Marjo J.T. van de Ven

Sleep, hypnotics and chronic obstructive pulmonary disease

The quality of sleep is significantly compromised in many patients with chronic obstructive pulmonary disease (COPD) and may be further diminished when certain comorbidities are present. A reduced sleep quality is associated with daytime consequences like fatigue, psychiatric problems and an impaired quality of life. Sleep induces physiologic alterations in respiratory function, which can become pathologic and may provoke or worsen hypoxemia and hypercapnia in COPD. Dyspnea, cough and excessive mucus production should be optimised to minimise causes for sleep disturbance. Pharmacological therapy may be helpful; sedatives like benzodiazepines and non-benzodiazepine benzodiazepine-receptor agonists (NBBRAs) are (equally) effective in improving sleep quality. Whether or not these hypnotics produce serious adverse respiratory effects during sleep, remains unclear due to opposing studies. Therefore, their use should be as short as possible.

Temazepam 10mg does not affect breathing and gas exchange in patients with severe normocapnic COPD.

BACKGROUND Benzodiazepines can improve sleep quality, but are also thought to cause respiratory depression in patients with chronic obstructive pulmonary disease (COPD). The aims of this study were to assess the effects of temazepam on indices of circadian respiratory function, dyspnea, sleep quality, and sleepiness in patients with severe COPD and insomnia. METHODS In a double-blind, randomized, placebo-controlled, cross-over study in 14 stable patients with COPD (mean FEV(1) 0.99+/-0.3L) with insomnia, polysomnography with continuous transcutaneous capnography and oximetry, arterial gas sampling, hypercapnic ventilatory response, multiple sleep latency test, Epworth Sleepiness Scale, dyspnea and sleep visual analogue scales (VAS) were performed at baseline, after one week of temazepam 10mg at bedtime and after one week of placebo. RESULTS Temazepam did not cause statistically significant changes in mean transcutaneous carbon dioxide tension during sleep compared to placebo (5.9+/-1.0 kPa vs. 6.3+/-1.4 kPa, p-value 0.27), nor in mean oxygen saturation (92+/-3% vs. 92+/-2%, p-value 0.31), nor in any of the other investigated variables, except for the total sleep time and sleep latency VAS, which improved with temazepam. CONCLUSIONS One week usage of temazepam 10mg does not influence circadian respiratory function, dyspnea, and sleepiness in patients with stable, severe, normocapnic COPD and insomnia and it improves total sleep time and subjective sleep latency. However, this is a preliminary explorative study for assessing the feasibility to perform a larger study on this topic. The clinical implications of this study are very limited.

Accuracy of transcutaneous carbon dioxide tension measurements during cardiopulmonary exercise testing.

Background: Measurements of transcutaneous carbon dioxide tension (PtcCO₂) with current devices are proven to provide clinically acceptable agreement with measurements of partial arterial carbon dioxide tension (PaCO₂) in several settings but not during cardiopulmonary exercise testing (CPET). Objectives: The primary objective of this study was to investigate the agreement between PaCO₂ and PtcCO₂ measurements (using a Tosca 500 with a Tosca sensor 92) during CPET. A secondary objective was to investigate the agreement between arterial and transcutaneous oxygen saturation (SaO₂, SpO₂) as measured with this sensor during CPET. Methods: In patients with various pulmonary diseases, PtcCO₂ and SpO₂ were continuously measured and compared with arterial blood gas samples during CPET. A maximum bias of 0.5 kPa and 95% limits of agreement (LOA) of 1 kPa between carbon dioxide pressure (PCO₂) measurements were determined as clinically acceptable. Results: In total 101 ‘paired’ arterial and transcutaneous measurements were obtained from 21 patients. Bias between PaCO₂ and PtcCO₂ was –0.03 kPa with LOA from –0.78 to 0.71 kPa. Bias between SaO₂ and SpO₂ was –1.0% with LOA from –2.83 to 0.83%. Conclusions: Transcutaneous estimations of PCO₂ and SpO₂ are accurate and can be used in CPET, circumvening the need for arterial cannulation.

Can Cerebral Blood Volume Be Measured Reproducibly With an Improved Near Infrared Spectroscopy System

In some circumstances, cerebral blood volume (CBV) can be used as a measure for cerebral blood flow. A new near infrared spectroscope was used for determining the reproducibility of CBV measurements assessed by the O2-method. Twenty-seven healthy subjects were investigated. An intrasubject coefficient of variation (CV) was calculated, based on four identical episodes of desaturation–resaturation (O2-method) procedures for CBV measurements. Two trials were performed, with (trial 1) and without (trial 2) disconnecting the equipment. A mean CV of 12.6% and 10.0% was found in trial 1 and 2, respectively. Cerebral blood volume values yield 3.60 ± 0.82 mL 100 g−1. Cerebral blood volume could be measured reproducible in adults using near infrared spectroscopy, if the arterial desaturation is limited to approximately 5% from baseline level.

Age dependency of cerebral oxygenation assessed with near infrared spectroscopy.

Near infrared spectroscopy (NIRS) is an optical technique that provides information on cerebral tissue oxygenation and hemodynamics on a continuous, direct, and noninvasive basis. It is used to determine cerebral blood volume (CBV) and cerebrovascular CO 2 reactivity during normoxic hyper- and hypocapnia in a group of 28 healthy volunteers aged 20 to 83 years. The main focus is on to the age dependency of the measured variables. The influence of changes in minute ventilation during normocapnia on the cerebral oxygenation was also studied. The mean CBV (±SD) in age was, for 20 to 30 years, 2.14±0.51 ml/100 g of brain tissue; for 45 to 50 years, 1.92±0.40 ml/100 g; and for 70 to 83 years, 1.47±0.55 ml/100 g. The CBV showed a significant decrease with advancing age. No influence was found for a change in minute ventilation on cerebral oxygenation. During hypercapnia cerebral blood flow (CBF) significantly increased in all age groups, with a factor of 1.31±0.17 kPa -1 , 1.64±1.39 kPa -1 , and 2.4±1.7 kPa -1 , respectively, for the three age groups. The difference in change among the age groups was not statistically significant (p=0.09). The trend seen was an increased change in CBF with advancing age. During hypocapnia, the CBF significantly decreased in all age groups, with a factor of 0.89±0.08 kPa -1 , 0.89±0.04 kPa -1 , and 0.85±0.11 kPa -1 , respectively. There was no significant difference among the age groups (p=0.50).

Ventilatory response in metabolic acidosis and cerebral blood volume in humans

The relationship between alterations in cerebral blood volume (CBV) and central chemosensitivity regulation was studied under neutral metabolic conditions and during metabolic acidosis. Fifteen healthy subjects (56+/-10 years) were investigated. To induce metabolic acidosis, ammonium chloride (NH(4)Cl) was given orally. CBV was measured using Near Infrared Spectroscopy during normo- and hypercapnia and related to inspired ventilation (V(i)). A mean acute metabolic acidosis of Delta pH - 0.04 was realized with a mean decreased arterialized capillary PCO(2) (P(c)CO(2)) of 0.20 kPa (1.5 mmHg) (both P<0.001). During normocapnia, CBV was 3.51+/-0.71 and 3.65+/-0.56 ml 100 g(-1) (mean+/-S.D.), measured under neutral metabolic conditions and during acute metabolic acidosis, respectively (ns). Corresponding values of V(i) were 7.6+/-1.4 and 10.0+/-2.4 l min(-1) (P<0.01), respectively. The slopes of the CO(2)-responsiveness (DeltaCBV/DeltaP(c)CO(2) and DeltaV(i)/DeltaP(c)CO(2)), were not significantly different during both metabolic conditions. A significant correlation between DeltaCBV/DeltaP(c)CO(2) and DeltaV(i)/DeltaP(c)CO(2) was found during metabolic acidosis (P<0.01), but not under neutral metabolic conditions. CBV does not contribute in a predictable way to the regulation of central chemoreceptors.

Respiratory muscle strength and muscle endurance are not affected by acute metabolic acidemia.

Respiratory muscle fatigue in asthma and chronic obstructive lung disease (COPD) contributes to respiratory failure with hypercapnia, and subsequent respiratory acidosis. Therapeutic induction of acute metabolic acidosis further increases the respiratory drive and, therefore, may diminish ventilatory failure and hypercapnia. On the other hand, it is known that acute metabolic acidosis can also negatively affect (respiratory) muscle function and, therefore, could lead to a deterioration of respiratory failure. Moreover, we reasoned that the impact of metabolic acidosis on respiratory muscle strength and respiratory muscle endurance could be more pronounced in COPD patients as compared to asthma patients and healthy subjects, due to already impaired respiratory muscle function. In this study, the effect of metabolic acidosis was studied on peripheral muscle strength, peripheral muscle endurance, airway resistance, and on arterial carbon dioxide tension (PaCO2). Acute metabolic acidosis was induced by administration of ammonium chloride (NH4Cl). The effect of metabolic acidosis was studied on inspiratory and expiratory muscle strength and on respiratory muscle endurance. Effects were studied in a randomized, placebo‐controlled cross‐over design in 15 healthy subjects (4 male; age 33·2 ± 11·5 years; FEV1 108·3 ± 16·2% predicted), 14 asthma patients (5 male; age 48·1 ± 16·1 years; FEV1 101·6 ± 15·3% predicted), and 15 moderate to severe COPD patients (9 male; age 62·8 ± 6·8 years; FEV1 50·0 ± 11·8% predicted). An acute metabolic acidemia of BE –3·1 mmol.L−1 was induced. Acute metabolic acidemia did not significantly affect strength or endurance of respiratory and peripheral muscles, respectively. In all subjects airway resistance was significantly decreased after induction of metabolic acidemia (mean difference –0·1 kPa.sec.L−1 [95%‐CI: −0·1 –−0·02]. In COPD patients PaCO2 was significantly lowered during metabolic acidemia (mean difference –1·73 mmHg [−3·0 –−0·08]. In healthy subjects and in asthma patients no such effect was found. Acute metabolic acidemia did not significantly decrease respiratory or peripheral muscle strength, respectively muscle endurance in nomal subjects, asthma, or COPD patients. Metabolic acidemia significantly decreased airway resistance in asthma and COPD patients, as well as in healthy subjects. Moreover, acute metabolic acidemia slightly improved blood gas values in COPD patients. The results suggest that stimulation of ventilation in respiratory failure, by induction of metabolic acidemia will not lead to deterioration of the respiratory failure.

Manual vs. automated analysis of polysomnographic recordings in patients with chronic obstructive pulmonary disease.

PurposeThe sleep quality, as assessed by polysomnography (PSG), of patients with chronic obstructive pulmonary disease (COPD) can be severely disturbed. The manual analysis of PSGs is time-consuming, and computer systems have been developed to automatically analyze PSGs. Studies on the reliability of automated analyses in healthy subjects show varying results, and the purpose of this study was to assess whether automated analysis of PSG by one certain automatic system in patients with COPD provide accurate outcomes when compared to manual analysis.MethodsIn a retrospective study, the full-night polysomnographic recordings of patients with and without COPD were analyzed automatically by Matrix Sleep Analysis software and manually. The outcomes of manual and automated analyses in both groups were compared using Bland–Altman plots and Students’ paired t tests.ResultsFifty PSGs from patients with COPD and 57 PSGs from patients without COPD were included. In both study groups, agreement between manual and automated analysis was poor in nearly all sleep and respiratory parameters, like total sleep time, sleep efficiency, sleep latency, amount of rapid eye movement sleep and other sleep stages, number of arousals, apnea–hypopnea index, and desaturation index.ConclusionAutomated analysis of PSGs by the studied automated system in patients with COPD has poor agreement with manual analysis when looking at sleep and respiratory parameters and should, therefore, not replace the manual analysis of PSG recordings in patients with COPD.