Will Intranasal Leptin Mitigate Opioid-induced Sleep-disordered Breathing?
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ABSTRACT:
SUBMITTER: Prasad B
PROVIDER: S-EPMC7528931 | biostudies-literature | 2020 Oct
REPOSITORIES: biostudies-literature
Publications
Will Intranasal Leptin Mitigate Opioid-induced Sleep-disordered Breathing?
Prasad Bharati B Chowdhuri Susmita S
American journal of respiratory cell and molecular biology 20201001 4
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Project description:Respiratory depression is the main cause of morbidity and mortality associated with opioids. Obesity increases opioid-related mortality, which is mostly related to comorbid obstructive sleep apnea. Naloxone, a μ-opioid receptor blocker, is an effective antidote, but it reverses analgesia. Like humans with obesity, mice with diet-induced obesity hypoventilate during sleep and develop obstructive sleep apnea, which can be treated with intranasal leptin. We hypothesized that intranasal leptin reverses opioid-induced sleep-disordered breathing in obese mice without decreasing analgesia. To test this hypothesis, mice with diet-induced obesity were treated with morphine at 10 mg/kg subcutaneously and with leptin or placebo intranasally. Sleep and breathing were recorded by barometric plethysmography, and pain sensitivity was measured by the tail-flick test. Excitatory postsynaptic currents were recorded in vitro from hypoglossal motor neurons after the application of the μ-opioid receptor agonist [D-Ala2, N-MePhe4, Gly-ol]-enkephalin and leptin. Morphine dramatically increased the frequency of apneas and greatly increased the severity of hypoventilation and obstructive sleep apnea. Leptin decreased the frequency of apneas, improved obstructive sleep apnea, and completely reversed hypoventilation, whereas morphine analgesia was enhanced. Our in vitro studies demonstrated that [D-Ala2, N-MePhe4, Gly-ol]-enkephalin reduced the frequency of excitatory postsynaptic currents in hypoglossal motoneurons and that application of leptin restored excitatory synaptic neurotransmission. Our findings suggest that intranasal leptin may prevent opioid respiratory depression during sleep in patients with obesity receiving opioids without reducing analgesia.
| S-EPMC7528928 | biostudies-literature
Project description: Not available
| S-EPMC6423110 | biostudies-literature
Project description:BACKGROUND:Bariatric surgery patients are vulnerable to sleep-disordered breathing (SDB) early after recovery from surgery and anesthesia. The authors hypothesized that continuous positive airway pressure (CPAP) improves postoperative oxygenation and SDB and mitigates opioid-induced respiratory depression. METHODS:In a randomized crossover trial, patients after bariatric surgery received 30% oxygen in the postanesthesia care unit (PACU) under two conditions: atmospheric pressure and CPAP (8 to 10?cm H2O). During 1?h of each treatment, breathing across cortical arousal states was analyzed using polysomnography and spirometry. Arousal state and respiratory events were scored in accordance with American Academy of Sleep Medicine guidelines. Data on opioid boluses in the PACU were collected. The primary and secondary outcomes were the apnea hypopnea index (AHI) and apnea after self-administration of opioids in the PACU. Linear mixed model analysis was used to compare physiologic measures of breathing. RESULTS:Sixty-four percent of the 33 patients with complete postoperative polysomnography data demonstrated SDB (AHI greater than 5/h) early after recovery from anesthesia. CPAP treatment decreased AHI (8?±?2/h vs. 25?±?5/h, P < 0.001), decreased oxygen desaturations (5?±?10/h vs. 16?±?20/h, P < 0.001), and increased the mean oxygen saturation by 3% (P = 0.003). CPAP significantly decreased the respiratory-depressant effects observed during wakefulness-sleep transitions without affecting hemodynamics. The interaction effects between CPAP treatment and opioid dose for the dependent variables AHI (P < 0.001), inspiratory flow (P = 0.002), and minute ventilation (P = 0.015) were significant. CONCLUSIONS:This pharmacophysiologic interaction trial shows that supervised CPAP treatment early after surgery improves SDB and ameliorates the respiratory-depressant effects of opioids without undue hemodynamic effects.
| S-EPMC5321128 | biostudies-literature
Project description:Sleep-disordered breathing (SDB) is a common comorbidity in a number of cardiovascular diseases, and mounting clinical evidence demonstrates that it has important implications in the long-term outcomes of patients with cardiovascular disease (CVD). While recognition among clinicians of the role of SDB in CVD is increasing, it too often remains neglected in the routine care of patients with CVD, and therefore remains widely undiagnosed and untreated. In this article, we provide an overview of SDB and its relationship to CVD, with the goal of helping cardiovascular clinicians better recognize and treat this important comorbidity in their patients. We will describe the two major types of SDB and discuss the pathophysiologic, diagnostic, and therapeutic considerations of SDB in patients with CVD.
| S-EPMC4824338 | biostudies-other
Project description:Over the past two decades, various methods of sophisticated diagnostics of the upper airway have been tested in patients with sleep disordered breathing (SDB). In this context, endoscopic techniques and pharyngeal pressure recordings are of special interest for the otorhinolaryngologist.Whereas the basic otorhinolaryngological examination is able to detect anatomical pathologies which need to and can be corrected, the Müller-Manoeuvre seems to help exclude patients from uvulopalatopharyngoplasty.To a large extent, videoendoscopy during natural sleep has been replaced by videoendoscopy under sedation. Despite good methodological preparation and impressive presentability of the obstructions, there is not sufficent evidence to demonstrate that videoendoscopy under sedation improves the success rate of surgery in SDB. However, in assessing the impact of the epiglottis on upper airway obstructions in the individual patient, videoendoscopy is the only existing option.Multi-channel pressure recordings permit analysing the entire sleep period and are well tolerated. They can be used to determine the Apnea-Hypopnea-Index as well as to quantify obstructive events in the upper and lower pharyngeal segment. On the other hand, obstructions of the tongue base cannot be distinguished from obstructions related to the epiglottis. According to the data available so far, the benefit of sophisticated diagnostics of the upper airway still has to be judged with caution. Therefore, the promising approaches of both videoendoscopy under sedation and multi-channel pressure recordings deserve further intensive research. According to the personal estimation of the author, they will nevertheless become valuable tools for otorhinolaryngologists in the near future, thus complementing the basic ENT-examination and improving the treatment of patients.
| S-EPMC3199806 | biostudies-other
Project description:Sleep-disordered breathing (SDB) comprises a diverse set of disorders marked by abnormal respiration during sleep. Clinicians should realize that SDB may present as acute cardiopulmonary failure in susceptible patients. In this review, we discuss three clinical phenotypes of acute cardiopulmonary failure from SDB: acute ventilatory failure, acute congestive heart failure, and sudden death. We review the pathophysiologic mechanisms and recommend general principles for management. Timely recognition of, and therapy for, SDB in the setting of acute cardiopulmonary failure may improve short- and long-term outcomes.
| S-EPMC3296458 | biostudies-other
Project description:ImportanceObstructive sleep-disordered breathing (SDB) in children is characterized by snoring and difficulty breathing during sleep. SDB affects at least 12% of otherwise healthy children and is associated with significant morbidity. Evidence from small clinical trials suggests that intranasal corticosteroids improve SDB as measured by polysomnography; however, the effect on symptoms and quality of life is unclear.ObjectiveTo determine whether intranasal mometasone furoate is more effective than intranasal saline for improving symptoms and quality of life in children with SDB.Design, setting, and participantsThe MIST trial was a multicenter, randomized, double-blind, placebo-controlled trial, recruiting participants from June 8, 2018, to February 13, 2020. Children aged 3 to 12 years who were referred to a specialist for significant SDB symptoms were included; exclusions were previous adenotonsillectomy, body mass index greater than the 97th percentile, and severe SDB. Randomization was stratified by site, and data were analyzed on an intention-to-treat basis from October 28, 2020, to September 25, 2022.InterventionsParticipants were randomly assigned to receive mometasone furoate, 50 μg, or sodium chloride (saline), 0.9%, 1 spray per nostril daily, dispensed in identical bottles.Main outcomes and measuresThe primary outcome was resolution of significant SDB symptoms (ie, reduction to a level no longer requiring referral to a specialist as per the American Academy of Pediatrics guidelines) at 6 weeks, measured by parental report of symptoms using the SDB Score.ResultsA total of 276 participants (mean [SD] age, 6.1 [2.3] years; 146 male individuals [53%]) were recruited, 138 in each treatment arm. Resolution of significant SDB symptoms occurred in 56 of 127 participants (44%) in the mometasone group and 50 of 123 participants (41%) in the saline group (risk difference, 4%; 95% CI, -8% to 16%; P = .51) with 26 participants lost to follow-up and missing values managed by multiple imputation. The main adverse effects were epistaxis, affecting 12 of 124 participants (9.7%) in the mometasone group and 18 of 120 participants (15%) in the saline group, and nasal itch/irritation, affecting 12 of 124 participants (9.7%) in the mometasone group and 22 of 120 participants (18%) in the saline group.Conclusions and relevanceResults of this randomized clinical trial suggest that there was no difference in treatment effect between intranasal mometasone and saline for the management of SDB symptoms. The results suggest that almost one-half of children with SDB could be initially managed in the primary care setting and may not require referral to specialist services, as is currently recommended.Trial registrationAustralian New Zealand Clinical Trials Registry: ANZCTRN12618000448246.
| S-EPMC9857783 | biostudies-literature
Project description:Obesity leads to sleep-disordered breathing (SDB) manifested by recurrent upper airway obstructions termed obstructive sleep apnea (OSA) and carbon dioxide retention due to hypoventilation. The objective of this work was to characterize breathing during sleep in C57BL6/J mice with diet-induced obesity (DIO). Arterial blood gas was measured in nine obese and nine lean mice during wakefulness. Nine male mice with DIO and six lean male C57BL/6J mice were head mounted with electroencephalogram (EEG) and electromyogram (EMG) electrodes. Sleep recordings were performed in the whole body plethysmography chamber; upper airway obstruction was characterized by the presence of inspiratory flow limitation in which airflow plateaus with increases in inspiratory effort. Obese mice showed significantly lower pH and higher partial pressure of arterial CO2 (PaCO2) in arterial blood gas compared to lean mice, 7.35 ± 0.04 versus 7.46 ± 0.06 (p < 0.001) and 38 ± 8 mm Hg versus 30 ± 5 mm Hg (p < 0.001). Obese mice had similar levels of minute ventilation to lean mice during sleep and wakefulness, despite higher body weight and temperature, indicating an increase in the metabolic rate and hypoventilation. Obese mice also showed baseline hypoxemia with decreased mean oxyhemoglobin saturation across sleep/wake states. Obese mice had a higher prevalence of flow-limited breathing compared to lean mice during sleep. However, the oxygen desaturation index in lean and obese mice did not differ. We conclude that DIO in mice leads to hypoventilation. Obesity also increases the frequency of inspiratory limited breaths, but it does not translate into progression of OSA.
| S-EPMC6093346 | biostudies-literature
Project description:BackgroundThere are limited data on the effect of bronchopulmonary dysplasia (BPD) on sleep disordered breathing (SDB). We hypothesized that both the severity of prematurity and BPD would increase the likelihood of SDB in early childhood. Our secondary aim was to evaluate the association of demographic factors on the development of SDB.MethodsThis is a retrospective study of patient factors and overnight polysomnogram (PSG) data of children enrolled in our BPD registry between 2008 and 2015. Association between PSG results and studied variables was assessed using multiple linear regression analysis.ResultsOne-hundred-forty children underwent at least one sleep study on room air. The mean respiratory disturbance index (RDI) was elevated at 9.9 events/hr (SD: 10.1). The mean obstructive apnea-hypopnea index (OAHI) was 6.5 (9.1) events/hr and the mean central event rate of 3.0 (3.7) events/hr. RDI had decreased by 22% or 1.5 events/hour (95%CI: 0.6, 1.9) with each year of age (P = 0.005). Subjects with more severe respiratory disease had 38% more central events (P = 0.02). Infants exposed to secondhand smoke had 2.4% lower (P = 0.04) oxygen saturation nadirs and a pattern for more desaturation events. Non-white subjects were found to have 33% higher OAHI (P = 0.05), while white subjects had a 61% higher rate of central events (P < 0.001).ConclusionsRDI was elevated in a selected BPD population compared to norms for non-preterm children. BPD severity, smoke exposure, and race may augment the severity of SDB. RDI improved with age but was still elevated by age 4, suggesting that this population is at risk for the sequelae of SDB.
| S-EPMC5693767 | biostudies-literature
Project description:OBJECTIVE/BACKGROUND:Limited data are available on sleep-disordered breathing (SDB) following intracerebral hemorrhage (ICH). Our aim was to characterize the objective measures of post-ICH SDB and questionnaire-reported pre-ICH sleep characteristics, overall and by ethnicity. PATIENTS/METHODS:Participants with ICH who were enrolled in the population-based Brain Attack Surveillance in Corpus Christi project (2010-2016) reported their pre-ICH sleep duration and completed the Berlin Questionnaire to characterize pre-ICH risk of SDB. A subsample was screened for SDB (respiratory event index ≥10) using ApneaLink Plus portable monitoring. Ethnic differences in post-ICH SDB or questionnaire-reported pre-ICH sleep characteristics were assessed using a log binomial model or a linear regression model or a Fisher's exact test. RESULTS:ICH cases (n = 298) were enrolled (median age = 68 years, 67% Mexican American). Among 62 cases with complete ApneaLink data, median time to post-ICH SDB screening was 11 days (IQR: 6, 19). Post-ICH SDB prevalence was 46.8% (95% CI: 34.4-59.2), and this rate did not differ by ethnicity (p = 1.0). Berlin Questionnaires for 109 of the 298 ICH cases (36.6% (95% CI: 31.1-42.0)) suggested a high risk for pre-ICH SDB, and the median pre-ICH sleep duration was eight hours (IQR: 6, 8). After adjusting for confounders, there was no difference in ethnicity in high risk for pre-ICH SDB or pre-ICH sleep duration. CONCLUSIONS:Nearly half of the patients had objective confirmation of SDB after ICH, and more than one-third had questionnaire evidence of high risk for pre-ICH SDB. Opportunities to address SDB may be common both before and after ICH.
| S-EPMC6082385 | biostudies-literature