Monitoring of residual cisatracurium besylate in elderly patients plasma at post operation by UPLC-MS/MS / 药学实践杂志

Objective To establish a method for the determination of cisatracurium besylate in human plasma by UPLC-MS/MS which could be used in the monitoring of drug residual in plasma of elderly patients after operation. Methods The samples were precipitated with 0.1% formic acid-acetonitrile solution and separated by an SHISEIDO ADME column(3.0 mm×100 mm, 2.7 μm) for isocratic elution with the mobile phase of water containing 0.1% formic acid with 2 mmol/L ammonium acetate and acetonitrile (30:70, V/V). MS condition was optimized in the positive ion detection mode by multiple reaction monitoring (MRM), along with the Agilent jet stream electrospray source interface (AJS-ESI). The precursors to the product ion transitions were m/z 464.3→358.2 for cisatracurium besylate and m/z 557.4→356.3 for vecuronium bromide (the internal standard, IS). Plasma samples of elderly patients undergoing spinal surgery were collected after anesthesia induction, at the end of surgery, 0.5 h and 1 h after surgery, and from the blood bags while autologous blood transfusion, and stored in cryopreservation tubes with 2% formic acid solution. Then the contents of cisatracurium besylate were determined. The effects of autogenous blood transfusion on plasma concentration of cisatracurium besylate in elderly patients after surgery evaluated. Results The calibration curve was linear in the range of 20-5 000 ng/ml for cisatracurium besylate in human plasma, r=0.999 7. The intra-day and inter-day precision and accuracy were good (RSD<10%, RE<±10%). The matrix effect of different concentrations was 71.88%~80.64%. The recovery of different concentrations was 83.62%~88.87%. The recovery of vecuronium bromide (IS) was 125.91%, which conformed with the requirement of methodological validation. There was a certain degree of residual cisatracurium besylate in the plasma of elderly patients, so the extubation time should be strictly controlled and the stay time of patients in the anesthesia recovery room should be appropriately extended. Conclusion The method is sensitive, accurate, and efficient, which could be used for the determination of cisatracurium besylate in human plasma of elderly patients after operation.

Research of Perioperative Muscle Relaxant Monitor / 中国医疗器械杂志

Muscle relaxant monitor is a research hotspot in the field of clinical anesthesiology. According to the research status at home and abroad, combing the developing history of muscle relaxant monitor, detecting principle, a variety of electrical stimulation mode, and a variety of detection ways, this study reviews and analyzes the advantages and disadvantages of various testing methods and application status, provides technical research foundation for the degree of nerve block for quantitative assessment of muscle relaxant monitor instrument design. Meanwhile, we advocate that clinicians should use quantitative muscle relaxant monitor as much as possible in the perioperative period to reasonably guide the use of muscle relaxants so as to reduce the risk of complications caused by residual effects of muscle relaxants and provide more scientific and accurate digital guidance for assessing the degree of muscle relaxants of patients.

Use of protocol and evaluation of postoperative residual curarization incidence in the absence of intraoperative acceleromyography - Randomized clinical trial / Aplicação de protocolo e avaliação da incidência de curarização residual pós-operatória na ausência de aceleromiografia intraoperatória - Ensaio clínico randomizado

Abstract Objective Evaluate the incidence of postoperative residual curarization (PORC) in the post-anesthesia care unit (PACU) after the use of protocol and absence of intraoperative acceleromyography (AMG). Methods Randomized clinical trial with 122 patients allocated into two groups (protocol and control). Protocol group received initial and additional doses of rocuronium (0.6 mg·kg-1 and 10 mg, respectively); the use of rocuronium was avoided in the final 45 min; blockade reversal with neostigmine (50 µg·kg-1); time ≥15 min between reversion and extubation. Control: initial and additional doses of rocuronium, blockade reversal, neostigmine dose, and extubation time, all at the discretion of the anesthesiologist. AMG was used in the PACU and PORC considered at T4/T1 ratio <1.0. Results The incidence of PORC was lower in protocol group than in control group (25% vs. 45.2%, p = 0.02). In control group, total dose of rocuronium was higher in patients with PORC than without PORC (0.43 vs. 0.35 mg·kg-1·h-1, p = 0.03) and the time interval between the last administration of rocuronium and neostigmine was lower (75.0 vs. 101.0 min, p < 0.01). In protocol group, there was no difference regarding the analyzed parameters (with PORC vs. without PORC). Considering the entire study population and the presence or absence of PORC, total dose of rocuronium was higher in patients with PORC (0.42 vs. 0.31 mg·kg-1·h-1, p = 0.01), while the time interval between the last administration of rocuronium and neostigmine was lower (72.5 vs. 99.0 min, p ≤ 0.01). Conclusion The proposed systematization reduced PORC incidence in PACU in the absence of intraoperative AMG.

Resumo Objetivo Avaliou-se a incidência de curarização residual pós-operatória (CRPO) na sala de recuperação pós-anestésica (SRPA) após emprego de protocolo e ausência de aceleromiografia (AMG) intraoperatória. Métodos Ensaio clínico, aleatório, com 122 pacientes, distribuídas em dois grupos: protocolo e controle. Protocolo: dose inicial e adicionais de rocurônio foram de 0,6 mg.kg-1 e 10 mg, respectivamente; evitou-se o uso de rocurônio nos 45 minutos finais; reversão do bloqueio com neostigmina (50 µg.kg-1); tempo ≥ 15 minutos entre reversão e extubação. Controle: doses inicial e adicional de rocurônio, reversão do bloqueio, dose de neostigmina e momento da extubação decididos pelo anestesiologista. Foi usada AMG na SRPA e considerado CRPO razão T4/T1 < 1,0. Resultados A incidência de CRPO foi menor no grupo protocolo em relação ao controle (25% vs. 45,2%; p = 0,02). No grupo controle, a dose total de rocurônio foi maior em pacientes com CRPO em relação àqueles sem CRPO (0,43 vs. 0,35 mg.kg-1.h-1; p = 0,03) e o intervalo entre a última administração de rocurônio e a neostigmina foi menor (75,0 vs. 101,0 min; p < 0,01). No grupo protocolo não houve diferença dos parâmetros analisados (com CRPO vs. sem CRPO). Considerando toda a população de estudo e a presença ou não de CRPO, a dose total de rocurônio foi maior em pacientes com CRPO (0,42 vs. 0,31 mg.kg-1.h-1; p = 0,01), enquanto o intervalo entre a última administração de rocurônio e a neostigmina foi menor (72,5 vs. 99,0 min; p ≤ 0,01). Conclusão A sistematização proposta reduziu a incidência de CRPO na SRPA na ausência de AMG intraoperatória.

What anesthesiologists ask to know and should know about the neuromuscular monitoring: an updated review

The increase in mortality and morbidity associated with the use of muscle relaxants, is associated with a lack of clinical pharmacological knowledge of the drugs, and a lack of understanding the risk of postoperative residual curarization. This is due to the absence of standards for neuromuscular monitoring. Clinicians experienced in neuromuscular monitoring and using muscle relaxants in the clinic may have some queries regarding the monitoring: Why should neuromuscular monitoring be done? Are clinical tests really not effective? Why is it not good when I actually perform neuromuscular monitoring? Would using sugammadex not require neuromuscular monitoring? This review answers most of the questions that many clinicians have, and also forwards the knowledge required of clinicians.

Survey of postoperative residual curarization, acute respiratory events and approach of anesthesiologists / Pesquisa de curarização residual no pós-operatório, eventos respiratórios agudos e abordagem de anestesiologistas

BACKGROUND AND OBJECTIVES: residual paralysis following the use of neuromuscular blocking drugs (NMBDs) without neuromuscular monitoring remains a clinical problem, even when NMBDs are used. This study surveys postoperative residual curarization and critical respiratory events in the recovery room, as well as the clinical approach to PORC of anesthesiologists in our institution. METHODS: This observational study included 415 patients who received general anesthesia with intermediate-acting NMBDs. Anesthesia was maintained by non-participating anesthesiologists who were blinded to the study. Neuromuscular monitoring was performed upon arrival in the recovery room. A CRE was defined as requiring airway support, peripheral oxygen saturation <90% and 90-93% despite receiving 3 L/min nasal O2, respiratory rate >20 breaths/min, accessory muscle usage, difficulty with swallowing or speaking, and requiring reintubation. The clinical approach of our anesthesiologists toward reversal agents was examined using an 8-question mini-survey shortly after the study. RESULTS: The incidence of PORC was 43% (n = 179) for TOFR <0.9, and 15% (n = 61) for TOFR <0.7. The incidence of TOFR <0.9 was significantly higher in women, in those with ASA physical status 3, and with anesthesia of short duration (p < 0.05). In addition, 66% (n = 272) of the 415 patients arriving at the recovery room had received neostigmine. A TOFR <0.9 was found in 46% (n = 126) of the patients receiving neostigmine. CONCLUSIONS: When routine objective neuromuscular monitoring is not available, PORC remains a clinical problem despite the use of NMBDs. The timing and optimal antagonism of the neuromuscular blockade, and routine objective neuromuscular monitoring is recommended to enhance patient safety.

JUSTIFICATIVA E OBJETIVOS: A paralisia residual após o uso de bloqueadores neuromusculares (BNMs) sem monitoração neuromuscular continua sendo um problema clínico, mesmo quando BNMs são usados. Este estudo pesquisou a curarização residual pós-operatória e os eventos respiratórios críticos em sala de recuperação, bem como a abordagem clínica da CRPO feita pelos anestesiologistas em nossa instituição. MÉTODOS: Este estudo observacional incluiu 415 pacientes que receberam anestesia geral com BNMs de ação intermediária. A manutenção da anestesia foi feita por anestesiologistas não participantes, "cegos" para o estudo. A monitoração neuromuscular foi realizada no momento da chegada à sala de recuperação. Um ERC foi definido como necessidade de suporte ventilatório; saturação periférica de oxigênio <90% e 90-93%, a despeito de receber 3 L/min de O2 via cânula nasal; frequência respiratória >20 bpm; uso de musculatura acessória; dificuldade de engolir ou falar e necessidade de reintubação. A abordagem clínica de nossos anestesiologistas, em relação aos agentes de reversão, foi avaliada usando um miniquestionário de oito perguntas logo após o estudo. RESULTADOS: A incidência de CRPO foi de 43% (n = 179) para a SQE <0 e 15% (n = 61) para a SQE <0,7. A incidência de SQE <0,9 foi significativamente maior em mulheres, pacientes com estado físico ASA III e com anestesia de curta duração (p < 0,05). Além disso, 66% (n = 272) dos 415 pacientes que chegam à sala de recuperação haviam recebido neostigmina. Uma SQE <0,9 foi encontrada em 46% (n = 126) dos pacientes que receberam neostigmina. CONCLUSÃO: Quando a monitoração neuromuscular objetiva de rotina não está disponível, a CRPO continua sendo um problema clínico, a despeito do uso de BNMs. O momento e o antagonismo ideais do bloqueio neuromuscular e a monitoração neuromuscular objetiva de rotina são recomendados para aumentar a segurança do paciente.

Incidence and risk factors of postoperative residual curarization in patients with breast cancer: Prospective cohort study / 解放军医学杂志

Objective To determine the incidence and risk factors of postoperative residual curarization (PORC) in patients with breast cancer after total intravenous anesthesia (TIVA) with vecuronium. Methods Two hundred and fiftyseven female patients with breast cancer undergoing breast-cancer surgery were enrolled into the present study. Anesthesia was induced with target-controlled infusion of propofol (Cp 3-4µg/ml) and remifentanil (2-3 ng/ml). A bolus of vecuronium 0.1mg/ kg was administered intravenously over 5-10s as soon as the patient lost consciousness, and laryngeal mask was placed 3min later. Mechanical ventilation and TIVA were performed for maintaining anesthesia and keeping bispectral index (BIS) between 40 to 60 during the operation. According to the duration of operation, 0.02mg/kg of vecuronium was administrated intermittently. Extubation of the laryngeal tube was performed according to clinical criteria. Train-of-four ratios (TOFr) were immediately measured with Veryark-TOF (Guangzhou Weilifangzhou Technology Ltd, China) in the recovery room. The patients were divided into two groups (Group N and Group R) according to the value of TOFr at the time of extubation. N denoted the non-residual neuromuscular blockade group (TOF=0.7), and R denoted the residual neuromuscular blockade group (TOF0.05). In group R, age and hemoglobin level were lower (P0.05). More patients in Group R received neoadjuvant chemotherapy and multiple boluses of vecuronium administration, and the duration between last dose of vecuronium to extubation was also prolonged compared with Group N (P<0.05). Multivariate logistic regression analysis identified that age, neoadjuvant chemotherapy and multiple boluses of vecuronium administration were not associated with increased risk of PORC. Duration from last dose of vecuronium to extubation was associated with increased risk of PORC (OR=0.970, 95%CI 0.956-0.984, P<0.001). Conclusions PORC is commonly used in patients with breast cancer. Duration from last dose of vecuronium to extubation is associated with increased risk of PORC.

Comparison of recovery times from deep neuromuscular blockade between single bolus and continuous infusion of rocuronium

BACKGROUND: To prevent sudden unexpected movement of patients during surgery, muscle relaxants are used to maintain intense neuromuscular blockade.They are administered by intermittent bolus or continuous infusion.Rocuronium is often used for continuous infusion because it is known to lack cumulative effects. The purpose of this study was to compare recovery times from intense neuromuscular block to reappearance of muscle twitches after 0.1 Hz single twitch stimulation. MATERIALS AND METHODS: Seventy five patients were randomized to one of 3 groups.Patients in group 1 were administered a single bolus of rocuronium; groups 2 and 3 were given continuous infusion of rocuronium for 1 and 2 h, respectively.During anesthesia, neuromuscular blockade was monitored by TOF-watch(R) and regulated so as not to exceed more than 5 (PTC) during the infusion. After infusion, PTC was counted every 5 min until single twitch heights had reappeared and the time till the twitch reappeared was calculated. RESULTS: There was a good correlation between the time it took to observe a PTC and the first response of TOF time in each group.In a parallelism test, there were no significant differences. There were also no significant differences in recovery times from PTC to the reappearance of a single twitch between groups. CONCLUSIONS: There are no significant differences in recovery times-from deep neuromuscular blockade to reappearance of single twitch-regardless of the infusion time.When a PTC occurs during deep neuromuscular blockade, it may predict the remaining time of reappearance of a single twitch response.

Validity and reliability of head lift and tongue depressor test for diagnosis of the residual block

BACKGROUND: Head lift (HL) for 5 seconds and tongue depressor (TD) test have been used for diagnosis of the residual block after using the nondepolarizing muscle relaxants. We investigated validity and reliability of HL, TD, and both of them (HLTD). METHODS: Four-hundred-thirteen patients were enrolled in this study. Neuromuscular blockade was maintained with rocuronium and reversed with pyridostigmine and glycopyrrolate. TOF ratio was quantified by acceleromyograph in the recovery room. HL and TD test were performed in the patients who could respond to verbal command of the investigator. We analyzed the sensitivity, specificity, positive and negative predictive value, positive and negative likelihood ratio, area under the cure (AUC) from ROC analysis and kappa statistics. RESULTS: Prevalences of residual block were 13%, 32% and 78% at 0.7, 0.9 and 1.0 of TOF ratio cutoff value, respectively. Specificity was good for HL (79.7-86.8%), TD (94.2-97.8%) and HLTD (77.8-85.7%), but sensitivity was not. Positive predictive value was higher in TD than HL and HLTD, and negative predictive value was similar among them. Positive and negative likelihood ratio was higher in TD than HL and HLTD. AUC had no difference among HL, TD and LTD. Kappa statistics were showed minimal or moderate relationship between clinical test and train of four responses. CONCLUSIONS: We concluded that HL, TD and HLTD were not good tools for diagnosis of the residual block in a view of validity and reliability.

Postoperative Residual Curarization in the Recovery Room after Vecuronium or Rocuronium Use

BACKGROUND: Postoperative residual curarization subsequent to the use of neuromuscular blocking drugs can cause respiratory problems. This study examined the incidence of postoperative residual curarization on the arrival of patients in the recovery room. METHODS: Two-hundred-fifty-nine patients were enrolled in the study. The neuromuscular blockade was maintained with vecuronium or rocuronium and all subjects were reversed with pyridostigmine. The train of four ratios (TR) was quantified by acceleromyography immediately upon their arrival in the recovery room. The residual curarization was defined as a TR of 0.9 (104.5 +/- 51.1 min) patients. The total dose of muscle relaxants corrected by the ED95 was significantly different between TR or = 0.9 patients. The total dose of vecuronium or rocuronium, and the dose of pyridostimine was similar in the TR or = 0.9 patients. CONCLUSIONS: Significant postoperative residual curarization waspresent in the majority of patients, even with the use of intermediate- acting neuromuscular blocking drugs. In addition, the time from the last dose of muscle relaxants to the TR assessment in the recovery room is a major factor that affects the residual curarization.

Postoperative Residual Curarization either after Continuous Infusions or Intermittent Bolus of Rocuronium or Vecuronium / 대한마취과학회지

BACKGROUND: Although the incidence of postoperative residual curarization (PORC) following the use of intermediate-acting neuromuscular blocking agents is lower than that of longer-acting neuromuscular blocking agents, it has been reported in many studies. We compared the incidence of PORC following either rocuronium or vecuronium given by intermittent bolus or continuous infusion dosing. METHODS: Ninety-eight patients were included in this study. Neuromuscular blocking drugs were administered based solely on clinical criteria, and the reversal agent pyridostigmine was given to all patients. Residual block following rocuronium infusion (Group R-I), rocuronium bolus (Group R-B), vecuronium infusion (Group V-I), or vecuronium bolus dosing (Group V-B) was evaluated on arrival in the postanesthesia care unit. Neuromuscular function was assessed acceleromyographically (using TOF-Watch(R) to measure the train-of-four (TOF) ratio) and also clinically. PORC was defined as a TOF ratio of < 0.8. RESULTS: The incidence of PORC on arrival in the postanesthesia care unit was 20% in Group R-I, 23% in Group R-B, 42% in Group V-I, and 19% in Group V-B. Mean TOF ratio in Group V-I was less than those of the other groups (P < 0.05). CONCLUSIONS: PORC is still common following vecuronium or rocuronium, even after the block is antagonized, if neuromuscular blocking agents are administered according to clinical criteria alone.