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Item A multicenter study to evaluate the pharmacokinetics and safety of liposomal bupivacaine for postsurgical analgesia in pediatric patients aged 6 to less than 17 years (PLAY)(Elsevier, 2021) Tirotta, Christopher F.; de Armendi, Alberto J.; Horn, Nicole D.; Hammer, Gregory B.; Szczodry, Michal; Matuszczak, Maria; Wang, Natalie Q.; Scranton, Richard; Ballock, Robert Tracy; Anesthesia, School of MedicineStudy objective: To evaluate the pharmacokinetics and safety of liposomal bupivacaine in pediatric patients undergoing spine or cardiac surgery. Design: Multicenter, open-label, phase 3, randomized trial (PLAY; NCT03682302). Setting: Operating room. Patients: Two separate age groups were evaluated (age group 1: patients 12 to <17 years undergoing spine surgery; age group 2: patients 6 to <12 years undergoing spine or cardiac surgery). Intervention: Randomized allocation of liposomal bupivacaine 4 mg/kg or bupivacaine hydrochloride (HCl) 2 mg/kg via local infiltration at the end of spine surgery (age group 1); liposomal bupivacaine 4 mg/kg via local infiltration at the end of spine or cardiac surgery (age group 2). Measurements: The primary and secondary objectives were to evaluate the pharmacokinetics (eg, maximum plasma bupivacaine concentrations [Cmax], time to Cmax) and safety of liposomal bupivacaine, respectively. Main results: Baseline characteristics were comparable across groups. Mean Cmax after liposomal bupivacaine administration was lower versus bupivacaine HCl in age group 1 (357 vs 564 ng/mL); mean Cmax in age group 2 was 320 and 447 ng/mL for spine and cardiac surgery, respectively. Median time to Cmax of liposomal bupivacaine occurred later with cardiac surgery versus spine surgery (22.7 vs 7.4 h). In age group 1, the incidence of adverse events (AEs) was comparable between liposomal bupivacaine (61% [ 19/31] ) and bupivacaine HCl (73% [ 22/30 ]). In age group 2, 100% (5/5) and 31% (9/29) of patients undergoing spine and cardiac surgery experienced AEs, respectively. AEs were generally mild or moderate, with no discontinuations due to AEs or deaths. Conclusions: Plasma bupivacaine levels following local infiltration with liposomal bupivacaine remained below the toxic threshold in adults (~2000-4000 ng/mL) across age groups and procedures. AEs were mild to moderate, supporting the safety of liposomal bupivacaine in pediatric patients undergoing spine or cardiac surgery.Item Behind the Curtain: Impact of Anesthesia Volume on Outcomes(American Medical Association, 2021) Joung, Rachel Hae-Soo; Bilimoria, Karl Y.; Merkow, Ryan P.; Surgery, School of MedicineItem Bias in Rating of Rodent Distress during Anesthesia Induction for Anesthesia Compared with Euthanasia(2018-03) Baker, Brittany A.; Hickman, Debra L.; Department of Medicine, School of MedicineSelection of an appropriate method of euthanasia involves balancing the wellbeing of the animal during the procedure with the intended use of the animal after death and the physical and psychologic safety of the observer or operator. The recommended practices for anesthesia as compared with euthanasia are very disparate, despite the fact that all chemical methods of euthanasia are anesthetic overdoses. To explain this disparity, this study sought to determine whether perception bias is inherent in the discussion of euthanasia compared with anesthesia. In this study, participants viewed videorecordings of the anesthesia of either 4 rats or 4 mice, from induction to loss of consciousness. Half of the participants were told that they were observing anesthesia; the other half understood that they were observing euthanasia. Participants were asked to rate the distress of the animals by scoring escape behaviors, fear behaviors, respiratory distress, and other distress markers. For mice, the participants generally rated the distress as high when they were told that the mouse was being euthanized, as compared with the participants who were told that the mouse was being anesthetized. For rats, the effect was not as strong, and the distress was generally rated higher when participants were told they were watching anesthesia. Because the interpretation of distress showed bias in both species—even though the bias differed regarding the procedure that interpreted as distressing—this study demonstrates that laboratory animal professionals must consider the influence of potential perception bias when developing policies for euthanasia and anesthesia.Item Cardiac arrest after induction of anesthesia in a 2-month-old infant with undiagnosed Williams syndrome(Wolters Kluwer, 2019) Dunlap, Julie D.; Green, Morton C.; Shah, Aali M.; Kibby, Brandon T.; Billmire, Deobrah F.; Pediatrics, School of MedicineA 2-month-old male infant presented for elective repair of inguinal hernias. His preoperative medical history and physical examination were unremarkable. During induction of anesthesia, the infant sustained an adverse cardiac event. The event was characterized by tachycardia, hypotension, and massive ST-segment elevation. Despite vigorous resuscitation, spontaneous hemodynamic stability could not be achieved and extracorporeal membrane oxygenation was required. A transthoracic echocardiogram revealed severe hypoplasia of the ascending aorta. As effective cardiac function did not recover and there was evidence of diffuse ischemic brain injury, life support was withdrawn. Genetic testing performed postoperatively was definitive for Williams syndrome.Item Career Mentors & 5-Year Data on the IUSM Anesthesiology Match(2022-09-17) Yu, Corinna J.; Ye, Jian; Boyer, Tanna J.; Mitchell, Sally A.Item Comparison of isoflurane and α-chloralose in an anesthetized swine model of acute pulmonary embolism producing right ventricular dysfunction(American Association for Laboratory Animal Science, 2015-02) Beam, Daren M.; Neto-Neves, Evandro M.; Stubblefield, William B.; Alves, Nathan J.; Tune, Johnathan D.; Kline, Jeffrey A.; Department of Emergency Medicine, IU School of MedicinePulmonary embolism (PE) is a leading cause of sudden cardiac death, and a model is needed for testing potential treatments. In developing a model, we compared the hemodynamic effects of isoflurane and α-chloralose in an acute swine model of PE because the choice of anesthesia will likely affect the cardiovascular responses of an animal to PE. At baseline, swine that received α-chloralose (n = 6) had a lower heart rate and cardiac output and higher SpO2, end-tidal CO2, and mean arterial pressure than did those given isoflurane (n = 9). After PE induction, swine given α-chloralose compared with isoflurane exhibited a lower heart rate (63 ± 10 compared with 116 ± 15 bpm) and peripheral arterial pressure (52 ± 12 compared with 61 ± 12 mm Hg); higher SpO2 (98% ± 3% compared with 95% ± 1%), end-tidal CO2 (35 ± 4 compared with 32 ± 5), and systolic blood pressure (121 ± 8 compared with 104 ± 20 mm Hg); and equivalent right ventricular:left ventricular ratios (1.32 ± 0.50 compared with 1.23 ± 0.19) and troponin I mean values (0.09 ± 0.07 ng/mL compared with 0.09 ± 0.06 ng/mL). Isoflurane was associated with widely variable fibrinogen and activated partial thromboplastin time. Intraexperiment mortality was 0 of 6 animals for α-chloralose and 2 of 9 swine for isoflurane. All swine anesthetized with α-chloralose survived with sustained pulmonary hypertension, RV-dilation-associated cardiac injury without the confounding vasodilatory or coagulatory effects of isoflurane. These data demonstrate the physiologic advantages of α-chloralose over isoflurane for anesthesia in a swine model of severe submassive PE.Item Comparison of lidocaine-dexmedetomidine and lidocaine-saline on the characteristics of the modified forearm bier block: A clinical trial(Wolters Kluwer, 2021) Ghaderi, Kamal; Rahmani, Khaled; Rahmanpanah, Nasser; Shami, Shoaleh; Zahedi, Farhad; Nasseri, Karim; Medicine, School of MedicineBackground and aims: Forearm Modified Bier Block (FMBB) reduces local anesthetic systemic toxicity risks compared to the traditional method. This study was designed and implemented to compare the effects of lidocaine-dexmedetomidine (LD) and lidocaine-saline (LS) on the characteristics of the MFBB in distal forearm and hand surgery. Material and methods: In this randomized double-blind trial, which was conducted after obtaining institutional ethical committee approval, 60 patients were enrolled and randomly divided into two groups. In both groups, the analgesic base of the block was 20 mL lidocaine 0.5% that was supplemented by 1 μg/kg dexmedetomidine in the LD group or 1 mL of 0.9% saline in the LS group. Patients were evaluated for the onset and duration of sensory block, time of the first request for postoperative analgesic, and analgesic request frequency during the first 24 h after surgery. Results: Sensory block onset in the LD group (7.1 ± 1.4 min) compared to the LS group (8.4 ± 1.4) was faster (P = 0.008). Duration of the sensory block in LD group (49.7 ± 7.2 min) was longer than LS group (33.3 ± 2.6) (P < 0.001). Compared to LS group, time of the first request for postoperative analgesic in LD group was later (P = 0.6), and had lesser analgesic requests during the first 24 h after surgery (P < 0.001). Conclusion: Based on our study's finding, adding dexmedetomidine to lidocaine in the MFBB increases the duration of sensory block.Item Development of a primate model to evaluate the effects of ketamine and surgical stress on the neonatal brain(Sage, 2023) Wang, Cheng; Bhutta, Adnan; Zhang, Xuan; Liu, Fang; Liu, Shuliang; Latham, Leah E.; Talpos, John C.; Patterson, Tucker A.; Slikker, William, Jr.; Pediatrics, School of MedicineWith advances in pediatric and obstetric surgery, pediatric patients are subject to complex procedures under general anesthesia. The effects of anesthetic exposure on the developing brain may be confounded by several factors including pre-existing disorders and surgery-induced stress. Ketamine, a noncompetitive N-methyl-d-aspartate (NMDA) receptor antagonist, is routinely used as a pediatric general anesthetic. However, controversy remains about whether ketamine exposure may be neuroprotective or induce neuronal degeneration in the developing brain. Here, we report the effects of ketamine exposure on the neonatal nonhuman primate brain under surgical stress. Eight neonatal rhesus monkeys (postnatal days 5-7) were randomly assigned to each of two groups: Group A (n = 4) received 2 mg/kg ketamine via intravenous bolus prior to surgery and a 0.5 mg/kg/h ketamine infusion during surgery in the presence of a standardized pediatric anesthetic regimen; Group B (n = 4) received volumes of normal saline equivalent to those of ketamine given to Group A animals prior to and during surgery, also in the presence of a standardized pediatric anesthetic regimen. Under anesthesia, the surgery consisted of a thoracotomy followed by closing the pleural space and tissue in layers using standard surgical techniques. Vital signs were monitored to be within normal ranges throughout anesthesia. Elevated levels of cytokines interleukin (IL)-8, IL-15, monocyte chemoattractant protein-1 (MCP-1), and macrophage inflammatory protein (MIP)-1β at 6 and 24 h after surgery were detected in ketamine-exposed animals. Fluoro-Jade C staining revealed significantly higher neuronal degeneration in the frontal cortex of ketamine-exposed animals, compared with control animals. Intravenous ketamine administration prior to and throughout surgery in a clinically relevant neonatal primate model appears to elevate cytokine levels and increase neuronal degeneration. Consistent with previous data on the effects of ketamine on the developing brain, the results from the current randomized controlled study in neonatal monkeys undergoing simulated surgery show that ketamine does not provide neuroprotective or anti-inflammatory effects.Item Emergency Department Utilization After Administration of Peripheral Nerve Blocks for Upper Extremity Surgery(Sage, 2022) Loewenstein, Scott N.; Bamba, Ravinder; Adkinson, Joshua M.; Surgery, School of MedicineBackground: The purpose of this study was to determine the impact of upper extremity peripheral nerve blocks on emergency department (ED) utilization after hand and upper extremity surgery. Methods: We reviewed all outpatient upper extremity surgeries performed in a single Midwestern state between January 2009 and June 2019 using the Indiana Network for Patient Care. These encounters were used to develop a database of patient demographics, comorbidities, concurrent procedures, and postoperative ED visit utilization data. We performed univariate, bivariate, and multivariate logistic regression analyses. Results: Among 108 451 outpatient surgical patients, 9079 (8.4%) received blocks. Within 1 week of surgery, a greater proportion of patients who received peripheral nerve blocks (1.4%) presented to the ED than patients who did not (0.9%) (P < .001). The greatest risk was in the first 2 postoperative days (relative risk, 1.78; P < .001). Pain was the principal reason for ED utilization in the block cohort (53.6%) compared with those who did not undergo a block (35.1%) (P < .001). When controlling for comorbidities and demographics, only peripheral nerve blocks (adjusted odds ratio [OR], 1.71; P = 0.007) and preprocedural opioid use (adjusted OR, 1.43; P = .020) conferred an independently increased risk of ED utilization within the first 2 postoperative days. Conclusions: Peripheral nerve blocks used for upper extremity surgery are associated with a higher risk of unplanned ED utilization, most likely related to rebound pain. Through proper patient education and pain management, we can minimize this unnecessary resource utilization.