Predictors of severe chest infections in pediatric neuromuscular disorders.

Chest infections are serious complications in neuromuscular disorders. The predictive values of lung and respiratory muscle function including peak cough flow still remain unclear. We performed retrospective analysis of 46 children and adolescents (12.7+/-3.7 years) in whom lung function, respiratory muscle function and peak cough flows had been obtained. Data were related to: (1). number of chest infections and days of antibiotic treatment the year prior to the study and (2). history of severe chest infection requiring hospital admission. The number of chest infections and the number of days treated with antibiotics correlated with Inspiratory Vital Capacity IVC, peak cough flow PCF and Peak Expiratory Pressure PEP. Twenty-two patients were hospitalized at least once due to severe chest infection. IVC (0.65 vs. 1.44 l; P<0.0001) and PCF (116 vs. 211 l/min; P<0.0005) in these patients were significantly lower than in the non-hospitalized group. IVC<1.1l and PCF<160 l/min were specific and sensitive thresholds to discriminate between patients who had already suffered severe chest infections and those who had not. Therefore, spirometry and peak cough flow are reliable tests to identify patients at high risk for severe chest infections. Patients with IVC below 1.1l and/or PCF below 160 l/min should be well monitored and introduced to assisted coughing techniques.

[Diaphragmatic weakness and its impact on respiratory function in primary myopathies]. / Einfluss der Zwerchfellschwäche auf die respiratorische Funktion bei primären Myopathien.

BACKGROUND: Diaphragmatic weakness (DW) is a potential manifestation of primary myopathies. Prevalence and impact on respiratory function have not been defined. METHODS: Respiratory function (inspiratory vital capacity, IVC; maximal inspiratory muscle pressure, PImax; respiratory muscle effort, P (0.1)/PImax) and polysomnography/nocturnal capnometry (PtcCO(2)) was analysed in 49 patients with primary myopathies. DW was defined as > 25 % drop of IVC upon shift from upright to supine position. RESULTS: 19/54 (35 %) of patients, mostly AMD (68 %) and DMD (42 %) had DW. Restrictive ventilatory defect was moderate (IVC 37.2 +/- 26.2 %) in patients with and without DW (IVC 46 +/- 26 %, p = n. s.). DW caused a -33 %, respective - 25 %, supine drop of IVC and PImax, resulting in severe restriction in supine position (IVC (supine) 24.9 +/- 19.1 %, PImax (supine) 2.0 +/- 1.0 kPa, P (0.1)/PImax (supine) 19.9 +/- 12,8 %). All patients with DW and 75 % without had sleep-disordered breathing. This was significantly more severe in DW: 90 % (vs 17 % without DW) had continuous nocturnal hypoventilation (PtcCO(2) 62 +/- 2 mm Hg), 70 % (vs 18 % without DW) had combined nocturnal and diurnal hypercapnic respiratory failure (PaCO(2) 54,7 +/- 11.8 mm Hg). DW was an independent risk factor for sleep disordered breathing, for nocturnal and diurnal respiratory failure (r = 0.95, p < 0,05). Predictive thresholds thereof were accurate and identical to previously determined only for supine function data. CONCLUSION: DW is common in primary myopathies and predictive of nocturnal and diurnal respiratory failure. Supine respiratory function tests are necessary for clinical diagnosis and respiratory risk stratification.

Respiratory failure in Pompe disease: treatment with noninvasive ventilation.

In this study, noninvasive ventilation (NIV) was prospectively applied to eight patients (35.8 +/- 11.4 years) with late-onset Pompe disease and respiratory failure apparent from severe restrictive lung disease, nocturnal hypoxemia (83 +/- 8%), and daytime hypercapnia (66.7 +/- 17.9 mm Hg). The impact of NIV on respiratory function was followed for 34 +/- 17 months. Despite further decrease of vital capacity and inspiratory muscle strength, NIV normalized oxygen saturation during sleep (96 +/- 1%), daytime carbon dioxide tensions (44.1 +/- 3.6 mm Hg), and symptoms.

[Sleep-disordered breathing in neuromuscular diseases]. / Schlafbezogene Atmungsstörungen bei neuromuskulären Erkrankungen.

UNLABELLED: Sleep-disordered breathing is common in neuromuscular diseases but remains poorly defined in its relationship to daytime respiratory function. METHODS: We prospectively compared supine lung and respiratory muscle function with results of polysomnography/capnometry in 35 patients with progressive myopathies (age 32.5 +/- 15 years). RESULTS: 32/35 patients had restrictive ventilatory defect, 9/32 had hypercapnic respiratory failure by day (PaCO(2) 66.0 +/- 15.7 mm Hg). Supine inspiratory vital capacity (IVC(S)) correlated with maximal inspiratory muscle pressure (R = 0.75), respiratory muscle strain (P0.1/PImax, R = - 0.68), and daytime blood gases (p < 0.005 for all). SDB in the way of REM-sleep hypopneas, circumscribed hypoventilation episodes and sleep-stage independent continuous hypoventilation (PtcCO(2) > 50 mmHg > 50% of sleep time) was common at IVC(S)< 60% pred, and preceded daytime hypercapnia. IVC(S) correlated with nocturnal SaO(2) (R = 0.64), PtcCO(2) (R = - 0.87), percent light sleep (R = 0.67) and deep sleep (R = - 0.76). IVC(S) correlated only marginally with respiratory disturbance index (total sleep, R = - 0.45; REM-sleep, R = - 0.44). IVC(S) < 60% was 96% sensitive, 78% specific for presence of SDB. IVC(S) < 20 % was 89% sensitive, 96% specific for daytime hypercapnia. CONCLUSIONS: IVC(S) correlates with respiratory muscle function, daytime and nocturnal blood gases, and is highly predictive of SDB and daytime hypercapnia.

Long-term noninvasive ventilation in children and adolescents with neuromuscular disorders.

The aim of the current study was to investigate the long-term impact of nocturnal noninvasive (positive-pressure) ventilation (NIV) on sleep, sleep-disordered breathing (SDB) and respiratory function in children and adolescents with progressive neuromuscular disorders (NMD). Thirty patients (12.3 +/- 4.1 yrs) with various inherited NMD were treated with NIV for ventilatory insufficiency (n=14) or symptomatic SDB (n=16). Patients were prospectively followed with sleep studies, spirometry and peak inspiratory muscle pressure. Ten patients were studied before and after 3 nights withdrawal from NIV. NIV normalised nocturnal gas exchange in all patients and diurnal gas exchange in patients with ventilatory insufficiency. The effects persisted over 25.3 +/- 12.7 months. Nocturnal transcutaneous partial pressure of carbon dioxide improved from (baseline versus latest control) 7.1 +/- 1.3 to 5.5 +/- 0.6 kPa (53.7 +/- 9.9 to 41.6 +/- 4.8 mmHg), diurnal carbon dioxide arterial tension from 6.3 +/- 1.6 to 5.4 +/- 0.5 kPa (47.5 +/- 11.9 to 40.6 +/- 3.6 mmHg). NIV improved respiratory disturbance index, arousals from sleep, nocturnal heart rate and sleep architecture. Vital capacity decreased in five adolescents with Duchenne muscular dystrophy -183 +/- 111 mL x yr(-1) but remained stable in 25 children with other conditions (8 +/- 78 mL x yr(-1)). Three nights withdrawal of NIV in 10 previously stable patients resulted in prompt deterioration of SDB and gas exchange back to baseline but could be instantly normalised by resumption of NIV. Noninvasive (positive-pressure) ventilation has favourable long-term impact on nocturnal and diurnal gas exchange and sleep and in patients with non-Duchenne neuromuscular disorders on vital capacity as well. It is indicated in children and adolescents with symptomatic sleep-disordered breathing or ventilatory insufficiency due to neuromuscular disorders.

Patterns and predictors of sleep disordered breathing in primary myopathies.

BACKGROUND: Sleep disordered breathing (SDB) is common in neuromuscular diseases but its relationship to respiratory function is poorly defined. A study was undertaken to identify distinct patterns of SDB, to clarify the relationships between SDB and lung and respiratory muscle function, and to identify daytime predictors for SDB at its onset, for SDB with continuous hypercapnic hypoventilation, and for diurnal respiratory failure. METHODS: Upright and supine inspiratory vital capacity (IVC, % predicted), maximal inspiratory muscle pressure (PImax), respiratory drive (P(0.1)), respiratory muscle effort (P(0.1)/PImax), and arterial blood gas tensions were prospectively compared with polysomnography and capnometry (PtcCO(2)) in 42 patients with primary myopathies. RESULTS: IVC correlated with respiratory muscle function and gas exchange by day and night. SDB evolved in three distinct patterns from REM hypopnoeas, to REM hypopnoeas with REM hypoventilation, to REM/non-REM (continuous) hypoventilation, and preceded diurnal respiratory failure. SDB correlated with IVC and PImax which yielded highly predictive thresholds for SDB onset (IVC <60%, PImax <4.5 kPa), SDB with continuous hypoventilation (IVC <40%, PImax <4.0 kPa), and SDB with diurnal respiratory failure (IVC <25%, PImax <3.5 kPa). CONCLUSION: Progressive ventilatory restriction in neuromuscular diseases correlates with respiratory muscle weakness and results in progressive SDB which, by pattern and severity, can be predicted from daytime lung and respiratory muscle function.

Sleep-disordered breathing and respiratory failure in acid maltase deficiency.

BACKGROUND: Sleep-disordered breathing (SDB) and respiratory failure (RF) are complications of acid maltase deficiency (AMD), a rare hereditary myopathy. OBJECTIVE: To define the relationship between lung and respiratory muscle function, to establish incidence and patterns of SDB, and to determine daytime predictors of SDB. METHODS: Sitting and supine lung and respiratory muscle function tests were obtained in 27 subjects with juvenile and adult AMD (aged 39 +/- 19 years) and compared with outcomes of polysomnography. RESULTS: Ventilatory restriction was present in 17/27 subjects. Inspiratory vital capacity (IVC) correlated (p < 0.005) with peak inspiratory muscle pressure (PIP, R = 0.61), respiratory muscle strain (P(0.1)/P(0.1max), R = -0.68), and gas exchange by day (PaO(2): R = 0.71; PaCO(2): R = -0.64) and night (SaO(2): R = 0.73; P(tc)CO(2): R = -0.75). Diaphragm weakness (DW) was present in 13 subjects, 10 of whom had hypercapnic RF (PaCO(2) 65 +/- 7 mm Hg), and was associated with longer disease course. SDB was found in 13 subjects, 12 with DW. It was characterized by REM-sleep hypopneas that, as ventilatory restriction worsened, were complemented by hypoventilation (P(tc)CO(2) > 50 mm Hg) first in REM sleep, then in non-REM sleep (p < 0.005). SDB was predicted by DW (sensitivity 80%, specificity 86%) and nocturnal hypoventilation by IVC < 40% (sensitivity 80%, specificity 93%). Noninvasive ventilation, instituted for daytime respiratory failure or nocturnal hypoventilation, normalized daytime and nocturnal gas exchange (p < 0.005). CONCLUSION: Vital capacity correlates with respiratory muscle function in AMD. Diaphragm weakness is the major cause of SDB and RF. SDB and nocturnal hypoventilation are predictable from daytime function tests.

[Importance of medical history in diagnosis of respiratory insufficiency in patients suffering from neuromuscular diseases and thoracic deformities]. / Stellenwert der Anamnese in der Diagnostik der respiratorischen Insuffizienz bei Patienten mit neuromuskulären Erkrankungen und Thoraxdeformitäten.

Patients suffering from neuromuscular diseases and thoracic deformities may develop global respiratory failure during their illness. We wanted to judge clinical parameters and information from the patients' medical history to reliably, quickly and noninvasively diagnose a ventilatory failure. Therefore we evaluated 105 situations with and without mechanical ventilation from 29 patients with indication for noninvasive nocturnal mask ventilation. 6 clinical parameters (e.g. heart rate, oxygen saturation, relative vital capacity), 2 test results (pH and partial pressure of carbon dioxide (pCO2)) and 6 parameters from the patients' medical history (e.g. nycturia, frontal headache in the morning, breathlessness) were investigated. After statistical evaluation we could show a relation between heart rate and pCO2 (Spearman's correlation: r = 0.331, p = 0.001, n = 105; one-tailed significance: r = 0.335, p = 0.038, n = 29). Significant differences between the groups of nycturia incidence indicate a tight relation between the incidence of nycturia and the height of hypercapnia levels (ANOVA--analysis of variance: p = 0.001). Using logistic regression we could show that information regarding medical history, especially nycturia, frontal headache and indrawings, gives important indications for global respiratory failure (sensitivity 97.62-100%, specificity 57.14-76.19%). Pathogenesis needs to be elaborated further.

Effect of mouth leak on effectiveness of nasal bilevel ventilatory assistance and sleep architecture.

Mouth leak is common during nasal ventilatory assistance, but its effects on ventilatory support and on sleep architecture are unknown. The acute effect of sealing the mouth on sleep architecture and transcutaneous carbon dioxide tension (Ptc,CO2) was tested in 9 patients (7 hypercapnic) on longterm nasal bilevel ventilation with symptomatic mouth leak. Patients slept with nasal bilevel ventilation at their usual settings on two nights in random order. On one night, the mouth was taped closed. Leak was measured with a pneumotachograph. Median leak fell from 0.35+/-0.07 (mean +/- SEM) L x s(-1) untaped to 0.06+/-0.03 L x s(-1) taped. Ptc,CO2 fell in 8/9, including all hypercapnic patients. Across all patients, the mean Ptc,CO2 fell by 1.02+/-0.28 kPa (7.7+/-2.1 mm Hg) with taping (p = 0.007). Arousal index fell in every patient. Mean arousal index fell from 35.0+/-3.0 to 13.9+/-1.2 h(-1) (p<0.0001), and rapid eye movement (REM) sleep increased from 12.9+/-1.5% to 21.1+/-1.8% sleep time (p = 0.0016). Slow wave sleep changed inconsistently, from a mean of 13.1+/-1.6% to 19.5+/-2.2% of sleep (p = 0.09). Sleep latency and efficiency were unchanged. In four healthy volunteers ventilator-induced awake hypopharyngeal pressure swing during timed bilevel ventilation fell by 35+/-5% L(-1) x s(-1) of voluntary mouth leak (p<0.0001). Mouth leak reduces effective nasal bilevel ventilatory support, increases transcutaneous carbon dioxide tension, and disrupts sleep architecture.

Barrier effects of hyperosmolar signaling in microvascular endothelium of rat lung.

We determined the effects of hyperosmolarity on lung microvascular barrier properties by means of the split-drop technique in single venular capillaries of the isolated, blood-perfused rat lung. Using isosmolar and hyperosmolar test solutions (colloid osmotic pressure = 21 cm H2O), we quantified transcapillary flux at a fixed absorptive capillary pressure, and the capillary hydraulic conductivity (Lp). Loss of barrier function was indicated in flux reversal from isosmolar absorption to hyperosmolar filtration (P < 0. 01), and by hyperosmolarity-induced Lp increase (P < 0.01). Barrier recovery after a 1-min hyperosmolar exposure was delayed > 25 min. The flux reversal was blocked by the tyrosine kinase inhibitors genistein and MDC (P < 0.01). Genistein also inhibited the Lp increase (P < 0.01). Immunoblots of hyperosmolarity-exposed, cultured rat lung microvascular endothelial cells (RLMEC) and of endothelial cells freshly harvested from lungs given hyperosmolar infusions indicated a genistein-inhibitable enhancement of protein tyrosine phosphorylation. Immunoprecipitation studies indicated tyrosine phosphorylation of the mitogen activated protein kinases (MAPK) ERK1 and ERK2 and the adaptor protein Shc in lysates of RLMEC exposed to hyperosmolar conditions. We conclude that in lung venular capillaries hyperosmolarity deteriorates barrier properties, possibly by inducing tyrosine phosphorylation of endothelial proteins.

Nosocomial bacteremia due to Enterococcus faecalis without endocarditis.

During a 2-year observation period at a 2,200-bed university hospital, bacteremia due to Enterococcus faecalis was observed in 111 patients. Fifty-five patients with nosocomial bacteremia due to E. faecalis could be evaluated. The most common entry sites were the urinary tract (25%), the intraabdominal cavity (13%), and burn and decubital wounds (11%). Bacteremia was preceded by administration of cephalosporins, imipenem, and aztreonam (n = 39); ciprofloxacin (n = 11); and other antibiotics (n = 4). Age, sex, underlying disease, portal of entry, previous antibiotic therapy, and bacteremia due to other organisms had no influence on mortality. Treatment of bacteremia with penicillins (n = 45) and glycopeptides (n = 4) resulted in a mortality rate of 37%. The addition of a high-dose aminoglycoside to a penicillin did not result in a better survival rate.