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Palliating breathlessness in patients with advanced cancer
Comment
Breathlessness is a dominant aspect of end-stage disease across a wide spectrum—cancer, heart failure, and chronic lung disorders. As a subjective sensation, it can vary between pathophysiologies but individuals can recognise and measure changes in ventilatory impedance, thoracic displacement, hypoxaemia, and respiratory muscle force.1 Breathlessness is also dependent on psychological, behavioural, and contextual factors. Efforts to diminish the sensation of breathlessness focus on measures to blunt patients’ perception, reduce hypoxaemia, decrease respiratory drive, reduce load on the respiratory muscles, or lower ventilatory impedance, but these are rarely fully effective. In patients with hypercapnic exacerbations of chronic obstructive pulmonary disease (COPD), positive pressure non-invasive ventilation (NIV) has been shown to correct acidosis and hypercapnia, halve mortality and morbidity, and reduce the duration of breathlessness.2 In The Lancet Oncology, Stefano Nava and colleagues have explored the tolerability of NIV in patients with solid tumours and acute respiratory failure, in a randomised comparison to high-flow oxygen therapy.3 Morphine was used in both groups and the primary outcomes were reduction in breathlessness and amount of morphine used in 48 h. Patients with end-stage solid tumours and acute respiratory failure due to an acute exacerbation of COPD or heart failure were excluded from this trial because the researchers felt there was sufficient evidence already to support use of NIV in these situations. Their findings showed that breathlessness decreased more in the NIV group than the oxygen group (average change in Borg scale –0·58, 95% CI –0·92 to –0·23; p=0·0012), as did patients’ need for morphine (59·3 mg [SD 67·1] for oxygen vs 26·9 mg [37·3] for NIV; p<0·05). Patients were stratified by hypercapnic status on entry to trial—with improvements in breathlessness and the reduced need for morphine occurring predominantly in the hypercapnic patients (PaCO2>45 mm Hg). 11 (11%) of the 99 patients in the NIV group stopped treatment early, whereas all 101 patients in the oxygen group could tolerate high-flow oxygen therapy. It would have been helpful to have a patient-reported measure of NIV tolerance, rather than staff assessment. Side-effects were generally minor.
The more favourable results in hypercapnic patients suggest that, mechanistically, NIV reduces the work of breathing when the ventilatory load is greater than respiratory-system capacity, resulting in alveolar hypoventilation. This suggestion ties in with previous findings4 in other causes of acute respiratory failure in which patients with hypoxaemia and normocapnia or hypocapnia due to ventilation–perfusion mismatch or alveolar–arterial diffusion defects fare less well than those with hypercapnia, because NIV does little to correct these pathological defects. Clinical teams should set goals such as reduction in dyspnoea or symptom burden5 when the aim of NIV is to palliate symptoms rather than act as life support, so that if these objectives are not achieved NIV can be rapidly withdrawn and will not add to a patient’s burdens. By contrast with gradual changes in arterial blood gas tensions, breathlessness should be relieved rapidly after starting NIV (if the ventilator settings are correct) and so the efficacy of treatment can be judged by the patient and team within minutes or hours. As well as reducing breathlessness, NIV might allow more effective use of morphine or other sedative analgesia without causing excessive sleepiness or progressive CO2 retention. Hypercapnic patients in Nava and colleagues’ trial given NIV had a better-than-expected survival over time compared with patients given oxygen,3 although the trial was not designed to assess the effect of NIV on survival. This finding, too, fits with the outcome in acute hypercapnic exacerbations of COPD when patients who had a course of NIV had better survival at 3 months, 6 months, and 12 months compared with those who received controlled oxygen therapy without NIV.6 Overall, NIV was used for 23 h (SD 15), and the investigators detected no evidence that it protracted death. One unusual point is that in many of the precipitating causes of acute respiratory failure—eg, bronchial obstruction, lymphangitis, carcinomatosis, and pleural effusion— rapid resolution would not be expected, so the carryover effects after the discontinuation of NIV cannot be easily explained. This finding might be partly because of the fact that although the trial ended at 48 h, some patients opted to continue NIV for longer periods (Nava S, Sant’Orsola Malpighi Hospital, Bologna,
www.thelancet.com/oncology Published online February 11, 2013 http://dx.doi.org/10.1016/S1470-2045(13)70052-4
A J Photo/Science Photo Library
Palliating breathlessness in patients with advanced cancer
Published Online February 11, 2013 http://dx.doi.org/10.1016/ S1470-2045(13)70052-4 See Online/Articles http://dx.doi.org/10.1016/ S1470-2045(13)70009-3
1
Comment
personal communication). Also, as the investigators suggest, the main role for NIV might be to buy time for other interventions to work. Practicalities matter, because setting up NIV differs greatly from prescribing oxygen therapy, or an analgesic infusion. Nava and colleagues used standard bilevel pressure support settings delivered via a small number of interfaces. However, the implementation of NIV in acute respiratory units has been shown to be restricted by the shortage of experienced physicians and appropriate equipment. Nava and colleagues’ trial was done by expert NIV teams using the technique daily in high volumes of patients. So if NIV does palliate symptoms in at least a subgroup of patients, how can it be delivered effectively and safely by oncology and palliative care teams? The obvious answer is by exploiting the growing dialogue by which palliative care teams have cascaded advice to respiratory teams to improve end-of-life symptom control for non-cancer respiratory patients— but in reverse direction. As a result, both patients with cancer and those without should have the best palliativecare practices in a multidisciplinary fashion, while further
2
breaking down barriers in specialist care to the benefit of all breathless end-stage patients. Anita K Simonds Academic and Clinical Department of Sleep and Breathing, NIHR Respiratory Biomedical Research Unit, Royal Brompton and Harefield NHS Foundation Trust, Sydney Street, London SW3 6NP, UK [email protected] I declare that I have no conflicts of interest. 1
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3
4
5
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Altose MD. Management of breathlessness. In: Jones NL, Killian KJ, eds. Breathlessness: The Campbell Symposium. Ontario: McMaster University, 1992. 162–69. Lightowler J, Wedzicha JA, Elliott MW, Ram FS. Non-invasive positive pressure ventilation to treat respiratory failure resulting from exacerbations of chronic obstructive pulmonary disease: Cochrane systematic review and meta-analysis. BMJ 2003; 326: 185. Nava S, Ferrer M, Esquinas A, et al. Palliative use of non-invasive ventilation in end-of-life patients with solid tumours: a randomised feasibility trial. Lancet Oncol 2013; published online Feb 11. DOI:10.1016/S14702045(13)70009-3. Antonelli M, Conti G, Rocco M, et al. A comparison of noninvasive positive-pressure ventilation and conventional mechanical ventilation in patients with acute respiratory failure. N Engl J Med 1998; 339: 429–35. Curtis JR, Cook DJ, Sinuff T, et al. Noninvasive positive pressure ventilation in critical and palliative care settings: understanding the goals of therapy. Crit Care Med 2007; 35: 939. Plant PK, Owen JL, Elliott MW. One year period prevalence study of respiratory acidosis in acute exacerbations of COPD: implications for the provision of non-invasive ventilation and oxygen provision. Thorax 2000; 55: 550–54.
www.thelancet.com/oncology Published online February 11, 2013 http://dx.doi.org/10.1016/S1470-2045(13)70052-4
Breathlessness is a dominant aspect of end-stage disease across a wide spectrum—cancer, heart failure, and chronic lung disorders. As a subjective sensation, it can vary between pathophysiologies but individuals can recognise and measure changes in ventilatory impedance, thoracic displacement, hypoxaemia, and respiratory muscle force.1 Breathlessness is also dependent on psychological, behavioural, and contextual factors. Efforts to diminish the sensation of breathlessness focus on measures to blunt patients’ perception, reduce hypoxaemia, decrease respiratory drive, reduce load on the respiratory muscles, or lower ventilatory impedance, but these are rarely fully effective. In patients with hypercapnic exacerbations of chronic obstructive pulmonary disease (COPD), positive pressure non-invasive ventilation (NIV) has been shown to correct acidosis and hypercapnia, halve mortality and morbidity, and reduce the duration of breathlessness.2 In The Lancet Oncology, Stefano Nava and colleagues have explored the tolerability of NIV in patients with solid tumours and acute respiratory failure, in a randomised comparison to high-flow oxygen therapy.3 Morphine was used in both groups and the primary outcomes were reduction in breathlessness and amount of morphine used in 48 h. Patients with end-stage solid tumours and acute respiratory failure due to an acute exacerbation of COPD or heart failure were excluded from this trial because the researchers felt there was sufficient evidence already to support use of NIV in these situations. Their findings showed that breathlessness decreased more in the NIV group than the oxygen group (average change in Borg scale –0·58, 95% CI –0·92 to –0·23; p=0·0012), as did patients’ need for morphine (59·3 mg [SD 67·1] for oxygen vs 26·9 mg [37·3] for NIV; p<0·05). Patients were stratified by hypercapnic status on entry to trial—with improvements in breathlessness and the reduced need for morphine occurring predominantly in the hypercapnic patients (PaCO2>45 mm Hg). 11 (11%) of the 99 patients in the NIV group stopped treatment early, whereas all 101 patients in the oxygen group could tolerate high-flow oxygen therapy. It would have been helpful to have a patient-reported measure of NIV tolerance, rather than staff assessment. Side-effects were generally minor.
The more favourable results in hypercapnic patients suggest that, mechanistically, NIV reduces the work of breathing when the ventilatory load is greater than respiratory-system capacity, resulting in alveolar hypoventilation. This suggestion ties in with previous findings4 in other causes of acute respiratory failure in which patients with hypoxaemia and normocapnia or hypocapnia due to ventilation–perfusion mismatch or alveolar–arterial diffusion defects fare less well than those with hypercapnia, because NIV does little to correct these pathological defects. Clinical teams should set goals such as reduction in dyspnoea or symptom burden5 when the aim of NIV is to palliate symptoms rather than act as life support, so that if these objectives are not achieved NIV can be rapidly withdrawn and will not add to a patient’s burdens. By contrast with gradual changes in arterial blood gas tensions, breathlessness should be relieved rapidly after starting NIV (if the ventilator settings are correct) and so the efficacy of treatment can be judged by the patient and team within minutes or hours. As well as reducing breathlessness, NIV might allow more effective use of morphine or other sedative analgesia without causing excessive sleepiness or progressive CO2 retention. Hypercapnic patients in Nava and colleagues’ trial given NIV had a better-than-expected survival over time compared with patients given oxygen,3 although the trial was not designed to assess the effect of NIV on survival. This finding, too, fits with the outcome in acute hypercapnic exacerbations of COPD when patients who had a course of NIV had better survival at 3 months, 6 months, and 12 months compared with those who received controlled oxygen therapy without NIV.6 Overall, NIV was used for 23 h (SD 15), and the investigators detected no evidence that it protracted death. One unusual point is that in many of the precipitating causes of acute respiratory failure—eg, bronchial obstruction, lymphangitis, carcinomatosis, and pleural effusion— rapid resolution would not be expected, so the carryover effects after the discontinuation of NIV cannot be easily explained. This finding might be partly because of the fact that although the trial ended at 48 h, some patients opted to continue NIV for longer periods (Nava S, Sant’Orsola Malpighi Hospital, Bologna,
www.thelancet.com/oncology Published online February 11, 2013 http://dx.doi.org/10.1016/S1470-2045(13)70052-4
A J Photo/Science Photo Library
Palliating breathlessness in patients with advanced cancer
Published Online February 11, 2013 http://dx.doi.org/10.1016/ S1470-2045(13)70052-4 See Online/Articles http://dx.doi.org/10.1016/ S1470-2045(13)70009-3
1
Comment
personal communication). Also, as the investigators suggest, the main role for NIV might be to buy time for other interventions to work. Practicalities matter, because setting up NIV differs greatly from prescribing oxygen therapy, or an analgesic infusion. Nava and colleagues used standard bilevel pressure support settings delivered via a small number of interfaces. However, the implementation of NIV in acute respiratory units has been shown to be restricted by the shortage of experienced physicians and appropriate equipment. Nava and colleagues’ trial was done by expert NIV teams using the technique daily in high volumes of patients. So if NIV does palliate symptoms in at least a subgroup of patients, how can it be delivered effectively and safely by oncology and palliative care teams? The obvious answer is by exploiting the growing dialogue by which palliative care teams have cascaded advice to respiratory teams to improve end-of-life symptom control for non-cancer respiratory patients— but in reverse direction. As a result, both patients with cancer and those without should have the best palliativecare practices in a multidisciplinary fashion, while further
2
breaking down barriers in specialist care to the benefit of all breathless end-stage patients. Anita K Simonds Academic and Clinical Department of Sleep and Breathing, NIHR Respiratory Biomedical Research Unit, Royal Brompton and Harefield NHS Foundation Trust, Sydney Street, London SW3 6NP, UK [email protected] I declare that I have no conflicts of interest. 1
2
3
4
5
6
Altose MD. Management of breathlessness. In: Jones NL, Killian KJ, eds. Breathlessness: The Campbell Symposium. Ontario: McMaster University, 1992. 162–69. Lightowler J, Wedzicha JA, Elliott MW, Ram FS. Non-invasive positive pressure ventilation to treat respiratory failure resulting from exacerbations of chronic obstructive pulmonary disease: Cochrane systematic review and meta-analysis. BMJ 2003; 326: 185. Nava S, Ferrer M, Esquinas A, et al. Palliative use of non-invasive ventilation in end-of-life patients with solid tumours: a randomised feasibility trial. Lancet Oncol 2013; published online Feb 11. DOI:10.1016/S14702045(13)70009-3. Antonelli M, Conti G, Rocco M, et al. A comparison of noninvasive positive-pressure ventilation and conventional mechanical ventilation in patients with acute respiratory failure. N Engl J Med 1998; 339: 429–35. Curtis JR, Cook DJ, Sinuff T, et al. Noninvasive positive pressure ventilation in critical and palliative care settings: understanding the goals of therapy. Crit Care Med 2007; 35: 939. Plant PK, Owen JL, Elliott MW. One year period prevalence study of respiratory acidosis in acute exacerbations of COPD: implications for the provision of non-invasive ventilation and oxygen provision. Thorax 2000; 55: 550–54.
www.thelancet.com/oncology Published online February 11, 2013 http://dx.doi.org/10.1016/S1470-2045(13)70052-4