Lee K. Brown

Reversal of sleep apnea hypopnea syndrome in end-stage renal disease after kidney transplantation.

Sleep apnea hypopnea syndrome (SAHS) is extremely common in patients with end-stage renal disease (ESRD). Although the underlying mechanisms linking these 2 conditions remain to be better defined, it is likely that multiple factors are involved. We report an individual with ESRD with severe SAHS that resolved after kidney transplantation. The improvement in SAHS paralleling the effective treatment of ESRD suggests the pathogenesis involves an unstable breathing pattern, possibly caused by an altered metabolic state, uremia, and changes in volume status. The possibility that elevations in cytokine levels could be involved also is discussed and deserves further attention.

Prevalence of Diagnosed Sleep Apnea Among Patients With Type 2 Diabetes in Primary Care

BACKGROUND Although up to 90% of patients with type 2 diabetes mellitus (T2DM) have obstructive sleep apnea (OSA), the rate at which primary care providers diagnose OSA in patients with diabetes has not been assessed. METHODS A retrospective, population-based, multiclinic study was performed to determine the proportion of patients with T2DM managed in primary care clinics who were given a diagnosis of OSA and to identify factors associated with an OSA diagnosis. Electronic health records of adult patients with a diagnosis of T2DM were reviewed for a coexisting diagnosis of OSA, and the diagnostic prevalence of OSA was compared with the expected prevalence. RESULTS A total of 16,066 patients with diabetes with one or more primary care office visits in 27 primary care ambulatory practices during an 18-month period from 2009 to 2010 were identified. Analysis revealed that 18% of the study population received an OSA diagnosis, which is less than the 54% to 94% prevalence reported previously. The 23% prevalence of OSA among obese study patients was lower than the expected 87% prevalence. In a logistic model, male sex, BMI, several chronic conditions, and lower low-density lipoprotein levels and hemoglobin A1c identified patients more likely to carry an OSA diagnosis (likelihood ratio, χ(2) = 1,713; P < .0001). CONCLUSIONS Primary care providers underdiagnose OSA in patients with T2DM. Obese men with comorbid chronic health conditions are more likely to receive a diagnosis of OSA. Efforts to improve awareness of the association of OSA with T2DM and to implement OSA screening tools should target primary care physicians.

Disopyramide (Norpace®)-induced hypoglycemia

Disopyramide (Norpace) is a recently released antiarrhythmic agent with quinidine-like actions, but structurally unique. We describe a patient in whom impressive hypoglycemia developed following treatment with this agent. Blood glucose levels returned to normal after cessation of therapy, but dropped again following rechallenge with the drug. The pathogenesis of the hypoglycemia was investigated by assessment of serum insulin, plasma glucagon and serum alanine levels during disopyramide rechallenge. Clinicians should be aware of fasting hypoglycemia as an unusual but potentially serious complication of disopyramide therapy.

Positive airway pressure therapy with adaptive servoventilation: part 1: operational algorithms.

The beginning of the 21st century witnessed the advent of new positive airway pressure (PAP) technologies for the treatment of central and complex (mixtures of obstructive and central) sleep apnea syndromes. Adaptive servoventilation (ASV) devices applied noninvasively via mask that act to maintain a stable level of ventilation regardless of mechanism are now widely available. These PAP devices function by continually measuring either minute ventilation or airflow to calculate a target ventilation to be applied as needed. The apparatus changes inspiratory PAP on an ongoing basis to maintain the chosen parameter near the target level, effectively controlling hypopneas of any mechanism. In addition, by applying pressure support levels anticyclic to the patients own respiratory pattern and a backup rate, this technology is able to suppress central sleep apnea, including that of Hunter-Cheyne-Stokes breathing. Moreover, ASV units have become available that incorporate autotitration of expiratory PAP to fully automate the treatment of all varieties of sleep-disordered breathing. Although extremely effective in many patients when used properly, these are complex devices that demand from the clinician a high degree of expertise in understanding how they work and how to determine the proper settings for any given patient. In part one of this series we detail the underlying technology, whereas in part two we will describe the application of ASV in the clinical setting.

SERVE-HF: More Questions Than Answers

The recent online publication of the SERVE-HF trial that evaluated the effect of treating central sleep apnea (CSA) with an adaptive servoventilation (ASV) device in patients with heart failure and reduced ejection fraction (HFrEF) has raised serious concerns about the safety of ASV in these patients. Not only was ASV ineffective but post hoc analysis found excess cardiovascular mortality in treated patients. The authors cited as one explanation an unfounded notion that CSA is a compensatory mechanism with a protective effect in HFrEF patients. We believe that there are several possible considerations that are more likely to explain the results of SERVE-HF. In this commentary, we consider methodological issues including the use of a previous-generation ASV device that constrained therapeutic settings to choices that are no longer in wide clinical use. Patient selection, data collection, and treatment adherence as well as group crossovers were not discussed in the trial as potential confounding factors. We have developed alternative reasons that could potentially explain the results and that can be explored by post hoc analysis of the SERVE-HF data. We believe that our analysis is of critical value to the field and of particular importance to clinicians treating these patients.

Respiratory dysfunction due to L-Dopa therapy for parkinsnism: Diagnosis using serial pulmonary function tests and respiratory inductive plethysmography

Dyskinesias involving the respiratory muscles have been described in a variety of movement disorders, especially the tardive dyskinesia associated with long-term use of neuroleptic agents [l-5]. A few reports of respiratory dysfunction after L-dopa therapy for Parkinson’s disease have suggested that this drug induces a similar respiratory dyskinesia, but detailed analyses of respiratory pattern and pulmonary function have been lacking [6-91. We report herein two patients with L-dopa-induced respiratory dysfunction appearing in association with choreiform movements of muscles not related to respiration. These patients were studied using serial monitoring of breathing pattern with the respiratory inductive plethysmograph and serial monitoring of alterations in pulmonary function as assessed by forced expiratory flow volume maneuvers and peak inspiratory and expiratory mouth pressures. CASE REPORTS

Clinical Applications of Adaptive Servoventilation Devices: Part 2

Adaptive servoventilation (ASV) is an automated treatment modality used to treat many types of sleep-disordered breathing. Although default settings are available, clinician-specified settings determined in the sleep laboratory are preferred. Depending on the device, setting choices may include a fixed expiratory positive airway pressure (EPAP) level or a range for autotitrating EPAP; minimum and maximum inspiratory positive airway pressure or pressure support values; and type of backup rate algorithm or a selectable fixed backup rate. ASV was initially proposed for treatment of central sleep apnea and Hunter-Cheyne-Stokes breathing associated with congestive heart failure (CHF), and numerous observational studies have demonstrated value in this setting. Other studies have reported varying efficacy in patients with complex sleep apnea syndromes, including those with mixtures of obstructive and central sleep-disordered breathing associated with CHF, renal failure, or OSA with central apneas developing on conventional positive airway pressure therapy. Patients with opioid-induced sleep apnea, both obstructive and central, may also respond to ASV. The variability in response to ASV in a given patient along with the myriad choices of specific models and settings demand a high degree of expertise from the clinician. Finally, randomized controlled studies are needed to determine long-term clinical efficacy of these devices.

Obesity hypoventilation syndrome: current theories of pathogenesis.

Purpose of review To summarize recent primary publications and discuss the impact these finding have on current understanding on the development of hypoventilation in obesity hypoventilation syndrome (OHS), also known as Pickwickian syndrome. Recent findings As a result of the significant morbidity and mortality associated with OHS, evidence is building for pre-OHS intermediate states that can be identified earlier and treated sooner, with the goal of modifying disease course. Findings of alterations in respiratory mechanics with obesity remain unchanged; however, elevated metabolism and CO2 production may be instrumental in OHS-related hypercapnia. Ongoing positive airway pressure trials continue to demonstrate that correction of nocturnal obstructive sleep apnea and hypoventilation improves diurnal respiratory physiology, metabolic profiles, quality of life, and morbidity/mortality. Finally, CNS effects of leptin on respiratory mechanics and chemoreceptor sensitivity are becoming better understood; however, characterization remains incomplete. Summary OHS is a complex multiorgan system disease process that appears to be driven by adaptive changes in respiratory physiology and compensatory changes in metabolic processes, both of which are ultimately counter-productive. The diurnal hypercapnia and hypoxia induce pathologic effects that further worsen sleep-related breathing, resulting in a slowly progressive worsening of disease. In addition, leptin resistance in obesity and OHS likely contributes to blunting of ventilatory drive and inadequate chemoreceptor response to hypercarbia and hypoxemia.

Aerosol rebreathing method for assessment of airway abnormalities: theoretical analysis and validation

An aerosol rebreathing method which determines total aerosol deposition in the lung by rebreathing non-radioactive inert aerosol was investigated theoretically for its performance characteristics. The method was then validated experimentally by examining a system response to various operating parameters, its reproducibility and convenience in clinical use. It was found from the theoretical analysis that an optimum performance would be achieved by breathing an aerosol of particles 1 micrometer in diameter with a 500-cm3 tidal volume at the breathing rate of 30 breaths/min. With these optimum parameters, experimental results of 10 normals and 10 patients with obstructive airway disease revealed an excellent measurement reproducibility within subjects (+/- 10% from means). There was a wide separation between the two groups in terms of number of rebreathing breaths to reach 90% aerosol deposition (N90) (mean +/- S.E. = 10.8 +/- 1.6 for normals vs. 3.9 +/- 1.1 for patients) and cumulative percentage of aerosol deposition at the fourth breath (AD4) (mean +/- S.E. = 68 +/- 4.4% for normals vs. 90 +/- 3.5% for patients).

Can sleep deprivation studies explain why human adults sleep

Purpose of review This review will concentrate on the consequences of sleep deprivation in adult humans. These findings form a paradigm that serves to demonstrate many of the critical functions of the sleep states. Recent findings The drive to obtain food, water, and sleep constitutes important vegetative appetites throughout the animal kingdom. Unlike nutrition and hydration, the reasons for sleep have largely remained speculative. When adult humans are nonspecifically sleep-deprived, systemic effects may include defects in cognition, vigilance, emotional stability, risk-taking, and, possibly, moral reasoning. Appetite (for foodstuffs) increases and glucose intolerance may ensue. Procedural, declarative, and emotional memory are affected. Widespread alterations of immune function and inflammatory regulators can be observed, and functional MRI reveals profound changes in regional cerebral activity related to attention and memory. Selective deprivation of rapid eye movement (REM) sleep, on the contrary, appears to be more activating and to have lesser effects on immunity and inflammation. Summary The findings support a critical need for sleep due to the widespread effects on the adult human that result from nonselective sleep deprivation. The effects of selective REM deprivation appear to be different and possibly less profound, and the functions of this sleep state remain enigmatic.