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- Electromyographic assessment of blink reflex throughout the transition from responsiveness to unresponsiveness during induction with propofol and remifentanilPublication . Ferreira, Ana Isabel Leitão; Vide, Sérgio; Felgueiras, João; Cardoso, Márcio; Nunes, Catarina S.; Mendes, Joaquim; Amorim, PedroGeneral anesthesia is a reversible drug-induced state of altered arousal characterized by loss of responsiveness due to brainstem inactivation. Precise identification of the moment in which responsiveness is lost during the induction of general anesthesia is extremely important to provide information regarding an individual's anesthetic requirements and help intraoperative drug titration. To characterize the transition from responsiveness to unresponsiveness more objectively, we studied neurophysiologic-derived parameters of electromyographic records of electrically evoked blink reflex as a means of identifying the precise moment of loss of responsiveness. Twenty-five patients received a slow infusion of propofol until loss of corneal reflex while successive blink reflexes were elicited and recorded every 6 s. The level of anesthesia was assessed using an adapted version of the Richmond Agitation-Sedation Scale. Different variables of the blink reflex components were calculated and compared to the adapted version of the Richmond Agitation-Sedation score and the estimated effect-site propofol concentration. Baselines of the blink reflex responses were similar to those in literature. After propofol infusion started, the most susceptible component of the blink reflex to propofol was R2 (EC50 = 1.358 (95% CI 1.321, 1.396) µg/mL) and the most resistant was R1 (EC50 = 3.025 (95% CI 2.960, 3.090) µg/mL). Most of the patients (24 out of 25) lost the R1 component when they were still responsive to shaking and shouting and corneal reflex could be elicited clinically (time = 102.48 ± 33.00 s). Habituation was present in R2 but not in R1. The R1 component of the blink reflex was found to have a strong correlation with the adapted version of the Richmond Agitation-Sedation Scale, with amplitude correlating better than areas (ρ = - 0.721 (0.123) versus ρ = - 0.688 (0.165)). We found a strong correlation between the R1 component with the estimated propofol effect-site concentration, with amplitude correlating better than areas (ρ = - 0.838 (0.113) versus ρ = - 0.823 (0.153)) and between the clinical scale and the propofol concentration (ρ = 0.856 (0.060)). The area and amplitude of the R1 component showed to be indicators of predicting different levels of anesthesia (Pk = 0.672 (0.183) versus Pk = 0.709 (0.134)) and these are connected to the propofol concentrations (Pk = 0.593 (0.10)). Our results suggest that electrically evoked blink reflex could be used during the induction of anesthesia as a surrogate of the Richmond Agitation-Sedation Scale to provide an objective endpoint as far as a - 4. At this point, at the moment of loss of R1, the propofol infusion may be stopped, as overshooting increases slightly the effect-site concentration afterward and eventually reaching loss of responsiveness. If the desired target is not achieved, the infusion can then be resumed.
- Comparison of two pharmacokinetic–pharmacodynamic models of rocuronium bromide during profound neuromuscular block: analysis of estimated and measured post-tetanic count effectPublication . Couto, Mafalda; Vide, Sérgio; Marco-Ariño, Nicolás; Troconiz, Iñaki F.; Esteves, Simão; Nunes, Catarina S.; Amorim, Pedro; Mendes, JoaquimBackground: Profound neuromuscular block (NMB) is important in surgeries where complete immobility is considered essential to improve tracheal intubation and surgical conditions. Rocuronium bromide is a commonly used NMB agent. This work describes a noninvasive approach for estimation of post-tetanic count (PTC) based on two pharmacokinetic (PK) models, the Saldien and the De Haes models. The aim was to investigate the rocuronium bromide PKepharmacodynamic (PD) relationship in estimating the PTC effect during profound NMB. Methods: In this prospective, non-randomised, observational study, an induction bolus of rocuronium bromide was administered followed by continuous infusion for maintenance of a PTC of 1-2. measured every 3 min. Measurements were analysed as discrete categorical data and by applying the nonlinear mixed-effect modelling approach. Performance of the selected models was evaluated through simulation model-based diagnostics, further assessing the precision of the parameter estimates and the performance of the models at the individual level. Results: Data from 30 adult patients undergoing elective abdominal or neurosurgical procedures were included. Posttetanic count response profiles during rocuronium bromide infusion were successfully characterised using the population PD analysis. The models showed a good performance for all PTC categories, albeit with a moderate over-prediction of PTC >6. Conclusions: Our findings indicate that using plasma concentrations of rocuronium bromide estimated with either of the two models, combined with a PD model, provides equal model performance when predicting PTC. These promising results may provide an important advance in guiding rocuronium bromide administration when profound NMB in routine clinical practice is desired.
- Implementation of neural networks to frontal electroencephalography for the identification of the transition responsiveness/unresponsiveness during induction of general anesthesiaPublication . Ferreira, Ana Isabel Leitão; Vide, Sérgio; Nunes, Catarina S.; Neto, Joaquim; Amorim, Pedro; Mendes, JoaquimObjective: General anesthesia is a reversible drug-induced state of altered arousal characterized by loss of responsiveness (LOR) due to brainstem inactivation. Precise identification of the LOR during the induction of general anesthesia is extremely important to provide personalized information on anesthetic requirements and could help maintain an adequate level of anesthesia throughout surgery, ensuring safe and effective care and balancing the avoidance of intraoperative awareness and overdose. So, main objective of this paper was to investigate whether a Convolutional Neural Network (CNN) applied to bilateral frontal electroencephalography (EEG) dataset recorded from patients during opioid-propofol anesthetic procedures identified the exact moment of LOR. Material and methods: A clinical protocol was designed to allow for the characterization of different clinical endpoints throughout the transition to unresponsiveness. Fifty (50) patients were enrolled in the study and data from all was included in the final dataset analysis. While under a constant estimated effect-site concentration of 2.5 ng/mL of remifentanil, an 1% propofol infusion was started at 3.3 mL//h until LOR. The level of responsiveness was assessed by an anesthesiologist every six seconds using a modified version of the Richmond Agitation-Sedation Scale (aRASS). The frontal EEG was acquired using a bilateral bispectral (BIS VISTA (TM) v2.0, Medtronic, Ireland) sensor. EEG data was then split into 5-second epochs, and for each epoch, the anesthesiologist's classification was used to label it as responsiveness (no-LOR) or unresponsiveness (LOR). All 5-second epochs were then used as inputs for the CNN model to classify the untrained segment as no-LOR or LOR. Results: The CNN model was able to identify the transition from no-LOR to LOR successfully, achieving 97.90 +/- 0.07% accuracy on the cross-validation set. Conclusion: The obtained results showed that the proposed CNN model was quite efficient in the responsiveness/unresponsiveness classification. We consider our approach constitutes an additional technique to the current methods used in the daily clinical setting where LOR is identified by the loss of response to verbal commands or mechanical stimulus. We therefore hypothesized that automated EEG analysis could be a useful tool to detect the moment of LOR, especially using machine learning approaches.
- Systematic review on Rocuronium continuous infusion for deep neuromuscular blockadePublication . Couto, Mafalda; Couto, J. Guilherme; Nunes, Catarina S.; Vide, Sérgio; Amorim, Pedro; Mendes, JoaquimBackground: Rocuronium is a muscle relaxant with increased use due to its binding relation with the reversal agent sugammadex. The purpose of this review entails the investigation of its use for the maintenance of Deep Neuromuscular Block (NMB) via continuous infusion. Methods: Based on PRISMA systematic search guidelines, databases included PubMed, ISI Web of Science, Cochrane Library and Google Scholar. This comprehensive search addresses surgical patients under deep muscle relaxation via continuous rocuronium infusion. The main indicators were the rocuronium administration, NMB monitoring approaches and effects in order to maintain the deep level of relaxation, as well as reversal time after a standard dose of sugammadex. Results: Despite the variance in approaches found in the literature, findings show the overall maintenance of deep NMB requires approximately 0.758 mg.kg-1h-1 of rocuronium (according to the PTC target of 0-10, 0-5 and 1-2, mean estimates are 0.445, 0.65 and 0.833 mg.kg-1h-1 respectively), suggesting that a lower range and a smaller maximum of PTC response require higher amount of rocuronium for its maintenance. The standard dose of sugammadex (4 mg/kg), administered at the end of the surgery takes longer [2.85 (1.17) min] than when they are administered after moderate NMB recovery [1.68 (0.47) min]. Conclusion: Continuous infusion for deep NMB presents inherent advantages in terms of maintenance and stability of muscle relaxation. Monitoring and rocuronium administration approaches are fundamental and intrinsically connected to provide a stable and improved maintenance of deep NMB.
- Hypnotic effect: inducing unconsciousness and emergence from anaesthesiaPublication . Vide, Sérgio; Nunes, Catarina S.; Amorim, Pedro
- Patterns of hysteresis between induction and emergence of neuroanesthesia are present in spinal and intracranial surgeriesPublication . Ferreira, Ana Isabel Leitão; Correia, Rui; Vide, Sérgio; Ferreira, Ana Dias; Kelz, Max B.; Mendes, Joaquim; Nunes, Catarina S.; Amorim, PedroRecovery of consciousness is usually seen as a passive process, with emergence from anesthesia depicted as the inverse process of induction resulting from the elimination of anesthetic drugs from their central nervous system sites of action. However, that need not be the case. Recently it has been argued that we might encounter hysteresis to changes in the state of consciousness, known as neural inertia. This phenomenon has been debated in neuroanesthesia, as manipulation of the brain might further influence recovery of consciousness. The present study is aimed at assessing hysteresis between induction and emergence under propofol-opioid neuroanesthesia in humans using estimated propofol concentrations in both spinal and intracranial surgeries.
- Foreseeing postoperative pain in neurosurgical patients: pupillometry predicts postoperative pain ratings: an observational studyPublication . Vide, Sérgio; Castro, Ana; Correia, Rui; Cabral, Tiago; Lima, Deolinda; Nunes, Catarina S.; Gambús, Pedro; Amorim, PedroPupillary reflex dilation (PRD) is triggered by noxious stimuli and diminished by opioid administration. In the postoperative period, PRD has been shown to be correlated with pain reporting and a useful tool to guide opioid administration. In this study we assessed whether pupillary measurements taken before extubation were related with the patient's reported pain in the Post-Anesthesia Care Unit (PACU) using the Numerical Rating Scale (NRS). Our objective was to evaluate the correlation of PRD and pupillary variables measured intraoperatively with postoperative pain under the same opioid concentration. This was a prospective observational study of 26 neurosurgical patients undergoing general anesthesia exclusively with propofol and remifentanil. A portable infrared pupillometer was used to provide an objective measure of pupil size and PRD (using the Pupillary Pain Index) before extubation. Pain ratings were obtained from patients after recovery of consciousness, while remifentanil was maintained at 2 ng/mL. A significant correlation was observed between NRS scores and pre-extubation PPI (rS = 0.62; P = 0.002), as well as between NRS scores and pupil diameter before tetanic stimulation PPI (rS = 0.56, P = 0.006). We also found a negative correlation between pupil diameter and age (rS = - 0.42, P = 0.04). The statistically significant correlation between pre-extubation PPI scores and NRS scores, as well as between the pupillary diameter before tetanic stimulation and NRS scores suggest the possibility of titrating analgesia at the end of the intraoperative period based on individual responses. This could allow clinicians to identify the ideal remifentanil concentration for the postoperative period.
- Performance of blink reflex in patients during anesthesia induction with propofol and remifentanil: prediction probabilities and multinomial logistic analysisPublication . Ferreira, Ana Isabel Leitão; Vide, Sérgio; Felgueiras, João; Cardoso, Márcio; Amorim, Pedro; Mendes, Joaquim; Nunes, Catarina S.The amount of propofol needed to induce loss of responsiveness varied widely among patients, and they usually required less than the initial dose recommended by the drug package inserts. Identifying precisely the moment of loss of responsiveness will determine the amount of propofol each patient needs. Currently, methods to decide the exact moment of loss of responsiveness are based on subjective analysis, and the monitors that use objective methods fail in precision. Based on previous studies, we believe that the blink reflex can be useful to characterize, more objectively, the transition from responsiveness to unresponsiveness. The purpose of this study is to investigate the relation between the electrically evoked blink reflex and the level of sedation/anesthesia measured with an adapted version of the Richmond Agitation-Sedation Scale, during the induction phase of general anesthesia with propofol and remifentanil. Adding the blink reflex to other variables may allow a more objective assessment of the exact moment of loss of responsiveness and a more personalized approach to anesthesia induction.