C89 THE ALS NUTRITION/NIPPV STUDY
KASARSKIS EJ, MENDIONDO M, KRYSCIO R, TANDAN R, HEIMAN-PATTERSON T, NIPPV STUDY TEAM ALS NUTRITION
University of Kentucky, Lexingto, KY, United States
E-mail address for correspondence: [email protected]
Keywords: Nutrition, NIPPV, early intervention
Background: Intervention with nutritional support and NIPPV are important in the management of ALS and are thought to prolong survival and maintain quality of life. The optimal timing of these interventions has yet to be defined. Currently, nutritional support via PEG is advocated based on symptoms (e.g., dysphagia, weight loss) and NIPPV on the basis of FVC. Ideally, recommendations for these interventions should be based on evidence of either nutritional or ventilatory insufficiency.
Objectives: The objectives are: 1) to develop equations to predict total daily energy (calorie) expenditure (TDEE), 2) to evaluate acceptance, compliance, and tolerability of NIPPV at FVC 50% vs 80%, 3) to examine early predictors of respiratory insufficiency, and 4) to evaluate the effect of interventions on QOL of patients and caregivers.
Methods: In a multi-center pilot study, ALS patients with FVC> 50% of predicted were entered into a nutrition arm (n = 80) or a NIPPV arm (n = 73) and studied at baseline, 16, 32 and 48 weeks. In the nutrition arm, TDEE was measured using the “gold standard” doubly labelled water (DLW) method to serve as the reference against which predictive equations will be developed. Other factors measured longitudinally include: demographics, ALSFRS, FVC, body composition (BIS, DXA), physical activity (accelerometers, Bouchard scale), resting metabolic rate, clinimetric scales (spasticity, cramps, fasciculations, fatigue), food intake, laboratory measures, and psychosocial scales. Subjects in the NIPPV arm were divided into an Early Intervention Group (Group 1; NIPPV initiated with FVC 75–85%) and the Standard of Care Group (Group 2; NIPPV initiated with FVC 45–55%). Acceptance, tolerability, and compliance were determined by self-report and NIPPV meter readings. Longitudinal measures of ventilatory status were determined (SNP, NIV, MVV, supine FVC, scales) to evaluate early changes.
Results: 153 ALS patients were enrolled from 12 participating study sites (5, nutrition arm; 7, NIPPV arm). The characteristics of the subjects at baseline were: age (54.9±11.5 yrs), gender (M/F; n/%; 98/64%; 55/36%), site of onset (limb/bulbar, n/%; 115/75%, 38/25%), months from onset to enrolment (23.5±18.1), and ALSFRS (35.6±6.2). Entry characteristics were comparable in the two study arms. For analysis and modelling, the nutrition participants were divided into 4 groups based on their entry FVC (>80% vs 50–80%) and on ambulatory status (ALSFRS question 8; “4” vs “3, 2, 1, or 0”). Although analyses for TDEE are in progress, measurements to date indicate TDEE ranged between 1199 and 3614 kcal/d with a mean of 2276±600 kcal/d at baseline. Longitudinal assessments of TDEE, water intake, calorie intake and physical activity are in progress to complete modelling procedures. 55 out of 73 NIPPV participants reached criteria for intervention with NIPPV.
Discussion and Conclusions: We project that we will have >200 individual TDEE determinations and associated clinical measures to successfully develop ALS-specific predictive equations for TDEE as the disease progresses. Statistical analyses are in progress to evaluate factors contributing to NIPPV acceptance and tolerance to project sample size for a definitive trial of early NIPPV intervention.
C90 PREDICTIVE VALUE OF RESPIRATORY TESTS FOR RESPIRATORY INSUFFICIENCY IN AMYOTROPHIC LATERAL SCLEROSIS
PINTO S1, TURKMAN A2, PINTO A3, SWASH M4, DE CARVALHO M5
1Instituto de Medicina Molecular. Neuromuscular Unit. Faculty of Medicine. 2Centro de Estatística e Aplicações. Faculty of Sciences. University of Lisbon, 3Department of Physical and Rehabilitation Medicine. Hospital de Santa Maria., Lisbon, Portugal, 4Department of Neurology, Royal London Hospital, Queen Mary School of Medicine, University of London, United Kingdom, 5Department of Neurology. Hospital de Santa Maria, Lisbon, Portugal
E-mail address for correspondence: [email protected]
Keywords: Respiratory function tests, hypercapnia, phrenic nerve stimulation
Background: A large number of respiratory function tests (RFT) have been studied to detect earlier signs of hypoventilation in amyotrophic lateral sclerosis (ALS). However, few reports have studied the predictive values of those tests for global hypoventilation. This is important as non-invasive ventilation (NIV) can correct hypoventilation.
Objectives: We investigated the predictive value of a large number of volitional and non-volitional respiratory tests for hypoventilation in ALS. In particular, we aimed to address phrenic nerve motor response.
Methods: We analyzed data from 199 ALS patients with probable or definite disease (revised El Escorial criteria) followed in our Unit. Sixty-eight patients had bulbar-onset (G1) and 131 spinal-onset (G2). Twenty-five had hypercapnia (pCO2>45 mmHg), which was considered the “gold standard” to define hypoventilation. The following measurements were recorded: forced vital capacity (FVC); maximal static inspiratory and expiratory pressures (PImax and PEmax); mouth inspiratory pressure at 100ms (P0.1); amplitude of the motor responses to phrenic nerve stimulation (Ampl). We analyzed the results obtained at these patient's first visit to our Clinic. For each group the sensitivity and specificity of positive (PPV) and negative (NPV) predicted values, as well as their accuracy as determined by ROC (receiver operator characteristics) analysis were determined. A logistic regression model was applied to identify test results that were significantly related to hypercapnia.
Results: The mean age was 61 years and 99 (50%) patients were women. The mean disease duration was 17.2 months. The disease onset was bulbar in 68 patients and spinal in 131 (in upper limbs in 63). Twenty-five (12.6%) patients had hypercapnia at the first observation. Defining the “cut-off” point by the normative values, PPV was low and NPV high for all measurements. ROC analysis and a logistic regression model confirmed that FVC (cut-off = 63.4%) and Ampl (cut-off = 0.25mV) was discriminative for the whole group of 199 patients, and G1, and Ampl (cut-off = 0.37mV) for G2.
Discussion: Phrenic nerve stimulation is a simple, comfortable and objective test that seems useful to predict hypoventilation in ALS, in both spinal and bulbar-onset patients. FVC was predictive for bulbar patients but not for spinal-onset patients. This might be because decreased expiratory efficacy influenced the value of FVC as a surrogate for diaphragm function. We assessed central respiratory drive by measuring P01; we concluded that central hypoventilation does not seem relevant in bulbar-onset patients. Maximal inspiratory pressure is sensitive in detecting early respiratory change but does not predict global hypoventilation.
C91 FACTORS ASSOCIATED WITH NON-INVASIVE POSITIVE PRESSURE VENTILATION (NIPPV) COMPLIANCE IN PATIENTS WITH ALS/MND
JACKSON C1, HEIMAN-PATTERSON T2, SHERMAN M2, MENDIONDO M8, ROLLINS Y3, VERMA A4, SHEFNER J5, SCELSA S6, NEWMAN D7, KASARSKIS E8, N/A ALS NUTRITION/NIPPV STUDY TEAM9
1University of Texas Health Science Center, San Antonio, Texas, United States, 2Drexel University College of Medicine, Philadelphia, Pennsylvania, United States, 3University of Colorado, Denver, Colorado, United States, 4University of Miami, Miami, Florida, United States, 5State University of New York, Syracuse, New York, United States, 6Beth Israel Medical Center, New York City, New York, United States, 7Henry Ford Hospital, Detroit, Michigan, United States, 8University of Kentucky, Lexington, Kentucky, United States, 9ALS Nutrition/NIPPV Study Team, United States
E-mail address for correspondence: [email protected]
Keywords: Non-invasive positive pressure ventilation, respiratory management, compliance
Background: Despite growing evidence demonstrating that non-invasive positive pressure ventilation (NIPPV) prolongs survival and improves quality of life, a large percentage of patients initiated on this treatment remain non-compliant. Prior reports have suggested that compliance is most strongly correlated with symptoms of orthopnea and dyspnea Citation[1], Citation[2].
Objectives: To prospectively examine factors which influence NIPPV compliance in patients with ALS/MND.
Methods: Seventy-three ALS patients with a forced vital capacity (FVC) > 50% were enrolled in the multi-center pilot study of Early Nutrition and NIPPV. Patients with a FVC over 80% at baseline were initiated on NIPPV when their FVC was 75–85% (Group 1 – Early intervention). Patients with a FVC between 50–80% were started when their FVC was 45–55% (Group 2 – Standard of Care). Patients received an educational video prior to the initiation of NIPPV and the information presented was discussed in detail with the site investigator. A respiratory therapist made home visits three times a week for the first week, twice the second week, once the third and fourth weeks and then monthly throughout the study period. NIPPV compliance was defined as consistent use of at least > 4 hours per night based on machine meter readings and patient report. Chi-square and t-test were used to determine the association between compliance and participants’ characteristics at the time of NIPPV initiation.
Results: Of the 55 patients that initiated NIPPV, 35 patients (64%) were compliant with NIPPV. NIPPV compliance was associated with income over $50,000 (p = 0.004), higher educational level (p = 0.04). Compliance rates were 51% in patients initiated on NIPPV with an FVC between 75–85% and 82% in patients initiated on NIPPV with an FVC between 45–55% (p = 0.02). Age, gender, and site of disease onset did not predict compliance. There were no differences in compliance based on symptoms of dyspnea and orthopnea as measured by the Medical Research Council Modified Dyspnea Scale (MDS), the Borg Dyspnea scale, or the ALS Functional Dyspnea Score (ALSFDS), nor with the ALSFRS-R total score, upper extremity function, respiratory, or bulbar domains.
Discussion and Conclusions: This data suggests that the most predictive factors of NPPV compliance are advanced education and income > $50,000. The high overall compliance rate in this patient sample suggests the importance of patient education regarding the use of NIPPV as well as the need for aggressive respiratory therapy intervention at the initiation of treatment. Early initiation of NIPPV does not appear to improve tolerance.
This study was supported by NINDS, ALS Hope Foundation, and the Cynthia Shaw Crispen Endowment.
C92 WIRELESS PATIENT MONITORING FOR THE CONTROL OF COMPLIANCE TO NIV IN ALS PATIENTS: FUNCTIONAL AND SURVIVAL OUTCOME
PINTO A1, PINTO S2, ALMEIDA JP1, DE CARVALHO M2
1University Clinics of PMR, 2Molecular Medicine Institute, Faculty of Medicine, Santa Maria Hospital, Lisbon, Portugal
E-mail address for correspondence: [email protected]
Keywords: Non-invasive ventilation, compliance, breathing pattern
Background: Non-Invasive Ventilation (NIV) is an efficient method to treat respiratory insufficiency in ALS as it improves survival and quality of life in compliant patients. Non-compliant patients are recognized when daily ventilator usage is < 4 h/d. Recent technological advances allow the identification of abnormal breathing patterns which is frequently the cause of intolerance leading to therapy abandoment. Real time actions based on this evidence may facilitate decision-making and reduce the process of trial and error and costs.
Objectives: To evaluate the impact on function and survival of ALS ventilated patients, whose ventilator settings are controlled via modem communications, whenever a detection algorithm is perceived, from the received data, an abnormal breathing pattern the patient's medical attendant is called.
Methods: 54 probable or definite ALS, consecutive and ventilated patients (17 bulbar-onset and 37 spinal-onset) in the last three years, were randomized according to the locality of residence to check compliance and parameters settings in office visits (G1:n = 28) or to receive a device for remote controlling the Goodknight 425 ST (G2:n = 26). This machine forwards weekly data to an e-health monitoring room. All patients were followed-up every three months with RFT, ALS-FRS. Throughout the clinical evolution, we registered the number of office visits, the number and type of each parameters changed, breath frequencies, the percentages of spontaneous breathing, of attained predetermined pressures, of the total ventilator usage in days, of days with use greater than 6 hours. We also recorded survival from symptom onset and from NIV adaptation. Groups were compared and data analysed to find differences at admission in order to control for the confounding variables and subsequently identify possible predictors of long-term satisfaction (compliance), survival and functional outcome.
Results: G1 (9 bulbar-onset and 19 spinal-onset mean ages±SD 61±1,6), G2 (8 bulbar-onset and 18 spinal onset with mean ages±SD 59±2). There were no differences at admission regarding age, gender, type of disease-onset and disease duration. The number of non-compliant patients was lower in G2 though not statistically significant. The number of changes in the parameter settings was not different although the number of days to full compliance was significantly lower in G2. Total survival from symptoms onset until January 2008; as well as the total amount of ventilator usage in days was significantly increased in G2. There were significant differences regarding initial parameter settings, showing lower inspiratory pressures (IPAP), breathing frequencies in G2 and lower percentages of spontaneous breathing in G1.
Conclusions: This study shows that remote control is able to reduce the trial and error procedures, speeds up the process of NIV adaptation and therefore may contribute to the increased survival observed.
C93 ELECTIVE TERMINATION OF NON-INVASIVE AND MECHANICAL VENTILATION IN ALS
MEYER T1, DULLINGER J1, BORISOW N1, ROSSEAU S2, MÜNCH C3, LINKE P1
1Charité, Department of Neurology, Berlin, 2Charité, Department of Internal Medicine, Berlin, 3Jewish Hospital Berlin, Germany
E-mail address for correspondence: [email protected]
Keywords: termination of ventilation, discontinuation of therapy, palliative care
Background: Due to the growing use of ventilation therapy in ALS, physicians are increasingly confronted with patients who seek a discontinuation of non-invasive or mechanical ventilation. In Germany, termination of ventilation is legal and medico-ethically settled, yet there are few systematic investigations into withdrawal of ventilation therapy.
Objectives and Methods: In a retrospective investigation of 9 German ALS patients, clinical data were recorded from the discontinuation of non-invasive ventilation (n = 4) and mechanical ventilation (n = 5).
Results: In cases of residual spontaneous breathing (non-invasive ventilation, n = 3), an intensified symptom control of dyspnea and anxiety was possible with intravenous morphine sulfate (MSI) in a low dose rate (10 mg/h) but high cumulative dose (185–380 mg). The terminal phase after removal of the mask was protracted (22:10 h to 28:00 h). In cases of minimal or absent spontaneous breathing (invasive ventilation, n = 5; continuous non-invasive ventilation, n = 1), the disconnection was realized in a deep sedation, which required a moderate total dose (120 mg) but a high dosage rate (up to 300mg/h) of MSI. The terminal phase in deep sedation was short (15–80 min). In 2 patients, there were hypoxic myoclonus and automatisms.
Conclusion: The elective termination of ventilation requires a differentiated pharmacologic palliative care. In the future, controlled studies are required in order to establish evidence-based guidelines for the termination of ventilation.
C94 RESULTS OF PROSPECTIVE PILOT AND MULTI-CENTER PIVOTAL TRIALS OF DIAPHRAGM PACING IN AMYOTROPHIC LATERAL SCLEROSIS: MAINTAINING DIAPHRAGM FUNCTION AND IMPROVING SURVIVAL
ONDERS R1, KATIRJI B1, ELMO M1, SO Y2, KATZBERG H2, KATZ J3, MILLER R3, SIMPSON E4, APPEL S4, NEWMAN D5, BOYLAN K6, MARAGAKIS N7, ROTHSTEIN J7, SIVAK M8, WIEDAU-PAZOS M9, GONZALALEZ J10, SIMILOWSKI T10, MEININGER V10, SALACHAS F10, HEIMAN-PATTERSON T10
1University Hospitals Case Medical Center, Cleveland, Ohio, United States, 2Stanford, Palo Alto, CA, United States, 3California Pacific Medical Center, San Francisco, CA, United States, 4Methodist Hospital, Houston, TX, United States, 5Henry Ford Health System, Detroit, MI, United States, 6Mayo Clinic, Jacksonville, FL, United States, 7John Hopkins, Baltimore, MD, United States, 8Mount Sinai, New Yor, NY, United States, 9UCLA, Los Angelas, CA, United States, 10Hospital de al Salpetriere, Paris, France, 11Drexel University College of Medicine, Philadelphia, PA, France
E-mail address for correspondence: [email protected]
Keywords: diaphragm pacing, respiratory control, breathing
Background: Respiratory insufficiency is the major cause of mortality in patients with ALS/MND. Present therapies in ALS do not address diaphragm dysfunction. The diaphragm pacing system (DPS) is a standardized minimally invasive laparoscopic technique that is being utilized worldwide to maintain and provide natural diaphragm ventilation.
Objective: To analyze the safety and efficacy of DPS in ALS.
Methods: At 11 worldwide sites, a prospective lead-in design study obtaining a battery of three initial data sets were collected prior to treatment by laparoscopic placement of intramuscular diaphragm pacing electrodes. Subjects utilized DPS to condition their diaphragm with additional utilization depending on respiratory condition. Data was collected for another nine months post implant and until death.
Results: Recruitment was completed with 140 subjects (20 in pilot and 120 in pivotal with 20 European subjects). Of these 140 patients, 73 have been implanted, with 40 patients’ still in the lead-in and 27 patients falling out after consenting but prior to implantation (most commonly from FVC not meeting inclusion criteria- 13 patients). Patient demographics at implantation were 70% male, 60% NIPPV use, 34% use of gastrostomy, FVC 60 ±12% predicted with decline rate of 1.84% per month and ALSFRS-r score of 28 ±7.5. There were no perioperative mortalities with over 20% having FVC below 50 and over 30% having elevated pCO2. Non-device peri-operative morbidity included: one extended hospitalization from a pre-existing cardiomyopathy and one post-operative gastrostomy tube dislodgement requiring re-hospitalization. Total cumulative use of DPS is over 600 months with longest implants over 2 years with no non-tolerance of pacing post implantation. Subjects with declining FVC during the lead-in period showed a significant (p < 0.05) improvement in paired comparison to rate of decline with treatment with an average improvement of 1.33±2.45% per month. Overall there have been 19 patients that have reached the endpoint of death or tracheostomy with only 4 being the result of respiratory failure. The probability of survival is at a mean of 60.9±6.7 months for all patients. In patients undergoing DPS and gastrostomy (n = 18) the 30 day survival was 100% and the 1 year survival 75%. The ALSFRS-R score showed that while the overall symptoms of ALS progressed the respiratory subscore did not decline. Prior to implant the respiratory subscore represented 32% of the total and following treatment it was 41%. In paired comparison of pre- and post-treatment, the respiratory subscore increased by 8±12% of the total ALSFRS-R score (p < 0.001). DPS can continuously assess diaphragm EMG activity which has allowed the identification of instability of respiratory control and central hypoventilation. Sleep assessments performed at one site showed 23 of 47 patients utilize DPS during sleep. Greater fluoroscopic diaphragm movement is visualized with DPS stimulation in patients with more upper motor neuron diaphragm involvement. DPS has been able to lower pCO2 levels with increased daily use.
Conclusion: The DPS system can be safely implanted and utilized in ALS patients with a positive effect on diaphragm function. DPS minimizes the impact of NIPPV on diaphragm dysfunction and positively impacts patients with identified instability of respiratory control.
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