Effects and Side-Effects of Surgery for Snoring and Obstructive Sleep Apnea – A Systematic Review

Study Objectives:

Many patients undergo surgery for snoring and sleep apnea, although the efficacy and safety of such procedures have not been clearly established. Our aim was systematically to review studies of the efficacy and adverse effects of surgery for snoring and obstructive sleep apnea.

Design:

Systematic review.

Measurements:

PubMed and Cochrane databases were searched in September 2007. Randomized controlled trials of surgery vs. sham surgery or conservative treatment in adults, with daytime sleepiness, quality of life, apnea-hypopnea index, and snoring as outcomes were included. Observational studies were also reviewed to assess adverse effects. Evidence of effect required at least two studies of medium and high quality reporting the same result.

Results:

Four studies of benefits and 45 studies of adverse effects were included. There was no significant effect on daytime sleepiness and quality of life after laser-assisted uvulopalatoplasty and radiofrequency ablation. The apnea-hypopnea index and snoring was reduced in one trial after laser-assisted uvulopalatoplasty but not in another trial. Subjective snoring was reduced in one trial after radiofrequency ablation. No trial investigating the effect of any other surgical modality met the inclusion criteria. Persistent side-effects occurred after uvulopalatopharyngoplasty and uvulopalatoplasty in about half the patients and difficulty in swallowing, globus sensation and voice changes were especially common.

Conclusions:

Only a small number of randomized controlled trials with a limited number of patients assessing some surgical modalities for snoring or sleep apnea are available. These studies do not provide any evidence of effect from laser-assisted uvulopalatoplasty or radiofrequency ablation on daytime sleepiness, apnea reduction, quality of life or snoring. We call for research of randomized, controlled trials of surgery other than uvulopalatopharyngoplasty and uvulopalatoplasty, as they are related to a high risk of long-term side-effects, especially difficulty swallowing.

Citation:

Franklin KA; Anttila H; Axelsson S; Gislason T; Maasilta P; Myhre KI; Rehnqvist N. Effects and side-effects of surgery for snoring and obstructive sleep apnea – a systematic review. SLEEP 2009;32(1):27–36.     

Sleep Homeostasis During Repeated Sleep Restriction and Recovery: Support from EEG Dynamics

Study Objectives:

Sleep reduction normally causes a homeostatic response during subsequent recovery sleep, but this does not seem to be true for repeated partial sleep loss. The aim of the present study was to test the response to repeated partial sleep loss through detailed focus on spectral data and parts of sleep.

Design:

The experiment involved 4 h of sleep across 5 days in the laboratory (partial sleep deprivation [PSD]), followed by 3 days of recovery sleep. PSD was achieved through a delayed bedtime. Nine individuals participated. To avoid “laboratory monotony,” subjects were permitted to leave the lab for a few hours each day.

Measurements and results:

All sleep stages and the latencies to sleep and slow wave sleep (SWS) showed a significant reduction during PSD. However, SWS and TST (total sleep time) during the first half of sleep increased gradually across days with PSD. During the first recovery sleep, SWS was significantly increased, while stage 1 and latency to stage 3 were reduced. All were back to baseline on the second night of recovery sleep. Summed spectral power during the first 3.8 h of sleep showed a gradual and robust increase (50% above baseline) in the range 1.25–7.25 Hz across days with PSD up to first recovery sleep and then returned to baseline.

Conclusions:

SWS and summed power density in a broad low-frequency band respond to repeated partial sleep deprivation in a dose-response fashion during the first 4 h sleep, apparently reflecting a robust and stable homeostatic response to sleep loss.

Citation:

Åkerstedt T; Kecklund G; Ingre M; Lekander M; Axelsson J. Sleep homeostasis during repeated sleep restriction and recovery: support from EEG dynamics. SLEEP 2009;32(2):217–222.     

Chronic systemic inflammation in dialysis patients: an update on causes and consequences

Despite marked improvements in dialysis technology during the last 20 years, the age-adjusted mortality rate in end-stage renal disease (ESRD) patients treated by dialysis is still unacceptably high and comparable to that of many cancer patients with metastases. The main cause of the increased mortality in ESRD patients is cardiovascular disease (CVD), which is twice as common and advances at twice the rate already in patients with early stages of chronic kidney disease as compared to the general population. Although traditional risk factors for CVD are common in dialysis patients, they can only in part explain the very high prevalence of CVD in this patient group. Recent evidence demonstrates that chronic inflammation, a non-traditional risk factor which is a commonly observed in dialysis patients, may cause progressive atherosclerotic CVD and malnutrition, itself an important risk factor for the development of CVD, by several pathogenetic mechanisms. The causes of inflammation in dialysis are multifactorial and include both dialysis-related and unrelated factors. While the long-term effects of chronic inflammation may be most important in the pathogenesis of CVD, the acute-phase reaction may also cause vascular damage by several pathogenic mechanisms. Indeed, it seems logical to speculate that suppression of the vicious cycle of malnutrition, inflammation, and atherosclerosis (MIA syndrome) in ESRD would improve survival and decrease co-morbidity in dialysis patients. As there are currently no established guidelines for the treatment of chronic inflammation in ESRD patients, more studies on the long-term effects of various anti-inflammatory treatment strategies on the nutritional and cardiovascular status, as well as outcome in this patient group, are clearly warranted and will be helpful in identifying precisely which pathways are most involved in the pathogenic process.     

Mathematical modeling of the glucose-insulin system during peritoneal dialysis with glucose-based fluids

The purpose of this study was to analyze the effect of peritoneal dialysis with glucose-based solution on plasma glucose and insulin responses in patients on continuous ambulatory peritoneal dialysis (CAPD), describe the glucose-insulin system using a mathematical model, and identify abnormalities in this system. Six-hour dwell studies--using glucose 3.86% solution with a volume marker--were performed in 13 stable, fasting, nondiabetic CAPD patients. We used a mathematical model based on the previous works of Stolwijk and Hardy (1974) and Tolic et al (2000) to estimate the parameters of glucose-insulin system, insulin sensitivity index (Sl), and glucose effectiveness at basal (SG) and zero (GEZI) insulin. The individual peaks in plasma glucose and insulin concentrations occurred after 30-60 minutes of the dwell, with the average increase of 52% and 168% over the initial values, respectively. Increased insulin resistance was found in most of these patients. Both clinical and simulation results demonstrated a high interpatient variability in glucose and insulin kinetics and glucose-insulin system parameters in the patients. We demonstrated a successful control of increasing plasma glucose by insulin, despite an increased insulin resistance, during CAPD.     

Pregnancy outcome in women with polycystic ovary syndrome in relation to second-trimester testosterone levels

Research questionDo women with polycystic ovary syndrome (PCOS) have higher testosterone levels during pregnancy and what role does high testosterone play in the development of obstetric complications?DesignRetrospective cohort study from Uppsala University Hospital, Sweden. The study population consisted of women with PCOS (n = 159) and a comparison group of women without PCOS matched for body mass index (n = 320). Plasma testosterone levels were measured in the early second trimester by liquid chromatography with tandem mass spectrometry, and women with PCOS were grouped into tertiles according to their testosterone levels. Possible associations with obstetric complications, maternal metabolic factors and offspring birth weight were explored by multivariable logistic and linear regression models.ResultsCompared with women who do not have PCOS, women with PCOS had higher total testosterone (median 1.94, interquartile range [IQR] 1.21–2.64 versus 1.41, IQR 0.89–1.97; P < 0.001), and free androgen index (median 0.25, IQR 0.15–0.36 versus 0.18, IQR 0.11–0.28; P < 0.001). Women with PCOS who had the highest levels of testosterone had increased risk for preeclampsia, even when adjusted for age, parity, country of birth and smoking (adjusted OR 6.16, 95% CI 1.82 to 20.91). No association was found between high testosterone in women with PCOS and other obstetric complications.ConclusionsWomen with PCOS have higher levels of total testosterone and free androgen index during pregnancy than women without PCOS matched for body mass index. Preliminary evidence shows that women with PCOS and the highest maternal testosterone levels in early second trimester had the highest risk of developing preeclampsia. This finding, however, is driven by a limited number of cases and should be interpreted with caution.     

How does iron-sulfur cluster coordination regulate the activity of human glutaredoxin 2?

Human mitochondrial glutaredoxin (Grx2) was described as the first iron-sulfur protein from the thioredoxin superfamily of proteins. The [2Fe-2S] cluster was proposed to serve as redox sensor for the activation of Grx2 during oxidative stress. The authors have demonstrated that the iron-sulfur cluster is complexed by the two N-terminal active site thiols of two Grx2 monomers and two molecules of glutathione that are bound noncovalently to the proteins and in equilibrium with glutathione in solution. When reduced glutathione becomes the limiting factor for cluster coordination, the holo-Grx2 complex dissociates, yielding enzymatically active Grx2.     

Regulatory T cell phenotype and function 4 years after GAD–alum treatment in children with type 1 diabetes

Glutamic acid decarboxylase (GAD)₆₅ formulated with aluminium hydroxide (GAD‐alum) was effective in preserving insulin secretion in a Phase II clinical trial in children and adolescents with recent‐onset type 1 diabetes. In addition, GAD‐alum treated patients increased CD4⁺CD25^hi forkhead box protein 3⁺ (FoxP3⁺) cell numbers in response to in‐vitro GAD₆₅ stimulation. We have carried out a 4‐year follow‐up study of 59 of the original 70 patients to investigate long‐term effects on the frequency and function of regulatory T cells after GAD‐alum treatment. Peripheral blood mononuclear cells were stimulated in vitro with GAD₆₅ for 7 days and expression of regulatory T cell markers was measured by flow cytometry. Regulatory T cells (CD4⁺CD25^hiCD127^lo) and effector T cells (CD4⁺CD25^–CD127⁺) were further sorted, expanded and used in suppression assays to assess regulatory T cell function after GAD‐alum treatment. GAD‐alum‐treated patients displayed higher frequencies of in‐vitro GAD₆₅‐induced CD4⁺CD25⁺CD127⁺ as well as CD4⁺CD25^hiCD127^lo and CD4⁺FoxP3⁺ cells compared to placebo. Moreover, GAD₆₅ stimulation induced a population of CD4^hi cells consisting mainly of CD25⁺CD127⁺, which was specific of GAD‐alum‐treated patients (16 of 25 versus one of 25 in placebo). Assessment of suppressive function in expanded regulatory T cells revealed no difference between GAD‐alum‐ and placebo‐treated individuals. Regulatory T cell frequency did not correlate with C‐peptide secretion throughout the study. In conclusion, GAD‐alum treatment induced both GAD₆₅‐reactive CD25⁺CD127⁺ and CD25^hiCD127^lo cells, but no difference in regulatory T cell function 4 years after GAD‐alum treatment.     

MR coronary angiography in pigs with intraarterial injections of a hyperpolarized 13C substance.

A new diagnostic application of a water-soluble contrast medium (CM) based on the hyperpolarization of a 13C substance is introduced. The degree of polarization achieved is >30%, which is about a factor of 10(5) higher than the thermal equilibrium polarization level at 1.5 T. Imaging of hyperpolarized (HP) CM during a cardiac interventional MRI procedure was studied. Catheters were positioned in the left and right coronary arteries of pigs. A coil tuned to 13C was used for nonproton imaging. The HP-13C CM ( approximately 5 ml, 0.5 M, approximately 30% polarization) was injected during projection imaging using a fully balanced steady-state free precession (SSFP) pulse sequence with and without cardiac gating. The contrast agent-filled catheter was clearly visible during the procedure. The coronary arteries were well depicted and the signal-to-noise ratios (SNRs) were in the range of 10-40. The use of HP-13C CM may provide a new diagnostic procedure for interventional MRI.     

Patient-controlled regional analgesia (PCRA) with ropivacaine after arthroscopic subacromial decompression

BACKGROUND: The aim of the study was to evaluate postoperative analgesia and safety of wound instillation of ropivacaine either by a single dose or a patient-controlled regional anaesthesia (PCRA) technique. METHODS: In 40 patients undergoing arthroscopic subacromial decompression the surgeon placed a catheter into the subacromial space at the end of the operation. In Phase I (10 patients), ropivacaine 250 mg was injected twice within 1 h. In Phase II, 30 patients were randomised into three groups: group prilocaine-ropivacaine (PR) = 20 ml of 1% prilocaine-epinephrine injected preoperatively into the subacromial bursa + 20 ml of 0.5% ropivacaine infused in the catheter postoperatively; group saline-ropivacaine (SR) = saline-epinephrine (20 ml) preoperatively + 0.5% ropivacaine as in group PR; group saline-saline (SS) = saline-epinephrine (20 ml) preoperatively + saline postoperatively. The PCRA pump was filled with local anaesthetic or saline to allow boluses of 10-ml each, maximum one bolus/h, via the catheter. Pain relief, side-effects and venous plasma concentration of ropivacaine were evaluated during a 24-h-test period. RESULTS: The free plasma concentration of ropivacaine was 0.12 + 0.041 mg l-1 in Phase I. No adverse effects were seen. In Phase II pain at rest and on movement was lower in group PR than in group SS during the first 30 min postoperatively (P < 0.05). Group PR had the lowest morphine consumption (P < 0.05). Five to seven boluses were administered via the PCRA-pump, and 20 min after administration of the study solution, pain was lower in groups PR and SR compared with group SS (P < 0.001). CONCLUSIONS: Preoperative intrabursal prilocaine with epinephrine + postoperative subacromial administration of ropivacaine by PCRA-technique provided the most effective analgesia with no major side-effects. The free plasma concentrations of ropivacaine were far below toxic concentrations.