Effect of Trazodone on Upper Airway Resistance in Chronic Spinal Cord Injury

Background: Spinal cord injury (SCI) is a known risk factor for sleep-disordered breathing. While device-based therapies such as CPAP are beneficial in these individuals, adherence to these treatments is often low; consequently, pharmacotherapies for sleep-disordered breathing in patients with SCI are in high demand. Trazodone is an atypical antidepressant with a complex mechanism of action, including alpha adrenergic agonist activity and inhibition of serotonin reuptake. Serotonin (5-HT) is a known modulator of respiratory circuitry, which has been shown to influence the ventilatory drive. Trazodone is commonly prescribed as a sleep aid, but its impact on breathing during sleep is still unclear. Methods: We randomized 9 participants with chronic spinal cord injury and sleep-disordered breathing to receive either placebo or trazodone 100 mg for seven days. On day 7, participants underwent polysomnography with a supraglottic pressure catheter to determine upper airway pressure. Participants then underwent a 1-week washout period before crossing over to the other medication and repeating the same protocol. Parameters of interest included apnea-hypopnea index (AHI), obstructive apnea index (OAI), central apnea index (CAI), oxyhemoglobin desaturation index (ODI), and upper airway resistance (RUA). Results: 7 participants completed polysomnography on both medications, 5 of which had adequate data to calculate RUA. Trazodone did not result in significant improvement in AHI (47.86±24.27 on placebo vs 28.73±28.79 on trazodone, p=0.10), OAI (9.29±9.48 vs 2.86±3.39, p=0.13), CAI (1.14±1.46 vs 1.71±3.30, p=0.52), ODI (25.00±28.39 vs 19.44±33.61, p=0.34), or RUA (2.47±0.92 vs 8.98±11.02, p=0.23). Conclusion: Based on our preliminary data in a small number of subjects, trazodone is not effective in treating sleep-disordered breathing in individuals with spinal cord injury. Due to the limited sample size, our data may not accurately represent the clinical utility of trazodone, and further study in a larger number of patients is warranted

Sleep and Function in Patients with Multiple Sclerosis

Introduction: Fatigue is a core symptom of Multiple Sclerosis (MS) and impairs function and quality of life in this patient population. Studies show that sleep-disordered breathing is also common in persons with MS and may exacerbate fatigue symptoms. Within a larger study of patients with spinal cord injuries and disorders, we evaluated the relationships among sleep-disordered breathing (SDB) severity, sleep quality, and functional outcomes in patients with MS. Our objective was to examine the impact of SDB severity on the severity of fatigue and functional impairment in this population. Methods: Twenty-five subjects (average age=57(11), min=35, max=79; 80% male; average AHI=27(20) min=3, max=70; and 67% with AHI \u3e 15) 24 completed in-laboratory polysomnography (PSG) to measure apnea-hypopnea index (AHI) and sleep efficiency (SE) and questionnaires about sleep and function including: Craig Handicap Assessment and Reporting Technique (CHART), Insomnia Severity Index (ISI), Pittsburg Sleep Quality Index (PSQI), Epworth Sleepiness Scale (ESS), Flinders Fatigue Scale (FFS), PHQ-9 depression scale (excluding sleep item), Generalized Anxiety Disorder-7 (GAD-7), Brief Pain Inventory (BPI) and World Health Organization Quality of Life . Relationships between sleep measures (AHI and SE from PSG, ISI and PSQI) and measure of daytime function (ESS, FSS, SCIM III-SR, PHQ-9, GAD-7, and WHOQOL) were assessed by bivariate correlation. Results: At the baseline study visit, we assessed participant’s daytime sleepiness, fatigue, sleep quality, depression and anxiety. The mean scores on questionnaires are as follows: ESS was 8.0(5.6), ISI was 11.5(6.7), PSQI was 9.3(4.4), FFS was 17.3(8.7), BPI severity was 3.4 (3.12), BPI interference was 3.5 (3.5), PHQ-9 was 7.3(5.8). There were significant relationships between ISI and FSS (r=0.78, p=0.000), PSQI and FFS (r=0.68, p=0.001), as well as ISI and WHOQOL(r=-0.64 p=0.001). In terms of relationships between daytime and nighttime measurements: total AHI had a weak positive correlation with CHART physical independence (r=-0.49, p=0.016), Sleep efficiency has a weak positive correlation with quality of life (r=0.43, p=0.042) and sleep efficiency is weakly inversely correlated with fatigue (r=-0.45, p=0.041). Conclusion: Our data suggests that there is a strong association between the severity of insomnia and the severity of fatigue and depression in MS patients, a moderately strong correlation between reported sleep disturbances as fatigue, and a moderate association between severity of insomnia and reported quality of life. Although twenty-three out of twenty-four subjects in this study have SDB, severity of SDB had a weaker correlation with daytime measures such as fatigue, quality of life, and physical independence. Given that fatigue and depression are common among MS patients and negatively impact quality of life, treatment of insomnia and lessening of sleep disturbances through sleep hygiene and/or SDB treatment may improve patient outcomes

Mortality of emergency abdominal surgery in high-, middle- and low-income countries

Background: Surgical mortality data are collected routinely in high-income countries, yet virtually no low- or middle-income countries have outcome surveillance in place. The aim was prospectively to collect worldwide mortality data following emergency abdominal surgery, comparing findings across countries with a low, middle or high Human Development Index (HDI). Methods: This was a prospective, multicentre, cohort study. Self-selected hospitals performing emergency surgery submitted prespecified data for consecutive patients from at least one 2-week interval during July to December 2014. Postoperative mortality was analysed by hierarchical multivariable logistic regression. Results: Data were obtained for 10 745 patients from 357 centres in 58 countries; 6538 were from high-, 2889 from middle- and 1318 from low-HDI settings. The overall mortality rate was 1⋅6 per cent at 24 h (high 1⋅1 per cent, middle 1⋅9 per cent, low 3⋅4 per cent; P < 0⋅001), increasing to 5⋅4 per cent by 30 days (high 4⋅5 per cent, middle 6⋅0 per cent, low 8⋅6 per cent; P < 0⋅001). Of the 578 patients who died, 404 (69⋅9 per cent) did so between 24 h and 30 days following surgery (high 74⋅2 per cent, middle 68⋅8 per cent, low 60⋅5 per cent). After adjustment, 30-day mortality remained higher in middle-income (odds ratio (OR) 2⋅78, 95 per cent c.i. 1⋅84 to 4⋅20) and low-income (OR 2⋅97, 1⋅84 to 4⋅81) countries. Surgical safety checklist use was less frequent in low- and middle-income countries, but when used was associated with reduced mortality at 30 days. Conclusion: Mortality is three times higher in low- compared with high-HDI countries even when adjusted for prognostic factors. Patient safety factors may have an important role. Registration number: NCT02179112 (http://www.clinicaltrials.gov)