Meghna P. Mansukhani

Zolpidem is independently associated with increased risk of inpatient falls.

BACKGROUND Inpatient falls are associated with significant morbidity and increased healthcare costs. Zolpidem has been reported to decrease balance and is associated with falls. Yet, it is a commonly used hypnotic agent in the inpatient setting. Zolpidem use in hospitalized patients may be a significant and potentially modifiable risk factor for falling. OBJECTIVE To determine whether inpatients administered zolpidem are at greater risk of falling. DESIGN Retrospective cohort study. SETTING Adult non-intensive care unit (non-ICU) inpatients at a tertiary care center. METHODS Adult inpatients who were prescribed zolpidem were identified. Electronic medical records were reviewed to capture demographics and other risk factors for falls. The fall rate was compared in those administered zolpidem versus those only prescribed zolpidem. Multivariate analyses were performed to determine whether zolpidem was independently associated with falls. RESULTS The fall rate among patients who were prescribed and received zolpidem (n = 4962) was significantly greater than among patients who were prescribed but did not receive zolpidem (n = 11,358) (3.04% vs 0.71%; P < 0.001). Zolpidem use continued to remain significantly associated with increased fall risk after accounting for age, gender, insomnia, delirium status, dose of zolpidem, Charlson comorbidity index, Hendrichs fall risk score, length of hospital stay, presence of visual impairment, gait abnormalities, and dementia/cognitive impairment (adjusted odds ratio [OR] 4.37, 95% confidence interval [CI] = 3.34-5.76; P < 0.001). Additionally, patients taking zolpidem who experienced a fall did not differ from other hospitalized adult patients who fell in terms of age, opioids, antidepressants, sedative-antidepressants, antipsychotics, benzodiazepine, or antihistamine use. CONCLUSION Zolpidem use was a strong, independent, and potentially modifiable risk factor for inpatient falls.

Sleep Deprivation in Resident Physicians, Work Hour Limitations, and Related Outcomes: A Systematic Review of the Literature

Abstract Extended work hours, interrupted sleep, and shift work are integral parts of medical training among all specialties. The need for 24-hour patient care coverage and economic factors have resulted in prolonged work hours for resident physicians. This has traditionally been thought to enhance medical educational experience. These long and erratic work hours lead to acute and chronic sleep deprivation and poor sleep quality, resulting in numerous adverse consequences. Impairments may occur in several domains, including attention, cognition, motor skills, and mood. Resident performance, professionalism, safety, and well–being are affected by sleep deprivation, causing potentially adverse implications for patient care. Studies have shown adverse health consequences, motor vehicle accidents, increased alcohol and medication use, and serious medical errors to occur in association with both sleep deprivation and shift work. Resident work hour limitations have been mandated by the Accreditation Council for Graduate Medical Education in response to patient safety concerns. Studies evaluating the impact of these regulations on resident physicians have generated conflicting reports on patient outcomes, demonstrating only a modest increase in sleep duration for resident physicians, along with negative perceptions regarding their education. This literature review summarizes research on the effects of sleep deprivation and shift work, and examines current literature on the impact of recent work hour limitations on resident physicians and patient–related outcomes.

Chemoreflexes, Sleep Apnea, and Sympathetic Dysregulation

Obstructive sleep apnea (OSA) and hypertension are closely linked conditions. Disordered breathing events in OSA are characterized by increasing efforts against an occluded airway while asleep, resulting in a marked sympathetic response. This is predominantly due to hypoxemia activating the chemoreflexes, resulting in reflex increases in sympathetic neural outflow. In addition, apnea – and the consequent lack of inhibition of the sympathetic system that occurs with lung inflation during normal breathing – potentiates central sympathetic outflow. Sympathetic activation persists into the daytime, and is thought to contribute to hypertension and other adverse cardiovascular outcomes. This review discusses chemoreflex physiology and sympathetic modulation during normal sleep, as well as the sympathetic dysregulation seen in OSA, its extension into wakefulness, and changes after treatment. Evidence supporting the role of the peripheral chemoreflex in the sympathetic dysregulation seen in OSA, including in the context of comorbid obesity, metabolic syndrome, and systemic hypertension, is reviewed. Finally, alterations in cardiovascular variability and other potential mechanisms that may play a role in the autonomic imbalance in OSA are also discussed.

Valproate-induced hyperammonemic encephalopathy: an update on risk factors, clinical correlates and management

INTRODUCTION Valproate (VPA)-induced hyperammonemic encephalopathy (VHE) is a serious drug-related adverse effect characterized by lethargy, vomiting, cognitive slowing, focal neurological deficits and decreased levels of consciousness ranging from drowsiness to coma. METHODS We present a case series (n=5) and also review previous cases of VHE (n=30) in psychiatric patients to provide an update on risk factors, clinical correlates and management of VHE. RESULTS To our knowledge, there are 30 (16 female, 14 male) previously reported VHE cases in psychiatric patients. Risk factors for VHE include VPA-drug interactions, mental retardation, carnitine deficiency and presence of urea cycle disorders. Length of VPA treatment, VPA dosage, serum VPA levels and serum ammonia levels do not appear to correlate with onset or severity of VHE.VPA discontinuation is the primary treatment of VHE, although, l-carnitine, lactulose and neomycin have been used adjunctively in some patients. CONCLUSION Clinicians should consider VHE in patients taking VPA who present with lethargy, gastrointestinal symptoms, confusion and decreased levels of drowsiness. VPA discontinuation is currently the mainstay of treatment for VHE, although more research is warranted to delineate the underlying risk factors for VHE and consolidate treatment modalities for this potentially life-threatening drug adverse effect.

Worse Outcome after Stroke in Patients with Obstructive Sleep Apnea: An Observational Cohort Study

To evaluate the risk and presence of obstructive sleep apnea (OSA) in patients presenting with acute ischemic stroke, and examine the correlation of OSA with age, sex, ischemic stroke subtype, disability, and death, a prospective cohort study was conducted in all consecutive patients presenting with acute ischemic stroke between June 2007 and March 2008. Exclusion criteria were age < 18 years, refusal of consent for the study, and incomplete questionnaire. The Berlin Sleep Questionnaire was used to identify patients at high risk for OSA. A total of 174 patients with acute ischemic stroke were included; 130 (74.7%) had a modified Rankin Scale (mRS) score ≥ 3 at dismissal, and 11 patients (6.3%) died within 1 month. The Berlin Sleep Questionnaire identified 105 patients (60.4%) at high risk for OSA, along with 7 patients (4%) with a previous diagnosis of OSA. Those with a previous diagnosis of OSA were more likely to die within the first month after stroke (relative risk, 5.3; 95% confidence interval, 1.4-20.1) compared with those without OSA. Patients at high risk for OSA did not demonstrate increased mortality at 30 days (P = 1.0). In multivariate analysis, after adjusting for age and National Institutes of Health Stroke Scale score, previous diagnosis of OSA was an independent predictor of worse functional outcome, that is, worse mRS score at hospital discharge (P = .004). The mRS score was 1.2 points higher (adjusted R², 40%) in those with OSA. Our findings suggest that patients considered at high risk for ischemic stroke should be screened for OSA, the prevalence of which may be as high as 60%. Those with definitive diagnosis of OSA before stroke are at increased risk of death within the first month after an acute ischemic stroke.

The association between atrial fibrillation and stroke in patients with obstructive sleep apnea: a population-based case-control study.

BACKGROUND Obstructive sleep apnea (OSA) has been shown to be an independent risk factor for ischemic stroke and may increase the risk of atrial fibrillation (AF) by up to fourfold. Given these relationships, it is possible that OSA may provide a link between stroke and AF. A case-control study was conducted to examine the association between AF and stroke in patients with OSA. METHODS Olmsted County, MN, USA, residents with a new diagnosis of OSA based on polysomnography (PSG) between 2005 and 2010 (N = 2980) who suffered a first-time ischemic stroke during the same period were identified as cases. Controls with no history of stroke were randomly chosen from the same database. Univariate and multiple logistic regression analyses were performed with age, gender, body mass index (BMI), smoking, hypertension, hyperlipidemia, diabetes mellitus, apnea-hypopnea index (AHI) and coronary artery disease (CAD) as co-variates, with the diagnosis of AF as the variable of interest. RESULTS A total of 108 subjects were studied. Mean age of cases (n = 34) was 73 ± 12 years and 53% were men. Among controls (n = 74), mean age was 61 ± 16 years and 55% were male. On univariate analyses, AF was significantly more common in the cases than among controls (50.0% vs 10.8%, p < 0.01). On multivariate regression analyses, the association between AF and stroke was significant after controlling for age, BMI, coronary artery disease, hypertension, diabetes mellitus, hyperlipidemia and smoking status (corrected odds ratio (OR): 5.34; 95% confidence interval (CI): 1.79-17.29). CONCLUSIONS Patients with OSA who had a stroke had higher rates of AF even after accounting for potential confounders.

Consumer sleep tracking devices: a review of mechanisms, validity and utility

ABSTRACT Consumer sleep tracking devices such as fitness trackers and smartphone apps have become increasingly popular. These devices claim to measure the sleep duration of their users and in some cases purport to measure sleep quality and awaken users from light sleep, potentially improving overall sleep. Most of these devices appear to utilize data generated from in-built accelerometers to determine sleep parameters but the exact mechanisms and algorithms are proprietary. The growing literature comparing these devices against polysomnography/actigraphy shows that they tend to underestimate sleep disruptions and overestimate total sleep times and sleep efficiency in normal subjects. In this review, we evaluate the current literature comparing the accuracy of consumer sleep tracking devices against more conventional methods used to measure sleep duration and quality. We discuss the current technology that these devices utilize as well as summarize the value of these devices in clinical evaluations and their potential limitations.

Chemoreflex physiology and implications for sleep apnoea: insights from studies in humans

What is the topic of this review? This review summarizes chemoreflex physiology in health and disease, with specific focus on chemoreflex‐mediated pathophysiology in obstructive and central sleep apnoea. What advances does it highlight? Chemoreflex mechanisms are thought to contribute significantly to the pathophysiology and adverse outcomes seen in sleep apnoea. Clinical implications of altered chemoreflex function in sleep apnoea from recent studies in humans, including cardiac arrhythmias, coronary artery disease, systolic/diastolic heart failure and sudden cardiac death are highlighted.

Sodium oxybate in the treatment of childhood narcolepsy-cataplexy: A retrospective study

OBJECTIVE To evaluate the efficacy and side effect profile of sodium oxybate in the treatment for narcolepsy-cataplexy in the pediatric age group. METHODS A retrospective study was conducted on 15 children and adolescents with narcolepsy-cataplexy who had been treated with sodium oxybate. The mean age at diagnosis of narcolepsy was 11 years (range 3-17 years). Subjects were followed for 3-90 months (mean 33) after starting sodium oxybate. During this period of time they were also maintained on other medications for sleepiness (n=14) and cataplexy (n=6). The charts were reviewed for documentation of improvement in sleepiness or cataplexy, side effects, and functioning in daily life. RESULTS Subsequent to the addition of sodium oxybate, sleepiness improved in 13/15 patients. In patients who had Epworth Sleepiness Scale (ESS) assessments, the score fell from a baseline median of 18 to 12 (n=10, p=0.01). The number of cataplexy episodes estimated by parents decreased from a median of 38/week pre-treatment to <1/week post treatment (n=14, p<0.001). Cataplexy severity, measured on an arbitrary scale, fell from a median of 3 (severe) to 1 (mild) in all 15 subjects (p<0.001). Two of the 15 patients (13%) discontinued sodium oxybate, one for insurance reasons and the other due to constipation and dissociative feelings. A third patient stopped the medication temporarily due to body aches and dizziness, but then resumed treatment without recurrence of symptoms. Side effects in four others included tremor, blurring of vision, nocturnal awakenings, and increased nightmares. Overall, side effects occurred in 6/15 (40%) individuals. Improvement in social/academic spheres was noted in 11/15 (73%) subjects after starting sodium oxybate. The median BMI before and after treatment remained unchanged at 23 (n=14, p=0.99). Median values of height and weight before and after treatment also did not change significantly. The mean dose of sodium oxybate was 5 ± 2 g. Dose escalation owing to development of tolerance was not encountered. CONCLUSIONS Sodium oxybate is effective in alleviating sleepiness and cataplexy in childhood onset narcolepsy-cataplexy. The therapeutic response was sustained over time, and without development of tolerance. Forty percent of the subjects experienced adverse effects.

Pharmacological treatment of insomnia in alcohol recovery: a systematic review.

AIMS To conduct a systematic review of pharmacological agents used to treat sleep problems in alcohol recovery. METHODS In accordance with the Quorum statement, we searched PubMed, EMBASE, Psych Info and Medline databases using the terms alcohol, insomnia/sleep and treatment/management with no year/language restrictions. RESULTS The search revealed 1239 articles and 20 met inclusion criteria. Trazodone was compared against placebo and found to be superior in two trials. Trazodone and gabapentin improved sleep measures with gabapentin performing significantly better in an open-label study. The data regarding gabapentin are equivocal with few studies showing a clear benefit. In one randomized trial, topiramate resulted in improved subjective sleep measures and a reduction in the percentage of heavy drinking days. Two randomized control trials of carbamazepine revealed improvement in subjective sleep measures. A randomized study showed lormetazepam was better than zopiclone on some measures. In a small placebo-controlled trial, acamprosate was found to result in improvements on some sleep measures. In single, small, mostly open-label studies, quetiapine, triazolam, ritanserin, bright light and magnesium have shown efficacy, while chlormethiazole, scopolamine and melperone showed no difference or worsening. CONCLUSION Trazodone has the most data suggesting efficacy. This finding is tempered by a study suggesting its association with a return to heavy drinking in some patients. Data regarding the efficacy of gabapentin are unclear at this point.