Local anaesthetic systemic toxicity following oral ingestion in a child: Revisiting dibucaine.
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ABSTRACT:
SUBMITTER: Dias R
PROVIDER: S-EPMC5530745 | biostudies-other | 2017 Jul
REPOSITORIES: biostudies-other
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Project description:Over 16?000 mastectomies are performed in England and Wales annually. Acute postoperative pain and nausea are common. The most frequently occurring long-term complications are chronic pain (up to 50%) and reduced shoulder function (reported at 35%). Regional techniques that improve acute postoperative pain relief may reduce the incidence of these complications. This study assesses the effectiveness of a 24-hour continuous local anaesthetic in the subpectoral plane in improving postoperative pain and quality of life in patients undergoing mastectomy.This is a randomised, double blind, placebo-controlled, two-centre, parallel group trial in women undergoing mastectomy with or without axillary involvement. One hundred and sixty participants will be randomised in a 1:1 ratio to receive either 0.25% levobupivacaine or 0.9% saline by subpectoral infusion postoperatively for 24?h. All participants will be provided with an intravenous morphine patient-controlled analgesia (PCA) system. Participants will be followed-up for 24?h in hospital and at approximately 14?days and 6?months postoperatively. Joint primary outcome measures are total morphine consumption and total pain score (captured via patient-recorded visual analogue scale (VAS) 4 hourly) during the first 24?h postoperatively. Primary statistical analysis of total pain is based on the area under the curve of pain versus time graph. Secondary outcomes include PCA attempts in first 24?h; VAS pain scores and shoulder function by goniometry at 24?h, 14?days (approximately) and 6?months; Verbal Rating Scale pain scores in first 24?h; Brief Pain Inventory and Oxford Shoulder Score at 6?months; duration of hospital stay; incidence of postoperative nausea and vomiting; cost-effectiveness.The study is approved by the South West England Research Ethics Committee (12/SW/0149).will be published in a peer-reviewed journal and presented at local, national and international scientific meetings.ISRCTN46621916. EudraCT 2011-005775-16.
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Project description:Regulatory agencies rely upon rodent in vivo acute oral toxicity data to determine hazard categorization, require appropriate precautionary labeling, and perform quantitative risk assessments. As the field of toxicology moves toward animal-free new approach methodologies (NAMs), there is a pressing need to develop a reliable, robust reference data set to characterize the reproducibility and inherent variability in the in vivo acute oral toxicity test method, which would serve to contextualize results and set expectations regarding NAM performance. Such a data set is also needed for training and evaluating computational models. To meet these needs, rat acute oral LD50 data from multiple databases were compiled, curated, and analyzed to characterize variability and reproducibility of results across a set of up to 2441 chemicals with multiple independent study records. Conditional probability analyses reveal that replicate studies only result in the same hazard categorization on average at 60% likelihood. Although we did not have sufficient study metadata to evaluate the impact of specific protocol components (eg, strain, age, or sex of rat, feed used, treatment vehicle, etc.), studies were assumed to follow standard test guidelines. We investigated, but could not attribute, various chemical properties as the sources of variability (ie, chemical structure, physiochemical properties, functional use). Thus, we conclude that inherent biological or protocol variability likely underlies the variance in the results. Based on the observed variability, we were able to quantify a margin of uncertainty of ±0.24 log10 (mg/kg) associated with discrete in vivo rat acute oral LD50 values.
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