C92 CLINICAL CHARACTERISTICS AND OUTCOMES OF NIV IN ALS
CHIO A1, MORA G2
1Department of Neuroscience, University of Torino, Torino, Italy, 2ALS Center, Fondazione Salvatore Maugeri, Instituto Scientifico di Milano, Milano, Italy
Email address for correspondence: [email protected]
Keywords: non-invasive ventilation, outcome
In amyotrophic lateral sclerosis (ALS) the involvement of respiratory muscles can occur at different clinical stages, and respiratory failure is the most frequent cause of death (Gil et al, 2008), sometimes complicated by the coexistence of bulbar involvement. A correct management thus requires frequent and accurate evaluations of symptoms and serial tests. According to current clinical guidelines (Andersen et al, 2007; Miller et al, 2009) and a Cochrane systematic review (Radunovic et al, 2009), non-invasive ventilation (NIV) is the treatment of choice in the management of respiratory disturbances in ALS. This statement is largely based on the only controlled trial on NIV in ALS, which demonstrated a clear benefit of this treatment, particularly in patients without severe bulbar symptoms.
In recent years NIV has been increasingly used in current practice. According to a population based study (the Piemonte and Valle d'Aosta register for ALS), the frequency of NIV augmented from 15% in the 1995-1999 period to 25% in the 2000-2004 period. This increase, however, was mainly limited to patients followed by tertiary ALS centers. NIV was performed more frequently by young people, married, and of male gender. Social status can also influence the likelihood to undergo NIV, according to differences in national health systems; in fact sometimes NIV is given free, in other cases could be partly or totally charged to patients. Other (negative) aspects that influence provision of NIV services include the lack of knowledge of many neurologists for timely identification of respiratory problems in their patients, and that not enough chest physicians have the appropriate skills for managing respiratory failure in ALS patients.
Median survival time after NIV is in the range of 6 to 12 months both in clinical and in epidemiological studies. Several factors influence the outcome of NIV. These include patients’ clinical status (severity of bulbar impairment, lower ALSFRS-R score, poor nutritional status) and respiratory function (lower forced vital capacity) at the time of NIV initiation. Other factors are patients’ age and airway mucus accumulation. Both frontotemporal dementia and isolate executive dysfunction negatively influence the acceptance and the compliance to NIV.
Compliance to NIV can be improved if patients are adequately trained, for example with initial acclimatization, possibly in a hospital multidisciplinary setting with specific competences; careful choice of an appropriate interface (usually more than one); aggressive management of secretions and maintenance of effective cough; a continuum of care, training and support to patients, families and caregivers.
C93 CARER INFLUENCE ON NON-INVASIVE VENTILATION TREATMENT IN MOTOR NEURONE DISEASE
COUSINS R1, ANDO H1,2, YOUNG C2
1Liverpool Hope University, Liverpool, UK, 2The Walton Centre for Neurology & Neurosurgery, Liverpool, UK
Email address for correspondence: [email protected]
Keywords: caregiving, NIV treatment, resilience
Background: Caregiving plays a significant and central role in the management of motor neurone disease (MND). Patients come to rely on substantial physical assistance with almost every activity of daily living. Although there is a paucity of research describing caregiving in MND, the extant data points to reduced quality of life, increased distress and negative impacts on health for carers. Caregiver variables, as well as patient variables, will predict patient outcomes, including compliance with treatment options. During the course of MND patients may be offered non-invasive ventilation (NIV) to ameliorate breathing difficulties, prolong survival, and improve quality of life. However, not all patients accept this treatment. Knowing that NIV treatment option requires carers that are willing and able to help, an important question is whether the caregiving situation influences uptake of NIV treatment.
Objectives: To measure caregiving variables at the time when the possibility of NIV treatment is presented to someone with MND and his or her carer to identify predictors of those who decline NIV treatment.
Methods: Thirty-five dyads were recruited to the study at the time of assessment for ventilatory support. Seventeen patients went on to accept NIV treatment, and 11 patients declined or were not tolerant of NIV treatment. Seven patients did not yet need NIV, so were excluded. Dispositional and illness-related measures were collected for quantitative analysis using data taken as close to the NIV decision date as possible to minimise differences in the illness situation.
Results: There were no differences in patient illness variables between the NIV group and the no-NIV group. Levels of carer distress were high across both groups; the only significant difference in means was higher anxiety in no-NIV carers (t = 2.07, p < 0.05). Caregiver health was negatively affected in both groups, particularly emotionally and psychologically with SF36 means significantly below norms; additionally no-NIV carers scored significantly lower for social functioning (t = −2.10, p < 0.05). For dispositional variables: carers in no-NIV dyads were more neurotic (t = 2.06, p < 0.05), and less resilient overall (t = −2.42, p < 0.05), and with respect to commitment (t = −2.51, p < 0.05). A stepwise regression analysis indicated that resilience: commitment was the single significant predictor of the use of NIV, explaining over 20% of the variance.
Discussion and conclusions: In line with other research, we found that levels of carer distress are high in MND, and that health is negatively affected. Additionally we found a difference in the two NIV groups with respect to dispositional variables: commitment - which is described as being involved rather than alienated from aspects of one's life, served to predict uptake of NIV treatment. Some carers may be more naturally inclined to find purpose in their situation; the meaning of the illness situation impacts upon the management of MND.
C94 TRADITIONAL VENTILATION MONITORING MAY UNDERESTIMATE THE VENTILATOR REQUIREMENTS OF MOTOR NEURONE DISEASE PATIENTS
CHAKRABARTI B, YOUNG CA, ANDO H, FORD V, THORNTON E, ANGUS R
Walton Centre for Neurology & Neurosurgery, Liverpool, UK
Email address for correspondence: [email protected]
Keywords: NIV, patient-ventilator interaction, oximetry
Background: Non-invasive ventilation (NIV) is a recommended treatment option for selected patients with motor neurone disease (MND) with ventilatory failure because of its positive impact on survival. However, what constitutes optimal ventilation remains undefined. Most centres assess adequacy of ventilation with overnight pulse oximetry at regular intervals (Leger et al. 2002). Modern “domiciliary” ventilators possess technology recording aspects of ventilation such as leak, triggering and Minute Ventilation (MV) (Rabec et al. 2009). It is unclear if analysis of Patient-Ventilator interaction (PVI) ultimately yields useful additional information over that gained from measuring pulse oximetry.
Objectives: This prospective study analyses patient-ventilator interaction in longitudinal fashion over a 12 month period in MND patients following initiation of NIV and relationship to nocturnal oximetry and disease state as assessed by ALS-FRS, ALSAQ40, and HADS at 2 time points: 4-6 months post initiation (Point A) and 10-12 months (Point B) post initiation of NIV.
Methods: Ten subjects (mean age 62 (SD 10) years; 9 male) had at least 12 months follow up on NIV and thus were analysed for this study. In all cases, NIV was administered without supplementary oxygen. All were ventilated with a Respironics© Synchrony 2 ventilator; PVI was performed by interrogation of the Encore© Smartcard storage.
Results: In the group, the mean ALS-FRS score fell significantly between points A (27 SD(5.7) and B (23.6 SD (7.68) t = 2.78; p = 0.021), MV falling in 5 subjects (range −1.14 to −3.53 l/min). A significant correlation was found between MV and ALS-FRS score at points A (r = 0.74; p = 0.014) and B (r = 0.65; p = 0.043). At point A, MV correlated significantly with ALS-AQ40 total (r = −0.63; p = 0.05) and ALS-AQ40 Mobility domain (r = −0.74; p = 0.014). Tidal volume (TV) fell in 5 subjects (range -3 to -5 l/min) from points A to B. TV correlated significantly with ALS-FRS at point A (r = 0.70; p = 0.025). In the group, the median oxygen saturation on pulse oximetry was 94% at both time points following initiation of NIV (Point A IQR 89-95%; point B IQR 91-95%). In 7 subjects, pulse oximetry showed < 20 minutes spent below 90% saturation during points A and B suggesting adequate ventilation. Triggering also fell but no association was seen between ΔMV (r = −0.26; p = 0.46) and ΔTriggering (r = −0.32; p = 0.40) with adequate oximetry at points A and B. Mask leak did not correlate with MV or ventilator triggering.
Discussion: This data suggests that falling minute ventilation is linked to worsening disability in MND patients receiving domiciliary NIV despite apparently adequate ventilation assessed by overnight oximetry. The insensitivity of oximetry is illustrated in that marked decreases in ventilator triggering and minute ventilation did not necessarily translate into “suboptimal” oximetry.
Conclusion: Analysing patient-ventilator interaction may be an important adjunct to oximetry for clinicians when optimising ventilation in MND.
Grant from Motor Neurone Disease Association UK.
C95 CURRENT AND PRACTICAL UTILIZATION OF DIAPHRAGM PACING IN ALS/MND: FROM PILOT TRIAL EXPERIENCE TO FDA HUMANITARIAN DEVICE APPROVAL INDICATIONS FOR HELPING RESPIRATION
ONDERS R, KATIRJI B, ELMO M, KAPLAN C, SCHILZ R
University Hospitals Case Medical Center, Cleveland, Ohio, USA
Email address for correspondence: [email protected]
Keywords: diaphragm, respiration, gastrostomy
Background: Diaphragm pacing (DP) has been proven to be an acceptable alternative therapy to help with respiration in patients with ALS/MND receiving FDA approval in 2011. This report will review the experience of a single institution throughout the trials and highlight the utilization of DP in current clinical practice.
Objective: Review results of DP from trials and describe the 2011 evaluations of patients for suitability and implementation of DP.
Methods: Two sources of patients: 1) Prospective, nonrandomized, controlled, interventional trials under IRB and/or FDA approval for use of DP at a single institution; 2) Clinical use of DP for ALS following humanitarian use designation (HUD) implantation criteria which involves evidence of chronic hypoventilation (MIP less than 60cm H20, FVC less than 50% predicted, PCO2 greater than 45mm Hg or SaO2 less than 88% for 5 consecutive minutes during sleep) with stimulatable diaphragms as shown by radiographic volitional diaphragm contractions or neurophysiologic evaluation with phrenic nerve conduction studies.
Results: From 2005-2009 during three prospective studies 66 subjects were enrolled with 52 being implanted. The key end result of these trials include: DP can be safely implanted; survival with DP from onset is 4.7 years using Kaplan-Meir survival analysis with many patients still surviving; in a case match comparison patients who used DP and non-invasive ventilation (NIV) survived 16 months longer than those using NIV alone; and patients undergoing combined DP and PEG had a 0% thirty day mortality and 70% one year survival. From 2010-2011 in clinical practice 23 patients were evaluated with implantation occurring in 15 patients following the HUD criteria. Evaluations included pulmonary functions tests (FVC and MIP), arterial blood gases, fluoroscopic sniff test, phrenic nerve conduction studies and overnight pulse oximetry. Reasons for not implanting included: no evidence of hypoventilation (1), non-stimulatable diaphragms (4), excessive secretions where aspiration would to lead to death or tracheostomy before respiratory failure (2) and one patient declined after discussing end of life issues. Current practice includes discussion of end of life issues and cessation of pacing to allow natural death. 80% (12 out of 15) patients had simultaneous PEG and DP. Post-operative DP use involved 5 initial 30 minute sessions and then increased based on patient presumed benefits. DP is always utilized whenever NIV is used to prevent ensuing atrophy of the diaphragm from NIV suppressing diaphragm function. Ongoing DP adjustments are made according to the patients’ need.
Conclusion: DP improves survival and delays tracheostomy ventilation. DP is easily integrated into clinical practice with the primary time of implantation at the time of a PEG. Combining both improves the safety of PEG alone and should decrease total health care cost from separate procedures and hospitalizations.
C96 HIGH FREQUENCY CHEST WALL OSCILLATION (HFCWO) IN AMYOTROPHIC LATERAL SCLEROSIS (ALS) PATIENTS DECREASES RESPIRATORY INFECTIONS REQUIRING ANTIBIOTICS AND/OR HOSPITALIZATION: A PRE-POST OBSERVATIONAL STUDY
BROOKS BR1,3, LANGFORD VL1, WARD AL1, WILLIAMS NM1, NICHOLS MS1, BRAVVER E1,3, LINDBLOM SC2,3
1Department of Neurology, Neuromuscular/ALS-MDA Center; 2Department of Internal Medicine, Carolinas Medical Center, Charlotte, NC, USA, 3University of North Carolina School of Medicine, Charlotte Campus, Charlotte, NC, USA
Email address for correspondence: [email protected]
Keywords: high-frequency chest wall oscillation, VEST
Background: Patients with ALS/MND are vulnerable to respiratory infections due to decreased vital capacity, decreased diaphragmatic muscle function, decreased mobility and difficulty managing secretions. Respiratory care in ALS patients with increasing restricted pulmonary function requires attention to clearing pulmonary secretions. HFCWO therapy gently compresses and releases the chest wall up to 25 times per second. This process creates mini-coughs that dislodge mucus from the bronchial walls, increase mobilization, and move it along toward central airways. The action also works to thin thick secretions, making them easier to clear. The HFCWO can be used in a wheelchair, recliner or in bed, and is very easy to place around a person with impaired mobility. Chaisson, et al. (1) and Lange, et al. (2) demonstrated respiratory function improvement but did not show an effect of HFCWO on infection rate. HFCWO is used with patients with ALS/MND, although there have been no studies to date reporting utilization or the effect of HFCWO on respiratory quality of life.
Objective: To evaluate in an ALS Clinic setting whether there is a decrease in the prevalence of infections requiring antibiotics and/or hospitalization following HFCWO.
Methods: Data was gathered from calls made to patients and caregivers at 5, 15 and 30 days. A validated 7-question respiratory quality of life scale using a 5 point Likert scale (1-5) was completed at each call. The minutes use per day was queried. Surveillance period per patient pre-HFCWO and post-HFCWO was recorded and infections per month of surveillance per patient were calculated for each patient before and after introduction of HFCWO and compared by Wilcoxon rank tests.
Results: ALS patients (36) patients pre-HFCWO had 0.07 ± 0.13 (SD) infections/month which reduced to 0.02 ± 0.06 infections/month (Wilcoxon ranked test p = 0.0415). Daily use of HFCWO was 15.9 ± 10.4 minutes for ALS Clinic patients compared with 16.9 ± 12.6 minutes for mean national compliance assessed by Hill-Rom in non-ALS neuromuscular disease patients. The overall respiratory quality of life score was 4.1 (range 3-5) for our ALS patients compared with the national mean 3.8 (range 2-5) for neuromuscular disease patients using HFCWO.
Conclusion: HFCWO significantly reduces the per-patient infection rate in ALS patients. Observational studies employing pre-post-intervention design can provide important clinically meaningful information supporting certain respiratory interventions in ALS patients. HCFWO is a beneficial and effective airway clearance treatment for the patient with ALS/MND.
References
- Chaisson KM, Walsh S, Simmons Z, Vender RL. Amyotrophic Lateral Sclerosis. 2006 June;7(2):107–11.
- Lange DJ, Lechtzin N, Davey C, et al. Neurology. 2006 Sep 26;67(6):991–7.
C97 MECHANICAL INSUFFLATION-EXSUFFLATION IMPROVES INFLAMMATORY PANEL IN PATIENTS WITH AMYOTROPHIC LATERAL SCLEROSIS
YOSHII Y, IKEDA K, KANO O, MURATA K, NAGATA R, HIRAYAMA T, MIURA K, KAWABE K, IWASAKI Y
Toho University Omori Medical Center, Tokyo, Japan
Email address for correspondence: [email protected]
Keywords: mechanical insufflation-exsufflation, high sensitive C-reactive protein, serum biomarker
Background: Various biomarkers including serum proteins, cerebrospinal fluid proteins and neuroimaging or neurophysiology studies are currently being identified to make an early diagnosis, monitor the disease progression or measure early therapeutic effects in ALS. Although expectation is high, some of the potential biomarkers are not fully understood in terms of the process behind their abnormal levels. Mechanical Insufflation-Exsufflation (MIE) (CoughAssist: Phillips Respironics) is a noninvasive therapy that removes secretions in patients with an ineffective ability to cough (peak cough flow < 270 L/min). It also expands the lung and reduces atelectasis and promotes airway clearance, so could reduce the frequency of respiratory complications, thereby reducing the rate of respiratory-related hospitalizations in patients with tetraplegia.
Objectives: We aimed to evaluate whether the respiratory condition affects serum inflammatory panels before and after MIE.
Methods: Eight consecutive patients with ALS were enrolled. All patients were hospitalized and in a stable condition, and no procedures were performed within a month. Patients who suffered infections were excluded in this study. Typically patients were waiting for the transfer. We obtain serum samples before and after one week's use of MIE. We measured high sensitive C-reactive protein (hs-CRP), Tumor necrosis factor alpha (TNF-α), Interleukin-1 beta (IL-1β), Interleukin-6 (IL-6) and pulmonary Surfactant Protein-D (SP-D). We also obtained information on satisfaction with MIE by questionnaires and analyzed if satisfaction was correlated with the improvement of serum inflammation panel. Paired student's t test was used for statistical analysis.
Results: The groups of patients with ALS were associated with higher levels of hs-CRP, IL-6 and SP-D compared to the control groups (hs-CRP 2506 ng/mL: 82 ng/mL, IL-6 2.9 pg/mL: 1.0pg/mL, SP-D 60.3 pg/mL: 17.3pg/mL). MIE therapy for one week significantly reduced hs-CRP (1777 ± 2096 ng/mL (95% CI, 25.1 to 3530, p = 0.048)). Patients who do not use non-invasive positive pressure ventilation (NPPV) had higher levels of hs-CRP. MIE decreased the level of hs-CRP more effectively in the patients without NPPV use. No correlations were observed between the patients’ satisfaction and hs-CRP reduction.
Discussion: Patients with ALS have higher levels of serum inflammatory panel. It is not fully elucidated why the serum inflammatory markers are elevated. The present study indicated that short-term use of MIE significantly decreased serum hs-CRP levels. This suggests that respiratory complications such as microatelectasis could contribute to an increase in inflammatory proteins. MIE assists removing secretions and expanding alveoli effectively. This could explain why the MIE did not decrease hs-CRP effectively in the patients who had already been using NPPV. Early use of non-invasive ventilation is reported to prolong survival in patients with ALS although the mechanism remains unclear. It could be the key to improve ALS treatments to study further the relationship between the respiratory condition and inflammatory status.
C98 THE EFFECTS OF HIGH FAT VERSUS HIGH CARBOHYDRATE ENTERAL NUTRITION IN ALS PATIENTS WITH RESPIRATORY DYSFUNCTION
ROWIN J, CURSIO J
University of Illinois, Chicago, Illinois, USA
Email address for correspondence: [email protected]
Keywords: respiratory, nutrition, PEG tube
Background: There is evidence to support an increased mortality rate in ALS patients when PEG placement occurs in the setting of ventilatory failure. We propose that the increased mortality may be due in part to the increased metabolic demand on the ventilatory system in the post-prandial state.
Objectives: 1) To examine the respiratory effects of high carbohydrate enteral feeding formula (Nutren); 2) To determine if A) slow (continuous) enteral feeding or B) high fat enteral feedings (50%, Pulmocare) would avoid the increased respiratory demands on ALS patients with ventilatory dysfunction.
Methods: We prospectively examined minute ventilation, respiratory rate, tidal volume, end-tidal CO2, CO2 elimination rates and arterial blood gases in the fasting state and one hour after a high fat or high carbohydrate bolus or high carbohydrate continuous enteral feeding in ALS patients with PEG placement and ventilatory dysfunction.
Subjects: Eleven subjects age 18-80 with definite or probable ALS who met the following criteria: 1) PEG placed for the treatment of dysphagia/undernutrition; 2) FVC < 70% predicted or PaCO2 > 45 mmHg or nocturnal oxygen desaturation to 88% for > 5 minutes were enrolled. The primary outcome measure was the mean difference between PaCO2 in the fasting and post-prandial states.
Results: Statistical analysis used a one-sided signed rank test. All statistical results were obtained using SAS Version 9.1.3. Demographic measures included mean age (68.8 years), mean BMI (26.0), and mean weight (72.8 kg) for the10 patients given high carbohydrate bolus feeding. Mean days between PEG placement and day of visit (22.6), and between PEG placement and feeding (2.9 days) were calculated for all 10 patients receiving bolus high carbohydrate enteral feeding. Differences in fasting and post-prandial state were obtained for the variables: PaCO2, minute ventilation, respiratory rate, tidal volume, end-title CO2, CO2 elimination, FVC %, FVC (L), PaO2, pH, NIF %. Because of the small sample size of ten patients, all differences were tested for significance using a t-test. Respiratory rate (p = 0.021), CO2 elimination (p = 0.01), and pH (p = 0.01) were found to be significantly increased in post-prandial state compared to the fasting state in the bolus high carbohydrate group (N = 10).
CO2 elimination rate did increase during continuous feeding of high carbohydrate formula, but not after a high fat bolus. There was no difference in respiratory rate during continuous feeding of high carbohydrate or after high fat bolus feeding in the patient (N = 1) studied thus far.
Conclusions: 1) Respiratory rate, minute ventilation, and CO2 elimination increased after enteral bolus feedings, adding to the work of breathing. 2) Continuous slow enteral feeding or high fat, low carbohydrate feedings may place less respiratory demands on the ALS patient with ventilatory failure. 3) Further study in a large cohort of patients is needed to determine the clinical significance of these results.
SESSION 12 JOINT CLOSING SESSION
C99 ALS RESEARCH AND TREATMENT: WHERE TO FROM HERE?
TALBOT K
University of Oxford, Oxford, UK
Email address for correspondence: [email protected]
The last decade has seen unprecedented progress in ALS research and care. However, disease modifying therapy of major effect is still an aspiration rather than a reality. We now understand that ALS is not a single disease with one cause, but a clinicopathological syndrome resulting from a complex convergence of genetic susceptibility, age-related damage and possible environmental influences. The precise biological pathways underlying this complexity are beginning to emerge from genetic studies and neuropathology.
The combination of larger genome-wide association studies, whole exome sequencing and RNA expression studies will rapidly expand the number of genes which are implicated in ALS, for both familial and sporadic cases. Almost two decades after the identification of the first genetic cause of ALS (SOD1), we still do not know the exact disease mechanism. Therefore the major challenge is how to extract meaningful biological insights into ALS from the resulting huge quantity of data. To exploit this rapid expansion in information for the benefit of patients, sophisticated pathway analysis is required to produce points of convergence which can serve as targets for therapy. Better pre-clinical models of disease, including stem cell derived human motor neurons will be widely available to test the relevance of these pathways. However, a complete description of the origin of ALS and the nature disease heterogeneity requires an understanding of the disease as a system failure, not just as a disorder of a specific population of cells.
Most patients entering clinical trials have well established disease. It is imperative that we find ways of identifying and studying the disease in its earliest, potentially most therapeutically tractable, stages. To this end international efforts to coordinate biomarker studies and detailed epidemiology to understand whether specific populations are at risk are also critical. In combination with multidisciplinary, proactive management of nutrition, respiratory function and disability, multimodal treatment of ALS in its earliest phases offers a tangible hope for making an impact in what is one of the most challenging diseases known to medicine.