The usefulness of dual channel elastomeric pump for intravenous patient-controlled analgesia in geriatrics: a randomized, double-blind, prospective study.

BACKGROUND: Intravenous patient-controlled analgesia (IV-PCA) is often used in the postoperative period. However, determining an appropriate opioid dose is difficult. A previous study suggested the usefulness of variable-rate feedback infusion. In this study, we used a dual-channel elastomeric infusion pump to provide changes in PCA infusion rate by pain feedback. METHODS: Ninety patients undergoing orthopedic surgery of American Society of Anesthesiologists grade I-III and 65 to 79 years of age participated in the study. All patients were given a dual-chamber PCA. Patients were randomly allocated to a treatment group (Group D; PCA drugs divided into both chambers) or control group (Group C; PCA drugs only in the constant flow chamber with normal saline in the adjustable flow chamber). The primary outcome was the amount of fentanyl consumption via PCA bolus. The secondary outcome variables were pain score, total fentanyl consumption, rescue analgesic use, patient satisfaction, recovery scores, and adverse events including postoperative nausea and vomiting (PONV). RESULTS: Group D showed decreased fentanyl consumption of the PCA bolus, a decrease in rescue analgesic use, and better patient satisfaction compared with group C. The incidence of PONV was much higher in group C. There was no difference in other adverse events. CONCLUSIONS: We showed the usefulness of dual chamber IV-PCA to change the flow rate related to pain feedback without any complications. Our results suggest a noble system that might improve existing IV-PCA equipment. TRIAL REGISTRATION: The study registered at UMIN clinical trial registry (registered date: 05/03/2020, registration number: UMIN000039702 ).

Efficacy and Safety of Sugammadex for the Reversal of Rocuronium-Induced Neuromuscular Blockade in Patients with End-Stage Renal Disease: A Systematic Review and Meta-Analysis.

Background and Objectives: Sugammadex is widely used in anesthesia to reverse rocuronium-induced neuromuscular blockade (NMB). In patients with compromised kidney function, most drugs show alteration of their pharmacokinetic profile with reduced clearance. The purpose of this article is to examine the efficacy, pharmacokinetics, and safety of sugammadex in end-stage renal disease (ESRD) patients receiving general anesthesia, using a systematic review. Materials and Methods: The databases of PubMed, EMBASE, the Cochrane Library, Web of Science, Scopus, KoreaMed, and ClinicalTrials.gov were searched for studies comparing the efficacy or safety outcomes of sugammadex administration for the reversal of rocuronium-induced NMB, in ESRD patients (group R) or in those with normal renal function (group N) undergoing surgery under general anesthesia. Results: We identified nine studies with 655 patients-six prospective, case-control studies with 179 patients (89 and 90 in groups R and N) and three retrospective observational studies with 476 ESRD patients. In the six prospective studies, the times taken to reach a train-of-four ratio ≥0.9, 0.8, and 0.7 were significantly longer in group R than in group N (weighted mean difference [95% confidence interval] [min]: 1.14 [0.29 to 2.00], 0.9 [0.24 to 1.57], 0.89 [0.20 to 1.57], respectively). The total plasma clearance of sugammadex was significantly lower in group R than in group N. There was no significant difference in the incidence of NMB recurrence and prolonged time to recovery between the groups. In the three retrospective studies, the possibility of sugammadex-related adverse events appears to be insignificant. Conclusions: Sugammadex may effectively and safely reverse rocuronium-induced NMB in patients with ESRD, although the recovery to a TOF ratio of 0.9 may be prolonged compared to patients with normal renal function. Further studies are needed, considering the small number of studies included and the high heterogeneity of some of the results.

Brain Region-Dependent Alternative Splicing of Alzheimer Disease (AD)-Risk Genes Is Associated With Neuropathological Features in AD.

PURPOSE: Alzheimer disease (AD) is one of the most complex diseases and is characterized by AD-related neuropathological features, including accumulation of amyloid-ß plaques and tau neurofibrillary tangles. Dysregulation of alternative splicing (AS) contributes to these features, and there is heterogeneity in features across brain regions between AD patients, leading to different severity and progression rates; however, brain region-specific AS mechanisms still remain unclear. Therefore, we aimed to systemically investigate AS in multiple brain regions of AD patients and how they affect clinical features. METHODS: We analyzed RNA sequencing (RNA-Seq) data obtained from brain regions (frontal and temporal) of AD patients. Reads were mapped to the hg19 reference genome using the STAR aligner, and exon skipping (ES) rates were estimated as percent spliced in (PSI) by rMATs. We focused on AD-risk genes discovered by genome-wide association studies, and accordingly evaluated associations between PSI of skipped exons in AD-risk genes and Braak stage and plaque density mean (PM) for each brain region. We also integrated whole-genome sequencing data of the ascertained samples with RNA-Seq data to identify genetic regulators of feature-associated ES. RESULTS: We identified 26 and 41 ES associated with Braak stage in frontal and temporal regions, respectively, and 10 and 50 ES associated with PM. Among those, 10 were frontal-specific (CLU and NTRK2), 65 temporal-specific (HIF1A and TRPC4AP), and 26 shared ES (APP) that accompanied functional Gene Ontology terms, including axonogenesis in shared-ES genes. We further identified genetic regulators that account for 44 ES (44% of the total). Finally, we present as a case study the systematic regulation of an ES in APP, which is important in AD pathogenesis. CONCLUSION: This study provides new insights into brain region-dependent AS regulation of the architecture of AD-risk genes that contributes to AD pathologies, ultimately allowing identification of a treatment target and region-specific biomarkers for AD.