The effect of low flow oxygen on sleep-disordered breathing and oxygen desaturation. A study of patients with chronic obstructive lung disease

Oxygen desaturation occurs during sleep in many patients with chronic obstructive lung disease (COLD) and is often caused by sleep-disordered breathing (SDB). Nocturnal oxygen therapy should improve nighttime hypoxemia, but might also worsen SDB. Using standard polysomnographic techniques, we evaluated the frequency and duration of oxygen desaturation and SDB during sleep in 11 patients with stable COLD. During half of the night the patients breathed air through a nasal cannula and during the other half of the night they breathed oxygen at 2 liters per minute. Five patients had arterial lines inserted for determination of arterial blood gas levels during periods of SDB or desaturation. The ten men and one woman slept 70 minutes (52 percent of time in bed) while on air and 111 minutes (80 percent of time in bed) while on oxygen (p < 0.001). Oxygen therapy reduced the number of episodes of desaturation per hour and the time spent in desaturation. However, there was no difference between air and oxygen in episodes of SDB per hour, the duration of episodes of SDB, baseline sleeping PaCO2 or PaCO2 during episodes of desaturation or SDB. Therefore, in most patients with stable COLD, administration of oxygen at 2 liters per minute improves oxygenation, prolongs sleep, but does not adversely affect SDB.     

Paradoxical response to valproic acid in a patient with a hypothalamic hamartoma

We investigated factors of daytime sleepiness in 22 middle-aged male patients with sleep apnea syndrome (SAS) using the Epworth sleepiness scale (ESS) and polysomnography. The subjects were classified into two groups according to ESS score as follows; low ESS group: ESS score < 10, and high ESS group; ESS score > or = 10. ESS score was significantly correlated with duration in which nocturnal oxygen saturation decreased below 90% (Time of SpO2 < 90%) (r = 0.54, p < 0.05). Time of SpO2 < 90% and percent of movement arousals at the termination of apnea/hypopnea (number of movement arousal/total number of apnea/hypopneas x 100) were significantly higher in high ESS group than in low ESS group. Our findings suggest that the severity of oxygen desaturation and sleep fragmentation caused by arousal response at the termination of apnea/hypopnea may be important factors of daytime sleepiness in patients with SAS.     

Twenty-four-hour ambulatory oxygen desaturation and electrocardiographic recording in obstructive sleep apnea syndrome

BACKGROUND: Although nocturnal pulseoximetry is routinely performed in obstructive sleep apnea syndrome (OSAS), pulseoximetry over a 24-h period has not been studied. HYPOTHESIS: The purpose of the study was to determine whether simultaneous 24-h oxygen desaturation and electrocardiographic (ECG) recording might be used to screen for daytime sleep sequelae in patients with OSAS. METHODS: Simultaneous recording of arterial oxygen saturation (SpO2) and ECG was conducted over a 24-h period in 18 male patients with OSAS (mean age 51.3 years) who were diagnosed by standard polysomnography (PSG), and in 15 age-matched healthy subjects (mean age 52.7 years) as controls to evaluate circadian variation of these parameters. The measures of heart rate variability (HRV) were calculated from 24-h ambulatory ECGs. Seventeen patients with OSAS showed excessive daytime sleepiness (EDS). We calculated the duration in which SpO2 decreased to < 90% (duration of SpO2 < 90%). The number of apnea/hypopneas per hour (AHI) during sleep was investigated with Apnomonitors (Chest MI, Co., Tokyo) on the same day as the SpO2 recordings. RESULTS: Controls showed no episodes of oxygen desaturation. In patients with OSAS, driving (33.3% of patients with OSAS) was the most common activity in which SpO2 decreased to < 90%, followed by daytime napping (27.8%) and resting after meals (22.2%). The duration of SpO2 < 90% over a 24-h period correlated significantly with the duration levels recorded during sleep (r = 0.99, p < 0.05) and in the afternoon (r = 0.62, p < 0.05), and with the AHI (r = 0.55, p < 0.05), but not with the duration of SpO2 < 90% in the morning. The number of ventricular premature beats correlated significantly with the duration of SpO2 < 90% for a 24-h period, but not with measures of HRV. Ventricular tachycardia was found in two (11.1%) and ST-T depression in three patients (16.6%) with underlying cardiac diseases. CONCLUSION: Our results suggest that daytime sleep attacks accompanied by oxygen desaturation in patients with moderate to severe OSAS may contribute to the occurrence of traffic or cardiovascular accidents. We conclude that 24-h ambulatory recordings of SpO2 and ECG are useful for screening for daytime sleep sequelae associated with the potential risk of this pathology in OSAS during social activities.     

Peripheral vascular disease evaluated with reduced-dose gadolinium-enhanced MR angiography

OBJECTIVE: To examine the effect of oxygen on apneas and sleep quality in patients with frequent central apneas during sleep. DESIGN/SUBJECTS: Prospective intervention study of 20 consecutive patients with predominant central apnea identified from 570 patients referred for suspected sleep apnea syndrome. Sixteen patients had congestive heart failure and seven of them had a previous stroke. Three of the remaining four patients without heart failure had experienced a previous stroke, and one was being treated with morphine. SETTING: The Department of Pulmonary Medicine at Ume? (Sweden) University Hospital. INTERVENTIONS: The patients were investigated for one night receiving nasal oxygen and one night without it. MEASUREMENTS: Overnight polysomnography with transcutaneous PCO2 and arterial blood gases. RESULTS: Central apneas occurred during Cheyne-Stokes respiration in 18 of 20 patients and two patients had idiopathic central apneas. Without oxygen, the median number of all central apneas and hypopneas was 33.5 (range, 8.0 to 52.0) per hour of sleep. These episodes decreased to 5.0 (range, 0.0 to 31.0)(p < 0.01) during oxygen therapy. In 17 of 20 patients, the frequency of central apneas was reduced by more than 50%. Central apneas were reduced by oxygen irrespective of the presence or absence of heart failure or Cheyne-Stokes respiration. The arousal frequency was reduced during oxygen treatment. Daytime sleepiness, difficulty falling asleep, snoring, and self-scored awakenings were reduced in seven patients who were given nocturnal oxygen at home. Obstructive and mixed apneas were unaffected by oxygen. CONCLUSIONS: Oxygen effectively reduces central sleep apnea in eucapnic patients.     

Acute von Willebrand factor secretion from the endothelium in vivo: assessment through plasma propeptide (vWf:AgII) Levels

STUDY OBJECTIVES: Patients with coronary heart disease (CHD) and obstructive sleep apnea may have an increased cardiac risk due to nocturnal myocardial ischemia triggered by apnea-associated oxygen desaturation. Sleep structure in patients with obstructive sleep apnea is fragmented by activation of the central nervous system (CNS) (arousal) due to obstructive apneas. Nocturnal myocardial ischemia may lead to activation of the CNS as well. PATIENTS: Fourteen patients with obstructive sleep apnea and CHD disease and seven patients suffering from obstructive sleep apnea without CHD were studied. Overnight sleep studies and simultaneous six-lead ECG recordings were performed. In addition, sleep studies and ECG recordings were performed with administration of a sustained-release nitrate in these patients in a double-blinded crossover design. RESULTS: Analysis of three nights' recordings revealed 144 episodes of nocturnal myocardial ischemia in six subjects. Five patients had underlying CHD and one patient exhibited diffuse wall defects of the coronary arteries; also, 85.4% of ischemic episodes were concomitant with apneas and oxygen desaturation > 3%, and 77.8% of ischemic episodes occurred during rapid eye movement (REM) sleep, although total amount of REM sleep was only 18% of total sleep time. Mean oxygen saturation was significantly lower (p < 0.05) during apnea-associated ischemic episodes than during nonapnea-associated ischemia (77.3% vs 93.1%). Nitrate administration did not reduce ischemic episodes. Sleep architecture (macrostructure) exhibited a reduction in sleep stages non-REM 3 and 4 and REM sleep. Comparing the microstructure of sleep (arousals) within episodes with and without ischemia but similar criteria like sleep stage, apnea activity, and oxygen saturation, we found significantly more (p < 0.01) and severe (p < 0.001) arousals during periods with myocardial ischemia than during control episodes. In addition, microstructure of sleep was disturbed by myocardial ischemia itself in absence of apneas. CONCLUSION: It is concluded that patients with CHD and obstructive sleep apnea are endangered by apnea-associated ischemia and that these ischemic episodes lead to activation of the CNS and additional fragmentation of sleep. Patients with nocturnal ischemia should be screened for underlying sleep apnea even if nitrate therapy fails.     

Screening of sleep apnea/hypopnea syndrome by home pulse oximetry

We evaluated the diagnostic accuracy and reproducibility of results obtained by home oximetry for the screening of sleep apnea/hypopnea syndrome. Our subjects were 40 patients who underwent home oximetry (12 patients for 1 night, 28 patients for 2 nights) followed by all-night polysomnography. Their mean age was 50.7 +/- 11.2 years; mean body mass index (BMI), 27.6 +/- 4.4 kg/m2; and mean apnea/hypopnea index (AHI), 36.0 +/- 26.0 hr-1. The data obtained by home pulse oximetry were fed into a personal computer, and utilized to calculate the desaturation cycles per hour (oxygen desaturation index (ODI) of 2-4%) and the percentage of time that SpO2 measured less than 90% (T 90). Polysomnography was used to monitor the number of apnea and hypopnea episodes per hour of sleep (AHI). With sleep apnea/hypopnea syndrome defined as AHI > or = 15, the diagnostic sensitivity and specificity of home pulse oximetry were 73.5% and 83.3%, respectively, when ODI-3 > or = 15 was used as the diagnostic standard. Patients who showed false negative results had a lower mean BMI (25.5 +/- 3.0) than those who showed true positive results (28.8 +/- 4.6). The reproducibility of ODI-3 data obtained at home was very high (r = 0.964, n = 28). In conclusion, home pulse oximetry seems to be a very useful tool for the detection of apnea/hypopnea syndrome, but false negative results should be considered a possibility, especially in patients who are not obese.     

Treatment of a patient with obstructive sleep apnea syndrome superimposed on chronic obstructive pulmonary disease

History of a middle aged obese male, presenting with severe obstructive sleep apnea (OSA) and chronic obstructive pulmonary disease (COPD) is described. Provisionally patient was started on CPAP and long-term domiciliary oxygen therapy (LTOT). OSA was successfully treated by surgical repair of nasal patency and partial uvulectomy. There was also remarkable improvement in ventilatory indices after steroid therapy. There was no further need for CPAP and LTOT.     

Effects of inhaled CO2 and added dead space on idiopathic central sleep apnea

We hypothesized that reductions in arterial PCO2 (PaCO2) below the apnea threshold play a key role in the pathogenesis of idiopathic central sleep apnea syndrome (ICSAS). If so, we reasoned that raising PaCO2 would abolish apneas in these patients. Accordingly, patients with ICSAS were studied overnight on four occasions during which the fraction of end-tidal CO2 and transcutaneous PCO2 were measured: during room air breathing (N1), alternating room air and CO2 breathing (N2), CO2 breathing all night (N3), and addition of dead space via a face mask all night (N4). Central apneas were invariably preceded by reductions in fraction of end-tidal CO2. Both administration of a CO2-enriched gas mixture and addition of dead space induced 1- to 3-Torr increases in transcutaneous PCO2, which virtually eliminated apneas and hypopneas; they decreased from 43.7 +/- 7.3 apneas and hypopneas/h on N1 to 5.8 +/- 0.9 apneas and hypopneas/h during N3 (P < 0.005), from 43.8 +/- 6.9 apneas and hypopneas/h during room air breathing to 5.9 +/- 2.5 apneas and hypopneas/h of sleep during CO2 inhalation during N2 (P < 0.01), and to 11.6% of the room air level while the patients were breathing through added dead space during N4 (P < 0.005). Because raising PaCO2 through two different means virtually eliminated central sleep apneas, we conclude that central apneas during sleep in ICSA are due to reductions in PaCO2 below the apnea threshold.     

Relapsing neurological melioidosis from the top end of the Northern Territory

We investigated the prevalence of ischemic heart disease (IHD) in sleep apnea syndrome (SAS) and the presence of coronary risk factors involved in the onset of IHD in 386 subjects with suspected SAS due to heavy snoring. The prevalence of IHD among patients with untreated SAS was found to be 23.8%, and the percentage of patients having SAS complicated with IHD was high among those with moderate or severe SAS. Sleep apnea syndrome patients with IHD also showed high prevalences of hypertension and hyperlipidemia. It appears that sleep apnea aggravates the factors that cause coronary vascular disorders, and is involved in the onset of IHD.     

Effects of inhaled nitric oxide and oxygen in high-altitude pulmonary edema

BACKGROUND: High-altitude pulmonary edema (HAPE) is characterized by pulmonary hypertension, increased pulmonary capillary permeability, and hypoxemia. Treatment is limited to descent to lower altitude and administration of oxygen. METHODS AND RESULTS: We studied the acute effects of inhaled nitric oxide (NO), 50% oxygen, and a mixture of NO plus 50% oxygen on hemodynamics and gas exchange in 14 patients with HAPE. Each gas mixture was given in random order for 30 minutes followed by 30 minutes washout with room air. All patients had severe HAPE as judged by Lake Louise score (6.4+/-0.7), PaO2 (35+/-3. 1 mm Hg), and alveolar to arterial oxygen tension difference (AaDO2) (26+/-3 mm Hg). NO had a selective effect on the pulmonary vasculature and did not alter systemic hemodynamics. Compared with room air, pulmonary vascular resistance fell 36% with NO (P<0.001), 23% with oxygen (P<0.001 versus air, P<0.05 versus NO alone), and 54% with NO plus 50% oxygen (P<0.001 versus air, P<0.005 versus oxygen and versus NO). NO alone improved PaO2 (+14%) and AaDO2 (-31%). Compared with 50% oxygen alone, NO plus 50% oxygen had a greater effect on AaDO2 (-18%) and PaO2 (+21%). CONCLUSIONS: Inhaled NO may have a therapeutic role in the management of HAPE. The combined use of inhaled NO and oxygen has additive effects on pulmonary hemodynamics and even greater effects on gas exchange. These findings indicate that oxygen and NO may act on separate but interactive mechanisms in the pulmonary vasculature.     

The effect of low-dose inhalation of nitric oxide in patients with pulmonary fibrosis

The aim of this study was to determine whether low-dose inhalation of nitric oxide (NO) improves pulmonary haemodynamics and gas exchange in patients with stable idiopathic pulmonary fibrosis (IPF). The investigation included 10 IPF patients breathing spontaneously. Haemodynamic and blood gas parameters were measured under the following conditions: 1) breathing room air; 2) during inhalation of 2 parts per million (ppm) NO with room air; 3) whilst breathing O2 alone (1 L.min-1); and 4) during combined inhalation of 2 ppm NO and O2 (1 L.min-1). During inhalation of 2 ppm NO with room air the mean pulmonary arterial pressure (Ppa 25 +/- 3 vs 30 +/- 4 mmHg) and the pulmonary vascular resistance (PVR 529 +/- 80 vs 699 +/- 110 dyn.s.cm-5) were significantly (p < 0.01) lower than levels measured whilst breathing room air alone. However the arterial oxygen tension (Pa,O2) did not improve. The combined inhalation of NO and O2 produced not only a significant (p < 0.01) decrease of Ppa (23 +/- 2 vs 28 +/- 3 mmHg) but also, a remarkable improvement (p < 0.05) in Pa,O2 (14.2 +/- 1.2 vs 11.7 +/- 1.0 kPa) (107 +/- 9 vs 88 +/- 7 mmHg)) as compared with the values observed during the inhalation of O2 alone. These findings suggest that the combined use of nitric oxide and oxygen might constitute an alternative therapeutic approach for treating idiopathic pulmonary fibrosis patients with pulmonary hypertension. However, further studies must first be carried out to demonstrate the beneficial effect of oxygen therapy on pulmonary haemodynamics and prognosis in patients with idiopathic pulmonary fibrosis and to rule out the potential toxicity of inhaled nitric oxide, particularly when used in combination with oxygen.     

Reduced visual capacity increases the risk of accidents in street traffic]

Six patients diagnosed with obstructive sleep apnea completed titration of an adjustable oral appliance, called the Silencer, during a single night of polysomnography. This protocol allowed for rapid titration of the oral appliance and effective treatment of sleep apnea. Variables which showed improvement included frequency of obstructive events, oxyhemoglobin saturation and snoring. Dental appliance adjustments with the silencer device can be made within three minutes. We have demonstrated that incremental mandibular advancement and repositioning allow us to determine the most effective jaw position to treat sleep apnea and snoring, which is also most likely to be tolerated by the patient.     

Endosteal hyperostosis--differential diagnosis and possible therapeutic outlook]

BACKGROUND: The sleep apnea syndrome (SAS) is a frequent disease associated with significant morbidity. The aim of our study was to investigate diseases associated with the sleep apnea syndrome (SAS) in general population. METHODS: We selected a random sample of 110 people from the electoral census. These people were invited to the clinic where medical history, physical examination and monitoring for sleep-disordered breathing was done. RESULTS: Twenty two subjects were diagnosed of SAS. The prevalence of arterial hypertension in the SAS group was 36.4%, and coronary artery disease 13.6%. CONCLUSIONS: Although the prevalence of this diseases was increased in the SAS group, we do not see significant association with this disease.     

Sleep apnea

Regular and unobstructed breathing during the night is the prerequisite for an undisturbed and restful sleep. The most prevalent nocturnal breathing disturbance with morbid consequences is the obstructive sleep apnea syndrome. Forms severe enough to need therapy and, therefore, a thorough work-up, can be usually detected by a detailed history. Pathophysiology, clinical findings, differential diagnosis as well as work-up and therapy of the sleep apnea syndrome are discussed.     

Capsular transformation of a multidrug-resistant Streptococcus pneumoniae in vivo

OBJECTIVE: To evaluate the effects of a mandibular advancement device on apneas and sleep in mild, moderate, and severe obstructive sleep apnea. DESIGN: Prospective study. SUBJECTS: Forty-four of 47 patients included. INTERVENTION: Individually adjusted mandibular advancement devices. MEASUREMENTS: Polysomnographic sleep recordings for 1 night without the device and 1 night with it, with a median of 1 day and no changes in weight, medication, or sleep position between the recordings. RESULTS: The device reduced the median obstructive apnea-hypopnea index from 11 (range, 7 to 19) to 5 (range, 0 to 17) (p<0.001) in 21 patients with mild sleep apnea, from 27 (range, 20 to 38) to 7 (range, 1 to 19) (p<0.001) in 15 patients with moderate sleep apnea, and from 53 (range, 44 to 66) to 14 (range, 2 to 32) (p<0.05) in 8 patients with severe sleep apnea. The arousal index decreased and the sleep stage patterns improved in all severity groups. Twenty-eight of 44 patients were successfully treated with an obstructive apnea-hypopnea index of below 10 and a subjective reduction in snoring. Nine of 16 patients with treatment failure still reported a reduction in snoring. The success rate correlated inversely to the disease severity (r=-0.41; p<0.01). CONCLUSIONS: A mandibular advancement device reduces apneas and improves sleep quality in patients with obstructive sleep apnea, especially in those with mild and moderate disease. A follow-up sleep recording during treatment is necessary because of the risk of silent obstructive apneas without subjective snoring with the device.     

Obstructive sleep apnea during pregnancy resulting in pulmonary hypertension

Obesity is known to increase maternal morbidity and mortality. We describe a case of obstructive sleep apnea due to obesity and discuss our treatment of the resulting pulmonary hypertension. A patient was transferred to our hospital at 29 weeks' gestation with severe anasarca and more than a 100-pound weight gain during pregnancy. Pulmonary hypertension due to obstructive sleep apnea was diagnosed. The patient was treated with nasal continuous positive airway pressure (CPAP) during sleep and remained in the hospital the remainder of her pregnancy. She had a massive spontaneous diuresis during her hospital stay and lost more than 100 pounds. She was delivered at term via cesarean section because of transverse lie. Preoperative hemodynamic monitoring confirmed the diagnosis of pulmonary hypertension. This represents the first case in the literature of obstructive sleep apnea leading to pulmonary hypertension in pregnancy. This patient responded well to nasal CPAP as evident by the massive diuresis and good maternal outcome.     

Successful surgical repair for a patient with atrial septal defect and severe pulmonary hypertension--its surgical indication and prostaglandin E1 use for postoperative pulmonary hypertensive crisis

A 45-year-old woman with atrial septal defect and pulmonary hypertension was admitted for surgical repair. Cardiac catheterization data revealed pulmonary to systemic flow ratio (Qp/Qs) of 1.81, pulmonary artery pressure (PAP) of 82/30 mmHg and pulmonary vascular resistance (PVR) of 10.8 unit. Open lung biopsy was added to evaluate pulmonary vascular obstructive disease (PVOD) which was shown Heath-Edwards grade 3 PVOD. Following closure of the defect, PAP (systolic) exceeded momentarily systemic level after cardiopulmonary bypass. Prostaglandin E1 drip was remarkably effective to bring down PAP during early postoperative period. Although PAP has not been shown significant decrease on catheterization of one year after surgery, great symptomatic improvement has been achieved.     

Neuropeptide regulation of proinflammatory cytokine responses

Severe postoperative hypoxaemia during sleep may increase the risk of postoperative cardiovascular complications. We hypothesized that the severity of hypoxic episodes after surgery are related to the presence of preoperative sleep-disordered breathing (SDB). We tested this hypothesis in a multicentre study designed to elucidate the major risk factors for development of postoperative nocturnal desaturations. We performed overnight oximetry before operation and for one night between the second and fourth day after operation in 80 patients undergoing major surgery. We calculated oximetry variables such as oxygen desaturation index (ODI), defined as the number of oxygen desaturations exceeding 4% below baseline, percentage time spent at SpO2 < 90% (CT90, %) and lowest SpO2 value. After operation, although the change in ODI was not significant (P = 0.34), deterioration in CT90 and lowest SpO2 values were significant (P = 0.036 and P = 0.007, respectively). Multivariate analysis of possible risk factors for postoperative desaturations revealed that preoperative hypoxaemia and apnoea witnessed by others were highly correlated with postoperative hypoxaemia.     

Chronic respiratory insufficiency: evaluation, evolution, prognosis

Chronic respiratory failure (CRF) is a major cause of morbidity and mortality. It is estimated that in France at least 60,000 patients exhibit severe CRF and that about 15,000 patients die each year from CRF. Chronic obstructive pulmonary disease (COPD) (chronic obstructive bronchitis, emphysema and their association) is by far the first cause of CRF (90% of the cases). The clinical picture of CRF depends on the causal disease, but exertional dyspnea is observed in almost all patients. Pulmonary function testing allows to assess whether the ventilatory defect is obstructive (COPD), restrictive or mixed. Severe CRF is usually defined by a Pa02 < 55 mmHg, in a stable state of the disease, with or without hypercapnia (PaC02 > 45 mmHg). The two major complications of CRF are acute exacerbations of the disease, with clinical and gasometric worsening, and pulmonary hypertension which may lead with time to right heart failure. Prognosis is poor in CRF since the 5 year survival rate is of 50% in COPD patients. Under long-term oxygen therapy (LTOT) the survival rate has been somewhat improved, being of 60-65% at 5 years. The best prognostic indices in CRF complicating COPD are the level of FEV1, Pa02, PaC02, the level of pulmonary artery mean pressure (PAP) and age. In COPD patients under LTOT the best prognostic indices are PAP and age.     

Precapillary pulmonary arterial hypertension disclosing systemic lupus erythematosus

Precapillary pulmonary hypertension was diagnosed in a 29 year old woman who became progressively more breathless (NYHA Class III) after her pregnancy, two years previously: systolic pulmonary artery pressure was 120 mmHg with an arterio-capillary pressure gradient of 30 mmHg. She had anti-nuclear autoantibodies detectable at 1/1000 and anti-DNA autoantibodies at 1/800 without any other manifestation of lupus. Treatment with prednisone (2 mg/kg/day) resulted in regression of her dyspnoea with a decrease of systolic pulmonary artery pressure to 65 mmHg, and of the arterio-capillary gradient to 15 mmHg; the lupus serology became negative with a clinical follow-up of 37 months. This observation shows that systemic lupus erythematosus may present with precapillary pulmonary hypertension, the conventional treatment of which may be successfully completed by steroid therapy.