Daily Anesthesiology Research Analysis

BACKGROUND: Preclinical evidence suggests that young plasma has beneficial effects on multiple organ systems in aged mice. Whether young plasma exerts beneficial effects in an aging human population remains highly controversial. Despite lacking data, young donor plasma infusions have been promoted for age-related conditions. Given the preclinical evidence that young plasma exerts beneficial effects by attenuating inflammation, this study examined whether administering a young plasma protein fraction to an elderly population would exert anti-inflammatory and immune modulating effects in humans, using surgery as a tissue injury model. METHODS: This double-blind, placebo-controlled study enrolled and randomized 38 patients undergoing major joint replacement surgery. Patients received four separate infusions of a plasma protein fraction derived from young donors, or placebo one day before surgery, before and after surgery on the day of surgery, and one day after surgery. Blood specimens for proteomic and immunological analyses were collected before each infusion. Based on the high-content assessment of circulating plasma proteins with single-cell analyses of peripheral immune cells, proteomic signatures and cell-type-specific signaling responses that separated the treatment groups were derived with regression models. RESULTS: Elastic net regression models revealed that administration a young plasma protein fraction significantly altered the proteomic (AUC = 0.796, p = 0.002) and the cellular immune response (AUC 0.904, p < 0.001) to surgical trauma resulting in signaling pathway- and cell type-specific anti-inflammatory immune modulation. Affected proteomic pathways regulating inflammation included JAK-STAT, NF-kappa B, and MAPK (p < 0.001). These findings were confirmed at the cellular level as the MAPK and JAK/STAT signaling responses were diminished and IkB, the negative regulator of NFkB, was elevated in adaptive immune cells. CONCLUSION: Reported findings provide a first proof of principle in humans that a young plasma protein fraction actively regulates inflammatory and immune responses in an elderly population. They provide a solid rationale for elucidating active principles in young plasma that may be of therapeutic benefits for a range of age-related pathologies. TRIAL REGISTRATION: ClinicalTrials.gov, NCT03981419.

Neuraxial anesthesia is used for pain management in surgical and nonsurgical settings. Spinal/epidural hematomas likely occur in between 1:10 000 and 1:200 000 procedures. Risk is believed to be greater in patients with bleeding disorders/thrombocytopenia, and there are no existing comprehensive recommendations to guide neuraxial anesthesia in these patients. The study's objective was to develop recommendations to advise clinicians on treatment thresholds for neuraxial anesthesia in patients with platelet disorders/coagulation defects. A 4-round electronic modified Delphi consensus study was conducted. A steering committee generated the original Delphi statements and refined them based on panelist feedback. Consensus was achieved if ≥70% of participants agreed/strongly agreed or disagreed/strongly disagreed with a statement. This project was endorsed by the International Society on Thrombosis and Haemostasis Scientific and Standardization Committee Subcommittee on von Willebrand Factor. Forty-five experts participated (42% response rate) with an essentially equal number of hematologists and anesthesiologists. Thirty consensus statements were developed for 11 disorders ranging from various causes of thrombocytopenia, inherited platelet function disorders, and single or multiple coagulation defects in obstetrical and nonobstetrical patients. Risk of sampling bias is present due to a predominantly North American sample, attrition (common in Delphi studies), and steering committee participation in the Delphi rounds. This is the first set of consensus recommendations for neuraxial anesthesia in adult patients with an array of platelet disorders/coagulation defects. These recommendations, based on the best available evidence and expert opinion, provide a decision framework for clinicians when faced with this challenging scenario.

INTRODUCTION: Glucagon-like peptide-1 receptor (GLP-1R) agonists have been increasingly prescribed for weight loss and glycemic control. The potential side effect of slowed gastric emptying may increase risk of regurgitation and aspiration. Our primary aim was to investigate the incidence of retained gastric contents (RGCs) among appropriately fasted patients taking a GLP-1R agonist compared to those not taking a GLP-1R agonist presenting for upper gastrointestinal endoscopy (UE). METHODS: A retrospective chart review of patients undergoing UE was conducted. For the GLP-1R group, included were patients aged 18 years or older who had documentation of taking a GLP-1R agonist within 30 days prior to the procedure, adhered to standard fasting guidelines, and had clear documentation in the electronic medical record of gastric findings during endoscopy. This group was compared to a group of agematched controls. The primary outcome was the incidence of RGCs. Secondary outcome included a propensity-weighted analysis of the odds ratio of taking a GLP-1R and having RGCs. RESULTS: Included were 940 patients who presented for UE between July 2022 and December 2023 (470 GLP-1R and 470 controls). RGCs were found in 59/470 (12.6 %) of GLP-1R patients compared to 26/470 (5.5 %) of controls (P < 0.001). Propensity-weighted analysis found a significant association between the use of GLP-1R and retained gastric contents [OR = 1.92, 95 % CI (1.04, 3.53)]. CONCLUSIONS: A higher incidence of RGCs was found in appropriately fasted patients on a GLP-1R agonist who presented for UE. After controlling for the differences between the two study groups, RGC's were correlated to GLP-1R agonist use. Anesthesiologists should remain vigilant regarding a potential increased risk of RGCs in appropriately fasted patients taking a GLP-1R agonist who present for surgery.