Home Mechanical Ventilation in COPD: Do We Know When and How To Use It?

Abstract

In the end stage of COPD, chronic respiratory failure isusually present and most patients are prescribed long-term oxygentherapy.1Continuous or nocturnal oxygen therapy in hypoxemic chronic obstructive lung disease: a clinical trial: Nocturnal Oxygen Therapy Trial Group.Ann Intern Med. 1980; 93: 391-398Crossref PubMed Scopus (2087) Google Scholar2Long term domiciliary oxygen therapy in chronic hypoxic cor pulmonale complicating chronic bronchitis and emphysema: report of the Medical Research Council Working Party.Lancet. 1981; 1: 681-686PubMed Google Scholar However, significant hypercapnia oftendevelops with oxygen administration, particularly atnight,3Goldstein RS Ramcharan V Bowes G et al.Effect of supplemental nocturnal oxygen on gas exchange in patients with severe obstructive lung disease.N Engl J Med. 1984; 310: 425-429Crossref PubMed Scopus (117) Google Scholar even when oxygen flow has beenadjusted.4Tárrega J Antón A Jerez FR et al.Early morning blood gases measures in the management of patients on long-term oxygen [abstract].Eur Respir J. 1999; 14: A270PubMed Google Scholar Alternatives to oxygen therapy are scarce, butone promising candidate, noninvasive ventilation (NIV), cantheoretically provide benefits by compensating for nighttimehypoventilation,5Douglas NJ Calverley PMA Legget RJE et al.Transient hypoxaemia during sleep in chronic bronchitis and emphysema.Lancet. 1979; 1: 1-4Abstract PubMed Scopus (209) Google Scholar allowing respiratory muscles to rest, improving nocturnal gas exchange, and resetting central respiratorycontrol in response to Paco2concentration. Sleep quality should thereby improve, as should arterialblood gas measures and perhaps daytime symptoms and patient survival.Solid clinical evidence of the usefulness of NIV in COPD patients islacking, yet the technique is being applied with mixed results, asshown by discrepant reports in literature. In a randomized crossoverstudy by Strumpf et al,6Strumpf DA Millman RP Carlisle CC et al.Nocturnal positive-pressure ventilation via nasal mask in patients with severe chronic obstructive pulmonary disease.Am Rev Respir Dis. 1991; 144: 1234-1239Crossref PubMed Scopus (281) Google Scholar in which NIV was comparedto conventional treatment of 19 patients over 3 months, compliance waspoor (only 7 patients completed the study) and no changes in pulmonaryfunction, gas exchange, sleep quality, exercise tolerance, orneurophysiologic variables were observed with either treatment. Theauthors therefore concluded that NIV provides no apparent clinicalbenefit. Meecham Jones et al7Meecham Jones JD Paul EA Jones PW et al.Nasal pressure support ventilation plus oxygen compared with oxygen therapy alone in hypercapnic COPD.Am J Respir Crit Care Med. 1995; 152: 538-544Crossref PubMed Scopus (477) Google Scholar then reported strikinglydifferent results after a similarly designed study of 18 patients withchronic respiratory hypercapnic failure due to COPD. NIV plus oxygentherapy was compared to oxygen therapy alone. Significant improvementsin daytime gas exchange, overnight, Paco2, sleep efficiency, andquality-of-life scores were observed in the NIV group. Moreover, improved daytime gas exchange correlated with changes in overnight, Paco2, suggesting that improvedventilation during the night (reducedPaco2) accounted for the response to, NIV. Other studies of NIV are also inconclusive, particularly as theyfeature methodologic shortcomings such as a short clinicalfollow-up,8Lin CC Comparison between nocturnal nasal positive pressure ventilation combined with oxygen therapy and oxygen monotherapy in patients with severe COPD.Am J Respir Crit Care Med. 1996; 154: 353-358Crossref PubMed Scopus (169) Google Scholar a small number of patients,9Gay PC Hubmayr RD Stroetz RW et al.Efficacy of nocturnal nasal ventilation in stable, severe chronic obstructive pulmonary disease during a 3-month controlled trial.Mayo Clin Proc. 1996; 71: 533-542Abstract Full Text Full Text PDF PubMed Scopus (171) Google Scholar oronly retrospective analysis.9Gay PC Hubmayr RD Stroetz RW et al.Efficacy of nocturnal nasal ventilation in stable, severe chronic obstructive pulmonary disease during a 3-month controlled trial.Mayo Clin Proc. 1996; 71: 533-542Abstract Full Text Full Text PDF PubMed Scopus (171) Google Scholar10Perrin C El Far Y Vandenbos F et al.Domiciliary nasal intermittent positive pressure ventilation in severe COPD: effects on lung function and quality of life.Eur Respir J. 1997; 10: 2835-2839Crossref PubMed Scopus (91) Google Scholar11Jones SE Packhan S Hebden M et al.Domiciliary nocturnal intermittent positive pressure ventilation in patients with respiratory failure due to severe COPD: long term follow up and effect on survival.Thorax. 1998; 53: 495-498Crossref PubMed Scopus (122) Google Scholar At present, we thereforehave no adequate analyses of the impact of home mechanical ventilationon the survival of COPD patients.In this issue of CHEST (see page 1582), Casanova et alpresent the most ambitious study published to date, with the largestnumber of patients and the longest period of follow-up (1 year), thusmaking a valuable contribution toward clarifying the possibleusefulness of NIV. In this randomized, controlled trial enrolling 52patients with severe COPD, standard treatment alone was compared tonasal NIV plus standard treatment. Most patients in both treatmentgroups also received domiciliary oxygen therapy. No statisticallysignificant differences in respiratory lung function or survival werefound, although the authors did not analyze important variables such asquality of life or sleep.What might account for such mixed results from the application of homemechanical ventilation of stable COPD patients? It may be thatdifferences in enrollment criteria from study to study are responsiblefor the disparity. Thus, it may be relevant that a favorable outcomewas seen in patients with high initial, Paco2, as in the study by Meecham Jones et al,7Meecham Jones JD Paul EA Jones PW et al.Nasal pressure support ventilation plus oxygen compared with oxygen therapy alone in hypercapnic COPD.Am J Respir Crit Care Med. 1995; 152: 538-544Crossref PubMed Scopus (477) Google Scholar while patients with nearly normocapnia atthe beginning of another trial received no benefit.6Strumpf DA Millman RP Carlisle CC et al.Nocturnal positive-pressure ventilation via nasal mask in patients with severe chronic obstructive pulmonary disease.Am Rev Respir Dis. 1991; 144: 1234-1239Crossref PubMed Scopus (281) Google ScholarHypercapnic patients can be assumed to have developed high nocturnalhypoventilation and, therefore, to respond better to nocturnalventilation, as was in fact observed by Meecham Jones etal.7Meecham Jones JD Paul EA Jones PW et al.Nasal pressure support ventilation plus oxygen compared with oxygen therapy alone in hypercapnic COPD.Am J Respir Crit Care Med. 1995; 152: 538-544Crossref PubMed Scopus (477) Google Scholar A decrease in daytime, Paco2 would then undoubtedly lead tosome alleviation of symptoms. Nocturnal hypoventilation analysis maytherefore be needed to explain the clinical results in trials such asthese, above all when oxygen is administered. The studies by Meecham Jones et al7Meecham Jones JD Paul EA Jones PW et al.Nasal pressure support ventilation plus oxygen compared with oxygen therapy alone in hypercapnic COPD.Am J Respir Crit Care Med. 1995; 152: 538-544Crossref PubMed Scopus (477) Google Scholar and Sivasothy et al,12Sivasothy P Smith IE Shneerson JM Mask intermittent positive pressure ventilation in chronic hypercapnic respiratory failure due to chronic obstructive pulmonary disease.Eur Respir J. 1998; 11: 34-40Crossref PubMed Scopus (93) Google Scholar the onlyones that analyzed this factor, demonstrated that patients with greateralteration of nighttime ventilation are those who show a greaterresponse to NIV,7Meecham Jones JD Paul EA Jones PW et al.Nasal pressure support ventilation plus oxygen compared with oxygen therapy alone in hypercapnic COPD.Am J Respir Crit Care Med. 1995; 152: 538-544Crossref PubMed Scopus (477) Google Scholar and it may well be that studiesreporting little or no benefit from NIV were those enrolling patientswithout meaningful nocturnal hypoventilation. A second likely source ofdiscrepant results may lie in the differences in adjustment of NIVparameters and, above all, the monitoring of response to NIV therapy. In the study by Strumpf et al,6Strumpf DA Millman RP Carlisle CC et al.Nocturnal positive-pressure ventilation via nasal mask in patients with severe chronic obstructive pulmonary disease.Am Rev Respir Dis. 1991; 144: 1234-1239Crossref PubMed Scopus (281) Google Scholar ventilation was adjustedwhen patients were ambulatory, making it impossible to confidentlyassess response to NIV. Only Meecham Jones et al7Meecham Jones JD Paul EA Jones PW et al.Nasal pressure support ventilation plus oxygen compared with oxygen therapy alone in hypercapnic COPD.Am J Respir Crit Care Med. 1995; 152: 538-544Crossref PubMed Scopus (477) Google Scholar and, Sivasothy et al12Sivasothy P Smith IE Shneerson JM Mask intermittent positive pressure ventilation in chronic hypercapnic respiratory failure due to chronic obstructive pulmonary disease.Eur Respir J. 1998; 11: 34-40Crossref PubMed Scopus (93) Google Scholar adjusted NIV parameters to monitorchanges in nighttime arterial oxygen saturation and, Paco2 until they had obtained anappropriate response to treatment, defined as compensation fornocturnal hypoventilation. Finally, it is important to emphasize thelow ventilatory assistance levels (inspiratory pressure) used in thestudies reporting poor response to NIV. Again, only Meecham Jones etal7Meecham Jones JD Paul EA Jones PW et al.Nasal pressure support ventilation plus oxygen compared with oxygen therapy alone in hypercapnic COPD.Am J Respir Crit Care Med. 1995; 152: 538-544Crossref PubMed Scopus (477) Google Scholar used inspiratory pressures that seem to be sufficientto compensate for nocturnal hypoventilation in end-stage COPD patients. In this sense, the ventilatory parameters chosen by Casanova etal may also be too low. Ventilatory parameters must be selectedconsidering changes of gas exchange parameters in response to nighttime, NIV together with effects seen during the day. Thus, the poor resultsof the trial carried out by Casanova et al may simply be attributableto failure to achieve effective ventilation.NIV should not be used as a blanket treatment for all patients with, COPD, even when disease is severe, as Casanova et al rightly suggest intheir conclusion. However, a selected group of patients may wellbenefit from domiciliary mechanical ventilation, and we need to be ableto identify who they are. It has been suggested that goodcandidates for such treatment may be those patients who have developedsignificant hypercapnic respiratory failure and poor response tolong-term oxygen therapy, in whom nocturnal hypoventilation has beenshown to be corrected by NIV, and who are motivated to comply withtherapy and willing to be trained.13Rossi A Noninvasive ventilation has not been shown to be ineffective in stable COPD.Am J Respir Crit Care Med. 2000; 161: 688-691Crossref PubMed Scopus (52) Google Scholar14Wedzicha JA Long-term oxygen therapy vs long-term ventilatory assistance.Respir Care. 2000; 45: 178-185PubMed Google Scholar Such patientsshould be enrolled by researchers carrying out the next wave ofrandomized, controlled trials if we are to answer the question ofwhether or not to administer ventilation to patients with COPD. In the end stage of COPD, chronic respiratory failure isusually present and most patients are prescribed long-term oxygentherapy.1Continuous or nocturnal oxygen therapy in hypoxemic chronic obstructive lung disease: a clinical trial: Nocturnal Oxygen Therapy Trial Group.Ann Intern Med. 1980; 93: 391-398Crossref PubMed Scopus (2087) Google Scholar2Long term domiciliary oxygen therapy in chronic hypoxic cor pulmonale complicating chronic bronchitis and emphysema: report of the Medical Research Council Working Party.Lancet. 1981; 1: 681-686PubMed Google Scholar However, significant hypercapnia oftendevelops with oxygen administration, particularly atnight,3Goldstein RS Ramcharan V Bowes G et al.Effect of supplemental nocturnal oxygen on gas exchange in patients with severe obstructive lung disease.N Engl J Med. 1984; 310: 425-429Crossref PubMed Scopus (117) Google Scholar even when oxygen flow has beenadjusted.4Tárrega J Antón A Jerez FR et al.Early morning blood gases measures in the management of patients on long-term oxygen [abstract].Eur Respir J. 1999; 14: A270PubMed Google Scholar Alternatives to oxygen therapy are scarce, butone promising candidate, noninvasive ventilation (NIV), cantheoretically provide benefits by compensating for nighttimehypoventilation,5Douglas NJ Calverley PMA Legget RJE et al.Transient hypoxaemia during sleep in chronic bronchitis and emphysema.Lancet. 1979; 1: 1-4Abstract PubMed Scopus (209) Google Scholar allowing respiratory muscles to rest, improving nocturnal gas exchange, and resetting central respiratorycontrol in response to Paco2concentration. Sleep quality should thereby improve, as should arterialblood gas measures and perhaps daytime symptoms and patient survival. Solid clinical evidence of the usefulness of NIV in COPD patients islacking, yet the technique is being applied with mixed results, asshown by discrepant reports in literature. In a randomized crossoverstudy by Strumpf et al,6Strumpf DA Millman RP Carlisle CC et al.Nocturnal positive-pressure ventilation via nasal mask in patients with severe chronic obstructive pulmonary disease.Am Rev Respir Dis. 1991; 144: 1234-1239Crossref PubMed Scopus (281) Google Scholar in which NIV was comparedto conventional treatment of 19 patients over 3 months, compliance waspoor (only 7 patients completed the study) and no changes in pulmonaryfunction, gas exchange, sleep quality, exercise tolerance, orneurophysiologic variables were observed with either treatment. Theauthors therefore concluded that NIV provides no apparent clinicalbenefit. Meecham Jones et al7Meecham Jones JD Paul EA Jones PW et al.Nasal pressure support ventilation plus oxygen compared with oxygen therapy alone in hypercapnic COPD.Am J Respir Crit Care Med. 1995; 152: 538-544Crossref PubMed Scopus (477) Google Scholar then reported strikinglydifferent results after a similarly designed study of 18 patients withchronic respiratory hypercapnic failure due to COPD. NIV plus oxygentherapy was compared to oxygen therapy alone. Significant improvementsin daytime gas exchange, overnight, Paco2, sleep efficiency, andquality-of-life scores were observed in the NIV group. Moreover, improved daytime gas exchange correlated with changes in overnight, Paco2, suggesting that improvedventilation during the night (reducedPaco2) accounted for the response to, NIV. Other studies of NIV are also inconclusive, particularly as theyfeature methodologic shortcomings such as a short clinicalfollow-up,8Lin CC Comparison between nocturnal nasal positive pressure ventilation combined with oxygen therapy and oxygen monotherapy in patients with severe COPD.Am J Respir Crit Care Med. 1996; 154: 353-358Crossref PubMed Scopus (169) Google Scholar a small number of patients,9Gay PC Hubmayr RD Stroetz RW et al.Efficacy of nocturnal nasal ventilation in stable, severe chronic obstructive pulmonary disease during a 3-month controlled trial.Mayo Clin Proc. 1996; 71: 533-542Abstract Full Text Full Text PDF PubMed Scopus (171) Google Scholar oronly retrospective analysis.9Gay PC Hubmayr RD Stroetz RW et al.Efficacy of nocturnal nasal ventilation in stable, severe chronic obstructive pulmonary disease during a 3-month controlled trial.Mayo Clin Proc. 1996; 71: 533-542Abstract Full Text Full Text PDF PubMed Scopus (171) Google Scholar10Perrin C El Far Y Vandenbos F et al.Domiciliary nasal intermittent positive pressure ventilation in severe COPD: effects on lung function and quality of life.Eur Respir J. 1997; 10: 2835-2839Crossref PubMed Scopus (91) Google Scholar11Jones SE Packhan S Hebden M et al.Domiciliary nocturnal intermittent positive pressure ventilation in patients with respiratory failure due to severe COPD: long term follow up and effect on survival.Thorax. 1998; 53: 495-498Crossref PubMed Scopus (122) Google Scholar At present, we thereforehave no adequate analyses of the impact of home mechanical ventilationon the survival of COPD patients. In this issue of CHEST (see page 1582), Casanova et alpresent the most ambitious study published to date, with the largestnumber of patients and the longest period of follow-up (1 year), thusmaking a valuable contribution toward clarifying the possibleusefulness of NIV. In this randomized, controlled trial enrolling 52patients with severe COPD, standard treatment alone was compared tonasal NIV plus standard treatment. Most patients in both treatmentgroups also received domiciliary oxygen therapy. No statisticallysignificant differences in respiratory lung function or survival werefound, although the authors did not analyze important variables such asquality of life or sleep. What might account for such mixed results from the application of homemechanical ventilation of stable COPD patients? It may be thatdifferences in enrollment criteria from study to study are responsiblefor the disparity. Thus, it may be relevant that a favorable outcomewas seen in patients with high initial, Paco2, as in the study by Meecham Jones et al,7Meecham Jones JD Paul EA Jones PW et al.Nasal pressure support ventilation plus oxygen compared with oxygen therapy alone in hypercapnic COPD.Am J Respir Crit Care Med. 1995; 152: 538-544Crossref PubMed Scopus (477) Google Scholar while patients with nearly normocapnia atthe beginning of another trial received no benefit.6Strumpf DA Millman RP Carlisle CC et al.Nocturnal positive-pressure ventilation via nasal mask in patients with severe chronic obstructive pulmonary disease.Am Rev Respir Dis. 1991; 144: 1234-1239Crossref PubMed Scopus (281) Google ScholarHypercapnic patients can be assumed to have developed high nocturnalhypoventilation and, therefore, to respond better to nocturnalventilation, as was in fact observed by Meecham Jones etal.7Meecham Jones JD Paul EA Jones PW et al.Nasal pressure support ventilation plus oxygen compared with oxygen therapy alone in hypercapnic COPD.Am J Respir Crit Care Med. 1995; 152: 538-544Crossref PubMed Scopus (477) Google Scholar A decrease in daytime, Paco2 would then undoubtedly lead tosome alleviation of symptoms. Nocturnal hypoventilation analysis maytherefore be needed to explain the clinical results in trials such asthese, above all when oxygen is administered. The studies by Meecham Jones et al7Meecham Jones JD Paul EA Jones PW et al.Nasal pressure support ventilation plus oxygen compared with oxygen therapy alone in hypercapnic COPD.Am J Respir Crit Care Med. 1995; 152: 538-544Crossref PubMed Scopus (477) Google Scholar and Sivasothy et al,12Sivasothy P Smith IE Shneerson JM Mask intermittent positive pressure ventilation in chronic hypercapnic respiratory failure due to chronic obstructive pulmonary disease.Eur Respir J. 1998; 11: 34-40Crossref PubMed Scopus (93) Google Scholar the onlyones that analyzed this factor, demonstrated that patients with greateralteration of nighttime ventilation are those who show a greaterresponse to NIV,7Meecham Jones JD Paul EA Jones PW et al.Nasal pressure support ventilation plus oxygen compared with oxygen therapy alone in hypercapnic COPD.Am J Respir Crit Care Med. 1995; 152: 538-544Crossref PubMed Scopus (477) Google Scholar and it may well be that studiesreporting little or no benefit from NIV were those enrolling patientswithout meaningful nocturnal hypoventilation. A second likely source ofdiscrepant results may lie in the differences in adjustment of NIVparameters and, above all, the monitoring of response to NIV therapy. In the study by Strumpf et al,6Strumpf DA Millman RP Carlisle CC et al.Nocturnal positive-pressure ventilation via nasal mask in patients with severe chronic obstructive pulmonary disease.Am Rev Respir Dis. 1991; 144: 1234-1239Crossref PubMed Scopus (281) Google Scholar ventilation was adjustedwhen patients were ambulatory, making it impossible to confidentlyassess response to NIV. Only Meecham Jones et al7Meecham Jones JD Paul EA Jones PW et al.Nasal pressure support ventilation plus oxygen compared with oxygen therapy alone in hypercapnic COPD.Am J Respir Crit Care Med. 1995; 152: 538-544Crossref PubMed Scopus (477) Google Scholar and, Sivasothy et al12Sivasothy P Smith IE Shneerson JM Mask intermittent positive pressure ventilation in chronic hypercapnic respiratory failure due to chronic obstructive pulmonary disease.Eur Respir J. 1998; 11: 34-40Crossref PubMed Scopus (93) Google Scholar adjusted NIV parameters to monitorchanges in nighttime arterial oxygen saturation and, Paco2 until they had obtained anappropriate response to treatment, defined as compensation fornocturnal hypoventilation. Finally, it is important to emphasize thelow ventilatory assistance levels (inspiratory pressure) used in thestudies reporting poor response to NIV. Again, only Meecham Jones etal7Meecham Jones JD Paul EA Jones PW et al.Nasal pressure support ventilation plus oxygen compared with oxygen therapy alone in hypercapnic COPD.Am J Respir Crit Care Med. 1995; 152: 538-544Crossref PubMed Scopus (477) Google Scholar used inspiratory pressures that seem to be sufficientto compensate for nocturnal hypoventilation in end-stage COPD patients. In this sense, the ventilatory parameters chosen by Casanova etal may also be too low. Ventilatory parameters must be selectedconsidering changes of gas exchange parameters in response to nighttime, NIV together with effects seen during the day. Thus, the poor resultsof the trial carried out by Casanova et al may simply be attributableto failure to achieve effective ventilation. NIV should not be used as a blanket treatment for all patients with, COPD, even when disease is severe, as Casanova et al rightly suggest intheir conclusion. However, a selected group of patients may wellbenefit from domiciliary mechanical ventilation, and we need to be ableto identify who they are. It has been suggested that goodcandidates for such treatment may be those patients who have developedsignificant hypercapnic respiratory failure and poor response tolong-term oxygen therapy, in whom nocturnal hypoventilation has beenshown to be corrected by NIV, and who are motivated to comply withtherapy and willing to be trained.13Rossi A Noninvasive ventilation has not been shown to be ineffective in stable COPD.Am J Respir Crit Care Med. 2000; 161: 688-691Crossref PubMed Scopus (52) Google Scholar14Wedzicha JA Long-term oxygen therapy vs long-term ventilatory assistance.Respir Care. 2000; 45: 178-185PubMed Google Scholar Such patientsshould be enrolled by researchers carrying out the next wave ofrandomized, controlled trials if we are to answer the question ofwhether or not to administer ventilation to patients with COPD.