Neuromuscular Blockade Monitoring: Having It but Knowing When Not to Trust It.

Butyrylcholinesterase (BChE) is an enzyme involved in the degradation of depolarizing and non-depolarizing neuromuscular blocking agents (NMBA), such as succinylcholine and mivacurium, respectively. Its deficiency is inherited or acquired, and results in paralysis of skeletal muscles after NMBA administration. We report a case of a 32-year-old pregnant woman proposed for cesarean section. General anesthesia (GA) was induced using propofol and succinylcholine. The surgical procedure was uneventful but after 40 minutes, there was no reversal of neuromuscular block (NMB). Other differential diagnoses were excluded and a deficit of BChe was assumed. When the train-of-four ratio (TOFr) achieved 40%, neostigmine/atropine led to the slow recovery of NMB up to TOFr 88%. The patient was extubated, but ventilation proved ineffective, so GA was induced and the patient was reintubated. A new measurement found a TOFr of 60%. Sedation and ventilatory support were maintained until the complete reversal of NMB (4 hours after succinylcholine). Prolonged block is a rare but serious complication of the use of succinylcholine in patients with BChE deficiency. This report not only highlights the importance of intraoperative NMB monitoring in homozygotic patients for atypical cholinesterase but also raises awareness for its careful interpretation.

Incidence of postoperative residual neuromuscular blockade - A multicenter, observational study in Portugal (INSPIRE 2).

Background: Although the use of neuromuscular blocking agents (NMBAs) optimizes surgical conditions and facilitates tracheal intubation, it can lead to residual neuromuscular blockade (RNMB), with postoperative complications. This study aimed to assess RNMB incidence and management in Portugal. Methods: Prospective observational study of patients admitted for elective surgery requiring general anesthesia with nondepolarizing NMBAs between July 2018 and July 2019 at 10 Portuguese hospitals. The primary endpoint was the proportion of patients arriving at postanesthesia care unit (PACU) with a TOF ratio <0.9. Results: A total of 366 patients were included, with a median age of 59 years, and 89.1% classified as ASA II or III. Rocuronium was the most used NMBA (99.5%). A total of 96.2% of patients received a reversal agent, 96.6% of which sugammadex and 3.4% neostigmine. Twenty patients displayed a TOF ratio <0.9 at PACU arrival, representing an RNMB incidence of 5.5% (95% CI, 3.1%-7.8%). Only two patients displayed a TOF ratio <0.7. RNMB incidence was 16.7% with neostigmine and 5.3% with sugammadex (P = .114). In patients with intraoperative neuromuscular blockade (NMB) monitoring, RNMB incidence was 5% (95% CI, 2%-8%), which varied significantly according to the type of monitoring (P = .018). Incidence of adverse events was 3.3% (2 severe and 10 moderate). Conclusions: The reported overall incidence of 5.5% is numerically lower than results from similar observational studies. An appropriate pharmacological neuromuscular reversal strategy, guided by quantitative neuromuscular monitoring, has the potential to achieve even better results, converting RNMB from an unusual to a very rare or even inexistent event.

Comparison of two pharmacokinetic-pharmacodynamic models of rocuronium bromide during profound neuromuscular block: analysis of estimated and measured post-tetanic count effect.

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 PK-pharmacodynamic (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. Post-tetanic 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.

Validation of the Portuguese Version of the Postoperative Quality Recovery Scale (PostopQRS).

INTRODUCTION: The Postoperative Quality Recovery Scale is a brief instrument of six domains designed to assess quality of recovery from early to long term after surgery. This study aims to validate the Portuguese version of the Postoperative Quality Recovery Scale. MATERIAL AND METHODS: In this observational study 101 adult patients undergoing elective surgery completed the Postoperative Quality Recovery Scale at 15 minutes and 40 minutes, one and three days after surgery. Three constructs were assessed for validity: increased recovery over time; effect of gender and recovery association with muscle strength. Reliability, responsiveness, feasibility and acceptability were also assessed. RESULTS: Construct validity was shown by increased recovery over time; worse recovery for female patients in emotive, nociceptive, activities of daily living and overall recovery; improved muscle strength in recovered patients. Internal consistency for activities of daily living was acceptable at all-time points (Cronbach's α value of 0.772 or higher), indicating scale reliability. The scale was able to detect differences in postoperative quality of recovery between the neuromuscular blockade reversal agents, neostigmine and sugammadex, indicating scale responsiveness. The time to conduct the Portuguese version at baseline was 95 - 581 seconds (median 319 seconds) and it was reduced with subsequent assessments. The proportion of patients completing all scale items was 87%, 75%, 65% and 94% for the four time periods evaluated, indicating scale feasibility and acceptability. DISCUSSION: This study shows that the Portuguese version of the Postoperative Quality Recovery Scale, demonstrates construct validity, reliability, responsiveness, feasibility and acceptability. CONCLUSIONS: This study allowed validation of the Portuguese version of the Postoperative Quality Recovery Scale.

Introdução: A Escala da Qualidade da Recuperação Pós-Operatória é um instrumento de seis domínios, desenhada para avaliar a qualidade da recuperação no período pós-operatório precoce e tardio. Este estudo teve como objetivo validar a versão portuguesa da Escala da Qualidade da Recuperação Pós-Operatória. Material e Métodos: Neste estudo observacional foi obtida uma amostra de 101 doentes adultos submetidos a cirurgia eletiva e que preencheu a Escala da Qualidade da Recuperação Pós-Operatória aos 15 e 40 minutos, um e três dias após a cirurgia. Três teorias foram avaliadas para aferir a validade teórica da escala: aumento da recuperação ao longo do tempo, efeito do género e a associação da recuperação com a força muscular. Foram também avaliadas a fiabilidade, poder de resposta, viabilidade e aceitabilidade. Resultados: A validade teórica foi demonstrada pelo aumento da recuperação ao longo do tempo, assim como uma pior recuperação para doentes do sexo feminino em atividades emotivas, nociceptivas, diárias e de recuperação geral. Detetou-se ainda uma melhoria da força muscular em doentes recuperados. A coerência interna no domínio das atividades da vida diária foi aceitável em todos os tempos (valor α de Cronbach de 0,772 ou superior), indicando a fiabilidade da escala. Com esta escala foi possível detetar diferenças na qualidade pós-operatória da recuperação entre os agentes de reversão de bloqueio neuromuscular, a neostigmina e o sugammadex, indicando que a escala apresenta poder de resposta. O tempo para aplicar a versão portuguesa no período inicial (baseline) foi de 95 - 581 segundos (mediana 319 segundos) com uma diminuição em avaliações subsequentes. A proporção de doentes que completaram todos os itens da escala foi de 87%, 75%, 65% e 94% nos quatro períodos avaliados, indicando viabilidade e aceitabilidade da escala. Discussão: A versão portuguesa da Escala da Qualidade da Recuperação Pós-Operatória demonstrou ter validade, fiabilidade, poder de resposta, viabilidade e aceitabilidade. Conclusões: Este estudo permitiu a validação da versão Portuguesa da Escala da Qualidade da Recuperação Pós-Operatória.

Incidence of postoperative residual neuromuscular blockade in the postanaesthesia care unit: an observational multicentre study in Portugal.

CONTEXT: Residual neuromuscular blockade still presents despite the use of intermediate duration muscle relaxants and is a risk factor for postoperative morbidity. OBJECTIVE: To determine the incidence of incomplete postoperative neuromuscular recovery from anaesthesia in a postanaesthesia care unit. DESIGN: Multicentre observational study. SETTING: Public Portuguese hospitals. PATIENTS: Adult patients scheduled for elective surgery requiring general anaesthesia with neuromuscular blocking agents. MAIN OUTCOME MEASURES: An independent anaesthesiologist measured neuromuscular transmission by the TOF-Watch SX acceleromyograph. Train-of-four ratios at least 0.9 and less than 0.9 were assessed as complete and incomplete neuromuscular recovery following general anaesthesia, respectively. RESULTS: The study population consisted of 350 patients [134 men and 216 women, mean (SD) age 54.3 (15.9) years]. Ninety-one patients had a train-of-four ratio less than 0.9 on arrival in the postanaesthesia care unit, an incidence of residual neuromuscular blockade of 26% [95% confidence interval (CI) 21 to 31%]. The most frequent neuromuscular blockers were rocuronium (44.2%) and cisatracurium (32%). A neuromuscular block reversal agent was used in 66.6% of the patients (neostigmine in 97%). The incidence of residual neuromuscular blockade in patients receiving reversal agents was 30% (95% CI 25 to 37%). There were no statistically significant differences in the occurrence of residual blockade relating to the neuromuscular blocker used, although higher percentages were observed for cisatracurium (32.4%) and vecuronium (32%) compared with atracurium (23.6%) and rocuronium (20.8%). Incomplete neuromuscular recovery was significantly more frequent among patients who had received a reversal agent (30.5 vs. 17.1%, P = 0.01). Incomplete neuromuscular recovery was more frequent in patients given propofol than in those exposed to sevoflurane (26.2 vs. 14.3%). CONCLUSION: The incidence of incomplete neuromuscular recovery of 26% confirms that it is relatively frequent in the postoperative period and calls attention to the dimension of this problem in Portugal.

Personalized neuromuscular blockade through control: clinical and technical evaluation.

This paper presents a statistical analysis of clinical data collected in surgeries under automatic closed-loop control of neuromuscular blockade. Four different control strategies have been applied in patients undergoing elective surgeries and clinical and technical evaluations of the control system were performed. Both transient and steady-state behaviour were analysed in detail and clearly suggest an automatic control approach relying on the information about the patient dynamics. The results can be a valuable start point to design personalized drug infusion control in anaesthesia.

Observer design in switching control of neuromuscular blockade: clinical cases.

This paper concerns the application of multiple model switched methods to the control of neuromuscular blockade of patients undergoing anaesthesia. Since the model representing the neuromuscular blockade process is subject to a high level of uncertainty due both to inter-patient variability and time variations, switched methods provide the adaptation capability needed to achieve the desired performance. The paper contributions are twofold: first, it is shown that, for the type of process control problem considered, the design of the associated observer must be carefully performed. Guidelines are provided for adequate selection of the characteristic polynomial defining the observer error dynamics. Second, clinical results using atracurium as blocking agent are reported in order to illustrate the use of the proposed control structure in actual clinical practice.

Hipocrates: a robust system for the control of neuromuscular blockade.

OBJECTIVE: Development of an automatic system (software package Hipocrates) for the control of neuromuscular blockade by continuous infusion of the non-depolarising types of muscle relaxant drugs presently used in anaesthesia, namely atracurium, cisatracurium, vecuronium and rocuronium. METHODS: Hipocrates incorporates control strategies based upon classical, adaptive and robust control, as well as a wide range of noise reduction techniques and on-line adaptation to patient-specific characteristics. Therefore, the system provides strong robustness to inter- and intra-individual variability of the patients responses or unexpected circumstances and adaptation to the individual requirements. RESULTS: The control system is easy to set up and to use in a clinical environment. It consists of a portable PC computer, a Datex AS/3 NMT sensor and a B/Braun compact perfusion pump. In the simulation mode the software package incorporates sophisticated generation of pharmacokinetic/pharmacodynamic models driven by simulated drug administration regimes (bolus, continuous infusion and a combination of both). CONCLUSIONS: Hipocrates is an advanced standalone application for the control of neuromuscular blockade with a friendly graphic interface. It has been extensively validated, and it can be used on patients undergoing surgery as well as for simulation studies. Therefore Hipocrates also provides an excellent environment for education and training purposes.