Effects of intermittent hypoxia on erythropoietin, soluble erythropoietin receptor and ventilation in humans.

Erythropoietin (EPO) and soluble EPO receptors (sEPOR) have been proposed to play a central role in the ventilatory acclimatisation to continuous hypoxia in mice. In this study, we demonstrated for the first time in humans (n = 9) that sEPOR is downregulated upon daytime exposure to 4 days of intermittent hypoxia (IH; 6 h·day⁻¹, cycles of 2 min of hypoxia followed by 2 min of reoxygenation; peak end-tidal oxygen tension (P(ET,O2)) 88 Torr, nadir P(ET,O2)) 45 Torr), thereby allowing EPO concentration to rise. We also determined the strength of the association between these haematological adaptations and alterations in the acute hypoxic ventilatory response (AHVR). We observed a nadir in sEPOR on day 2 (-70%), concomitant with the peak in EPO concentration (+50%). Following exposure to IH, tidal volume (V(T)) increased, respiratory frequency remained unchanged, and minute ventilation (V'(E)) was increased. There was a negative correlation between EPO and sEPOR (r = -0.261; p = 0.05), and between sEPOR and V(T) (r = -0.331; p = 0.02). EPO was positively correlated with V'(E) (r = 0.458; p = 0.001). In conclusion, the downregulation of sEPOR by IH modulates the subsequent EPO response. Furthermore, the alterations in AHVR and breathing pattern following IH appear to be mediated, at least in part, by the increase in EPO.

Shift in sleep apnoea type in heart failure patients in the CANPAP trial.

In patients with heart failure (HF), the predominant type of sleep apnoea can change over time in association with alterations in circulation time. The aim of this study was to determine whether, in some patients with HF, a spontaneous shift from mainly central (>50% central events) to mainly obstructive (>50% obstructive events) sleep apnoea (CSA and OSA, respectively) over time coincides with improvement in left ventricular ejection fraction (LVEF). Therefore, sleep studies and LVEFs of HF patients with CSA from the control arm of the Canadian Continuous Positive Airway Pressure for Patients with Central Sleep Apnea and Heart Failure (CANPAP) trial were examined to determine whether some converted to mainly OSA and, if so, whether this was associated with an increase in LVEF. Of 98 patients with follow-up sleep studies and LVEFs, 18 converted spontaneously to predominantly OSA. Compared with those in the nonconversion group, those in the conversion group had a significantly greater increase in the LVEF (2.8% versus -0.07%) and a significantly greater fall in the lung-to-ear circulation time (-7.6 s versus 0.6 s). In patients with HF, spontaneous conversion from predominantly CSA to OSA is associated with an improvement in left ventricular systolic function. Future studies will be necessary to further examine this relationship.

Obstructive sleep apnoea is associated with diabetes in sleepy subjects.

BACKGROUND: Although obstructive sleep apnoea (OSA) has been linked to insulin resistance and glucose intolerance, it is unclear whether there is an independent association between OSA and diabetes mellitus (DM) and whether all patients with OSA are at risk. The objective of this study was to determine the association between OSA and DM in a large cohort of patients referred for sleep diagnostic testing. METHODS: A cross-sectional analysis of participants in a clinic-based study was conducted between July 2005 and August 2007. DM was defined by self-report and concurrent use of diabetic medications (oral hypoglycaemics and/or insulin). Sensitivity analysis was performed using a validated administrative definition of diabetes. OSA was defined by the respiratory disturbance index (RDI) using polysomnography or ambulatory monitoring. Severe OSA was defined as an RDI > or = 30/h. Subjective sleepiness was defined as an Epworth Sleepiness Scale score > or = 10. RESULTS: Complete data were available for 2149 patients. The prevalence of DM increased with increasing OSA severity (p<0.001). Severe OSA was associated with DM following adjustment for patient demographics, weight and neck circumference (odds ratio (OR) 2.18; 95% CI 1.22 to 3.89; p<0.01). Following a stratified analysis, this relationship was observed exclusively in sleepy patients (OR 2.59 (95% CI 1.35 to 4.97) vs 1.16 (95% CI 0.31 to 4.37) in non-sleepy patients). CONCLUSIONS: Severe OSA is independently associated with DM in patients who report excessive sleepiness. Future studies investigating the impact of OSA treatment on DM may wish to focus on this patient population.

The effect of L-tryptophan on daytime sleep latency in normals: correlation with blood levels.

L-Tryptophan, an essential amino acid, is readily converted to serotonin, which is thought to be important for expression of slow wave sleep and possibly rapid eye movement (REM) sleep. A vast but often confusing literature exists on L-tryptophan effects on inducing, maintaining, or altering sleep. In this study we measured the effects of L-tryptophan on objective (multiple sleep latency) and subjective [Stanford Sleepiness Scale (SSS)] measures of sleepiness and examined their relationship to blood L-tryptophan levels. Ten healthy volunteers (eight men and two women; mean +/- SD age 34 +/- 10 years) received placebo or 1.2 or 2.4 g or L-tryptophan on separate days in random double-blind fashion. Sleep latency and SSS were measured initially and at 60 and 120 min after ingestion. Blood and urine were collected at regular intervals. Compared with placebo both L-tryptophan doses reduced sleep latency at 1 h, with the reduction persisting at 2 h for the 2.4-g dose only (p less than 0.05). There was a positive correlation between subjective and objective sleepiness measures but only with the 2.4-g dose (rs = 0.76, p less than 0.01). There was a highly significant correlation between blood L-tryptophan and sleep latency at 0, 60, and 120 min in all subjects for all drug conditions (r = 0.276, df = 79, p = 0.013). Very small amounts of free L-tryptophan or its metabolites were found in the urine, with the exception of kynurenic acid. We conclude that L-tryptophan consistently reduced sleep latency in normals and that this correlates with blood levels.(ABSTRACT TRUNCATED AT 250 WORDS)

Periodic limb movements during sleep in patients with congestive heart failure.

The prevalence of periodic limb movements (PLM) during sleep and their effect on sleep and daytime alertness were determined in 23 men with severe, stable congestive heart failure (CHF) and 9 healthy control subjects. Each subject had overnight polysomnography and the following day completed a subjective assessment of daytime sleepiness (Epworth Sleepiness Scale [ESS]) and a multiple sleep latency test (MSLT). The proportion of CHF patients with moderately severe PLM (>25/h) was significantly higher (52%) than control subjects (11%). CHF patients were subdivided into two groups, those with more than 10 PLM per hour (group 1, n=15) and those with less than 10 PLM per hour (group 2, n=8). Group 1 had a significantly higher frequency of PLM (group 1, 73 +/- 50; group 2, 4 +/- 4; control, 11 +/- 12/h) and associated arousals from sleep (group 1, 14 +/- 13; group 2, 2 +/- 3; control subjects, 1 +/- 1/h) than group 2 and the control group, and had more stage 1 and 2 nonrapid eye movement sleep than the control group (group 1, 77 +/- 11; group 2, 71 +/- 11; control, 63 +/- 9% total sleep time). Mean sleep latency on the MSLT was significantly shorter in group 1 than the control group (group 1, 6.1 +/- 2.9; group 2, 9 +/- 6.7; control subjects, 12.4 +/- 1.9 min). Although the ESS score was highest in group 1, this did not reach statistical significance. We conclude that PLM are more prevalent in patients with CHF and may contribute to their sleep/wake complaints.

Heart rate response to breath-hold, valsalva and Mueller maneuvers in obstructive sleep apnea.

We wished to assess the role of increased vagal tone and arterial oxygen saturation (SaO2) as determinants of HR response to voluntary respiratory maneuvers in OSAS. The changes in HR and SaO2 during breath-hold (B), Valsalva (V) and Mueller (M) maneuvers were determined in nine male subjects with OSAS while breathing RA or O2. Oxygen saturation was significantly lower breathing RA than O2 at the end of B (92.6 +/- 1.6 vs 97.2 +/- 0.8 percent), V (92.9 +/- 1.3 vs 95.2 +/- 1.7 percent), and M (92.7 +/- 1.2 vs 95.3 +/- 1.9 percent). Despite this, there was no significant difference between the HR change while breathing RA and O2 during B (12 +/- 18 vs 7 +/- 15 beats/minute), V (-2 +/- 12 vs -5 +/- 17 beats/minute), and M (5 +/- 16 vs 1 +/- 8 beats/minute). The change in HR was not related to the duration of B, V, or M or to the mouth pressure generated during V and M. In order to determine if awake HR response to the maneuvers reflected HR response to obstructive apnea, we examined the relationship between the HR response to B, V, and M during wakefulness and the response to obstructive apnea of similar duration while asleep. A significant correlation was found between the HR response to obstructive sleep apnea during sleep and the response to awake B (r = 0.67, p less than 0.001), V (r = 0.51, p less than 0.05), and M (r = 0.75, p less than 0.001). We conclude that in OSAS, increased vagal tone is a major determinant of HR response to voluntary respiratory maneuvers, that bradycardia can occur in the absence of hypoxemia, and that HR response to these maneuvers, especially to M, during wakefulness predicts HR response to obstructive apnea while asleep.

The entrainment of low frequency breathing periodicity.

It has been predicted by mathematical models of the respiratory control system that the delay between the lung and the respiratory controller may determine the cycle time found in periodic breathing. We examined cycle time of periodic breathing and circulation time in 11 patients known to have circulation delay due to heart failure. We did not find a significant relationship between the amount of periodic breathing and circulation delay, but found a very high correlation between circulation delay and the cycle time of periodic breathing (r2 = 0.825; p = 0.0001).

Impact of menopause on the prevalence and severity of sleep apnea.

STUDY OBJECTIVES: To compare the prevalence and severity of sleep apnea between premenopausal and postmenopausal women, and to determine whether these differences are affected by the body mass index (BMI) and neck circumference. DESIGN: Cross-sectional study utilizing a sleep clinic patient database. SETTING: University hospital. PATIENTS: A total of 1,315 women, classified into premenopausal and postmenopausal groups based on age (< 45 years and > 55 years, respectively). MEASUREMENTS: Anthropometric measurements included height, weight, and neck circumference. Sleep measurements included full nocturnal polysomnography. Sleep apnea was defined as an apnea-hypopnea index (AHI) > 10/h. RESULTS: There were 797 premenopausal and 518 postmenopausal women. The latter group was more obese (mean +/- SE BMI, 32.2 +/- 0.4 kg/m(2) vs 30.2 +/- 0.4 kg/m(2); p < 0.0001) and had larger neck circumference (37.1 +/- 0.2 cm vs 35.8 +/- 0.2 cm; p < 0.0001). The prevalence of sleep apnea was greater in postmenopausal women than premenopausal women (47% vs 21%; chi(2) < 0.0001). There were proportionately more postmenopausal than premenopausal women in all ranges of apnea severity (AHI, 10 to 30/h, 30 to 50/h, and > 50/h). Postmenopausal women had a significantly higher mean AHI compared to premenopausal women (17.0 +/- 0.9/h vs 8.7 +/- 0.6/h; p < 0.0001); this significant difference persisted even after adjusting for BMI and neck circumference. CONCLUSION: There may be functional, rather than anatomic, differences in the upper airway between premenopausal and postmenopausal women, which may account for the observed differences in apnea prevalence and severity.

Respiration and abnormal sleep in patients with congestive heart failure.

We investigated the interaction between respiration and sleep in ten male outpatients with severe, stable, maximally treated congestive heart failure (CHF). Cheyne-Stokes respiration (CSR), defined as periodic breathing with apnea or hypopnea, was found in all patients with a mean duration of 120 +/- 87 minutes [50.2 +/- 34.4 percent total sleep time (TST)]. The CSR was found predominantly during stage 1 (20.6 +/- 6.7 percent TST) and stage 2 (25.8 +/- 6 percent TST) NREM sleep and occurred rarely during slow wave sleep (SWS) (1.6 +/- 1 percent TST) and REM sleep (1.6 +/- 0.5 percent TST). All apneas and hypopneas were central. Despite normal awake arterial oxygenation (SaO2) (96.1 +/- 1.6 percent), significant, severe hypoxemia was found during sleep in seven patients with SaO2 less than 90 percent for 9 to 59 percent TST (mean +/- SD, 23 +/- 23 percent TST), and this was significantly related to the duration of CSR (r = 0.66, p less than 0.05). The mean minimum SaO2 for sleep stage was lowest during stage 1 (82.1 percent +/- 2.6 percent) and stage 2 (78.9 percent +/- 2.8 percent) NREM sleep, intermediate during REM sleep (84.5 percent +/- 1.8 percent) and highest during SWS (87.6 percent +/- 2.7 percent). Sleep was disrupted to a variable extent in all patients with a short mean TST (287 +/- 106 minutes), a high proportion of stage 1 sleep (26 +/- 19 percent TST), virtual absence of SWS (5 +/- 7 percent TST) which was found in only four patients, and a high number of sleep stage changes (30 +/- 27/hour) and arousals (28 +/- 25/hour). Arousals occurred predominantly during stage 1 (17 +/- 20/hour) and stage 2 (10 +/- 7/hour) NREM sleep and the majority immediately followed the hyperpneic phase of CSR. The amount of CSR (percent TST) was inversely related to the length of TST (r = -0.73, p less than 0.05), and directly related to the number of sleep stage changes (r = 0.79, p less than 0.01) and the number of arousals (r = 0.66, p less than 0.05). We conclude that in severe, stable CHF, CSR occurs predominantly during light sleep, that despite normal awake arterial oxygen saturation, significant hypoxemia may develop during sleep due to CSR, and that sleep is unstable and disrupted due to frequent arousals caused by the hyperpneic phase of CSR. These sequelae of CSR may be important determinants of the clinical status and outcome of patients with severe CHF.

Pulmonary hypertension and cardiac function in adult cystic fibrosis: role of hypoxemia.

STUDY OBJECTIVES: To determine (1) the prevalence of pulmonary hypertension and cardiac dysfunction in adult cystic fibrosis (CF) patients with severe lung disease, (2) the relationship between these cardiovascular abnormalities and hypoxemia, and (3) the impact of subclinical pulmonary hypertension on survival. DESIGN: Single-blind, cross-sectional study. SETTING: Ambulatory clinic of the Adult CF program at a tertiary-level hospital. PATIENTS: Clinically stable patients with severe lung disease (FEV1 < 40% of predicted normal value) who were not receiving supplemental oxygen. A second cohort of patients in stable condition with less severe lung disease (FEV1 40 to 65% predicted) was also recruited to enable multivariate analysis for the determinants of pulmonary hypertension. MEASUREMENTS AND RESULTS: Eighteen patients with severe lung disease (FEV1 28 +/- 7% of predicted normal value) were initially studied. Each patient had overnight polysomnography, pulmonary function tests, and Doppler echocardiography. Arterial oxygen saturation (SaO2) was reduced during wakefulness (87.1 +/- 6.1%) and fell during sleep (84.0 +/- 6.6%) while transcutaneous PCO2 was normal during wakefulness (41.1 +/- 6.9 mm Hg) and increased during sleep (46.6 +/- 4.7 mm Hg). Left ventricular size, systolic function, and diastolic function were normal except in one patient who had had a previous silent myocardial infarction due to coronary artery disease. Qualitative assessment of right ventricular function was normal in all patients. Pulmonary artery systolic pressure (PASP) was increased (> 35 mm Hg) in seven patients without clinical evidence of cor pulmonale. Regression analysis was performed by combining these data with data from an additional 15 CF patients with moderately severe lung disease (FEV1 56.3 +/- 8.9% predicted normal) who were recruited to a modified study protocol that included overnight oximetry, pulmonary function tests, and Doppler echocardiography. None of these patients had evidence of hypoxemia and only three had mild elevation of PASP (36, 37, and 39 mm Hg). Linear regression analysis revealed that PASP was significantly correlated with FEV1 (r = -0.44; p = 0.013), and SaO2 during wakefulness (r =-0.60; p = 0.0003), during sleep (r = -0.56; p = 0.0008), and after 6 min of exercise (r = -0.75; p < 0.0001). Multivariate analysis revealed that awake SaO2 was a significantly better predictor of PASP than FEV1 (p = 0.0104). Clinical follow-up of the original cohort for up to 5 years revealed that mortality was significantly higher in those with pulmonary hypertension than those without pulmonary hypertension (p = 0.0129). CONCLUSIONS: In adult CF patients with severe stable lung disease, left and right ventricular function is well maintained in the absence of significant coronary artery disease; pulmonary hypertension develops in a significant proportion of patients and is strongly correlated with oxygen status, independent of lung function; and subclinical pulmonary hypertension is associated with an increased mortality.

Sleep in critically ill patients requiring mechanical ventilation.

STUDY OBJECTIVES: To objectively measure sleep in critically ill patients requiring mechanical ventilation and to define selection criteria for future studies of sleep continuity in this population. DESIGN: Prospective cohort analysis. SETTING: University teaching hospital medical-surgical ICU. PATIENTS: Twenty critically ill (APACHE II [acute physiology and chronic health evaluation II] acute physiology score [APS], 10 +/- 5), mechanically ventilated adults (male 12, female 8, age 62 +/- 15 years) with mild to moderate acute lung injury (lung injury score, 1.8 +/- 0.9) 10 +/- 7 days after admission to the ICU. MEASUREMENTS AND RESULTS: Patients were divided into three groups based on 24-h polysomnography (PSG) findings. No patient demonstrated normal sleep. In the "disrupted sleep" group (n = 8), electrophysiologic sleep was identified and was distributed throughout the day (6:00 AM to 10:00 PM; 4.0 +/- 2.9 h) and night (10:00 PM to 6:00 AM; 3.0 +/- 1.9 h) with equivalent proportions of non-rapid eye movement (NREM) and rapid eye movement (REM) sleep. Nocturnal sleep efficiency was severely reduced (38 +/- 24%) with an increased proportion of stage 1 NREM sleep (40 +/- 28% total sleep time [TST]) and a reduced proportion of REM sleep (10 +/- 14% TST). Severe sleep fragmentation was reflected by a high frequency of arousals (20 +/- 17/h) and awakenings (22 +/- 25/h). Electrophysiologic sleep was not identifiable in the PSG recordings of the remaining patients. These were classified either as "atypical sleep" (n = 5), characterized by transitions from stage 1 NREM to slow wave sleep with a virtual absence of stage 2 NREM and reduced stage REM sleep, or "coma" (n = 7), characterized by > 50% delta or theta EEG activity with (n = 5) and without (n = 2) evidence of EEG activation either spontaneously or in response to deep painful stimuli. The combined atypical sleep and coma groups had a higher APS (13 +/- 4 vs 6 +/- 4) and higher doses of sedative medications than the disrupted sleep group. CONCLUSION: Sleep, as it is conventionally measured, was identified only in a subgroup of critically ill patients requiring mechanical ventilation and was severely disrupted. We have proposed specific criteria to select patients for future studies to evaluate potential causes of sleep disruption in this population.

Gastrobronchial fistula: an unusual complication of esophagectomy.

Gastrobronchial fistula is an extremely rare condition. A case of gastrobronchial fistula secondary to a benign gastric ulcer 9 years after esophagectomy and gastric pull-up for treatment of esophageal carcinoma is described. A review of the literature is provided.

Pharyngeal narrowing in end-stage renal disease: implications for obstructive sleep apnoea.

Sleep apnoea is common in patients with end-stage renal disease (ESRD). It was hypothesised that this is related to a narrower upper airway. Upper airway dimensions in patients with and without ESRD and sleep apnoea were compared, in order to determine whether upper airway changes associated with ESRD could contribute to the development of sleep apnoea. An acoustic reflection technique was used to estimate pharyngeal cross-sectional area. Sleep apnoea was assessed by overnight polysomnography. A total of 44 patients with ESRD receiving conventional haemodialysis and 41 subjects with normal renal function were studied. ESRD and control groups were further categorised by the presence or absence of sleep apnoea (apnoea/hypopnoea index > or =10 events.h(-1)). The pharyngeal area was smaller in patients with ESRD compared with subjects with normal renal function: 3.04 +/- 0.84 versus 3.46 +/- 0.80 cm(2) for the functional residual capacity and 1.99 +/- 0.51 versus 2.14 +/- 0.58 cm(2) for the residual volume. The pharynx is narrower in patients with ESRD than in subjects with normal renal function. In conclusion, since a narrower upper airway predisposes to upper airway occlusion during sleep, it is suggested that this factor contributes to the pathogenesis of sleep apnoea in dialysis-dependent patients.

Enhanced chemo-responsiveness in patients with sleep apnoea and end-stage renal disease.

Although sleep apnoea is very common in patients with end-stage renal disease, the physiological mechanisms for this association have not yet been determined. The current authors hypothesised that altered respiratory chemo-responsiveness may play an important role. In total, 58 patients receiving treatment with chronic dialysis were recruited for overnight polysomnography. A modified Read rebreathing technique, which is used to assess basal ventilation, ventilatory sensitivity and threshold, was completed before and after overnight polysomnography. Patients were divided into apnoeic (n = 38; apnoea/hypopnoea index (AHI) 35+/-22 events.h(-1)) and nonapnoeic (n = 20; AHI 3+/-3 events.h(-1)) groups, with the presence of sleep apnoea defined as an AHI >10 events.h(-1). While basal ventilation and the ventilatory recruitment threshold were similar between groups, ventilatory sensitivity during isoxic hypoxia (partial pressure of oxygen (PO2) 6.65 kPa) and hyperoxia (PO2) 19.95 kPa) was significantly greater in apnoeic patients. Overnight changes in chemoreflex responsiveness were similar between groups. In conclusion, these data indicate that the responsiveness of both the central and peripheral chemoreflexes is augmented in patients with sleep apnoea and end-stage renal disease. Since increased ventilatory sensitivity to hypercapnia destabilises respiratory control, the current authors suggest this contributes to the pathogenesis of sleep apnoea in this patient population.

Improvement in Cheyne-Stokes respiration following cardiac resynchronisation therapy.

The effect of standard cardiac resynchronisation therapy (CRT) on the severity of Cheyne-Stokes respiration (CSR) in patients with congestive heart failure was studied. It was hypothesised that CRT, through its known beneficial effects on cardiac function, would stabilise the control of breathing and reduce CSR. Twenty-eight patients who were eligible for CRT and receiving optimised medical treatment for congestive heart failure were referred for overnight polysomnography, including monitoring of thoracic and abdominal movements to identify CSR and obstructive sleep apnoea events. Patients underwent repeat polysomnography after 6 months of CRT to re-evaluate sleep quality and sleep-disordered breathing. Twelve of the 28 patients had significant CSR (43%); 10 patients had a successful implantation and underwent repeat polysomnography a mean+/-SD 27+/-7 weeks after continuous biventricular pacing. Six of the 10 patients experienced a significant decrease in CSR severity following CRT, associated with correction of congestive heart failure-related hyperventilation and hypocapnia. Circulation time, oxygen saturation, frequency of obstructive apnoeas and sleep quality did not change. In conclusion, cardiac resynchronisation therapy is associated with a reduction in Cheyne-Stokes respiration, which may contribute to improved clinical outcome in patients treated with cardiac resynchronisation therapy.

Mechanisms and management of central sleep apnea.

Central sleep apnea is not a single disease but represents the final pathway in a large group of heterogeneous disorders. Control of normal breathing during sleep relies upon finely coordinated anatomical and physiological mechanisms and their destabilization leads to central apnea. The causes of central sleep apnea can be classified into 4 groups: neurologic disorders, periodic breathing, upper airway abnormalities, and idiopathic syndromes. Clinical features result from the interaction between the underlying disorder and control of respiration. Two different prototypes emerge: patients who are hypercapnic (central hypoventilation and/or impaired respiratory mechanics) and those who are eucapnic or hypocapnic (periodic breathing and idiopathic hyperventilation). The causes and severity of apnea can be determined by clinical assessment, pulmonary function testing, and overnight polysomnography. Further management involves specific treatment of the underlying condition and reducing the sequelae of recurrent apneas during sleep, namely cardiorespiratory dysfunction and sleep disruption. This review outlines an approach to the management of central sleep apnea based upon an understanding of its pathophysiology.

Improvement of sleep apnea in patients with chronic renal failure who undergo nocturnal hemodialysis.

BACKGROUND: Sleep apnea is common in patients with chronic renal failure and is not improved by either conventional hemodialysis or peritoneal dialysis. With nocturnal hemodialysis, patients undergo hemodialysis seven nights per week at home while sleeping. We hypothesized that nocturnal hemodialysis would correct sleep apnea in patients with chronic renal failure because of its greater effectiveness. METHODS: Fourteen patients who were undergoing conventional hemodialysis for four hours on each of three days per week underwent overnight polysomnography. The patients were then switched to nocturnal hemodialysis for eight hours during each of six or seven nights a week. They underwent polysomnography again 6 to 15 months later on one night when they were undergoing nocturnal hemodialysis and on another night when they were not. RESULTS: The mean (+/-SD) serum creatinine concentration was significantly lower during the period when the patients were undergoing nocturnal hemodialysis than during the period when they were undergoing conventional hemodialysis (3.9+/-1.1 vs. 12.8+/-3.2 mg per deciliter [342+/-101 vs. 1131+/-287 micromol per liter], P<0.001). The conversion from conventional hemodialysis to nocturnal hemodialysis was associated with a reduction in the frequency of apnea and hypopnea from 25+/-25 to 8+/-8 episodes per hour of sleep (P=0.03). This reduction occurred predominantly in seven patients with sleep apnea, in whom the frequency of episodes fell from 46+/-19 to 9+/-9 per hour (P= 0.006), accompanied by increases in the minimal oxygen saturation (from 89.2+/-1.8 to 94.1+/-1.6 percent, P=0.005), transcutaneous partial pressure of carbon dioxide (from 38.5+/-4.3 to 48.3+/-4.9 mm Hg, P=0.006), and serum bicarbonate concentration (from 23.2+/-1.8 to 27.8+/-0.8 mmol per liter, P<0.001). During the period when these seven patients were undergoing nocturnal hemodialysis, the apnea-hypopnea index measured on nights when they were not undergoing nocturnal hemodialysis was greater than that on nights when they were undergoing nocturnal hemodialysis, but it still remained lower than it had been during the period when they were undergoing conventional hemodialysis (P=0.05). CONCLUSIONS: Nocturnal hemodialysis corrects sleep apnea associated with chronic renal failure.

Role of prostacyclin and thromboxane in the circulatory changes of acute bacteremic Pseudomonas pneumonia in dogs.

We investigated the role of prostacyclin (PGI2) and thromboxane A2 (TxA2), as evidenced by changes in their stable metabolites, 6-keto-prostaglandin F1 alpha (6-keto-PGF1 alpha) and thromboxane B2 (TxB2), in the pathophysiology of acute bacteremic gram-negative pneumonia. Three groups of dogs were inoculated endotracheally: Group I (n = 5) with sterile broth, and Groups II (n = 5) and III (n = 10) with Pseudomonas aeruginosa. Gas exchange, hemodynamics, and plasma prostaglandins were measured before inoculation and hourly thereafter for 5 h in Groups I and II but only once in Group III, 5 h after inoculation. All animals were then killed, and the extent of pneumonia was assessed by lung wet weight and measurement of the percentage of cardiac output (CO) perfusing pneumonic lung using radionuclide-labeled microspheres. None of these measurements changed significantly in Group I, but all dogs in Groups II and III developed severe pneumonia. In Group II, mean arterial oxygen tension fell from 575 +/- 17 to 237 +/- 59 mm Hg (FIO2 = 1.0), with an increase in pulmonary shunt from 6 +/- 2% to 24 +/- 6%. Although TxB2 levels did not change, plasma 6-keto-PGF1 alpha rose progressively as pneumonia developed from baseline levels (less than 100 pg/ml) to a peak level of 890 +/- 114 pg/ml 5 h after inoculation.(ABSTRACT TRUNCATED AT 250 WORDS)

Gender differences in the polysomnographic features of obstructive sleep apnea.

We examined the influence of gender on the polysomnographic features of obstructive sleep apnea (OSA) in a retrospective study of 830 patients with OSA diagnosed by overnight polysomnography (PSG). The severity of OSA was determined from the apnea- hypopnea index (AHI) for total sleep time (AHI(TST)), and was classified as mild (5 to 25 events/h), moderate (26 to 50 events/h), and severe (> 50/events/h). Differences in OSA during different stages of sleep were assessed by comparing the AHI during non-rapid eye movement (NREM) (AHI(NREM)) and rapid eye movement (REM) (AHI(REM)) sleep and calculating the "REM difference" (AHI(REM) - AHI(NREM)). Additionally, each overnight polysomnographic study was classified as showing one of three mutually exclusive types of OSA: (1) mild OSA, which occurred predominantly during REM sleep (REM OSA); (2) OSA of any severity, which occurred predominantly in the supine position (S OSA); or (3) OSA without a predominance in a single sleep stage or body position (A OSA). The mean AHI(TST) for men was significantly higher than that for women (31.8 +/- 1.0 versus 20.2 +/- 1.5 events/h, p < 0. 001). The male-to-female ratio was 3.2:1 for all OSA patients, and increased from 2.2:1 for patients with mild OSA to 7.9:1 for those with severe OSA. Women had a lower AHI(NREM) than did men (14.6 +/- 1.6 versus 29.6 +/- 1.1 events/h, p < 0.001), but had a similar AHI(REM) (42.7 +/- 1.6 versus 39.9 +/- 1.2 events/h). Women had a significantly higher REM difference than did men (28.1 +/- 1.5 versus 10.3 +/- 1.1 events/h, p < 0.01). REM OSA occurred in 62% of women and 24% of men with OSA. S OSA occurred almost exclusively in men. We conclude that: (1) OSA is less severe in women because of milder OSA during NREM sleep; (2) women have a greater clustering of respiratory events during REM sleep than do men; (3) REM OSA is disproportionately more common in women than in men; and (4) S OSA is disproportionately more common in men than in women. These findings may reflect differences between the sexes in upper airway function during sleep in patients with OSA.

Sleep in the critically ill patient.

The sleep of intensive care unit (ICU) patients is remarkably disrupted. Several studies, employing both subjective and objective measures of sleep quality, have demonstrated that critically ill patients exhibit severe sleep fragmentation and reduced restorative sleep, particularly a suppression of rapid eye movement (REM) sleep. The cause of sleep disruption in the ICU appears to be multifactorial and includes both the patients' acute and chronic illnesses and factors that are unique to the ICU environment. Noise has been a significant focus of investigation, and the effects of medications, light, and patient-care activities have also been examined. Several questions remain to be answered so that caregivers can improve sleep in ICU patients, including the relative contribution of different sleep-disrupting factors and possible changes in patient susceptibility to these factors over time.