The influence of the volatile anaesthetic agents enflurane, isoflurane, halothane and the halothane metabolite trifluoroacetic acid was studied on the hepatic elimination of diazepam, by incubating precision-cut slices of rat liver in a closed system. The impact of anaesthetic-induced action on enzyme activity and diazepam binding to human serum albumin (HSA) was assessed in protein free and protein containing buffers, respectively. Human serum albumin reduced the elimination of diazepam by 12 and 50% at concentrations of 1 and 10 mg ml-1, respectively. In the absence of albumin, halothane 1 mmol litre-1 reduced the elimination of diazepam by 13%, whereas enflurane at 1.5 mmol litre-1 caused a reduction of 8%. No effect was seen from isoflurane 1 mmol litre-1 and trifluoroacetic acid 4 mmol litre-1. In the presence of the highest concentration of albumin, however, an increased elimination of diazepam of 24% resulted from exposure to enflurane and trifluoroacetic acid, while no statistically significant changes were seen for isoflurane and halothane. The present work supports the view that volatile anaesthetic agents may cause pharmacokinetic drug interactions by interference with both enzyme activity and drug protein binding.
Objectives Intranasal fentanyl and midazolam use is increasing in the acute care setting for analgesia and anxiolysis, but there is a lack of literature demonstrating their use, alone or in combination, at pediatric urgent care centers. Methods This retrospective study investigated intranasal fentanyl and midazolam use at an urgent care center located within Le Bonheur Children's Hospital and 2 affiliated off-site centers from September 22, 2011, to December 30, 2015. Data collected included patient demographics, initial fentanyl dose, initial midazolam dose, type of procedure, and serious adverse drug reactions. Results Of the 490 patients who met the inclusion criteria, 143 patients received intranasal fentanyl alone, 92 received intranasal midazolam alone, and 255 received fentanyl in combination with midazolam. The overall patient population was 50% male with a median (range) age of 4.5 (0.2–17.9) years, and most patients were black at 57.1%. The median (range) initial intranasal fentanyl dose was 2.02 (0.99–4.22) μg/kg, and the median initial (range) intranasal midazolam dose was 0.19 (0.07–0.42) mg/kg. In cases where fentanyl and midazolam were administered in combination, the median (range) initial fentanyl dose was 2.23 (0.6–4.98) μg/kg and median (range) initial midazolam dose was 0.2 (0.03–0.45) mg/kg. There were no serious adverse drug reactions reported. Conclusions Intranasal fentanyl and midazolam when administrated alone and in combination can provide analgesia and anxiolysis for minor procedures in pediatric patients treated in the urgent care setting.
Introduction: Pain management is a critical aspect of effective long bone fracture treatment. Pediatric patients frequently report suboptimal pain management, which is an area of growing public concern. The purpose of this quality improvement project was to develop a protocol with the goal to administer pain medication to children presenting with suspected long bone fractures ≤47 minutes of emergency department arrival. Methods: A multidisciplinary team developed a standardized protocol for pain management of patients presenting with musculoskeletal pain utilizing acetaminophen as the first-line agent under a nurse-initiated order. Following education and implementation, weekly reports generated using the International Classification of Diseases codes of fractures were reviewed to assess compliance with the protocol. This study evaluates the frequency of a second pain medication administration and reduction in vital signs and pain scores. Results: Implementation of a pain management protocol reduced median time to pain medication administration to 26 minutes. Overall, 63% (n = 638) of patients required a second pain medication. Of these, 66.5% (348/523) who initially received acetaminophen and 59.7% (286/479) who initially received an opioid required a second pain medication. No significant changes in pre and posttreatment vital signs were found between groups. Patients who initially received opioids experienced a greater reduction in posttreatment pain scores. Conclusions: Using a standardized pain management protocol in combination with comprehensive education effectively reduces median time to pain medication administration in pediatric patients with long bone fractures. Acetaminophen is a rapid and effective first-line agent for managing pain in this population.
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