C86 RESPIRATORY PHYSIOLOGY AND MANAGEMENT STRATEGIES
Polkey MI
Royal Brompton Hospital, London, UK
E‐mail address for correspondence: [email protected]
ALS/MND is a progressive disease for which no satisfactory treatment presently exists; muscles supplied by the degenerating nervous system develop weakness and this process affects the respiratory muscles in the same way as limb muscles. Thus respiratory muscle weakness is a common feature in ALS/MND although it is the presenting feature in just 3–5% of cases. In the respiratory management of ALS/MND the following issues require consideration:
Identification of respiratory muscle involvement. Respiratory muscle weakness is suggested by breathlessness particularly if accentuated by lying flat. Nocturnal hypoventilation (and CO2 retention) is suggested by morning headache and daytime sleepiness. The simplest investigation to confirm or exclude respiratory muscle weakness is the vital capacity but this test is unreliable in advanced disease and recent data suggest that the maximal sniff nasal inspiratory pressure is more sensitive and specific for the identification of hypercapnia (1).
Screening for respiratory failure. Frank respiratory failure is usually preceded by hypoventilation during sleep. This can be evaluated by polysomnography but transcutaneous O2/CO2 monitoring may also be used to identify incipient respiratory failure. Alternative measures include arterial bicarbonate or serum chloride (2).
Treatment. Following earlier cohort studies it has become established, using a randomized controlled trial, that non‐invasive ventilation extends life and improves quality of life in patients with non‐bulbar ALS/MND (3), although the advantages are less clear‐cut for patients with bulbar disease who tolerate NIV less well. Adjunctive strategies including physiotherapy and mechanical insufflation‐exsufflation (4) may also be useful in patients who experience problems with sputum clearance. Although the burden of care experienced by caregivers increases as MND progresses, NIV does not significantly increase most aspects of caregiver burden (5).
Some issues are unresolved and may vary between healthcare systems. These are if and when to use tracheotomy ventilation and management of end of life care.
References
- Lyall RA, Donaldson N, Polkey MI, et al. Respiratory muscle strength and ventilatory failure in amyotrophic lateral sclerosis. Brain 2001;124:2000–13.
- Stambler N, Charatan M, Cedarbaum JM, et al. Prognostic indicators of survival in ALS. Neurology 1998;50:66–72.
- Bourke SC, Tomlinson M, Williams TL, et al. Effects of non-invasive ventilation on survival and quality of life in patients with amyotrophic lateral sclerosis: a randomized controlled trial. Lancet Neurol. 2006;5:140–7.
- Mustfa N, Aiello M, Lyall RA, et al. Cough augmentation in amyotrophic lateral sclerosis. Neurology 2003;61:1285–7.
- Mustfa N, Walsh E, Bryant V, et al. The effect of noninvasive ventilation on ALS patients and their caregivers. Neurology 2006;66:1211–7.
C87 CLINICAL CHARACTERISTICS OF RESPIRATORY ONSET ALS AND RESPIRATORY SYMPTOMS AT DIAGNOSIS IN PATIENTS WITH ALS
Andrews JA1, Gordon PH1, Gooch C2, Basner RC1, Mitsumoto H1
1Eleanor and Lou Gehrig MDA/ALS Research Center, The Neurological Institute, Columbia University, New York, USA, 2Department of Medicine, Columbia University, New York, NY, USA
E‐mail address for correspondence: [email protected]
Background: ALS can have respiratory muscle weakness as the initial symptom. When the disease begins with respiratory failure, the diagnosis can be difficult to make, and survival may be shorter.
Objective: To describe the frequency, demographics, clinical features and survival of patients with respiratory onset ALS and respiratory symptoms at diagnosis.
Methods: We retrospectively reviewed 502 consecutive charts of patients evaluated at our outpatient ALS Center with IRB approval. All met El Escorial criteria for the diagnosis of ALS. Patients were segregated into respiratory onset (RO) and non‐respiratory onset groups. The non‐respiratory onset group was further subdivided by the presence (RS) or absence (NR) of respiratory symptoms at the time of diagnosis. Information regarding demographics, site of onset, symptoms at diagnosis, age, gender, EMG findings, ventilation, and death were obtained. Information was obtained by phone for those patients not evaluated during the past year. Data were analysed using unpaired t‐tests.
Results: Two per cent (11/502) of patients were in the RO group, 8% (42/502) in the RS group, and 90% (449/502) in the NR group. The RO group consisted of 81% (9/11) males compared to 52% (22/42) in the RS group and 56% (249/449) in the NR group. Mean age of onset in the RO (65±6 years) and RS groups (65±9 years) were significantly higher than the non‐respiratory onset group (60±13 years, p = 0.024, p = 0.021). The most frequent symptom was dyspnea on exertion in the RO (7/11, 64%) and RS (19/42, 45%) groups. Only one patient had respiratory failure requiring invasive ventilation as the first sign. Mean time from onset to diagnosis in the RO group was 14.4±9 months and was not statistically different from the NR group (15.7±15 months, p = 0.76). At the time of diagnosis, most patients with respiratory onset had arm (5/11) or leg (4/11) weakness. Only two of 11patients had bulbar weakness. EMGs of the parapsinal muscles were available in 65% of patients but there was no difference in involvement of the thoracic paraspinal muscles in the RO group (60%) compared to the NR group (68%). In the RO group, 73% used NIPPV (mean time from onset to NIPPV = 8.7±5 months) and 63% used NIPPV (mean time from onset to NIPPV = 21.1±18 months) in the RS group. Five of 11 patients in the RO group died, two were maintained on mechanical ventilation and one was lost to follow‐up. Mean survival from symptom onset to death in the RO (30.4±6 months) and RS (27.8±19 months) groups was not statistically different from the NR group (30.6±19 months, p = 0.98, p = 0.48).
Conclusion: These data suggest that respiratory onset ALS is rare and occurs more commonly in males. Respiratory onset and respiratory symptoms at diagnosis occurred in older individuals and dyspnea on exertion was the most frequent initial symptom. Onset to diagnosis and survival was not different from non‐respiratory onset ALS.
Acknowledgement: This study was supported by the MDA, Wings over Wall Street, and Ride for Life.
C88 THE USE OF MAXIMAL INSPIRATORY PRESSURE (MIP) AS AN INDICATOR FOR EARLY INITIATION OF NIPPV IN ALS PATIENTS
Simpson EP1, Gonzalez M2, Rosenfield DB1, Pleitez Milvia1, Appel SH1
1Methodist Neurological Institute, Houston, TX, USA, 2Department of Pulmonology/Methodist Hospital, Houston, TX, USA
E‐mail address for correspondence: [email protected]
Background: The early use of non‐invasive positive pressure ventilation (NIPPV) in ALS patients is associated with improved quality of life and survival (1,2). Current AAN and American College of Chest Physicians guidelines recommend initiation of NIPPV when the forced vital capacity (FVC) decreases below 50% of predicted (3,4). However, supine FVC and maximal inspiratory pressures (MIP) are considered more sensitive indicators of diaphragmatic muscle weakness and better predictors of survival than upright FVC (5–7). In those patients unable to comply with a supine FVC measurement due to orthopnea, MIP is a useful and sensitive indicator of respiratory dysfunction and for early initiation of NIPPV, even in those patients with FVCs above 50%.
Objectives: To determine the prevalence of diaphragmatic dysfunction as measured by upright MIP in ALS patients with FVCs above 50% and 70%. To determine the relationship of MIP and FVC and the association with other measures of respiratory dysfunction, disease disability and progression.
Methods: One hundred and fifty‐two patients with a diagnosis of definite or probable ALS were studied at the Methodist Neurological Institute. Forced vital capacity and maximal inspiratory pressures were measured and studies were interpreted by the clinic pulmonologist for all patients. Disease disability was assessed with the Appel ALS rating scale at time of testing. EMG studies of the diaphragm were performed for a sub‐set of patients. Correlation analyses of study variables were performed with linear regression and χ2 testing.
Results: One hundred and twenty‐six ALS patients had both FVC and MIP measured during the study period (39% females, 31% bulbar). The average AALS score was 81±28 at time of study and disease duration was 35±36 months. FVC and MIP were 72±26 and 46±26, respectively. FVC and MIP were significantly correlated (p<0.0001; r = 0.63), yet 61% with FVCs>70 had MIPs<60. For patients with FVC⩽70, 98% had MIPs<60. Of patients with FVC⩾50%, 26% of patients had MIPs<60, whereas of those with FVC⩽50, 93% had MIPs<60. Both FVC and MIP correlated with AALS score at time of measurement, but only the FVC was significantly associated with bulbar onset ALS (p = 0.025). Diaphragmatic denervation was present in 7% of patients. Twenty‐five per cent of these had MIPs<60 and FVCs>70.
Conclusions: Respiratory dysfunction as measured by MIP is present in one‐quarter of ALS patients who would not otherwise meet current guidelines for NIPPV initiation (FVCs>50). Furthermore, more than 50% of patients with FVC>70 had evidence of diaphragmatic weakness as measured by a MIP<60. Thus, MIP is a more sensitive indicator of respiratory dysfunction in ALS and provides the basis for earlier initiation of NIPPV.
References
- Lyall RA, Donaldson N, Fleming T, Wood C, Newsom-Davis I, Polkey MI, et al. A prospective study of quality of life in ALS patients treated with non-invasive ventilation. Neurology 2001;57:153–6.
- Bourke SC, Bullock RE, Williams TL, Shaw PJ, Gibson GJ. Non-invasive ventilation in ALS: indications and effect on quality of life. Neurology 2003;61:171–7.
- Miller RG, Rosenberg JA, Gelinas DF, et al. Practice parameter: the care of the patient with amyotrophic lateral sclerosis (an evidence-based review): report of the Quality Standards Subcommittee of the American Academy of Neurology: ALS Practice Parameters Task Force. Neurology 1999;52:1311–23.
- Clinical indications for non-invasive positive pressure ventilation. I. Chronic respiratory failure due to restrictive lung disease, COPD, and nocturnal hypoventilation – a consensus conference report. Chest 1999;116:521–34.
- Jackson CE, Rosenfeld J, Moore DH, Bryan WW, Barohn RJ, Wrench M, et al. A preliminary evaluation of a prospective study of pulmonary function studies and symptoms of hypoventilation in ALS/MND patients. J Neurol Sci. 2001;191:75–8.
- Lechtzin N, Wiener CM, Shade DM, Clawson L, Diette GB. Spirometry in the supine position improves the detection of diaphragmatic weakness in patients with amyotrophic lateral sclerosis. Chest 2002;121:436–42.
- Schmidt EP, Drachman DB, Wiener CM, Clawson L, Kimball R, Lechtzin N. Pulmonary predictors of survival in amyotrophic lateral sclerosis: use in clinical trial design. Muscle Nerve 2006;33:127–32.
C89 USE OF NIPPV COMPLIANCE AND EFFICACY DATA
Wolfe L, Armstrong J, Casey P, Sufit R
1Northwestern University, Chicago, IL, USA, 2Les Turner ALS Foundation, Chicago, IL, USA
E‐mail address for correspondence: [email protected]
Background: The use of non‐invasive positive air pressure ventilation (NIPPV) has benefits for people with ALS (1). Both quality, as well as quantity of life can be improved. However, there is not an ALS standard of care for management of NIPPV therapy. It has been reported that the use of frequent monitoring of spirometry is paramount in the timeliness of initiation of NIPPV (1). NIPPV devices contain internal pressure monitors (pneumotachographs) that measure parameters of both compliance (numbers of hours used) and efficacy (minute ventilation, leak, respiratory rate, tidal volume, and apnea/hypopnea index). These data are available on current commercial home NIPPV devices. The interpretation of these data and its relevance to clinical management of ALS patients has not been described. Frequent home monitoring of NIPPV devices may help standardize NIPPV therapy for people with ALS and improve respiratory function.
Objectives: To review data collected from home NIPPV devices; to identify how often the data obtained prompted a change in the therapy and to describe the types of changes made.
Methods: Compliance and efficacy data were obtained from a retrospective review of nine people with ALS using NIPPV. The routine for collecting the data is a minimum of three months. Changes are made more frequently with reported symptoms. This information included how often data were obtained and how frequently those data influenced changes in therapy. Therapy was managed by the pulmonologist in the ALS Center. An effective breathing pattern was determined by calculating the shallow breathing index (respiratory rate/tidal volume) which has been shown to predict successful liberation from mechanical ventilation (2). The ALSFRS‐R score, FVC, tidal volume, compliance data, and patient's disease status were all collected to describe patient sample characteristics.
Results: NIPPV was initiated when FVC reached 50% (mean = 19 months). Compliance and efficacy data were collected an average of every 2.5 months. Four changes in therapy were prescribed after data review. Oxygen was added due to low saturation. Conversion to a new device occurred because of a high apnea/hypopnea index, high respiratory rate or high total usage hours. Changes in pressures or inspiratory time minimum or maximum settings were made due to low tidal volumes or high shallow breathing index results. Increases were made to back up rates because of high apnea/hypopnea index results. A change in therapy occurred 42% of the time when data were collected.
Discussions and conclusions: Compliance and efficacy data interpretation can assist healthcare professionals in maximizing NIPPV therapy for people with ALS. Managing the shallow breathing index has proved helpful. Further studies are needed to confirm the reliability of this index to improve respiratory function and reduce the work of breathing. Patients may benefit from monitoring data at a minimum of every three months, or as frequently as symptoms are reported. Further studies may indicate more frequent monitoring is needed.
References
- Kleopa K, Sherman M, Neal B, et al. Bipap improves survival and rate of pulmonary function decline in patients with ALS. Journal of Neurological Sciences 1999;164:82–8.
- Tobin MJ. Advances in mechanical ventilation. New England Journal of Medicine 2001:344:1986–96.
C90 RESULTS OF DIAPHRAGM PACING IN AMYOTROPHIC LATERAL SCLEROSIS (ALS): DECREASING THE DECLINE IN RESPIRATORY FAILURE AND INCREASING DIAPHRAGM MOVEMENT
Onders RP, Schilz R, Katirji B, Elmo MJ, Ignagni A
Case Medical Center, Cleveland, Ohio, USA
E‐mail address for correspondence: [email protected]
Background: ALS patients develop respiratory insufficiency which is ultimately responsible for the majority of deaths. Therapeutic electrical stimulation has been shown to maintain the strength of other peripheral muscles in ALS by maintaining physiological activity, contractile properties and calcium levels. Motor units can be compensated for by collateral axon sprouting and the rate of sprouting increases with electrical stimulation. The laparoscopic diaphragm pacing system (DPS) is a low‐risk outpatient system to stimulate and condition the diaphragm.
Objective: To evaluate in a phase I trial that the DPS system can be safely implanted and used for conditioning the diaphragm in ALS patients. Secondary objectives are to show that life threatening respiratory muscle dysfunction may be delayed with diaphragm pacing.
Methods: Patients diagnosed with ALS and with a forced vital capacity (FVC) above 50% predicted were eligible. Each patient had three lead‐in assessments, at four‐week intervals prior to implantation, with pulmonary function tests, fluoroscopic evaluation of diaphragm movement, speech phonation times, ultrasound analysis of diaphragm thickness, phrenic nerve conduction tests and quality of life tests. Patients underwent laparoscopic mapping of their diaphragm to locate the phrenic nerve motor points and two electrodes were implanted in each hemidiaphragm. Two weeks after surgery, stimulus/output characteristics of each electrode were determined. The patients then conditioned the diaphragm with five 30‐min sessions of therapeutic electrical stimulation per day. Patients were similarly assessed post‐operatively.
Results: Eight patients have been safely implanted and have started on diaphragm conditioning with the DPS system with no adverse events. There have been no deaths or need for tracheostomy. In all patients, more fluoroscopically observed diaphragm excursion occurs with diaphragm stimulation than under maximal patient control. The first four patients (average FVC at implantation was 49%) have an average 12‐month follow‐up. Their monthly decline in FVC went from 4.1% pre‐implant to 1.4% post‐ implant. Patient 3 utilizes DPS continuously to augment respiration and has no diaphragm movement without DPS. Phonation time has improved and muscle thickness (mass) has increased with DPS. With the exception of patient 3, there has been no change in the respiratory sub‐score of the ALSFRS‐R, although overall score has declined. There has been no decline in the SF‐36 emotional domain quality of life scores although the SF ‐36 physical function has declined.
Conclusion: The diaphragm pacing system can be safely implanted and utilized in patients with ALS. There has been a documented decrease in the decline of respiratory failure which leads to an increased survival. The ability to cause more diaphragm movement with DPS is a surprising and beneficial finding. This may be best explained by intact phrenic nerve motor neurons that are no longer controlled by the medullary respiratory center, cerebral cortex, or central or peripheral chemoreceptors, but can be stimulated with DPS. DPS may also have a trophic effect on increasing the survival of these motor neurons. DPS also converts the remaining motor units to usable slow twitch oxidative units. These findings of DPS may lead to improved night time ventilation, decreased posterior lung lobe atelectasis and subsequent pneumonia.
C91 PHRENIC NERVE PACING TO IMPROVE RESPIRATORY FUNCTION IN PATIENTS WITH AMYOTROPHIC LATERAL SCLEROSIS
Rosenfeld J1, King R1, Blythe A1, Lindblom S2, Skipper E3
1Carolinas Medical Center, Neuromuscular/ALS Center, Charlotte, 2Charlotte Medical Clinic, Charlotte, 3Sanger Cardiology Associates, Charlotte, NC, USA
E‐mail address for correspondence: [email protected]
Background: Surgical implantation of electrodes for direct stimulation of the phrenic nerve has been used as an alternative to invasive ventilation in patients with spinal cord and nerve injury. Phrenic nerve function has been enhanced and nerve viability preserved via programmed electrical pulses delivered to the nerve and then transmitted to the diaphragm muscles. To date, use of this procedure has not been reported in patients with motor neuron disease due to the progressive degenerative nature of the disease.
Objective: To describe our experience with surgical implantation of a phrenic nerve pacemaker in three patients with advanced ALS and significant respiratory compromise.
Methods: The number of hours per day of non‐invasive positive pressure ventilation was measured prior to and after implantation of a bilateral phrenic nerve pacemaker. A receiver was implanted in the upper chest and connected to electrodes placed around the phrenic nerve in the chest. Forced vital capacity, Bipap dependence and the patient's subjective assessment of their respiratory function were recorded. A pre‐implantation phrenic nerve conduction study was performed to assist in our selection of appropriate patients.
Results: Two of our three patients noted significant benefit within 48 h from onset of pacing. Tolerance for increasing time on the pacemaker was favourable and in both patients who benefited, significant improvement in their quality of life and respiratory function resulted. Forced vital capacity had dropped aggressively in the ten months preceding implantation in all patients. After use of the pacemaker for at least one month, the rate of FVC decline was abated and respiratory function stabilized.
Conclusion: Despite the logical contraindication to aggressive surgical intervention with a phrenic nerve pacemaker, the procedure was beneficial in two patients we studied with respiratory impairment due to ALS. Decline in forced vital capacity was stabilized, use of BiPAP decreased and subjective assessment of functional ability greatly increased. In appropriately selected patients with some preserved phrenic nerve conduction and precipitous respiratory decline, surgical implantation of a phrenic neve pacemaker may be an appropriate alternative therapy. Implanted patients were able to increase time off Bipap and prolong latency to initiation of invasive ventilation.