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1.  A systematic review of the effects of sedatives and anesthetics in patients with obstructive sleep apnea 
The objective of this review is to determine the effects of perioperative sedatives and anesthetics in surgical patients with obstructive sleep apnea (OSA) on respiratory events, medication requirements, hemodynamics, pain, emergence, and hospital stay. We searched The Cochrane CENTRAL Register of Controlled Trials, Medline, Embase, and Cochrane Database of Systematic Reviews from 1950 to June 2010 for relevant articles. All prospective and retrospective studies were eligible for inclusion if the effects of perioperative administration of sedation and anesthetics on medication requirements, pain, emergence, hemodynamics, respiratory events, and length of hospital stay in OSA patients were reported. The search strategy yielded 18 studies of 1467 patients. Of these, 456 patients were documented as having OSA. Few adverse respiratory effects were reported. Eight out of 700 (1.14%) patients undergoing middle ear surgery with midazolam and fentanyl had impaired upper airway patency and were retrospectively diagnosed as having OSA by polysomnography. Also, intraoperative snoring causing uvular edema in the postoperative period was described in an OSA patient undergoing upper limb surgery when propofol was administered with midazolam and fentanyl for sedation. A decrease in oxygen saturation in the postoperative period was described with propofol and isoflurane in 21 OSA patients undergoing uvulo-palato-pharyngoplasty and tonsillectomy surgery (P<0.05). Perioperative alpha 2 agonists were shown to decrease the use of anesthetics (P<0.05), analgesics (P=0.008) and anti-hypertensives (P<0.001) in OSA patients. Contradictory reports regarding emergence occurred with intraoperative dexmedetomidine. Intraoperative opioids decreased the analgesic consumption (P=0.03) and pain scores (P<0.05) in the postoperative period. There was limited data on the length of hospital stay. There were few adverse effects reported when patients with known OSA underwent elective surgery with the currently available sedatives and anesthetics. Adverse events were reported with midazolam. However, the quality and number of patients in the studies were limited. There is a need for further trials with large numbers and uniform reporting of outcomes.
doi:10.4103/0970-9185.86574
PMCID: PMC3214547  PMID: 22096275
Anesthetics; effects; obstructive sleep apnea; sedative
2.  Loud snoring is a risk factor for occupational injury in farmers 
BACKGROUND:
Loud snoring is a common symptom in the general population. The evidence-based literature indicates that snoring may be associated with sleep fragmentation and sleep apnea, which may affect cognitive function and predispose to occupational injury. High rates of occupational injury occur on farms and may be related to personal and health factors. Thus, loud snoring may not be a trivial symptom and should be considered as important in medical assessments.
METHODS:
A prospective cohort study was conducted in Saskatchewan. Baseline questionnaires were completed for 5502 individuals by representatives from 2390 farms. Sleep patterns at baseline were categorized as the following: no reported sleep disorders; physician-diagnosed sleep apnea (treatment unknown); and loud snoring. Survival analyses were used to relate sleep patterns with subsequent injury.
RESULTS:
A total of 6.7% (369 of 5502) of participants reported a possible sleep disorder. Of these, 69.4% (256 of 369) reported loud snoring only. Loud snoring was only associated with a consistent increase in risk (eg, HR 1.45 [95 CI 1.07 to 1.99 for work-related injury]) for five farm injury outcomes. Relationships between physician-diagnosed sleep apnea and time to first injury were not significant, presumably because a diagnosis of sleep apnea implied treatment for sleep apnea.
DISCUSSION:
Sleep disorders are an important potential risk factor for occupational injury on farms. Substantial proportions of farm residents report loud snoring and this is related to subsequent injury. Some of these cases may represent sleep fragmentation or undiagnosed obstructive sleep apnea. Identification and clinical management of sleep disorders related to snoring should be part of health assessments conducted by physicians.
PMCID: PMC3628646  PMID: 23457674
Agriculture; Farming; Injury; Occupational health; Sleep disorders; Snoring
3.  Increased Cerebral Blood Flow Velocity in Children with Mild Sleep-Disordered Breathing 
Pediatrics  2006;118(4):e1100-e1108.
Objective
Sleep-disordered breathing describes a spectrum of upper airway obstruction in sleep from simple primary snoring, estimated to affect 10% of preschool children, to the syndrome of obstructive sleep apnea. Emerging evidence has challenged previous assumptions that primary snoring is benign. A recent report identified reduced attention and higher levels of social problems and anxiety/depressive symptoms in snoring children compared with controls. Uncertainty persists regarding clinical thresholds for medical or surgical intervention in sleep-disordered breathing, underlining the need to better understand the pathophysiology of this condition. Adults with sleep-disordered breathing have an increased risk of cerebrovascular disease independent of atherosclerotic risk factors. There has been little focus on cerebrovascular function in children with sleep-disordered breathing, although this would seem an important line of investigation, because studies have identified abnormalities of the systemic vasculature. Raised cerebral blood flow velocities on transcranial Doppler, compatible with raised blood flow and/or vascular narrowing, are associated with neuropsychological deficits in children with sickle cell disease, a condition in which sleep-disordered breathing is common. We hypothesized that there would be cerebral blood flow velocity differences in sleep-disordered breathing children without sickle cell disease that might contribute to the association with neuropsychological deficits.
Design
Thirty-one snoring children aged 3 to 7 years were recruited from adenotonsillectomy waiting lists, and 17 control children were identified through a local Sunday school or as siblings of cases. Children with craniofacial abnormalities, neuromuscular disorders, moderate or severe learning disabilities, chronic respiratory/cardiac conditions, or allergic rhinitis were excluded. Severity of sleep-disordered breathing in snoring children was categorized by attended polysomnography. Weight, height, and head circumference were measured in all of the children. BMI and occipitofrontal circumference z scores were computed. Resting systolic and diastolic blood pressure were obtained. Both sleep-disordered breathing children and the age- and BMI-similar controls were assessed using the Behavior Rating Inventory of Executive Function (BRIEF), Neuropsychological Test Battery for Children (NEPSY) visual attention and visuomotor integration, and IQ assessment (Wechsler Preschool and Primary Scale of Intelligence Version III). Transcranial Doppler was performed using a TL2-64b 2-MHz pulsed Doppler device between 2 PM and 7 PM in all of the patients and the majority of controls while awake. Time-averaged mean of the maximal cerebral blood flow velocities was measured in the left and right middle cerebral artery and the higher used for analysis.
Results
Twenty-one snoring children had an apnea/hypopnea index <5, consistent with mild sleep-disordered breathing below the conventional threshold for surgical intervention. Compared with 17 nonsnoring controls, these children had significantly raised middle cerebral artery blood flow velocities. There was no correlation between cerebral blood flow velocities and BMI or systolic or diastolic blood pressure indices. Exploratory analyses did not reveal any significant associations with apnea/hypopnea index, apnea index, hypopnea index, mean pulse oxygen saturation, lowest pulse oxygen saturation, accumulated time at pulse oxygen saturation <90%, or respiratory arousals when examined in separate bivariate correlations or in aggregate when entered simultaneously. Similarly, there was no significant association between cerebral blood flow velocities and parental estimation of child’s exposure to sleep-disordered breathing. However, it is important to note that whereas the sleep-disordered breathing group did not exhibit significant hypoxia at the time of study, it was unclear to what extent this may have been a feature of their sleep-disordered breathing in the past. IQ measures were in the average range and comparable between groups. Measures of processing speed and visual attention were significantly lower in sleep-disordered breathing children compared with controls, although within the average range. There were similar group differences in parental-reported executive function behavior. Although there were no direct correlations, adjusting for cerebral blood flow velocities eliminated significant group differences between processing speed and visual attention and decreased the significance of differences in Behavior Rating Inventory of Executive Function scores, suggesting that cerebral hemodynamic factors contribute to the relationship between mild sleep-disordered breathing and these outcome measures.
Conclusions
Cerebral blood flow velocities measured by noninvasive transcranial Doppler provide evidence for increased cerebral blood flow and/or vascular narrowing in childhood sleep-disordered breathing; the relationship with neuropsychological deficits requires further exploration. A number of physiologic changes might alter cerebral blood flow and/or vessel diameter and, therefore, affect cerebral blood flow velocities. We were able to explore potential confounding influences of obesity and hypertension, neither of which explained our findings. Second, although cerebral blood flow velocities increase with increasing partial pressure of carbon dioxide and hypoxia, it is unlikely that the observed differences could be accounted for by arterial blood gas tensions, because all of the children in the study were healthy, with no cardiorespiratory disease, other than sleep-disordered breathing in the snoring group. Although arterial partial pressure of oxygen and partial pressure of carbon dioxide were not monitored during cerebral blood flow velocity measurement, assessment was undertaken during the afternoon/early evening when the child was awake, and all of the sleep-disordered breathing children had normal resting oxyhemoglobin saturation at the outset of their subsequent sleep studies that day. Finally, there is an inverse linear relationship between cerebral blood flow and hematocrit in adults, and it is known that iron-deficient erythropoiesis is associated with chronic infection, such as recurrent tonsillitis, a clinical feature of many of the snoring children in the study. Preoperative full blood counts were not performed routinely in these children, and, therefore, it was not possible to exclude anemia as a cause of increased cerebral blood flow velocity in the sleep-disordered breathing group. However, hemoglobin levels were obtained in 4 children, 2 of whom had borderline low levels (10.9 and 10.2 g/dL). Although there was no apparent relationship with cerebral blood flow velocity in these children (cerebral blood flow velocity values of 131 and 130 cm/second compared with 130 and 137 cm/second in the 2 children with normal hemoglobin levels), this requires verification. It is of particular interest that our data suggest a relationship among snoring, increased cerebral blood flow velocities and indices of cognition (processing speed and visual attention) and perhaps behavioral (Behavior Rating Inventory of Executive Function) function. This finding is preliminary: a causal relationship is not established, and the physiologic mechanisms underlying such a relationship are not clear. Prospective studies that quantify cumulative exposure to the physiologic consequences of sleep-disordered breathing, such as hypoxia, would be informative.
doi:10.1542/peds.2006-0092
PMCID: PMC1995426  PMID: 17015501
sleep disordered breathing; cerebral blood flow; transcranial Doppler; executive function; neuropsychological function
4.  Capability of a neck worn device to measure sleep/wake, airway position, and differentiate benign snoring from obstructive sleep apnea 
To evaluate the accuracy of a neck-worn device in measuring sleep/wake, detecting supine airway position, and using loud snoring to screen for obstructive sleep apnea. Study A included 20 subjects who wore the neck-device during polysomnography (PSG), with 31 records obtained from diagnostic and split-night studies. Study B included 24 community-based snorers studied in-home for up to three-nights with obstructive sleep apnea (OSA) severity measured with a validated Level III recorder. The accuracy of neck actigraphy-based sleep/wake was measured by assessing sleep efficiency (SE). Differences in sleep position measured at the chest and neck during PSG were compared to video-editing. Loud snoring acquired with an acoustic microphone was compared to the apnea-hypopnea index (AHI) by- and acrosspositions. Over-reported SE by neck actigraphy was inversely related to OSA severity. Measurement of neck and chest supine position were highly correlated with video-edits (r = 0.93, 0.78). Chest was bias toward over-estimating supine time while the majority of neck-device supine position errors occurred during CPAP titrations. Snoring was highly correlated with the overall, supine, and non-supine PSG-AHI (r = 0.79, 0.74, 0.83) and was both sensitive and specific in detecting overall, supine, and non-supine PSGAHI >10 (sensitivity = 81, 88, 82 %; specificity = 87, 79, 100 %). At home sleep testing-AHI > 10, the sensitivity and specificity of loud snoring was superior when users were predominantly non-supine as compared to baseline (sensitivity = 100, 92 %; specificity = 88, 77 %). Neck actigraphy appears capable of estimating sleep/wake. The accuracy of supine airway detection with the neck-device warrants further investigation. Measurement of loud snoring appears to provide a screening tool for differentiating positional apneic and benign snorers.
doi:10.1007/s10877-014-9569-3
PMCID: PMC4309901  PMID: 24599632
OSA; Positional; Snoring; Screening; Actigraphy; Validation
5.  Risk of sedation for diagnostic esophagogastroduodenoscopy in obstructive sleep apnea patients 
AIM: To investigate whether patients with obstructive sleep apnea (OSA) are at risk of sedation-related complications during diagnostic esophagogastroduodenoscopy (EGD).
METHODS: A prospective study was performed in consecutive patients with OSA, who were confirmed with full-night polysomnography between July 2010 and April 2011. The occurrence of cardiopulmonary complications related to sedation during diagnostic EGD was compared between OSA and control groups.
RESULTS: During the study period, 31 patients with OSA and 65 controls were enrolled. Compared with the control group, a higher dosage of midazolam was administered (P = 0.000) and a higher proportion of deep sedation was performed (P = 0.024) in the OSA group. However, all adverse events, including sedation failure, paradoxical responses, snoring or apnea, hypoxia, hypotension, oxygen or flumazenil administration, and other adverse events were not different between the two groups (all P > 0.1). Patients with OSA were not predisposed to hypoxia with multivariate logistic regression analysis (P = 0.068).
CONCLUSION: In patients with OSA, this limited sized study did not disclose an increased risk of cardiopulmonary complications during diagnostic EGD under sedation.
doi:10.3748/wjg.v19.i29.4745
PMCID: PMC3732847  PMID: 23922472
Conscious sedation; Obstructive sleep apnea; Endoscopy; Complications; Safety
6.  Energy Types of Snoring Sounds in Patients with Obstructive Sleep Apnea Syndrome: A Preliminary Observation 
PLoS ONE  2012;7(12):e53481.
Background
Annoying snore is the principle symptom and problem in obstructive sleep apnea syndrome (OSAS). However, investigation has been hampered by the complex snoring sound analyses.
Objective
This study was aimed to investigate the energy types of the full-night snoring sounds in patients with OSAS.
Patients and Method
Twenty male OSAS patients underwent snoring sound recording throughout 6 hours of in-lab overnight polysomnogragphy. Snoring sounds were processed and analyzed by a new sound analytic program, named as Snore Map®. We transformed the 6-hour snoring sound power spectra into the energy spectrum and classified it as snore map type 1 (monosyllabic low-frequency snore), type 2 (duplex low-&mid-frequency snore), type 3 (duplex low- & high-frequency snore), and type 4 (triplex low-, mid-, & high-frequency snore). The interrator and test-retest reliabilities of snore map typing were assessed. The snore map types and their associations among demographic data, subjective snoring questionnaires, and polysomnographic parameters were explored.
Results
The interrator reliability of snore map typing were almost perfect (κ = 0.87) and the test-retest reliability was high (r = 0.71). The snore map type was proportional to the body mass index (r = 0.63, P = 0.003) and neck circumference (r = 0.52, P = 0.018). Snore map types were unrelated to subjective snoring questionnaire scores (All P>0.05). After adjustment for body mass index and neck circumference, snore map type 3–4 was significantly associated with severity of OSAS (r = 0.52, P = 0.026).
Conclusions
Snore map typing of a full-night energy spectrum is feasible and reliable. The presence of a higher snore map type is a warning sign of severe OSAS and indicated priority OSAS management. Future studies are warranted to evaluate whether snore map type can be used to discriminate OSAS from primary snoring and whether it is affected by OSAS management.
doi:10.1371/journal.pone.0053481
PMCID: PMC3534069  PMID: 23300931
7.  Deep sedation during gastrointestinal endoscopy: Propofol-fentanyl and midazolam-fentanyl regimens 
AIM: To compare deep sedation with propofol-fentanyl and midazolam-fentanyl regimens during upper gastrointestinal endoscopy.
METHODS: After obtaining approval of the research ethics committee and informed consent, 200 patients were evaluated and referred for upper gastrointestinal endoscopy. Patients were randomized to receive propofol-fentanyl or midazolam-fentanyl (n = 100/group). We assessed the level of sedation using the observer’s assessment of alertness/sedation (OAA/S) score and bispectral index (BIS). We evaluated patient and physician satisfaction, as well as the recovery time and complication rates. The statistical analysis was performed using SPSS statistical software and included the Mann-Whitney test, χ2 test, measurement of analysis of variance, and the κ statistic.
RESULTS: The times to induction of sedation, recovery, and discharge were shorter in the propofol-fentanyl group than the midazolam-fentanyl group. According to the OAA/S score, deep sedation events occurred in 25% of the propofol-fentanyl group and 11% of the midazolam-fentanyl group (P = 0.014). Additionally, deep sedation events occurred in 19% of the propofol-fentanyl group and 7% of the midazolam-fentanyl group according to the BIS scale (P = 0.039). There was good concordance between the OAA/S score and BIS for both groups (κ = 0.71 and κ = 0.63, respectively). Oxygen supplementation was required in 42% of the propofol-fentanyl group and 26% of the midazolam-fentanyl group (P = 0.025). The mean time to recovery was 28.82 and 44.13 min in the propofol-fentanyl and midazolam-fentanyl groups, respectively (P < 0.001). There were no severe complications in either group. Although patients were equally satisfied with both drug combinations, physicians were more satisfied with the propofol-fentanyl combination.
CONCLUSION: Deep sedation occurred with propofol-fentanyl and midazolam-fentanyl, but was more frequent in the former. Recovery was faster in the propofol-fentanyl group.
doi:10.3748/wjg.v19.i22.3439
PMCID: PMC3683682  PMID: 23801836
Endoscopy; Deep sedation; Anesthetic administration; Anesthetic dose; Adverse effects
8.  Automatic Detection of Whole Night Snoring Events Using Non-Contact Microphone 
PLoS ONE  2013;8(12):e84139.
Objective
Although awareness of sleep disorders is increasing, limited information is available on whole night detection of snoring. Our study aimed to develop and validate a robust, high performance, and sensitive whole-night snore detector based on non-contact technology.
Design
Sounds during polysomnography (PSG) were recorded using a directional condenser microphone placed 1 m above the bed. An AdaBoost classifier was trained and validated on manually labeled snoring and non-snoring acoustic events.
Patients
Sixty-seven subjects (age 52.5±13.5 years, BMI 30.8±4.7 kg/m2, m/f 40/27) referred for PSG for obstructive sleep apnea diagnoses were prospectively and consecutively recruited. Twenty-five subjects were used for the design study; the validation study was blindly performed on the remaining forty-two subjects.
Measurements and Results
To train the proposed sound detector, >76,600 acoustic episodes collected in the design study were manually classified by three scorers into snore and non-snore episodes (e.g., bedding noise, coughing, environmental). A feature selection process was applied to select the most discriminative features extracted from time and spectral domains. The average snore/non-snore detection rate (accuracy) for the design group was 98.4% based on a ten-fold cross-validation technique. When tested on the validation group, the average detection rate was 98.2% with sensitivity of 98.0% (snore as a snore) and specificity of 98.3% (noise as noise).
Conclusions
Audio-based features extracted from time and spectral domains can accurately discriminate between snore and non-snore acoustic events. This audio analysis approach enables detection and analysis of snoring sounds from a full night in order to produce quantified measures for objective follow-up of patients.
doi:10.1371/journal.pone.0084139
PMCID: PMC3877189  PMID: 24391903
9.  Comparative Effects of Snoring Sound between Two Minimally Invasive Surgeries in the Treatment of Snoring: A Randomized Controlled Trial 
PLoS ONE  2014;9(5):e97186.
Background
Minimally invasive surgeries of the soft palate have emerged as a less-invasive treatment for habitual snoring. To date, there is only limited information available comparing the effects of snoring sound between different minimally invasive surgeries in the treatment of habitual snoring.
Objective
To compare the efficacy of palatal implant and radiofrequency surgery, in the reduction of snoring through subjective evaluation of snoring and objective snoring sound analysis.
Patients and Method
Thirty patients with habitual snoring due to palatal obstruction (apnea-hypopnea index ≤15, body max index ≤30) were prospectively enrolled and randomized to undergo a single session of palatal implant or temperature-controlled radiofrequency surgery of the soft palate under local anesthesia. Snoring was primarily evaluated by the patient with a 10 cm visual analogue scale (VAS) at baseline and at a 3-month follow-up visit and the change in VAS was the primary outcome. Moreover, life qualities, measured by snore outcomes survey, and full-night snoring sounds, analyzed by a sound analytic program (Snore Map), were also investigated at the same time.
Results
Twenty-eight patients completed the study; 14 received palatal implant surgery and 14 underwent radiofrequency surgery. The VAS and snore outcomes survey scores were significantly improved in both groups. However, the good response (postoperative VAS ≤3 or postoperative VAS ≤5 plus snore outcomes survey score ≥60) rate of the palatal implant group was significantly higher than that of the radiofrequency group (79% vs. 29%, P = 0.021). The maximal loudness of low-frequency (40–300 Hz) snores was reduced significantly in the palatal implant group. In addition, the snoring index was significantly reduced in the radiofrequency group.
Conclusions
Both palatal implants and a single-stage radiofrequency surgery improve subjective snoring outcomes, but palatal implants have a greater effect on most measures of subjective and objective snoring. Multi-stage radiofrequency surgery was not tested.
Trial Registration
ClinicalTrials.gov NCT01955083
doi:10.1371/journal.pone.0097186
PMCID: PMC4016275  PMID: 24816691
10.  Obstructive Sleep Apnea and Risk of Cardiovascular Events and All-Cause Mortality: A Decade-Long Historical Cohort Study 
PLoS Medicine  2014;11(2):e1001599.
Tetyana Kendzerska and colleagues explore the association between physiological measures of obstructive sleep apnea other than the apnea-hypopnea index and the risk of cardiovascular events.
Please see later in the article for the Editors' Summary
Background
Obstructive sleep apnea (OSA) has been reported to be a risk factor for cardiovascular (CV) disease. Although the apnea-hypopnea index (AHI) is the most commonly used measure of OSA, other less well studied OSA-related variables may be more pathophysiologically relevant and offer better prediction. The objective of this study was to evaluate the relationship between OSA-related variables and risk of CV events.
Methods and Findings
A historical cohort study was conducted using clinical database and health administrative data. Adults referred for suspected OSA who underwent diagnostic polysomnography at the sleep laboratory at St Michael's Hospital (Toronto, Canada) between 1994 and 2010 were followed through provincial health administrative data (Ontario, Canada) until May 2011 to examine the occurrence of a composite outcome (myocardial infarction, stroke, congestive heart failure, revascularization procedures, or death from any cause). Cox regression models were used to investigate the association between baseline OSA-related variables and composite outcome controlling for traditional risk factors. The results were expressed as hazard ratios (HRs) and 95% CIs; for continuous variables, HRs compare the 75th and 25th percentiles. Over a median follow-up of 68 months, 1,172 (11.5%) of 10,149 participants experienced our composite outcome. In a fully adjusted model, other than AHI OSA-related variables were significant independent predictors: time spent with oxygen saturation <90% (9 minutes versus 0; HR = 1.50, 95% CI 1.25–1.79), sleep time (4.9 versus 6.4 hours; HR = 1.20, 95% CI 1.12–1.27), awakenings (35 versus 18; HR = 1.06, 95% CI 1.02–1.10), periodic leg movements (13 versus 0/hour; HR = 1.05, 95% CI 1.03–1.07), heart rate (70 versus 56 beats per minute [bpm]; HR = 1.28, 95% CI 1.19–1.37), and daytime sleepiness (HR = 1.13, 95% CI 1.01–1.28).The main study limitation was lack of information about continuous positive airway pressure (CPAP) adherence.
Conclusion
OSA-related factors other than AHI were shown as important predictors of composite CV outcome and should be considered in future studies and clinical practice.
Please see later in the article for the Editors' Summary
Editors' Summary
Background
Obstructive sleep apnea (OSA) is a common sleep-related breathing disorder, particularly among middle-aged and elderly people. It is characterized by apnea—a brief interruption in breathing that lasts at least 10 seconds—and hypopnea—a decrease of more than 50% in the amplitude of breathing that lasts at least 10 seconds or clear but smaller decrease in amplitude associated with either oxygen desaturation or an arousal. Patients with OSA experience numerous episodes of apnea and hypopnea during the night; severe OSA is defined as having 30 or more episodes per hour (an apnea-hypopnea index [AHI] of >30). These breathing interruptions occur when relaxation of the upper airway muscles decreases the airflow, which lowers the amount of oxygen in the blood. As a result, affected individuals frequently wake from deep sleep as they struggle to breathe. Symptoms of OSA include loud snoring and daytime sleepiness. Treatments include lifestyle changes such as losing weight (excess fat around the neck increases airway collapse) and smoking cessation. For severe OSA, doctors recommend continuous positive airway pressure (CPAP), in which a machine blows pressurized air through a face mask into the airway to keep it open.
Why Was This Study Done?
OSA can be life-threatening. Most directly, daytime sleepiness can cause accidents, but OSA is also associated with an increased risk of developing cardiovascular disease (CVD, disease that affects the heart and the circulation). To date, studies that have investigated the association between OSA and the risk of myocardial infarction (heart attack), congestive heart failure, stroke, and other CVDs have used the AHI to diagnose and categorize the severity of OSA. However, by focussing on AHI, clinicians and researchers may be missing opportunities to improve their ability to predict which patients are at the highest risk of CVD. In this historical cohort study, the researchers investigate the association between other OSA-related variables (for example, blood oxygen saturation and sleep fragmentation) and the risk of cardiovascular events and all-cause mortality (death). A historical cohort study examines the medical records of groups of individuals who have different characteristics at baseline for the subsequent occurrence of specific outcomes.
What Did the Researchers Do and Find?
The researchers used administrative data (including hospitalization records and physicians' claims for services supplied to patients) to follow up adults referred for suspected OSA who underwent diagnostic polysomnography (a sleep study) at a single Canadian hospital between 1994 and 2010. A database of the polysomnography results provided information on OSA-related variables for all the study participants. Over an average follow-up of about 6 years, 11.5% of the 10,149 participants were hospitalized for a myocardial infarction, stroke, or congestive heart failure, underwent a revascularization procedure (an intervention that restores the blood supply to an organ or tissue after CVD has blocked a blood vessel), or had died from any cause. After adjusting for multiple established risk factors for CVD such as smoking and age in Cox regression models (a statistical approach that examines associations between patient variables and outcomes), several OSA-related variables (but not AHI) were significant predictors of CVD. The strongest OSA-related predictor of cardiovascular events or all-cause mortality was total sleep time spent with oxygen saturation below 90%, which increased the risk of a cardiovascular event or death by 50%. Other statistically significant OSA-related predictors (predictors that were unlikely to be associated with the outcome through chance) of cardiovascular events or death included total sleep time, number of awakenings, frequency of periodic leg movements, heart rate, and daytime sleepiness.
What Do These Findings Mean?
These findings indicate that OSA-related factors other than AHI are important predictors of the composite outcome of a cardiovascular event or all-cause mortality. Indeed, although AHI was significantly associated with the researchers' composite outcome in an analysis that did not consider other established risk factors for CVD (“confounders”), the association became non-significant after controlling for potential confounders. The accuracy of these findings, which need to be confirmed in other settings, is likely to be limited by the lack of information available about the use of CPAP by study participants and by the lack of adjustment for some important confounders. Importantly, however, these findings suggest that OSA-related factors other than AHI should be considered as predictors of CVD in future studies and in clinical practice.
Additional Information
Please access these websites via the online version of this summary at http://dx.doi.org/10.1371/journal.pmed.1001599.
The US National Heart Lung and Blood Institute has information (including several videos) about obstructive sleep apnea (in English and Spanish), sleep studies, heart disease, and other cardiovascular diseases (some information in English and Spanish)
The UK National Health Service Choices website provides information (including personal stories) about sleep apnea and about cardiovascular disease
The not-for-profit American Sleep Apnea Association provides detailed information about sleep apnea for patients and health-care professionals, including personal stories about the condition
The MedlinePlus encyclopedia has pages on obstructive sleep apnea and on polysomnography; MedlinePlus provides links to further information and advice about obstructive sleep apnea, heart diseases, and vascular diseases (in English and Spanish)
doi:10.1371/journal.pmed.1001599
PMCID: PMC3913558  PMID: 24503600
11.  Comparison of Propofol-Remifentanil Versus Propofol-Ketamine Deep Sedation for Third Molar Surgery 
Anesthesia Progress  2012;59(3):107-117.
This study aimed to compare continuous intravenous infusion combinations of propofol-remifentanil and propofol-ketamine for deep sedation for surgical extraction of all 4 third molars. In a prospective, randomized, double-blinded controlled study, participants received 1 of 2 sedative combinations for deep sedation for the surgery. Both groups initially received midazolam 0.03 mg/kg for baseline sedation. The control group then received a combination of propofol-remifentanil in a ratio of 10 mg propofol to 5 μg of remifentanil per milliliter, and the experimental group received a combination of propofol-ketamine in a ratio of 10 mg of propofol to 2.5 mg of ketamine per milliliter; both were given at an initial propofol infusion rate of 100 μg/kg/min. Each group received an induction loading bolus of 500 μg/kg of the assigned propofol combination along with the appropriate continuous infusion combination . Measured outcomes included emergence and recovery times, various sedation parameters, hemodynamic and respiratory stability, patient and surgeon satisfaction, postoperative course, and associated drug costs. Thirty-seven participants were enrolled in the study. Both groups demonstrated similar sedation parameters and hemodynamic and respiratory stability; however, the ketamine group had prolonged emergence (13.6 ± 6.6 versus 7.1 ± 3.7 minutes, P = .0009) and recovery (42.9 ± 18.7 versus 24.7 ± 7.6 minutes, P = .0004) times. The prolonged recovery profile of continuously infused propofol-ketamine may limit its effectiveness as an alternative to propofol-remifentanil for deep sedation for third molar extraction and perhaps other short oral surgical procedures, especially in the ambulatory dental setting.
doi:10.2344/12-00001.1
PMCID: PMC3468288  PMID: 23050750
Propofol; Ketamine; Remifentanil; Deep sedation; TIVA
12.  Excessive daytime sleepiness among rural residents in Saskatchewan 
Obstructive sleep apnea and its sequelae are emerging public health issues in North America, and symptoms are often under-recognized or under-reported. Although several patient factors have been identified, limited data regarding the prevalence of and predictors for excessive daytime sleepiness in rural or remote populations area available. Accordingly, this study used Epworth Sleepiness Scale scores to evaluate daytime sleepiness in a large rural population participating in the Saskatchewan Rural Health Study.
BACKGROUND:
Obstructive sleep apnea (OSA) is a common diagnosis in clinical practice. Excessive daytime sleepiness may be a warning for possible OSA.
OBJECTIVES:
To assess the prevalence of excessive daytime sleepiness as measured by the Epworth Sleepiness Scale (ESS) in a rural community population; potential risk factors for OSA were also assessed.
METHODS:
In 2010, a baseline respiratory health questionnaire within the Saskatchewan Rural Health Study was mailed to 11,982 households in Saskatchewan. A total of 7597 adults within the 4624 (42%) respondent households completed the ESS questionnaire. Participants were categorized according to normal or high (>10) ESS scores. Data obtained included respiratory symptoms, doctor-diagnosed sleep apnea, snoring, hypertension, smoking and demographics. Body mass index was calculated. Multivariable logistic regression analysis examined associations between high ESS scores and possible risk factors. Generalized estimating equations accounted for the two-tiered sampling procedure of the study design.
RESULTS:
The mean age of respondents was 55.0 years and 49.2% were male. The prevalence of ESS>10 and ‘doctor diagnosed’ OSA were 15.9% and 6.0%, respectively. Approximately 23% of respondents reported loud snoring and 30% had a body mass index >30 kg/m2. Of those with ‘doctor-diagnosed’ OSA, 37.7% reported ESS>10 (P<0.0001) and 47.7% reported loud snoring (P<0.0001). Risk of having an ESS>10 score increased with age, male sex, obesity, lower socioeconomic status, marriage, loud snoring and doctor-diagnosed sinus trouble.
CONCLUSIONS:
High levels of excessive daytime sleepiness in this particular rural population are common and men >55 years of age are at highest risk. Examination of reasons for residual sleepiness and snoring in persons with and without sleep apnea is warranted.
PMCID: PMC4173890  PMID: 24791255
Epworth Sleepiness Scale; Farm; Nonfarm; Obesity; Rural; Sleep apnea; Snoring; Socioeconomic
13.  Assessment of the effects of ketamine-fentanyl combination versus propofol-remifentanil combination for sedation during endoscopic retrograde cholangiopancreatography 
Background:
Endoscopic retrograde cholangiopancreatography (ERCP) as a diagnostic and treatment procedure is used in most biliary tract and pancreatic. Either sedation or general anesthesia could be considered for this procedure. Combining a sedative with an opioid agent can provide effective moderate sedation. This study compared the impact of ketamine-fentanyl (KF) versus propofol-remifentanil (PR) on sedation scale in patients undergoing ERCP.
Materials and Methods:
As a double-blinded randomized clinical trial, 80 patients selected by convenient sampling, allocated randomly into two groups. KF group received ketamine 0.5 mg/kg body weight intravenously over 60 s and then fentanyl 1 mcg/kg body weight intravenously. PR group received propofol l mg/kg body weight intravenously over 60 s and then remifentanil 0.05 mcg/kg body weight/min intravenously. Intravenous (IV) infusion of propofol was maintained by 50 mcg/kg body weight/min throughout ERCP. Ramsay Sedation Score, vital signs, oxygen saturation (SpO2), recovery score (modified Aldrete score) and visual analog scales of pain intensity, and endoscopist's satisfaction were considered as measured outcomes. All analysis were analyzed by SPSS Statistics version 22 and using t-test, Chi-square and repeated measured ANOVA and Mann-Whitney tests for data analysis.
Results:
Respiratory rate and SpO2 level during the time intervals were lower in PR group (P < 0.001). Sedation score at intervals was not significantly different (P = 0.07). The frequency of apnea in PR group was significantly higher than the KF group (P = 0.003). The percentage of need to supplemental oxygen in PR group was 35.1% that was also significantly higher than 8.8% in the KF group (P = 0.008), but the dosage frequency was significantly higher in KF group (P < 0.001). The KF and PR groups average length of stay in the recovery room were 50.71 standard deviation (SD = 9.99) and 42.57 (SD = 11.99) minutes, respectively, indicating a significant difference (P = 0.003). The mean severity of nausea in KF and PR groups was, respectively, 2.74 confidence interval (CI = 1.68-3.81) and 0.43 (CI = 0.11-0.75), that was significantly higher in KF group (P < 0.001). The average score of surgeon satisfaction in both KF and PR groups were 7.69 (CI = 7.16-8.21) and 8.65 (CI = 8.25-9.05), respectively, which was higher in KF group (P = 0.004), but the average level of patients satisfaction in KF group was 8.86 (CI = 8.53-9.19) and in PR group was 8.95 (CI - 8.54-9.35) that were not significantly different (P = 0.074).
Conclusion:
There is no statistically significant difference between KF and PR combinations in sedation score, but PR combination provides better pain control, with less nausea and shorter recovery time while causing more respiratory side effects, that is, apnea and need to oxygen.
PMCID: PMC4268195  PMID: 25535501
Endoscopic retrograde cholangiopancreatography; fentanyl; ketamine; propofol; remifentanil
14.  Effect of Treatment of Obstructive Sleep Apnea on Depressive Symptoms: Systematic Review and Meta-Analysis 
PLoS Medicine  2014;11(11):e1001762.
In a meta-analysis of randomized controlled trials, Matthew James and colleagues investigate the effects of continuous positive airway pressure or mandibular advancement devices on depression.
Please see later in the article for the Editors' Summary
Background
Obstructive sleep apnea (OSA) is associated with increased morbidity and mortality, and decreased quality of life. Treatment with continuous positive airway pressure (CPAP) or mandibular advancement devices (MADs) is effective for many symptoms of OSA. However, it remains controversial whether treatment with CPAP or MAD also improves depressive symptoms.
Methods and Findings
We performed a systematic review and meta-analysis of randomized controlled trials that examined the effect of CPAP or MADs on depressive symptoms in patients with OSA. We searched Medline, EMBASE, the Cochrane Central Registry of Controlled Trials, and PsycINFO from the inception of the databases until August 15, 2014, for relevant articles.
In a random effects meta-analysis of 19 identified trials, CPAP treatment resulted in an improvement in depressive symptoms compared to control, but with significant heterogeneity between trials (Q statistic, p<0.001; I2 = 71.3%, 95% CI: 54%, 82%). CPAP treatment resulted in significantly greater improvement in depressive symptoms in the two trials with a higher burden of depression at baseline (meta-regression, p<0.001). The pooled standardized mean difference (SMD) in depressive symptoms with CPAP treatment in these two trial populations with baseline depression was 2.004 (95% CI: 1.387, 2.621), compared to 0.197 (95% CI: 0.059, 0.334) for 15 trials of populations without depression at baseline. Pooled estimates of the treatment effect of CPAP were greater in parallel arm trials than in crossover trials (meta-regression, p = 0.076). Random effects meta-analysis of five trials of MADs showed a significant improvement in depressive symptoms with MADs versus controls: SMD = 0.214 (95% CI: 0.026, 0.401) without significant heterogeneity (I2 = 0%, 95% CI: 0%, 79%). Studies were limited by the use of depressive symptom scales that have not been validated specifically in people with OSA.
Conclusions
CPAP and MADs may be useful components of treatment of depressive symptoms in individuals with OSA and depression. The efficacy of CPAP and MADs compared to standard therapies for depression is unknown.
Please see later in the article for the Editors' Summary
Editors' Summary
Background
Obstructive sleep apnea (OSA) is a sleep-related breathing disorder that is particularly common among middle-aged and elderly people, although most are unaware that they have the condition. It is characterized by the occurrence of numerous brief (ten seconds or so) breathing interruptions during sleep. These “apneas” occur when relaxation of the upper airway muscles decreases airflow, which lowers the level of oxygen in the blood. Consequently, affected individuals are frequently aroused from deep sleep as they struggle to breathe. Symptoms of OSA include loud snoring and daytime sleepiness. Treatments include lifestyle changes such as losing weight (excess fat around the neck increases airway collapse) and smoking cessation. Mild to moderate OSA can also be treated using a mandibular advancement device (MAD), a “splint” that fits inside the mouth and pushes the jaw and tongue forward to increase the space at the back of the throat and reduce airway narrowing. For severe OSA, doctors recommend continuous positive airway pressure (CPAP), in which a machine blows pressurized air into the airway through a facemask to keep it open.
Why Was This Study Done?
OSA is a serious condition that is associated with an increased risk of illness and death. Clinical depression (long-lasting, overwhelming feelings of sadness and hopelessness), for example, is common among people with OSA. The interaction between these frequently co-morbid (co-existing) conditions is complex. The sleep disruption and weight gain that are often associated with depression could cause or worsen OSA. Conversely, OSA could trigger depression by causing sleep disruption and by inducing cognitive changes (changes in thinking) by intermittently starving the brain of oxygen. If the latter scenario is correct, then treating OSA with CPAP or MADs might improve depressive symptoms. Several trials have investigated this possibility, but their results have been equivocal. Here, the researchers undertake a systematic review and meta-analysis of randomized controlled trials that have examined the effect of CPAP or MADs on depressive symptoms in patients with OSA to find out whether treating co-morbid OSA in patients with depression can help to treat depression. A randomized controlled trial compares the outcomes of individuals chosen to receive different interventions through the play of chance, a systematic review uses predefined criteria to identify all the research on a given topic, and meta-analysis uses statistical methods to combine the results of several studies.
What Did the Researchers Do and Find?
The researchers identified 22 trials that investigated the effects of CPAP or MAD treatment in patients with OSA and that measured depressive symptoms before and after treatment. Meta-analysis of the results of 19 trials that provided information about the effect of CPAP on depressive symptoms indicated that CPAP improved depressive symptoms compared to the control intervention (usually sham CPAP) but revealed considerable heterogeneity (variability) between trials. Notably, CPAP treatment resulted in a greater improvement in depressive symptoms in trials in which there was a high prevalence of depression at baseline than in trials in which there was a low prevalence of depression at baseline. Moreover, the magnitude of this improvement in depressive symptoms in trials with a high prevalence of depression at baseline was large enough to be clinically relevant. Meta-analysis of five trials that provided information about the effect of MADs on depressive symptoms indicated that MADs also improved depressive symptoms compared to the control intervention (sham MAD).
What Do These Findings Mean?
These findings suggest that both CPAP and MAD treatment for OSA can result in modest improvements in depressive symptoms and that populations with high initial levels of depressive symptoms may reap the greatest benefits of CPAP treatment. These findings give no indication of the efficacy of CPAP and MADs compared to standard treatments for depression such as antidepressant medications. Moreover, their accuracy may be limited by methodological limitations within the trials included in the meta-analyses reported here. For example, the questionnaires used to measure depression in these trials were not validated for use in people with OSA. Further high-quality randomized controlled trials are therefore needed to confirm the findings of this systematic review and meta-analysis. For now, however, these findings suggest that the use of CPAP and MADs may help improve depressive symptoms among people with OSA.
Additional Information
Please access these websites via the online version of this summary at http://dx.doi.org/10.1371/journal.pmed.1001762.
The US National Heart, Lung, and Blood Institute has information (including several videos) about sleep apnea (in English and Spanish)
The UK National Health Service Choices website provides information and personal stories about obstructive sleep apnea and depression
The not-for-profit American Sleep Apnea Association provides detailed information about sleep apnea for patients and healthcare professionals, including personal stories about the condition
The US National Institute of Mental Health provides information on all aspects of depression (in English and Spanish)
The Anxiety and Depression Association of America provides information about sleep disorders
The MedlinePlus encyclopedia has a page on obstructive sleep apnea; MedlinePlus provides links to further information and advice about obstructive sleep apnea and about depression (in English and Spanish)
doi:10.1371/journal.pmed.1001762
PMCID: PMC4244041  PMID: 25423175
15.  Snoring during pregnancy and its relation to sleepiness and pregnancy outcome - a prospective study 
Background
The incidence of snoring and sleepiness is known to increase during pregnancy, and this might impact maternal health and obstetric outcome. However, the association between snoring and sleepiness during pregnancy is not fully understood. This study was aimed at investigating the development of snoring during pregnancy and prospectively assessing if there is an association between snoring and sleepiness or adverse pregnancy outcomes, such as preeclampsia, mode of delivery, and fetal complications.
Methods
Consecutively recruited pregnant women (n = 500) received a questionnaire concerning snoring and sleep at the 1st and 3rd trimester of pregnancy. The women who had rated their frequency of snoring at both occasions (n = 340) were divided into subgroups according to the development of snoring they reported and included in the subsequent analyses. Additional medical data were collected from the medical records.
Results
The frequency of snoring was 7.9% in the 1st trimester and increased to 21.2% in the 3rd trimester of pregnancy. The women who snored already in early pregnancy had significantly higher baseline BMI (p = 0.001) than the women who never snored, but snoring was not associated with the magnitude of weight gain during pregnancy. Snoring women were more likely to experience edema in late pregnancy than the non-snorers. Women who started to snore during pregnancy had higher Epworth Sleepiness Scores than the non snorers in both early and late pregnancy. No significant association between obstetric outcome and snoring was found.
Conclusion
Snoring does increase during pregnancy, and this increase is associated with sleepiness, higher BMI at the start of pregnancy and higher prevalence of edema, but not with weight gain.
doi:10.1186/1471-2393-14-15
PMCID: PMC3893487  PMID: 24418321
Pregnancy; Snoring; Sleepiness; Epworth sleepiness score; Body mass index; Edema; Pregnancy outcome
16.  Comparison between the recovery time of alfentanil and fentanyl in balanced propofol sedation for gastrointestinal and colonoscopy: a prospective, randomized study 
BMC Gastroenterology  2012;12:164.
Background
There is increasing interest in balanced propofol sedation (BPS) titrated to moderate sedation (conscious sedation) for endoscopic procedures. However, few controlled studies on BPS targeted to deep sedation for diagnostic endoscopy were found. Alfentanil, a rapid and short-acting synthetic analog of fentanyl, appears to offer clinically significant advantages over fentanyl during outpatient anesthesia.
It is reasonable to hypothesize that low dose of alfentanil used in BPS might also result in more rapid recovery as compared with fentanyl.
Methods
A prospective, randomized and double-blinded clinical trial of alfentanil, midazolam and propofol versus fentanyl, midazolam and propofol in 272 outpatients undergoing diagnostic esophagogastroduodenal endoscopy (EGD) and colonoscopy for health examination were enrolled. Randomization was achieved by using the computer-generated random sequence. Each combination regimen was titrated to deep sedation. The recovery time, patient satisfaction, safety and the efficacy and cost benefit between groups were compared.
Results
260 participants were analyzed, 129 in alfentanil group and 131 in fentanyl group. There is no significant difference in sex, age, body weight, BMI and ASA distribution between two groups. Also, there is no significant difference in recovery time, satisfaction score from patients, propofol consumption, awake time from sedation, and sedation-related cardiopulmonary complications between two groups. Though deep sedation was targeted, all cardiopulmonary complications were minor and transient (10.8%, 28/260). No serious adverse events including the use of flumazenil, assisted ventilation, permanent injury or death, and temporary or permanent interruption of procedure were found in both groups. However, fentanyl is New Taiwan Dollar (NT$) 103 (approximate US$ 4) cheaper than alfentanil, leading to a significant difference in total cost between two groups.
Conclusions
This randomized, double-blinded clinical trial showed that there is no significant difference in the recovery time, satisfaction score from patients, propofol consumption, awake time from sedation, and sedation-related cardiopulmonary complications between the two most common sedation regimens for EGD and colonoscopy in our hospital. However, fentanyl is NT$103 (US$ 4) cheaper than alfentanil in each case.
Trial registration
Institutional Review Board of Buddhist Tzu Chi General Hospital (IRB097-18) and Chinese Clinical Trial Registry (ChiCTR-TRC-12002575)
doi:10.1186/1471-230X-12-164
PMCID: PMC3607964  PMID: 23170921
Balanced propofol sedation; Alfentanil; Fentanyl; Deep sedation; Diagnostic endoscopy; Cost benefit
17.  Childhood Obstructive Sleep Apnea Associates with Neuropsychological Deficits and Neuronal Brain Injury 
PLoS Medicine  2006;3(8):e301.
Background
Childhood obstructive sleep apnea (OSA) is associated with neuropsychological deficits of memory, learning, and executive function. There is no evidence of neuronal brain injury in children with OSA. We hypothesized that childhood OSA is associated with neuropsychological performance dysfunction, and with neuronal metabolite alterations in the brain, indicative of neuronal injury in areas corresponding to neuropsychological function.
Methods and Findings
We conducted a cross-sectional study of 31 children (19 with OSA and 12 healthy controls, aged 6–16 y) group-matched by age, ethnicity, gender, and socioeconomic status. Participants underwent polysomnography and neuropsychological assessments. Proton magnetic resonance spectroscopic imaging was performed on a subset of children with OSA and on matched controls. Neuropsychological test scores and mean neuronal metabolite ratios of target brain areas were compared.
Relative to controls, children with severe OSA had significant deficits in IQ and executive functions (verbal working memory and verbal fluency). Children with OSA demonstrated decreases of the mean neuronal metabolite ratio N-acetyl aspartate/choline in the left hippocampus (controls: 1.29, standard deviation [SD] 0.21; OSA: 0.91, SD 0.05; p = 0.001) and right frontal cortex (controls: 2.2, SD 0.4; OSA: 1.6, SD 0.4; p = 0.03).
Conclusions
Childhood OSA is associated with deficits of IQ and executive function and also with possible neuronal injury in the hippocampus and frontal cortex. We speculate that untreated childhood OSA could permanently alter a developing child's cognitive potential.
Childhood obstructive sleep apnea is associated with deficits of IQ and executive function and also with possible neuronal injury in the hippocampus and frontal cortex.
Editors' Summary
Background.
Sleep is essential for health, and in children it is crucial to normal development. Symptomatic childhood sleep-disordered breathing (SDB) is the name for a range of conditions in which children have difficulties with breathing when they are asleep. The conditions range from simple snoring to the most severe condition, known as obstructive sleep apnea (OSA). Apnea means a temporary absence of breathing, and in OSA this is caused by a temporary but repeated blockage of the flow of air to the lungs. In children, OSA occurs for a number of reasons including enlarged tonsils, long-term allergy, and obesity. About two in every hundred children have OSA. The symptoms of OSA are loud snoring at night, disrupted, restless sleep, undue tiredness, and difficulties in concentration. The main test for it is a sleep study (polysomnography). If untreated, researchers believe that it may lead to a number of long-term problems with health and learning; children with disorders of sleep have been shown to have memory problems, lower general intelligence, and worse executive function (the ability to adapt to new situations), and may have behavioral problems similar to those of attention deficit hyperactivity disorder (ADHD).
Why Was This Study Done?
Adults with sleep apnea have been shown to have abnormalities of parts of their brain, specifically the frontal cortex, cerebellum, and hippocampus, but so far there are no data on whether there are similar changes in children. Children with sleep apnea may have cognitive deficits, but the research on this topic is limited.
What Did the Researchers Do and Find?
The researchers wanted to investigate the brains of children with OSA to see if there was any evidence of changes in the brain and if these changes were associated with any learning problems. They studied 31 children (19 with OSA and 12 healthy controls, aged 6–16 y). Participants underwent polysomnography and neuropsychological assessments, such as IQ tests and tests of their ability to perform tasks involving decision making. Some of the children also had specialized scans of their brains (known as proton magnetic resonance spectroscopic imaging) that can measure the levels of certain metabolites—substances that are produced as a result of brain activity. The researchers then compared the neuropsychological test scores with the levels of the metabolites. They found that relative to controls, children with severe OSA had lower IQ and ability to perform tasks involving decision making. Children with OSA also had changes in metabolites in the brain similar to those seen in diseases in which there is damage to brain cells.
What Do These Findings Mean?
It seems clear that OSA in children is associated with learning problems, and that these learning problems may in turn be associated with changes in brain metabolites. The changes in metabolites are not necessarily permanent—in other diseases where changes have been found they can be reversed with treatment. If these results are confirmed in other children with OSA, it will highlight the importance of treating children for OSA as soon as possible. In addition, the measurement of metabolites may be a way of measuring how well children are responding to treatment.
Additional Information.
Please access these Web sites via the online version of this summary at http://dx.doi.org/10.1371/journal.pmed.0030301.
MedlinePlus's encyclopedia has an entry on sleep apnea
The American Sleep Apnea Association has information about having a child investigated for sleep apnea
The National Sleep Foundation also provides information about sleep disorders
doi:10.1371/journal.pmed.0030301
PMCID: PMC1551912  PMID: 16933960
18.  A Comparison between Sedative Effect of Propofol-Fentanyl and Propofol-Midazolam Combinations in Microlaryngeal Surgeries 
Considering the growing trend of laryngeal surgeries and the need to protect the airway during and after surgery, among several therapeutic regimens to induce sedation, two regimens of propofol-fentanyl and propofol-midazolam were compared in microlaryngeal surgeries.
Forty ASA I-II class patients undergoing microlaryngeal surgeries and referring routinely for postoperative visits were randomly recruited into two groups. For all the patients, 0.5 mg/Kg of propofol was used as bolus and then, 50 mcg/Kg/min of the drug was infused intravenously. For one group, 0.03 mg/Kg bolus of midazolam and for the other group, 2 mcg/Kg bolus of fentanyl was administered in combination with propofol. Ramsay system was used in order to evaluate the effect of the two drugs in inducing sedation. The need for additional dose, blood pressure, heart rate, arterial blood oxygen saturation, and also recovery time and adverse effects such as nausea/vomiting and recalling intra-operative memories, were assessed.
The patients in the two groups were not statistically different regarding the number of patients, age, sex, preoperative vital signs, the need for additional doses of propofol, systolic blood pressure and mean systolic blood pressure during laryngoscopy. However, mean systolic blood pressure 1 min after removal of laryngoscope returned faster to the baseline in midazolam group (p < 0.01). Mean heart rate returned sooner to the baseline in fentanyl group following removal of stimulation. Besides, heart rate showed a more reduction following administration of fentanyl (p < 0.02). Mean arterial blood oxygen saturation during laryngoscopy significantly decreased in fentanyl group (p < 0.05) compared to the other group. The time it took to achieve a full consciousness was shorter in midazolam group (p < 0.01). Nausea/vomiting was significantly more prevalent in fentanyl group while the patients in midazolam group apparently experienced more of amnesia, comparatively (p < 0.01).
Inducing laryngeal block and local anesthesia using propofol-midazolam regimen is not only associated with a more rapid recovery and less recalling of unpleasant memories, but also better in preventing reduction of arterial oxygen saturation during laryngoscopy compared with propofol-fentanyl regimen.
PMCID: PMC3813093  PMID: 24250451
Sedation; Microlaryngeal surgery; Propofol; Midazolam; Fentanyl
19.  Habitual Snoring and Asthma Comorbidity Among Pregnant Women 
Background
Obstructive sleep apnea (OSA) or habitual snoring and asthma are known comorbid conditions in men and non-pregnant women. This comorbidity has not been evaluated among pregnant women. We assessed the habitual snoring-asthma relationship among pregnant women.
Methods
A cohort of women (N=1,335) were interviewed during pregnancy, and we ascertained participants’ asthma status and collected information about habitual snoring, before and during pregnancy. Logistic regression procedures were used to estimate odds ratios (ORs) and 95% confidence intervals (CIs).
Results
Compared with non-asthmatics, the adjusted OR among asthmatics for snoring before pregnancy was 2.13 (95%CI 1.10–4.12). The odds of snoring during early pregnancy was 1.79-fold (OR=1.79; 95%CI 1.07–3.01). Associations were more pronounced among overweight (≥25 kg/m2) asthmatics (OR=5.39; 95%CI 2.27–12.75).
Conclusions
We report a cross-sectional association of habitual snoring and asthma among pregnant women. If confirmed, pregnant asthmatics may benefit from more vigilant screening and management of OSA or habitual snoring during pregnancy.
doi:10.3109/02770903.2010.535882
PMCID: PMC3040561  PMID: 21091394
Asthma; Obstructive Sleep Apnea; Sleep Disordered Breathing; Habitual Snoring; Obesity; Pregnancy
20.  Sleep-Disordered Breathing and Mortality: A Prospective Cohort Study 
PLoS Medicine  2009;6(8):e1000132.
In a cohort of 6,441 volunteers followed over an average of 8.2 years, Naresh Punjabi and colleagues find sleep-disordered breathing to be independently associated with mortality and identify predictive characteristics.
Background
Sleep-disordered breathing is a common condition associated with adverse health outcomes including hypertension and cardiovascular disease. The overall objective of this study was to determine whether sleep-disordered breathing and its sequelae of intermittent hypoxemia and recurrent arousals are associated with mortality in a community sample of adults aged 40 years or older.
Methods and Findings
We prospectively examined whether sleep-disordered breathing was associated with an increased risk of death from any cause in 6,441 men and women participating in the Sleep Heart Health Study. Sleep-disordered breathing was assessed with the apnea–hypopnea index (AHI) based on an in-home polysomnogram. Survival analysis and proportional hazards regression models were used to calculate hazard ratios for mortality after adjusting for age, sex, race, smoking status, body mass index, and prevalent medical conditions. The average follow-up period for the cohort was 8.2 y during which 1,047 participants (587 men and 460 women) died. Compared to those without sleep-disordered breathing (AHI: <5 events/h), the fully adjusted hazard ratios for all-cause mortality in those with mild (AHI: 5.0–14.9 events/h), moderate (AHI: 15.0–29.9 events/h), and severe (AHI: ≥30.0 events/h) sleep-disordered breathing were 0.93 (95% CI: 0.80–1.08), 1.17 (95% CI: 0.97–1.42), and 1.46 (95% CI: 1.14–1.86), respectively. Stratified analyses by sex and age showed that the increased risk of death associated with severe sleep-disordered breathing was statistically significant in men aged 40–70 y (hazard ratio: 2.09; 95% CI: 1.31–3.33). Measures of sleep-related intermittent hypoxemia, but not sleep fragmentation, were independently associated with all-cause mortality. Coronary artery disease–related mortality associated with sleep-disordered breathing showed a pattern of association similar to all-cause mortality.
Conclusions
Sleep-disordered breathing is associated with all-cause mortality and specifically that due to coronary artery disease, particularly in men aged 40–70 y with severe sleep-disordered breathing.
Please see later in the article for the Editors' Summary
Editors' Summary
Background
About 1 in 10 women and 1 in 4 men have a chronic condition called sleep-disordered breathing although most are unaware of their problem. Sleep-disordered breathing, which is commonest in middle-aged and elderly people, is characterized by numerous, brief (10 second or so) interruptions of breathing during sleep. These interruptions, which usually occur when relaxation of the upper airway muscles decreases airflow, lower the level of oxygen in the blood and, as a result, affected individuals are frequently aroused from deep sleep as they struggle to breathe. Symptoms of sleep-disordered breathing include loud snoring and daytime sleepiness. Treatments include lifestyle changes such as losing weight (excess fat around the neck increases airway collapse) and smoking cessation. Affected people can also use special devices to prevent them sleeping on their backs, but for severe sleep-disordered breathing, doctors often recommend continuous positive airway pressure (CPAP), a machine that pressurizes the upper airway through a face mask to keep it open.
Why Was This Study Done?
Sleep-disordered breathing is a serious condition. It is associated with several adverse health conditions including coronary artery disease (narrowing of the blood vessels that supply the heart, a condition that can cause a heart attack) and daytime sleepiness that can affect an individual's driving ability. In addition, several clinic- and community-based studies suggest that sleep-disordered sleeping may increase a person's risk of dying. However, because these studies have been small and have often failed to allow for other conditions and characteristics that affect an individual's risk of dying (“confounding factors”), they provide inconsistent or incomplete information about the potential association between sleep-disordered breathing and the risk of death. In this prospective cohort study (part of the Sleep Heart Health Study, which is researching the effects of sleep-disordered breathing on cardiovascular health), the researchers examine whether sleep-disordered breathing is associated with all-cause mortality (death from any cause) in a large community sample of adults. A prospective cohort study is one in which a group of participants is enrolled and then followed forward in time (in this case for several years) to see what happens to them.
What Did the Researchers Do and Find?
At enrollment, the study participants—more than 6,000 people aged 40 years or older, none of whom were being treated for sleep-disordered breathing—had a health examination. Their night-time breathing, sleep patterns, and blood oxygen levels were also assessed and these data used to calculate each participant's apnea-hypopnea index (AHI)—the number of apneas and hypopneas per hour. During the study follow-up period, 1,047 participants died. Compared to participants without sleep-disordered sleeping, participants with severe sleep-disordered breathing (an AHI of ≥30) were about one and a half times as likely to die from any cause after adjustment for potential confounding factors. People with milder sleep-disordered breathing did not have a statistically significant increased risk of dying. After dividing the participants into subgroups according to their age and sex, men aged 40–70 years with severe sleep-disordered breathing had a statistically increased risk of dying from any cause (twice the risk of men of a similar age without sleep-disordered breathing). Finally, death from coronary artery disease was also associated with sleep-disordered breathing in men but not in women.
What Do These Findings Mean?
These findings indicate that sleep-disordered breathing is associated with an increased risk of all-cause mortality, particularly in men aged 40–70 years, even after allowing for known confounding factors. They also suggest that the increased risk of death is specifically associated with coronary artery disease although further studies are needed to confirm this finding because it was based on the analysis of a small subgroup of study participants. Although this study is much larger than previous investigations into the association between sleep-disordered breathing and all-cause mortality, it has several limitations including its reliance on a single night's measurements for the diagnosis of sleep-disordered breathing. Nevertheless, these findings suggest that clinical trials should now be started to assess whether treatment can reduce the increased risk of death that seems to be associated with this common disorder.
Additional Information
Please access these Web sites via the online version of this summary at http://dx.doi.org/10.1371/journal.pmed.1000132.
The US National Heart Lung and Blood Institute has information (including a video) about sleep-disordered breathing (sleep apnea) (in English and Spanish)
The UK National Heath Service also provides information for patients about sleep apnea
MedlinePlus provides links to further information and advice about sleep-disordered breathing (in English and Spanish)
More information on the Sleep Heart Health Study is available
doi:10.1371/journal.pmed.1000132
PMCID: PMC2722083  PMID: 19688045
21.  Effect of asthma on the risk of obstructive sleep apnea syndrome in atopic women 
Background
Obstructive sleep apnea syndrome is associated with significant morbidity and remains underdiagnosed in women. Identification of high-risk groups among women is important for early detection and treatment.
Objective
To describe the prevalence of snoring in young women with atopy and to determine the risk factors for snoring in these individuals.
Methods
The Cincinnati Childhood Allergy and Air Pollution Study is an ongoing prospective birth cohort study of infants with at least 1 atopic parent. Mothers of study participants were evaluated by questionnaire for snoring, respiratory symptoms, and smoking status. Women who snored were compared with those who did not snore. Logistic regression analysis was performed to determine risk factors for snoring.
Results
Data were available on 677 women who had at least 1 live birth. Of these 677 women, 546 (81%) were white, 122 (18%) were African American, and 9 (1%) were biracial or Asian. The mean ± SD age of the cohort at the time of evaluation for snoring was 29.6 ± 5.6 years. Of the 677 women, 231 (34%) reported snoring at least 1 night per week, and snoring almost always (5–7 nights per week) was reported by 85 (13%). An almost 2-fold risk of snoring was associated with asthma (diagnosis and current symptoms) (odds ratio, 1.8; 95% confidence interval, 1.1–2.8) and African American race (odds ratio, 1.6; 95% confidence interval, 1.04–2.6) after controlling for income level and smoking status.
Conclusions
We found a high prevalence of snoring in young women with atopy and a significant association with asthma.
PMCID: PMC2233949  PMID: 16937757
22.  Use of sevoflurane inhalation sedation for outpatient third molar surgery. 
Anesthesia Progress  1999;46(1):21-29.
This study attempted to determine if sevoflurane in oxygen inhaled via a nasal hood as a sole sedative agent would provide an appropriate level of deep sedation for outpatient third molar surgery. Twenty-four patients scheduled for third molar removal were randomly assigned to receive either nasal hood inhalation sevoflurane or an intravenous deep sedation using midazolam and fentanyl followed by a propofol infusion. In addition to measuring patient, surgeon, and dentist anesthesiologist subjective satisfaction with the technique, physiological parameters, amnesia, and psychomotor recovery were also assessed. No statistically significant difference was found between the sevoflurane and midazolam-fentanyl-propofol sedative groups in physiological parameters, degree of amnesia, reported quality of sedation, or patient willingness to again undergo a similar deep sedation. A trend toward earlier recovery in the sevoflurane group was identified. Sevoflurane can be successfully employed as a deep sedative rather than a general anesthetic for extraction of third molars in healthy subjects.
PMCID: PMC2148884  PMID: 10551056
23.  A randomized trial evaluating low doses of propofol infusion after intravenous ketamine for ambulatory pediatric magnetic resonance imaging 
Saudi Journal of Anaesthesia  2014;8(4):510-516.
Objective:
Our study compared the discharge time after pediatric magnetic resonance imaging (MRI) following sedation with propofol infusion dose of 100, 75 and 50 mcg/kg/min given after a bolus dose of ketamine and propofol.
Materials and Methods:
One hundred children of American Society of Anesthesiologists status 1/2, aged 6 months to 8 years, scheduled for elective MRI were enrolled and randomized to three groups to receive propofol infusion of 100, 75 or 50 mcg/kg/min (Groups A, B, and C, respectively). After premedicating children with midazolam 0.05 mg/kg intravenous (i.v.), sedation was induced with bolus dose of ketamine and propofol (1 mg/kg each) and the propofol infusion was connected. During the scan, heart rate, noninvasive blood pressure, respiratory rate, and oxygen saturation were monitored.
Results:
The primary outcome that is, discharge time was shortest for Group C (44.06 ± 18.64 min) and longest for Group A (60.00 ± 18.66 min), the difference being statistically and clinically significant. The secondary outcomes that is, additional propofol boluses, scan quality and awakening time were comparable for the three groups. The systolic blood pressure at 20, 25 and 30 min was significantly lower in Groups A and B compared with Group C. The incidence of sedation related adverse events was highest in Group A and least in Group C.
Conclusion:
After a bolus dose of ketamine and propofol (1 mg/kg each), propofol infusion of 50 mcg/kg/min provided sedation with shortest discharge time for MRI in children premedicated with midazolam 0.05 mg/kg i.v. It also enabled stable hemodynamics with less adverse events.
doi:10.4103/1658-354X.140871
PMCID: PMC4236939  PMID: 25422610
Ambulatory; ketamine; magnetic resonance imaging; pediatric; propofol; sedation
24.  Identification of obstructive sites and patterns in obstructive sleep apnoea syndrome by sleep endoscopy in 614 patients 
SUMMARY
The aim of this study was to analyze and report sites and patterns of obstruction observed during sleep endoscopy in a large group of patients and suggest consequent therapeutic prescriptions. 614 consecutive patients who approached the Centre for Diagnosis and Treatment of Respiratory Sleep Disorders underwent sleep endoscopy. We used propofol to induce sleep, monitoring the value of bispectral index to evaluate the depth of sedation. For each patient, we recorded obstruction sites,obstruction patterns and the effects of the mandibular pull-up manoeuvre on both obstruction and snoring. We ascertained that, in almost all patients, the noise of snoring was generated at the oropharyngeal level. The obstruction at the oropharyngeal level, either in isolation or in combination with other structures, is far more common. The mandibular pull-up manoeuvre was effective in reducing or resolving the obstruction in a large number of patients, even though their AHI values were high. For those patients having an AHI over 15, we point out the various therapeutic indications gained from the sleep endoscopy examinations. Drug-induced (propofol) sleep endoscopy can be considered be a safe procedure, easily practicable, valid and reliable; we therefore consider it a fundamental clinical investigation that can be essential when choosing treatment.
PMCID: PMC3773958  PMID: 24043914
Sleep endoscopy; Obstructive sleep apnoea syndrome; Mandibular pull-up manoeuvre; Oral device
25.  Analgesic effects of ketamine infusion therapy in korean patients with neuropathic pain: A 2-week, open-label, uncontrolled study 
Background: The overexcitation of the N-methyl-D-aspartate receptor complex appears to play a critical role in the development of neuropathic pain, and ketamine acts as an antagonist to that receptor. Some publications have reported on the prominent relief of neuropathic pain with intravenous or subcutaneous ketamine infusions or a single-dose intravenous ketamine injection despite adverse effects.
Objectives: The primary objective of this study was to determine the analgesic effect of intravenous ketamine infusion therapy for neuropathic pain refractory to conventional treatments. Secondary objectives included identifying the variables related to the analgesic effect and the pain descriptors susceptible to ketamine infusion.
Methods: This 2-week, open-label, uncontrolled study was conducted in Korean patients with neuropathic pain recruited from the Samsung Seoul Hospital (Seoul, Republic of Korea) outpatient pain management unit. Patients were required to have a pain severity score >5 (visual analog scale [VAS], where 0 = no pain and 10 = worst pain imaginable) over a period of ≥1 month while on standard treatment. The patients were required to have shown no benefit from standard treatment and no pain relief lasting over 1 month. The ketamine infusion therapy was composed of 3 sessions performed consecutively every other day. Midazolam was administered concomitantly to reduce the occurrence of central nervous system-related adverse events (AEs) secondary to ketamine. Each session was as follows: ketamine 0.2 mg/kg and midazolam 0.1 mg/kg were administered intravenously for 5 minutes as a loading dose, followed by a continuous infusion of ketamine 0.5 mg/kg/h and midazolam 0.025 mg/kg/h for 2 hours. AEs were assessed in the following ways: close monitoring of ECG, blood pressure, oxygen saturation, and evaluating the need for treatment of AEs during infu- sion and until discharge by an attending anesthesiologist; an open question about discomfort at the end of each session; spontaneous reports about AEs during each session; and the patients' and caregivers' checklist of AEs occurring at home for 2 weeks after discharge. All the descriptors of pain expressed by the patients in Korean were recorded and translated into appropriate English terminology on the basis of the literature on Korean verbal descriptors of pain. Each of the translated pain descriptors was then classified into 1 of 18 sensory items.
Results: The overall VAS score for pain decreased from a baseline mean (SD) of 7.20 (1.77) to 5.46 (2.29) (P < 0.001) 2 weeks after treatment in 103 patients (53 males and 50 females; mean age, 52.56 [17.33] years) who completed the study. Variables such as age, sex, and the duration and diagnosis of pain were not found to be associated with analgesic effect. Seven of the 18 pain descriptors were found to have a significant response to ketamine infusion treatment between baseline and 2 weeks follow-up: burning pain (P = 0.008); dull, aching pain (P < 0.001); overly sensitive to touch (P = 0.002); stabbing pain (P = 0.008); electric pain (P = 0.031); tingling pain (P < 0.001); and squeezing pain (P < 0.001). A total of 52 patients reported AEs: 33 during infusion and 44 during recovery and up to 2 weeks follow up. The most commonly reported AEs were snoring (15 [15%]) during infusion and dizziness (43 [42%]) during recovery.
Conclusions: Ketamine infusion therapy was associated with reduced severity of neuropathic pain and generally well tolerated for up to 2 weeks in these patients with neuropathic pain refractory to standard treatment. Variables such as sex, age, and the diagnosis and duration of pain had no association with the analgesic effect of this treatment. Randomized controlled trials are needed to evaluate the efficacy and tolerability of treatment with ketamine infusion.
doi:10.1016/j.curtheres.2010.04.001
PMCID: PMC3967276  PMID: 24683255
ketamine; infusion therapy; neuropathic pain; pain descriptor

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