preliminary report Improvement in Exercise Capacity after Nocturnal Positive Pressure Ventilation and Tracheostomy in a Postpoliomyelitis Patient* Carlos A. Vaz Fragoso, M.D.;t Robert M. Kocmarek, Ph.D.; and David M. Systrom, M.D.:t:
Progressive neuromuscular symptoms years after recovery from acute paralytic poliomyelitis have been termed the PPS. We describe a 52-year-old man who contracted poliomyelitis at age 9 years who fully recovered and 33 years later developed progressive dyspnea. Neurologic evaluation revealed bilateral paralysis of the vocal cords, generalized weakness, and accentuated mouth occlusion pressure and ventilatory responses to hypercapnic, hyperoxic breathing. An EMG and muscle biopsy showed changes consistent with acute and chronic denervation. Cardiopulmonary exercise evaluation demonstrated a pulmonary mechanical limit with excessive ventilation relative to C01 output. Tracheostomy and nocturnal positive pressure ven-
0
f the 300,000 survivors of acute paralytic poliomyelitis in the United States, 20 to 60 percent may develop PPS. 1•2 The onset of PPS occurs on the average 29 years after recovery from polio and at a mean age of 51 years. 1•2 Symptoms include weakness, shortness of breath, exercise intolerance, sleep disturbances and other nonspecific complaints. These range in severity from mild, stable disease to a progressive form resembling amyotrophic lateral sclerosis. 1•2 The pathophysiology appears to be one of denervation and aberrant re-innervation. 1•2 Exertional dyspnea may result when there is an imbalance between central respiratory drive and ventilatory capacity. In PPS, central respiratory drive may be abnormal, respiratory muscles may be weak, and WOB may be increased due to chest wall stiffness, atelectasis or bulbar involvement or both. 1•2 We present a case of PPS manifested by dyspnea and an abnormal response to exercise. An extensive physiologic evaluation was undertaken, the results of which may serve to provide further insight into PPS. The benefits of therapy resulting in decreased WOB and *From the Medical Services (Pulmonary and Critical Care Unit) and Department of Respiratory Care, Massachusetts General Hospital and Harvard Medical School, Boston. tSupported by a fellowship training grant (HL07534-12) from the National Institutes of Health. tSupported by NIH grant M01RR01066-1152. Manuscript received March 12; revision accepted June 7. Reprint requests: Dr. \flz Fragoso, Danbury Hospital, Danbury, Conn06810
254
tilation resulted in increased respiratory muscle strength, normalization of ventilatory drive and marked improve(Chest 1992; 101:254-57) ment in exercise capacity.
AT= anaerobic threshold; Keo= transfer factor; MVo. =oxygen consumption at peak exercise; NPPV =nocturnal positive pressure ventilation; PlOO =mouth occlusion pressure; Pdimax =maximal transdiaphragmatic pressure; PetC01 =endtidal C01 ; PK HR=peak heart rate; P-M=Passey-Muir; PPS= post-polio syndrome; REH= respiratory exchange; RMS= respiratory muscle stren&th; RVEF =right ventricular ejection fraction; VT/IC= ratio of tidal volume at peak exercise to inspiratory capacity; WORK= achieved work load during exercise
respiratory muscle rest are also described. CASE REPORT
A 52-year-old white man presented with a history of acute paralytic poliomyelitis at age 9 years. His course was complicated by respiratory failure requiring ventilatory support (iron lung) for nine months. His subsequent recovery was remarkable in that at age 17 years he was able to complete a marathon. In 1979, at age 42, he began to notice the gradual loss of strength of the shoulders and arms. By early 1988, he was experiencing orthopnea, sleeping difficulties and progressive dyspnea. An initial evaluation at an outside institution demonstrated respiratory muscle weakness and no evidence of obstructive or central sleep apnea on polysomnography. Support with a variety of nocturnal, noninvasive mechanical ventilators was attempted but discontinued due to patient discomfort (gastric distension with the nasal and face-mask ventilation; respiratory distress with body ventilators). He was admitted to the Massachusetts General Hospital in November 1988 for further study. Physical examination on admission was remarkable for orthopnea, easy fatigability of speech, wasting of the shoulder muscles and left calf, and a grade 3 of 5 weakness in neck and hip 8exors, deltoids, biceps, triceps, and grip. A chest x-ray film demonstrated low lung volumes with a mild elevation of the right hemidiaphragm relative to the left and a mild dextroconvex thoracic scoliosis. As a result of EMG testing and biopsy of the left deltoid muscle, acute and chronic denervation were evidenced. Cardiopulmonary evaluation was then pursued to define the individual factors limiting exertion. This included PFTs, measurement of respiratory muscle pressures, response to hyperoxic, hypercapnic breathing, and maximal incremental exercise testing. These results are shown in Tables 1 and 2. Predicted values for lung volumes and 8ow rates are derived from Crapo et al, 3 respiratory muscle pressures from Black and Hyatt,• maximal transdiaphrag-
Improvement in Exercise C8pacity in PostpoHomyelilis Patient (Vaz Fragoso, Kacmerek, Systrom)
matic pressures from Braun et al" and exercise performance from Wasserman et al.• The PFrs were performed with the patient in the sitting position. They revealed a moderate restrictive defect with preserved gas exchange by KCO. The Row-volume loop showed no segmental plateau defects. The ratio of VE to PlOO at rest was 3.30. A value less than 7 is consistent with a pulmonary mechanical abnormality, either restriction or obstruction. 7 Maximal respiratory muscle pressures measured at the mouth (MIP from RV and MEP from TLC) and Pdi max measured by esophageal and gastric balloons with a Mueller maneuver from RV confirmed severe inspiratory and expiratory muscle weakness. Central respiratory drive was increased as evidenced by exaggerated PlOO and VE responses to hyperoxic, hypercapnic breathing. Normal responses" are a PUXVPetC01 ratio of0.49±0.15 cm H10/ mm Hg and a VEIPetC01 ratio of 1.99±0.40 Umin/mm Hg. An upright maximal incremental bicycle exercise test was perfurmed. Breath-b)"breath collection of expired gases was accomplished through a two-way, non-rebreathing valve, pneumotachograph, 0 1 and CO, analyzers. Arterial blood samples for gases, pH and lactate were obtained at rest, every minute during exercise and 2.5 minutes fullowing exercise. First-pass radionuclide scan for determination of LVEF and RVEF were obtained prior to and at peak exercise.• The KI was determined in a manner similar to that described by Wasserman et al.• The results were as fullows: The MVo. was only 910 ml (38 percent predicted), indicating severely compromised exercise tolerance. The limit to exercise was characterized by a high dyspnea index and failure to achieve a lactate or ventilatory AT. (I'he dyspnea index" is the ratio of the VEmax to the MBC; the MBC is obtained by multiplying the FEV, by 35.) The MIP and MEP decreased even further following exercise and were associated with a breathing pattern at peak exercise of shallow breaths: peak respiratory rate of 50 breaths per minute, V1 of 863 ml, V1 to inspiratory capacity ratio of 0.47. Of interest, especially in view of the patient's response to C01 rebreathing, was the respiratory allcalosis observed throughout exercise. This occurred in the setting of a normal P (A-a)01 response. Stridor also was noted ' at peak exercise and was later shown by direct laryngoscopy to be due to bilateral vocal cord paralysis. (At rest, the vocal cords were in the paramedial position; there was some movement with phonation but no active abduction on deep inspiration.) Markers of pulmonary vascular disease" were minimal in view of the normal KCO at rest and the normal responses to exercise of the RVEF and P (A-a)01 • The elevated Vo/VT at rest and during exercise occurred in the setting of a shallow and rapid breathing pattern. Central cardiovascular function was normal for this level of exercise as shown by the normal increase in the LVEF and RVEF with exercise. As a result of severe respiratory muscle weakness, symptomatic UAO at the relatively low exercise 'WOrk load, and the intolerance to nocturnal, noninvasive mechanical ventilators, the patient underwent a tracheostomy to be followed by NPPY. Following discharge, the tracheostomy stoma was buttoned (modi&ed Olympic button) and a P.M valve attached during the day. At night, he received 8 to 10 h ofNPPV via a Life Care PLV-100 home mechanical ventilator. Controlled mechanical ventilation was achieved at a rate of9 breaths per minute in the assist-control mode with a VT of 1.0 Land a 8ow of 50 Umin. At fullow-up three months later, the patient related a marked increase in exercise capacity and resolution of sleep disturbances. This occurred in the absence of any formal exercise training program. 'Illbles 1 and 2 illustrate the dramatic improvement in PFrs, RMS and exercise performance. Exercise testing was perfurmed with the tracheostomy buttoned but without attachment of the P.M valve nor ABG measurements. The limit to exercise was now characterized by an early KI and a high PK HR (lld>le 2). The dyspnea index remained elevated but this occurred well after the
Pris FEV, (L) VC(L) FEV,NC PEFR(Us) TLC(L) FRC(L) RV(L) KCO (cc/min/mm HWL) MVV (%of MBC) MIP(cm H10) MEP(cm H.O) Pdi max A (cm H.O) PllXVPetC01 (cm H10/mm Hg) VEIPetCO,, (Umin/mm Hg)
Before Therapy
After Therapy
1.73 (49%) 1.86 (43%) (115%) 93 4.71 (55%) 3.95 (68%) 2.13 (63%) 2.09 (107%) 4.89 (96%) 113% A24(34%); B 15(21%) A59(44%); B 22(16%) 34 (38%) 0.77 (157%)
1.93 (63%) 2.38 (58%) (81%) 81 5.59 (67%) 4.35 (72%) 3.42 (105%) 2.14 (105%) 5.14 (104%) ND A63(89%); B 78(110%) A79(59%); B 104(75%) 53 (60%) 0.35 (71%)
3.5 (184%)
(84%)
1.6
*In the sitting position, before and after tracheostomy and NPPV (Rx) in a patient with PPS. Values in parentheses are percent predicted. A= before exercise; 8 =after exercise; ND= not determined. KI. Other noteworthy observations included a decrease in the PlOO and VE responses to C01 and an increase in the VEIPlOO ratio. These improvements were sustained at nine months post NPPV/ tracheostomy and were not significantly different from those at three months with the exception ofthe respiratory muscle pressures. These continued to improve, such that the MIP and MEP at rest were 71 (100 percent ofpredicted) and 135 (100 percent of predicted) cm H,O, respectively. COMMENT
In the case under discussion, a 52-ye~ld man presented with symptoms, signs, muscle biopsy, and Table 1-Eurciae Data• PFrs MV01 (Umin) WORK(W)
VEmax!MBC (%) VT/IC VEIPlOO (Umin/cm H.O) KI (Umin) + as % predicted Vo1max P(A-a)d01 (mm Hg) Vo/VT(%) LVEF(%) RVEF(%) PKHR pH Paco.
Before Therapy
After Therapy
0.91 (38%) 19 82 0.47 R3.3 P2.5
1.26 (5.1%) 108
none achieved
0.66 (28%)
R20t P21 t R56 P41 R62 P69 RSI P60 120 (73%) R7.47 P7.46 R33 P34
ND ND ND ND 165 (100%) ND ND
79 0.63 R4.7
*Maximal upright cycling befure and after tracheostomy and NPPV (I'herapy). Values in parentheses are percent predicted. R =rest, prior to exercise; P =at peak exercise; ND= not determined. tThis is equivalent to a Pa01 at rest of 89 and at peak exercise of 87. CHEST I 101 I 1 I JANUARY, 1992
255
EM G evidence of PPS developing 30 years after recovery from polio. His progressive exercise intolerance was due to a combination of an accentuated central respiratory drive, bilateral vocal cord paralysis and diminished RMS. Subsequent NPPV/tracheostomy was associated with normalization of central respiratory drive, improved RMS, and an increased exercise capacity. Central respiratory drive in neuromuscular disease is variable. Resting hyperventilation and an elevated response to hyperoxic, hypercapnic breathing has been noted in some of these patients. 111- 13 In PPS, little is known about central drive except that some of these patients have central sleep apnea. 1•2 Our patient had no evidence of central apnea by formal sleep testing. Rather, he exhibited an exaggerated ventilatory response at rest, during exercise and during C02 rebreathing. The normalization of central respiratory drive following NPPV/tracheostomy argues against the initial exaggerated response being the result of polioinduced damage to the ventilatory control center, but suggests its genesis to be the result of peripheral factors. Alternatively, changes in the PlOO values may have been due solely to changes in the FRC. The VE response to C02 rebreathing and to exercise, however, provided further confirmation of an exaggerated central respiratory drive. Although WOB curves were not obtained, the improvements in the FRC and the VE/PlOO ratio and the elimination of stridor at peak exercise imply that the WOB was reduced. Tracheostomy resulting in bypass of the UAO may have improved resistive work. Through a more effective spontaneous breathing pattern and by a periodic delivery of large V1 values (NPPV), an improvement in atelactasis may have led to a reduction in elastic work. (The latter does not necessarily contradict the work of De Troyer and Deisser since their findings are limited to IPPB. 14 ) The degree to which each component of the WOB or its subsequent intervention played a dominant role could not be ascertained at our level of testing. It is reasonable, however, to expect that once the patient's symptoms improved and remained stable that bypassing the UAO would be all that was needed. The finding of the UAO is at first glance surprising in view of the relatively preserved flow-volume loop and the results of the sleep polysomnography. This is not unusual, however, given that the course of a UAO may be insidious and brought on primarily by exercise. Furthermore, the discovery of the UAO probably explains why the patient tolerated so poorly the various forms of noninvasive ventilation. The patient's marked reduction in respiratory muscle pressures may have been secondary to weakness or fatigue or both. Recently, an NHLBI workshop 12 summarized muscle weakness as "a condition in which 256
the capacity of a rested muscle to generate force is impaired." Muscle fatigue was defined as a "loss in the capacity for developing force and/or velocity of a muscle, resulting from muscle activity under load and which is reversible by rest." 12 In our patient, reduced levels ofload may have been accomplished by a bypass of the UAO and relief of atelectasis. Respiratory muscle rest may have been achieved by the NPPV. This would thus suggest that the dramatic improvement in the patient's RMS following NPPV/tracheostomy could have been in part due to reduced respiratory muscle fatigue. Alternatively, it can be argued that the improvement in RMS was due to a spontaneous remission in the patient's PPS. Previous long-term follow-up studies of such patients, however, show at best plateaus in muscle strength rather than normalization. 2 In neuromuscular disease, the MVV and the VEmax (at peak exercise) usually decrease in direct proportion to the level of respiratory muscle weakness, but out of proportion to the predicted MBC. 5 •11 This is because a significant reduction in respiratory muscle pressures often precedes decreases in the lung volume on which the predicted MBC is based. In our case, however, a MVV maneuver and the VEmax at peak exercise approximated the MBC. It is likely that, despite respiratory muscle weakness and increased WOB, increased central respiratory drive was able to push VE toward its mechanical limit. Alternatively, the restrictive defect was due more to increased lung elastic recoil rather than to weakness. The dramatic improvement in the FRC following therapy argues in favor of the latter explanation. A normal response to a maximal incremental exercise test is characterized by a high PKHR and a normal AT and MVo2 •6 In PPS, exercise limits have been shown to include a high PKHR and a high RER in response to maximal incremental exercise. 15 Specific measures of exercise-related cardiopulmonary parameters such as the AT or dyspnea index have not been previously reported in the literature. In our patient, the initial exercise response was markedly abnormal and associated with a low MVo2 and PKHR as well as a failure to achieve an AT. This occurred in the setting of a high dyspnea index (VEmax/MBC) and is descriptive of a primary pulmonary mechanical limit. 6 The etiology of this limit is most likely due to the patient's diminished RMS and increased WOB (reduced MBC), as well as the accentuated central respiratory drive (elevated VEmax). Following NPPV/tracheostomy, exercise performance showed a dramatic improvement. This was in part due to improvements in the aforementioned factors which contributed to the elevated dyspnea index (RMS, WOB, central drive), thereby permitting a more prolonged exercise effort. The exercise performance, however, remained abnormal hut was now characterized by an early AT. This
lmproYllRllll1t In Exercise Capaclly In Poslpollomy8lll Patient (Vaz Fragoso, Kat:metek, Systmm)
suggested a limit in either oxygen delivery or extraction. 6 In view of the patients normal central cardiovascular function by radionuclide ventrlculography and of the normal P(A-a)02 response, the limit was thus more suggestive of problems in peripheral 0 2 distribution and utilization. 6 The presumed etiology was involvement of the peripheral exercising musculature by PPS, vasoregulatory asthenia or deconditioning or both of the latter. It must be emphasized that our patient's improved exercise capacity with NPPV/tracheostomy was not improvement in aerobic capacity, given related to the absence of an /(f on the initial testing. Rather, the improvement was due to a normalization of the ve~tilatory response and an increase in the MBC. This suggests that in PPS the exercise limit may be of two types. Type 1 may be secondary to a pulmonary mechanical limit (high dyspnea index), while type 2 may be related to a peripheral 0 2 limit (early Kf with normal central cardiovascular function). The first would occur in the setting of severe respiratory muscle compromise and be treated primarily by measures directed at relieving respiratory muscle fatigue, such as through NPPV or tracheostomy (depending on the clinical presentation). The second would not have a primary respiratory limit but rather a peripheral 0 2 limit that could potentially be improved by a conditioning program such as that outlined by Jones et al15 and Owen and Jones. 16 Thus by determining whether a PPS patient has a type 1 or 2 exercise limit, one may be able to more specifically target therapy. This could be critical as attempts which only emphasize aerobic training may further compromise respiratory muscle function and exercise capacity in the type 1 limit. Further study is needed to confirm the existence and frequency of such limits. In conclusion, exercise intolerance in this patient with PPS seemed to be related to a ventilatory pump being fatigued by an increased work load and an abnormal central respiratory controller. Tracheostomy and NPPV resulted in near-normalization of RMS, central respiratory ~ve and exercise capacity. The relative importance of NPPV vs tracheostomy could
an
not be determined at our level of testing. Whether these observations apply to all patients with PPS requires further investigation. REFERENCES 1 Dalabs M, Hallet M. The post-polio syndrome. In: Plum F, ed. Advances in contemporary neurology. Philadelphia: FA Davis Co, 1988:51-94 2 Dala1cas M, Elder G, Hallett M, Ravitts J, Baker M, Papadopoulos N, et al. A long-term fullow-up study of patients with post-poliomyelitis neuromuscular symptoms. N Engl J Med 1986; 314:959-63 3 Crapo RO, Morris AH, Gardner RM. Reference spirometric values using techniques and equipment that meet ATS recommendations. Am Bev Respir Dis 1981; 123:185-90 4 Black LF, Hyatt RE. Maximal respiratory pressures: normal values and relationship to age and sex. Am Bev Respir Dis 1969;
99:696-702 5 Braun NMT, Arora NS, &chester DF. Respiratory muscle and 6
7 8 9
10
11 12 13
14
15
16
pulmonary function in proximal myopathies. Thorax 1983; 38:616-23 Wasserman IC, Hansen JE, Sue DY, Whipp BJ. Principles of exercise testing and interpretation. Philadelphia: Lea and Febiger, 1987 Scott GC, Burki NK. The ratio of resting ventilation to mouth occlusion pressure: an index of resting respiratory function. Chest 1986; 89:4595 Burki NIC. Measurements of ventilatory regulation. Clin Chest Med 1989; 10:215-26 System seventy-seven, multicrystal scanning gamma camera. User handbook. Bedfurd, MA: Baird Corp, Nuclear Division, 1980 Rochester DF, Findley LJ. The lungs and neuromuscular and chest wall diseases. In: Murray JF, Nadel JA, eds. Textbook of respiratory medicine. Philadelphia: WB Saunders Co, 1988:1942-71 Celli BR. Clinical and physiologic evaluation of respiratory muscle function. Clin Chest Med 1989; 10:199-214 NHLBI workshop summary-respiratory muscle fatigue. Am Bev Respir Dis 1990; 142:474-80 Gorini M, Ginanni R, Spinelli A, Duranti R, Andreotti L, Scano G. Inspiratory muscle strength and respiratory drive in patients with rheumatoid arthritis. Am Bev Respir Dis 1990; 142:289-94 De Troyer A, Deisser P. The effects of intermittent positive pressure breathing on patients with respiratory muscle weakness. Am Bev Respir Dis 1981; 124:132-37 Jones DR, Speier J, Canine IC, Owen R, Stull A. Cardiorespiratory responses to aerobic training by patients with postpoliomyelitis sequelae. JAMA 1989; 261:3255-58 Owen RR, Jones D. Polio residuals clinic: conditioning exercise program. Orthopedics 1985; 8:882-83
CHEST/ 101 / 1 I JANUARY, 1992
257
Progressive neuromuscular symptoms years after recovery from acute paralytic poliomyelitis have been termed the PPS. We describe a 52-year-old man who contracted poliomyelitis at age 9 years who fully recovered and 33 years later developed progressive dyspnea. Neurologic evaluation revealed bilateral paralysis of the vocal cords, generalized weakness, and accentuated mouth occlusion pressure and ventilatory responses to hypercapnic, hyperoxic breathing. An EMG and muscle biopsy showed changes consistent with acute and chronic denervation. Cardiopulmonary exercise evaluation demonstrated a pulmonary mechanical limit with excessive ventilation relative to C01 output. Tracheostomy and nocturnal positive pressure ven-
0
f the 300,000 survivors of acute paralytic poliomyelitis in the United States, 20 to 60 percent may develop PPS. 1•2 The onset of PPS occurs on the average 29 years after recovery from polio and at a mean age of 51 years. 1•2 Symptoms include weakness, shortness of breath, exercise intolerance, sleep disturbances and other nonspecific complaints. These range in severity from mild, stable disease to a progressive form resembling amyotrophic lateral sclerosis. 1•2 The pathophysiology appears to be one of denervation and aberrant re-innervation. 1•2 Exertional dyspnea may result when there is an imbalance between central respiratory drive and ventilatory capacity. In PPS, central respiratory drive may be abnormal, respiratory muscles may be weak, and WOB may be increased due to chest wall stiffness, atelectasis or bulbar involvement or both. 1•2 We present a case of PPS manifested by dyspnea and an abnormal response to exercise. An extensive physiologic evaluation was undertaken, the results of which may serve to provide further insight into PPS. The benefits of therapy resulting in decreased WOB and *From the Medical Services (Pulmonary and Critical Care Unit) and Department of Respiratory Care, Massachusetts General Hospital and Harvard Medical School, Boston. tSupported by a fellowship training grant (HL07534-12) from the National Institutes of Health. tSupported by NIH grant M01RR01066-1152. Manuscript received March 12; revision accepted June 7. Reprint requests: Dr. \flz Fragoso, Danbury Hospital, Danbury, Conn06810
254
tilation resulted in increased respiratory muscle strength, normalization of ventilatory drive and marked improve(Chest 1992; 101:254-57) ment in exercise capacity.
AT= anaerobic threshold; Keo= transfer factor; MVo. =oxygen consumption at peak exercise; NPPV =nocturnal positive pressure ventilation; PlOO =mouth occlusion pressure; Pdimax =maximal transdiaphragmatic pressure; PetC01 =endtidal C01 ; PK HR=peak heart rate; P-M=Passey-Muir; PPS= post-polio syndrome; REH= respiratory exchange; RMS= respiratory muscle stren&th; RVEF =right ventricular ejection fraction; VT/IC= ratio of tidal volume at peak exercise to inspiratory capacity; WORK= achieved work load during exercise
respiratory muscle rest are also described. CASE REPORT
A 52-year-old white man presented with a history of acute paralytic poliomyelitis at age 9 years. His course was complicated by respiratory failure requiring ventilatory support (iron lung) for nine months. His subsequent recovery was remarkable in that at age 17 years he was able to complete a marathon. In 1979, at age 42, he began to notice the gradual loss of strength of the shoulders and arms. By early 1988, he was experiencing orthopnea, sleeping difficulties and progressive dyspnea. An initial evaluation at an outside institution demonstrated respiratory muscle weakness and no evidence of obstructive or central sleep apnea on polysomnography. Support with a variety of nocturnal, noninvasive mechanical ventilators was attempted but discontinued due to patient discomfort (gastric distension with the nasal and face-mask ventilation; respiratory distress with body ventilators). He was admitted to the Massachusetts General Hospital in November 1988 for further study. Physical examination on admission was remarkable for orthopnea, easy fatigability of speech, wasting of the shoulder muscles and left calf, and a grade 3 of 5 weakness in neck and hip 8exors, deltoids, biceps, triceps, and grip. A chest x-ray film demonstrated low lung volumes with a mild elevation of the right hemidiaphragm relative to the left and a mild dextroconvex thoracic scoliosis. As a result of EMG testing and biopsy of the left deltoid muscle, acute and chronic denervation were evidenced. Cardiopulmonary evaluation was then pursued to define the individual factors limiting exertion. This included PFTs, measurement of respiratory muscle pressures, response to hyperoxic, hypercapnic breathing, and maximal incremental exercise testing. These results are shown in Tables 1 and 2. Predicted values for lung volumes and 8ow rates are derived from Crapo et al, 3 respiratory muscle pressures from Black and Hyatt,• maximal transdiaphrag-
Improvement in Exercise C8pacity in PostpoHomyelilis Patient (Vaz Fragoso, Kacmerek, Systrom)
matic pressures from Braun et al" and exercise performance from Wasserman et al.• The PFrs were performed with the patient in the sitting position. They revealed a moderate restrictive defect with preserved gas exchange by KCO. The Row-volume loop showed no segmental plateau defects. The ratio of VE to PlOO at rest was 3.30. A value less than 7 is consistent with a pulmonary mechanical abnormality, either restriction or obstruction. 7 Maximal respiratory muscle pressures measured at the mouth (MIP from RV and MEP from TLC) and Pdi max measured by esophageal and gastric balloons with a Mueller maneuver from RV confirmed severe inspiratory and expiratory muscle weakness. Central respiratory drive was increased as evidenced by exaggerated PlOO and VE responses to hyperoxic, hypercapnic breathing. Normal responses" are a PUXVPetC01 ratio of0.49±0.15 cm H10/ mm Hg and a VEIPetC01 ratio of 1.99±0.40 Umin/mm Hg. An upright maximal incremental bicycle exercise test was perfurmed. Breath-b)"breath collection of expired gases was accomplished through a two-way, non-rebreathing valve, pneumotachograph, 0 1 and CO, analyzers. Arterial blood samples for gases, pH and lactate were obtained at rest, every minute during exercise and 2.5 minutes fullowing exercise. First-pass radionuclide scan for determination of LVEF and RVEF were obtained prior to and at peak exercise.• The KI was determined in a manner similar to that described by Wasserman et al.• The results were as fullows: The MVo. was only 910 ml (38 percent predicted), indicating severely compromised exercise tolerance. The limit to exercise was characterized by a high dyspnea index and failure to achieve a lactate or ventilatory AT. (I'he dyspnea index" is the ratio of the VEmax to the MBC; the MBC is obtained by multiplying the FEV, by 35.) The MIP and MEP decreased even further following exercise and were associated with a breathing pattern at peak exercise of shallow breaths: peak respiratory rate of 50 breaths per minute, V1 of 863 ml, V1 to inspiratory capacity ratio of 0.47. Of interest, especially in view of the patient's response to C01 rebreathing, was the respiratory allcalosis observed throughout exercise. This occurred in the setting of a normal P (A-a)01 response. Stridor also was noted ' at peak exercise and was later shown by direct laryngoscopy to be due to bilateral vocal cord paralysis. (At rest, the vocal cords were in the paramedial position; there was some movement with phonation but no active abduction on deep inspiration.) Markers of pulmonary vascular disease" were minimal in view of the normal KCO at rest and the normal responses to exercise of the RVEF and P (A-a)01 • The elevated Vo/VT at rest and during exercise occurred in the setting of a shallow and rapid breathing pattern. Central cardiovascular function was normal for this level of exercise as shown by the normal increase in the LVEF and RVEF with exercise. As a result of severe respiratory muscle weakness, symptomatic UAO at the relatively low exercise 'WOrk load, and the intolerance to nocturnal, noninvasive mechanical ventilators, the patient underwent a tracheostomy to be followed by NPPY. Following discharge, the tracheostomy stoma was buttoned (modi&ed Olympic button) and a P.M valve attached during the day. At night, he received 8 to 10 h ofNPPV via a Life Care PLV-100 home mechanical ventilator. Controlled mechanical ventilation was achieved at a rate of9 breaths per minute in the assist-control mode with a VT of 1.0 Land a 8ow of 50 Umin. At fullow-up three months later, the patient related a marked increase in exercise capacity and resolution of sleep disturbances. This occurred in the absence of any formal exercise training program. 'Illbles 1 and 2 illustrate the dramatic improvement in PFrs, RMS and exercise performance. Exercise testing was perfurmed with the tracheostomy buttoned but without attachment of the P.M valve nor ABG measurements. The limit to exercise was now characterized by an early KI and a high PK HR (lld>le 2). The dyspnea index remained elevated but this occurred well after the
Pris FEV, (L) VC(L) FEV,NC PEFR(Us) TLC(L) FRC(L) RV(L) KCO (cc/min/mm HWL) MVV (%of MBC) MIP(cm H10) MEP(cm H.O) Pdi max A (cm H.O) PllXVPetC01 (cm H10/mm Hg) VEIPetCO,, (Umin/mm Hg)
Before Therapy
After Therapy
1.73 (49%) 1.86 (43%) (115%) 93 4.71 (55%) 3.95 (68%) 2.13 (63%) 2.09 (107%) 4.89 (96%) 113% A24(34%); B 15(21%) A59(44%); B 22(16%) 34 (38%) 0.77 (157%)
1.93 (63%) 2.38 (58%) (81%) 81 5.59 (67%) 4.35 (72%) 3.42 (105%) 2.14 (105%) 5.14 (104%) ND A63(89%); B 78(110%) A79(59%); B 104(75%) 53 (60%) 0.35 (71%)
3.5 (184%)
(84%)
1.6
*In the sitting position, before and after tracheostomy and NPPV (Rx) in a patient with PPS. Values in parentheses are percent predicted. A= before exercise; 8 =after exercise; ND= not determined. KI. Other noteworthy observations included a decrease in the PlOO and VE responses to C01 and an increase in the VEIPlOO ratio. These improvements were sustained at nine months post NPPV/ tracheostomy and were not significantly different from those at three months with the exception ofthe respiratory muscle pressures. These continued to improve, such that the MIP and MEP at rest were 71 (100 percent ofpredicted) and 135 (100 percent of predicted) cm H,O, respectively. COMMENT
In the case under discussion, a 52-ye~ld man presented with symptoms, signs, muscle biopsy, and Table 1-Eurciae Data• PFrs MV01 (Umin) WORK(W)
VEmax!MBC (%) VT/IC VEIPlOO (Umin/cm H.O) KI (Umin) + as % predicted Vo1max P(A-a)d01 (mm Hg) Vo/VT(%) LVEF(%) RVEF(%) PKHR pH Paco.
Before Therapy
After Therapy
0.91 (38%) 19 82 0.47 R3.3 P2.5
1.26 (5.1%) 108
none achieved
0.66 (28%)
R20t P21 t R56 P41 R62 P69 RSI P60 120 (73%) R7.47 P7.46 R33 P34
ND ND ND ND 165 (100%) ND ND
79 0.63 R4.7
*Maximal upright cycling befure and after tracheostomy and NPPV (I'herapy). Values in parentheses are percent predicted. R =rest, prior to exercise; P =at peak exercise; ND= not determined. tThis is equivalent to a Pa01 at rest of 89 and at peak exercise of 87. CHEST I 101 I 1 I JANUARY, 1992
255
EM G evidence of PPS developing 30 years after recovery from polio. His progressive exercise intolerance was due to a combination of an accentuated central respiratory drive, bilateral vocal cord paralysis and diminished RMS. Subsequent NPPV/tracheostomy was associated with normalization of central respiratory drive, improved RMS, and an increased exercise capacity. Central respiratory drive in neuromuscular disease is variable. Resting hyperventilation and an elevated response to hyperoxic, hypercapnic breathing has been noted in some of these patients. 111- 13 In PPS, little is known about central drive except that some of these patients have central sleep apnea. 1•2 Our patient had no evidence of central apnea by formal sleep testing. Rather, he exhibited an exaggerated ventilatory response at rest, during exercise and during C02 rebreathing. The normalization of central respiratory drive following NPPV/tracheostomy argues against the initial exaggerated response being the result of polioinduced damage to the ventilatory control center, but suggests its genesis to be the result of peripheral factors. Alternatively, changes in the PlOO values may have been due solely to changes in the FRC. The VE response to C02 rebreathing and to exercise, however, provided further confirmation of an exaggerated central respiratory drive. Although WOB curves were not obtained, the improvements in the FRC and the VE/PlOO ratio and the elimination of stridor at peak exercise imply that the WOB was reduced. Tracheostomy resulting in bypass of the UAO may have improved resistive work. Through a more effective spontaneous breathing pattern and by a periodic delivery of large V1 values (NPPV), an improvement in atelactasis may have led to a reduction in elastic work. (The latter does not necessarily contradict the work of De Troyer and Deisser since their findings are limited to IPPB. 14 ) The degree to which each component of the WOB or its subsequent intervention played a dominant role could not be ascertained at our level of testing. It is reasonable, however, to expect that once the patient's symptoms improved and remained stable that bypassing the UAO would be all that was needed. The finding of the UAO is at first glance surprising in view of the relatively preserved flow-volume loop and the results of the sleep polysomnography. This is not unusual, however, given that the course of a UAO may be insidious and brought on primarily by exercise. Furthermore, the discovery of the UAO probably explains why the patient tolerated so poorly the various forms of noninvasive ventilation. The patient's marked reduction in respiratory muscle pressures may have been secondary to weakness or fatigue or both. Recently, an NHLBI workshop 12 summarized muscle weakness as "a condition in which 256
the capacity of a rested muscle to generate force is impaired." Muscle fatigue was defined as a "loss in the capacity for developing force and/or velocity of a muscle, resulting from muscle activity under load and which is reversible by rest." 12 In our patient, reduced levels ofload may have been accomplished by a bypass of the UAO and relief of atelectasis. Respiratory muscle rest may have been achieved by the NPPV. This would thus suggest that the dramatic improvement in the patient's RMS following NPPV/tracheostomy could have been in part due to reduced respiratory muscle fatigue. Alternatively, it can be argued that the improvement in RMS was due to a spontaneous remission in the patient's PPS. Previous long-term follow-up studies of such patients, however, show at best plateaus in muscle strength rather than normalization. 2 In neuromuscular disease, the MVV and the VEmax (at peak exercise) usually decrease in direct proportion to the level of respiratory muscle weakness, but out of proportion to the predicted MBC. 5 •11 This is because a significant reduction in respiratory muscle pressures often precedes decreases in the lung volume on which the predicted MBC is based. In our case, however, a MVV maneuver and the VEmax at peak exercise approximated the MBC. It is likely that, despite respiratory muscle weakness and increased WOB, increased central respiratory drive was able to push VE toward its mechanical limit. Alternatively, the restrictive defect was due more to increased lung elastic recoil rather than to weakness. The dramatic improvement in the FRC following therapy argues in favor of the latter explanation. A normal response to a maximal incremental exercise test is characterized by a high PKHR and a normal AT and MVo2 •6 In PPS, exercise limits have been shown to include a high PKHR and a high RER in response to maximal incremental exercise. 15 Specific measures of exercise-related cardiopulmonary parameters such as the AT or dyspnea index have not been previously reported in the literature. In our patient, the initial exercise response was markedly abnormal and associated with a low MVo2 and PKHR as well as a failure to achieve an AT. This occurred in the setting of a high dyspnea index (VEmax/MBC) and is descriptive of a primary pulmonary mechanical limit. 6 The etiology of this limit is most likely due to the patient's diminished RMS and increased WOB (reduced MBC), as well as the accentuated central respiratory drive (elevated VEmax). Following NPPV/tracheostomy, exercise performance showed a dramatic improvement. This was in part due to improvements in the aforementioned factors which contributed to the elevated dyspnea index (RMS, WOB, central drive), thereby permitting a more prolonged exercise effort. The exercise performance, however, remained abnormal hut was now characterized by an early AT. This
lmproYllRllll1t In Exercise Capaclly In Poslpollomy8lll Patient (Vaz Fragoso, Kat:metek, Systmm)
suggested a limit in either oxygen delivery or extraction. 6 In view of the patients normal central cardiovascular function by radionuclide ventrlculography and of the normal P(A-a)02 response, the limit was thus more suggestive of problems in peripheral 0 2 distribution and utilization. 6 The presumed etiology was involvement of the peripheral exercising musculature by PPS, vasoregulatory asthenia or deconditioning or both of the latter. It must be emphasized that our patient's improved exercise capacity with NPPV/tracheostomy was not improvement in aerobic capacity, given related to the absence of an /(f on the initial testing. Rather, the improvement was due to a normalization of the ve~tilatory response and an increase in the MBC. This suggests that in PPS the exercise limit may be of two types. Type 1 may be secondary to a pulmonary mechanical limit (high dyspnea index), while type 2 may be related to a peripheral 0 2 limit (early Kf with normal central cardiovascular function). The first would occur in the setting of severe respiratory muscle compromise and be treated primarily by measures directed at relieving respiratory muscle fatigue, such as through NPPV or tracheostomy (depending on the clinical presentation). The second would not have a primary respiratory limit but rather a peripheral 0 2 limit that could potentially be improved by a conditioning program such as that outlined by Jones et al15 and Owen and Jones. 16 Thus by determining whether a PPS patient has a type 1 or 2 exercise limit, one may be able to more specifically target therapy. This could be critical as attempts which only emphasize aerobic training may further compromise respiratory muscle function and exercise capacity in the type 1 limit. Further study is needed to confirm the existence and frequency of such limits. In conclusion, exercise intolerance in this patient with PPS seemed to be related to a ventilatory pump being fatigued by an increased work load and an abnormal central respiratory controller. Tracheostomy and NPPV resulted in near-normalization of RMS, central respiratory ~ve and exercise capacity. The relative importance of NPPV vs tracheostomy could
an
not be determined at our level of testing. Whether these observations apply to all patients with PPS requires further investigation. REFERENCES 1 Dalabs M, Hallet M. The post-polio syndrome. In: Plum F, ed. Advances in contemporary neurology. Philadelphia: FA Davis Co, 1988:51-94 2 Dala1cas M, Elder G, Hallett M, Ravitts J, Baker M, Papadopoulos N, et al. A long-term fullow-up study of patients with post-poliomyelitis neuromuscular symptoms. N Engl J Med 1986; 314:959-63 3 Crapo RO, Morris AH, Gardner RM. Reference spirometric values using techniques and equipment that meet ATS recommendations. Am Bev Respir Dis 1981; 123:185-90 4 Black LF, Hyatt RE. Maximal respiratory pressures: normal values and relationship to age and sex. Am Bev Respir Dis 1969;
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pulmonary function in proximal myopathies. Thorax 1983; 38:616-23 Wasserman IC, Hansen JE, Sue DY, Whipp BJ. Principles of exercise testing and interpretation. Philadelphia: Lea and Febiger, 1987 Scott GC, Burki NK. The ratio of resting ventilation to mouth occlusion pressure: an index of resting respiratory function. Chest 1986; 89:4595 Burki NIC. Measurements of ventilatory regulation. Clin Chest Med 1989; 10:215-26 System seventy-seven, multicrystal scanning gamma camera. User handbook. Bedfurd, MA: Baird Corp, Nuclear Division, 1980 Rochester DF, Findley LJ. The lungs and neuromuscular and chest wall diseases. In: Murray JF, Nadel JA, eds. Textbook of respiratory medicine. Philadelphia: WB Saunders Co, 1988:1942-71 Celli BR. Clinical and physiologic evaluation of respiratory muscle function. Clin Chest Med 1989; 10:199-214 NHLBI workshop summary-respiratory muscle fatigue. Am Bev Respir Dis 1990; 142:474-80 Gorini M, Ginanni R, Spinelli A, Duranti R, Andreotti L, Scano G. Inspiratory muscle strength and respiratory drive in patients with rheumatoid arthritis. Am Bev Respir Dis 1990; 142:289-94 De Troyer A, Deisser P. The effects of intermittent positive pressure breathing on patients with respiratory muscle weakness. Am Bev Respir Dis 1981; 124:132-37 Jones DR, Speier J, Canine IC, Owen R, Stull A. Cardiorespiratory responses to aerobic training by patients with postpoliomyelitis sequelae. JAMA 1989; 261:3255-58 Owen RR, Jones D. Polio residuals clinic: conditioning exercise program. Orthopedics 1985; 8:882-83
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