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- The dose effect of ephedrine on the onset time and intubating conditions after cisatracurium administration. [Journal Article]
- Korean J Anesthesiol 2014 Jul; 67(1):26-31.
The aim of this randomized, double-blind, placebo-controlled study was to evaluate dose effects of ephedrine pretreatment on the onset time and intubating conditions after cisatracurium administration.A total of 140 adult patients were randomized into 4 groups to receive either 30 µg/kg ephedrine (Group 30, n = 35), 70 µg/kg ephedrine (Group 70, n = 35), 110 µg/kg ephedrine (Group 110, n = 35), 3 ml normal saline (Group C, n = 35) as pretreatment given 30 s before anesthetic induction. Neuromuscular block was achieved with 0.15 mg/kg cisatracurium, evaluated accelomyographically with train-of-four stimulation. An anesthesiologist blinded to patient grouping assessed the intubating conditions 1.5 min after cisatracurium administration.An onset time of 70 s was obtained in the ephedrine groups (Group 30: 155.4 ± 44.7 s, Group 70: 152.6 ± 40.3 s, Group 110: 151.2 ± 51.6 s) compared to Group C (224.6 ± 56.9 s) after 0.15 mg/kg of cisatracurium (P < 0.001). Ephedrine doses of either 70 or 110 µg/kg for pretreatment significantly improved intubating conditions (P < 0.05). Systolic and diastolic blood pressure and heart rate at 1 min after tracheal intubation were significantly increased than other times in all groups (P < 0.001), with no differences among the groups. However, 5 patients in Group 110 experienced marked hypertension (systolic/diastolic blood pressure: > 200/100 mmHg) 1 min after tracheal intubation with no patients in other groups.We conclude that pre-treatment with ephedrine 70 µg/kg improved intubating conditions 1.5 min after cisatracurium administration and facilitated the onset of neuromuscular block (70 s) without adverse hemodynamic effects.
- Differences between acceleromyography and electromyography during neuromuscular function monitoring in anesthetized Beagle dogs. [JOURNAL ARTICLE]
- Vet Anaesth Analg 2014 Jul 2.
Quantitative neuromuscular monitoring is essential for studies of potency and duration of neuromuscular blocking agents, and for detecting residual paralysis in anesthetized patients. This investigation evaluates whether there are systematic differences between acceleromyography (AMG) and electromyography (EMG); two quantitative methods for monitoring neuromuscular block.Prospective.Ten healthy Beagle dogs.Dogs were anesthetized with isoflurane and dexmedetomidine. Both ulnar nerves were stimulated with a train-of-four (TOF) pattern every 15 seconds. The magnitude of the first twitch (T1) and the TOF ratio (magnitude of T4/T1; TOFR) were quantified simultaneously with AMG and EMG, applied randomly to each extremity. The extent of maximal block (T1 depression) and onset time were measured by AMG and EMG during TOF monitoring after the administration of cisatracurium (0.05 mg kg(-1) ). In addition, recovery of T1 to 25% and 75%, the recovery index (time between T1 of 25% and 75%), and recovery of the TOFR to 0.9 were used to characterize recovery from cisatracurium and were compared between monitors. Regression and Bland-Altman plots for T1 and TOFR were also created.Maximal block and onset time were not different between monitors. Time to recovery of T1 to 25% and 75%, and time to TOF ratio 0.9 was significantly shorter with AMG. The recovery index was not different between monitors. When the TOFR returned to 0.9 with AMG, EMG still measured considerable residual block (TOFR 0.47).Electromyography consistently detected residual NMB when recovery from NMB was complete as assessed by AMG.
- Flowcytometric diagnosis of atracurium-induced anaphylaxis. [JOURNAL ARTICLE]
- Allergy 2014 Jun 24.
Allergy to atracurium is a rare condition with serious consequences of diagnostic error. However, correct diagnosis is not always straightforward.To assess the utility of the basophil activation test (BAT) in atracurium sensitization and to investigate its role in identifying cross-reactivity between muscle relaxants.For validation 8 patients with perioperative anaphylaxis to atracurium and 7 individuals experiencing perioperative anaphylaxis but not exposed to neuromuscular blocking agents (NMBA) were included. Furthermore, 5 other patient groups were included in the study, all individuals exposed to different NMBA, either sensitized or not to the drug. Basophil activation with atracurium was analysed flow cytometrically.ROC analyses between 8 atracurium sensitized patients and 7 non-exposed controls allowed identification of 5% as the decision threshold for BAT positivity. For this cut off the BAT attained a sensitivity of 63%, specificity of 100%, positive predictive value of 100% and negative predictive value of 70%. Of the atracurium-exposed individuals with a negative atracurium skin test, 2 individuals had a clear positive BAT. BAT atracurium was positive in one cisatracurium sensitised patient and negative in all cisatracurium exposed patients with a negative skin test to cisatracurium. All rocuronium and suxamethonium-sensitized patients displayed a negative BAT with atracurium.The BAT proves to be a useful diagnostic for atracurium-induced anaphylaxis and may be complementary to skin tests. The technique enables quick and simultaneous testing of potentially cross-reactive NMBA and the identification of safe alternatives for future surgery. This article is protected by copyright. All rights reserved.
- Effect of dexmedetomidine-etomidate-fentanyl combined anesthesia on somatosensory- and motor-evoked potentials in patients undergoing spinal surgery. [JOURNAL ARTICLE]
- Exp Ther Med 2014 May; 7(5):1383-1387.
This aim of the present study was to evaluate the effects of dexmedetomidine (DEX) on the intraoperative monitoring of somatosensory-evoked potentials (SEPs) and motor-evoked potentials (MEPs) in patients undergoing spinal surgery. A total of 36 patients who received spinal surgery under general anesthesia were randomly divided into two groups (n=18 per group), group C, the test group and group D, the control group, and these groups were subjected to a matching anesthesia induction. In brief, the anesthesia was administered via injection of etomidate and fentanyl; once the patients were unconscious, a laryngeal mask airway (LMA) was inserted, SEPs and MEPs were monitored and the collected data were considered to be basic data. Cisatracurium was subsequently injected and an endotracheal tube (7#) was inserted to replace the LMA. The following procedures were conducted for anesthesia maintenance: Group C, the anesthesia was maintained via target-controlled infusion of etomidate and intermittent injection of fentanyl; and group D, DEX (0.5 μg/kg) was injected over a duration of 10 min and then pumped at a rate of 0.5 μg/kg/h. In the two groups, all of the other drugs used were the same and a muscle relaxant was not administered. The bispectral index was maintained between 45 and 55 during surgery, and the SEPs and MEPs were monitored continuously until the surgery was completed. No significant difference in duration and amplitude of the SEPs (P15-N20) was identified between group C and D (P>0.05). Furthermore, the MEPs were monitored in the two groups at specific durations and no significant difference was observed between the two groups (P>0.05). The SEPs and MEPs were maintained in the patients who were administered with the DEX-etomidate-fentanyl combined anesthesia during spinal surgery.
- Pharmacological treatments for acute respiratory distress syndrome: systematic review. [JOURNAL ARTICLE]
- Minerva Anestesiol 2014 Jun 17.
Our objective was to systematically review the effect of pharmacological therapies on mortality in patients with acute respiratory distress syndrome (ARDS), focusing on randomized controlled trials (RCTs) published since a previous review in 2004.We updated previous searches and searched OVID versions of MEDLINE, EMBASE and CENTRAL (to January 2013) and proceedings from conferences and bibliographies of included studies. We included RCTs of pharmacologic therapies compared with placebo or no therapy for adult patients with ARDS, using authors' definitions, which reported on mortality (≤3 months after randomization). We excluded subgroups of patients with ARDS reported in RCTs enrolling other populations and RCTs of therapies to prevent ARDS, nutritional or fluid interventions, inhaled nitric oxide, therapies coupled to a mechanical ventilation strategy, or oxygen. Two reviewers independently screened citations, selected articles for inclusion, and abstracted clinical and methodological data from included studies with disagreements resolved by a third reviewer. Mortality data were pooled using randomeffects models.From 13461 citations, 58 trials (6635 patients) of 21 classes of medications met selection criteria; 26 trials (3880 patients) were published after 2003. Meta-analyses reduced 28-day mortality with a 48-hour infusion of cisatracurium in early ARDS (relative risk 0.66, 95% confidence interval 0.50 to 0.87; 431 patients, 138 deaths). There was no effect on mortality with granulocyte-macrophage colony stimulating factor, late low-dose methylprednisolone, neutrophil elastase inhibitors, intravenous salbutamol, surfactant, or N-acetylcysteine; each metaanalysis included ≥1 trial published after 2003. Seven single trials of other treatments published after 2003 showed no effect. Metaanalysis of older trials of prostaglandin E1 also showed no effect.Effective pharmacotherapy for ARDS remains extremely limited. Cisatracurium is a promising treatment for early moderate-severe ARDS (using Berlin definition nomenclature) and merits further investigation in a large RCT.
- Intubation without muscle relaxation for suspension laryngoscopy: A randomized, controlled study. [Journal Article]
- Niger J Clin Pract 2014 Jul-Aug; 17(4):456-61.
Aim:The objective of the following study is to examine the effectiveness and safety of suspension laryngoscopy under intubation with propofol and remifentanil alone for vocal fold nodule (VFN) excision. Materials and
Methods:A total of 40 patients were equally and randomly assigned to elective VFN excision using suspension laryngoscopy under intubation with propofol and remifentanil alone (Group A) or with supplementary cisatracurium (Group B).
Results:Intubation time was significantly longer in Group A than in Group B (300.0 ± 30.0 s vs. 265.2 ± 38.7 s, P = 0.003). The two groups showed similar Cormack-Lehane classifications, intubation conditions and ease of suspension laryngoscopy. Both groups showed favorable cardiopulmonary safety profiles. Post-anesthesia recovery was significantly more rapid in Group A than in Group B, in terms of times to spontaneous breathing return (7.2 ± 1.4 min vs. 10.9 ± 1.6 min, P < 0.001), consciousness return (7.4 ± 1.5 min vs. 12.3 ± 1.8 min, P < 0.001), removal of tracheal intubation (8.1 ± 1.5 min vs. 13.2 ± 1.7 min, P < 0.001) and operating room discharge (12.7 ± 1.4 min vs. 22.1 ± 1.3 min, P < 0.001).
Conclusion:Use of propofol and remifentanil alone provides favorable intubation and anesthesia conditions for suspension laryngoscopic VFN excision and accelerates post-anesthesia recovery.
- Predictive value of allergy tests for neuromuscular blocking agents: tackling an unmet need. [Journal Article]
- Clin Exp Allergy 2014 Aug; 44(8):1069-75.
Neuromuscular blocking agents (NMBAs) are a predominant cause of perioperative anaphylaxis in Europe. Diagnosis of NMBA allergy relies upon the careful review of the anaesthetic report complemented with skin tests. Additional diagnostic tests are quantification of specific IgE antibodies (sIgE) and basophil activation test (BAT). However, data on the predictive value of the skin tests, the BAT and the sIgE assays (drug-specific and substituted ammonium structures) are limited or not available, mainly because such exploration requires dangerous NMBA provocation tests.In this study, the predictive value of skin test, BAT and measurement of sIgE to substituted ammonium structures is gathered from a review of anaesthetic records of subsequent surgical procedures with NMBA administration and/or occurrence of perioperative incidents.We investigated a series of 272 patients with perioperative anaphylaxis, of whom 100 had undergone second general anaesthesia. Negative skin test and negative BAT assisted the selection of alternative NMBA, which were well tolerated in all cases. Five patients with a positive sIgE to rocuronium but with negative skin testing and BAT safely received rocuronium during second anaesthesia. Twelve patients with sIgE reactivity to morphine, but negative skin test and BAT to benzylisoquinolines, tolerated administration of cisatracurium or atracurium. Alternatively, benzylisoquinoline allergy went undetected in the morphine solid-phase assay.Skin test and BAT have an excellent negative predictive value in our series. The uneventful re-exposure of rocuronium in patients with an isolated positive sIgE result to rocuronium calls into question the predictive value of this assay and suggests sIgE serology to be less clinically predictive than the functional investigations relying upon activation of mast cells or basophils. The presence of a positive sIgE to substituted ammonium structures such as morphine does not preclude further use of benzylisoquinolines.
- Comparative Pharmacodynamics of Pancuronium, Cisatracurium, and CW002 in Rabbits. [Journal Article]
- J Am Assoc Lab Anim Sci 2014; 53(3):283-9.
Pancuronium is a long-duration neuromuscular blocking drug (NMBD) that has been used in anesthetized rabbits at 0.1 mg/kg. However, there are limited data regarding the time course for recovery from this dose either spontaneously or with pharmacologic reversal. Here we defined the potency, onset, and recovery characteristics for the intermediate-duration NMBD cisatracurium and CW002 (a novel cysteine-inactivated molecule) in the rabbit, and test the hypothesis that these drugs may be alternatives to 0.1 mg/kg pancuronium for survival procedures. New Zealand white rabbits anesthetized with isoflurane were studied in a cross-over design. Potencies of cisatracurium and CW002 were defined as the effective dose for 95% depression of evoked muscle twitch (ED95). Responses to 3×ED95 were used to define onset (time to maximal effect), recovery index (RI; time from 25% to 75% recovery of twitch), and duration (time to complete recovery). Responses to all drugs were determined with and without reversal by neostigmine-glycopyrrolate or L-cysteine. CW002 was 4-fold more potent than was cisatracurium, but their onset, RI, and duration were similar. Pancuronium had similar onset and RI but longer duration, compared with cisatracurium and CW002. Reversal shortened the recovery index and duration for all 3 drugs. At 3×ED95, cisatracurium and CW002 had the same onset as did standard-dose pancuronium, but durations were shorter and more predictable. In addition, CW002 can be reversed without the potential side effects of cholinergic manipulation. We conclude that cisatracurium and CW002 are viable alternatives to pancuronium for survival studies in rabbits.
- [Physicochemical stability study of injectable solutions of cisatracurium besilate in clinical conditions.] [JOURNAL ARTICLE]
- Ann Fr Anesth Reanim 2014 Apr 28.
To assess the stability of cisatracurium besilate solution stored at 5°C and 25°C.Cisatracurium solutions at 2, 5 and 0.1mg/mL in 0.9 % sodium chloride or 5 % glucose were exposed to 5°C and 25°C under 60 % relative humidity for seven days. The physicochemical stability was assessed at 24, 48hours and seven days with dosage of the active substance, detection of degradation products and a possible racemization, measuring pH, osmolality and turbidity, assessment of coloration, visible particles and invisible particles count.Cisatracurium besilate present good stability for 24hours at 5°C and 25°C for concentrations between 0.1 and 5mg/mL. Beyond 24hours, the solutions at 2 and 5mg/mL remained stable for seven days at 5°C. At 25°C, potentially toxic degradation products appear in solutions of 0.1mg/mL between 24 and 48hours. No racemization was detected, the drug remains in its active form cis.Cisatracurium solutions at 2 and 5mg/mL may be stored at 5°C or 25°C for seven days. It's advisable to keep the solutions in a dilution of 0.1mg/mL in 0.9 % sodium chloride or 5 % glucose in the refrigerator. No diluted solution should be stored at room temperature beyond 24hours.
- Consumption of Cisatracurium in different age groups, using a closed loop computer controlled system. [JOURNAL ARTICLE]
- BMC Anesthesiol 2014 Apr 21; 14(1):29.
We devised this study to quantify the effect of age on the consumption of cisatracurium under general anaesthesia, using a computer controlled closed loop infusion system. We further investigated this effect on, sufentanil and propofol consumption.74 patients of physical status I and II, requiring general anaesthesia for elective abdominal surgery, were assigned to three groups. Patients in group 1 were aged from 20 to 45, group were from 46 to 64, and group 3 above 65 years old. General Anesthesia was maintained with propofol and muscle paralysis was maintained using a closed-loop computer controlled infusion of cisatracurium. For analgesia, intermittent bolus of sufentanil 10 mug was given.Cisatracurium consumption in group 1, 2 and 3 were 1.8 +/- 0.3, 1.6 +/- 0.4 and 1.3 +/- 0.4 mug/kg/min respectively. There was significant difference of cisatracurium consumption between group 1 and 3 (P = 0.002), and the consumption of cisatracurium in group 3 was less as compared with group 2 (P = 0.04). The average recovery index of patients in group 1, 2 and 3 were 8.8 +/- 2.6, 11.5 +/- 2.9 and 12.7 +/- 2.5 minutes respectively. There were difference between group 1 and 2 (P = 0.02). As compared with group 1, the recovery index was still longer in group 3 (P = 0.001). Patients in group 1, 2 and 3 consumed an average sufentanil 0.4 +/- 0.1, 0.4 +/- 0.1 and 0.3 +/- 0.1 mug/kg/hr, respectively. There were statistical significant between group 1 and 3(P < 0.0001), and the same trend was found between group 2 and 3(P = 0.03). The Consumption of propofol in group 1, 2 and 3 were 5.1 +/- 0.4, 4.3 +/- 0.6 and 3.1 +/- 0.5 mg/kg/hr. The difference in the propofol consumption was found statistically significant when comparing between any two groups.We concluded that the sensitivity of anesthetic agents increased with age. Less medication was required to achieve a desirable effect in older patients specially those above 65 years of age, and the drug effect was prolonged.Trial registration: ClinicalTrials.gov Identifier: NCT01785446.