Alternatives to Endotracheal Intubation for Patients with Neuromuscular Diseases

Authors: Emilio Servera, MD Jesús Sancho, MD Ma Jesús Zafra, RN Ana Catalá, RN Pedro Vergara, RT Julio Marín, MD Affiliations: From the Rehabilitation and Ventilation Unit, Department of Respiratory Medicine, Hospital Clínico Universitario, Universitat de València, Valencia, Spain. Correspondence: All correspondence and requests for reprints should be addressed to Emilio Servera, MD, Avda. Blasco Ibáñez 84, E 46021 Valencia, Spain. 0894-9115/05/8411-0851/0 American Journal of Physical Medicine & Rehabilitation Copyright 2005 by Lippincott Williams & Wilkins DOI: 10.1097/01.phm.0000184097.17189.93 RESEARCH ARTICLE Alternatives to Endotracheal Intubation for Patients with Neuromuscular Diseases ABSTRACT Pulmonary Servera E, Sancho J, Zafra MJ, Catalá A, Vergara P, Marín J: Alternatives to endotracheal intubation for patients with neuromuscular diseases. Am J Phys Med Rehabil 2005;84:851 857. Objective: To evaluate the usefulness of continuous noninvasive mechanical ventilation and mechanical coughing aids to avoid endotracheal intubation and tracheostomy during episodes of acute respiratory failure in patients with neuromuscular disease. Design: We conducted a prospective cohort study at the respiratory medicine ward of a university hospital to study the success rate of the use of continuous noninvasive mechanical ventilation and manually and mechanically (CoughAssist) assisted coughing to avert endotracheal intubation in 24 consecutive episodes of acute respiratory failure for 17 patients with neuromuscular disease. The noninvasive mechanical ventilation and coughing aids were used to reverse decreases in oxyhemoglobin saturation and relieve respiratory distress that occurred despite oxygen therapy and appropriate medication. Noninvasive mechanical ventilation was delivered by volume ventilators (Breas PV 501) alternating nasal/oronasal and oral interfaces. Results: Noninvasive management was successful in averting death and endotracheal intubation in 79.2% of the acute episodes. There were no significant differences in respiratory function between the successfully treated and unsuccessfully treated groups before the current episode. Bulbar dysfunction was the independent risk factor for failure of noninvasive treatment (P 0.05; odds ratio, 35.99%; 95% confidence interval, 1.71 757.68). Conclusions: Intubation can be avoided for some patients with neuromuscular disease in acute respiratory failure by some combination of noninvasive mechanical ventilation and mechanically assisted coughing. Severe bulbar involvement can limit the effectiveness of noninvasive management. Key Words: Noninvasive Ventilation, Assisted Coughing, Hypoxemic Respiratory Failure, Neuromuscular Disease, Mechanical Insufflation Exsufflation November 2005 Alternatives to Endotracheal Intubation for Patients with Neuromuscular Diseases 851

Acute respiratory failure (ARF) caused by respiratory muscle weakness is the most common cause of death in patients with chronic neuromuscular diseases (NMDs), 1 and most of these ARF episodes are triggered by otherwise benign upper respiratory tract infections. 2 4 During these acute episodes, respiratory (inspiratory and expiratory) muscle strength decreases dramatically, 3 resulting in ineffective alveolar ventilation, ineffective coughing, and respiratory distress. 5 When this occurs, patients are transferred to an intensive care unit for endotracheal intubation (ETI) and continuous mechanical ventilatory support. ETI, however, has associated morbidity, 6,7 including nosocomial pneumonia and tracheal mucosa damage, and in NMD patients, difficulties in ventilatory weaning commonly result in the patient undergoing tracheostomy. 8 Moreover, around 33.7% of amyotrophic lateral sclerosis (ALS) patients have been reported to categorically refuse ETI. 9 Noninvasive mechanical ventilation (NIV) has been reported to decrease the need for ETI of patients during acute exacerbations of chronic obstructive pulmonary disease, 10,11 and NIV and mechanically assisted coughing have been used for decades to prolong life as an alternative to tracheostomy (the only alternative to support life in those patients who refuse ETI) and to decrease hospital admissions for patients with NMD. 12 14 The most important and commonly used method of NIV in NMD patients is intermittent positive-pressure ventilation delivered via nasal or oronasal mask during sleep and via a mouthpiece interface for daytime ventilatory support. 12,13 The purpose of ABBREVIATIONS ALS: amyotrophic lateral sclerosis ETI: endotracheal intubation FEV 1 : forced expiratory volume in 1 sec FVC: forced vital capacity %FVC: percentage predicted FVC MIC: maximum insufflation capacity NIV: noninvasive ventilation NMD: neuromuscular disease PCF: peak cough flow PCF MIC : manually assisted PCF PImax: maximum mouth inspiratory pressure PEmax: maximum expiratory pressure SpO 2 : pulse oxyhemoglobin saturation this study was to determine the effectiveness of the use of continuous NIV together with coughing aids to avoid ETI for patients with NMD during acute pulmonary illnesses that cause continuous respirator dependence. MATERIALS AND METHODS Patients This is a prospective study of all of the patients with NMD admitted between March 2001 and June 2003 to the respiratory medicine ward via the emergency service of a university hospital. All had acute hypoxemic respiratory illness that necessitated mechanical ventilation and oxygen therapy to relieve respiratory distress. After informed consent had been obtained, admission criteria to the study was the need for both continuous mechanical ventilation with no ventilator-free breathing ability and the need for aggressive coughing assistance to relieve respiratory distress and decreases in oxyhemoglobin saturation (SpO 2 )to 90% despite supplemental oxygen and specific drug therapy. Exclusion criteria were the inability to use NIV because of the inability to use the noninvasive interfaces or because of previous barotrauma or pulmonary bullae. All the patients but one were followed up in our rehabilitation ventilator unit as outpatients and were trained in NIV and assisted coughing before hospitalization, receiving periodic clinical and pulmonary function assessments. Before hospitalization, all patients were also asked to sign advance directives concerning ETI and tracheostomy. Diagnosis and Functional Assessment Procedures The diagnosis of NMD was made by a consulting neurologist. Bulbar impairment was estimated using the Norris score bulbar subscale. 15 Pulmonary function and cough capacity variables were recorded 1 3 mos before the acute illness, when the patients were medically stable. All measurements were made while the subjects were seated. Spirometry was performed (MS 2000, C. Schatzman, Madrid, Spain) using a mouthpiece and a nose clip. Forced vital capacity (FVC), forced expiratory volume in 1 sec (FEV 1 ), and FEV 1 /FVC were recorded in accordance with European Respiratory Society guidelines and suggested normal values. 16 Maximum mouth inspiratory pressure (PImax) and maximum expiratory pressure (PEmax) were measured (Electrometer 78.905A, Hewlett-Packard, Boston, MA) with both cheeks held. PImax was performed close to residual volume, PEmax was performed close to total lung capacity, and the pressures sustained for 1 sec were used. Peak cough flows were measured using a sealed oronasal mask (King Mask, King System, 852 Servera et al. Am. J. Phys. Med. Rehabil. Vol. 84, No. 11

Noblesville, IN) connected to a pneumotachograph spirometer (MS 2000, C. Schatzman) when the subjects performed a maximal cough effort after a deep inspiration. For all the functional evaluations described above, three measurements with 5% variability were recorded, and the highest value was used for the data analysis. Inpatient Therapeutic Procedures During crises, all patients were provided with full medical care, with careful attention to details and psychosocial support. An easily masticated and swallowed diet was provided with small but frequent meals. Ventilatory Support Noninvasive intermittent positive-pressure ventilation was delivered via a volume-cycled ventilator using the assist/control mode (PV 501, Breas Medical, Mölndal, Sweden). If the patient had premorbidly been using NIV, changes in ventilation variables were made as needed to relieve dyspnea during the acute episode. If the patients had not been using a ventilator at home, the ventilator was initially adjusted to obtain a tidal volume of about 15 ml/kg, an inspiratory/expiratory ratio of 1/1.2 or 1/1.5, a respiratory rate near spontaneous breathing that was usually reduced as the patient s spontaneous breathing rate decreased with assisted ventilation, and trigger sensitivity of 0.5 cm H 2 O. The ventilator settings were then readjusted based on the patient s comfort and arterial blood gas values to attempt to maintain arterial oxygen saturation at 95% and PaCO 2 at 45 mm Hg (Radiometer ABL 520, Radiometer, Copenhagen, Denmark). Supplemental oxygen was delivered when necessary to increase pulse SpO 2 (Oxipulse, Radiometer) to 95%. Patients received NIV using nasal interfaces (Healthdyne, Marietta, GA) or oronasal masks (Mirage NV, Resmed, Madrid, Spain) during the night in accordance with the presence of mouth leaks. During the day, a simple 15-mm mouthpiece (Puritan Bennett, Carlsbad, CA) or, if patients had oral leaks, a Lipseal mouthpiece (Respironics International, Murrysville, PA) was used. All patients became continuously dependent on NIV with no significant ventilator-free breathing ability as hypercapnia resolved. ETI was considered (if the patient had previously agreed to it) when NIV and mechanically assisted coughing could not relieve respiratory distress or lethargy nor ameliorate rapidly decreasing SpO 2 and hypercapnia. 17,18 As the patients physical condition improved (which was made apparent by relieved accessory respiratory muscle use, improved chest wall movements, and lessened respiratory distress), NIV use became intermittent and assisted coughing was used more sparingly. Because simply using the mouthpiece for intermittent positive-pressure ventilation does not in any way impair speech or eating, patients received nutritional support and fluids when receiving NIV via a mouthpiece. NIV weaning was facilitated as patients took fewer and fewer mouthpiece intermittent positive-pressure ventilation assisted breaths as needed while maintaining normal SpO 2, pulse rate, and normal breathing frequency. Expiratory Muscle Aids Coughing capacity was increased mainly by mechanically assisted coughing applied by the nurses, respiratory therapist, and trained relatives. Mechanically assisted coughing (CoughAssist, J. H. Emerson, Cambridge, MA) was used at least twice every 8 hrs and whenever SpO 2 decreased, ventilator peak inspiratory pressure increased, or the patient had an increase in dyspnea or sense of retained secretions. It was often used as frequently as every 5 10 mins. The CoughAssist was applied via a full-face mask (King Mask). It was set at 40 cm H 2 O of insufflation and 40 cm H 2 O of exsufflation pressure, with an insufflation/exsufflation time ratio of 2 secs/3 secs and a pause of 1 sec between each cycle. 19 Eight cycles were applied in every session. The patient was asked to keep his airway open while a thoracoabdominal thrust was applied during the exsufflation cycle. As the patients clinical status improved, the CoughAssist was used less and simple manually assisted coughing was used more. A manual resuscitator (Revivator, Hersill, Madrid, Spain) insufflated the patient s lungs to the highest volume that could be retained with a closed glottis (maximal insufflation capacity). The insufflations were provided via oronasal masks (King Mask). The patient was then asked to cough forcefully as a thoracoabdominal thrust was applied. 20 Study Endpoints and Statistical Analysis Treatment success was defined as successful management of a respiratory failure requiring continuous support with NIV without resorting to ETI or tracheostomy. Treatment failure was defined as death or ETI. Data were expressed as mean SD. Data comparisons were performed with the Mann- Whitney test, the analysis of variance test, and Wilcoxon s test. Categorical data were compared using Fisher s exact test. Forward stepwise logistic regression was used for the risk factor for treatment failure assessment. The level for statistical significance was taken as P 0.05. The statistical analysis was performed with the statistical package SPSS 10.0 for Windows (SPSS, Chicago, IL). November 2005 Alternatives to Endotracheal Intubation for Patients with Neuromuscular Diseases 853

RESULTS All patients in acute respiratory distress without exclusion criteria agreed to use NIV for ventilatory support instead of ETI, and none were excluded from the study. A total of 17 patients (ten male and seven female patients; age, 48.67 20.93 yrs) hospitalized a total of 24 times were enrolled. Before 19 of these 24 hospital admissions (79.2%), the patients had been trained in NIV and assisted coughing and were using it at home a mean of 11.89 6.55 hrs/day (range, 8 24 hrs/day) via oronasal or nasal (three) interfaces for sleeping and a mouthpiece when awake. Four patients (23.52%) signed advance directives refusing ETI. A total of 11 patients were diagnosed with ALS, including five patients with bulbar dysfunction (severe in four instances); four patients were diagnosed with Duchenne s muscular dystrophy; one patient was diagnosed with transverse myelitis; and one patient was diagnosed with nonspecific myopathy. Two ALS patients also had chronic bronchitis, but they were included because they had refused invasive interventions and they did not have bullous emphysema. The causes of ARF were respiratory tract infection (acute bronchitis) (17 patients), pneumonia (six patients), and atelectasis caused by mucus plugging (one patient). When hospitalized, none of the patients were able to generate effective unassisted peak cough flows (flows of 160 liters/min) and all needed manually or mechanically assisted coughing. 21 At admission to the hospital, none of the patients had a gastrostomy tube. The mean length of continuous need for NIV was 7.00 6.50 days (range, 2 21 days; median, 5 days). The mean hospital stay was 12.05 7.03 days. Noninvasive management failed for five episodes (20.8%). Three patients (12.5%), with both ALS and severe bulbar dysfunction, underwent ETI (day 2, day 2, and day 5) with repeated increases in ventilator peak inspiratory pressure, severe decreases in SpO 2, increases in PaCO 2, and respiratory distress. These three patients were ultimately discharged and returned home using ventilatory support via a tracheostomy tube and nutrition via a percutaneous endoscopic gastrostomy tube. Two patients died (8.3%). One was an ALS patient without bulbar dysfunction who had an unexpected cardiac arrest. The other was an ALS patient with severe bulbar impairment who tolerated NIV poorly and for whom assisted coughing was ineffective because of airway stridor. He received palliative medical therapy because he refused ETI and tracheostomy. The other three patients who refused ETI were successfully managed with NIV. In 19 of the acute respiratory episodes (79.2%), the noninvasive management was successful with improvement in the clinical condition and blood gas exchange (Table 1). None of the patients with hypercapnia at hospital admission needed to be intubated. In two cases, nonrespiratory complications necessitated parenteral nutrition (paralytic ileus during one episode and ascites due to hypoproteinemia in another). Both resolved and only resulted in prolonging the hospital stay. In another acute episode, nosocomial pneumonia was diagnosed and resolved with treatment. Data for pulmonary function and coughing capacity variables are shown in Table 2. No statistically significant differences were found between those using noninvasive management successfully or unsuccessfully, but from the time of the examination shown here to the time of hospital admission (range, 1 3 mos), there was a noticeable worsening in bulbar involvement of the patients for whom mechanically assisted coughing failed (Norris bulbar score: 11 5.35 vs. 3 5.54, P 0.05). 17 The logistic regression analysis for the risk of treatment failure found that the bulbar dysfunction (P 0.05; odds ratio, 35.99; 95% confidence TABLE 1 Arterial blood gases in the successfully treated group a Arterial Blood Gases Before Admission At Hospital Admission At End of Stay ph 7.43 0.04 7.38 0.10 7.42 0.04 PaO 2, mm Hg 79.58 7.33 60.86 15.61 b 79.04 6.50 c PaCO 2, mm Hg 39.67 4.14 49.15 18.11 39.38 3.74 SaO 2, % 95.83 1.47 86.06 15.19 96.08 1.50 c PaO 2, partial pressure of arterial oxygen; PaCO 2, partial pressure of carbon dioxide in arterial gas; SaO 2, arterial oxygen saturation. a At the time of obtaining the arterial blood samples at admission to the hospital (n 19), all patients were receiving oxygen therapy, ten were using noninvasive mechanical ventilation, and nine were not. Before admission and at the end of stay, FiO 2 was 21%. The values are expressed as mean SD. b P 0.05 (comparing previous values with hospital admission values). c P 0.05 (comparing hospital admission values with end-of-stay values). 854 Servera et al. Am. J. Phys. Med. Rehabil. Vol. 84, No. 11

TABLE 2 Previous functional data of the groups successfully treated (n 19) and unsuccessfully treated (n 5) with noninvasive management Success Failure P Value Age, yrs 44.11 21.28 66.00 2.65 0.17 FVC, liters 0.77 0.36 1.10 0.97 0.54 FVC% 24.61 11.10 41.00 26.98 0.23 MIC, liters 1.68 0.52 1.33 1.00 0.33 FEV 1 /FVC 87.95 13.41 91.03 10.84 0.65 PCF, liters/sec 2.08 0.73 2.01 0.67 0.71 PCF MIC, liters/sec 3.85 1.06 3.40 2.19 1.00 PImax, cm H 2 O 38.12 21.98 30.66 13.20 0.71 PEmax, cm H 2 O 33.87 31.99 41.66 20.59 0.35 n 19 5 FVC, forced vital capacity; %FVC, percentage predicted FVC; MIC, maximal insufflation capacity; FEV 1, forced expiratory volume in 1 sec; PCF, peak cough flow; PCF MIC, manually assisted PCF; PImax, maximal inspiratory pressure; PEmax, maximal expiratory pressure. Values are expressed as mean SD. interval, 1.71 757.68) was the independent predictive factor for treatment failure. After the 19 successfully managed episodes (79.2%), 12 of the 17 patients continued to be stable 3 mos posthospitalization and went back to using NIV a mean of 12.80 6.20 hrs/day at home (range, 8.00 24.00 hrs/day), alternating an oronasal mask with a nasal mask during sleep and a mouthpiece when awake. No statistically significant differences were found between the time using NIV before and 3 mos after hospital admission. Two patients died, unpredictably, in their sleep. Both had ALS and chronic obstructive pulmonary disease. The two patients using tracheostomy ventilation were also stable 3 mos posthospitalization. DISCUSSION The main finding of our study was that in many neuromuscular patients without severe bulbar impairment, ARF requiring continuous ventilation dependence could be managed without resorting to ETI. Moreover, all of the patients with NMD other than ALS were treated successfully; none of them had significant bulbar impairment. To be included in the study, all of our patients had to become continuously ventilator dependent during the acute episode. It has been known for 50 yrs that NIV can be used for continuous respiratory support 22 in stable patients with NMD; in this study, we wanted to show that ARF requiring continuous ventilatory support could be managed without resorting to ETI in NMD. This presumes that noninvasive management is a desirable alternative to ETI, the efficacy of both being equal. Successful noninvasive intervention requires cooperative patients, specifically trained staff/family members, and appropriate equipment (different interfaces and mechanical coughing aids). This approach is often possible in non intensive care settings. 23 Avoidance of intensive care reduces cost and decreases suffering and complications related to invasive management. Noninvasive management can also prevent death for patients rejecting ETI/tracheotomy as an option, so long as they are not suffering severe bulbar impairment. 14 Recent studies conducted in intensive care units evaluated the usefulness of NIV as first-line intervention for NMD patients in acute decompensation. 24 26 Vianello et al. 24 studied the usefulness of NIV delivered by a volume ventilator using the assist/control mode (the same procedure as in our study) for 14 NMD patients by means of comparing them with 14 matched historical controls, and they found that NIV was safer and an effective alternative to ETI. The NIV patients received ventilation via custom-made nasal interfaces complemented at times by a cricothyroid mini-tracheostomy to clear airway secretions. The authors do not describe using assisted coughing before resorting to a mini-tracheostomy. From the information provided, one can deduce that the duration of their continuous NIV was shorter than ours, a fact that would justify the absence of need to interchange interfaces. Their NIV group had intensive care stays of 13.6 9.7 days and a treatment failure rate of 28.57%, which are similar to our outcomes (12.05 7.03 days and 20.8%, respectively). However, in comparison with the study by Vianello et al., 24 we counted the hospital stay beyond the intensive care unit stay. If mini-tracheostomy is considered as an invasive procedure, the noninvasive treatment failure rate in the patients of Vianello et al. 24 was 57.14%, much greater than ours. This difference is probably due to the more effective handling of secretions in our group by means of mechanical aids administered from the time the patient feels the need for them and also due to SpO 2 monitoring and minimization of supplemental oxygen therapy. November 2005 Alternatives to Endotracheal Intubation for Patients with Neuromuscular Diseases 855

Anytime the patient s SpO 2 decreased to below 95%, mechanically assisted coughing was used to expel secretions and re-normalize SpO 2. Our treatment successes highlight the importance of assisted coughing interventions. 2,12,13 In a more recent study by Vianello et al., 25 11 neuromuscular patients were treated noninvasively with continuous NIV and mechanical insufflation exsufflation during respiratory tract infections. In this study, the need for mini-tracheostomy was considered treatment failure. The rate of treatment failure was lower in the noninvasive group (18.8%) and similar to our results. However, in 45.5% of the patients, it was necessary to perform a bronchoscopy to remove airway secretions. In our study, none of the patients needed a bronchoscopy. This difference is probably related to the lower pressures used in the study by Vianello et al. 25 (11.1 3cmH 2 O for insufflation and 33.2 4.6 cm H 2 O for exsufflation). Rabinstein and Wijdicks 26 studied the usefulness of NIV using bi-level positive airway pressure devices during myasthenic crises in 11 episodes of nine selected patients. Unlike the studies by Vianello et al. and ours, the patients did not have pulmonary pathogeneses for their hospitalizations but rather a generalized worsening of muscle function. Use of NIV averted ETI for 63.64% of their patients but failed for previously hypercapnic patients. The authors do not describe what type of NIV interface they used nor what bi-level positive airway pressure settings were used, nor how they handled secretions, nor whether the secretions posed problems during NIV, but they do state that none of the failures was due to excessive respiratory secretions. Despite the fact that their use of NIV was shorter than in our study, NIV with bilevel positive airway pressure did not maintain adequate ventilatory support for their hypercapnic patients. This can best be explained by their using inadequate bi-level positive airway pressure spans for full respiratory muscle rest and ventilatory support. By using our volumetric devices, providing full noninvasive ventilatory support, and by alternating interfaces and using a convenient mouthpiece for daytime support, none of our hypercapnic patients had to undergo ETI, and NIV permitted adequate gas exchange without which the patients would have required ETI for ventilatory support. 17 On reviewing the results obtained by conventional management, we can see that in a recent study 8 invasive ventilation failed for 29% of NMD patients who died because of ARF. For those who survived, the median time required for weaning before discharge to the community was 10 wks. The results of our study show that continuous NIV resulted in less mortality (8.3%) and a shorter hospital stay (12.05 7.03 days). Thus, there are likely to be fewer complications associated with NIV, including fewer cases of nosocomial pneumonia. Another study 27 in patients with ALS demonstrated a mortality rate of 32.8% when respiratory failure was the primary diagnosis. Only two of our nine ALS patients died, one of whom died after refusing treatment. If one analyzes our results, although the size of the sample is small, it may be surprising to see that in the previous functional examination there were no differences between the peak cough flows of the patients for whom noninvasive management was subsequently successful or a failure during their hospital stay. But if one observes the rapid worsening in bulbar function, from the time of their functional examination to the time of hospitalization of the patients who did not respond well to noninvasive management, one can accept that the reason for this was the alteration in the spontaneous or assisted coughing that is associated with this severe bulbar involvement. 13,14,23,28 Literature data show that long-term NIV was ineffective or not tolerated by NMD patients with severe bulbar dysfunction. 13,14,29 With current knowledge, we can say that bulbar dysfunction can contribute to the development of obstructive episodes in the upper airway, and malfunction of the upper airway muscles can increase resistance to airflow 30,31 and hamper the expulsion of airway secretions. This can impede successful use of NIV and assisted coughing. 28 Likewise, with our acutely ill patients, NIV does not succeed for very long when assisted coughing is ineffective, and ETI or palliative treatment become the only alternatives. 29,32 In conclusion, for patients who do not have severe bulbar impairment, noninvasive management carried out with a suitable combination of NIV and mechanically assisted coughing used during acute episodes can be an effective alternative to invasive ventilation to maintain life. Moreover, this could be the only way to maintain life for NMD patients who refuse ETI and tracheostomy. ACKNOWLEDGMENTS We thank Drs. E. A. Oppenheimer and J. R. Bach for their invaluable help in reviewing the manuscript. REFERENCES 1. Haverkamp LJ, Appel V, Appel SH: Natural history of amyotrophic lateral sclerosis in a database population: Validation of a scoring system and a model for survival prediction. Brain 1995;118:707 19 2. 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