David Wang

Randomised trial of CPAP vs bilevel support in the treatment of obesity hypoventilation syndrome without severe nocturnal desaturation

Background: Untreated, obesity hypoventilation is associated with significant use of health care resources and high mortality. It remains unclear whether continuous positive airway pressure (CPAP) or bilevel ventilatory support (BVS) should be used as initial management. The aim of this study was to determine if one form of positive pressure is superior to the other in improving daytime respiratory failure. Methods: A prospective randomised study was performed in patients with obesity hypoventilation referred with respiratory failure. After exclusion of patients with persisting severe nocturnal hypoxaemia (Spo2 <80% for >10 min) or carbon dioxide retention (>10 mm Hg) despite optimal CPAP, the remaining patients were randomly assigned to receive either CPAP or BVS over a 3-month period. The primary outcome was change in daytime carbon dioxide level. Secondary outcome measures included daytime sleepiness, quality of life, compliance with treatment and psychomotor vigilance testing. Results: Thirty-six patients were randomised to either home CPAP (n = 18) or BVS (n = 18). The two groups did not differ significantly at baseline with regard to physiological or clinical characteristics. Following 3 months of treatment, daytime carbon dioxide levels decreased in both groups (CPAP 6 (8) mm Hg; BVS 7 (7) mm Hg) with no between-group differences. There was no difference in compliance between the two treatment groups (5.8 (2.4) h/night CPAP vs 6.1 (2.1) h/night BVS). Although both groups reported an improvement in daytime sleepiness, subjective sleep quality and psychomotor vigilance performance were better with BVS. Conclusions: Both CPAP and BVS appear to be equally effective in improving daytime hypercapnia in a subgroup of patients with obesity hypoventilation syndrome without severe nocturnal hypoxaemia. Trial registration number: Australian Clinical Trials Registry ACTRN01205000096651.

Surface code quantum computing with error rates over 1

Large-scale quantum computation will only be achieved if experimentally implementable quantum error correction procedures are devised that can tolerate experimentally achievable error rates. We describe a quantum error correction procedure that requires only a 2-D square lattice of qubits that can interact with their nearest neighbors, yet can tolerate quantum gate error rates over 1%. The precise maximum tolerable error rate depends on the error model, and we calculate values in the range 1.1--1.4% for various physically reasonable models. Even the lowest value represents the highest threshold error rate calculated to date in a geometrically constrained setting, and a 50% improvement over the previous record.

Surface code quantum communication

Quantum communication typically involves a linear chain of repeater stations, each capable of reliable local quantum computation and connected to their nearest neighbors by unreliable communication links. The communication rate of existing protocols is low as two-way classical communication is used. By using a surface code across the repeater chain and generating Bell pairs between neighboring stations with probability of heralded success greater than 0.65 and fidelity greater than 0.96, we show that two-way communication can be avoided and quantum information can be sent over arbitrary distances with arbitrarily low error at a rate limited only by the local gate speed. This is achieved by using the unreliable Bell pairs to measure nonlocal stabilizers and feeding heralded failure information into post-transmission error correction. Our scheme also applies when the probability of heralded success is arbitrarily low.

Physiology in Medicine: Obstructive sleep apnea pathogenesis and treatment—considerations beyond airway anatomy

We review evidence in support of significant contributions to the pathogenesis of obstructive sleep apnea (OSA) from pathophysiological factors beyond the well-accepted importance of airway anatomy. Emphasis is placed on contributions from neurochemical control of central respiratory motor output through its effects on output stability, upper airway dilator muscle activation, and arousability. In turn, we consider the evidence demonstrating effective treatment of OSA via approaches that address each of these pathophysiologic risk factors. Finally, a case is made for combining treatments aimed at both anatomical and ventilatory control system deficiencies and for individualizing treatment to address a patients own specific risk factors.

The effects of testosterone on ventilatory responses in men with obstructive sleep apnea: a randomised, placebo-controlled trial

We recently showed that testosterone therapy worsens sleep‐disordered breathing at 6–7 weeks, but not after 18 weeks, in men with obstructive sleep apnea. Changes in ventilatory chemoreflexes may be responsible. The effect of testosterone on ventilatory chemoreflexes in men with obstructive sleep apnea has not been systematically studied before. Twenty‐one obese men with obstructive sleep apnea, a subgroup of our recent report, were randomised in an 18‐week, randomised, double‐blind, placebo‐controlled, parallel group trial to three intramuscular injections (0, 6, 12 weeks) of either 1000 mg testosterone undecanoate (n = 10) or placebo (n = 11). Awake ventilatory chemoreflex testing was performed before (week 0), during (week 6) and at the end of treatment (week 18) to determine the ventilatory carbon dioxide recruitment threshold and chemosensitivity. Sleep and breathing was assessed by overnight polysomnography at 0, 7 and 18 weeks. Serum hormones levels were measured at every visit. A significant increase in blood testosterone levels (5.65 nmol L−1, 0.51–10.8 nmol L−1, P = 0.03) and lean muscle mass (2.36 kg, 0.8–3.9 kg, P = 0.007) between the two groups was observed as expected. No significant differences were seen in ventilatory chemoreflexes between the two groups at 6 weeks or at 18 weeks. However, positive correlations were observed between changes in serum testosterone and hyperoxic ventilatory recruitment threshold (r = 0.55, P = 0.03), and between changes in hyperoxic ventilatory recruitment threshold and time spent with oxygen saturations during sleep <90% (r = 0.57, P = 0.03) at 6–7 weeks, but not at 18 weeks. Time‐dependent alterations in ventilatory recruitment threshold may therefore mediate the time‐dependent changes in sleep breathing observed with testosterone.

Phenotyping interindividual variability in obstructive sleep apnoea response to temazepam using ventilatory chemoreflexes during wakefulness

Centrally active agents have a variable impact in patients with obstructive sleep apnoea (OSA) that is unexplained. How to phenotype the individual OSA response is clinically important, as it may help to identify who will be at risk of respiratory depression and who will benefit from a centrally active agent. Based on loop gain theory, we hypothesized that OSA patients with higher central chemosensitivity have higher breathing instability following the use of a hypnosedative, temazepam. In 20 men with OSA in a double‐blind, placebo‐controlled cross‐over trial we tested the polysomnographically (PSG) measured effects of temazepam 10 mg versus placebo on sleep apnoea. Treatment nights were at least 1 week apart. Ventilatory chemoreflexes were also measured during wakefulness in each subject. The patients (mean ± standard deviation; 44 ± 12 years) had predominantly mild‐to‐moderate OSA [baseline apnoea–hypopnoea index (AHI) = 16.8 ± 14.1]. Patients’ baseline awake central chemosensitivity correlated significantly with both the change of SpO2 nadir between temazepam and placebo (r = −0.468, P = 0.038) and oxygen desaturation index (ODI; r = 0.485, P = 0.03), but not with the change of AHI (r = 0.18, P = 0.44). Peripheral chemosensitivity and ventilatory recruitment threshold were not correlated with the change of SpO2 nadir, ODI or AHI (all P > 0.05). Mild–moderate OSA patients with higher awake central chemosensitivity had greater respiratory impairment during sleep with temazepam. Relatively simple daytime tests of respiratory control may provide a method of determining the effect of sedative–hypnotic medication on breathing during sleep in OSA patients.

Sleep-disordered breathing with chronic opioid use

Chronic opioid use for pain relief or as substitution therapy for illicit drug abuse is prevalent in our societies. In the US, retail distribution of methadone and oxycodone has increased by 824 and 660%, respectively, between 1997 and 2003. μ-Opioids depress respiration and deaths related to illicit and non illicit chronic opioid use are not uncommon. Since 2001 there has been an emerging literature that suggests that chronic opioid use is related to central sleep apnoea of both periodic and non-periodic breathing types, and occurs in ∼ 30% of these subjects. The clinical significance of these sleep-related abnormalities are unknown. This review addresses the present knowledge of control of ventilation mechanisms during wakefulness and sleep, the effects of opioids on ventilatory control mechanisms, the sleep-disordered breathing found with chronic opioid use and a discussion regarding the future research directions in this area.

Scoring polysomnography respiratory events: the utility of nasal pressure and oro-nasal thermal sensor recordings

OBJECTIVE To evaluate the clinical utility of nasal cannula/pressure (NP) and oro-nasal thermal sensor (Th) recordings, alone and in combination for scoring respiratory events during routine diagnostic polysomnography (PSG). BACKGROUND The use of Th devices to measure airflow during PSG is not recommended because Th are insensitive to airflow changes other then complete airflow cessation. It has been suggested that NP recording is a better measure of airflow and can also detect increased upper airway resistance during PSG. METHODS Thirty consecutive PSGs were examined using 13 standard channels including Th and NP recordings. Respiratory events were scored separately utilizing NP+Th, Th alone and NP alone in a blinded fashion using modified AASM criteria. Respiratory events were time matched to within 5 s for each of the recording methods. RESULTS NP+Th detected more events than Th alone (P<0.0001); NP+Th detected more events than NP alone (P<0.0001) and NP alone detected more events than Th alone (P<0.0001). For AHI >50, NP alone and Th alone each detected 90% of matched NP+Th events. However, for AHI <50, NP alone detects 54% and Th alone detects 42% (P<0.005) of matched NP+Th events. For AHI >50, NP alone scored 97% of matched Th alone scored respiratory events, and Th alone scored 94% of NP alone scored respiratory events (P>0.05). However, for AHI<50, NP alone scored 90% of matched Th alone scored respiratory events, whereas Th alone scored 62% of matched NP alone scored events (P<0.0001). CONCLUSIONS In severe sleep disordered breathing (AHI >50), NP+Th, NP alone and Th alone have similar ability to detect respiratory events. When AHI <50, NP+Th appears better for detecting respiratory events than NP or Th alone. If only one measure of airflow is used, NP detects more events than Th.

The effects of a single mild dose of morphine on chemoreflexes and breathing in obstructive sleep apnea

The effect of morphine on breathing and ventilatory chemoreflexes in obstructive sleep apnea (OSA) is unknown. It has been assumed that acute morphine use may induce deeper respiratory depression in OSA but this has not been investigated. We evaluated awake ventilatory chemoreflexes and overnight polysomnography on 10 mild-moderate OSA patients before and after giving 30 mg oral controlled-release morphine. Morphine plasma concentrations were analysed. We found a 30-fold range of morphine plasma concentrations with the fixed dose of morphine, and a higher plasma morphine concentration was associated with a higher CO(2) recruitment threshold (VRT) (r=0.86, p=0.006) and an improvement in sleep time with Sp(O(2)) (T90) (r=-0.87, p=0.005) compared to the baseline. The improvement in T90 also significantly correlated with the increase of VRT (r=-0.79, r=0.02). In conclusion, in mild-to-moderate OSA patients, a single common dose of oral morphine may paradoxically improve OSA through modulating chemoreflexes. There is a large inter-individual variability in the responses, which may relate to individual morphine metabolism.

Cardiorespiratory function in stable methadone maintenance treatment (MMT) patients.

Patients in methadone maintenance programmes (MMT) often smoke tobacco and cannabis and many have ongoing illicit drug use. There is therefore potential for these patients to have abnormal cardiorespiratory function; however, few studies address this in stable MMT patients. We assessed resting cardiorespiratory function on 50 stable MMT patients (25 males, 25 females). Forty‐six MMT patients were current tobacco smokers, 19 were current cannabis users and none were currently using opioids other than prescribed methadone. We defined abnormalities of respiratory function as those results outside the 95% confidence interval of reference values for normal subjects adjusted for age, weight, height and sex. Thirty‐one (62%) MMT patients had reduced carbon monoxide transfer factor (D L CO); 17 (34%) had elevated single breath alveolar volume (V A) and 43 (86%) had a reduced D L CO/V A ratio. Six patients (12%) had reduced FEV 1; one (2%) had reduced FVC; and nine (18%) had an obstructive ventilatory defect. Ten (20%) patients had PaCO 2 higher than 45 mmHg and 14 (28%) had alveolar to arterial oxygen gradient (A‐aPO 2) higher than 15 mmHg. CXR, Echocardiography and ECG showed no significant abnormalities. We conclude that stable MMT patients have abnormalities of resting respiratory function which may be due to ongoing tobacco cigarette and current or past cannabis smoking.