Naloxone Continuous Infusion for Spinal Cord Protection in Endovascular Aortic Surgery Leads to Higher Opioid Administration and More Pain.

OBJECTIVE: Compare total perioperative opioid use in patients receiving naloxone continuousinfusion (NCI) for spinal cord ischemia prophylaxis, versus patients not receiving NCI, in endovascular aortic repair. DESIGN: Single-center, retrospective cohort review. SETTING: Academic medical center. PARTICIPANTS: Patients undergoing elective thoracic, thoracoabdominal, or abdominal aortic endovascular repair. INTERVENTIONS: Patients were separated based on the use of naloxone continuous infusion as part of a spinal protection protocol. Primary endpoint was opioid requirements, in milligram morphine equivalents (MME), during the first 48 hours or during NCI. Secondary endpoints included: postoperative pain scores during the same interval; opioid requirements during hours 48 to 72; and pain scores during hours 48 to 72. MEASUREMENTS AND MAIN RESULTS: Ninety-five procedures were included; 43 received naloxone continuous infusion and 52 patients were in the non-naloxone group. Opioid use from a linear mixed model was elevated across the entire continuum in the naloxone group (18 MMEs, 95% CI 13-24), with the greatest difference seen at the 24-to-48-hour interval (51 MMEs, 95% CI 26-75) after adjustment for age, incisions, and prehospital opioid use. In the naloxone group, pain score estimates were elevated at each postoperative interval of evaluation, with similar adjustment. Across the continuum this was 0.7 higher (95% CI 0.2-1.3); the zero-six-hour and six-to-12-hour intervals were 0.9 (95% CI 0.4-1.4) and 1.2 higher (95% CI 0.7-1.7). CONCLUSIONS: Patients receiving anloxone continuous infusion to prevent spinal cord ischemia required greater quantities of opioids and had higher postoperative pain, compared with patients not requiring naloxone.

Azithromycin and Major Adverse Kidney Events in Critically Ill Patients With Sepsis-Associated Acute Kidney Injury.

BACKGROUND: Sepsis-associated acute kidney injury (SA-AKI) is associated with significant morbidity and mortality. Immune dysregulation is a hallmark of sepsis, with important contributions to organ dysfunction including injury and repair mechanisms in AKI. Macrolide antibiotics, such as azithromycin, have previously demonstrated in preclinical models a myriad of immunomodulatory effects that may benefit critically ill patients with SA-AKI. The aim of this study was to determine if early receipt of azithromycin in SA-AKI is associated with a reduction in major adverse kidney events (MAKE) at hospital discharge. METHODS: This was a single center, retrospective cohort study of critically ill adult patients with SA-AKI. Early exposure to azithromycin was defined as receipt of one or more doses within 48 h of a hospital admission with SA-AKI. The primary outcome of MAKE assessed at hospital discharge was the composite of death, requirement for kidney replacement therapy, or a decline in estimated glomerular filtration rate of 25% or more. Multivariable logistic regression was used to account for potential confounders in the assessment. RESULTS: Of 737 included patients with SA-AKI, 152 (20.6%) received azithromycin. Patients that received early azithromycin were less likely to experience MAKE at hospital discharge when compared to those patients not receiving azithromycin: 38.8% versus 48.4% (P = 0.035). In multivariable logistic regression, receipt of azithromycin was independently associated with a decreased odds of MAKE at hospital discharge (aOR 0.62, 95% CI 0.41-0.93). CONCLUSIONS: Early exposure to azithromycin in SA-AKI is independently associated with lower odds of MAKE at hospital discharge.

Lipid Bilayers Are Long-Lived on Solvent Cleaned Plasma-Oxidized poly(dimethyl)siloxane (ox-PDMS).

Although it is well known that phospholipids self-assemble on hydrophilic plasma-oxidized PMDS surfaces (ox-PDMS) to form cell membrane mimetic bilayers, the temporal stability of phospholipid membranes on these surfaces is unknown. Here we report that phospholipid bilayers remain stable on solvent-cleaned ox-PDMS for at least 132 hours after preparation. Absent solvent cleaning, the bilayers were stable for only 36 hours. We characterized the phospholipid bilayers, i) through quantitative comparative analysis of the fluorescence intensity of phospholipid bilayers on ox-PDMS and phospholipid monolayers on native PDMS and, ii) through measurements of the diffusive mobility of the lipids through fluorescence recovery after photobleaching (FRAP). The fluorescence intensity of the phospholipid layer remained consistent with that of a bilayer for 132 hours. The evolution of the diffusive mobility of the phospholipids in the bilayer on ox-PDMS over time was similar to lipids in control bilayers prepared on glass surfaces. Solvent cleaning was essential for the long-term stability of the bilayers on ox-PDMS. Without cleaning in acetone and isopropanol, phospholipid bilayers prepared on ox-PDMS surfaces peeled off in large patches within 36 hours. Importantly, we find that phospholipid bilayers supported on solvent-cleaned ox-PDMS were indistinguishable from phospholipid bilayers supported on glass for at least 36 hours after preparation. Our results provide a link between the two common surfaces used to prepare in vitro biomimetic phospholipid membranes-i) glass surfaces used predominantly in fundamental biophysical experiments, for which there is abundant physicochemical information, with ii) ox-PDMS, the dominant material used in practical, applications-oriented systems to build micro-devices, topographically-patterned surfaces, and biosensors where there is a dearth of information.