New Synthetic Opioids: Clinical Considerations and Dangers.

Since the early 2010s, synthetic opioids have significantly contributed to overall opioid-related overdose mortalities. For point of reference, of the 68,630 opioid-related deaths recorded in 2020, 56,516 involved synthetic opioids. During much of this period, fentanyl has been the most commonly used synthetic opioid. This time when fentanyl was the most popular opioid has been called the "third wave" of the opioid crisis, partly because it led to a sharp rise in deaths from overdoses. Other synthetic opioids, such as carfentanil, protonitazene, and isotonitazene, have also become more widely diverted for nonmedical used. Carfentanil is an even more potent fentanyl derivative that was initially used in the mid-1980s as a general anesthetic for large animals such as elephants. Related to its strong affinity for mu opioid receptors, carfentanil is still utilized in medicine and science today as a radiotracer for positron emission tomography imaging. Protonitazene and isotonitazene belong to a novel class of synthetic opioids called benzimidazoles that were manufactured in the 1950s as novel analgesics. These agents have come under recent scrutiny as designer synthetic opioids becoming more prevalent. However, to date, there is incomplete data regarding the prevalence of synthetic opioids, as traditional toxicology screenings may not be sensitive to detect these compounds at such low doses post-mortem, particularly when blood is drawn from the periphery instead of central tissues such as the brain, lung, or heart. This narrative review aims to highlight the clinical challenges presented by these new synthetic opioids.

Critical care telemedicine: evolution and state of the art.

OBJECTIVES: To review the growth and current penetration of ICU telemedicine programs, association with outcomes, studies of their impact on medical education, associations with medicolegal risks, identify program revenue sources and costs, regulatory aspects, and the ICU telemedicine research agenda. DATA SOURCES: Review of the published medical literature, governmental documents, and opinions of experts from the Society of Critical Care Medicine ICU Telemedicine Committee. DATA SYNTHESIS: Formal ICU telemedicine programs now support 11% of nonfederal hospital critically ill adult patients. There is increasingly robust evidence of association with lower ICU (0.79; 95% CI, 0.65-0.96) and hospital mortality (0.83; 95% CI, 0.73-0.94) and shorter ICU (-0.62 d; 95% CI, -1.21 to -0.04 d) and hospital (-1.26 d; 95% CI, -2.49 to -0.03 d) length of stay. Physicians in training report experiences with telemedicine intensivists that are positive and increased patient safety. Early studies suggest that implementation of ICU telemedicine programs has been associated with lower numbers of malpractice claims and costs. The requirements for Medicare reimbursement and states with legislation addressing providing professional services by telemedicine are detailed. CONCLUSIONS: The inclusion of an ICU telemedicine program as a major part of their critical care delivery paradigm has been implemented for 11% of critically ill U.S. adults as a solution for the problem of access to adult critical care services. Implementation of an ICU telemedicine program is one practical way to increase access and reduce mortality as well as length of stay. ICU telemedicine research including comparative effectiveness studies is urgently needed.

Down regulation of COX-2 is involved in hyperbaric oxygen treatment in a rat transient focal cerebral ischemia model.

The effect of hyperbaric oxygen (HBO) on cyclooxygenase-2 (COX-2) expression after transient focal ischemia was evaluated. A rat middle cerebral artery occlusion/reperfusion (MCAO) model was produced using the intraluminal filament method. After 2 h of occlusion, 24 h of reperfusion, brains were removed. Three atmospheres absolute HBO for 1 h was administered at 6 h after reperfusion. The infarct volume was evaluated by 2,3,7-triphenyltetrazolium chloride staining. COX-2 mRNA expression was measured by reverse transcription polymerase chain reaction, and COX-2 protein expression was analyzed by Western blot. The results showed that HBO applied at 6 h after reperfusion significantly reduces infarct area as compared with no-treatment group. HBO decreased COX-2 mRNA and protein levels, which were upregulated after ischemia/reperfusion. HBO had no direct effect on COX-2 protein expression in matched normal rats. We conclude that (1) early intervention with HBO within 6 h reduces infarction. (2) The neuroprotective effect of HBO might lead to an inhibition of COX-2 over-expression in cerebral cortex.