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  • Comparison of two pharmacokinetic–pharmacodynamic models of rocuronium bromide during profound neuromuscular block: analysis of estimated and measured post-tetanic count effect
    Publication . Couto, Mafalda; Vide, Sérgio; Marco-Ariño, Nicolás; Troconiz, Iñaki F.; Esteves, Simão; Nunes, Catarina S.; Amorim, Pedro; Mendes, Joaquim
    Background: 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.
  • TOF-Watch NMB monitoring misleading display output during moderate neuromuscular blockade
    Publication . Couto, Mafalda; Nunes, Catarina S.; Amorim, Pedro; Mendes, Joaquim
    In general anesthesia, Neuromuscular Blockade (NMB) agents are administered to ensure intubation quality and complete immobilization. Monitoring NMB, based on the evoked response evaluation after a peripheral nerve stimulation, is essential to provide insight on medication dosing and suitable approaches for NMB reversal. Professionals often rely on the data displayed on the monitor screen after TOF stimuli, assuming measurements present the expected fade and a TOF-ratio > 90% is enough to rule out residual paralysis. This can be inaccurate and mislead the clinician to extubate before adequate NMB curarization. Data from 31 patients that underwent general anesthesia were retrospectively analyzed. All patients received a standard dose of rocuronium (0.6 mg/kg) for intubation, during maintenance additional rocuronium boluses were administered if solicited. NMB monitoring was done continuously applying TOF stimuli at the adductor pollicis with TOF-Watch SX®. Two types of monitoring display errors were studied: (1) valid TOF value without fade effect (invalid T1 > T2 > T3 > T4); (2) in the 30 min before extubation a valid TOF-ratio value > 90% (without error type 1) with T1 < 70%. Results show a mean (SD) of type 1 error on 42.0 (17.5)% of valid TOF measurements, type 2 error in 63 (45)%. Only 9 patients (29%) presented a TOF with no errors before extubation. These results may increase the distrust in the NMB monitoring devices, however its use should not be rejected when NMB agents are administered. Careful evaluation of the NMB is recommended and additional efforts should be placed in the accuracy of monitors data display to avoid errors.
  • Systematic review on Rocuronium continuous infusion for deep neuromuscular blockade
    Publication . Couto, Mafalda; Couto, J. Guilherme; Nunes, Catarina S.; Vide, Sérgio; Amorim, Pedro; Mendes, Joaquim
    Background: 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.
  • Rocuronium continuous infusion for profound neuromuscular blockade: a systematic review and meta-analysis
    Publication . Couto, Mafalda; Nunes, Catarina S.; Vide, Sérgio; Amorim, Pedro; Mendes, Joaquim
    Rocuronium is a muscle relaxant with increased use, because of the binding relation with the reversal agent sugammadex. Its continuous infusion benefits the maintenance of deeper levels of neuromuscular blockade (NMB) ensuring an improved and stable solution for daily surgical anesthesia. This is systematic review on current approaches on rocuronium infusion and monitoring parameters when using rocuronium continuous infusion for profound muscle relaxation (0-2 posttetanic count).