Nocturnal Nasal IPPV Stabilizes Patients with Cystic Fibrosis and Hypercapnic Respiratory Failure* Amanda) Piper; M.Ed.; Sally Parker; Paul) Torzillo, M.B., B.S.; Colin E. SuUioon, M.B., B.S., Ph.D.; and Peter L R Bye, M.B., B.S., Ph.D., F.C.C.R Nocturnal nasal intermittent positive pressure ventilation (nIPpv) has been used successfully in the management of patients with respiratory failure due to chest wall deformity and neuromuscular disease. In order to determine if nIPPV is useful in patients with cystic 6brosis (CF) complicated by respiratory failure, we treated four hypercapnic patients £Or up to 18 months. All patients had failed to respond to intensive conventional therapy, including nocturnal nasal CPAP in three of the patients. Within a few days of commencing nIPPV, all reported improved length and quality of sleep. There was lessening of the degree of hypercapnia and an increase in respiratory muscle strength. After stabilization in the hospital, all patients were able to
be discharged home receiving nocturnal assisted ventilation. The improvements seen in these patients have been maintained for up to 18 months. We believe nIPPV offers an effective therapeutic approach for patients with endstage CF in hypercapnic respiratory failure and may be particularly advantageous for those awaiting heart-lung transplant. (Chat 1992; 102:846-50)
For some years, nocturnal nasal intermittent positive pressure ventilation (nIPPY) has been used successfully in the management of patients with chronic respiratory failure due to neuromuscular disease or chest wall deformityl"" with improvement in both oxygenation during sleep and awake arterial blood gas tensions. More recently, this or similar techniques with use of a face mask have been studied in patients with chronic obstructive lung disease complicated by hypercapnic respiratory failure.5-7 We considered that this technique could also be useful in the management of patients with end-stage cystic fibrosis (CF) presenting with hypercapnia. We reasoned that ventilatory assistance during sleep might improve gas exchange and symptoms while awake. In addition, decrements in arterial oxygen saturation during rapid eye movement (REM) sleep have been documented in patients with CF and severe lung disease.8-l0 We felt that nocturnal hypoventilation with arterial oxygen desaturation and carbon dioxide retention could contribute to the progression of respiratory failure seen in these patients. Moreover, it has been
suggested that hypercapnia, a late occurrence in patients with CF, is a poor prognostic sign.ll Accordingly, we treated four patients with CF complicated by hypercapnic respiratory failure in order to determine if their clinical course, symptoms, and gas exchange would respond to nIPP~
*From the Department of Thoracic Medicine and Sleep Disorders U nit, Royal Prince Alfred Hospital, Camperdown, Australia. Manuscript received May 17; revision acce~ted December 30. &print requests: Ms. Piper; Sleep Unit, Roytilltince Alfred Hospital, Missenden Road, Camper-down NSW 2131, Australia
=
=
CF cystic fibrosis; nIPPV oasa1 intermittent positive pressure ventilation; NREM non-rapid eye movement; PEmus expiratory muscle pressure at tOtal I~ capacity; PImos = inspiratory muscle pressure at residual volume; REM rapid eye movement
=
=
=
METHODS
Patient details are given in 1able 1. Patients were scored for disease severity according to the standard NIH score. 12 Forced expiratory volume in one second and forced vital capacity were obtained with a wedge bellows spirometer. Inspiratory muscle pressure at residual volume (Plmus) and expiratory muscle pressure at total lung capacity (PEmus) were recorded using a hand-held pressure gauge calibrated from 0 to 200 em H 20. The gauge mouthpiece had a I-mm air lealc to prevent glottic closure during testing. Subjects were instructed to inhale and exhale with the glottis open and not to use their buccal muscles. The values quoted are the highest attained from five tests. Arterial oxygen and carbon dioxide tensions were measured by a blood gas analyzer from radial artery samples. These samples were usually taken in the morning, in the upright position, during outpatient clinic visits or prior to a hospital discharge. Nasal intermittent positive pressure ventilation was established using a Sullivan CPAP mask connected to a volume-cycled home ventilator in assist control mode. Oxygen at a flow of 2 Umin was added through a port in the nasal mask. A chin strap was needed in each patient to prevent excessive mouth leaks. On the first night of treatment, aU patients were closely observed either in the sleep unit (patients 1 and 3) or on a thoracic ward in
Table I-Clinical Detai& ofR>ur lbtient8 with CF and Hypercapnic Be8piratory Failure Patient No.lSexlAge, yr lIMI25 2/MfJO 3IMI29
4/F125
848
FEV.,L
FVC,L
FEV., %Pred
FVC,%Pred
NIHu Score
Body Mass Index, IqVsq m
0.55 0.55 0.5 0.55
1.2 1.45 1.8
14 16 11 14
30 36 16
25
46 44 35 53
18.8 18.1 17.3 17.5
0.69
Nocturnal Nasal IPPV Stabilzes Patients with CV (Piper et aI)
before
Table 1-Ser:W ArleriGl Blood Ga MetJiUnrnentI and after AtIminiItrtJliori of nlPPV Patient No. 11me Period
Measurement
Before IPPV 6mo
pll PaO.on air PaO.on2LO. PaCO.on air PaO.OD2LO. Base excess 1-2mo pH PaO.on air PaO.on2LO. PaCO.on air PaCO. on 2L O. Base excess Immediately pH prior PaO.onair PaO.on2LO. PaCO.on air PaCO. on 2L O. Base excess DuringIPPV lmo pH PaO.'on air PaO.on2LO. PaCO. on air PaCO. on 2L 0. Base excess 2mo pH NO. on air Pa~.on2LO.
6mo
PaCO. on ai:r Paeo. on 2L 0 1 Base excess pH Pa0lon air PaO.on2LO. PaCOlon air PaCO. on 2L O. Base excess
2
1
7.36
7.31
63
66
3
7.27 7.38 74
84
55
68 +11 7.29 37
+3 7.30 28
56 65 75
66 +5
4
36 65
+1 +1 7.33 7.37 70
95
68 75 +5 +13 7.30 7.30
+6 7.20
7.30
61
73
92
67 +5
85 88 +11 +9
7.29
7.40 53
7.30 7.29
+14
83
43
65
+4
+2 7.42
50
T*
45
67
64
86
67
67 55 +7 -1 7.40 7.34 49 69
55
49 +7 +4 +8 7.32t 7.45* 7.42 7.42 53 72 62 92 48
41 +6 +5 65
53 +6 +6
*Patient went to transplantation. tMeasurements taken after patient bad discontinued nIPPV for 6
days.
fl8ken several days after nIPPV recommenced. the immediate proximity of the sleep unit (patients 2 and 4). Once
the patient was comfortable with the ventilation equipment, over-
rdght recordings of oxygen saturation and transcutaneous carbon dioxide were made to ensure that: optimum settings for tidal volume and breathing rate had been achieved. Patient 2 bad a 10 em H.O PEEP valve added to the exhalation port of the nonrebreathing valve, as residual upper airway obstroction was observed. CASE REPORTS CASE 1
A 25-year-old man with CF had reqUired multiple hospital admissions and was progressively deteriorating. All night polysomnogr&phy performed in September 1987 revealed a drop in arterial 0X)'len saturation to 84 percent during non-REM (NREM) sleep, and to 74 percent during REM sleep, for which 2 Umin of oxygen during sleep was administered. The CPAP at 10 em H.O was
introduced in December 1988 when routine blood gas saIupling revealed a PaOI of38 mm Hg and PaC02 of69 mm Hg. He received this therapy for seven months. In June 1989, he was accepted into the heart-lung transplant program. One month later, he was readmitted to the hospital in severe respiratory failure and was producing copious quantities of green sputum. He was treated with intravenous antibiotics with minimal improvement. He reported poor sleep ciualit~ with frequent nocturnal awakenings. Despite CPAP and 2 Umin of oxygen, his PaO. remained in the 44 to 48 mm Hg range and the PaCOI continued to rise into the mid-90s. He experienced increasing difficulty expectorating, complaining of severe headaches and gradually became more difBeult to arouse. He was also extremely aggressive and confused when awake. A trial of riasal ventilation was started, and within two days, he began to feel subjectively much ~tter, despite his PaCO. remaining around 90 mm Hg with oxygen saturations between 85 percent and 88 percent. Initially, he slept for long peri~ on the ventilator both day and night. \Vithin three days of starting ventilation the~ he was able to tolerate physiotherapy sessions of up to 1 h, and he began producing large amounts of sputum. He also became less confused and aggressive, Nasal ventilation was continued in hospital for another four weeks before the patient was discharged home. Arterial carbon dioxide values showed a steady downward trend during this time (Table 2). Improvement in respiratory muscle strength after assisted ventilation also occurred (Table 3), although there \\'as no change in spirometric values. He received nocturnal nIPPV at home for three weeks before undergoing heart-lung transplantation. CASE
2
A 3o-YeaN>ld man with severe CF was first seen by our unit in February 1987. In August 1988, he required intubation and mechanical ventilation for acute hypercapnic respiratory failure from which he recovered weil. An all-night polysomnography study perfonned two months later revealed desaturations in NREM down to 88 percent, and in REM to 49 percent, despite 2 Umin of supplemental oxygen. CPAP of 10 em HIO pressure with 2 L of oxygen was commenced, and this was continued at home. His clinical condition remained relatively stable over the next few months, although his PaCOt continued to rise (49 to 55 mm Hg) aDd his FEV. was only 16 percent of predicted. In December 1989, he was again readmitted after routine blood gas samplings in the outpatient department showed a PaO. of 28 mm Hg and a PaCOI of 66 mm Hg, despite no obvious acute respiratory exacerbation. Although CPAP and oxygen therapy were continued, he began complaining of early morning headaches. He became extremely aggressive and very sleepy. Three weeks of intensive therapy failed to reverse his hypercapnia, and the decision to begin a trial ofnIPPV was made. Within ~ few days, his headaches bad resolved, daytime measurements of PaCO. started to fall (Table 2), and he was subjectively much improved. There was an improvement in respiratory muscle strength (Table 3), and his FEV. increased from a preventilation value of 0.5 L to 0.85 L after three months of treatment. In November 1990, he was readmitted for depression. During this time, he was taken off nocturnal ventilation for six days. The PaCO. while awake rose from a baseline of 43 mm Hg to 65 mm Hg. Reintroduction of nIPPV was associated with the return of the PaCO. back to normal levels (Table 2). CASE
3
A 29-year-old man with CF complicated by insulin-dependent
diabetes and malabsorption had used continuous home oxygen since 1988. An overnight sleep study performed in March 1989 demonstrated falls in oxygen saturation to 80 percent during NREM, and to 77 percent during REM. Two liters of oxygen prevented the desaturation. Prior to 1989, he had an average of one admission a CHEST I 102 I 3 I SEPTEMBER, 1992
847
Table 3-&.piratory Muck Strength
CASE 4
Patient No.
Pre-niPPY, cm H.O
One Month niPPY, cmH.O
Insp
Exp
Insp
Exp
1 2 3 4
48:t2· 62:t4 72:t3 55:t0
117:t2 72:t2 98:t3 75:t3
62:t2 87:t9 93:t2 68:t2
127:t2 120:t5 145:t3 143:t2
A 24-yeaM)ld woman with CF presented to our clinic for further management in November 1988. At that time, FEV, was ~ percent and FVC, 65 percent predicted. She was well nourisbed and had attended regular aerobic classes, and in fact, had a normal maximum exercise capacity. In July 1990, the patient became pregnant. She had a respiratory exacerbation in the few weeks prior to pregnancy and her FEV, had dropped to 52 percent predicted. Unfortunately, the patient deteriorated dramatically during the pregnancy. At 19 weeks' gestation, her spirometry had halved to an FEV, of 0.9 L and a vital capacity of 1.4 L. She was not treated with intravenous antibiotics during the first trimester, but thereafter, received regular treatment with intravenous ceftazidime and a short course of cipro80xacin. Despite prolonged hospitalization, she continued to deteriorate and at 30 weeks, she developed increasing respiratory distress. She was treated with nasal CPAP for five days but remained in respiratory distress with the onset of hypercapnia (Fig 1). An urgent cesarean section was performed at 30 weeks under epidural anesthesia, with subsequent transfer to the Intensive Care Unit. Initially, face mask and pressure support was used, but her hypercapnia did not improve and two weeks later, with PaCO. values still in the 80 to 90 mm Hg range, sbe was intubated and mechanically ventilated. Approximately one month later, a tracheostomy was performed. She was gradually weaned from assisted ventilation but still required either CPAP or pressure support at night with PaCO. values in the 70 to 85 mm Hg range. She was eventually discharged from the ICU after a stay of seven weeks and was transferred to the thoracic ward receiving 50 percent oxygen and the tracheostomy tube was removed. At this time, her PaCO. was still in the 80 to 90 mm Hg range. Five days after this transfer, she was given a further short trial of CPAP, but she did not tolerate this well and in view of her ongoing respiratory failure, it was decided to give her a trial of niPPY. The
·Values are mean:t SO. year for chest infections, but in the following 18 months, he had required four admissions, during which time PaCO. was in the range of54 to 65 mm Hg. In June 1990, he was again admitted with increasing dyspnea, cough, and sputum. The FEV, was 11 percent predicted. His condition began to deteriorate rapidly, and he was unable to move about in bed without marked shortness of breath. His cough was weak, and he became increasingly drowsy with severe headaches. Despite maximum medical therapy, his PaCO. continued to rise (78 to 93 mm Hg). A trial ofCPAP was unsuccessful. In view of his deterioration, nlPPV was started. Three days later, he was clinically improved, felt better, and was able to sleep throughout the night on the ventilator. He was no longer dyspneic at rest, and carbon dioxide levels began to fall ('Thble 2). Some days later, he developed hemoptysis of up to 120 ml a day, but this resolved spontaneously and did not prevent nocturnal assisted ventilation. Three weeks later, he was assessed by the heart-lung transplant team and accepted into the program. He has returned home receiving nocturnal ventilation to await transplant. Over the past 15 months, his Plmus has remained similar to the one-month postventilation value ('Thble 3), with the PEmus improving and plateauing at 165 cm H.O after three months. There has been no change in FEV, over the same time period.
I I
v
v
t'
V V
-CIt
" vv
80
E
E
oCJ
•
40
FICURE I. Changes in PaCO. measurements prior to and after the administration of nlPPV in patient 4, shown by diamonds. Triangles represent CO. values while in ICU where the patient was intubated and mechanically ventilated and later underwent tracheotomy. The bar graphs illustrate the changes in respiratory muscle strength over the treatment period.
• 00
180-
•~%COl
120-
· .. ·..
848
>-c>
o~
.. .c ~
CIt
Q,
:
~ ~f/)
~.
v
v
"
,• I
I. I
I I I I I
•
80
A.
2 E
.:•••
" • •• \'v " •I v
%
COl
•
v
90
• •
80-
40=
•
Pmus
.
8
5
•
• I•
!
•
•
niPPY commenced
• • •
•
-
inspD exp 111111 4
3
2
1
...
3
-
4
5
8
TIME SCALE (month.) NoctumaJ NasalIPPV SlabIIzes Patients with CV (Piper et aI)
patient started this therapy o~ March 8, 1991, and has progressively improved (Fig 1, Table 2). Five week$ after the initiation of nIPP~ the patient was discharged froni hospital. Her daytime energy level and exercise capacity have greatly improved, as has her respiratory muscle strength (Fig 1). The increase in respiratory muscle strength correlated with the faIl in PaCOI (r~O.89 for PImus and r=O.97 for PEmus). Her spirometry? which had been FEV. = O.55IFVC = 0.7 L immediately prior to nIPPV improved to 0.7511.2 L. She is able to attend an exercise rehabilitation program three times per week and has been accepted into the heart-lung transplant program. The baby is doing very weD. DiSCUSSION
Four patients with CF complicated by respiratory failure failed conventional therap~ Each was treated with and easily tolerated nIPP~ All demonstrated improved, blood gas values, lessening of severe dyspnea, .and subjec~ve improvement in sleep and in their level of daily activities. In addition, respiratory muscle stren~ improved and each individual was then better able to tolerate postural drainage and physiotherapy. This benefit and the increased expiratory muscle strength may coritribute to a more effective cough, as two patients reported improved secretion clearaD:ce after nasal ventilation was started. Screening sleep ~dies in our patients confirmed that during REM sleep, there was a fall in arterial oxy'gen saturation ~d a rise in arterial carbon dioxide levels.8-10 In the .pres~nce of hypercapnia, hypoxia, and acidosis, respiratory muscle function is compromised,13,14 further predisposing the patient to respiratory muscle fatigue. The patients improved rapidly with nIPP~ particularly in the first few weeks, and the mechanisms of improvement are probably multifactorial. During nIPP~ the spontaneous inspiratory effort of the patient is reduced,15 thereby lessening inspiratory muscle e.nergy expenditure and decreasing the work of breathing. Recently several workers 1&-19 have shown that intermittent rest of the respiratory muscles mcreases ~espiratory muscle strength and reduces PaC02~ rhese studies involved the use of negative pressure ventilators in patients with chronically stable prolonged airflow limitation. There hav~ .been fewer studies dU,ring nasal positive pressure ven.tilation where its role in the treatment of acute exace~bations of long-term lung disease have been investigated.5-7 Immediately prior to assisted ventilation, all our patients had a net acidosis despite the metabolic compensation indicated by a positive base excess. This progressively reversed with nasal IPP~ The correction of acid-base disturbances provides a more favorable milieu for optimum respiratory muscle function (Tables 2 and 3). Although serial tests of ventilatory responsiveness to hypoxia and hypercapnia were not performed in this stud~ the improved length and quality of sleep combined with improved oxygenation are likely to be associated with restoration ofchemoreceptor function.
Improved chemoreceptor function may help explain the trend toward more normal PaC02 levels in each of our patients. Nocturnal nIPPY is noninvasive, can be performed outside of an ICU, and does not necessitate sedation and immobilization of the patient. Our patients received nasal ventilation either on a respiratory medical ward or in the diagnostic sleep unit. After the initial stabilization period in the hospital, all patients were discharged home in a more stable and satisfactory clinical condition. In addition, it is possible that nlPPV may substantially reduce the demand on both hospital beds and ICU resources by patients awaiting heartlung transplantation. With the potential for long waiting periods prior to transplant, the clinical condition of many patients with end-stage disease is likely to deteriorate considerably, despite maximum conventional therap~ At present, the statistics from many centers suggest that approximately one quarter of patients will die while on the active waiting list for lung transplantation. The mortality rate for patients with CF awaiting transplant has been reported to be higher than that for other groupS.20 Nasal IPPV may retard this deterioration and may reduce the mortality rate for those awaiting transplant. Ofcourse, further long-term studies are required. The maintenance of good quality of life and adequate functional capacity are important goals of therapy for all patients with CF and severe lung disease. Use of nlPPV with consequent improvement in daytime function and arterial carbon dioxide tensions may facilitate patient involvement in rehabilitation! training programs appropriate for their clinical status. For patients awaiting lung transplantation, this is especially relevant as it has recently been reported that work capacity may still be only about one half of the predicted normal value even one to two years after transplantation. 21,22 We have demonstrated that nasal IPPV will improve hypercapnic respiratory failure, respiratory muscle strength, quality of life, and functional capacity in four patients with end-stage CF. Improvement in quality of sleep and daytime function has been observed for up to 18 months after initiation of this therapy. Nasal IPPV may offer an effective ~erapeutic approach for patients with end-stage CF with hypercapnic respiratory failure. We believe that this form of therapy is sufficiently promising to warrant further evaluation in a randomized and controlled trial. ACKNOWLEDGMENTS: The authors are grateful to the staff of the Sleep Disorders Unit, Royal Prince Alfred Hospital, for their technical assistance with the sleep studies, and to Professor Cliff Zwillich for his helpful comments. CHEST I 102 I 3 I SEPTEMBER, 1992
849
REFERENCES
1 Ellis ER, By~ ~ Bruderer ~ Sullivan CEo Treatment of respiratory failure during sleep in patients with neuroiriuscular disease. Am Rev Respir Dis 1987; 135:148-52 2 Kerby GR, Mayer LS, Pingleton st. N ~ positive p~ure ventilation via nas8I mask. Am Rev Respir Dis 1987; 135:738-40 3 Carroll N, Branthwaite MA. Control of nocturnai hypoventilation by nas8I intermittent positive preSsure ventilation. Thorax 1988; 43:349-53 4 Bach JR, Alba. A, Mosher R, Delaubie A. Intermittent positive pressure ventilation via nas8I access in the management of respiratory insufficiency. Chest 1987; 92:168-70 5 Bell D, Riordan JF, McNicol M~ Pratt C, Lam S. Noninvasive mechanical ventilation for acute respiratory failure. BMJ 1990;
300:944 6 Elliott M~ Stevens MH, Phillips GD, Branthwaite MA.
7
8
9 10
Noninvasive mechanical ventilation for acUte respiratory failure. BMJ 1990; 300:358-60 Bfochard L, Isabey D, Piquet J, Amaro ~ Mancebo J, Messadi A, et ale Reversal of acute exacerbations of chronic obstructive lung disease by inspiratory assistance with a face mask. N Engi J Med 1990; 323:1523-30 Muller N, Frances ~ Gurwitz D, Levison H, Bryan AC. Mechanism of hemoglobin desafuratiob during rapid eye move. ment sleep in normal subjects and in patients with cystic fibrosis. Am Rev Respir Dis 1980; 121:463-69 Frances PWJ, Muller NL, Gurwitz D, Milligan D, Levison H, Bryan A. Hemoglobin desaturation: its occurrence during sleep in patients with cystic fibrosis. Am J Dis Child 1980; 134:734-40 Tepper RS, Skatrud JB, Dempsey JA. Ventilation and oxygenation changes during sleep in cystic fibrosis. Chest 1983; 84:388-
93 11 di SanfAgnese PA, Davis PD. Cystic fibrosis in adults. Am J Med 1979; 66:121-30 12 Taussig LM, Kattwinkel J, Friedwald WI', di S8Ot'agnese PA. A new prognostic score and clinical evaluation system for cystic
850
fibrosis. J Pediatr 1973; 82:380-90 13 Juan G, Calverley ~ Talamo C, Schnader J, Roussos C. Effect of carbon di~xi~e on diaphragm function in human beings. N Engl J Med 1984; 310:874-79 14 Jardim J, Farkas G, Prefaut C, Thomas D, Macklem PT, Roussos CH. The failing inspiratory muscles under normoxic and hypoxic conditions. Am Rev Respir Dis i981; 124:274-79 15 Carrey Z, Gottfried SB, Levy RD. Ventilatory muscle support in respiratory failure with nasal positive pressure ventilation. Chest 1990; 97:150-58 16 Cropp A, Dimarco AF. Effects of intermittent negative pressure on respiratory muscle function in patients with severe chronic obstructive pulmonary disease. Am Rev Respir Dis 1987; 135:1056-61 17 Scano G, Gigliotti G, Duranti R, Spinelli A, Gorini M, Schiavina M. Changes in ventilatory muscle function with negative pressure ventilation in patients with severe COPD. Chest 1990; 97:322-27 18 Gutierrez M, Beroiza T, Contreras G, Diaz 0, Cruz E, Moreno R, et ale Weekly cuirass ventilation improves blood gases and inspiratory muscle strength in patients with chronic airflow limitation and hypercarbia. Am Rev Respir Dis 1988; 138:61723 19 Ambrosino N, Montagna T, Nava S, Negri A, Brega S, Fracchia C, et ale Short term effect of intermittent negative pressure ventilation in COPD patients with respiratory failure. Eur Respir J 1990; 3:502-08 20 Morrison D, Williams 1}, Patterson GA, Maurer JR. Selection of patients for lung transplantation. Am Rev Hespir Dis 1990; 141:682 21 Williams TJ, Grossman RF, Maurer JR. Long-term functional follow up of lung transplant recipients. Clin Chest Med 1990; 11:347-58 22 Miyoshi S, Trulock E~ Schaefers H, Hsieh C, Patterson GA, Cooper JD. Cardiopulmonary exercise testing after single and double lung transplantation. Chest 1990; 97:1130-36
Nocturnal NasalIPPV StabiIzes Patients with CV (Piper et 81)
be discharged home receiving nocturnal assisted ventilation. The improvements seen in these patients have been maintained for up to 18 months. We believe nIPPV offers an effective therapeutic approach for patients with endstage CF in hypercapnic respiratory failure and may be particularly advantageous for those awaiting heart-lung transplant. (Chat 1992; 102:846-50)
For some years, nocturnal nasal intermittent positive pressure ventilation (nIPPY) has been used successfully in the management of patients with chronic respiratory failure due to neuromuscular disease or chest wall deformityl"" with improvement in both oxygenation during sleep and awake arterial blood gas tensions. More recently, this or similar techniques with use of a face mask have been studied in patients with chronic obstructive lung disease complicated by hypercapnic respiratory failure.5-7 We considered that this technique could also be useful in the management of patients with end-stage cystic fibrosis (CF) presenting with hypercapnia. We reasoned that ventilatory assistance during sleep might improve gas exchange and symptoms while awake. In addition, decrements in arterial oxygen saturation during rapid eye movement (REM) sleep have been documented in patients with CF and severe lung disease.8-l0 We felt that nocturnal hypoventilation with arterial oxygen desaturation and carbon dioxide retention could contribute to the progression of respiratory failure seen in these patients. Moreover, it has been
suggested that hypercapnia, a late occurrence in patients with CF, is a poor prognostic sign.ll Accordingly, we treated four patients with CF complicated by hypercapnic respiratory failure in order to determine if their clinical course, symptoms, and gas exchange would respond to nIPP~
*From the Department of Thoracic Medicine and Sleep Disorders U nit, Royal Prince Alfred Hospital, Camperdown, Australia. Manuscript received May 17; revision acce~ted December 30. &print requests: Ms. Piper; Sleep Unit, Roytilltince Alfred Hospital, Missenden Road, Camper-down NSW 2131, Australia
=
=
CF cystic fibrosis; nIPPV oasa1 intermittent positive pressure ventilation; NREM non-rapid eye movement; PEmus expiratory muscle pressure at tOtal I~ capacity; PImos = inspiratory muscle pressure at residual volume; REM rapid eye movement
=
=
=
METHODS
Patient details are given in 1able 1. Patients were scored for disease severity according to the standard NIH score. 12 Forced expiratory volume in one second and forced vital capacity were obtained with a wedge bellows spirometer. Inspiratory muscle pressure at residual volume (Plmus) and expiratory muscle pressure at total lung capacity (PEmus) were recorded using a hand-held pressure gauge calibrated from 0 to 200 em H 20. The gauge mouthpiece had a I-mm air lealc to prevent glottic closure during testing. Subjects were instructed to inhale and exhale with the glottis open and not to use their buccal muscles. The values quoted are the highest attained from five tests. Arterial oxygen and carbon dioxide tensions were measured by a blood gas analyzer from radial artery samples. These samples were usually taken in the morning, in the upright position, during outpatient clinic visits or prior to a hospital discharge. Nasal intermittent positive pressure ventilation was established using a Sullivan CPAP mask connected to a volume-cycled home ventilator in assist control mode. Oxygen at a flow of 2 Umin was added through a port in the nasal mask. A chin strap was needed in each patient to prevent excessive mouth leaks. On the first night of treatment, aU patients were closely observed either in the sleep unit (patients 1 and 3) or on a thoracic ward in
Table I-Clinical Detai& ofR>ur lbtient8 with CF and Hypercapnic Be8piratory Failure Patient No.lSexlAge, yr lIMI25 2/MfJO 3IMI29
4/F125
848
FEV.,L
FVC,L
FEV., %Pred
FVC,%Pred
NIHu Score
Body Mass Index, IqVsq m
0.55 0.55 0.5 0.55
1.2 1.45 1.8
14 16 11 14
30 36 16
25
46 44 35 53
18.8 18.1 17.3 17.5
0.69
Nocturnal Nasal IPPV Stabilzes Patients with CV (Piper et aI)
before
Table 1-Ser:W ArleriGl Blood Ga MetJiUnrnentI and after AtIminiItrtJliori of nlPPV Patient No. 11me Period
Measurement
Before IPPV 6mo
pll PaO.on air PaO.on2LO. PaCO.on air PaO.OD2LO. Base excess 1-2mo pH PaO.on air PaO.on2LO. PaCO.on air PaCO. on 2L O. Base excess Immediately pH prior PaO.onair PaO.on2LO. PaCO.on air PaCO. on 2L O. Base excess DuringIPPV lmo pH PaO.'on air PaO.on2LO. PaCO. on air PaCO. on 2L 0. Base excess 2mo pH NO. on air Pa~.on2LO.
6mo
PaCO. on ai:r Paeo. on 2L 0 1 Base excess pH Pa0lon air PaO.on2LO. PaCOlon air PaCO. on 2L O. Base excess
2
1
7.36
7.31
63
66
3
7.27 7.38 74
84
55
68 +11 7.29 37
+3 7.30 28
56 65 75
66 +5
4
36 65
+1 +1 7.33 7.37 70
95
68 75 +5 +13 7.30 7.30
+6 7.20
7.30
61
73
92
67 +5
85 88 +11 +9
7.29
7.40 53
7.30 7.29
+14
83
43
65
+4
+2 7.42
50
T*
45
67
64
86
67
67 55 +7 -1 7.40 7.34 49 69
55
49 +7 +4 +8 7.32t 7.45* 7.42 7.42 53 72 62 92 48
41 +6 +5 65
53 +6 +6
*Patient went to transplantation. tMeasurements taken after patient bad discontinued nIPPV for 6
days.
fl8ken several days after nIPPV recommenced. the immediate proximity of the sleep unit (patients 2 and 4). Once
the patient was comfortable with the ventilation equipment, over-
rdght recordings of oxygen saturation and transcutaneous carbon dioxide were made to ensure that: optimum settings for tidal volume and breathing rate had been achieved. Patient 2 bad a 10 em H.O PEEP valve added to the exhalation port of the nonrebreathing valve, as residual upper airway obstroction was observed. CASE REPORTS CASE 1
A 25-year-old man with CF had reqUired multiple hospital admissions and was progressively deteriorating. All night polysomnogr&phy performed in September 1987 revealed a drop in arterial 0X)'len saturation to 84 percent during non-REM (NREM) sleep, and to 74 percent during REM sleep, for which 2 Umin of oxygen during sleep was administered. The CPAP at 10 em H.O was
introduced in December 1988 when routine blood gas saIupling revealed a PaOI of38 mm Hg and PaC02 of69 mm Hg. He received this therapy for seven months. In June 1989, he was accepted into the heart-lung transplant program. One month later, he was readmitted to the hospital in severe respiratory failure and was producing copious quantities of green sputum. He was treated with intravenous antibiotics with minimal improvement. He reported poor sleep ciualit~ with frequent nocturnal awakenings. Despite CPAP and 2 Umin of oxygen, his PaO. remained in the 44 to 48 mm Hg range and the PaCOI continued to rise into the mid-90s. He experienced increasing difficulty expectorating, complaining of severe headaches and gradually became more difBeult to arouse. He was also extremely aggressive and confused when awake. A trial of riasal ventilation was started, and within two days, he began to feel subjectively much ~tter, despite his PaCO. remaining around 90 mm Hg with oxygen saturations between 85 percent and 88 percent. Initially, he slept for long peri~ on the ventilator both day and night. \Vithin three days of starting ventilation the~ he was able to tolerate physiotherapy sessions of up to 1 h, and he began producing large amounts of sputum. He also became less confused and aggressive, Nasal ventilation was continued in hospital for another four weeks before the patient was discharged home. Arterial carbon dioxide values showed a steady downward trend during this time (Table 2). Improvement in respiratory muscle strength after assisted ventilation also occurred (Table 3), although there \\'as no change in spirometric values. He received nocturnal nIPPV at home for three weeks before undergoing heart-lung transplantation. CASE
2
A 3o-YeaN>ld man with severe CF was first seen by our unit in February 1987. In August 1988, he required intubation and mechanical ventilation for acute hypercapnic respiratory failure from which he recovered weil. An all-night polysomnography study perfonned two months later revealed desaturations in NREM down to 88 percent, and in REM to 49 percent, despite 2 Umin of supplemental oxygen. CPAP of 10 em HIO pressure with 2 L of oxygen was commenced, and this was continued at home. His clinical condition remained relatively stable over the next few months, although his PaCOt continued to rise (49 to 55 mm Hg) aDd his FEV. was only 16 percent of predicted. In December 1989, he was again readmitted after routine blood gas samplings in the outpatient department showed a PaO. of 28 mm Hg and a PaCOI of 66 mm Hg, despite no obvious acute respiratory exacerbation. Although CPAP and oxygen therapy were continued, he began complaining of early morning headaches. He became extremely aggressive and very sleepy. Three weeks of intensive therapy failed to reverse his hypercapnia, and the decision to begin a trial ofnIPPV was made. Within ~ few days, his headaches bad resolved, daytime measurements of PaCO. started to fall (Table 2), and he was subjectively much improved. There was an improvement in respiratory muscle strength (Table 3), and his FEV. increased from a preventilation value of 0.5 L to 0.85 L after three months of treatment. In November 1990, he was readmitted for depression. During this time, he was taken off nocturnal ventilation for six days. The PaCO. while awake rose from a baseline of 43 mm Hg to 65 mm Hg. Reintroduction of nIPPV was associated with the return of the PaCO. back to normal levels (Table 2). CASE
3
A 29-year-old man with CF complicated by insulin-dependent
diabetes and malabsorption had used continuous home oxygen since 1988. An overnight sleep study performed in March 1989 demonstrated falls in oxygen saturation to 80 percent during NREM, and to 77 percent during REM. Two liters of oxygen prevented the desaturation. Prior to 1989, he had an average of one admission a CHEST I 102 I 3 I SEPTEMBER, 1992
847
Table 3-&.piratory Muck Strength
CASE 4
Patient No.
Pre-niPPY, cm H.O
One Month niPPY, cmH.O
Insp
Exp
Insp
Exp
1 2 3 4
48:t2· 62:t4 72:t3 55:t0
117:t2 72:t2 98:t3 75:t3
62:t2 87:t9 93:t2 68:t2
127:t2 120:t5 145:t3 143:t2
A 24-yeaM)ld woman with CF presented to our clinic for further management in November 1988. At that time, FEV, was ~ percent and FVC, 65 percent predicted. She was well nourisbed and had attended regular aerobic classes, and in fact, had a normal maximum exercise capacity. In July 1990, the patient became pregnant. She had a respiratory exacerbation in the few weeks prior to pregnancy and her FEV, had dropped to 52 percent predicted. Unfortunately, the patient deteriorated dramatically during the pregnancy. At 19 weeks' gestation, her spirometry had halved to an FEV, of 0.9 L and a vital capacity of 1.4 L. She was not treated with intravenous antibiotics during the first trimester, but thereafter, received regular treatment with intravenous ceftazidime and a short course of cipro80xacin. Despite prolonged hospitalization, she continued to deteriorate and at 30 weeks, she developed increasing respiratory distress. She was treated with nasal CPAP for five days but remained in respiratory distress with the onset of hypercapnia (Fig 1). An urgent cesarean section was performed at 30 weeks under epidural anesthesia, with subsequent transfer to the Intensive Care Unit. Initially, face mask and pressure support was used, but her hypercapnia did not improve and two weeks later, with PaCO. values still in the 80 to 90 mm Hg range, sbe was intubated and mechanically ventilated. Approximately one month later, a tracheostomy was performed. She was gradually weaned from assisted ventilation but still required either CPAP or pressure support at night with PaCO. values in the 70 to 85 mm Hg range. She was eventually discharged from the ICU after a stay of seven weeks and was transferred to the thoracic ward receiving 50 percent oxygen and the tracheostomy tube was removed. At this time, her PaCO. was still in the 80 to 90 mm Hg range. Five days after this transfer, she was given a further short trial of CPAP, but she did not tolerate this well and in view of her ongoing respiratory failure, it was decided to give her a trial of niPPY. The
·Values are mean:t SO. year for chest infections, but in the following 18 months, he had required four admissions, during which time PaCO. was in the range of54 to 65 mm Hg. In June 1990, he was again admitted with increasing dyspnea, cough, and sputum. The FEV, was 11 percent predicted. His condition began to deteriorate rapidly, and he was unable to move about in bed without marked shortness of breath. His cough was weak, and he became increasingly drowsy with severe headaches. Despite maximum medical therapy, his PaCO. continued to rise (78 to 93 mm Hg). A trial ofCPAP was unsuccessful. In view of his deterioration, nlPPV was started. Three days later, he was clinically improved, felt better, and was able to sleep throughout the night on the ventilator. He was no longer dyspneic at rest, and carbon dioxide levels began to fall ('Thble 2). Some days later, he developed hemoptysis of up to 120 ml a day, but this resolved spontaneously and did not prevent nocturnal assisted ventilation. Three weeks later, he was assessed by the heart-lung transplant team and accepted into the program. He has returned home receiving nocturnal ventilation to await transplant. Over the past 15 months, his Plmus has remained similar to the one-month postventilation value ('Thble 3), with the PEmus improving and plateauing at 165 cm H.O after three months. There has been no change in FEV, over the same time period.
I I
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FICURE I. Changes in PaCO. measurements prior to and after the administration of nlPPV in patient 4, shown by diamonds. Triangles represent CO. values while in ICU where the patient was intubated and mechanically ventilated and later underwent tracheotomy. The bar graphs illustrate the changes in respiratory muscle strength over the treatment period.
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8
TIME SCALE (month.) NoctumaJ NasalIPPV SlabIIzes Patients with CV (Piper et aI)
patient started this therapy o~ March 8, 1991, and has progressively improved (Fig 1, Table 2). Five week$ after the initiation of nIPP~ the patient was discharged froni hospital. Her daytime energy level and exercise capacity have greatly improved, as has her respiratory muscle strength (Fig 1). The increase in respiratory muscle strength correlated with the faIl in PaCOI (r~O.89 for PImus and r=O.97 for PEmus). Her spirometry? which had been FEV. = O.55IFVC = 0.7 L immediately prior to nIPPV improved to 0.7511.2 L. She is able to attend an exercise rehabilitation program three times per week and has been accepted into the heart-lung transplant program. The baby is doing very weD. DiSCUSSION
Four patients with CF complicated by respiratory failure failed conventional therap~ Each was treated with and easily tolerated nIPP~ All demonstrated improved, blood gas values, lessening of severe dyspnea, .and subjec~ve improvement in sleep and in their level of daily activities. In addition, respiratory muscle stren~ improved and each individual was then better able to tolerate postural drainage and physiotherapy. This benefit and the increased expiratory muscle strength may coritribute to a more effective cough, as two patients reported improved secretion clearaD:ce after nasal ventilation was started. Screening sleep ~dies in our patients confirmed that during REM sleep, there was a fall in arterial oxy'gen saturation ~d a rise in arterial carbon dioxide levels.8-10 In the .pres~nce of hypercapnia, hypoxia, and acidosis, respiratory muscle function is compromised,13,14 further predisposing the patient to respiratory muscle fatigue. The patients improved rapidly with nIPP~ particularly in the first few weeks, and the mechanisms of improvement are probably multifactorial. During nIPP~ the spontaneous inspiratory effort of the patient is reduced,15 thereby lessening inspiratory muscle e.nergy expenditure and decreasing the work of breathing. Recently several workers 1&-19 have shown that intermittent rest of the respiratory muscles mcreases ~espiratory muscle strength and reduces PaC02~ rhese studies involved the use of negative pressure ventilators in patients with chronically stable prolonged airflow limitation. There hav~ .been fewer studies dU,ring nasal positive pressure ven.tilation where its role in the treatment of acute exace~bations of long-term lung disease have been investigated.5-7 Immediately prior to assisted ventilation, all our patients had a net acidosis despite the metabolic compensation indicated by a positive base excess. This progressively reversed with nasal IPP~ The correction of acid-base disturbances provides a more favorable milieu for optimum respiratory muscle function (Tables 2 and 3). Although serial tests of ventilatory responsiveness to hypoxia and hypercapnia were not performed in this stud~ the improved length and quality of sleep combined with improved oxygenation are likely to be associated with restoration ofchemoreceptor function.
Improved chemoreceptor function may help explain the trend toward more normal PaC02 levels in each of our patients. Nocturnal nIPPY is noninvasive, can be performed outside of an ICU, and does not necessitate sedation and immobilization of the patient. Our patients received nasal ventilation either on a respiratory medical ward or in the diagnostic sleep unit. After the initial stabilization period in the hospital, all patients were discharged home in a more stable and satisfactory clinical condition. In addition, it is possible that nlPPV may substantially reduce the demand on both hospital beds and ICU resources by patients awaiting heartlung transplantation. With the potential for long waiting periods prior to transplant, the clinical condition of many patients with end-stage disease is likely to deteriorate considerably, despite maximum conventional therap~ At present, the statistics from many centers suggest that approximately one quarter of patients will die while on the active waiting list for lung transplantation. The mortality rate for patients with CF awaiting transplant has been reported to be higher than that for other groupS.20 Nasal IPPV may retard this deterioration and may reduce the mortality rate for those awaiting transplant. Ofcourse, further long-term studies are required. The maintenance of good quality of life and adequate functional capacity are important goals of therapy for all patients with CF and severe lung disease. Use of nlPPV with consequent improvement in daytime function and arterial carbon dioxide tensions may facilitate patient involvement in rehabilitation! training programs appropriate for their clinical status. For patients awaiting lung transplantation, this is especially relevant as it has recently been reported that work capacity may still be only about one half of the predicted normal value even one to two years after transplantation. 21,22 We have demonstrated that nasal IPPV will improve hypercapnic respiratory failure, respiratory muscle strength, quality of life, and functional capacity in four patients with end-stage CF. Improvement in quality of sleep and daytime function has been observed for up to 18 months after initiation of this therapy. Nasal IPPV may offer an effective ~erapeutic approach for patients with end-stage CF with hypercapnic respiratory failure. We believe that this form of therapy is sufficiently promising to warrant further evaluation in a randomized and controlled trial. ACKNOWLEDGMENTS: The authors are grateful to the staff of the Sleep Disorders Unit, Royal Prince Alfred Hospital, for their technical assistance with the sleep studies, and to Professor Cliff Zwillich for his helpful comments. CHEST I 102 I 3 I SEPTEMBER, 1992
849
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850
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Nocturnal NasalIPPV StabiIzes Patients with CV (Piper et 81)
