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(Chest. 2000;118:1390-1396.)
© 2000 American College of Chest Physicians

Prevention of Pulmonary Morbidity for Patients With Neuromuscular Disease*

Alice C. Tzeng, MD and John R. Bach, MD, FCCP

* From the Departments of Physical Medicine and Rehabilitation (Dr. Tzeng) and Neurosciences (Dr. Bach), University of Medicine and Dentistry of New Jersey (UMDNJ)–New Jersey Medical School, Newark, NJ.

Correspondence to: John R. Bach, MD, FCCP, Department of Physical Medicine and Rehabilitation, University Hospital B-403, UMDNJ-New Jersey Medical School, 150 Bergen St, Newark, NJ 07103; e-mail: bachjr{at}umdnj.edu


   Abstract
TOP
 Abstract
Introduction
 Materials and Methods
 Results
 Discussion
 References
 
Study objective: To evaluate the effects of a respiratory muscle aid protocol on hospitalization rates for respiratory complications of neuromuscular disease.

Design: A retrospective cohort study.

Methods: A home protocol was developed in which oxyhemoglobin desaturation was prevented or reversed by the use of noninvasive intermittent positive-pressure ventilation and manually and mechanically assisted coughing as needed. The patients who had more than one episode of respiratory failure before having access to the protocol were considered to have had preprotocol periods (group 1). Other patients were given access to the protocol when their assisted peak cough flows decreased to < 270 L/min before any episodes of respiratory distress (group 2). The number of hospitalizations and days hospitalized were compared longitudinally for preprotocol and protocol access periods (group 1). In addition, avoided hospitalizations were identified as "episodes" of need for continuous ventilatory support and desaturations reversed by assisted coughing that were managed at home. Data were segregated by access to protocol and by extent of baseline ventilator use.

Results: Of the 47 group 1 patients with preprotocol periods who have subsequently had episodes, 10 had episodes before requiring ongoing ventilator use. They had 1.06 ± 0.84 preprotocol hospitalizations per year per patient and 20.76 ± 36.01 hospitalization days per year per patient over 3.42 ± 3.36 years per patient vs 0.03 ± 0.11 hospitalizations per year per patient and 0.06 ± 0.20 hospitalization days per year per patient with protocol use over 1.94 ± 0.74 years per patient. Of these 47 group 1 patients, 33 eventually required part-time ventilatory aid and, using the protocol as needed, had 0.08 ± 0.17 hospitalizations per year per patient and 1.43 ± 3.71 hospitalization days per year per patient over 3.91 ± 3.50 years per patient, as opposed to 1.40 ± 1.96 hospitalizations per year per patient and 20.14 ± 41.15 hospitalization days per year per patient preprotocol and preventilator use over 5.89 ± 6.89 years per patient. Twelve patients in group 1 eventually required continuous noninvasive ventilation and, using the protocol as needed, had 0.07 ± 0.14 hospitalizations per year per patient and 0.39 ± 0.73 hospitalization days per year per patient over 5.35 ± 5.10 years per patient by comparison with 0.97 ± 0.74 hospitalizations per year per patient and 10.39 ± 8.66 hospitalization days per year per patient over 2.18 ± 1.91 years per patient preprotocol and preventilator use. For the 94 patients overall when having access to the protocol, 1.02 ± 0.99 hospitalizations per year per patient were avoided by 14 patients before requiring ongoing ventilator use over 4.82 ± 1.61 years, 0.99 ± 1.12 hospitalizations per year per patient were avoided by 73 part-time ventilator users over 3.21 ± 3.15 years, and 0.80 ± 0.85 hospitalizations per year per patient were avoided by 31 full-time ventilator users over 4.78 ± 4.88 years. All preprotocol and protocol rate comparisons were statistically significant at p < 0.004.

Conclusion: Patients have significantly fewer hospitalizations per year and days per year when using the protocol as needed than without the protocol. The use of inspiratory and expiratory aids can significantly decrease hospitalization rates for respiratory complications of neuromuscular disease.

Key Words: exsufflation • mechanical ventilation • neuromuscular disease • respiratory therapy


   Introduction
TOP
 Abstract
 Introduction
Materials and Methods
 Results
 Discussion
 References
 
The great majority of neuromuscular disease morbidity and mortality is caused by respiratory muscle weakness.1 Approximately 90% of episodes of respiratory failure occur during otherwise benign

upper respiratory tract infections ("chest infections") rather than from insidiously progressive CO2 narcosis or other respiratory abnormalities.2 During chest infections, already impaired pulmonary function is further compromised by airway mucus accumulation, fatigue, and worsening dysfunction of already weak inspiratory and expiratory muscles.3 Thus, for conventionally managed patients, chest infections result in repeated pneumonias, hospitalizations, endotracheal intubations, and ultimately, in tracheostomy and death.

Up to 24-h use of noninvasive intermittent positive-pressure ventilation (IPPV) has prolonged the survival of > 700 patients with neuromuscular ventilatory failure.4 For noninvasive IPPV to do this, however, the ability to clear the airway of secretions is critical, especially during chest infections and after surgical anesthesia. Peak cough flows (PCFs) of >= 160 L/min are the minimum required in adults to clear airway debris without resorting to tracheal intubation (Fig 1 ).5 6 In our experience, assisted PCFs of > 160 L/min can be attained for the great majority of adult patients with neuromuscular disease, except for those with advanced bulbar amyotrophic lateral sclerosis.7 We have found that when routinely measured assisted PCFs are < 270 L/min, they are very likely to decrease to < 160 L/min during chest infections, and the likelihood of pneumonia and respiratory failure increases greatly. Considering the fact that both hypercapnia and airway mucus accumulation can cause oxyhemoglobin desaturations, we hypothesized that if we could identify patients at high risk of developing acute respiratory failure on the basis of low PCFs, and train and equip these patients to prevent a sustained decrease in arterial oxygen saturation (SaO2) to < 95%, pulmonary morbidity and mortality could be prevented.



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  		Figure 1. Measurement of assisted PCFs after the patient’s lungs were fully insufflated by air stacking consecutively delivered volumes of air and a tussive squeeze was applied to the chest as the patient coughs through a peak flowmeter.

 

   Materials and Methods
TOP
 Abstract
 Introduction
 Materials and Methods
Results
 Discussion
 References
 
All of the patients in this study were referred to our Jerry Lewis Muscular Dystrophy Association clinic from neurologists who made the primary diagnoses or referred themselves to us once learning about us from other patients. Their diagnoses, confirmed in our clinic by standard criteria,8 mean ages when first experiencing respiratory distress, and pulmonary function are listed in Table 1 . All of the patients resided at home and had dedicated family members or personal-care attendants.


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  		Table 1. Patient Information*

 
The patients were routinely evaluated for vital capacity (VC) and maximum insufflation capacity (MIC) by spirometry (Wright spirometer; Mark 14; Ferraris Development and Engineering Co, Ltd; London, UK), end-tidal CO2 tension (PETCO2; Microspan 8090 capnograph; Biochem International; Waukesha, WI), SaO2 (Ohmeda model 3760; Ohmeda; Louisville, CO), and unassisted and assisted PCFs (Access peak flowmeter; HealthScan, Inc.; Cedar Grove, NJ; Fig 1 ). Once assisted PCFs were determined to be < 270 L/min, patients were trained in receiving deep volumes of air via nose or mouthpiece and in manually and mechanically assisted coughing, and they became candidates for this study. Of the patients so evaluated, 94 met the PCF criteria and had one or more episodes requiring ventilatory support. Although exclusion criteria for this study were substance abuse and chronic lung disease as defined by long-term radiographic abnormalities in conjunction with SaO2 chronically < 95% or ratio of FEV1 to FVC of 2 SDs less than normal, no patients were excluded on the basis of these criteria.

Once VCs were < 2,000 mL or approximately 50% of predicted normal, the patients were trained in "air stacking" consecutively delivered volumes of air delivered from a manual resuscitator or volume-cycled ventilator. The patients received the air volumes via simple mouthpieces,9 nasal interfaces, or, for those with weak lips and buccal muscles, via an oral-nasal interface or lip seal (Mallinkrodt, Pleasanton, CA; Fig 2 ). They stacked the consecutively delivered air volumes, holding them with a closed glottis, until the lungs and chest walls were as deeply insufflated as possible. The air-stacking capability or MIC was quantified spirometrically. Patients who could air stack in this manner could also use noninvasive IPPV, that is, receive IPPV via mouthpieces and nasal interfaces (inspiratory muscle aids) as ventilatory support,10 whereas those not capable of holding deeper volumes than their VCs (MIC = VC) have more difficulty using noninvasive ventilation because of air leakage.



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  		Figure 2. Air stacking via a lip seal.

 
Patients with symptoms suggesting hypoventilation, elevated PETCO2, or periods of daytime SaO2 < 95% underwent nocturnal SaO2 monitoring. With symptoms or nocturnal SaO2 means < 95%, the patients had trials of nocturnal nasal IPPV using a portable volume ventilator (PLV-100; Respironics Inc.; Murrysville, PA). The patients continued to use nocturnal nasal IPPV when they felt less fatigue or had relief of other symptoms of chronic hypoventilation and when nocturnal mean SaO2 was shown to increase. Assist-control mode at a rate of 12 breaths/min and delivered volumes of 800 to 1,500 mL were used for virtually all adolescent and adult patients. Rates were increased and volumes decreased for young children. With time, more than nocturnal use often became necessary. Nocturnal to 16 h/d was considered part-time, and > 16 h/d was considered full-time use. Most patients used noninvasive IPPV for daytime (continuous) ventilatory support for the first time during chest infections and weaned from continuous assistance, except during chest infections, often for at least several years.

The patients were also trained in manually and mechanically assisted coughing. Because normal cough volumes are 2.30 ± 0.5 L11 and assisted cough flows have been reported to be significantly increased by air stacking once VCs have decreased to < 1.5 L, to maximize assisted cough flows, the patients were told to air stack to deep lung volumes once their VCs were < 1,500 mL.12 Thus, an assisted cough most often consisted of insufflating patients to approach their MICs and then applying an abdominal thrust or tussive squeeze (Fig 1) , whichever produced the highest assisted PCFs, timed to glottic opening.12 The patients were told to practice this technique with care providers, and their success was monitored by routinely measuring assisted PCFs via a peak flowmeter.

Mechanical cough assistance was provided by mechanical insufflation-exsufflation (MI-E) with the use of an In-exsufflator (JH Emerson Company; Cambridge, MA).12 13 The In-exsufflator provides an independently adjusted deep insufflation via an anesthesia mask or a tube if the patient is intubated. The In-exsufflator insufflation pressure is usually set at +35 to +60 cm H2O. Insufflation is followed by an exsufflation caused by an immediate pressure drop to -35 to -60 cm H2O. Each insufflation and exsufflation is usually about 2 to 3 s. MI-E was particularly important when assisted PCFs were marginal (approximately 160 to 270 L/min), as bulbar muscle weakness prevented the retention of deep volumes of air, and when scoliosis prevented optimal manual thrusts. During the exsufflations, abdominal thrusts or tussive squeezes were applied to further increase exsufflation (cough) flows (Fig 3 ).



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  		Figure 3. A tussive squeeze applied during the exsufflation phase of MI-E.

 
The patients received pulse oximeters. The protocol consisted of using noninvasive IPPV continuously or as needed to maintain eucapnia and normal SaO2, and manually and mechanically assisted coughing as needed to promptly reverse any decreases in SaO2 < 95%, particularly during chest infections. They were told that the desaturations would be caused by some combination of hypercapnia and, most commonly, airway mucus accumulation and if these were not managed immediately, the desaturations would persist, and atelectasis and pneumonia would result. If not already using noninvasive IPPV or MI-E, they were provided with rapid access (< 2 h) to a portable volume ventilator and an In-exsufflator.14 No treated patients were symptomatic for under- or overventilation. Colds often necessitated almost continuous caregiver attention. This was especially true during severe episodes during which patients often slept poorly and required manually and mechanically assisted coughing essentially around the clock. No patients who were regularly evaluated failed to be properly trained and equipped or refused the protocol.

Conventional management was defined as any ambulatory management not including continuous ventilator use and mechanically assisted coughing with oximetry feedback. Differences between conventional and protocol approaches are summarized in Table 2 . Patients were considered in group 1 when, managed conventionally, they had one or more episodes of respiratory failure before introduction of the protocol. Those who had two or more episodes of respiratory failure had "preprotocol periods." For these patients, the hospitalization rates and days, number of intubations, and days intubated were quantitated during the preprotocol period beginning with the first episode, and compared with those subsequently while having access to the protocol but free of ongoing ventilator use, and when requiring ongoing part-time and full-time ventilatory assistance (Table 3 ). The group 1 patients who had access to the protocol immediately after the first episode of respiratory failure had no "preprotocol period."


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  		Table 2. Protocol vs Conventional Management of Intercurrent Respiratory Tract Infections for Patients With Neuromuscular Respiratory Muscle Weakness

 

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  		Table 3. Hospitalization Rate Comparisons for 47 Group 1 Patients With Preprotocol Periods and Subsequent Episodes of Respiratory Distress

 
Group 2 patients were those who were placed on the protocol when their assisted PCFs decreased to < 270 L/min and eventually had hospitalizations or "avoided hospitalizations" for respiratory distress. Avoided hospitalizations were tabulated for all patients (Table 4 ). Avoided hospitalizations were defined as acute episodes of respiratory distress and loss of autonomous ability to breathe during chest infections relieved by continuous ventilator use along with the use of assisted coughing and MI-E to reverse desaturation-associated mucus accumulation. For patients already requiring continuous ventilator use, only the acute need for increased use of assisted coughing and MI-E to reverse desaturation-associated mucus accumulation during febrile upper respiratory tract infections was the criterion for avoided hospitalizations.


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  		Table 4. Hospitalizations Avoided per Patient per Year

 
A paired t test was used to compare hospitalization rates and days, number of intubations, and intubated days for the preprotocol and protocol access periods. The Wilcoxon signed-rank test was used for nonparametric distributions. A p < 0.05 was considered to represent statistical significance.


   Results
TOP
 Abstract
 Introduction
 Materials and Methods
 Results
Discussion
 References
 
The 94 study patients included 68 men and 26 women, currently with the mean age of 31.09 ± 18.91 years (range, 2.5 to 73.5 years). All had sufficient bulbar muscle function to permit speech and had assisted PCFs > 160 L/min. PETCO2 levels were normal for all 24-h noninvasive ventilatory support users. No nonventilator users or part-time ventilator users had PETCO2 levels > 50 mm Hg.

Seventy-one group 1 patients had initial episodes of respiratory failure at 23.85 ± 17.68 years of age, 4.20 ± 5.66 years before being referred to us and having access to the protocol at age 27.24 ± 18.84 years. The 23 group 2 patients were put on the protocol at age 24.29 ± 14.91. This was 1.59 ± 1.13 years before their first potential episode of respiratory failure.

There were six patients in group 1 who were managed conventionally up to an initial hospitalization for respiratory failure and were then given access to the protocol. Their data are analyzed separately because they had no preprotocol period to compare with protocol periods. All six began the protocol along with nocturnal (part-time) ventilatory aid. Of the six, four avoided 0.95 ± 0.84 hospitalizations per year over 4.05 ± 3.27 years per patient (p = 0.11) and the other two have had no chest infections or episodes of respiratory distress since beginning the protocol. Eighteen of the group 1 patients have not had any chest infections or episodes of respiratory distress since learning the protocol.

The rates of hospitalizations, hospitalization days, number of intubations, and intubation days for the remaining 47 group 1 patients are noted in Table 3 . Avoided hospitalizations of both groups combined are summarized in Table 4 . The protocol was used by 11 group 1 patients for a mean of 0.98 ± 1.57 years before requiring ongoing ventilatory assistance, 2.90 ± 2.45 years for 51 group 1 patients while using ongoing part-time ventilatory assistance, and by 21 group 1 patients using ongoing full-time ventilatory assistance for 4.35 ± 4.81 years. The protocol was used by 3 group 2 patients 1.43 ± 2.37 years before requiring ongoing ventilatory assistance, 22 group 2 patients using part-time ventilatory assistance for 3.61 ± 2.88 years, and 9 group 2 patients using full-time ventilatory support for 5.29 ± 4.88 years. The p values as determined by t test compared the actual hospitalization rates with those that would have occurred with conventional management.

One 15-year-old patient with Duchenne muscular dystrophy, who had unassisted PCFs of 250 L/min and assisted PCFs of 300 L/min, did not meet the criteria for training and inclusion in this study. One month later, he experienced a chest infection, had pneumonia, and was hospitalized. The protocol was instituted. He did not require intubation and was discharged after a hospitalization of 8 days.


   Discussion
TOP
 Abstract
 Introduction
 Materials and Methods
 Results
 Discussion
References
 
This study has no true control group. However, it would be unethical to compare the hospitalization rates of an untreated group with the hospitalizations avoided by treatment. Conventional management includes the hospitalization and invasive respiratory management of any patient requiring ventilatory support with no ventilator-free breathing ability, whereas for us, the need for continuous ventilator use was a key criterion for establishing an "avoided hospitalization."

At least while they were free of chest infections, assisted PCFs of > 160 L/min were attainable for all the protocol-using patients throughout the study period. This was true despite the fact that 31 of these patients eventually went on to require full-time noninvasive ventilatory support and 1 patient had a VC < 100 mL. Thus, all of these patients were candidates for long-term management of ventilatory muscle failure without resort to tracheostomy.

The use of assisted PCF < 270 L/min as a threshold criterion for introduction of this protocol appears to be reasonable because we have only one patient who experienced pneumonia despite having assisted PCFs greater than this. Further, it was approximately 1.5 years from learning the protocol until needing to use it on the average. Earlier introduction of the protocol would further increase up-front expenses. It is also possible that other patients with PCFs > 270 L/min developed respiratory failure and never returned to our clinic.

The fact that assisted PCFs can exceed 270 L/min when patients are well does not mean that they will exceed 160 L/min or be adequate to clear airway secretions during chest infections (thus the great utility of MI-E for many), nor is it a guarantee that the patients will have access to assisted coughing when and as often as they need it during infections. All of the patients in this study had very dedicated, capable, and willing care providers who assisted coughing during chest infections, at times every 5 to 10 min, essentially around the clock. Patients without dedicated and effective care providers would not succeed in avoiding conventional invasive management.

Before initiating this protocol, we informed patients to contact us at the first sign of a chest infection, and we would provide them with an oximeter and respiratory muscle aids to avert hospitalization. However, two consecutive patients presented to us only after they had already developed severe oxyhemoglobin desaturation and pneumonia, and they required hospitalization and were intubated. We therefore believe that an oximeter in the home is especially important for immediate feedback to the patient during chest infections. Pneumonia and need for intubation are very unlikely when the SaO2 baseline is maintained at > 94% without supplemental oxygen.

Although the delivered volumes we used may appear to be high, the efficacy of noninvasive ventilation depends on the alertness of the CNS during sleep to decrease insufflation leakage to avoid asphyxia and hypercapnia, and to obstruct the airway and increase leakage to decrease insufflation volumes to avoid hyperventilation.4 Although we monitored PETCO2 during sleep in the past,15 16 we no longer think that this is necessary. As noted in the "Results," all treated patients were asymptomatic for under- or overventilation, and all maintained essentially normal PETCO2 levels. For patients using only nocturnal noninvasive IPPV, daytime hypercapnia was usually mild and well-tolerated when SaO2 remained within normal limits.

Most protocol patients first used noninvasive IPPV during chest infections and were weaned to ongoing nocturnal use of noninvasive IPPV after their first averted hospitalizations. Oximetry was useful in guiding the eventual ongoing daytime need and nocturnal use of noninvasive IPPV.14 16 17 Nonprotocol patients tended to have repeated episodes of respiratory failure until being introduced to the protocol or undergoing tracheostomy.

Although both tracheostomy and noninvasive respiratory aids can prolong life, tracheostomy is associated with numerous complications,18 an initial mean hospital stay of 72 days, and more hospitalization days subsequently than is noninvasive management.2 It might be that the significantly lower hospitalization rates of noninvasive vs tracheostomy mechanical ventilation users are related to reduced pulmonary inflammation, maintenance of physiologic airway defense mechanisms, and maintenance of pulmonary health long-term by avoiding invasive respiratory interventions. Further, patients almost invariably prefer noninvasive aids over tracheostomy for safety, convenience, appearance, comfort, facilitating effect on speech, sleep, and swallowing, and general acceptability.19 Noninvasive aids should also, therefore, be preferred by clinicians when effective.

Our patients were trained in the use of respiratory muscle aids, including volume-cycled ventilators, in the clinic and home settings. Unlike the pressure-cycled machines conventionally used for nocturnal nasal IPPV, the volume-cycled machines permitted the air stacking necessary to maximize cough flows. Fourteen noninvasive IPPV users went on to require definitive 24-h ventilatory support using volume-cycled ventilators without as yet ever being hospitalized. Thus, provided that proper attention is given to assisting cough, this study demonstrates that even long-term and full-time need for ventilatory support can be safely provided noninvasively.


   Footnotes
 
Abbreviations: IPPV = intermittent positive-pressure ventilation; MIC = maximum insufflation capacity; MI-E = mechanical insufflation-exsufflation; PCF = peak cough flow; PETCO2 = end-tidal carbon dioxide tension; SaO2 = arterial oxygen saturation; VC = vital capacity

Supported by a grant from the National Institute on Disability and Rehabilitation Research (H133 P 70011).

Received for publication June 23, 1999. Accepted for publication May 23, 2000.


   References
TOP
 Abstract
 Introduction
 Materials and Methods
 Results
 Discussion
 References
 

  1. Bach, JR (1996) Conventional approaches to managing neuromuscular ventilatory failure. Bach, JR eds. Pulmonary rehabilitation: the obstructive and paralytic conditions ,285-301 Hanley & Belfus Philadelphia, PA.
  2. Bach, JR, Rajaraman, R, Ballanger, F, et al (1998) Neuromuscular ventilatory insufficiency: the effect of home mechanical ventilator use vs oxygen therapy on pneumonia and hospitalization rates. Am J Phys Med Rehabil 77,8-19[CrossRef][ISI][Medline]
  3. Mier-Jedrzejowicz, A, Brophy, C, Green, M (1988) Respiratory muscle weakness during upper respiratory tract infections. Am Rev Respir Dis 138,5-7[ISI][Medline]
  4. Bach, JR (1996) Prevention of morbidity and mortality with the use of physical medicine aids. Bach, JR eds. Pulmonary rehabilitation: the obstructive and paralytic conditions ,303-329 Hanley & Belfus Philadelphia, PA.
  5. Bach, JR (1995) Amyotrophic lateral sclerosis: predictors for prolongation of life by noninvasive respiratory aids. Arch Phys Med Rehabil 76,828-832[CrossRef][ISI][Medline]
  6. Bach, JR, Saporito, LR (1996) Criteria for extubation and tracheostomy tube removal for patients with ventilatory failure: a different approach to weaning. Chest 110,1566-1571[Abstract/Free Full Text]
  7. Kang, SW, Bach, JR (2000) Maximum insufflation capacity: the relationships with vital capacity and cough flows for patients with neuromuscular disease. Am J Phys Med Rehabil 79,222-227[Medline]
  8. Emery, AEH (1994) Diagnostic criteria for neuromuscular disorders. European Neuromuscular Center Baarn, The Netherlands.
  9. Bach, JR, Alba, AS, Saporito, LR (1993) Intermittent positive pressure ventilation via the mouth as an alternative to tracheostomy for 257 ventilator users. Chest 103,174-182[Abstract/Free Full Text]
  10. Bach, JR (1994) Update and perspectives on noninvasive respiratory muscle aids: part 1. The inspiratory muscle aids. Chest 105,1230-1240[Free Full Text]
  11. Leith DE. Cough. In: Brain JD, Proctor D, Reid L, eds. Lung biology in health and disease: respiratory defense mechanisms, part 2. New York, NY: Marcel Dekker 1977; 545–592
  12. Bach, JR (1993) Mechanical insufflation-exsufflation: comparison of peak expiratory flows with manually assisted and unassisted coughing techniques. Chest 104,1553-1562[Abstract/Free Full Text]
  13. Bach, JR (1994) Update and perspectives on noninvasive respiratory muscle aids: part 2. The expiratory muscle aids. Chest 105,1538-1544[Free Full Text]
  14. Hill, NS, Eveloff, SE, Carlisle, CC, et al (1992) Efficacy of nocturnal nasal ventilation in patients with restrictive thoracic disease. Am Rev Respir Dis 145,365-371[ISI][Medline]
  15. Bach, JR, Alba, AS (1994) Sleep and nocturnal mouthpiece IPPV efficiency in post-poliomyelitis ventilator users. Chest 106,1705-1710[Abstract/Free Full Text]
  16. Bach, JR, Alba, AS (1990) Management of chronic alveolar hypoventilation by nasal ventilation. Chest 97,52-57[Abstract/Free Full Text]
  17. Jimenez, JFM, Sanchez de Cos Escuin, J, Vicente, CD, et al (1995) Nasal intermittent positive pressure ventilation: analysis of its withdrawal. Chest 107,382-388[Abstract/Free Full Text]
  18. Bach, JR, Intintola, P, Alba, AS, et al (1992) The ventilator-assisted individual: cost analysis of institutionalization versus rehabilitation and in-home management. Chest 101,26-30[Abstract/Free Full Text]
  19. Bach, JR (1993) A comparison of long-term ventilatory support alternatives from the perspective of the patient and care giver. Chest 104,1702-1706[Abstract/Free Full Text]



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