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- The use of cisatracurium in critical care: A review of the literature. [JOURNAL ARTICLE]
- Minerva Anestesiol 2014 Apr 10.
Cisatracurium is currently one of the most commonly used neuromuscular blocking agent (NMBA) in intensive care units. Cisatracurium was developed primarily for anaesthetic purposes in order to attempt to resolve some of the problems associated with earlier NMBAs, such as histamine release and laudanosine accumulation. Cisatracurium, the the R-cis-R-cis isomer of atracurium, is up to 5 times more potent than atracurium and so is administered in smaller quantities and produces a lesser degree of laudanosine accumulation in the plasma.In both adult and paediatric settings cisatracurium has favourable pharmacological characteristics compared to vecuronium, a steroid based NMBA often used in critical care. Recent randomised clinical trials suggested that the use of cisatracurium is associated with better outcome in ARDS. It's use has been associated with better outcomes in therapeutic hypothermia and in traumatic brain injury. Although it has many favourable pharmacological properties, it is more expensive than comparable agents and some safety concerns persist regarding adverse events associated with the drug. Our aim was to perform the first comprehensive review to date of all literature relating to the use of cisatracurium in critically ill patients.
- Effects of interventions on survival in acute respiratory distress syndrome: an umbrella review of 159 published randomized trials and 29 meta-analyses. [JOURNAL ARTICLE]
- Intensive Care Med 2014 Mar 26.
Multiple interventions have been tested in acute respiratory distress syndrome (ARDS). We examined the entire agenda of published randomized controlled trials (RCTs) in ARDS that reported on mortality and of respective meta-analyses.We searched PubMed, the Cochrane Library, and Web of Knowledge until July 2013. We included RCTs in ARDS published in English. We excluded trials of newborns and children; and those on short-term interventions, ARDS prevention, or post-traumatic lung injury. We also reviewed all meta-analyses of RCTs in this field that addressed mortality. Treatment modalities were grouped in five categories: mechanical ventilation strategies and respiratory care, enteral or parenteral therapies, inhaled/intratracheal medications, nutritional support, and hemodynamic monitoring.We identified 159 published RCTs of which 93 had overall mortality reported (n = 20,671 patients)-44 trials (14,426 patients) reported mortality as a primary outcome. A statistically significant survival benefit was observed in eight trials (seven interventions) and two trials reported an adverse effect on survival. Among RCTs with more than 50 deaths in at least one treatment arm (n = 21), two showed a statistically significant mortality benefit of the intervention (lower tidal volumes and prone positioning), one showed a statistically significant mortality benefit only in adjusted analyses (cisatracurium), and one (high-frequency oscillatory ventilation) showed a significant detrimental effect. Across 29 meta-analyses, the most consistent evidence was seen for low tidal volumes and prone positioning in severe ARDS.There is limited supportive evidence that specific interventions can decrease mortality in ARDS. While low tidal volumes and prone positioning in severe ARDS seem effective, most sporadic findings of interventions suggesting reduced mortality are not corroborated consistently in large-scale evidence including meta-analyses.
- High-performance liquid chromatography assay with programmed flow elution for cisatracurium in human plasma: Application to pharmacokinetics in infants and children. [Journal Article]
- J Chromatogr B Analyt Technol Biomed Life Sci 2014 Apr 1.:58-63.
A high-performance liquid chromatography (HPLC) assay with fluorescence detection (FLD) for quantification of cisatracurium in human plasma was developed and fully validated. Liquid-liquid extraction was employed for sample preparation. The separation was carried out on a C18 column with ternary mobile phase composed of 30mmolL(-1) phosphate buffer (pH 3.0), acetonitrile and methanol (60:35:5, v/v/v). Verapamil was used as the internal standard. The isocratic elution with programmed flow rate was employed by setting at 0.8mLmin(-1) from 0 to 3.5min, 0.5mLmin(-1) from 3.5 to 6min, and 1.0mLmin(-1) from 6 to 10min. The fluorescence detection was performed at 236nm for excitation and 324nm for emission. The assay was linear from 50 to 2800ngmL(-1), with a detection limit of 12ngmL(-1). The correlation coefficient (r) for linear regression was 0.9997. The intra-day coefficients of variation (CVs) were less than 2.0%, and the inter-day CVs were less than 4.0%. The mean recoveries were in the range of 92.1-100.4%. The total HPLC run time was less than 10min. The developed HPLC method was fast, simple, sensitive, accurate and suitable for studying the pharmacokinetics of cisatracurium in infants and children after intravenous administration.
- Cisatracurium pretreatment with tourniquet reduces propofol injection pain: A double-blind randomized controlled trial. [Journal Article]
- J Int Med Res 2014 Apr; 42(2):360-7.
To investigate the efficacy of pretreatment with cisatracurium for prevention of pain associated with propofol injection, and compare its efficacy with that of lidocaine.Patients undergoing general anaesthesia were randomized to receive normal saline (control group), lidocaine (0.5 mg/kg), 0.03 mg/kg cisatracurium or 0.15 mg/kg cisatracurium. All drugs were administered into the largest dorsal vein of the hand with venous occlusion for 30 s, followed by propofol (0.5 mg/kg). Pain was evaluated using a four-point scale.The incidence and severity of pain was significantly lower in the lidocaine and 0.15 mg/kg cisatracurium groups than the control and 0.03 mg/kg cisatracurium groups (n = 50/group). There was no significant difference between the lidocaine and 0.15 mg/kg cisatracurium groups in the incidence and severity of pain.0.15 mg/kg cisatracurium effectively decreases the incidence and severity of pain induced by propofol injection without any significant complications.
- A comparison of the clinical duration and recovery characteristics of cisatracurium after priming using rocuronium or cisatracurium: preliminary study. [Journal Article]
- Korean J Anesthesiol 2014 Jan; 66(1):18-22.
The priming technique can speed up the onset of cisatracurium during intubation. However, there have been no reports on the effect of the priming technique on duration or recovery profile of cisatracurium. Therefore, we attempted to determine whether or not a priming technique with rocuronium or cisatracurium can affect clinical duration or recovery profiles of cisatracurium.A total of 36 patients, ASA I and II, who were scheduled to undergo elective surgery, were enrolled. The patients were randomized into three groups and administered different drugs for the priming technique. Patients in group 1 received normal saline (control group). Patients in group 2 received rocuronium (0.06 mg/kg), and those in group 3 received cisatracurium (0.01 mg/kg) as a priming agent. Three minutes after injection of drugs, intubation doses of cisatracurium were administered (Group 1, 0.15 mg/kg; Groups 2 and 3, 0.14 mg/kg). Anesthesia was induced and maintained with propofol and remifentanil. Onset time, clinical duration, recovery index, recovery time, and total recovery time were measured by train of four monitoring.Onset time in the group 2 was significantly shorter than that of group 1 or 3 (P < 0.05). However, no significant differences in clinical duration, recovery index, recovery time, and total recovery time were observed among the three groups.Priming with rocuronium for 3 minutes resulted in significantly accelerated onset of cisatracurium. However, it did not affect the clinical duration and recovery profiles of cisatracurium.
- Inﬂuence of hypnotics on cisatracurium-induced neuromuscular block. Use of acceleromyograhpy. [Journal Article]
- Braz J Anesthesiol 2013 May-Jun; 63(3):249-53.
Different drugs, including hypnotics, may influence the pharmacodynamic effects of neuromuscular blockers (NMB). The aim of this study was to evaluate the influence of propofol and etomidate on cisatracurium-induced neuromuscular blockade.We included 60 patients, ASA I and II, undergoing elective surgery under general anesthesia in the study and randomly allocated them into two groups, according to their hypnotic drug: GI (propofol) and GII (etomidate). Patients received intramuscular (IM) midazolam (0.1mg.kg(-1)) as premedication and we performed induction with propofol (2.5mg.kg(-1)) or etomidate (0.3mg.kg(-1)), preceded by fentanyl (250 mg) and followed by cisatracurium (0.1mg.kg(-1)). The patients were ventilated with 100% oxygen until obtaining a reduction of 95% or more in the adductor pollicis response amplitude, with subsequent laryngoscopy and tracheal intubation. Neuromuscular function was monitored by accelomyography. We evaluated the onset of action of cisatracurium, tracheal intubation conditions, and hemodynamic repercussions.The mean time and standard deviations of cisatracurium onset were: GI (86.6 ± 14.3 s) and GII (116.9 ± 11.6 s), with a significant difference (p < 0, 0001). Intubation conditions were acceptable in 100% of GI and 53.3% of GII patients (p < 0.0001).Induction of neuromuscular blockade with cisatracurium was faster, with better intubation conditions in patients receiving propofol compared to those receiving etomidate, without hemodynamic repercussions.
- Pharmacodynamics of cisatracurium in the intensive care unit: an observational study. [Journal Article]
- Ann Intensive Care 2014; 4(1):3.
Data from previous studies indicate that optimal conditions for intubation are met 120 seconds after administration of 0.15 mg.kg-1 cisatracurium (ED95 × 3) following the induction of anesthesia. The aim of this study was to compare the doses required for complete paralysis after induction of anesthesia in ICU patients with the dose used in patients undergoing elective surgery.Seventeen ICU patients undergoing percutaneous tracheostomy and 17 patients undergoing an elective surgical procedure under muscle relaxation were included. In both groups, an initial intravenous bolus of cisatracurium besylate was given at a dose of 0.15 mg.kg-1 followed by repeated boluses of 0.03 mg.kg-1 every four minutes. The objective was to obtain no response to the train-of-four (TOF). The contractile response of the corrugator supercilii muscle was monitored every minute by observing the TOF in response to a peripheral nerve stimulator with a constant current set to 60 mA.After the initial dose of cisatracurium, none of ICU patients (0/17) versus 15/17 of the elective surgery patients were completely paralyzed (P < 0.0001). There was a delay in the onset of neuromuscular blockade among the ICU patients. The cumulative doses of cisatracurium were significantly higher in the ICU group with 38 ± 14 mg (that is, 10 ± 4.7 ED95) versus 11 ± 2 mg (that is, 3 ± 0.3 ED95) in the elective surgery group (P < 0.0001).The dosing of cisatracrurium for ICU patients, which is based on the dose recommended for elective anesthesia, is unsuitable because the onset is too slow. This phenomenon is probably caused by changes in the pharmacodynamics and pharmacokinetics. These data suggest that neuromuscular monitoring should be used in the ICU.
- Perioperative allergic reactions: Experience in a Flemish referral centre. [JOURNAL ARTICLE]
- Allergol Immunopathol (Madr) 2013 Oct 23.
The incidence of perioperative anaphylactic reactions is overall estimated to be 1 per 10,000-20,000 anaesthetic procedures. We performed a retrospective analysis of patients referred to a University Allergy Centre in Belgium with the suspicion of an allergic reaction during or shortly after general anaesthesia.Our aim was to assess the causes of perioperative allergic reactions, to evaluate cross-reactivity among neuromuscular blocking agents (NMBA) and to analyze the diagnostic relevance of tryptase levels in the discrimination between IgE and non-IgE-mediated reactions.A total of 119 patients, referred from 2007 to 2011 were included. The diagnostic protocol consisted in case history, serum tryptase measurements, immunoassays and skin tests.A diagnosis of IgE-mediated reaction was established in 76 cases (63.9%). The most common agents were NMBA (61.8%), antibiotics (14.5%), latex (9.2%) and chlorhexidine (5.2%). Rocuronium was the most frequently causative NMBA (48.9%). Vecuronium cross-reactivity was established by skin testing in 47.6% of cases. Cisatracurium was the NMBA most frequently tolerated (cross-reaction in 13.9%). In 23.4% of NMBA allergic patients, the reaction occurred on the first exposure. Most IgE-mediated reactions occurred during the induction phase (72.4%). Latex-induced reactions occurred mainly during maintenance and recovery phases (71.4%; p<0.02). Mean tryptase values were significantly higher in patients with IgE-mediated reactions (p=0.0001), than in those with no identified cause.NMBA, antibiotics, latex and chlorhexidine were the main culprits of IgE-mediated perioperative reactions. Uncertainties remain concerning the specificity and sensitivity of skin testing. Tryptase assays can be useful in the discrimination of IgE and non-IgE-mediated reactions.
- The effect of cisatracurium and rocuronium on lung function in anesthetized children. [Journal Article, Randomized Controlled Trial]
- Anesth Analg 2013 Dec; 117(6):1393-400.
Neuromuscular blocking drugs have been implicated in intraoperative bronchoconstrictive episodes. We examined the effects of clinically relevant doses of cisatracurium and rocuronium on the lung mechanics of pediatric subjects. We hypothesized that cisatracurium and rocuronium would have bronchoconstrictive effects.We studied ASA physical status I and II pediatric subjects having elective dental or urological procedures, requiring general anesthesia with endotracheal intubations with either cisatracurium or rocuronium. Pulmonary function tests were performed before and after neuromuscular blocking drug dosing and again after albuterol administration. Using forced deflation and passive deflation techniques, forced vital capacity (FVC) and maximum expiratory flow rate at 10% (MEF10) of FVC were obtained. Fractional changes from the baseline were used to compare subjects. Changes in MEF10 of >30% were considered clinically significant. A Shapiro-Wilk test, paired t test, and Wilcoxon rank sum test were used to analyze the data.Twenty-five subjects (median age = 5.25 years; range = 9 months-9.9 years) were studied; 12 subjects received cisatracurium and 13 subjects received rocuronium. Data are shown as mean proportional change ± SD or, in the case of not normally distributed, median proportional change (first, third quartile) with P values. In the cisatracurium group, there were no differences between baseline and postneuromuscular blocker administration in the fractional change from the baselines of FVC (1.00 ± 0.04, P = 0.5), but there was a significant decrease in MEF10 (0.80 ± 0.18, P = 0.002). In the rocuronium group, there were small yet significant decreases of FVC (0.99 [first quartile 0.97, third quartile 1], P = 0.02) and significant decreases in MEF10 (0.78 ± 0.26, P = 0.008). After administration of albuterol in the cisatracurium group, FVC increased slightly but significantly from baseline values (1.02 ± 0.02, P = 0.005). MEF10 increased significantly beyond baseline values (1.24 ± 0.43, P =0.04). In the rocuronium group, there were also significant differences between baseline and postalbuterol administration from the baseline value of FVC (1.02 ± 0.02, P = 0.004) and MEF10 (1.23 ± 0.29, P = 0.01).At clinically relevant doses, both cisatracurium and rocuronium caused changes in lung function, indicating constriction of smaller airways. In general, these changes were mild and not clinically detectable. However, in the rocuronium group, 3 of 13 patients showed more noticeable decreases in MEF10 (≤50%), demonstrating the potential for significant broncho-bronchiolar constriction in susceptible patients.
- Comparison between the Effects of Rocuronium, Vecuronium, and Cisatracurium Using Train-of-Four and Clinical Tests in Elderly Patients. [Journal Article]
- Anesth Pain Med 2013; 2(4):142-8.
Postoperative residual blockade, longer duration of action for neuromuscular blockade, and slower recovery were relatively common in elderly patients.We aimed to investigate the safety of train-of-four ratio and clinical tests in the assessment of patient recovery, and to determine the effects of the rocuronium, vecuronium, and cisatracurium on intubation, extubation and recovery times in elderly patients undergoing abdominal surgery.After obtaining institutional approval and informed consent, 60 patients over 60 years old and undergoing elective abdominal operations were included in this double-blind, randomized clinical trial. Following a standard anesthesia induction, 0.6mg kg-1 rocuronium, 0.1mg kg-1 vecuronium, and 0.1mg kg-1 cisatracurium were administered to the patients in Group R, Group V, and Group C, respectively. Train-of-four (TOF) ratios were recorded at 10-minute intervals during and after the operation. Modified Aldrete Score (MAS) and clinical tests were recorded in the recovery room at 10-minute intervals. In addition, intubation and extubation times, duration of recovery room stay, and any complications were recorded.Intubation time was found to be shorter in Group R than that in Groups V and C (P ˂ 0.001). Times to positive visual disturbances and grip strength tests were shorter in Group C than that in Group V (P = 0.016 and P = 0.011, respectively). In Group R and group C, time to TOF ≥ 0.9 was significantly longer than all positive clinical test times except grip strength (P < 0.05).We hold the opinion that cisatracurium is safer in elderly patients compared to other drugs. We also concluded that the usage of TOF ratio together with clinical tests is suitable for assessment of neuromuscular recovery in these patients.