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Introduction: Experimental studies on animals have demonstrated a higher neuroprotective efficacy of hypercapnic hypoxia compared to normocapnic hypoxia. Respiratory training with hypercapnic hypoxia has shown a positive impact on the functional state of the nervous system in children with cerebral palsy (CP). It can be presumed that the combined effect of moderate hypercapnia and hypoxia will be promising for clinical application within the context of early rehabilitation after ischemic stroke., Methods: A randomized triple-blind placebo-controlled study was conducted on 102 patients with ischemic stroke, aged 63.07 ± 12.1 years. All patients were diagnosed with ischemic stroke based on neuroimaging criteria and/or clinical criteria within the 48-72 hour timeframe. The experimental group ( n  = 50) underwent daily respiratory training with hypercapnic hypoxia (FetCO2 5-6%, FetO2 15-16%) using the 'Carbonic' device for 7-11 sessions of 20 minutes each day during the treatment process. The control group (placebo, n  = 52) underwent training on a similar device modified for breathing atmospheric air. Neurological examinations were conducted on all patients before the study and on the day after completing the training course., Results: The standard treatment demonstrated effectiveness in terms of neurological status scales in both groups. Intermittent exposure to hypercapnic hypoxia proved more effective in improving neurological function indicators in patients compared to the placebo group: NIHSS scale scores were 40% lower than in the placebo group ( p  < 0.001); mRS scale scores were 35% lower ( p  < 0.001); B-ADL-I and RMI indices were higher by 26% ( p  < 0.01) and 36% ( p  < 0.001), respectively; MoCA scale results were 13% higher ( p  < 0.05); HADS and BDI-II scale scores were lower by 35% ( p  < 0.05) and 25% ( p  < 0.05), respectively. The increase in MMSE scale scores in the intervention group was 54% higher ( p  < 0.001), and MoCA scale scores increased by 25% ( p  < 0.001)., Conclusion: Respiratory training with hypercapnic hypoxia improves the functional state of the nervous system in patients with ischemic stroke. After conducting further clarifying studies, hypercapnic hypoxia can be considered as an effective method of neurorehabilitation, which can be used as early as 48-72 hours after the onset of stroke.

Summary: We present the clinical case of a 74 years old patient undergoing tracheotomy for persistent hypercapnic respiratory failure after lower right lobectomy surgery, performed as a result of pulmonary cancer recurrence. The patient was transferred to the Department of Respiratory Sub Intensive Care for respiratory weaning, decannulation and cycle of motor and respiratory physiotherapy. The joint evaluation of physicians, nurses and physiotherapists has allowed the identification of ICD-9 and ICF codes of the severe disability shown by the patient in the first days of hospital stay (respiratory failure due to pneumonia that need invasive mechanical ventilation by tracheotomy, prolonged immobility, muscular deconditioning and inability to perform even the simplest activities of daily life; it required also artificial nutrition by naso gastric tube). ICF codes as respiratory functions (respiratory system functions, additional respiratory functions, sensations associated with cardiovascular and respiratory functions, moving with aids, walking, vestibular functions, muscle strength, tolerance to physical exercise, personal care, performing the routine daily sleep functions, energy and drive functions), were particularly compromised at admission. Medical intervention (antibiotic therapy based on microbiological isolations, optimization of inhalatory therapy, management of intestinal complications and cardiological which required cardiological treatment remodulation in order to obtain better heart rate control and better blood pressure control allowed a clear improvement of general and respiratory clinical conditions. The simultaneous physiotherapists'intervention (weaning not only from invasive mechanical ventilation but also from tracheotomic cannula and oxygen therapy, stationary and cycloergometer with arms and exercise training) and nurses'intervention (medication of pressure injuries, surveillance of the sleep-wake rhythm, management of the daily routine) allowed a gradual improvement of both motor and respiratory ability with a consequent indipendence in activities of daily living. Important were also psychological counseling and intervention of speech therapists (removal of naso gastric tube, once excluded dysphagia also by videofluoroscopy). During a long lasting clinical improvement, coincident with patient's discharge to home, has been assessed disability through ICF codes, largely improved under medical, nursing and physiotherapist profile., Competing Interests: The authors of this article have no conflict of interests to disclose., (Copyright© by Aracne Editrice, Roma, Italy.)

Background: This study is aimed to evaluate the effect of inspiratory muscle training (IMT) added to rehabilitation in patients with chronic obstructive pulmonary disease (COPD) who remain hypercapnic and use non-invasive ventilation after successful weaning., Methods: Patients received rehabilitation and were randomized to inspiratory muscle or sham training for 4 weeks. The primary outcome was distance walked within 6 min. Secondary outcomes were inspiratory muscle strength, endurance, lung function, and blood gas levels., Results: Twenty-nine patients participated in this study. Walking distance of the sham group increased from 93 ± 52 m at baseline to 196 ± 85 m at week 4 (p = 0.019, 95% CI: 11-196 m). Patients in the IMT group significantly improved their walking distance from 94 ± 32 to 290 ± 75 m (p < 0.0001 [107-286 m]; p = 0.04 [3-186 m] for between-group comparison). Patients in the IMT group increased their maximal inspiratory pressure from -35 ± 8 to -55 ± 11 cmH 2 O (p = 0.001; -6 to -33 cmH 2 O), while the increase in the sham group failed to reach significance (-29 ± 10 to -37 ± 13 cmH 2 O [-22 to 6 cmH 2 O]). Inspiratory power increased from 9.6 ± 5.4 to 20.7 ± 9.7 joules/min (2.6-19.5 joules/min, p = 0.003) in the IMT group, while no significant change occurred in the sham group (7.6 ± 4.2 joules/min at study entry and 11.1 ± 6.9 joules/min [-5.2-12.3 joules/min] at study end)., Conclusions: Rehabilitation of successfully weaned patients with COPD and persistent hypercapnia significantly improves functional exercise capacity. Additional IMT significantly enhances functional exercise capacity and increases respiratory muscle strength and power., (Copyright © 2016 Elsevier Ltd. All rights reserved.)

Background: Although the endurance shuttle walk test (ESWT) has proven to be responsive to change in exercise capacity after pulmonary rehabilitation (PR) for COPD, the minimally important difference (MID) has not yet been established. We aimed to establish the MID of the ESWT in patients with severe COPD and chronic hypercapnic respiratory failure following PR., Methods: Data were derived from a randomized controlled trial, investigating the value of noninvasive positive pressure ventilation added to PR. Fifty-five patients with stable COPD, GOLD stage IV, with chronic respiratory failure were included (mean (SD) FEV1 31.1 (12.0) % pred, age 62 (9) y). MID estimates of the ESWT in seconds, percentage and meters change were calculated with anchor based and distribution based methods. Six minute walking distance (6MWD), peak work rate on bicycle ergometry (Wpeak) and Chronic Respiratory Questionnaire (CRQ) were used as anchors and Cohen's effect size was used as distribution based method., Results: The estimated MID of the ESWT with the different anchors ranged from 186-199 s, 76-82% and 154-164 m. Using the distribution based method the MID was 144 s, 61% and 137 m., Conclusions: Estimates of the MID for the ESWT after PR showed only small differences using different anchors in patients with COPD and chronic respiratory failure. Therefore we recommend using a range of 186-199 s, 76-82% or 154-164 m as MID of the ESWT in COPD patients with chronic respiratory failure. Further research in larger populations should elucidate whether this cut-off value is also valid in other COPD populations and with other interventions., Trial Registration: ClinicalTrials.Gov (ID NCT00135538).

Background: Pulmonary rehabilitation (PR) has a positive impact on functional status and quality of life in patients with interstitial lung disease (ILD)., Objectives: This study investigated the effects of PR in hypercapnic ILD patients receiving nighttime noninvasive positive pressure ventilation (NPPV)., Methods: Consecutive ILD patients referred to a specialized inpatient PR center were included. All participated in a PR program. Those with hypercapnia received NPPV (NPPV group; n = 29); the remaining patients served as comparison group (n = 319)., Results: PR improved the 6-min walk distance by 64.4 ± 67.1 m versus baseline (p < 0.0001) in NPPV patients and by 43.2 ± 55.1 m (p < 0.0001) in the comparison group (difference 21.1 m, 95% confidence interval 0.5-41.8; p = 0.045). There was no change in total lung capacity during PR in NPPV recipients or the comparison group. Forced vital capacity significantly increased from baseline in the comparison, but not the NPPV group. NPPV recipients were significantly more likely than the comparison group to have improved dyspnea during PR (p = 0.049). There was no improvement in the 36-item Short Form (SF-36) physical component score in the NPPV group after PR, but there was in the comparison group. PR improved the SF-36 mental component score versus baseline in both groups., Conclusion: An individually tailored PR plus nighttime NPPV appears feasible in hypercapnic ILD patients and significantly improves exercise capacity and quality of life.

Background: Thoracic scoliosis is a lateral curvature of the spine associated with restrictive lung defects, manifested by a decrease in respiratory function tests. We undertook this study to evaluate the effect of a respiratory rehabilitation program over lung function in children with scoliosis., Methods: We carried out a prospective and deliberate intervention study including 25 consecutive patients, aged 6 to 18 years, diagnosed with thoracic scoliosis. The respiratory rehabilitation program was structured into two phases: institutional and private residence. Statistical analysis was carried out using descriptive parameters and paired t-test and Wilcoxon signed-ranks test. Spearman correlation was used to measure intensity of association among variables. Statistical significance was considered when p <0.05., Results: Idiopathic scoliosis was present in 52% of patients, with right dorsal curvature in 72%. Cobb angle average was 50.6° ± 29.7°. Most importantly, we found a negative correlation between this angle on left curvature and lung function. Initially, the main respiratory symptoms were dyspnea with poor effort tolerance in 52%. After treatment, 88% of patients were asymptomatic and only 4% presented poor effort tolerance. Oxygen saturation and forced vital capacity percentage had a significant increment after the program., Conclusion: Respiratory rehabilitation has a positive effect on increasing pulmonary function of children with scoliosis.

Background: COPD patients who remain hypercapnic after acute respiratory failure requiring mechanical ventilation have a poor prognosis. Long-term nocturnal non-invasive ventilation (NIV) may be beneficial for these patients. We hypothesized that stable patients on long-term NIV would experience clinical worsening after withdrawal of NIV., Methods: We included 26 consecutive COPD patients (63 ± 6 years, 58% male, FEV(1) 31 ± 14% predicted) who remained hypercapnic after acute respiratory failure requiring mechanical ventilation. After a six month run-in period, during which all patients received NIV, they were randomised to either continue (ventilation group, n = 13) or to stop NIV (withdrawal group, n = 13). The primary endpoint was time to clinical worsening defined as an escalation of mechanical ventilation., Results: All patients remained stable during the run-in period. After randomisation the withdrawal group had a higher probability of clinical worsening compared to the ventilation group (p = 0.0018). After 12 months, ten patients (77%) in the withdrawal group, but only two patients (15%) in the ventilation group, experienced clinical worsening (p = 0.0048). Six-minute walking distance increased in the ventilation group., Conclusion: COPD patients who remain hypercapnic after acute respiratory failure requiring mechanical ventilation may benefit from long-term NIV., (Copyright © 2010. Published by Elsevier Ltd.)

To determine the immediate effects of bilevel non-invasive ventilation plus oxygen (NIV+O(2)) during exercise compared to exercise with O(2) alone in people recovering from acute on chronic hypercapnic respiratory failure (HRF), a randomised crossover study with repeated measures was performed. Eighteen participants performed six minute walk tests (6MWT) and 16 participants performed unsupported arm exercise (UAE) tests with NIV+O(2) and with O(2) alone in random order. Distance walked increased by a mean of 43.4m (95% CI 14.1 to 72.8, p=0.006) with NIV+O(2) compared to exercise with O(2) alone. In addition, isotime oxygen saturation increased by a mean of 5% (95% CI 2-7, p=0.001) and isotime dyspnoea was reduced [median 2 (interquartile range (IQR) 1-4) versus 4 (3-5), p=0.028] with NIV+O(2). A statistically significant increase was also observed in UAE endurance time with NIV+O(2) [median 201s (IQR 93-414) versus 157 (90-342), p=0.033], and isotime perceived exertion (arm muscle fatigue) was reduced by a mean of 1.0 on the Borg scale (95% CI -1.9 to -0.1, p=0.037) compared with O(2) alone. Non-invasive ventilation plus O(2) during walking resulted in an immediate improvement in distance walked and oxygen saturation, and a reduction in dyspnoea compared to exercise with O(2) alone in people recovering from acute on chronic HRF. The reduction of dyspnoea during walking and arm muscle fatigue during UAE observed with NIV+O(2) may allow patients to better tolerate exercise early in the recovery period.

The prevalence of patients with severe COPD and chronic hypercapnic respiratory failure (CHRF) receiving non-invasive home ventilation has greatly increased. With regard to disease severity, a multidimensional assessment seems indicated. Base excess (BE), in particular, reflects the long-term metabolic response to chronic hypercapnia and thus constitutes a promising, easily accessible, integrative marker of CHRF. Infact, BE as well as nutritional status and lung hyperinflation have been identified as independent predictors of long-term survival. In addition and in a review with the literature, a broad panel of indices including frequent comorbidities are helpful for assessment and monitoring purposes of patients with CHRF. Accordingly, in view of the patients' individual risk profile, the decision about the initiation of NIV should probably not rely solely on symptoms and chronic persistent hypercapnia but include a spectrum of factors that specifically reflect disease severity. Owing to the physiologically positive effects of NIV and according to retrospective data, patients with COPD and recurrent hypercapnic respiratory decompensation and patients with prolonged mechanical ventilation and/or difficult weaning could also be considered for long-term non-invasive ventilation. This, however, has to be corroborated in future prospective trials., ((c) Georg Thieme Verlag KG Stuttgart-New York.)

Objective: Compared to oronasal interfaces, a cephalic mask has a larger inner volume, covers the entire anterior surface of the face and limits the risk of deleterious cutaneous side effects during noninvasive ventilation (NIV). The present clinical study aimed to compare the clinical efficacy of a cephalic mask versus an oronasal mask in patients with acute hypercapnic respiratory failure (AHRF)., Design and Setting: Randomized controlled study in a Respiratory Intermediate Care Unit., Patients: All consecutive patients admitted for AHRF were randomly assigned to receive bilevel NIV either with a cephalic mask (n = 17) or an oronasal mask (n = 17) during the first 48 h., Measurements: The main outcome criterion was the improvement of arterial pH, 24 h after NIV initiation. Secondary criteria included PaCO(2) and physiological parameters., Results: Compared to values at inclusion, pH, PaCO(2), encephalopathy score, respiratory distress score and respiratory frequency improved significantly and similarly with both masks. None of these parameters showed statistically significant differences between the masks at each time point throughout the study period. Mean delivered inspiratory and expiratory pressures were similar in both patient groups. Tolerance of the oronasal mask was improved at 24 h and further. One patient with the cephalic mask suffered from claustrophobia that did not lead to premature study interruption., Conclusions: In spite of its larger inner volume, the cephalic mask has the same clinical efficacy and requires the same ventilatory settings as the oronasal mask during AHRF.

Background: Long-term non-invasive positive pressure ventilation (NIPPV) might improve the outcomes of pulmonary rehabilitation in patients with chronic obstructive pulmonary disease (COPD) with chronic respiratory failure. A study was undertaken to investigate whether nocturnal NIPPV in addition to pulmonary rehabilitation improves health-related quality of life, functional status and gas exchange compared with pulmonary rehabilitation alone in patients with COPD with chronic hypercapnic respiratory failure., Methods: 72 patients with COPD were randomly assigned to nocturnal NIPPV in addition to rehabilitation (n = 37) or rehabilitation alone (n = 35). Outcome measures were assessed before and after the 3-month intervention period., Results: The Chronic Respiratory Questionnaire total score improved 15.1 points with NIPPV + rehabilitation compared with 8.7 points with rehabilitation alone. The difference of 7.5 points was not significant (p = 0.08). However, compared with rehabilitation alone, the difference in the fatigue domain was greater with NIPPV + rehabilitation (mean difference 3.3 points, p<0.01), as was the improvement in the Maugeri Respiratory Failure questionnaire total score (mean difference -10%, p<0.03) and its cognition domain (mean difference -22%, p<0.01). Furthermore, the addition of NIPPV improved daytime arterial carbon dioxide pressure (mean difference -0.3 kPa; p<0.01) and daily step count (mean difference 1269 steps/day, p<0.01). This was accompanied by an increased daytime minute ventilation (mean difference 1.4 l; p<0.001)., Conclusion: Non-invasive ventilation augments the benefits of pulmonary rehabilitation in patients with COPD with chronic hypercapnic respiratory failure as it improves several measures of health-related quality of life, functional status and gas exchange.

We measured the ventilatory responses and subjective sensations during arm exercise in patients with lower cervical and upper thoracic spinal cord injuries in order to evaluate the effects of chest wall deafferentation on these responses. Visual analog scales with verbal descriptors were used to quantify respiratory sensations of different affectional qualities. Patients as well as normal subjects reported stronger respiratory sensations upon CO2 rebreathing as compared to during arm exercise with an equivalent minute ventilation (p<0.05). There were no qualitative nor quantitative differences in the respiratory sensations during CO2 rebreathing between the patients and normal subjects. However, patients with spinal cord injuries showed a higher minute ventilation and a lower end-tidal PCO2 during incremental arm exercises (p<0.01), and thus tended to hyperventilate. We conclude that chest wall afferent denervation does not contribute significantly to the perception of breathlessness in patients with spinal cord injuries.

The purpose of the lung is intrapulmonary gas exchange. The circulatory system delivers the respiratory gases to the tissue. The ventilatory pump however is responsible for the circulation of air between the lungs and the ambient atmosphere. Due to better diffusing capabilities, hypercapnia always is a result of pump failure and little dependent on the lung. Ventilatory failure, either compensated with an increased demand on the muscles or decompensated with an additional increase in pCO2, should be separated from lung failure where primarily oxygen exchange is involved. Decompensated hypercapnic ventilatory failure is then the indication for intermittent mechanical ventilation. The pCO2, either arterial or transcutaneously registered together with the noninvasive evaluation of the mouth occlusion pressures during tidal breathing and during a maximal inspiratory effort, define well the severity of ventilatory failure. In acute on chronic ventilatory failure, noninvasive mechanical ventilation in three randomised and controlled studies resulted in a better survival compared to intubation. To fulfil certain weaning criteria is no longer required in difficult to wean patients, as a transfer from invasive to noninvasive mechanical ventilation can be performed if only cooperativity is preserved together with a minimal capacity of spontaneous breathing. Weaning will thereafter occur by progressive relief from intermittent noninvasive ventilation. 2300 difficult to wean patients in Germany should profit from this approach. Chronic ventilatory failure as a result of neuromuscular disease or scoliosis of the thoracic spine are the classical indications. COPD and myasthenia gravis are under discussion as indications for intermittent mechanical ventilation with an increasing tendency to ventilate. Epidemiological data however can only be roughly estimated due to the heterogeneity of indication and selection of the patients.

Background: Weaning from the mechanical ventilator often proves to be difficult after prolonged ventilation due to excessive load or decreased capacity of the respiratory muscles. In the present retrospective study we examined the impact of the nocturnal mechanical ventilation during the "post-weaning-period" of long-term ventilated patients., Patients and Methods: We studied 43 patients (23 men, 59.1 +/- 14.6 years) with chronic respiratory failure who were transmitted from external ICUs after a mechanical ventilation period of 57.5 +/- 60.3 days. The weaning regime consisted of an individually adapted volume-cycled ventilation. If the patients were hypercapnic (pCO2 > 48 mm Hg) after the first 24-hour-period of spontaneous breathing without supplemental oxygen nocturnal mechanical ventilation was initiated., Results and Conclusions: In a retrospective study we could show that the decision to initiate invasive or noninvasive nocturnal mechanical ventilation after successful weaning primarily depends on the question whether a chronic hypercapnic respiratory failure persisted also after weaning from long-term mechanical ventilation. In about 40% of unselected patients nocturnal mechanical ventilation stabilized the weaning success whereas 60% of the patients did not need any further nocturnal mechanical ventilation.

The Aims of Our Study Were: 1) to evaluate the long-term efficacy of nocturnal IPPV either via tracheostomy (tIPPV) or a nasal mask (nIPPV) as a means to improve alveolar ventilation in patients with chronic severe hypercapnia caused by kyphoscoliosis; and 2) to assess the effect of MV on hospitalizations and life-style. Twenty six patients with kyphoscoliosis in chronic respiratory failure were enrolled in the study. Patients were divided into two groups. The first group comprised 13 subjects who had been clinically stable for at least 1 month (arterial carbon dioxide tension (Pa,CO2) 81 +/- 1.5 kPa (60.8 +/- 10.9 mmHg), arterial oxygen tension (Pa,O2) 7.3 +/- 0.8 kPa (54.6 +/- 6.1 mmHg)). The second group comprised 13 patients who were either suffering or recovering from an episode of acute respiratory insufficiency (Pa,CO2 9.0 +/- 1.8 kPa (67.8 +/- 13.3 mmHg), Pa,O2 6.8 +/- 1.1 kPa (51.2 +/- 8.2 mmHg), breathing supplemental oxygen in seven cases). Patients in the first group were treated with nocturnal IPPV via a nasal mask, whilst those in the second received nocturnal IPPV via tracheostomy. Similar improvements in arterial blood gases (ABGs) were achieved with both methods. Despite the differences in the degree of severity at baseline, after 1 month, ABG values were: Pa,CO2 6.2 +/- 0.6 kPa (46.6 +/- 4.4 mmHg), Pa,O2 9.0 +/- 1.3 kPa (67.5 +/- 9.6 mmHg) (nIPPV patients); Pa,CO2 6.1 +/- 0.9 kPa (46.1 +/- 6.8 mmHg), Pa,O2 9.8 +/- 1.3 kPa (73.6 +/- 9.8 mmHg) (tIPPV patients). After 1 yr, this improvement was still evident. Days of hospitalization were significantly reduced in both groups during the first year of MV. We conclude that both tIPPV and nIPPV are effective in the long-term treatment of respiratory failure in patients with kyphoscoliosis. It would appear from our data that if nIPPV is initiated early in the evolution of chronic respiratory failure in patients with kyphoscoliosis it will delay the necessity to use an invasive technique; however, long-term follow-up studies and larger case series are needed to demonstrate this.

Exercise programs are a mainstay of pulmonary rehabilitation for COPD. COPD patients with elevated PCO2 are severely impaired and might benefit from rehabilitation more than other patients. However, there is no systematic data to indicate that hypercapnic COPD patients benefit from intensive rehabilitation. Indeed, in patients with hypercapnia, increased exercise might overtax respiratory muscles, which are weak relative to those of eucapnic patients. To investigate this issue, we reviewed all COPD patients admitted to our pulmonary inpatient program from 1983 to 1986 (n = 317). The program includes multiple daily sessions of upper and lower extremity exercise to tolerance. We assessed admission and discharge pulmonary function tests, arterial blood gases (room air), and functional status. Ambulation distance on a 6-min walk test was used as an objective measure of functional status. Patients were grouped according to the results of their admission room air PCO2. We found that eucapnic patients (n = 197) significantly increased ambulation (admission to discharge) from 409 to 816 feet (p less than 0.001). Hypercapnic patients improved as well. Patients with moderate hypercapnia (PCO2, 45 to 54 mm Hg; n = 86) increased their ambulation from 330 to 663 feet (p less than 0.0001). Patients with severe hypercapnia (PCO2 greater than 54 mm Hg; n = 34) increased their ambulation from 336 to 597 feet (p less than 0.0001). We found a small but significant improvement in discharge pulmonary function and arterial blood gas results. We conclude that COPD patients with hypercapnia, despite severe ventilatory impairment and weak respiratory muscles, tolerate exercise well and benefit significantly from intensive inpatient pulmonary rehabilitation.