Search

Background: Neuromuscular blocking agents (NMBAs) have been shown to improve the outcome of the most severely hypoxemic, acute respiratory distress syndrome (ARDS) patients. However, the recommended dosage as well as the necessity of monitoring the neuromuscular block is unknown. We aimed to evaluate the efficiency of a nurse-directed protocol of NMBA administration based on a train-of-four (TOF) assessment to ensure a profound neuromuscular block and decrease cisatracurium consumption compared to an elevated and constant dose regimen. A prospective open labeled study was conducted in two medical intensive care units of two French university hospitals. Consecutive ARDS patients with a PaO/FiO ratio less than 120 with a PEEP ≥5 cm HO were included. Cisatracurium administration was driven by the nurses according to an algorithm based on TOF monitoring. The primary endpoint was cisatracurium consumption. The secondary endpoints included the quality of the neuromuscular block, the occurrence of adverse events, and the evolution of ventilatory and blood gas parameters. Results: Thirty patients were included. NMBAs were used for 54 ± 30 h. According to this new algorithm, the initial dosage of cisatracurium was 11.8 ± 2 mg/h, and the final dosage was 14 ± 4 mg/h, which was significantly lower than in the ACURASYS study protocol (37.5 mg/h with a constant infusion rate ( p < 0.001). The overall cisatracurium dose used was 700 ± 470 mg in comparison with 2040 ± 1119 mg for patients had received the ACURASYS dosage for the same period ( p < 0.001). A profound neuromuscular block (TOF = 0, twitches at the ulnar site) was obtained from the first hour in 70% of patients. Modification of the cisatracurium dosage was not performed from the beginning to the end of the study in 60% of patients. Patient-ventilator asynchronies occurred in 4 patients. Conclusion: A nurse-driven protocol based on TOF monitoring for NMBA administration in ARDS patients was able to decrease cisatracurium consumption without significantly affecting the quality of the neuromuscular block. [ABSTRACT FROM AUTHOR]

Sepsis can often induce diaphragm dysfunction, which is associated with localized elaboration of cytokines within the diaphragm. The administration of cisatracurium has been shown to decrease the inflammatory response and to facilitate mechanical ventilation. In this study, we explored whether cisatracurium could attenuate sepsis-induced diaphragm dysfunction in rats. Animals were divided into three groups: (1) the control group: rats underwent a sham surgical procedure with cecal exposure, but the cecum was neither ligated nor punctured; (2) the CLP group: rats underwent cecal ligation and puncture (CLP) and received a continuous infusion of NaCl 0.9 %; and (3) the Cis + CLP group: rats underwent CLP and received a continuous infusion of cisatracurium. After the surgical procedure, all animals underwent controlled mechanical ventilation for 18 h. Plasma concentrations of interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), and high-mobility group box 1 (HMGB1) were measured using an enzyme-linked immunosorbent assay. Upon completion of the experimental protocol, diaphragm contractility and HMGB1 protein expression were analyzed. Impaired diaphragm contractile function, including both force-related properties and force-frequency responses, was pronounced after CLP in comparison with that observed in the control rats. Furthermore, CLP elevated serum levels of IL-6, TNF-α, and HMGB1, and induced HMGB1 protein expression in the diaphragm. In contrast, cisatracurium counteracted the sepsis-induced inflammation reaction in the diaphragm and serum and maintained diaphragm function. These data suggest that early infusion of cisatracurium attenuates sepsis-induced diaphragm dysfunction; this may be attributable to its anti-inflammatory action. [ABSTRACT FROM AUTHOR]

Background: During the induction of anesthesia, patients are at risk of aspiration while awaiting full muscle relaxation. Magnesium has been shown to have synergistic effects with neuromuscular blocking drugs. We tested if magnesium, as an adjunct, increases the speed of onset of muscle relaxation, thereby decreasing the risk of aspiration. Methods: Eighty-eight American Society of Anesthesiologists (ASA) physical status 1 or 2 patients were randomly assigned to three groups. Group Mg-0 received 100 mL of normal saline, whereas groups Mg-25 and Mg-50 received magnesium sulfate at doses of 25 and 50 mg/kg, respectively. Anesthesia was induced with thiopental 5 mg/kg and cisatracurium 0.15 mg/kg. A peripheral nerve stimulator and single-twitch test was performed on the ulnar nerve until the twitch responses to stimulation had disappeared, and the times were recorded. Then the patients were intubated and anesthesia was maintained with 100 μg/kg/min of propofol. The intensity of blockade was measured at regular time intervals with the post-tetanic count test. Results: The mean times to muscle relaxation in groups Mg-0, Mg-25, and Mg-50 were 226, 209, and 188 s, respectively ( P = 0.047). The intensity of the block increased with the dose of magnesium, and remained highest in group Mg-50 at all times measured ( P < 0.05). The speed of onset and the intensity of muscle relaxation increased as higher doses of magnesium were used. Conclusion: The increased speed of onset of muscle relaxation produced by magnesium is not substantial enough to justify its use in combination with cisatracurium in rapid sequence induction. [ABSTRACT FROM AUTHOR]

Objective: Dexmedetomidine is an α2-receptor agonist which is increasingly being used in coronary artery bypass grafting (CABG) surgery due to its suppressive effect on the stress responses against intubation and surgery. In this study effects of dexmedetomidine administration as an adjuvant agent during induction and maintenance of anesthesia on intraoperative hemodynamic changes were studied in patients undergoing CABG. Methods: A total of 20 patients undergoing CABG were included in the study. At the beginning dexmedetomidine infusion of 1 µg/kg body weight (BW)/h was performed for 10 min. After this the infusion dosage of dexmedetomidine was decreased to 0.2-0.4 µg/kgBW/h, 0.15 mg/kgBW of cisatracurium was administered for intubation and 0.5 MAC (minimum alveolar concentration) sevoflurane was administered as a volatile anesthetic. Heart rate (HR), mean arterial pressure (MAP), mean pulmonary artery pressure (MPAP), cardiac output (CO), systemic vascular resistance (SVR) and pulmonary vascular resistance (PVR) were recorded 10 min after dexmedetomidine infusion, following intubation, during skin incision and sternotomy, before and after the bypass and in the postoperative period. Results: With dexmedetomidine infusion HR and MAP were found to be moderately decreased in comparison to baseline values and no severe bradycardia or hypotension requiring intervention occurred. No increase in HR and MAP values were recorded during sternotomy and bypass. The MPAP evaluation showed no difference between the preoperative and intraoperative values (p>0.05). The cardiac output (CO) was found to be low starting from the time of skin incision to just before the bypass, compared to preoperative values (p<0.05) and SVR was moderately decreased with initial high dose infusion and after that increased to baseline values (p<0.05). Conclusion: Dexmedetomidine can be safely used in CABG operations delivering a stable hemodynamic status throughout the operative period. [ABSTRACT FROM AUTHOR]

We investigated whether presynaptic facilitatory M1 and/or inhibitory M2 muscarinic receptors contributed to pancuronium- and cisatracurium-induced tetanic fade. Phrenic nerve-diaphragm muscle preparations of rats were indirectly stimulated with tetanic frequency (75 ± 3.3 Hz; mean ± SD). Doses of pancuronium, cisatracurium, hexamethonium, and d-tubocurarine for producing approximately 25% fade were determined. The effects of pirenzepine and methoctramine, blockers of presynaptic M1 and M2 receptors, respectively, on the tetanic fade were investigated. The concentrations required for approximately 25% fade were 413 µM for hexamethonium (26.8 ± 2.4% 4% fade), 55 nM for d-tubocurarine (28.7 ± 2.55% fade), 0.32 µM for pancuronium (25.4 ± 2.2% fade), and 0.32 µM for cisatracurium (24.7 ± 0.8% fade). Pirenzepine or methoctramine alone did not produce the fade. Methoctramine, 1 µM, attenuated the fade induced by hexamethonium (to 16.0 ± 2.5% fade), d-tubocurarine (to 6.0 ± 1.6 fade), pancuronium (to 8.0 ± 4.0% fade), and cisatracurium (to 11.0 ± 3.3% fade). 10 nM pirenzepine attenuated only the fades produced by pancuronium (to 5.0 ± 0.11% fade) and cisatracurium (to 13.3 ± 5.3% fade). Cisatracurium (0.32 µM) showed antiacetylcholinesterase activity (in plasma, 14.2 ± 1.6%; 6%; in erythrocyt 17.2 ± 2.66%) similar to that of pancuronium (0.32 µM). The selective A1 receptor blocker, 8-cyclopentyl-1,3-dipropylxanthine (DPCPX; 2.5 nM), also attenuated the fades induced by pancuronium and cisatracurium. The tetanic fades produced by pancuronium and cisatracurium depend on the activation of presynaptic inhibitory M2 receptors; these agents also have anticholinesterase activities. The fades induced by these agents also depend on the activation of presynaptic inhibitory A1 receptors through the activation of stimulatory M1 receptors by acetylcholine. [ABSTRACT FROM AUTHOR]

Objective: To evaluate and compare the efficacy, infusion rate and recovery profile of vecuronium and cisatracurium continuous infusion in critically ill children requiring mechanical ventilation.Design and Setting: Prospective, randomised, double-blind, single-centre study in critically ill children in a paediatric intensive care unit in a tertiary children's hospital.Methods: Thirty-seven children from 3 months to 16 years old (median 4.1 year) were randomised to receive either drug; those already receiving more than 6 h of neuromuscular blocking drugs were excluded. The Train-of-Four (TOF) Watch maintained neuromuscular blockade to at least one twitch in the TOF response. Recovery time was measured from cessation of infusion until spontaneous TOF ratio recovery of 70%.Results: The cisatracurium infusion rate in nineteen children averaged 3.9+/-1.3 microg kg(-1) min(-1) with a median duration of 63 h (IQR 23-88). The vecuronium infusion rate in 18 children averaged mean 2.6+/-1.3 microg kg(-1) min(-1) with a median duration of 40 h (IQR 27-72). Median time to recovery was significantly shorter with cisatracurium (52 min, 35-73) than with vecuronium (123 min, 80-480). Prolonged recovery of neuromuscular function (>24 h) occurred in one child (6%) on vecuronium.Conclusions: Recovery of neuromuscular function after discontinuation of neuromuscular blocking drug infusion in children is significantly faster with cisatracurium than vecuronium. Neuromuscular monitoring was not sufficient to eliminate prolonged recovery in children on vecuronium infusions. [ABSTRACT FROM AUTHOR]

Objectives. To compare two levels of continuous cisatracurium-induced curarization in hypoxemic, ventilated patients. Design and setting. An open-labeled, multicenter, prospective, randomized study. Patients. Hundred two patients with a ratio between arterial oxygen tension and inspired oxygen tension (PaO2/FIO2) less than 200 despite optimization of sedation and ventilation were randomized into group 1 (n=52) with an end point of no response at orbicularis oculi to train-of-four (TOF) stimulation or group 2 (n=50) with an end point of two responses. Measurements and results. The PaO2/FIO2 and end-inspiratory plateau airway pressure (Pplat) were evaluated at baseline (before curarization) and at regular intervals once TOF end points had been attained for up to 2 h afterwards (T2 h). A decrease of 1 cmH2O or more of Pplat at T2 h compared to baseline was observed in 37% and 50% of the patients in groups 1 and 2, respectively (p=0.17). Time courses of PaO2/FIO2 (mmHg) and Pplat (cmH2O) [mean (SD)] were equivalent in both groups, with a mild increase in PaO2/FIO2 [p=0.0014; from 126 (33) to 141 (55) and from 134 (40) to 152 (52), respectively, in groups 1 and 2] and decrease in Pplat [p=0.016; from 29.1 (8.9) to 28.5 (8.8) and from 27.7 (7.5) to 26.6 (7.6)]. Median total durations of curarization were 28.9 h (3.1–219.7) in group 1 and 31.4 h (1.6–650.6) in group 2. Median cisatracurium infusion rates were 5.2 µg kg–1 min–1 (2.1–13.7) in group 1 and 3.6 µg kg1 min–1 (1.0–13.5) in group 2. The median delay to recovery from paralysis was shorter in group 2 (0.75 h vs 1.25 h; p=0.0008). Conclusion. When a prolonged curarization is decided upon in an ICU patient, a blockade at 2/4 at TOF at orbicularis oculi has similar effects on respiratory parameters as a blockade at 0/4, allowing a decrease in total administered doses and a shortening of the recovery of muscle strength after cessation of infusion. [ABSTRACT FROM AUTHOR]

Copyright of Anaesthesist is the property of Springer Nature and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Copyright of Anaesthesist is the property of Springer Nature and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Background: According to physical impairments of massive obesity, cardiac, respiratory and gastrointestinal physiology must be considered as much as pharmacokinetic behavior. Anesthetic management of morbidly obese patients has to be carefully planned, in order to minimize the increased risks of aspirative pneumonitis, hemodynamic instability and delay in recovery.The ideal anesthesia should provide a smooth and quick induction, allowing rapid airway control, prominent hemodynamic stability, and rapid emergence from anesthesia.To approach these ideal conditions,aTotal Intravenous Anesthesia (TIVA) with midazolam, remifentanil, propofol and cisatracurium was designed and analyzed. Methods: 10 consenting morbidly obese patients scheduled for elective Laparoscopic Adjustable Gastric Banding participated in the study.TIVA with midazolam, remifentanil, propofol and cisatracurium was used in all cases.Time to loss of consciousness, tracheal intubation, perianesthetic physiological parameters and complications, incidence of awareness with recall, recovery times, postoperative analgesia and costs of drugs were evaluated. Results:The analyzed data showed adequate time and physiological conditions for induction and tracheal intubation, stable maintenance with easy handling of deepness, low incidence of perianesthetic complications, excellent recovery performance and institutional efficiency. Conclusions: TIVA with midazolam, remifentanil, propofol and cisatracurium was found to be effective, secure, predictable and economic for the anesthetic management of morbidly obese patients. [ABSTRACT FROM AUTHOR]

Copyright of Anaesthesist is the property of Springer Nature and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Purpose. The population PK/PD approach was prospectively used to determine the PK/PD of cisatracurium in various subgroups of healthy surgical patients. Methods. Plasma concentration (Cp) and neuromuscular block data from 241 patients in 8 prospectively-designed Phase I−III trials were pooled and analyzed using NONMEM. The analyses included limited Cp-time data randomly collected from 186 patients in efficacy/safety studies and full Cp-time data from 55 patients in pharmacokinetic studies. The effects of covariates on the PK/PD parameters of cisatracurium were evaluated. The time course of neuromuscular block was predicted for various patient subgroups. Results. The population PK/PD model for cisatracurium revealed that anesthesia type, gender, age, creatinine clearance, and presence of obesity were associated with statistically significant ( p < 0.01) effects on the PK/PD parameters of cisatracurium. These covariates were not associated with any clinically significant changes in the predicted recovery profile of cisatracurium. Slight differences in onset were predicted in patients with renal impairment and patients receiving inhalation anesthesia. Based on the validation procedure, the model appears to be accurate and precise. Conclusions. The prospective incorporation of a population PK/PD strategy into the clinical development of cisatracurium generated information which influenced product labeling and reduced the number of studies needed during development. [ABSTRACT FROM AUTHOR]

Objective: To investigate the infusion requirements and recovery characteristics of cisatracurium compared with atracurium when both are administered by prolonged continuous infusion.Design: A prospective, randomised, single-blind study.Settings: The Intensive Care Unit of the Manchester Royal Infirmary.Patients: 20 patients requiring a continuous infusion of a neuromuscular blocking agent to facilitate mechanical ventilation. 12 patients received cisatracurium and 8 received atracurium.Interventions: Cisatracurium or atracurium was administered by continuous infusion for a minimum of 24 h. The level of neuromuscular blockade was measured by recording the train-of-four responses using acceleromyography, the aim being to maintain 1-2 twitch responses of the adductor pollicis. At the end of the infusion period, the train-of-four was recorded until the ratio was greater than 0.7.Measurements and Results: The mean infusion rate of cisatracurium was 0.23 mg kg-1 h-1, compared to 0.62 mg kg-1 h-1. No time-related increase in infusion requirements was seen for either drug. The mean recovery time to a train-of-four ratio greater than 0.7 was the same (46 min). There was no correlation between recovery time and age, duration of infusion or mean infusion rate.Conclusions: Cisatracurium provides a satisfactory level of neuromuscular blockade in adult ICU patients at approximately one-third the infusion rate of atracurium and with a similar recovery time. [ABSTRACT FROM AUTHOR]

Copyright of Anaesthesist is the property of Springer Nature and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Copyright of Anaesthesist is the property of Springer Nature and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)