Synthesis and antimicrobial testing of 5-fluorouracil derivatives.

Antibiotic resistance has increased the demand for novel treatments against multidrug-resistant microorganisms. In the research literature, 5-fluorouracil (5-FU) was proposed as an alternative due to its intrinsic antibacterial property. However, given its toxicity profile at high doses, its use in antibacterial therapy is dubious. In the quest for improving the efficacy of 5-FU, the present study intends to synthesise 5-FU derivatives and assess their susceptibility and mechanism against pathogenic bacteria. It was found that the compounds having tri-hexylphosphonium substitution on both nitrogen groups of 5-FU (6a, 6b and 6c) had considerable activity against both Gram-positive and Gram-negative bacteria. Among the active compounds, those with an asymmetric linker group 6c were found to have higher antibacterial efficacy. However, no conclusive efflux inhibition activity was found. As elucidated by electron microscopy studies, these self-assembling active phosphonium-based 5-FU derivatives caused considerable septal damage and cytosolic alterations in Staphylococcus aureus cells. In Escherichia coli, these compounds triggered plasmolysis. Interestingly, the minimal inhibitory concentration (MIC) of the most potent 5-FU derivative 6c remained constant, regardless of the bacteria's resistance profile. Further analysis revealed that compound 6c generated significant alterations in membrane permeabilization and depolarization in S. aureus and E. coli cells at the MIC. Compound 6c was found to substantially impede bacterial motility, suggesting its importance in regulating bacterial pathogenicity. Additionally, the nonhaemolytic activity of 6c suggested that it could be a potential therapeutic option for treating multidrug-resistant bacterial infections.

Ultrasound evaluation of inferior vena cava compression in tilted and supine term parturients.

PURPOSE: Hypotension is common following spinal anesthesia (SA) during elective Cesarean delivery (CD). Although common practice is to alleviate inferior vena cava (IVC) compression, limited evidence supports a 15° tilt for CD. We measured collapsibility of the IVC in supine and 15° left lateral tilt positions with ultrasound before and after SA and phenylephrine infusion in term parturients. METHODS: Twenty term parturients scheduled for CD were recruited for this prospective study. Ultrasound measurements of the IVC were taken 1) supine before SA, 2) tilted 15° before SA, 3) supine after SA, and 4) tilted 15° after SA. A phenylephrine infusion was begun after injection of SA. The primary outcome was to evaluate the impact of position on the IVC collapsibility index (IVCCI): a measure of the difference between the maximum and minimum IVC diameter with respiration. RESULTS: The mean (standard deviation) IVCCI (%) before SA was higher in the supine 19.5 (8.0) than in the tilted 15.0 (6.4) position (mean difference, 4.5; 95% confidence interval [CI], 0.1 to 8.9; P = 0.04). After SA, there was no significant difference between IVCCI (%) in the supine 17.8 (8.3) and tilted 14.2 (6.9) position (mean difference, 3.5; 95% CI, -0.9 to 7.9; P = 0.13). There was no correlation between the pre-spinal IVVCI measurements and the quantity of phenylephrine used during the surgery. CONCLUSION: The IVCCI was lower in the 15° tilt position than in the supine position, but not after SA with a phenylephrine infusion. Ultrasound imaging can help identify IVC compression. TRIAL REGISTRATION: www.clinicaltrials.gov (NCT03410199); registered 18 January 2018.

RéSUMé: OBJECTIF: L'hypotension est fréquente après une rachianesthésie pendant un accouchement par césarienne programmée (CP). Bien que la pratique courante consiste à atténuer la compression de la veine cave inférieure (VCI), des données probantes limitées encouragent une latéralisation de 15 ° durant la CP. Avec l'échographie, nous avons mesuré la collapsibilité de la VCI en décubitus dorsal et en position d'inclinaison latérale gauche de 15° avant et après la rachianesthésie et la perfusion de phényléphrine chez des parturientes à terme. MéTHODE: Vingt parturientes à terme devant subir une CP ont été recrutées dans le cadre de cette étude prospective. Les mesures échographiques de la VCI ont été prises 1) en décubitus dorsal avant la rachianesthésie, 2) avec une latéralisation de 15° avant la rachianesthésie, 3) en décubitus dorsal après la rachianesthésie, et 4) avec une latéralisation de 15° après la rachianesthésie. Une perfusion de phényléphrine a été amorcée après l'injection de la rachianesthésie. Le critère d'évaluation principal était l'impact de la position sur l'indice de collapsibilité de la VCI (ICVCI), soit une mesure de la différence entre les diamètres maximal et minimal de la VCI avec respiration. RéSULTATS: Le ICVCI moyen (écart type) (%) avant la rachianesthésie était plus élevé en décubitus dorsal, à 19,5 (8,0), qu'en position latéralisée, à 15,0 (6,4) (différence moyenne, 4,5; intervalle de confiance [IC] 95 %, 0,1 à 8,9; P = 0,04). Après la rachianesthésie, aucune différence significative n'a été observée entre l'ICVCI (%) en décubitus dorsal, à 17,8 (8,3), et en position latéralisée, à 14,2 (6,9) (différence moyenne, 3,5; IC 95 %, -0,9 à 7,9; P = 0,13). Il n'y avait aucune corrélation entre les mesures de l'ICVCI pré-rachianesthésie et la quantité de phényléphrine utilisée pendant la chirurgie. CONCLUSION: L'ICVCI était plus bas en position latéralisée à 15 ° qu'en décubitus dorsal, mais pas après une rachianesthésie avec une perfusion de phényléphrine. L'échographie peut aider à identifier la compression de la VCI. ENREGISTREMENT DE L'éTUDE: www.clinicaltrials.gov (NCT03410199); enregistrée le 18 janvier 2018.

Face transplantation: anesthesia and other organizational considerations.

In 2005, the first facial vascularized composite allotransplant was performed in France. In May 2018, our team at Maisonneuve-Rosemont Hospital, Montreal, Quebec, had the privilege to participate in the first facial transplant in Canada. Interdisciplinary collaboration, coordination, and communication formed the cornerstone of this medical undertaking and, ultimately, its success. This report details the anesthetic and organizational considerations of our experience.

RéSUMé: En 2005, la première allogreffe de tissu composite vascularisée faciale était réalisée en France. En mai 2018, notre équipe à l'Hôpital Maisonneuve-Rosemont, à Montréal, au Québec, a eu le privilège de participer à la première greffe faciale au Canada. La collaboration, la coordination et la communication interdisciplinaires ont constitué les pierres angulaires de ce projet médical et, ultimement, de son succès. Ce compte-rendu détaille les considérations anesthésiques et organisationnelles de notre expérience.

Impact of anesthesia management during cytoreductive surgery plus hyperthermic intraperitoneal chemotherapy for the treatment of colorectal peritoneal carcinomatosis on intra- and postoperative outcomes: A systematic review protocol.

BACKGROUND: The impact of the anesthesia management during cytoreductive surgery (CRS) plus hyperthermic intraperitoneal chemotherapy (HIPEC) for the treatment of colorectal peritoneal carcinomatosis (CRPC) on postoperative outcomes might be of major importance in the process of postoperative recovery. It might have a significant impact on intra- and postoperative outcomes, but the evaluation of this impact seems to be under-reported. To investigate the question whether the anesthesia management was reported in previous studies done in this population and if it had any impact on postoperative outcomes, we propose to conduct a systematic review of the published literature. METHODS: For this review, we will follow the Preferred Reporting Items for Systematic Reviews and Meta-Analyses Protocols (PRISMA-P). Medline/PubMed, Embase, EBM Reviews and the Cochrane Database of Systematic Reviews (CDSR) will be systematically consulted for eligible studies without age, gender, ethnic, and language restriction. The goal of this review will be to assess whether anesthesia monitoring, dosing, and analgesia protocols were reported in this literature on this specific procedure and whether the impact of the anesthesia management on intraoperative safety and postoperative recovery was evaluated. RESULTS: The results of this systematic review will allow to answer the initial question: has the impact of anesthesia management on intraoperative safety and patients' postoperative recovery already been studied and reported in the past for this type of major surgery? And does anesthesia have any impact on postoperative outcomes? DISCUSSION: In the hypothesis that the impact of anesthesia management on patients' postoperative recovery has never been studied, or very little reported in previous studies in this type of major surgery, it would be justified to conduct a randomized controlled trial on this specific objective. REGISTRATION: This systematic review protocol was registered in PROSPERO, under the registration number CRD42019124162.

A modified mid-femoral approach to the sciatic nerve block: a correlation between evoked motor response and sensory block.

BACKGROUND: The lateral sciatic mid-femoral block (LSMF), proved to be reliable, safe, and effective on both branches of the sciatic nerve with a single injection. However, we do not know which component of the sciatic nerve (the tibial [T] or the common peroneal [CP]) produces a better success rate when performing a LSMF with a single injection technique. In this prospective study we compared the success rate of the T motor response with the CP motor response. METHODS: Ninety-five patients undergoing ankle or foot surgery were enrolled. Thirty milliliters of 0.475% ropivacaine was injected at the first evoked motor response, either T or CP, with a minimal intensity between 0.3 and 0.5 mA. RESULTS: Seventy-two patients were included in group T and 23 in group CP. The block was considered a success when a complete sensory block of the sciatic nerve was obtained. The success rate was 90% (65) for the T response and 70% (16) for the CP response (P < 0.05). Time to perform the block (CP: 4.5 +/- 3 min vs T: 4.5 +/- 4 min; P = NS) as well as sensory and motor onset times were not significantly different between groups. No complications were observed in either group. CONCLUSION: We conclude that the evoked motor response of the T branch is associated with a higher success rate than a CP response using the modified LSMF block.