Dieter Köhler

Blood transfusion and lung function in chronically anemic patients with severe chronic obstructive pulmonary disease

OBJECTIVE To study in anemic patients with chronic obstructive pulmonary disease (COPD) whether blood transfusion reduces minute ventilation and work of breathing (WOB). DESIGN We prospectively evaluated the minute ventilation and WOB in 20 anemic adults (hemoglobin of <11 g/dL). Ten patients had severe COPD and ten patients were without lung disease. Measurements were made before and after receiving red blood cell transfusion; post-transfusion measurements were made 24 to 36 hrs after the last transfusion. SETTING The study was performed in the intensive care unit of a tertiary referral center for home mechanical ventilation and for patients considered difficult to wean from mechanical ventilation. PATIENTS Twenty clinically stable patients (12 female, eight male) with chronic anemia were studied. Ten patients with COPD (mean forced expiratory volume in 1 sec: 0.55+/-0.1 [SD] L) were compared with ten patients without lung disease. All participants had adequate renal and left ventricular function. INTERVENTIONS Patients received 1 unit of packed red blood cells for each g/dL that their hemoglobin value was less than an arbitrarily defined target value of 11.0 to 12.0 g/dL. Each unit was transfused over 2 hrs and < or =3 units in total was given. MEASUREMENTS AND MAIN RESULTS Esophageal pressure was measured from a catheter which was positioned in the middle of the esophagus. Flow was measured using a pneumotachygraph connected to a mouthpiece while a nose clip closed the nostrils during the measurements. From these data, respiratory rate, minute ventilation, and inspiratory resistive WOB were computed. Arterial blood gas values, oxygen saturation, hemoglobin, and hematocrit were also measured, and oxygen content was calculated before and 24 to 36 hrs after transfusion. In patients with COPD, hemoglobin increased from 9.8+/-0.8 to 12.3+/-1.1 g/dL due to a mean transfusion of 2.2+/-0.4 (SD) units of red blood cells. There was a reduction in the mean minute ventilation from 9.9+/-1.0 to 8.2+/-1.2 L/min (p < .0001); correspondingly, WOB decreased from 1.03+/-0.24 to 0.85+/-0.21 WOB/L (p< .0001). The capillary P(CO2) increased from 38.1+/-6.0 to 40.7+/-6.8 torr (5.1+/-0.8 to 5.8+/-0.9 kPa) (p < .05). Similarly, capillary P(O2) changed from 56.9+/-8.9 to 52.8+/-7.0 torr (7.6+/-1.2 to 7.0+/-0.9 kPa) (p < .05). In anemic patients without lung disease, minute ventilation, WOB, and the capillary blood gas values did not change after increase of the hemoglobin by a similar degree. CONCLUSIONS We conclude that red blood cell transfusion in anemic patients with COPD leads to a significant reduction of both the minute ventilation and the WOB. In these patients, transfusion may be associated with unloading of the respiratory muscles, but it may also result in mild hypoventilation.

Effect of non-invasive mechanical ventilation on sleep and nocturnal ventilation in patients with chronic respiratory failure

BACKGROUND Chronic respiratory failure (CRF) is associated with nocturnal hypoventilation. Due to the interaction of sleep and breathing, sleep quality is reduced during nocturnal hypoventilation. Non-invasive mechanical ventilation (NMV), usually performed overnight, relieves symptoms of hypoventilation and improves daytime blood gas tensions in patients with CRF. The time course of the long term effect of NMV on sleep and breathing during both spontaneous ventilation (withdrawing the intervention) and NMV was investigated in patients with CRF due to thoracic restriction. METHODS Fifteen consecutive patients (13 women) of mean (SD) age 57.9 (12.0) years with CRF due to thoracic restriction were included in the study. During the one year observation period four polysomnographic studies were performed: three during spontaneous breathing without NMV—before initiation of NMV (T0) and after withdrawing NMV for one night at six months (T6) and 12 months (T12–)—and the fourth during NMV after 12 months (T12+). Daytime blood gas tensions and lung function were also measured. RESULTS Spontaneous ventilation (in terms of mean oxygen saturation) progressively improved (from T0 to T12–) during both REM sleep (24.8%, 95% CI 12.9 to 36.9) and NREM sleep (21.5%, 95% CI 12.4 to 30.6). Sleep quality during spontaneous ventilation also improved in terms of increased total sleep time (26.8%, 95% CI 11.6 to 42.0) and sleep efficiency (17.5%, 95% CI 5.4 to 29.6) and decreased awakenings (54.0%, 95% CI 70.3 to 37.7). Accordingly, REM and NREM sleep stages 3 and 4 significantly improved. However, the most significant improvements in both nocturnal ventilation and sleep quality were seen during NMV at 12 months. CONCLUSIONS After long term NMV both spontaneous ventilation during sleep and sleep quality in patients with CRF due to thoracic restriction showed evidence of progressive improvement compared with baseline after withdrawal of NMV for a single night at six and 12 months. However, the greatest improvements in nocturnal ventilation and sleep were achieved during NMV at 12 months.

Long term effects of non-invasive mechanical ventilation on pulmonary haemodynamics in patients with chronic respiratory failure

BACKGROUND It is not known whether long term nocturnal mechanical ventilation (NMV) reduces pulmonary hypertension in patients with chronic respiratory failure (CRF). METHODS Pulmonary haemodynamics, spirometric values, and gas exchange were studied in 33 patients requiring NMV due to CRF (20 with thoracic restriction, 13 with chronic obstructive pulmonary disease (COPD)) at baseline and after 1 year of NMV given in the volume cycled mode. Patients with COPD also received supplemental oxygen. RESULTS Long term NMV improved gas exchange while lung function remained unchanged. Mean pulmonary artery pressure at rest before NMV was higher in patients with thoracic restriction than in those with COPD (33 (10) mm Hgv 25 (6) mm Hg). After 1 year of NMV mean pulmonary artery pressure decreased in patients with thoracic restriction to 25 (6) mm Hg (mean change –8.5 mm Hg (95% CI –12.6 to –4.3), p<0.01) but did not change significantly in patients with COPD (mean change 2.2 mm Hg (95% CI –0.3 to 4.8)). CONCLUSIONS Long term NMV in CRF improves pulmonary haemodynamics in patients with thoracic restriction but not in patients with COPD.

New method for easy labeling of beta-2-agonists in the metered dose inhaler with Technetium 99m

The actual deposition pattern of micronized drugs from metered dose inhalers (MDI) is incompletely known because there are no methods available to label the drugs (beta 2-agonists) with gamma-emitters. Indirect measurements of the distribution of the drug in man differed greatly due to the method used. Our method uses the better solubility of 99mTcO4- in the beta 2-agonist-micronized drug in relation to the propellant with surfactant. The principle is to extract the 99mTcO4- from the original water phase into the liquid phase of the propellant with ethyl methyl ketone. For labeling the micronized drug particles, the original MDI must be cooled to -60 degrees C and some labeled propellant (including surfactant) with high specific activity of 99mTcO4- is added through an aperture in the bottom of the container. The aperture is sealed with a screw. After rewarming the MDI, more than 90% of the added 99mTcO4- is dissolved in the beta 2-agonist-micronized drug in relation to its volume. This is proved by comparing the distribution of the radioactivity component with chemical analysis. The pattern of deposition of both MDIs - placebo and beta 2-agonist-micronized drug - was shown to be similar in healthy volunteers. With a labeled MDI a preliminary study with 2 different inhaling maneuvers was performed in 7 volunteers: inhaling from residual volume after a pause of 2 s the intrabronchial deposition was 18.7%, and inhaling at 50% of vital capacity maneuver the intrabronchial deposition was 33.0%. The data obtained with actual measurement of the inhaled drug from MDI suggest greater intrabronchial deposition than was assumed before in the literature.

Long-Term Oxygen Therapy Stops the Natural Decline of Endurance in COPD Patients with Reversible Hypercapnia

Background: Respiratory muscle weakness is one of the most important causes of hypercapnia in patients with COPD. There is evidence that stable hypercapnic patients will benefit from long-term oxygen therapy (LTOT). Objectives: The prognostic role of reversible hypercapnia in COPD is still unclear. Early implementation of LTOT in these patients may influence endurance time and mortality. Methods: In this pilot study, we investigated 28 patients (26 males, 49–74 years) with COPD, advanced airflow limitation [forced expiratory volume in 1 s (percentage of predicted value) 40.8 ± 10.2] and mild hypoxaemia (pO2 66.5 ± 6.3 mm Hg). All patients had developed a moderate reversible hypercapnia during an acute exacerbation or during exercise testing (peak pCO2 48.0 ± 2.5 mm Hg). Patients were allocated randomly to a control group (n = 14) or an LTOT group (n = 14). The two groups were well matched in terms of physiological data. Lung function, endurance time (cycle ergometer), dyspnoea score, blood gases and LTOT compliance were measured at baseline and every 6 months over a period of 3 years. Results: Endurance time increased from 6.4 ± 2.7 min at baseline to 7.1 ± 2.7 min after 1 year in the LTOT group and decreased from 6.1 ± 3.0 to 4.9 ± 3.8 min in the controls (p < 0.05). After 1 year, the end-exercise dyspnoea score was significantly lower in the LTOT group (4.5 ± 1.5) than in the controls (5.7 ± 1.9). Conclusion: COPD patients with reversible hypercapnia and mild hypoxaemia benefit from LTOT in terms of endurance time and a reduction of exertional dyspnoea after 1 year.

Usefulness of GOLD classification of COPD severity

In 2001 the US National Heart, Lung and Blood Institute (NHLBI) and the World Health Organization announced guidelines for the diagnosis, management, and treatment of COPD (Global Initiative for Chronic Obstructive Lung Disease, GOLD).1 One key aspect of these guidelines is that COPD is classified by severity into five stages which constitute the basis of treatment recommendations. However, to date there has been little evidence for the usefulness of these severity stages. We retrospectively reviewed 1000 patients with COPD diagnosed clinically in 2001; 500 patients originated from a pulmonary rehabilitation hospital. Patients’ symptoms (based on a standardised interview), findings of a standardised lung examination, lung function data, and chest radiographic findings are routinely documented in a …

Long-Term Lung Sequelae following Accidental Chlorine Gas Exposure

Acute exposure to sublethal doses of chlorine gas resulted in persistent pulmonary symptoms in 3 patients who had no past history of respiratory disease. The patients complained of intermittent dyspnea in association with respiratory irritants and physical exertion for more than 2.5 years postexposure. Four months after the accident bronchoalveolar lavage showed an inflammatory cell reaction, whereas 16 months later the differential cytology proved nearly normal. Moderate to severe nonspecific bronchial hyperresponsiveness was assessed in intervals of 4, 20 and 30 months after the accident. All patients showed the typical features of the reactive airways dysfunction syndrome defined as an asthma-like occupational illness after an acute exposure to highly concentrated respiratory irritants. We conclude that a single high exposure to chlorine gas may lead both to acute respiratory injury and to long-term reactive airway dysfunction with typical symptoms of inflammatory changes of the airways and nonspecific bronchial hyperresponsiveness.

Non-invasive mechanical ventilation improves walking distance but not quadriceps strength in chronic respiratory failure.

BACKGROUND In patients with chronic respiratory failure (CRF) nocturnal mechanical ventilation (NMV) confers increased exercise tolerance. The hypothesis tested in the present study was that the increased exercise performance is associated with increased quadriceps strength. METHODS In 28 patients with CRF due to chronic obstructive pulmonary disease and restrictive thoracic disease (post-tuberculosis-sequelae, scoliosis and obesity-hypoventilation) NMV was started. Before and after 2-month NMV the exercise tests, namely shuttle and 6-min walking distance, were performed. Furthermore, quadriceps strength was measured as the twitch tension elicited by magnetic stimulation the femoral nerve (TwQ) and the maximum voluntary contraction force (MVC). RESULTS After 2 months therapy with NMV there was significant clinical and blood gas improvement. NMV significantly improved the walking distance by approximately 18% but there was no improvement in TwQ or MVC, the data could exclude a 15% improvement in TwQ with 82% confidence. CONCLUSION The strength of quadriceps does not change after 2 months of effective NMV in patients with CRF despite a marked increase in endurance time. Factors other than quadriceps strength account for the improved performance.

Wertigkeit verschiedener intra- und extraoraler Therapieverfahren für die Behandlung der obstruktiven Schlafapnoe und des Schnarchens

ZusammenfassungHintergrundDer Stellenwert der intra- und extraoralen Hilfsmittel für die Therapie des obstruktiven Schlafapnoesyndroms (OSA) und des Schnarchens wird kontrovers diskutiert. Anhand der verfügbaren Literatur und eigener Ergebnisse nehmen wir eine Standortbestimmung zu dieser Thematik vor.Methodik und PatientenDie wesentliche Wirkung der Esmarch-Prothesen besteht in der Unterkiefervorverlagerung mit nachfolgender Erweiterung des Pharynxlumens. Das Wirkprinzip des Zungenextensors (SnorEx®) ist die Ventral- und Kaudalverlagerung des Zungengrundes mit Hilfe einer Pelotte; wir untersuchten 23 Patienten. Der Zungenretainer (Snore-Master®) besteht aus einem vor den Zahnreihen befindlichen geschlossenen Hohlkörper. Nach Einführen der Zungenspitze in diesen Hohlkörper hält der entstehende Unterdruck die Zunge in einer ventralen Position; 14 Patienten wurden von uns untersucht. Das Nasenpflaster (Breathe-Right®) enthält ein zentrales elastisches Plastikrückgrat, welches durch Zug der Nasenflügel nach kranial die Nasensotien erweitert und den Atemwegswiderstand reduzieren soll; es wurden 30 Patienten mit obstruktivem Schlafapnoesyndrom und 20 Schnarcher ohne obstruktives Schlafapnoesyndrom untersucht. Eine optisches Stimulationsverfahren („Brille”, Snore Stop®) besteht aus Augenkappen. Im Bereich des Nasenrückens sind ein Mikrophon und Leuchtdioden integriert. Nach Schnarchdetektion leuchten Lichtsignale auf, die über ein Arousal zum Wechsel der Körperlage führen sollen; 24 Patienten wurden untersucht.ErgebnisseEsmarch-Prothesen führten bei leicht- bis mittelgradigem obstruktivem Schlafapnoesyndrom zu einer Reduktion des Befundes, nicht jedoch zur Normalisierung der Atmung im Schlaf. Beim Zungenextensor kam es lediglich in 26% (17 von 23) der Fälle zu einer relevanten Reduktion von Apnoen und Schnarchen; eine komplette Beseitigung des obstruktiven Schlafapnoesyndroms gelang jedoch in keinem Fall. Im Gegensatz zu den Ergebnissen aus der Literatur konnten wir beim Zungenretainer keinen relevanten Therapieeffekt nachweisen. Bei dem Nasenpflaster und der Brille ergab sich keine Besserung des obstruktiven Schlafapnoesyndroms oder des Schnarchens. Lokale Beeinträchtigungen im Zungenbereich verursachten sowohl beim Zungenextensor als auch beim Zungenretainer häufig Intoleranz.SchlußfolgerungenInfolge fehlender Effektivität erwiesen sich das Nasenpflaster und das optische Stimulations-verfahren in der Therapie des obstruktiven Schlafapnoesyndroms und des Schnarchens als untauglich. Die Datenlage zum Therapieeeffekt des Zungenretainers ist widersprüchlich. Fehlende Prädiktoren zur Abschätzung des selten nachweisbaren Behandlungserfolges des Zungenextensors stehen einer häufigeren Anwendung entgegen. Insbesondere bei CPAP-Intoleranz bzw.-Incompliance von Patienten mit gering-bis mittelgradigem Befund scheint die Esmarch-Prothese eine therapeutische Alternative zu sein.SummaryBackgroundRecently intra- and extraoral devices are increasingly used in order to treat obstructive sleep apnea (OSA) and snoring. We examined the value of some devices according to the literature and our own results.Patients and MethodsThe mandibular advancing devices aim at increasing upper airway diameter. The active part of the tongue extending device (SnorEx®) is a stamp connected to a piston which exerts pressure at the base of the tongue causing its forward displacement; we studied 23 patients. The principle of an optically stimulating system („eye-cover”, Snore-Stop®) consists of a microphone and light diods which are integrated in the eyecover. After detecting acoustic signals (for example snoring) optical stimuli are generated in front of the eyes, which are thought to induce arousals causing a change of body position and the reduction of the snoring and apneas; we measured 24 patients. The principle of the tongue-retainer (Snore-Master®) is the fixation of the tongue in a ventral position, which is thought to enlarge the mesopharyngeal area; we studied 14 patients. The nose plaster (Breathe-Right®) contains an elastic spine that pulls the alae nasi cranial. This manipulation is thought to increase the diameter of the nostril and reduce the airway resistance. We measured 30 patients with obstructive sleep apnea and 20 snoring subjects without obstructive sleep apnea.ResultsRegarding the mandibular advancing due to different appliance designs and study protocols variable success rates have been documented. In patients with mild to moderate obstructive sleep apnea a reduction of the sleep related breathing disorder could be shown. Non compliance (NC) to the tongue extending device was 75% (17/23). Non-compliance-patients were characterized by unacceptable local-side-effects of the prosthesis, lacking improvement of symptoms and of the respiratory disturbance index. Both tongue-retainer and-extensor are characterized by a high incidence of local side effects. Neither the eye-cover nor the nose plaster could improve the severity of obstructive sleep apnoe or snoring. In contrast to another study we could not show a significant effect of the tongue-retainer.ConclusionsNeither the nose plaster nor the optical stimulating device influenced the degree of obstructive sleep apnea and snoring. There are conflicting data regarding the tongue retainer. The high rate of non-compliant subjects and the low efficacy of the tongue extending prosthesis precludes large-scale use of this treatment modality in patients with obstructive sleep apnea and snoring. In selected inviduals suffering from a mild to moderate degree of obstructive sleep apnea with CPAP-inefficiency and-incompliance the mandibular advancing principle may be an therapeutic alternative to CPAP.

Mucociliary Clearance in Patients with Chronic Bronchitis and Bronchial Carcinoma

We measured the mucociliary clearance rates and lung function data of 40 normal subjects, of 30 smokers with chronic bronchitis and of 64 patients with bronchial carcinoma. The mucociliary clearance rate of cancer patients was significantly lower than that of normal subjects and of patients with chronic bronchitis who smoked the same amount of cigarettes. The fast clearing phase of the central bronchial tree is more delayed than the peripheral mucociliary clearance rate in smokers with and without carcinoma. With our mucociliary clearance measurement we assessed the self-cleaning filter function of about the first 10 generations of the branching bronchial tree where also most bronchial carcinomas develop. The correlation between lung function data (MMEF) and smoking habits is much better (r = 0.73) than with the measured mucociliary clearance rates (r = 0.3), suggesting that inborn errors of mucociliary transport are nearly as important as external lung damage due to smoking and infection in the development of chronic bronchitis and bronchial carcinoma.