Neil T. Feldman

Obstructive sleep apnea in family members.

Two sons and their father had severe hypersomnolence and obstructive sleep apnea. A third son, although asymptomatic, was shown to have upper-airway obstruction during sleep. Electromyographic recordings of genioglossus activity in the two symptomatic sons revealed loss of tonic activity in early stages of sleep at times when sleep apnea occurred. The asymptomatic son showed loss of tonic activity during rapid-eye-movement sleep, the sleep period when upper-airway obstruction occurred. Two sudden deaths occurred in this family. A 30-year-old brother died at home while asleep, and a child of the asymptomatic brother died at the age of four months from presumed sudden-infant-death syndrome. Obstructive sleep apnea may have a familial basis; the tongue may be involved in the genesis of upper-airway obstruction during sleep.

Arterial Oxygenation during Hemodialysis

A FALL in partial pressure of arterial oxygen, or oxygen tension (Pao2), occurring during hemodialysis is a well described phenomenon.1 , 2 The published data, however, are disparate over its cause...

Bilateral diaphragmatic paralysis with hypercapnic respiratory failure: A physiologic assessment

Bilateral diaphragmatic paralysis was suspected in a patient presenting with hypercapnic respiratory failure who exhibited paradoxic (i.e., inward) abdominal movement on inspiration during tidal breathing in the supine posture; no paradoxic abdominal motion was observed at the bedside with the patient upright. Transdiaphragmatic pressure measurements established the diagnosis of diaphragmatic paralysis, although 20 cm H2O pressure developed across the diaphragm during the latter part of a forced expiration, presumably due to the development of passive tension in the diaphragm as it was stretched near residual volume. Analysis of the relative motion of the rib cage and abdomen during breathing by the use of magnetometers confirmed the presence of abdominal paradox throughout the breathing cycle when the patient was supine, and established that paradoxic motion of the abdomen also occurred when the patient was in the erect posture but only in the latter half of inspiration. Our findings confirm that the use of transdiaphragmatic pressure measurements and magnetometry will help to quantify diaphragmatic function, that passive tension develops in the paralyzed diaphragm near residual volume and should not be confused with active contraction, and that paradoxic motion of the abdomen may be masked from the clinician when the patient is erect.

Upper Airway Stimulation for Obstructive Sleep Apnea: Durability of the Treatment Effect at 18 Months.

OBJECTIVE To determine the stability of improvement in polysomnographic measures of sleep disordered breathing, patient reported outcomes, the durability of hypoglossal nerve recruitment and safety at 18 months in the Stimulation Treatment for Apnea Reduction (STAR) trial participants. DESIGN Prospective multicenter single group trial with participants serving as their own controls. SETTING Twenty-two community and academic sleep medicine and otolaryngology practices. MEASUREMENTS Primary outcome measures were the apnea-hypopnea index (AHI) and the 4% oxygen desaturation index (ODI). Secondary outcome measures were the Epworth Sleepiness Scale (ESS), the Functional Outcomes of Sleep Questionnaire (FOSQ), and oxygen saturation percent time < 90% during sleep. Stimulation level for each participant was collected at three predefined thresholds during awake testing. Procedure- and/or device-related adverse events were reviewed and coded by the Clinical Events Committee. RESULTS The median AHI was reduced by 67.4% from the baseline of 29.3 to 9.7/h at 18 mo. The median ODI was reduced by 67.5% from 25.4 to 8.6/h at 18 mo. The FOSQ and ESS improved significantly at 18 mo compared to baseline values. The functional threshold was unchanged from baseline at 18 mo. Two participants experienced a serious device-related adverse event requiring neurostimulator repositioning and fixation. No tongue weakness reported at 18 mo. CONCLUSION Upper airway stimulation via the hypoglossal nerve maintained a durable effect of improving airway stability during sleep and improved patient reported outcomes (Epworth Sleepiness Scale and Functional Outcomes of Sleep Questionnaire) without an increase of the stimulation thresholds or tongue injury at 18 mo of follow-up.

Effect of oral JZP-110 (ADX-N05) treatment on wakefulness and sleepiness in adults with narcolepsy

BACKGROUND JZP-110 is a wake-promoting agent with dopaminergic and noradrenergic activity. METHODS This double-blind, crossover study, randomized adults with narcolepsy with or without cataplexy (N = 33) to placebo or JZP-110 at 150 mg/day (weeks 1 and 3) increased to 300 mg/day (weeks 2 and 4). Patients had to have baseline Epworth Sleepiness Scale (ESS) scores ≥10 and mean sleep latencies ≤10 min on the Maintenance of Wakefulness Test (MWT). Efficacy end points included MWT sleep latency and ESS, and the percentage of patients improved on the Clinical Global Impression of Change. RESULTS Patients were primarily male (57.6%) and white (69.7%), with a mean (standard deviation) age of 37.1 (12.4) years. At two weeks, the change in the mean MWT sleep latency was 11.8 min longer with JZP-110 than with placebo (P = 0.0002); JZP-110 resulted in greater changes in sleep latency on each MWT trial (P <0.001). For ESS, JZP-110 was more efficacious relative to placebo after 1 (P <0.0001) and two weeks (P = 0.0002); final ESS scores were 10.8 with JZP-110 and 15.2 with placebo, changes of -6.7 and -2.4, respectively. JZP-110 was generally well tolerated; the most common adverse events with JZP-110 were nausea (12%), noncardiac chest discomfort (9.1%), and headache (9.1%). CONCLUSIONS The efficacy of JZP-110 for impaired wakefulness and excessive sleepiness was observed at 150-300 mg/day and as early as one week after initiating treatment (Clinicaltrials.gov identifier NCT01485770).

Xyrem safety: the debate continues.

An article appearing in this issue of Sleep Medicine describes three deaths associated with the use of Xyrem (sodium oxybate; Jazz Pharmaceuticals, Inc.). It appears the intent of these authors is to highlight safety concerns associated with the use of sodium oxybate; however, the information they present adds little to our present understanding about this valuable medication. Sodium oxybate is the synthetic form of gammahydroxybutyrate (GHB), an endogenous substance which appears to function as a neuromodulator or neurotransmitter in the mammalian central nervous system [1]. As an endogenous substance, blood levels of GHB as high as 1.5 mg/L can be measured in normal healthy individuals [2]. Interestingly, blood levels of GHB increase substantially post-mortem. Several studies have measured post-mortem GHB levels in blood samples taken from persons for whom the cause of death excluded any possible exposure to GHB [3–5]. One report demonstrated post-mortem blood GHB levels as high as 168 mg/L [3] and another found GHB levels as high as 409 mg/L [4]. A review of the forensic literature reveals that accurately establishing gamma-hydroxybutyrate-related deaths using laboratory means is a complex matter, requiring samples from cardiac and femoral blood, urine, vitreous humor and stomach contents and documenting the amount of time that elapsed between the time of death and when fluid samples were obtained. Dr. Zvosec and co-workers describe three cases of fatal overdose which they suggest are sodium oxybaterelated. In two cases, the drug was prescribed for narcolepsy with cataplexy and intractable insomnia. Both patients were obese and one was diagnosed with mild obstructive sleep apnea. In addition to making the cases more interesting and relevant to the readers of this journal, polysomnographic data which established the presence or severity of sleep disordered breathing in these patients and other information about their past medical history would have added support to the claims of the authors. It is not known whether these individuals were

Carbon monoxide poisoning in fire victims: A reappraisal of prognosis

In victims of carbon monoxide (CO) poisoning, metabolic acidosis has been considered a clinical finding of ominous prognostic importance. In previous studies, such patients either died or suffered serious neurologic sequelae, resulting in the recommendation by some authors that these patients require more complicated therapy, including hyperbaric oxygen and hypothermia. This report documents the full neurologic recovery of three patients with severe metabolic acidosis and CO poisoning. Our experience indicates that acidosis may not be as important a prognostic factor as previously thought, and that randomized prospective trials are needed in such patients before more complicated therapy becomes accepted medical practice.

Asthma: pathophysiology and clinical correlates.

Sufficient data has now accumulated that demonstrates that a careful analysis of the presenting signs and symptoms of a patient with acute asthma will permit clinically useful conclusions to be drawn regarding the magnitude and severity of the underlying airway obstruction and the expected response to therapy. If a patient with severe obstruction deviates from this expected course, objective measurements of mechanical function and gas exchange should be obtained. In our current state of knowledge, these measurements should then be used as the prime indices of therapeutic effectiveness and less reliance should be placed on traditional clinical approaches.

An Assessment of Transbronchial Lung Biopsy

For the patient with diffuse lung disease, lung biopsy has been a formidable procedure, and the clinician caring for such a patient has had to weigh most carefully the advantages of a tissue diagno...