As with all therapies the ultimate decision as to whether an intervention is indicated will be mandated by the balance between benefit versus burden of the treatment, taken together with the unique needs of the particular child.

Respiratory symptoms in children with life-limiting conditions are often life-threatening. Their management must be appropriate to the stage of the disease. Postponing death is not appropriate if prolonging life is counter to the child's best interests.

Healthcare professionals are generally well-trained in the management of acute cardio-respiratory failure. This expertise may be counterproductive in end of life care and when misapplied may compromise dignity and increase suffering of the dying child.

Dyspnoea

Breathlessness (dyspnoea) is described as a subjective, uncomfortable awareness of difficulty in breathing or of the need to breathe. Breathlessness can be one of the most frightening and distressing symptoms. It is often accompanied by considerable anxiety in both the child and the family. The vicious cycle in which anxiety aggravates breathlessness and breathlessness in turn creates further anxiety is experienced to some degree by most breathless patients. Some patients may experience a severe panic attack and become convinced that they are about to die. Such attacks may be more common than is acknowledged. Dyspnoea occurs in 40 65% of children with malignant conditions and there is evidence that the control of dyspnea may be less effective than that of pain in palliative care [3, 4, 5].

The precise origin of the sensation of breathlessness remains unknown. From a pathophysiologic point of view, dyspnoea is associated with three main abnormalities: (1) an increase in respiratory effort to overcome a certain load (e.g., obstructive or restrictive lung disease, pleural effusion), (2) an increase in the proportion of respiratory muscle required to maintain a normal workload, and (3) an increase in ventila-tory requirements (hypoxemia, hypercapnia, metabolic acidosis, anaemia, and so forth). In many cancer patients, different proportions of the three abnormalities may coexist making the pathophysiologic interpretation of the intensity of dyspnoea complex. Although it is well recognised that both hypoxia and hypercapnia may cause severe dyspnoea, it is not clear if this occurs as a direct perception of altered chemoreceptor stimulation or if the distress is due to the combination of this stimulation and a significant effect of efferent muscle stimulation which results in an increase in ventilation [6].

Dyspnoea has been described as a synthetic sensation, like that of thirst or hunger [7], that is the result of a complex

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interaction of signals arising from within the central nervous system, both from the automatic centres in the brain stem and from the motor cortex, and from a variety of receptors in the upper airway, lungs, and chest wall. Most conditions that cause breathlessness likely do so by more than one mechanism, and different conditions share common mechanisms. However, each condition probably has a unique combination of physiologic factors that determines the quality and intensity of dyspnoea in a particular patient at a given time.

Current hypotheses on the origin of dyspnoea emphasise the importance of respiratory muscle effort that reflects central motor command [8]. However, the role of the central mismatch between respiratory muscle effort and instantaneous feedback from sensory receptors throughout the respiratory system in the perception of dyspnoea has also been emphasised. This theory has its basis in the disparity between the respiratory motor output and the mechanical response of the system [9, 10, 11].

Both studies and clinical observations suggest that under a given set of conditions, the brain expects a certain pattern of ventilation and associated afferent feedback and that deviations from this pattern cause or intensify the sensation of dyspnoea. Even patients receiving mechanical ventilation are often breathless, despite a reduction in the work performed by the respiratory muscles. The process that necessitated mechanical ventilation in the first place is often responsible for the symptoms, but additional factors may play a part. For example, unless the output of the ventilator is matched to the patient's requirements for flow and tidal volume they may not match those desired by a patient with heightened respiratory drive, in which case the afferent mismatch may intensify dyspnoea [12].

Causes and assessment of dyspnoea

Causes of breathlessness are diverse and include anxiety, airway obstruction, anaemia, bronchospasm, chest pain (musculoskeletal, pleuritic, post-thoracotomy or rib fracture), elevated diaphragm (secondary to ascites, hepatomegaly or phrenic nerve lesion), hypercapnia, hypoxemia, metabolic disorders, pleural effusion, pneumonia, pulmonary oedema, pulmonary embolism, respiratory muscle weakness, and thick secretions. The sudden development of dyspnoea, headache, swelling and distension of the veins of the face, chest and upper limbs suggests the development of superior vena caval obstruction in cancer patients.

Breathlessness, like pain, is a symptom not a sign. Measures of respiratory rate, oxygen saturation, blood gas levels, and professional and family members perceptions do not necessarily correlate with the patient's perception of breathlessness. The only reliable measure of dyspnea is patient self-report which may be difficult or impossible to obtain from pre- and non-verbal children.

Dyspnoea is a difficult symptom to measure due to both its subjective and multidimensional nature. Because neither the initiation nor the perception of dyspnoea can be measured, assessment is based on the patient's self-report. The expression of the intensity of dyspnoea can be influenced by a number of factors such as cultural background, environment, life experiences, and psychological state [13, 14]. Additionally, the assessment of dyspnoea is not always expressed directly by the patient but rather by the proxy caregiver or professional staff introducing a potential bias. Moreover, there is always the possibility of mistaking tachypnoea for dyspnoea. Tachypnoea simply refers to an increased rate of breathing and says nothing about subjective unpleasantness.

The visual analogue scale (VAS) was introduced by Aitken in 1969 for the assessment of the intensity of dyspnoea [15]. VAS is a horizontal or vertical line anchored with terms that characterise two extremes of a possible subjective status from no breathlessness to worst possible breathlessness . Individuals are asked to mark the portion of line (creating an interval scale) that best reflects the intensity of dyspnoea at a given time. The use of the VAS for the comparison of different populations is of limited value, rather it is best to use the VAS for repeated measurements with the same patient in order to quantify disease severity and the effects of therapeutic interventions.

For inter-individual comparisons the Borg Category Scale is more convenient than the VAS. The Borg modified scale consists of a vertical scale labelled 0 10, with corresponding verbal expressions of progressively increasing sensation intensity from nothing at all to maximal [16]. Other methods of dyspnoea assessment include both a Lickert-type scale and a verbal rating scale.

Pulmonary function tests can be particularly useful in the assessment of obstructive and restrictive pulmonary disorders, as well as neuromuscular weakness. The following tests are available: forced vital capacity (FVC), expiratory and inspiratory slow vital capacity (VC/IVC), and maximum voluntary ventilation (MVV). These tests are useful to select patients both for palliative care or ventilatory support programmes (depending on the patient's choice), and also for the assessment of the response to different therapies. However, they remain inadequate to assess the intensity of dyspnoea. In one study the age of patients with Duchenne muscular dystrophy (DMD) when vital capacity fell below 1 l was a strong marker of subsequent mortality (5 year survival 8%) [17].

Management of dyspnoea

The first principle of management is to identify and treat the underlying cause of dyspnoea. This may not always be

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possible or appropriate in the setting of palliative care and needs to be considered on an individual basis. In patients with advanced disease, the burden of investigations and disease-modifying interventions may outweigh any potential benefit. There are three widely used medical approaches for the symptomatic relief of breathlessness: oxygen, opioids, and anxiolytics.

Oxygen is prescribed for breathless patients because some respond with a decreased sense of breathlessness while others have no change in their level of comfort. Some dyspnoeic patients may benefit from compressed air delivered by nasal prongs or from a fan. This is likely due to physiologic effect of stimulating the V2 branch of the fifth cranial nerve that has a central inhibitory effect on the sensation of breathlessness [18, 19, 20]. One practical approach to determining the potential benefit of inhaled oxygen is a trial with direct observation and self-report to best assess if oxygen achieves the primary goal of making patients more comfortable, regardless of whether or not their measured oxygen saturation is affected.

Nocturnal hypoventilation in children with neuro-degenerative diseases and muscle dysfunction can lead to poor sleep, tiredness, lethargy, headache and reduced appetite. Nocturnal hypoxia is assumed to be one of the most important causative factors of morning headaches. In the intermediate phase of neuromuscular disease hypoxia is difficult to diagnose and requires empirical treatment. Morning headaches may be improved by oxygen therapy.

Case A 16-year-old girl diagnosed with juvenile amyotrophic sclerosis was admitted to a hospice for children. Slowly, progressive muscle weakness was observed from her 8th year of life until eventually she was incapable of moving by herself. On admission she had significant bulbar dysfunction with slurred speech, snoring and dysphagia requiring a gastrostomy.

She had symptoms of nighttime hypoventilation including nightmares, disturbed sleep, tiredness and daytime fatigue. Severe headaches appeared suddenly after awakening and receded partially in the afternoon/evening. Oxygen provided during the night that was discontinued in the morning did not provide relief. A trial of opioids was similarly unsuccessful. It was only after oxygen therapy was continued until midday that a dramatic improvement in her headache pain was obtained [21].

Opioids may relieve the distress of breathlessness in many patients without a measurable effect on their respiratory rate or blood gas. In a placebo-controlled crossover study of 10 dyspnoeic adult cancer patients on regular morphine the intensity of dyspnoea was significantly improved after a test dose of morphine, which was 50% of the regular dose [22]. In a randomized continuous sequential controlled trial to compare the efficacy of two supplementary dosing regimens of opioids (25% vs. 50% of 4-hourly analgesic dose) on dyspnoea in terminally ill adult cancer patients, 25% of the equivalent of the 4-hourly dose of opioid was sufficient to reduce both dyspnoea intensity and tachpnea for 4 h; there was no obvious advantage of using more than one quarter of the regular dose [23].

Opioids can be commenced at a low dose (half of the usual starting dose) and increased as required to reduce symptoms (e.g. for a child aged over 6 months, start with oral morphine 0.1 0.25 mg/kg/dose q 4 h orally). Nebulized morphine may be effective in some patients with dyspnoea and has the potential advantage of being rapidly effective while producing fewer systemic side-effects. The starting dose is 2.5 5 mg morphine (injectable solution) via nebulizer. Caution is needed in using nebulised morphine both because of limited experience in its use and potential for causing bronchospasm in some children.

Benzodiazepines are often used in combination with opioids for their sedative and anxiolytic effects. Benzodiazepines are a group of drugs that reduce anxiety and aggression, sedate and improve sleep, suppress seizures, and relax muscles.

Radiotherapy may have a valuable palliative role in dyspnoea due to malignant chest disease. Radiotherapy is likely to provide benefit only where symptoms are caused by tumour that is close to one of the bronchi or other major airways. Tumours that are elsewhere in the lung parenchyma are usually asymptomatic and radiotherapy is often unnecessary. Tumours near a bronchus can also cause haemoptysis. Major haemorrhage is unlikely but even small amounts of haemoptysis can be very distressing for patients. Radiotherapy may also have an important role in superior vena caval obstruction. The potential benefits of radiotherapy need to be weighed carefully against the fact that the child may need to come to the hospital repeatedly or even be admitted for such treatments. Finally, some children will already have received maximum doses of radiotherapy to the chest during previous attempts to cure their disease.

Bronchospasm may contribute to dyspnea and respiratory distress and is often responsive to bronchodilators. Steroids can also be useful in alleviating bronchospasm and may reduce inflammation around pulmonary metastases. The prolonged use of steroids over months requires a balancing of their benefits versus their long-term side-effects that include weight gain and behavioural changes.

Additional measures to help relieve dyspnea include attending to the psychological impact of breathlessness. Anxious children benefit from the presence of confident and reassuring family members and staff. Breathing exercises (e.g. long, slow breaths), appropriate positioning (i.e. upright) and relaxation training may also be helpful.

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Neuromuscular diseases

Neuromuscular diseases (NMD) like Duchenne muscular dystrophy (DMD) and spinal muscular atrophy (SMA) are often associated with abnormalities of ventilatory control with associated hypoventilation, particularly during sleep, and a reduced ventilatory response to CO₂ and oxygen [24].

Patients with NMD exhibit a heightened neuromotor output [25, 26]. The latter is sensed as an increased respiratory muscle effort and as such is likely to be the principal mechanism of dyspnoea in patients with uncomplicated NMD [27]. Alternatively, the association of an increased respiratory system impedance with respiratory muscle weakness increases the respiratory muscle load and may affect the coupling between respiratory effort and volume; therefore, a greater-than-normal dyspnoea sensation might be expected.

DMD is an X-linked condition that affects approximately one in 3300 live male births and is caused by the absence or disruption of the protein dystrophin. The majority of affected boys die from respiratory failure but the time to death is variable. DMD is the most common and most severe form of childhood muscular dystrophies, resulting in early loss of ambulation between the ages of 7 and 13 years and death in the teens and twenties. Despite advances made in the understanding of the molecular genetics of the disease, no definitive cure has been found.

SMA is a severe disease of childhood characterised by degeneration of lower motor neurons associated with muscle paralysis and atrophy that eventually leads to pulmonary complications and early death in those most severely affected [28, 29]. Mutations of the SMN1 gene are responsible for SMA. On a clinical basis the subgrouping of three stages is now widely accepted [30]. Type I (Werdnig Hoffman) patients are the most severely affected, with symptoms presenting from birth to 6 months; they are never able to sit or stand. Children with the intermediate form, type II (Dubowitz), develop symptoms during the first 6 18 months. They are able to sit without support, but cannot walk. Type III (Kugelberg Welander) patients are able to stand and walk and the onset of symptoms before the age of 18 months are unusual. SMA type I is associated with impairment of respiratory function, which is probably caused by involvement of the intercostal muscles as well as the diaphragm [31]. Death as a result of respiratory insufficiency within the first 18 months of life is common. However, in one study 36 out of 349 SMA type I patients (10%) survived at least beyond their fifth birthday, in spite of total immobility and frequent respiratory infections [32]. Type II SMA is more heterogeneous than type 1, but respiratory function is the most important factor in determining prognosis. Type III affected children have no respiratory problems. Both type I and type II patients tend to develop scoliosis and other vertebral deformities. Scoliosis contributes to the impaired lung function by physically impeding respiratory movement and thereby reducing vital capacity, as well as increasing ventilation/perfusion mismatch [33]. Spinal bracing (wearing a rigid jacket) delays the progression of the spinal deformity [34, 35], however, bracing may also cause respiratory impairment.

Of important clinical significance is the fact that patients with certain NMD's may have significant changes in arterial blood gases without impressive symptoms. These patients increase their respiratory rate rather than tidal volume (TV) in response to hypercapnia and hypoxemia [36]. This rapid and shallow breathing response is thought to be an attempted compensation aimed at increasing ventilation with minimal increase in work of breathing. This is a particularly important feature of patients with chest wall deformities (kyphoscoliosis) in whom thoracic compliance is low. Accordingly, there is a less impressive increase in total alveolar ventilation due to increased dead space ventilation. This is in comparison with the normal response of increased TV in response to hypercapnia or hypoxemia. The tachypnoea may then cause worsening respiratory muscle fatigue leading to a further reduction in TV. Respiratory failure typically complicates advanced NMD by compromising effective respiratory muscle function. It is now known that nocturnal hypoventilation precedes resting daytime gas exchange abnormalities, probably accounting for the commonly presenting symptoms of disturbed sleep, increasing daytime hyper-somnolence, morning headaches, and features of cor-pulmonale, despite reasonably normal daytime gas exchange [37]. Regardless of the status of the associated muscle weakness, respiratory failure can be anticipated when the VC falls to 55% of predicted, and the maximum inspiratory force falls to 30% of predicted [38]. Death in these patients is usually caused by progressive respiratory failure and superimposed infections secondary to aspiration as a result of pharyngeal dysfunction [39].

Cystic fibrosis

Cystic fibrosis (CF) is a multi-system disorder affecting the respiratory, alimentary, hepatobiliary, and reproductive systems associated with a variety of endocrine and metabolic complications including diabetes and osteoporosis. With many therapeutic advances in the treatment of CF, the median survival in developed countries is now around 30 years [40]. Over 90% of deaths are from respiratory disease caused by a vicious cycle of infection, inflammation and progressive lung destruction leading to respiratory failure [41]. The terminal phase is usually heralded by increased frequency and severity

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of respiratory exacerbations, oxygen dependence and declining lung function. Patients who have already progressed to severe airflow obstruction with a forced expiratory volume in one second (FEV1) of less than 30% of the predicted value are much more likely to die, with an estimated 2 year mortality rate of approximately 50% [42, 43]. The initiation of discussions regarding end-of-life care should be considered in all patients with CF, in particular in those with an FEV1 30% or a rapid decline in functional status. These criteria are similar to those for referral for consideration of lung transplantation, and clearly the issues of transplantation and end-of-life care are intertwined [44].

In a retrospective study of 44 patients who died of CF-related respiratory failure the mean FEV1 was 23% of predicted. All patients had been designated as do-not-resuscitate (DNR) for at least 24 h before death. The mean duration of DNR status was 25 days. Forty-three patients died in the hospital; five died in ICU, four of which had been listed for lung transplantation, received assisted ventilation by means of biphasic positive airway pressure (BiPAP). Only one patient died at home under hospice care. Length of stay in the hospital before death varied from 24 h to several months; the typical length of stay was 2 3 weeks. Thirty-eight patients (86%) received opioids at the time of death. Thirty-three patients (75%) received intravenous antibiotics 12 h before death [45]. In contrast to this U.S. study, data from South Africa reported that 56% of their CF patients died at home [46]. These cross-country disparities of place and mode of death remain to be fully explained as to what is best for an individual child and family.

Suggested treatments of dyspnoea in patients with CF include [47]:

Physiotherapy to clear excessive secretions (fatigue and hypoxia may limit its use).
Nebulised saline or bronchodilators to assist with expectoration.
Nebulised amiloride and DNase as mucolytics.
Oxygen if comfort improves with its administration
Opioids for relief of dyspnoea.
Relaxation techniques and small doses of anxiolytics such as benzodiazepines.

Home palliative care may be considered when bacterial pneumonia's become resistant to available antibiotics. Pseudomonas aeruginosa respiratory infection was found to be a major predictor of morbidity and mortality in children with CF [48]. In the terminal stage antibiotics, physiotherapy and mucolytics could be withdrawn, though for many children oxygen, nebulised morphine [49], and sedation if required should be considered.

Life-prolonging medical treatments in CF include medication and artificially or technologically supplied respiration, nutrition, and hydration [50]. The development of lung transplantation in the 1980s offers a therapeutic opportunity for some patients with CF. However, palliative care is often needed for patients on a transplant list as in developed countries up to 40% of accepted patients will die awaiting a lung transplant. In one study the survival in a group of 190 children who underwent isolated lung transplant was 77% at 1 year, 62% at 3 years, and 55% at 5 years. There were 25 early (60 days) and 61 late deaths. The most common cause of early death was graft failure (52%), while the most common causes of late death were bronchiolitis obliterans (57%), infection (21%), and post-transplant malignancies (18%)[51]. Clearly, palliative care issues remain relevant both pre- and post-transplant for the majority of patients with CF who are transplant candidates.

Invasive mechanical ventilation (via a tracheostomy or endotracheal tube) for respiratory failure in CF is generally considered ineffective and is not usually recommended unless a clearly reversible component to the respiratory compromise exists. Non-invasive ventilation refers to the delivery of mechanical ventilation to the lungs using techniques that do not require an endotracheal airway (e.g. via a tight-fitting mask on the face). Non-invasive positive pressure ventilation has been used in patients with end-stage CF, often as a bridge to lung transplantation [52]. The use of mechanical ventilation in children with NMD is complex and requires a careful balance between potential benefits versus the burden of suffering for each individual patient.

Cough

Cough is a physiological reflex designed to expel particles and excess mucus from the airways. An effective cough depends on the ability to generate an adequate expiratory airflow, estimated at 160 L/min [53]. Expiratory airflow is determined by lung and chest wall elasticity, airway conductance, and, at least at higher lung volumes, expiratory muscle force. By generating an adequate vital capacity (in adults 2.5 L) to take advantage of respiratory system elasticity, inspiratory muscle function also contributes to cough adequacy. In addition, an effective cough requires intact glottis function, so that explosive release of intrathoracic pressure can generate high peak expiratory cough flows [54].

Cough can result from irritation to the upper or lower airway, pleura, pericardium or diaphragm. It may be caused by respiratory infection, airways disease, malignant obstruction, oesophageal reflux, aspiration of saliva, or induced by drugs.

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Cough is pathological when it is ineffective and when it adversely affects sleep, rest, eating, or social activity. Persistent cough can also precipitate vomiting, exhaustion, chest or abdominal pain, rib fracture, and syncope. The primary aim is to identify and treat the cause of the distressing cough but when this is not possible or is inappropriate a cough suppressant may be used. An example is a dry cough that is distressing to the patient, or a nocturnal wet cough that is disturbing sleep.

Tenacious or thick secretions can be loosened with nebulised saline allowing the child to then remove them by coughing. Use of nebulised saline, as well as other mucolytics can result in the production of copious liquid sputum, and this makes it unsuitable for those who are unable to expectorate. Physiotherapy can also be helpful. For upper airway irritation, it is worth seeing whether cough lozenges or a simple cough linctus can soothe the throat and alleviate a dry, irritating cough. Bronchospasm may also contribute to cough and treatment with salbutamol may be helpful.

Children with a persistent dry cough may benefit from opioids that are generally effective at reducing coughing and the distress associated with coughing. Children already receiving opioids for analgesia may need the dose increased.

In patients with neuromuscular disorders the diaphragm and intercostal muscles are often affected, causing hypoventilation and weak cough. Difficulty in clearing secretions, combined with aspiration due to problems in swallowing also predisposes these patients to chest infections. When weak expiratory muscles are combined with a markedly reduced vital capacity, as occurs in end-stage neuromuscular diseases, the cough mechanism is severely impaired. The inability to cough effectively is tolerable for patients who have minimal airway secretions and an intact swallowing mechanism, but an episode of acute bronchitis or aspiration of oral secretions can precipitate a life-threatening crisis. The simplest manoeuvre to augment cough flow is manually assisted or quad coughing. This consists of firm, quick thrusts applied to the abdomen using the palms of the hands, timed to coincide with the patient's cough effort. The technique should be taught to caregivers of patients with severe respiratory muscle weakness with instructions to use it whenever the patient encounters difficulty expectorating secretions. With practice, the technique can be applied effectively and frequently, with minimal discomfort to the patient. Peak expiratory flows can be increased several-fold when manually assisted coughing is applied successfully [55]. To minimise the risk of regurgitation and aspiration of gastric contents, the patient should be placed semi-upright when manually assisted coughing is applied, and the technique should be used cautiously after meals.

Although manually assisted coughing may enhance expiratory force, it does not augment inspired volume. Patients with severely restricted volumes, therefore, may still achieve insufficient cough flows, even when assisted by skilled caregivers. To overcome this problem, the inhaled volume should be augmented [56]. One approach is to stack breaths using glosso-pharyngeal breathing or volume-limited ventilation and then to cough using manual assistance. Another is to use a mechanical insufflator-exsufflator, a device that was developed during the polio epidemics to aid in airway secretion removal. This device delivers a positive inspiratory pressure of 30 40 cm H₂ O via a facemask and then rapidly switches to an equal negative pressure. The positive pressure assures the delivery of an adequate tidal volume, and the negative pressure has the effect of simulating the rapid expiratory flows generated by a cough.

Excessive secretions/noisy breathing

Excessive secretions or difficulty clearing pharyngeal secretions may lead to noisy or rattly breathing that commonly occurs during the terminal phase of the child's illness and is often associated with diminished consciousness. Positioning on the side or slightly head down will allow some postural drainage and this may be all that is required. Reassurance and explanation to the family is essential as the noise of the gurgling can be very distressing to the family, while the child is usually unaware and untroubled by the noise and sensation.

Anticholinergic drugs can be used to reduce the production of secretions and a portable suction machine at home may be of benefit for children with chronic conditions or for those who are unconscious. Hyoscine hydrobromide can be administered either subcutaneously as a bolus, via a continuous infusion, or via a transdermal patch. Glycopyrrolate (4 10 micrograms/kg q. 6 h; max 0.2 mg) also has anticholinergic properties and a selective and prolonged effect on salivary and sweat gland secretions. Consideration of the use of glycopyrrolate should be given if there is an inadequate response from hyoscine. Atropine can also be used but may lead to bradycardia with repeated dosing.

Haemoptysis

In studies of patients with haemoptysis a definite cause is established only half of the time. Even in patients with a proven malignancy, haemoptysis can be due to other causes. While lung cancer is the commonest cause of massive haemoptysis (200 ml/24 h), non-malignant disorders such as acute

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bronchitis, bronchiectasis, aspergellosis, and pulmonary embolism can cause mild to moderate haemoptysis. It is important to establish that the blood or blood stained material has come from the chest and not the nose, upper respiratory tract, or gastrointestinal tract. Management depends on the cause and prognosis. Radiotherapy (endobronchial or external beam) and laser therapy are particularly effective in controlling bleeding from endobronchial tumours. Rapid sedation may be required for massive hemoptysis using a combination of a parenterally administered strong opioid and a benzodiazepine [57]. As with the possibility of any acutely potentially traumatic event, the management of acute hemoptysis should begin with a plan and anticipatory guidance before the event occurs.

In CF patients recurrent haemoptysis has been managed with bronchial artery embolization (BAE). In one study the immediate success rate after embolization (i.e. no recurrent bleeding within 24 h) was 95% (36 of 38 BAEs). Eleven (55%) patients required more than one procedure, and the median time between first and second embolization was 4 months (range, 5 days to 61 months). Three patients died as a consequence of severe haemoptysis during induction of anaesthesia with intermittent positive pressure ventilation in preparation for the procedure. The median survival duration after the first embolization was 84 months [58].

Pleural effusion

A pleural effusion is an abnormal volume of fluid that has collected between the visceral and parietal pleura. Normally there is 10 20 ml of pleural fluid between these two layers of pleura. This is part of dynamic system that turns over 100 200 ml of pleural fluid a day. Fluid accumulation occurs when there is imbalance between fluid formation and resorption mainly due to a dysfunction of lymphatic drainage [59].

Mechanisms of malignant pleural effusion formation include:

Tumour involving the pleura increases capillary permeability, which produces an excess of fluid, and decreases pleural resorption area.
Low serum albumin decreases oncotic pressure.
Lymphadenopathy leading to thoracic duct obstruction.
Lymphangitic carcinomatosis leading to lymphatic system obstruction.

Non-malignant pleural effusions may be caused by heart failure, renal failure, pulmonary infection, and pulmonary infarction.

Thoracocentesis (insertion of a temporary or permanent chest drain to remove pleural fluid) is often of only marginal benefit. Although thoracentesis can relieve the symptoms of dyspnoea caused by pleural fluid, the procedure is uncomfortable and poorly tolerated by most children, especially if general anaesthetic is not available or appropriate. Furthermore, the benefit is typically limited to hours or days before the procedure needs to be repeated. It is possible to reduce the risk of this by pleurodesis in which the pleural membranes are made to adhere to one another by inducing inflammation. This is usually achieved by instilling an irritant such as tetracycline or talc. In general thoracocentesis should be reserved for those relatively few patients in whom the potential benefit is likely to outweigh the considerable discomfort of the intervention.

The management of distressing respiratory symptoms is a mainstay in palliative care for children. Assessment of respiratory symptoms begins by understanding and clarifying the difference between a comfortable child who with an increased respiratory rate (tachypnoea) versus the distressed or uncomfortable child with breathlessness (dyspnoea). Management strategies to help alleviate distressing respiratory symptoms are then evaluated in terms of what is best for the particular child and their family whilst balancing the benefits of an intervention with its possible burdens. As with the management of other symptoms, much can be gained by open discussion with the child and family about likely outcomes and risks and benefits of different therapies. Sensitive discussions with the child and family around advance care planning (e.g. these are some of the things we can do to make you comfortable if your breathing becomes difficult ) may provide comfort and security both for the child/family as well as for involved professional and non-professional caregivers.

Current ethical controversies in the withdrawal or withholding of mechanical ventilation

In all cultures, paediatric palliative care must advocate for children. It is often difficult for medical teams to recognise the need to withhold or even to withdraw interventions that may prolong life. In some societies, this may be due to reluctance to give autonomy to patients and families, or to allow them to participate in treatment decisions. It is expected that the family will do only what they are permitted to do by doctors. In other cultures, often where autonomy is given high priority, the same reluctance may be due to concerns about litigation that may follow if life is perceived to have been shortened deliberately. It can be a struggle even to persuade paediatric teams to allow a child to return home to die, or for paediatric oncology teams to discontinue chemotherapy even where it is recognised that cure is impossible.

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In any society, therefore, paediatric palliative care may find itself having to take on a role of advocate, allowing the voices of child and family to be heard in pleading for invasive and futile interventions to be withheld or even withdrawn. Where necessary this may mean representing their needs to professional colleagues in ways that will not always be popular, and may even be seen by some as ethically questionable.

Use of mechanical respirators is one of these issues. There are many countries in which patients have as yet no legal right to be disconnected from a respirator, nor physicians any legal right to extubate. Freedom, dignity and autonomy of the patient, and the medical principle primum non nocere ( First, do no harm ) are the most important ethical imperatives, rather than simply prolonging life. For patients in whom mechanical ventilation is not life-saving (such as those with DMD or SMA), there should be a free choice to withhold or even to withdraw this kind of treatment. Paediatric palliative care provides an active alternative that improves symptoms and quality of life for those patients who choose to reject mechanical ventilation. It is also important to remember that many boys in the terminal stages of DMD are adults in their own right, and do not need their parents'permission to make such a choice.

Where possible, futile or unwelcome ventilation should be avoided. This can best be done through repeated discussions and exploration of the issue with family and (where appropriate) the child. This can be a valuable role for those working in children's palliative care. The outcome of such discussions should always be clearly recorded and the record made accessible. This may mean allowing the family themselves to have a copy for presentation to ambulance drivers or emergency staff.

Despite such an approach, some children who are unlikely to benefit will find themselves undergoing mechanical ventilation. It can be difficult for staff to accept withholding ventilation as an option, even if it is clearly the family's wish, and at the moment a decision needs to be made, the child or family themselves may change their minds.

Actively withdrawing invasive mechanical ventilation needs to be done sensitively in an unhurried and considered manner. There are many protocols for approaching this which provide a practical and compassionate approach to relieving any symptoms associated with extubation. The tube may be withdrawn suddenly or gradually ( terminal weaning ), depending in part on the preferences of the patient, if known, as well as the family and staff. Terminal weaning, as the name suggests, involves a gradual reduction in ventilation parameters rate, inspiratory and expiratory pressures and inspired oxygen. Terminal weaning may be over as little as 30 60 min but can be much longer, and some patients may breathe spontaneously.

It is important that the needs of the family be considered during withdrawal. This may include playing music, the presence of a favourite toy, or simply enough physical space for family members to be present at the bedside. The paraphernalia of high-technology medicine, especially noisy and intrusive alarms, should be removed.

The two most common and feared physical symptoms associated with withdrawal of ventilation are breathlessness and anxiety. Both are readily managed with opioids and benzodiazepines. Prescription of medications at the time of extubation may cause concern among medical and nursing staff, who worry that they may cause respiratory depression and hasten death. The risks of respiratory depression are, in reality, small properly titrated, it is usually possible to find a dose for most patients that eases anxiety and dyspnoea without significantly impairing respiration.

In the past, invasive ventilation using an endotracheal tube was the only option available to families of children with life-limiting respiratory illnesses such as DMD. Increasingly, however, families are being offered the alternative of noninvasive positive pressure ventilation (NIPPV) in the United Kingdom (BiPAP in the United States) using a face-mask, usually at night. For many, this provides a third way ; there is growing evidence that it can relieve symptoms and improve both quality and even duration of life, sometimes by several years.

Despite the fact that NIPPV is less invasive than traditional mechanical ventilation, the same ethical issues apply and patients who fully understand the issues need to be allowed the chance to decline. For some patients it is too invasive or intrusive, sometimes for physical reasons and sometimes for less obvious ones. The mask can be very uncomfortable, causing pain or feelings of claustrophobia, and some patients simply find the presence of a ventilator in the home intolerable.

In summary, for children with life-limiting respiratory conditions, the benefits of mechanical ventilation in terms of prolonged life need to be carefully weighed against the impact on its quality. Where families, or even patients themselves, understand these issues and request that ventilation be withheld or withdrawn, their voice should be heard and their view respected. Advocating for such families is an important role for paediatric palliative care.

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