Amyotrophic Lateral Sclerosis:
Prolongation of Life by Noninvasive Respiratory Aids
      by John R. Bach, MD

Reference: Bach JR. Amyotrophic lateral sclerosis: prolongation of life by noninvasive respiratory aids.
Chest 2002 Jul;122(1):92-98

Department of Physical Medicine and Rehabilitation, University of Medicine and Dentistry of New Jersey (UMDNJ)-the New Jersey Medical School, Newark, N.J.

Abbreviations

ALSamyotrophic lateral sclerosis
BPAPbilevel positive airway pressure
MACmechanically assisted coughing
MICmaximum insufflation capacity
NPPVnoninvasive intermittent positive pressure ventilation
PCFpeak cough flows
TPPVtracheostomy intermittent positive pressure ventilation
VCvital capacity

Abstract

Study Objective

To describe prolongation of survival with amyotrophic lateral sclerosis (ALS) by continuous noninvasive intermittent positive pressure ventilation (NPPV) and mechanically assisted coughing (MAC) using oximetry as feedback.

Setting

A retrospective review of ALS patients visiting one center from 1990 to 2000.

Design

Patients were trained in mouth piece and nasal NPPV when symptomatic for hypoventilation and MAC with oximetry feedback when assisted peak cough flows (PCF) decreased below 270 L/m. Survival was considered to be prolonged when full-time NPPV was required with limited ventilator free breathing tolerance.

Results

Of 101 patients who met criteria for access to NPPV and MAC, 15 have not yet used them; and 11 severe bulbar patients died without ever successfully using them. Three patients used NPPV full-time, oximetry, and MAC episodically but do not yet require ongoing NPPV. Eighteen used NPPV part-time for 3.8 ±4.1 months. Nineteen others underwent tracheotomy after 4.7 ±4.5 months of part-time NPPV. Sixteen used part-time NPPV for 17.5 ±13.0 (maximum 25) months then full-time NPPV for 14.1 ±12.6 (maximum 40) months before undergoing tracheotomy. Nineteen used part-time and full-time NPPV for 25.2 ±19.8 (maximum 114) and 17.5 ±13.3 (maximum 87) months, respectively, without undergoing tracheotomy. Ten of these NPPV users died once bulbar dysfunction became severe.

Conclusion

We conclude that up to continuous use of NPPV along with MAC when needed can permit prolonged survival and delay the need for tracheotomy for a significant minority of ALS patients by over 1 year.

Introduction

The mean survival from onset of ALS has been reported as 2.4 to 4.1 years. Pulmonary complications and respiratory failure are responsible for at least 84% of mortality.1,2 Although survival can be prolonged for an average of 5 years by tracheotomy intermittent positive pressure ventilation (TPPV),3 many clinicians have ethical reservations about recommending it for ALS patients and, at least in some states, less than 10% of ALS patients are offered or consent to tracheotomy.4 Survival can also be statistically prolonged for up to 12 months by providing positive inspiratory pressure plus positive end-expiratory pressure, commonly known as bi-level positive airway pressure (BPAP).5,6 However, this is typically used only overnight and at inspiratory to expiratory pressure spans of less than 10 cm H2O. Such low spans are inadequate for patients with advanced inspiratory muscle dysfunction or during intercurrent chest infections.7 Further, patients using low span BPAP are not typically taught MAC to prevent respiratory failure from airway mucus accumulation and few, therefore, go on to require continuous ventilatory support without tracheostomy.8

Once peak cough flows (PCF) decrease below 270 L/m, patients are at risk of respiratory failure from inability to cough effectively, particularly from aspiration of saliva or during intercurrent chest infections.9 Once assisted PCF decrease below 160 L/m, bulbar muscle dysfunction is severe; patients fail to clear airway secretions and typically fail extubation;10 and tracheotomy can be required for survival when the airway becomes sufficiently obstructed with debris to decrease oxygen saturation (SpO2) baseline below 95%. The ability to generate assisted PCF in excess of 160 L/m and to hold an insufflation deeper than the vital capacity (VC) have been reported to be associated with the capacity to prolong survival by non-tracheostomy methods.10

While inspiratory muscle failure can be offset by NPPV, expiratory muscle dysfunction and cough impairment can be compensated by MAC.11 MAC is the use of mechanical insufflation-exsufflation (In-exsufflator™ or Cough-Assist™, J. H. Emerson Co., Cambridge, MA) with an abdominal thrust timed to exsufflation. This provides expiratory flow directly to the airways via oro-nasal interfaces or via invasive airway tubes when present.10 The Cough-Assist™ is used at about 40 to -40 cm H2O insufflation to exsufflation pressures. The efficacy of MAC is seen by the expulsion of airway debris and by increases in VC and SpO2 immediately following use.11,12

As early as 1970 the use of TPPV was delayed 4 years and 3 months for one ALS patient by the 24 hour use of mouth piece NPPV.13 There have been no similar subsequent reports for ALS patients. We consider prolongation of life to be indisputable when ventilator use is necessary 20 to 24 hours a day and breathing tolerance is very limited; that is, when acute respiratory distress and blood gas derangements occur within one or two hours and often within seconds of discontinuing ventilator use. The purpose of this work is to demonstrate the use of NPPV for prolonging survival and eliminating the need for tracheotomy for ALS patients with bulbar muscle function.

Patients and Methods

ALS patients were diagnosed on the basis of characteristic clinical course, physical and electrodiagnostic findings, and absence of evidence of spondylotic myelopathy, paraproteinemias, hyperparathyroidism, Lyme disease, glycoprotein antibodies, and vitamin E toxicity. They were managed by a Jerry Lewis Muscular Dystrophy Association Clinic. The patients were evaluated every 2 to 6 months, depending on rate of disease progression, until requiring 24 hour ventilatory support, and then monthly by respiratory therapists in the home.

They initially underwent pulmonary function testing (SensorMedics Horizon Spirometer model 2450, SensorMedics Inc., Yorba Linda, CA) and both initially and subsequently underwent measurements of VC in both sitting and supine positions, maximum insufflation capacity (MIC), MIC VC difference (Wright spirometer, Mark 14, Ferraris Development and Engineering Co., Ltd, London), unassisted PCF and assisted PCF following a deep insufflation and an abdominal thrust (Peak Flow Meter, model 710, Health Scan Products Inc., Cedar Grove, N.J.), end-tidal pCO2 (Microspan 8090 capnograph, Biochem International, Waukesha, WI), and SpO2 (Ohmeda Model #3760 oximeter, Louisville, Co.). Nocturnal oximetry and end-tidal pCO2 monitoring were performed for patients with symptoms of hypoventilation, with daytime hypercapnia, oxyhemoglobin desaturation, limited ability to breathe when supine, or with a 30% or more decrease in VC when going from sitting to supine. Sought for symptoms included dyspnea, frequent sleep arousal with dyspnea or tachycardia, nightmares, morning headaches, daytime somnolence, and fatigue.14 Exclusion criteria were lung disease on the basis of FEV1/FVC less than 70% or SpO2 less than 95% despite good bulbar muscle function (PCF>200 L/m), normal CO2, and absence of acute respiratory illness.

The following criteria were used for training and intervention. Once the VC was decreased from predicted normal levels the patients were prescribed air stacking, that is, holding consecutively delivered volumes of air from a manual resuscitator, with a closed glottis, to maximum lung volumes (MICs) multiple times three times a day. When PCF were found to be below 270 L/m they were trained in and were equipped to use MAC or given rapid access to MAC.15 Oximetry was prescribed for spot checks, in the event of breathing difficulty or airway encumberment, and for continuous monitoring during chest infections to guide in the use of NPPV and MAC by the patient and care providers. Portable volume ventilators (PLV-100, Respironics Inc., Murrysville, PA) were used for mouth piece and nasal NPPV, initially 8 to 20 hours per day (part-time) to treat symptomatic hypoventilation, but often eventually for up to full-time noninvasive ventilatory support. Volume ventilators also permit independent air stacking. Assist-control mode was used with a back-up rate of 10 to 12 per minute with delivered volumes of 800 to 1500 ml. The large volumes were provided to more quickly compensate for insufflation leakage out of the nose or mouth during sleep, for more efficient air stacking, and to provide the capability for independently varying tidal volumes. A variety of nasal interfaces and lipseals were offered to the patients and many patients alternated these interfaces nightly. Simple flexed mouth pieces (Respironics Inc., Murrysville, PA) or, when buccal musculature was inadequate, nasal interfaces were used for daytime ventilatory support. Four patients with inadequate buccal musculature for mouth piece NPPV also used intermittent abdominal pressure ventilators for daytime aid.16 Supplemental oxygen was not used except when patients required intubation and in 2 cases when patients with no measurable assisted PCF chose to die at home rather than undergo tracheotomy.

Besides routine re-evaluations, the patients were instructed to present for evaluation when unable to maintain SpO2 greater than 94%, especially when this occurred during chest infections. Thus, they were taught to use NPPV and MAC to maintain normal SpO2 or immediately return SpO2 to normal (greater than 94%) by eliminating airway secretions and marked hypoventilation.7,17,18 Besides being used for feedback, oximetry was used to screen for atelectasis and other pulmonary complications.7,9,11,14,19,20 Initially, NPPV was used only overnight or episodically. As weakness progressed and ventilator-free breathing tolerance was lost, patients spontaneously increased use up to 24 hours a day.

T-tests were used for all statistical comparisons.

Results

Patient Demographics

One hundred sixty-six ALS patients presented from 1990 to 2000. Fifty-seven visited our clinic one or more times and were informed about the utility of noninvasive aids but have not returned or do not yet meet the criteria for using respiratory aids. Four patients were prescribed NPPV but did not obtain it. Four patients presented using TPPV. The remaining 101 patients, 62 males and 39 females, met or would eventually meet the criteria and were trained and equipped for using NPPV and MAC. Data are presented as means ± standard deviations. These patients had onset at 51.4 ±14.4 (range 22 to 85.1) years of age, were diagnosed at 52.7 ±14.8 years of age, and became wheelchair dependent at 54.4 ±13.8 years of age. Gender differences were not significant for the demographic data. No ALS patients met criteria for exclusion from the study.

Pulmonary Function

The 101 patients had a total of 461 pulmonary function evaluations in the clinic that included VCs of 1749 ±327 ml when sitting and 1475 ±298 ml when supine. In four cases the former were as much as twice the latter and patients without difficulty breathing when erect or sitting had no breathing tolerance when supine and required nocturnal NPPV. The data for monthly spirometry evaluations done at home were not included.

Outcomes with NPPV, MAC, and Oximetry

Three of the four patients who presented having already required continuous TPPV had residual bulbar function and were decanulated. Two of the three who were decanulated came from out-of-state specifically because they were advised that they might be offered the option for decanulation even though they had no breathing tolerance. They were switched to continuous NPPV. Of the 3 decanulated patients, one had required 24 hour BPAP for 2 years before tracheotomy. One month post-tracheotomy, with relatively stable bulbar function, he referred himself to us and was decanulated. He had assisted PCF of 380 L/m. He has now used NPPV continuously for 78 months. A second patient underwent tracheotomy during an acute episode of respiratory failure and then used it for nocturnal ventilatory assistance for 4 months before decanulation. He had assisted PCF of 210 L/m. He began to require full-time NPPV 6 months later; his assisted PCF became unmeasurable; and when his SpO2 baseline decreased, he was informed that he required re-tracheotomy but preferred to die at home. The third decanulated patient had undergone tracheotomy during an episode of respiratory failure 2 years earlier but did not require ventilator use and had intact bulbar muscle function when we recommended decanulation. Two years after decanulation assisted PCF became unmeasurable. He refused re-tracheostomy during another episode of respiratory failure and died.

Of the remaining 101 trained and equipped patients 15 have not yet required use and 11 severe bulbar patients died without successfully using the equipment. Two of the deceased patients had become demented. Three patients used full-time NPPV and MAC during chest infections and to clear airway secretions in general but do not require ongoing use. Eighteen have used part-time NPPV for 3.8 ±4.1 months. Nineteen others underwent tracheotomy after 4.7 ±4.5 months of part-time NPPV. In all but 1 case assisted PCF became less than 160 L/s, and NPPV and MAC could no longer maintain normal SpO2. The patient with greater PCF was demented and uncooperative with noninvasive methods during a chest infection.

Sixteen other patients lost all autonomous ability to ventilate their lungs but retained sufficient bulbar muscle function (and assisted PCF) to use MAC and eventually continuous NPPV. They used part-time NPPV for 17.5 ±13.0 (maximum 25) months and full-time NPPV for 14.1 ±12.6 (maximum 40) months before PCF became ineffective and they underwent tracheotomy. Thus, 34 of 35 patients underwent tracheotomy only after assisted PCF were below 160 L/m; and 28 had MICs that could not exceed VC. Tracheotomy was, thus, delayed despite the fact that patients had less than 5 minutes of ventilator-free breathing tolerance. It was considered only after assisted PCF were less than 160 L/m, the airways were encumbered, and SpO2 baseline was less than 95%. Of the 35 patients who underwent tracheotomy, 23 survived for a mean of 4.7 ±3.8 years and 12 are still alive and with a tracheostomy for 2.2 ±3.4 years.

Nineteen patients who have not undergone tracheotomy have benefited from part-time and full-time NPPV for 25.2 ±19.8 (maximum 114) and 17.5 ±13.3 (maximum 87) months, respectively. This included one patient who used part-time NPPV for 39 months, then full-time for 87 months, with a VC of 10 ml for over 6 years. His assisted PCF continue to exceed 160 L/m. Ten of these patients died. In all cases the deceased patients died after their assisted PCF had decreased below 160 L/s but they refused tracheotomy. Thus, these 19, the just described 16 patients, and 1 decanulated patient, 27 males and 9 females, used NPPV without breathing tolerance. Their survival was prolonged without tracheotomy for a mean of 17.5, 14.1, and 87 months, respectively. Data comparing the 36 patients in these latter groupings who were successful in using full-time NPPV with limited ventilator free breathing ability and the 19 patients who used part-time but were unsuccessful in using full-time NPPV are in Table 1. The only significant differences (p<0.05) in the data are that those who did not use full-time NPPV could also not use part-time NPPV as long; they underwent tracheotomy with higher VCs; and when requiring tracheotomy they had significantly lower assisted PCF and MIC VC difference (p<0.005) than the successful users (see Table 1).

Considering the entire population of ALS patients, those evaluated when their assisted PCF were greater than 160 L/m (n=153) had VC 1197 ±1302 ml, MIC 1945 ±1921 ml, and MIC minus VC of 748 ±811 ml. The 534 evaluations done on patients with assisted PCF less than 160 L/m yielded 462 evaluations where MIC and VC both equaled 942 ±857 ml and 72 evaluations where the MIC was 861 ±923 ml and the VC was 788 ±894 ml for a difference of 73 ±121 ml. Thus, patients with effective assisted PCF also had significantly greater MIC than VC (p<0.001) whereas patients with ineffective assisted PCF usually had no MIC, VC difference and, therefore, severely dysfunctional bulbar musculature.

In one case, VC sitting, VC supine, and MIC were 520 ml, 350 ml, and 5600 ml, respectively. He had no measurable unassisted PCF but assisted PCF were 390 L/m. Over the next year he lost all breathing tolerance except by glossopharyngeal breathing.21 As his VC decreased to 400 ml sitting, 250 ml supine, he maintained 5240 ml of MIC and 370 L/m of assisted PCF. One year later his VC dropped to 50 ml and the MIC to 4340 ml but his assisted PCF were then below 160 L/m. One month later he developed a respiratory infection and died when refusing tracheotomy.

No patients symptomatic for hypoventilation were non-compliant with NPPV, however, patients who were dyspneic due to airway secretion encumberment never used NPPV. No patient intentionally withdrew from NPPV. Since patients were always offered the use of at least 3 or 4 nasal interfaces and encouraged to try lipseal use for nocturnal NPPV, peri-nasal skin pressure sores were never a persistent problem. Several patients reported nasal congestion. This was successfully treated by using heated humidification and, at times, vasoconstrictors. Portable volume-cycled ventilators were used when patients could air stack (MIC>VC), otherwise the BiPAP-STTM (Respironics Inc., Murrysville, PA) was often used for nocturnal-only NPPV. The mean follow up period for the 101 patients was 3.4 ±3.1 years.

Discussion

NPPV can be used as an alternative to TPPV provided that adequate ventilation volumes are used, assisted PCF exceed 160 L/m, supplemental oxygen is avoided, sedatives are avoided or minimized, and aspiration of airway secretions is not so severe as to cause a persistent decrease in SpO2 below 95%.10 Since the assisted PCF and MIC VC difference correlate with bulbar muscle function,15 the ability to use full-time NPPV long-term is a function of residual bulbar muscle function and is independent of VC or the extent of need for ventilatory support.10 While tracheotomy only needs to be considered once assisted PCF decrease below 160 L/m, likewise, decanulation can be safely performed when assisted PCF exceed this level.10 Besides being able to use mouthpiece and nasal NPPV up to continuously to prevent ventilatory failure, patients with adequate bulbar muscle function can use MAC to prevent respiratory failure from airway encumberment.7,9

In the ALS and neuromuscular disease literature, investigators have sought to demonstrate statistically prolonged survival by using nocturnal-only NPPV,5,6 using TPPV,3 and have sought to compare the two approaches.22 However, limiting NPPV to nocturnal-only BPAP5,6,22 renders the development of ventilatory failure inevitable. Since severe bulbar dysfunction is essentially inevitable in ALS, respiratory failure has to eventually develop from saliva obstructing the airways or during intercurrent chest infections.9,17 In addition, NPPV and TPPV are not mutually exclusive methods. In the acute setting it has been demonstrated that NPPV can be used to avoid intubation, but that when insufficient to do so, intubation can be done without untoward effects from the attempt at NPPV.23 Likewise, for ALS patients, once assisted PCF decrease below 160 L/m and the SpO2 baseline decreases below 95%, respiratory failure becomes imminent and patients must consent to tracheotomy to further prolong survival. Our data suggest that about 36 of 166 patients, or over 20%, can use MAC as needed and NPPV continuously for prolonged survival.7,9 Most others develop severe bulbar dysfunction before becoming dependent on continuous ventilatory support. Several patients were referred to our center specifically for noninvasive management who may not have been referred had they had severe bulbar ALS. This may have skewed the number of successful full-time NPPV users to some degree.

ALS patients have been routinely treated with aerosols, bronchodilators, methylxanthines, continuous positive airway pressure, chest physical therapy and tracheal suctioning,24,25 and supplemental oxygen26 without evidence of prolonging survival. Indeed, besides decreasing ventilatory drive, exacerbating hypercapnia, and increasing the risk of pneumonias and hospitalizations for respiratory failure,17 oxygen therapy can hinder the utility of oximetry as feedback for clearing airway secretions by MAC, maintaining alveolar ventilation by NPPV,7,9 and for monitoring alveolar ventilation during periods of autonomous breathing.

Failure to use noninvasive aids effectively often results in intubation. Intubated patients who fail to wean typically undergo tracheotomy. However, tracheostomy impairs physiologic airway secretion clearance mechanisms, leads to chronic mucus accumulation and atelectasis, is associated with a significantly higher incidence of respiratory complications and hospitalizations for ALS and other neuromuscular disease patients than is dependence on continuous NPPV, and often results in continuous ventilator dependence.17,27 Tracheotomy can also necessitate the presence of licensed health care professionals.28

The use of noninvasive respiratory aids, on the other hand, is preferred by most patients and care providers over invasive approaches.28 Noninvasive aids can decrease the patient and family's feelings of helplessness when shortness of breath or airway congestion occurs in the home. Use of NPPV and MAC test the family's resolve and commitment before tracheotomy needs to be considered. Patients initially managed by noninvasive aids who later undergo tracheotomy may be better prepared to do so and NPPV users can withdraw from ventilatory support without necessarily requiring personal assistance.

Although the medical literature has not demonstrated any clear advantages to the use of pressure-limited or volume-limited ventilators for managing ventilatory insufficiency, air stacking can not be done with pressure-limited machines. This was the primary reason that we used volume-limited machines for ALS patients capable of air stacking. Volume-limited machines were also more practical for daytime support because they have internal batteries and function readily with external batteries. ALS patients referred to us using pressure-limited machines for nocturnal-only aid and who were unable to air stack were generally left to continue to use pressure-limited machines for assisted ventilation and used manual resuscitators or the positive pressure of the Cough-AssistTM at pressures of 40 cm H2O or more for regular lung expansion.

Unlike for patients with Duchenne muscular dystrophy,9 spinal muscular atrophy,7 and most other neuromuscular diseases, ALS bulbar dysfunction eventually necessitates tracheotomy for prolonging survival. Thus, we do not offer decanulation unless bulbar muscle function is well preserved for an initially non-bulbar ALS patient or, at least, assisted PCF exceed 160 L/m and bulbar function has been relatively stable. ALS patients also tend to be more depressed than patients with other neuromuscular diseases,29 tend to have less familial support than pediatric patients, and, because of the lack of definitive diagnostic tests, tend to go "diagnosis shopping" rather than seek interventions that will prevent future complications. All of these factors may explain why one-third of the patients may not return for eventual use of NPPV and MAC. On the other hand, it should be pointed out that much of the patients' despair is due to the very negative counseling and lack of hope usually offered them when initially diagnosed, the extraordinary burdens placed on family caregivers, and the emphasis on institutionalizing or "warehousing"30 self-directed severely disabled people for lack of a national personal assistance services policy. A more positive approach as recommended by the American Academy of Neurology,31 a better explanation of respiratory management, and more emphasis on social services and personal care assistance would result in better affect.

In summary, NPPV and TPPV are not mutually exclusive approaches. Most ALS patients eventually require continuous ventilatory support to survive. This study demonstrates that, besides nocturnal-only BPAP, about 20% of ALS patients can use NPPV up to continuously to prolong survival for an additional 14 to 17 months and in some cases over 7 years. Noninvasive aids should not be considered extraordinary or heroic measures. Most ALS patients can benefit from their use before requiring tracheotomy. Because of an often short window of opportunity to institute these techniques if premature intubation is to be avoided, the techniques should become accessible to ALS patients as PCF decrease below 270 L/m. The assisted PCF may be the best measure of bulbar muscle function in patients with neuromuscular weakness and it can be related to pneumonia risk and the need for considering tracheotomy or decanulation. Clinicians not familiar with how to institute NPPV or MAC, the limitations of the various techniques, or how to prepare and fit interfaces, are referred to the literature.11,32-34

References

1. Mulder DW, Howard FM. Patient resistance and prognosis in amyotrophic lateral sclerosis. Mayo Clin Proc 1976; 51:537-41

2. Boman K, Meurman T. Prognosis of amyotrophic lateral sclerosis. Acta Neuro Scand 1967; 43:489-98

3. Bach JR. Amyotrophic lateral sclerosis: communication status and survival with ventilatory support. Am J Phys Med Rehabil 1993; 72:343-49

4. Moss AH, Casey P, Stocking CB, et al. Home ventilation for amyotrophic lateral sclerosis patients: outcomes, costs, and patient, family, and physician attitudes. Neurology 1993; 43:438-43

5. Pinto AC, Evangelista T, Carvalho M, et al. Respiratory assistance with a non-invasive ventilator in MND/ALS patients: survival rates in a controlled trial. J Neurol Sci 1995; 129(Suppl):19-26

6. Kleopa KA, Sherman M, Neal B, et al. Bipap improves survival and rate of pulmonary function decline in patients with ALS. J Neurol Sci 1999; 164:82-88

7. Tzeng AC, Bach JR. Prevention of pulmonary morbidity for patients with neuromuscular disease. Chest 2000; 118:1390-96

8. Bach JR, Chaudhry SS. Management approaches in muscular dystrophy association clinics. Am J Phys Med Rehabil 2000; 79:193-96

9. Bach JR, Ishikawa Y, Kim H. Prevention of pulmonary morbidity for patients with Duchenne muscular dystrophy. Chest 1997; 112:1024-28

10. Bach JR, Saporito LR. Criteria for extubation and tracheostomy tube removal for patients with ventilatory failure: a different approach to weaning. Chest 1996; 110:1566-71

11. Bach JR. Update and perspectives on noninvasive respiratory muscle aids: part 2--the expiratory muscle aids. Chest 1994; 105:1538-44

12. Bach JR, Smith WH, Michaels J, et al. Airway secretion clearance by mechanical exsufflation for post-poliomyelitis ventilator assisted individuals. Arch Phys Med Rehabil 1993; 74:170-77

13. Alba A, Pilkington LA, Kaplan E, et al. Long-term pulmonary care in amyotrophic lateral sclerosis. Resp Ther 1976; 6:49-56,102-05

14. Bach JR, Alba AS. Management of chronic alveolar hypoventilation by nasal ventilation. Chest 1990; 97:52-57

15. Kang SW, Bach JR. Maximum insufflation capacity. Chest 2000; 118:61-65

16. Bach JR, Alba AS. Intermittent abdominal pressure ventilator in a regimen of noninvasive ventilatory support. Chest 1991; 99:630-36

17. Bach JR, Rajaraman R, Ballanger F, et al. Neuromuscular ventilatory insufficiency: the effect of home mechanical ventilator use vs. oxygen therapy on pneumonia and hospitalization rates. Am J Phys Med Rehabil 1998; 77:8-19

18. Fukunaga H, Okubo R, Moritoyo T, et al. Long-term follow-up of patients with Duchenne muscular dystrophy receiving ventilatory support. Muscle Nerve 1993; 16:554-58

19. Bach JR, Alba AS, Saporito LR. Intermittent positive pressure ventilation via the mouth as an alternative to tracheostomy for 257 ventilator users. Chest 1993; 103:174-82

20. Bach JR. Mechanical insufflation-exsufflation: comparison of peak expiratory flows with manually assisted and unassisted coughing techniques. Chest 1993; 104:1553-62

21. Bach JR, Alba AS, Bodofsky E, et al. Glossopharyngeal breathing and non-invasive aids in the management of post-polio respiratory insufficiency. Birth Defects 1987; 23:99-113

22. Raphael J-C, Chevret S, Chastang C, et al. Randomised trial of preventive nasal ventilation in Duchenne muscular dystrophy. Lancet 1994; 343:1600-04

23. Brochard L, Mancebo J, Wysocki M, et al. Noninvasive ventilation for acute exacerbations of chronic obstructive pulmonary disease. N Engl J Med 1995; 333:817-22

24. Sivak ED, Gipson WT, Hanson MR. Long-term management of respiratory failure in amyotrophic lateral sclerosis. Ann Neurol 1982; 12:18-23

25. Fallat RJ, Norris FH, Holden D, et al. Respiratory monitoring and treatment: objective treatments using non-invasive measurements. Adv Experimental Med Biol 1987; 209:191-200

26. Gay PC, Edmonds LC. Severe hypercapnia after low-flow oxygen therapy in patents with neuromuscular disease and diaphragmatic dysfunction. Mayo Clin Proc 1995; 74:327-30

27. Bach JR (ed). Pulmonary Rehabilitation: The Obstructive and Paralytic Conditions. Philadelphia: Hanley & Belfus, 1996, 430 pages.

Noninvasive ventilation: mechanisms for inspiratory muscle substitution

28. Bach JR. A comparison of long-term ventilatory support alternatives from the perspective of the patient and care giver. Chest 1993; 104:1702-06

29. Bach JR, Barnett V. Psychosocial, vocational, quality of life and ethical issues In: Bach JR, (ed). Pulmonary rehabilitation: the obstructive and paralytic conditions. Philadelphia: Hanley & Belfus, 1996; 395-411

30. Gill C. "Right to die" threatens our right to live safe and free. Mainstream 1992:32-36

31. Miller RG, Rosenberg JA, Gelinas DF, et al. Practice parameter: the care of the patient with amyotrophic lateral sclerosis: report of the Quality Standards Subcommittee of the American Academy of Neurology ALS Practice Parameters Task Force. Neurology 1999; 52:1311-23

32. Bach JR, (ed). Noninvasive Mechanical Ventilation: Comprehensive Patient Care. Philadelphia: Hanley & Belfus, (in press)

33. Bach JR. Update and perspectives on noninvasive respiratory muscle aids: part 1--the inspiratory muscle aids. Chest 1994; 105:1230-40

34. Hill N, (ed). Long-Term Mechanical Ventilation. New York: Marcel Dekker, 2001

Table 1 - Comparison of ALS Patient Groups Successful or Unsuccessful at Using Full-Time Noninvasive Ventilation


 Successful UsersPart-Time Users
Number of Patients3619
 (years)(years)
Age at Onset49.5 ±13.2 (22-66)52.4 ±15.0 (26-85.1)
Age at Diagnosis51.3 ±13.0 (22.7-69.5)53.6 ±15.1 (28.1-85.2)
Time from Onset1.8 ±4.3 (0.1-19.5)1.2 ±1.3 (0-6.1)
Loss of Ambulation52.1 ±13.0 (25.6-70.1)55.3 ±14.1 (28-76.9)
From Diagnosis1.9 ±2.4 (0-10)1.6 ±2.0 (0-8.4)
From Onset2.6 ±3.1 (0.1-14.6)2.8 ±2.7 (0.2 ±14.6)
Age Onset Vent Aid54.3 ±11.1 (28.4-70.3)56.8 ±13.7 (31.7-85.2)
From Onset4.9 ±5.7 (0.5-24.0)4.5 ±4.8 (0.1-25.3)
From Diagnosis3.0 ±3.0 (0.3-13)3.4 ±4.6 (0-25)
Noninvasive Aid Use(months)(months)
Nocturnal-only22.5 ±17.64.7 ±4.5*
Full-time NPPV17.2 ±35.4 
 (ml)(ml)
VC at Tracheotomy n=16274 ±301 (10-800)1164 ±523 (640-1930)*
MIC at Tracheotomy n=16274 ±301 (10-800)1193 ±590 (640-2080)
MIC - VC at trach n=16029 ±58
recent VC n=19292 ±380 (10-615)145 ±258 (0-520)
recent MIC n=19840 ±436 (480-2330)----
recent MIC-VC n=19548 ±701 
assisted PCF at tracheotomy n=1630 ±24 L/m26 ±25 L/m
recent assisted PCF n=9192 ±92 L/m 

* = p<0.05; a--figures in years ± standard deviation

Table 2 - Stages of Respiratory Muscle Dysfunction


StageVCaSymptomspCO2bSpO2%cPCFdMICe
1>50%none<45>95%<6>1500
210%-50%dyspnea>45<95%>3>500
3<10%ventilator free breathing time <5 min>3>500
4<10%ventilator free breathing time <5 min<3<500

A--vital capacity
B--maximum nocturnal end-tidal pCO2 in mm Hg
C--mean nocturnal oxyhemoglobin saturation
D--assisted peak cough expiratory flows in L/s
E--maximum insufflation capacity in ml

We previously described the use of noninvasive IPPV for 25 ALS patients for 2.0 ±1.7 (0.1-5.4) years, including for 1.7 ±2.0 (0.1-5.4) years prior to tracheotomy for 12 patients, for 2.0 ±1.3 (0.3-4.2) years prior to death for 7 patients who never underwent tracheotomy, and 2.5 ±1.7 (0.1-4.3) years for 6 other noninvasive IPPV users. The 25 patients used all forms of ventilatory support for 3.9 ±5.2 (0.1-26.5) years including 3.0 ±2.7 (0.3-10) years for 16 deceased patients, and 5.5 ±8.0 (0.1-26.5) years for 9 patients still using ventilators.

Four clinical stages of respiratory muscle dysfunction were identified (Table 2). In the Lung Range-of-Motion Stage, PCF were below 270 L/m or VC below 50% and the patients were trained in assisted coughing and used a three times daily regimen of hyperinsufflations via an oral, nasal, or oro-nasal interface with the goal of approaching the maximum predicted inspiratory capacity and maximizing assisted PCF. The use of maximum insufflation therapy also accustomed the patient to noninvasive IPPV for eventually continuous use.

In the Part-time Noninvasive Ventilation Stage, patients who were symptomatic for hypercapnia or who could not be entirely weaned from noninvasive IPPV following a respiratory tract infection used ongoing noninvasive ventilation, nocturnally at first, and gradually up to 24 hours a day with less than 5 minutes of VFBA (Full-Time Stage). They used the IAPV and/or mouth piece/nasal IPPV during daytime hours and nasal or lipseal IPPV overnight. VFBA less than 5 minutes was defined by the appearance of dyspnea, oxyhemoglobin desaturation, and elevation of carbon dioxide tensions greater than 10 mm Hg in less than 5 minutes when off of ventilatory aid. During this stage mouthpiece or nasal IPPV and the use of occasional hyperinsufflations or air stacking27 was used to increase voice volume and assisted PCF. Although noninvasive IPPV was the predominant method of 24 hour ventilatory support, four patients preferred to use an IAPV for daytime, and in two cases, for 24 hour support.16 Some patients with predominantly severe bulbar muscle involvement whose assisted PCF decreased below 160 L/m and who developed respiratory failure underwent tracheostomy.

In the tracheostomy stage the MIC was no longer significantly greater than the VC,??? and the assisted PCF decreased under 160 L/m. Patients were invariably averbal at this time. Tracheostomy then became necessary as noninvasive IPPV leaked excessively or respiratory failure occurred during chest infections or from saliva aspiration so severe as to decrease baseline SpO2 below 95%.

The choice of long-term inspiratory muscle support was to a large degree left up to the VU. For nocturnal aid nasal IPPV was used by 21 VUs, mouthpiece IPPV with lipseal retention (Malincrodt, Pleasanton, CA) by three VUs, and the IAPV by two VUs. For daytime aid, four VUs used the IAPV, nine used mouthpiece IPPV, and 13 with inadequate lip and oral muscle function used nasal IPPV. Custom molded nasal interfaces were constructed for five nasal IPPV users. Most nasal IPPV users had two or more nasal interfaces, mostly commercially available continuous positive airway pressure (CPAP) masks. They alternated their use to avoid excessive pressures on skin surfaces in contact with any particular interface. The overall success in the use of noninvasive methods for full-time ventilatory support was the extent of 24 hour use in the Full-Time Stage.

The T-test was used to compare the means of the ages of the chronological milestones of the two groups noted in Table 1. A p value less than or equal to 0.05 was considered significant.

Robert D, Willig TN, Paulus J, et al. Leger P, Bach JR, Barois A, Chevrolet JC, Durocher A, Echenne B, Floret D, Gajdos P, Polu JM, Soudon P. Long-term nasal ventilation in neuromuscular disorders: report of a consensus conference. Eur Respir Rev 1993;6:599-606.

We demonstrated that for a population of patients with Duchenne muscular dystrophy hospitalizations and episodes of respiratory failure could be avoided by using noninvasive IPPV and manually and mechanically assisted coughing (In-exsufflator™, J. H. Emerson Co., Cambridge, MA) as needed to maintain oxyhemoglobin saturation (SpO2) greater than 94%. We used a similar protocol for ALS patients. The purpose of this study is to review the results of this approach.

Although there continues to be a common misconception that if ventilatory support is achieved by "a positive pressure system...tracheostomy is required,"17,18 patients with advanced NMDs have been managed by up to 24 hour a day noninvasive IPPV.19 Noninvasive IPPV can be delivered via oral, nasal, or oral-nasal interfaces19-21 and body ventilators like the intermittent abdominal pressure ventilator can be used.22 However, there are differences between ALS ventilator users and users with other NMDs. Although for most individuals with advanced NMD alveolar hypoventilation initially manifests itself during sleep once supine VCs are greatly diminished,20,23 many ALS patients develop acute respiratory failure with VCs exceeding 50% of normal.24 This is often due to early and severe weakness of bulbar muscles.25,26 In addition, expiratory muscle weakness usually exceeds inspiratory muscle weakness in ALS.27 Weakness of both inspiratory and expiratory musculature is exacerbated during respiratory tract infections28 during which assisted PCF often decrease below 160 L/m.6

References

9. Bach JR, Campagnolo DI, Hoeman S. Life satisfaction of individuals with Duchenne muscular dystrophy using long-term mechanical ventilatory support. Am J Phys Med Rehabil 1991; 70:129-35

10. Bach JR, Campagnola D. Psychosocial adjustment of post-poliomyelitis ventilator assisted individuals. Arch Phys Med Rehabil 1992; 73:934-39

11. Robert D, Willig TN, Paulus J, et al. Long-term nasal ventilation in neuromuscular disorders: report of a consensus conference. Eur Respir Rev 1993; 6:599-606

12. McDonald ER, Hillel A, Wiedenfeld SA. Evaluation of the psychological status of ventilatory-supported patients with ALS/MND. Palliat Med 1996; 10:35-41

13. Moss AH, Oppenheimer EA, Casey P, et al. Patients with amyotrophic lateral sclerosis receiving long-term mechanical ventilation: advance care planning and outcomes. Chest 1996; 110:249-55

14. Moss AH, Casey P, Stocking CB, Roos RP, Brooks BR, Siegler M. Home ventilation for amyotrophic lateral sclerosis patients: outcomes, costs, and patient, family and physician attitudes. Neurology 1993; 43:438-43

17. Hillel AD, Miller R. Bulbar amyotrophic lateral sclerosis: patterns of progression and clinical management. Head Neck 1989; 11:51-59

24. Fallat RJ, Jewitt B, Bass M, Kamm B, Norris FH Jr. Spirometry in amyotrophic lateral sclerosis. Arch Neurol 1979; 36:74-80 .

25. Griggs RC, Donohoe KM, Utell MJ, Goldblatt D, Moxley RT. Evaluation of pulmonary function in neuro-muscular disease. Arch Neurol 1981; 38:9-12

26. Kreitzer SM, Saunders N, Tyler HR, Ingram RH. Respiratory muscle function in amyotrophic lateral sclerosis. Am Rev Respir Dis 1978; 117:437-47

27. Kreitzer SM, Saunders N, Tyler HR, Ingram RH. Respiratory muscle function in amyotrophic lateral sclerosis. Chest 1978; 73(suppl): 266-67

28. Mier-Jedrzejowicz A, Brophy C, Green M. Respiratory muscle weakness during upper respiratory tract infections. Am Rev Respir Dis 1988; 138:5-7

1. Mulder DW, Howard FM. Patient resistance and prognosis in amyotrophic lateral sclerosis. Mayo Clin Proc 1976;51:537-41.

2. Boman K, Meurman T. Prognosis of amyotrophic lateral sclerosis. Acta Neuro Scand 1967; 43:489-98

3. Bach JR. Amyotrophic lateral sclerosis: communication status and survival with ventilatory support. Am J Phys Med Rehabil 1993; 72:343-49

4. Moss AH, Casey P, Stocking CB, Roos RP, Brooks BR, Siegler M. Home ventilation for amyotrophic lateral sclerosis patients: outcomes, costs, and patient, family, and physician attitudes. Neurology 1993; 43:438-43

5. Pinto AC, Evangelista T, Carvalho M, Alves MA, Sales Luis ML. Respiratory assistance with a non-invasive ventilator in MND/ALS patients: survival rates in a controlled trial. J Neurol Sci 1995; 129(Suppl):19-26

6. Kleopa KA, Sherman M, Neal B, Romano GJ, Heiman-Patterson T. Bipap improves survival and rate of pulmonary function decline in patients with ALS. J Neurol Sci 1999; 164:82-88

7. Tzeng AC, Bach JR. Prevention of pulmonary morbidity for patients with neuromuscular disease. Chest (in press)

8. Bach JR, Chaudhry SS. Management approaches in muscular dystrophy association clinics. Am J Phys Med Rehabil 2000; 79:193-96

9. Bach JR, Ishikawa Y, Kim H. Prevention of pulmonary morbidity for patients with Duchenne muscular dystrophy. Chest 1997; 112:1024-28

10. Bach JR, Saporito LR. Criteria for extubation and tracheostomy tube removal for patients with ventilatory failure: a different approach to weaning. Chest 1996; 110:1566-71

11. Bach JR. Update and perspectives on noninvasive respiratory muscle aids: part 2--the expiratory muscle aids. Chest 1994; 105:1538-44

12. Alba A, Pilkington LA, Kaplan E, Baum J, Schultheiss M, Ruggieri A, Lee MHM. Long-term pulmonary care in amyotrophic lateral sclerosis. Resp Ther 1976; 6:49-56,102-05

13. Bach JR, Alba AS. Management of chronic alveolar hypoventilation by nasal ventilation. Chest 1990; 97:52-57

14. Kang SW, Bach JR. Maximum insufflation capacity. Chest 2000; 118:61-65

15. Bach JR, Rajaraman R, Ballanger F, Tzeng AC, Ishikawa Y, Kulessa R, Bansal T. Neuromuscular ventilatory insufficiency: the effect of home mechanical ventilator use vs. oxygen therapy on pneumonia and hospitalization rates. Am J Phys Med Rehabil 1998; 77:8-19

16. Fukunaga H, Okubo R, Moritoyo T, Kawashima N, Osame M. Long-term follow-up of patients with Duchenne muscular dystrophy receiving ventilatory support. Muscle & Nerve 1993; 16:554-58

17. Bach JR, Alba AS, Saporito LR. Intermittent positive pressure ventilation via the mouth as an alternative to tracheostomy for 257 ventilator users. Chest 1993; 103:174-82

18. Bach JR, Alba AS. Total ventilatory support by the intermittent abdominal pressure ventilator. Chest 1991; 99:630-36

19. Bach JR. Mechanical insufflation-exsufflation: comparison of peak expiratory flows with manually assisted and unassisted coughing techniques. Chest 1993; 104:1553-62

20. Bach JR, Smith WH, Michaels J, Saporito LS, Alba AS, Dayal R, Pan J. Airway secretion clearance by mechanical exsufflation for post-poliomyelitis ventilator assisted individuals. Arch Phys Med Rehabil 1993; 74:170-77

21. Sivak ED, Gipson WT, Hanson MR. Long-term management of respiratory failure in amyotrophic lateral sclerosis. Ann Neurol 1982; 12:18-23

22. Fallat RJ, Norris FH, Holden D, Kandal K, Roggero PC. Respiratory monitoring and treatment: objective treatments using non-invasive measurements. Adv Experimental Med Biol 1987; 209:191-200

23. Bradley W. Amyotrophic lateral sclerosis and Duchenne muscular dystrophy: the diseases and the doctor-patient relationship. In: Charash LI, Lovelace RE, Wolf SG, Kutscher AH, Roye DP, Leach CF, eds. Realities in coping with progressive neuromuscular diseases. Philadelphia: The Charles Press, 1987

24. Bach JR, Intintola P, Alba AS, Holland I. The ventilator-assisted individual: cost analysis of institutionalization versus rehabilitation and in-home management. Chest 1992;101:26-30.

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Table 1 -- Comparison of ALS Patient Groupsa


 Stage 3 UsersUnsuccessful Users
Number of Patients2631
Age at Onset of ALS49.5 ±13.2 (22-66)52.4 ±15.0 (26-85.1)
Age at Diagnosis51.3 ±13.0 (22.7-69.5)53.6 ±15.1 (28.1-85.2)
Time from Onset1.8 ±4.3 (0.1-19.5)1.2 ±1.3 (0-6.1)
Loss of Ambulation52.1 ±13.0 (25.6-70.1)55.3 ±14.1 (28-76.9)
Time From Diagnosis1.9 ±2.4 (0-10)1.6 ±2.0 (0-8.4)
Time From Onset2.6 ±3.1 (0.1-14.6)2.8 ±2.7 (0.2 ±14.6)
Age Onset Vent Aid54.3 ±11.1 (28.4-70.3)56.8 ±13.7 (31.7-85.2)
Time From Onset4.9 ±5.7 (0.5-24.0)4.5 ±4.8 (0.1-25.3)
Time From Diagnosis3.0 ±3.0 (0.3-13)3.4 ±4.6 (0-25)
Noninvasive Aid Use1.9 ±1.6 (0.1-5.4)0
Stage 20.3 ±1.1 (0.1-1.8) 
Stage 31.5 ±1.1 (0.1-5.1) 
Total Ventb Support3.9 ±5.2 (0.1-26.5)4.6 ±3.2 (0.5-15.9)
Deceased1628
VC279 ±302 (0-660)c1164 ±523 (640-1930)d
MIC407 ±319 (280-610)e1309 ±641 (700-1930)f

a--All figures are in years ± standard deviation except where indicated
b--ventilatory
c--vital capacity when ventilator free breathing time noted to be under 5 minutes
d--vital capacity when undergoing tracheostomy
e--maximum insufflation capacity when ventilator free breathing time noted to be under 5 minutes
f--maximum insufflation capacity when undergoing tracheostomy

A particularly interesting case was that of a man with non-bulbar ALS onset November 1991, wheelchair dependent March 1993, part-time NPPV user from March 1995, and continuously dependent on daytime mouth piece and nocturnal nasal NPPV from June 1996 until dying from pneumonia when refusing tracheotomy in August 1998. In June 1996 while his VC in the sitting position was 520 ml and he had only minutes of autonomous breathing tolerance in this position, he had no autonomous breathing ability supine and a VC of 350 ml in this position. Despite the diminished VC his MIC was 5600 ml.



Author: John R. Bach, MD

Web page: Rich Clingman

Updated: 04/10/03

Reviewed:


ALS: Prolongation of Life by NIV Respiratory Aids
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