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.

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.

Sleep quality and daytime function in adults with cystic fibrosis and severe lung disease.

It was hypothesized that adult cystic fibrosis (CF) patients with severe lung disease have impaired daytime function related to nocturnal hypoxaemia and sleep disruption. Nineteen CF patients (forced expiratory volume in one second 28+/-7% predicted) and 10 healthy subjects completed sleep diaries, overnight polysomnography (PSG), and assessment of daytime sleepiness and neurocognitive function. CF patients tended to report more awakenings (0.7+/-0.5 versus 0.3+/-0.2 x h(-1), p=0.08), and PSG revealed reduced sleep efficiency (71+/-25 versus 93+/-4%, p=0.004) and a higher frequency of awakenings (4.2+/-2.7 versus 2.4+/-1.4 x h(-1), p=0.06). Mean arterial oxygen saturation during sleep was lower in CF patients (84.4+/-6.8 versus 94.3+/-1.5%, p<0.0001) and was associated with reduced sleep efficiency (regression coefficient (r)=0.57, p=0.014). CF patients had short sleep latency on the multiple sleep latency test (6.7+/-3 min). The CF group reported lower levels of activation and happiness and greater levels of fatigue (p<0.01), which correlated with indices of sleep loss, such as sleep efficiency (r=0.47, p=10.05). Objective neurocognitive performance was also impaired in CF patients, reflected by lower throughput for simple addition/subtraction, serial reaction and colour-word conflict. The authors concluded that adult cystic fibrosis patients with severe lung disease have impaired neurocognitive function and daytime sleepiness, which is partly related to chronic sleep loss and nocturnal hypoxaemia.

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.

Impact of obstructive sleep apnea on left ventricular mass and diastolic function.

We wished to determine if obstructive sleep apnea (OSA) is associated with increased left ventricular mass (LVM) and impaired left ventricular diastolic function (LVDF) independently of coexisting obesity, hypertension (HTN), and diabetes mellitus (DM). Patients without primary cardiac disease, referred for evaluation of OSA (n = 533), had overnight polysomnography and Doppler echocardiography while awake. Patients were divided, according to the apnea-hypopnea index (AHI), into an OSA group (AHI > or = 5/h, n = 353) and a non-OSA group (AHI < 5/h, n = 180). In men, LVM was greater in the OSA group (98.9 +/- 25.6 versus 92.3 +/- 22.5 g/m, p = 0.023) despite exclusion of those with HTN and DM. A similar trend was noted in women. Regression analysis revealed that LVM was correlated with body mass index (BMI) (beta = 0.480, p < 0.0005), age (beta = 0.16, p = 0.001), and the presence of HTN (beta = 0.137, p = 0.003) in men and with BMI (beta = 0.501, p < 0.0005) in women, but not with AHI or oxygen saturation during sleep. The ratio of peak early filling velocity to peak late filling velocity (E/A), an index of LVDF, was similar in both groups (1.28 +/- 0.32 versus 1.34 +/- 0.31, p = 0.058); it was correlated with age (beta = -0.474, p < 0.0005), but not with AHI or oxygen saturation during sleep. We conclude that OSA is not associated with increased LVM or impaired LVDF independently of obesity, HTN, or advancing age.

Sleep disruption in the intensive care unit.

Subjective and objective measures of sleep quality indicate that the sleep of patients in the intensive care unit (ICU) is extraordinarily disturbed. Several studies spanning the past two decades have demonstrated that critically ill patients exhibit reduced sleep efficiency, reduced restorative sleep, and frequent arousals and awakenings. A number of potential sleep disrupters exist in the ICU environment, with noise being the predominant focus of investigation. Excessive noise levels in the ICU correlate with poor sleep quality in healthy subjects and patients. Medications, light, and frequent care-related activities can also interfere with a patient's ability to obtain good-quality sleep. Sleep disruption can have significant adverse consequences for critically ill patients, such as immune system compromise and respiratory abnormalities. Although several questions remain unanswered, including the impact of sleep disruption on the clinical outcome of patients in the ICU, there is a growing interest in developing new strategies to improve sleep quality.

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.

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.

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 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.

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.

Long-term follow-up of survivors of acute lung injury: lack of effect of a ventilation strategy to prevent barotrauma.

OBJECTIVES: To determine the effect of a ventilation strategy to prevent barotrauma on long-term outcome in survivors of acute lung injury. DESIGN: Prospective blinded cohort analysis. SETTING: Three university-affiliated medical-surgical intensive care units. PATIENTS: A total of 28 survivors of acute lung injury, 1-2 yrs after diagnosis, from a multicenter prospective randomized controlled trial comparing pressure (peak inflation pressure < or =30 cm H2O) and volume (tidal volume < or =8 mL/kg) limited ventilation to a conventional (peak inflation pressure < or =50 cm H2O, tidal volume 10-15 mL/kg) ventilation strategy. MEASUREMENTS AND MAIN RESULTS: Physicians blinded as to treatment group evaluated 20 of 28 survivors (treatment group, 7; control group, 13). Exercise tolerance in the 6-minute walk test was comparable to patients with chronic respiratory disease and equivalent between groups (treatment group, 373+/-171 m vs. control group, 375+/-129 m; p = .84). Pulmonary function testing showed reduced diffusing capacity (treatment group, 64+/-29% predicted vs. control group, 74+/-14% predicted; p = .68) and normal volumes, flows, and blood gases. Two domains of disease-specific Health Related Quality of Life assessed by the Chronic Respiratory Questionnaire were worse for patients in the treatment group compared with the control group (Emotional Function 3.8+/-1.4 vs. 5.1+/-0.08; p = .05, Mastery 4.7+/-1.7 vs. 6.2+/-0.8; p = .03). There were no between-group differences in the scores of the Spitzer Quality of Life Index (a generic Health Related Quality of Life instrument), although they were reduced (7.5+/-1.9) and comparable to patients with chronic disease. CONCLUSIONS: We found that 1-2 yrs after the onset of their illness, survivors of acute lung injury have reductions in quality of life and exercise tolerance which are similar to patients with chronic diseases. We were unable to show that a limited ventilation strategy improves either long-term pulmonary function or quality of life in survivors of acute lung injury.

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.

Increased mortality associated with Cheyne-Stokes respiration in patients with congestive heart failure.

We hypothesized that mortality is higher in patients with congestive heart failure (CHF) who develop Cheyne-Stokes respiration (CSR) during sleep than CHF patients without CSR. Overnight polysomnography was performed on 16 male patients with chronic, stable CHF: nine had CSR during sleep (CSR group) and seven did not (CHF group). The CSR group had a higher apnea-hypopnea index (AHI: 41 +/- 17 versus 6 +/- 5/hr) and experienced greater sleep disruption. There were no significant intergroup differences between age, weight, cardiac function, and pulmonary function. After the initial sleep study, all patients were maintained on standard medical therapy for CHF without supplemental oxygen or nasal continuous positive airway pressure. Over the next 3.1 to 4.5 yr there was a significant difference between the number of deaths in each group. Five patients died in the CSR group and two received a heart transplant, whereas only one patient died in the CHF group. Regression analysis revealed that mortality was positively correlated with CSR, AHI, arousal index, and the amount of stage 1, 2 non-REM sleep and was inversely related to the total sleep time. We conclude that mortality is higher in CHF patients who develop CSR during sleep than CHF patients without CSR. Although the development of CSR may simply reflect more severe cardiac impairment, we suggest that CSR itself accelerates the deterioration in cardiac function.

Survival of acute myelogenous leukemia patients requiring intubation/ventilatory support.

A 5-y (1987-1992) retrospective chart review assessed the survival of patients with acute myelogenous leukemia (AML) who required intubation/ventilatory support in the intensive care unit (ICU). Thirty-two patients were identified, average age 52 +/- 19 (range 14-82) y. Seven patients had undergone bone marrow transplantation for AML 2 weeks to 4 months prior to admission. Of the remaining 25 patients, 16 received chemotherapy prior to admission, 6 started or continued chemotherapy in the ICU, and 3 patients did not receive any chemotherapy. The Apache II score, which quantifies illness severity, on admission to the ICU was 32.5 +/- 8.8. The average length of stay was 7.4 d. Twenty-nine patients had diffuse pulmonary infiltrates on admission, 2 patients had large pleural effusions, and 1 patient had severe bronchospasm with a clear chest X-ray. The average PaO2/FiO2, when first stabilized on mechanical ventilation, was 204 +/- 83. Of the 32 patients, 28 died in the ICU, and 3 died shortly after withdrawal of aggressive therapy and discharge to the ward. A single patient survived the hospital admission but died 4 months later at home. The observed vs. the predicted ICU mortality determined by Knaus' method, was significantly greater even for those with lower Apache II scores. Acute myelogenous leukemia patients had a greater mortality than 2 other intubated patient populations in our ICU admitted during the same time period, a group of 126 consecutive admissions and 53 patients with connective tissue disease. The latter 2 control groups only included patients requiring mechanical ventilation. We conclude that AML patients who require ventilatory support for acute respiratory failure rarely survive their ICU admission.