Propofol concentration to induce general anesthesia in children aged 3-11 years with the Kataria effect-site model.

BACKGROUND: The propofol pharmacokinetic model derived by Kataria et al. was recently modified to perform effect-site target-controlled infusion (TCI). Effect-site concentration (Ce) targets to induce general anesthesia with this model in children have not been described. The aim of this study was to identify propofol Ce targets associated with success rates of 50% (Ce50) and 95% (Ce95) among children 3-11 years of age. METHODS: Forty-two children were assigned to one of seven groups of six patients each according to propofol target Ce. After fentanyl administration propofol TCI was started with an assigned Ce target. A successful response was defined as loss of eyelash reflex and bispectral index < 50, 45 s after reaching the assigned Ce. Logistic regression analysis was performed to calculate propofol Ce50 and Ce95. RESULTS: Twenty-eight children had a successful response with the assigned propofol Ce. In these patients, a significant decrease in mean arterial blood pressure (79-59, P < 0.0001) and in heart rate (95-83, P < 0.0001) was observed. Propofol Ce and age showed a statistically significant effect in the logistic regression model. The overall calculated propofol Ce50 and Ce95 were 3.8 µg·ml(-1) (95% CI: 3.1-4.4 µg·ml(-1) ) and 6.1 µg·ml(-1) (95% CI: 4.6-7.6 µg·ml(-1) ), respectively. CONCLUSION: Our results identified useful propofol targets to be used with the Kataria effect-site model to induce anesthesia in children between 3 and 11 years. The recommended targets should be reduced progressively with increasing age most probably due to PK model misspecifications.

Cognitive function mediates the relationship between age and anaesthesia-induced oscillatory-specific alpha power.

Cognitive decline is common among older individuals, and although the underlying brain mechanisms are not entirely understood, researchers have suggested using EEG frontal alpha activity during general anaesthesia as a potential biomarker for cognitive decline. This is because frontal alpha activity associated with GABAergic general anaesthetics has been linked to cognitive function. However, oscillatory-specific alpha power has also been linked with chronological age. We hypothesize that cognitive function mediates the association between chronological age and (oscillatory-specific) alpha power. We analysed data from 380 participants (aged over 60) with baseline screening assessments and intraoperative EEG. We utilized the telephonic Montreal Cognitive Assessment to assess cognitive function. We computed total band power, oscillatory-specific alpha power, and aperiodics to measure anaesthesia-induced alpha activity. To test our mediation hypotheses, we employed structural equation modelling. Pairwise correlations between age, cognitive function and alpha activity were significant. Cognitive function mediated the association between age and classical alpha power [age → cognitive function → classical alpha; ß = -0.0168 (95% confidence interval: -0.0313 to -0.00521); P = 0.0016] as well as the association between age and oscillatory-specific alpha power [age → cognitive function → oscillatory-specific alpha power; ß = -0.00711 (95% confidence interval: -0.0154 to -0.000842); P = 0.028]. However, cognitive function did not mediate the association between age and aperiodic activity (1/f slope, P = 0.43; offset, P = 0.0996). This study is expected to provide valuable insights for anaesthesiologists, enabling them to make informed inferences about a patient's age and cognitive function from an analysis of anaesthetic-induced EEG signals in the operating room. To ensure generalizability, further studies across different populations are needed.

Clinical Presentation and Perioperative Management of Pheochromocytomas and Paragangliomas: A 4-Decade Experience.

PURPOSE: Latin American reports on pheochromocytomas and paragangliomas (PPGLs) are scarce. Recent studies demonstrate changes in clinical presentation and management of these patients. Herein, we assessed the main characteristics of PPGL patients in our academic center over the past 4 decades. METHODS: Demographic, clinical, biochemical, and perioperative data from 105 PPGL patients were retrospectively and prospectively collected over the 1980-2019 period. Data were organized into 4 periods by decade. RESULTS: Age at diagnosis, gender, tumor size and percentage of bilaterality, percentage of paragangliomas, and metastases remained stable across the 4 decades. The proportion of genetic testing and incidentalomas increased in recent decades (all P < 0.001). Therefore, we compared PPGLs diagnosed as incidentalomas (36%) with those clinically suspected (64%). Incidentalomas had fewer adrenergic symptoms (38 vs. 62%; P < 0.001) and lower rates of hypertension (64% vs. 80%; P = 0.01) and hypertensive crisis (28% vs. 44%; P = 0.02); also, they had lower functionality (79% vs. 100%; P = 0.01) and lower catecholamines levels (8.4-fold vs. 12.5-fold above upper cutoffs; P = 0.04). Regarding management of all PPGLs over the decades, we observed significant increases in both perioperative doxazosin dose (P = 0.003) and laparoscopic approach rates (P < 0.001), along with a decrease in the length of hospital stays (P = 0.007). CONCLUSIONS: We observed a change in the clinical presentation of PPGL in recent decades, with a marked increase in incidental cases and milder symptoms. The implementation of a multidisciplinary program for adrenal disorders in our institution has translated into more timely diagnoses, more genetic testing, and improvements in perioperative management.

Dexmedetomidine Improves Cardiovascular and Ventilatory Outcomes in Critically Ill Patients: Basic and Clinical Approaches.

Dexmedetomidine (DEX) is a highly selective α2-adrenergic agonist with sedative and analgesic properties, with minimal respiratory effects. It is used as a sedative in the intensive care unit and the operating room. The opioid-sparing effect and the absence of respiratory effects make dexmedetomidine an attractive adjuvant drug for anesthesia in obese patients who are at an increased risk for postoperative respiratory complications. The pharmacodynamic effects on the cardiovascular system are known; however the mechanisms that induce cardioprotection are still under study. Regarding the pharmacokinetics properties, this drug is extensively metabolized in the liver by the uridine diphosphate glucuronosyltransferases. It has a relatively high hepatic extraction ratio, and therefore, its metabolism is dependent on liver blood flow. This review shows, from a basic clinical approach, the evidence supporting the use of dexmedetomidine in different settings, from its use in animal models of ischemia-reperfusion, and cardioprotective signaling pathways. In addition, pharmacokinetics and pharmacodynamics studies in obese subjects and the management of patients subjected to mechanical ventilation are described. Moreover, the clinical efficacy of delirium incidence in patients with indication of non-invasive ventilation is shown. Finally, the available evidence from DEX is described by a group of Chilean pharmacologists and clinicians who have worked for more than 10 years on DEX.