Chronic opioid use and central sleep apnea: a review of the prevalence, mechanisms, and perioperative considerations.

BACKGROUND: Chronic opioid use has been associated with the development of sleep-disordered breathing (SDB) such as central sleep apnea (CSA). Patients receiving chronic opioids may suffer from unrecognized sleep apnea that contributes to opioid-overdose death. Currently, information regarding the perioperative management of patients with chronic opioid-associated CSA is limited. The objectives of this review are to define the clinical manifestations of SDB associated with chronic opioid therapy, especially CSA, and to highlight their prevalence, mechanisms, risk factors, and perioperative management. METHODS: We searched Medline (1983-2014), Medline In-Process and other nonindexed citations (July 2014), EMBASE (1983-2014), the Cochrane Database of Systematic Reviews (January 2005-2014), the Cochrane Central Registry of Controlled Trials (July 2014), and PubMed basic search for new materials (1983-2014). Anesthesia and Sleep Medicine meeting abstracts were also searched for relevant articles. We included all prospective, retrospective studies and case reports in which CSA and chronic opioid use was confirmed by polysomnography. CSA was defined as the absence of airflow for ≥ 10 seconds with the absence of breathing efforts. A Central Apnea Index ≥ 5 events/h was considered significant. RESULTS: The search strategy yielded 8 studies which included 560 patients. The overall prevalence of CSA in patients taking chronic opioids was high (24%). The morphine equivalent daily dose (MEDD) was strongly associated with the severity of the SDB, predominantly CSA, with an MEDD of >200 mg being a threshold of particular concern. Concurrent use of benzodiazepines or hypnotics was associated with the severity of CSA in one study. Body mass index was inversely related to the severity of SDB. There were various recommendations regarding the best type of positive airway pressure therapy for the treatment of opioid-associated CSA. Continuous positive airway pressure may be ineffective in eliminating, or may even increase, CSA. Adaptive servoventilation and bilevel positive airway pressure ventilation were effective according to some reports. CONCLUSIONS: The overall prevalence of CSA in patients taking chronic opioids was 24%. The most important risk factors for severity of CSA were an MEDD >200 mg, and low or normal body mass index. Continuous positive airway pressure is often ineffective for treating CSA. Limited data are available on the perioperative management of patients with CSA associated with chronic opioid use. Further prospective studies on the perioperative risks and management of these patients are needed.

Settlement dynamics, subsistence economies and climate change during the late Holocene at Nunura Bay (Sechura Desert, Peru): A multiproxy approach.

Long considered on the margins, far from the major cultural traditions, the Sechura Desert is situated at the crossroads between the cultures of southern Ecuador and those of the northern Peruvian coast and preserves a large number of varied archaeological sites. Despite this evidence, little is known about the societies that inhabited this region during the Holocene. Exposed to natural hazards, including El Niño events, and to major climatic changes, they were able to adapt and exploit the scarce resources that this extreme environment offered them. Because of this rich history, we have been conducting archaeological research in this region since 2012 in order to clarify the dynamics of human occupation and their links with climate oscillations and environmental changes. This paper present the results of a multidisciplinary study of Huaca Grande, a mound located on Nunura Bay, 300 m from the Pacific Ocean. The nature of the human occupations at Huaca Grande was varied, and several adjustments occurred over time. The subsistence economy was based mainly on local marine resources and a continual use of terrestrial vegetal resources. However, a major change occurred in the more recent occupations, with the apparition of non-local resources (maize and cotton) indicating that Huaca Grande was connected to trade networks. The results show two main phases of occupation separated by a long abandonment (mid-5th century CE to mid-7th century CE and mid-13th century to mid-15th century CE). The occupation of the site appears to have been influenced by changes in the local climate and by extreme El Niño events. Our results highlight the great adaptability of these human groups over the span of a millennium and their capacity to react to the climatic changes and hazards that characterise this region.

Synthesis, anti-inflammatory activity and molecular docking studies of 2,5-diarylfuran amino acid derivatives.

A series of 2,5-diaryl substituted furans functionalized with several amino acids were synthesized and evaluated as the cyclooxygenases COX-1 and COX-2 enzymes inhibitors. The proline-substituted compound inhibited PGE(2) secretion by LPS-stimulated neutrophils, suggesting selectivity for COX-2. Molecular docking studies in the binding site of COX-2 were performed.