Non-Invasive Ventilation Reduces Respiratory Tract Infections in Children With Neuromuscular Disorders

Transcription

1 Pediatric Pulmonology 43:67 71 (2008) Non-Invasive Ventilation Reduces Respiratory Tract Infections in Children With Neuromuscular Disorders C. Dohna-Schwake, MD,* P. Podlewski, MD, T. Voit, MD, and U. Mellies, MD Summary. Non-invasive ventilation (NIV) has been shown to improve gas exchange and survival in patients with chronic neuromuscular disorders. Little is known about its influence on respiratory tract infections (RTIs). Twenty-four patients with regular use of NIVand 11 patients without NIV with neuromuscular disorders answered a questionnaire concerning the use of NIV and assisted coughing techniques, the status of influenza and pneumococcus vaccination, and the frequency and severity of RTIs. Additionally, we performed a retrospective chart review of twelve patients who were ventilated over a period of at least 5 years. In the first year of NIV consultations of a general practitioner due to RTI decreased from to per year (P < 0.005), the number of antibiotic treatment due to RTI decreased from to per year (P < 0.005) and the number of hospital admissions due to RTI decreased from to per year (P < 0.005). Vaccinations against influenza and/or pneumococcus did not have a significant influence on the rate of infections. In 12 patients using NIV for more than 5 years the incidence of RTI requiring hospital admission decreased from /year in the pre-ventilation period to /year in the NIV period (P < 0.005). NIV had a favorable impact on respiratory infectious complications in children with neuromuscular disorders. Pediatr Pulmonol. 2008; 43: ß 2007 Wiley-Liss, Inc. Key words: non-invasive ventilation; assisted coughing; respiratory tract infection. INTRODUCTION Frequent respiratory tract infections (RTIs) significantly contribute to the morbidity and mortality of patients with advanced neuromuscular disorders and respiratory muscle weakness. In 2003 and 2004, 45 children older than 6 months with neurologic or neuromuscular disorders died of influenza infection in the US. 1 In spinal muscular atrophy type I respiratory complications 2,3 lead to death during the first year of life, if patients were not invasively ventilated via either tracheotomy or recurrent intubation. Incidences of pneumonia of 0.8/year for Duchenne muscular dystrophy (DMD) and of 1/year for other myopathies are reported. 4 We could show that in a mixed pediatric population of neuromuscular disorders almost half of the patients were at least once admitted to a hospital due to severe chest infection. 5 Specific treatment of respiratory complications is now available for most patients with respiratory muscle weakness. Non-invasive ventilation (NIV) is the standard therapy of chronic respiratory failure and nocturnal hypoventilation. 6 9 But it has also been shown to be effective during acute deterioration of respiratory function during chest infection. 10 Insufficient cough leads to reduced pulmonary secretion clearance and therefore increases the risk of pneumonia. Assisted coughing techniques such as glossopharyngeal breathing, the in-/exsufflator or IPPB (Intermittent Positive Pressure Breathing) assisted ß 2007 Wiley-Liss, Inc. coughing demonstrated positive effects on peak cough flows in neuromuscular patients Additional treatment such as early antibiotic treatment or influenza and pneumococcal vaccination may help to prevent severe respiratory complications. Reducing both incidence and severity of chest infections is a major goal of therapy in patients with respiratory muscle weakness, as it determines an important part of their quality of life. We hypothesize that the regular use of NIV reduces the rate and severity of RTIs. Therefore, we retrospectively explored the frequency of medical Department of Pediatrics and Pediatric Neurology, University of Essen, Essen, Germany. The authors declare no competing interests. Grant sponsor: VitalAire Deutschland GmbH; Grant sponsor: Heinen und Löwenstein GmbH. *Correspondence to: Dr. C. Dohna-Schwake, MD, Department of Pediatrics and Pediatric Neurology, University of Essen, Hufelandstr. 55, Essen, Germany. [email protected] Received 17 May 2007; Revised 24 August 2007; Accepted 23 September DOI /ppul Published online in Wiley InterScience (

2 68 Dohna-Schwake et al. treatment in neuromuscular patients using NIV and in a non-ventilated group. PATIENTS AND METHODS Patients Forty patients with neuromuscular disorders referred to our clinic for respiratory evaluation were included in the study. Thirty-five (87.5%) answered the questionnaire. Twenty-four patients had been using NIV for at least 1 year. Patients composed of 10 with spinal muscular atrophy SMA (7 type II, 3 type I), nine with congenital muscular dystrophy (5 merosin-negative, 2 Ullrich CMD, 2 unclassified CMD), three with centronuclear myopathy, one with DMD and one with hereditary sensomotoric neuropathy (HSMN). The indication to start NIV was given, when either overnight sleep study (polygraphy and capnometry) revealed nocturnal hypoventilation, or when patients were admitted with daytime hypercapnia. Of 11 patients not using NIV four patients suffered from SMA type II, three from DMD, three from CMD (1 merosin-negative, 1 rigid spine CMD, 1 unclassified), and one from centronuclear myopathy. Caregivers of all patients gave written consent to participate in this study. Questionnaire Aim of the questionnaire was the evaluation of infectious complications of the respiratory tract before and after initiation of NIV in children with neuromuscular disorders. Use of assisted coughing and status of pneumococcus- and influenza-vaccination were also evaluated. The questionnaire is divided into four parts. In part I patients were asked about their use of NIV: date of beginning; duration of ventilation per night; frequency of ventilation (nights/week). Patients indicated if there had been periods without ventilation or periods with intensified ventilation, and whether these latter periods were related to RTIs. Part II of the questionnaire scrutinized the usage of IPPB assisted coughing: frequency of assisted coughing maneuvers per day and duration of single application (minutes). In case of periods with intensified assisted coughing, we asked if it correlated with RTI. In part III patients were asked to quantify per year the number of general practitioner consultations, the number of antibiotic treatment and the number of hospital admission due to RTI before start of NIV compared to the first year with NIV. Patients were also asked to state if they had a history of invasive ventilation. Part IV surveyed the status of vaccination against influenza and/or pneumococcus. In addition, we performed a retrospective chart review of all patients who were ventilated for at least 5 years. In particular we compared the number of hospital admissions due to RTI before start of NIV to those during NIV. The incidence per year was calculated by dividing the number of hospital admissions through either the years without or with NIV. RTI in this association was defined as acute respiratory deterioration with fever and/or increased amount of respiratory secretions. Statistics Analysis was performed with Statistica 6.0 software package (StatSoft, Inc., Tulsa, OK). Data are presented as mean and standard deviation. Comparison of two groups was performed using the Mann Whitney U-test, and comparison of values before and after NIV was performed using the paired Wilcoxon-test. Correlations were calculated by Spearman s rank test. P < 0.05 was considered significant. RESULTS Thirty-five of a total of 40 patients returned the questionnaire (87.5%). Mean IVC% was significantly higher in the non-ventilated group than in the ventilated group (41 21% vs %). Age distribution of the two groups did not differ significantly ( years vs years). Six of 24 patients with NIV had been admitted to Intensive Care Unit ICU due to severe chest infections (four patients once, one patient twice, one patient four times). Eight of 10 ICU admissions occurred before initiation of NIV and 2 of 10 patients needed intubation. None of the patients needed intubation after initiation of NIV. In 5 of 24 children NIV was first introduced during acute RTI. All patients on NIVused pressure controlled devices via nose-mask or full face mask. Ventilation was started months before participation in this survey. Overall NIV was well tolerated without relevant side effects. All but three patients used the ventilator 7 nights/week. Three used it 5 6 nights/week. Mean duration of nocturnal NIV was stated to last hr ( hr), the mean ventilator hours per week were Fifteen patients in the ventilated group used IPPBassisted coughing technique on a regular basis ( times/day), two patients only during RTIs. Mean duration of a single assisted coughing application was stated to last min. The total number of visits to a general practitioner decreased after initiation of NIV from to times/year (P < 0.005). Patients of the nonventilated group visited their general practitioner times/year (P ¼ 0.06). The frequency of RTIs requiring antibiotic treatment significantly decreased from RTI/year in preventilation period to RTI/year in ventilation

3 NIV and Respiratory Tract Infections 69 period (P < 0.005). Patients in the non-ventilated group reported RTI/year, which was not significantly less than in the study group with ventilation. Hospital admissions due to RTIs decreased from to admissions per year (P < 0.005). In the non-ventilated group the frequency of hospital admissions was per year, but not significantly lower than in the study group. In the NIV group 12 patients stated that they applied intensified IPPB-assisted coughing to overcome a RTI. Three patients reported to have prolonged the duration of NIV. In Table 1 patients using NIV alone were compared with patients using NIV and IPPB-assisted coughing. Patients using NIV and IPPB tended to seek more RTI related medical treatment, but this was not statistically significant. In both groups GP consultations, antibiotic treatment and hospital admissions due to RTI were reduced after initiation of NIV (statistically significant only in the NIV and assisted coughing group). The duration of NIV (months) since initiation did not correlate with medical treatment either before or after starting NIV. The hours of NIV usage per week positively correlated with the number of hospital admissions before and after NIV (R ¼ 0.42, R ¼ 0.41, P < 0.05). Additionally, 12 patients who used NIV for at least 5 years (at mean years) were studied retrospectively by hospital chart review. Mean age at start of ventilation was years. The total amount of hospital admissions due to RTI decreased from before NIV to after NIV (P > 0.001), corresponding to a decrease in the incidence of RTI related hospital admissions from RTI/year to 0.12 RTI/year (P < 0.005). Twenty three of 35 patients (65%) received pneumococcal vaccination and 29 of 35 patients (83%) received both pneumococcal and influenza vaccination. Four patients in the NIV-group and two patients in the group without ventilation did not receive either vaccination. Although vaccinated patients reported less consultations of their general practitioner, less airway infections requiring antibiotic treatment and less hospital admissions due to chest infections, this difference did not reach statistical significance (Table 2). DISCUSSION In the present study we could demonstrate a clear positive impact of NIV on respiratory complications in children with neuromuscular disorders. Patients receiving NIV reported fewer consultations of their general practitioner and fewer episodes of antibiotic treatment due to RTIs. Moreover, the incidence of hospital admissions due to severe chest infections decreased significantly and was comparable to the incidence of a non-ventilated group. This is remarkable since due to a more severe course of muscle disorder the study population showed overall lower vital capacities. The data of the questionnaire were focused on the year before and the year after the initiation of NIV. These results were strongly confirmed by an additionally performed review of the patients who were ventilated for the longest time (>5 years). It could be shown that the overall incidence of hospital admissions due to RTI decreased from 0.54 RTI/year to 0.12 RTI/year. The results of our retrospective survey are consistent with a recent prospective uncontrolled study by Katz et al. 18 This study could show that the application of NIV reduced the incidence of hospital admissions in patients with neuromuscular disorders. Our study comes along with various other studies which proved beneficial effects of NIV for children with neuromuscular disorders. It has been shown that NIV improved sleep quality, corrected hypercapnia and hypoxemia and even improved survival. 19 Reduction in health care demand, demonstrated in this study, implies an improvement in the patients quality of life. It might also reduce health care costs and is likely to compensate for ventilator and assisted coughing device expenses. Vaccination against influenza is a voluntary vaccination in chronically ill children in Germany, vaccination against pneumococcus has only recently (2006) been claimed recommended vaccination for all children. In our collective two-thirds of patients received both proposed TABLE 1 Comparison of RTI Associated Medical Treatment in Patients With NIV Alone and Patients With NIV and Assisted Coughing NIV and assisted coughing (n ¼ 16) NIV without assisted coughing (n ¼ 8) Before NIV After NIV Before NIV After NIV GP consultation (/year) * Antibiotics (/year) * Hospital admission (/year) * Mean SD; RTI, respiratory tract infection; NIV, non-invasive ventilation; GP, general practitioner. *P < 0.05 compared to before NIV in the NIV and assisted coughing group.

4 70 Dohna-Schwake et al. TABLE 2 Relation of RTI Associated Medical Treatment to Vaccination Against Pneumococcus and Influenza N ¼ 34 No vaccination One vaccination Both vaccinations GP consultation (/year) Antibiotics (/year) Hospital admission (/year) Results in mean SD; RTI, respiratory tract infection; GP, general practitioner. vaccinations. Although there was a trend toward less infectious complications in vaccinated patients, vaccination status did not reach significance concerning the impact on the rate of RTIs in our patients. We believe that this was probably due to the small number of patients. The usefulness of assisted coughing by intermittent positive pressure breathing to enhance peak cough flow could be shown in a recent investigation. 17 In 12 of 15 patients of our study population assisted coughing was also helpful to overcome acute chest infection. Only three patients prolonged ventilation time. According to a study by Vianello et al. 20 assisted coughing is an important treatment of secretion recumbrance during RTIs. The investigators could demonstrate that patients with acute RTIs treated by mechanical insufflation-exsufflation suffered less treatment failures (intubation or minicricothyroidectomy) than a historical control group but only adults were included in this study. The present study is limited by the use of a nonvalidated questionnaire and by the small number of patients. Additionally, the influence of an intensified care as additional reduction factor of RTI coming along with NIV could not be ruled out. Despite these limitations we are convinced that the information gained by this questionnaire confirmed the benefit of respiratory aids for children with neuromuscular disorders and reduced respiratory function. To provide optimal respiratory support for these children, they should be monitored and treated by an experienced team (physician, physiotherapist, nurse). In our clinic patients are handed out a protocol before discharge for optimal home care. This protocol is based on a study by Tzeng and Bach 21 and includes instructions in case of a RTI: (1) early antibiotic treatment to reduce the risk of bacterial superinfection; (2) frequent use of assisted coughing maneuvers and expanded use of NIV to maintain the oxygen saturation >95%; (3) if the oxygen saturation cannot be increased >95% for more than half an hour, the patients physician should be contacted immediately; (4) regular vaccination against influenza and pneumococcus. In conclusion, our data provide strong evidence that NIV reduces the frequency and severity of RTIs. Additional to the benefit of correcting nocturnal hypoventilation and daytime hypercapnia, this reduction of infectious complications probably contributes to the prolonged survival in certain neuromuscular disorders. REFERENCES 1. Bhat N, Wright JG, Broder KR, Murray EL, Greenberg ME, Glover MJ, Likos AM, Posey DL, Klimov A, Lindstrom SE, Balish A, Medina MJ, Wallis TR, Guarner J, Paddock CD, Shieh W-J, Zaki SR, Sejvar JJ, Shay DK, Harper SA, Cox NJ, Fukuda K, Uyeki TM, Influenza Special Investigations Team. Influenzaassociated deaths among children in the United States, N Engl J Med 2005;353: Bach JR, Baird JS, Plosky D, Navado J, Weaver B. Spinal muscular atrophy type I: management and outcome. Pediatr Pulmonol 2002;34: Dubowitz V. Very severe spinal muscular atrophy (SMA type 0): an expanding clinical phenotype. Eur J Paediatr Neurol 1999;3: Bach JR, Rajaraman R, Ballanger F, Tzeng AC, Ishikawa Y, Kulesa R, Bansal T. Neuromuscular ventilatory insufficiency: effect of home mechanical ventilator use v oxygen therapy on pneumonia and hospitalization rates. Am J Phys Med Rehabil 1998;77: Dohna-Schwake C, Ragette R, Teschler H, Voit T, Mellies U. Predictors of severe chest infections in pediatric neuromuscular disorders. Neuromusc Disord 2006;16: Simonds AK, Ward S, Heather S, Bush A, Muntoni F. Outcome of paediatric domiciliary mask ventilation in neuromuscular and skeletal disease. Eur Respir J 2000;16: Mellies U, Ragette R, Dohna-Schwake C, Boehm H, Voit T, Teschler H. Long-term non-invasive ventilation in children and adolescents with neuromuscular disorders. Eur Respir J 2003;22: Ward S, Chatwin M, Heather S, Simonds AK. Randomised controlled trial of non-invasive ventilation (NIV) for nocturnal hypoventilation in neuromuscular and chest wall disease patients with daytime normocapnia. Thorax 2005;60: Mellies U, Dohna-Schwake C, Stehling F, Voit T. Sleep disordered breathing in spinal muscular atrophy. Neuromusc Disord 2004;14: Birnkrant DJ, Pope JF, Eiben RM. Management of the respiratory complications of neuromuscular diseases in the intensive care unit. J Child Neurol 1999;14: Bach JR. Mechanical insufflation-exsufflation. comparison of peak expiratory flows with manually assisted and unassisted coughing techniques. Chest 1993;104: Kang SW, Bach JR. Maximum insufflation capacity. Chest 2000;118: Bach JR, Smith WH, Michaels J, Saporito L, Alba AS, Dayal R, Pan J. Airway secretion clearance by mechanical exsufflation for post-poliomyelitis ventilator-assisted individuals. Arch Phys Med Rehabil 1993;74: Sivasothy P, Brown L, Smith IE, Shneerson JM. Effect of manually assisted cough and mechanical insufflation on cough flow of normal subjects, patients with chronic obstructive pulmonary disease (COPD), and patients with respiratory muscle weakness. Thorax 2001;56:

5 NIV and Respiratory Tract Infections Chatwin M, Ross E, Hart N, Nickol AH, Polkey MI, Simonds AK. Cough augmentation with mechanical insufflation/exsufflation in patients with neuromuscular weakness. Eur Respir J 2003;21: Feigelson CI, Dickinson DG, Talner NS, Wilson JL. Glossopharyngeal breathing as an aid to the coughing mechanism in the patient with chronic poliomyelitis in a respirator. N Engl J Med 1956;254: Dohna-Schwake C, Ragette R, Teschler H, Voit T, Mellies U. IPPB assisted coughing in pediatric neuromuscular disorders. Pediatr Pulmonol 2006;41: Katz S, Selvadurai H, Keilty K, Mitchell M, MacClutsky I. Outcome of non-invasive positive pressure ventilation paediatric neuromuscular disease. Arch Dis Child 2004;89: Eagle M, Baudouin SV, Chandler C, Giddings DR, Bullock R, Bushby K. Survival in Duchenne muscular dystrophy: improvements in life expectancy since 1967 and the impact of home nocturnal ventilation. Neuromuscul Disord 2002;12: Vianello A, Corrado A, Arcaro G, Gallan F, Ori C, Minuzzo M, Bevilacqua M. Mechanical insufflation-exsufflation improves outcomes for neuromuscular disease patients with respiratory tract infections. Am J Phys Med Rehabil 2005;84: Tzeng AC, Bach JR. Prevention of pulmonary morbidity for patients with neuromuscular disease. Chest 2000;118: