Mivacurium Research Articles

A novel BCHE frameshift mutation in a Chinese woman with butyrylcholinesterase deficiency: A case report and literature review.

Congenital butyrylcholinesterase deficiency (BCHED) is a rare autosomal recessive genetic disorder caused by a pathogenic mutation in the BCHE gene. Patients with BCHED may experience prolonged apnea or even death after the application of drugs such as succinylcholine. We aimed to identify the genetic basis of disease in a patient presenting with butyrylcholinesterase deficiency in order to confirm the diagnosis, expand BCHE gene mutation spectrum, and elucidate potential genotype-phenotype associations to inform management. A 51-year-old woman presented with "vague pain in the upper and middle abdomen." Her serum cholinesterase level was 211 U/L (reference value 4000-13,000 U/L). Other laboratory findings were normal. Genetic analysis revealed compound heterozygous mutations in BCHE gene, which was considered pathogenic in this case. The patient presented with low serum cholinesterase levels, which excluded common causes such as liver disease, drug toxicity, and chronic illness. Whole exon examination revealed compound heterozygous mutations in the BCHE gene; thus, the patient was diagnosed with congenital BCHED. Gastroscopy without succinylcholine or mivacurium chloride was recommended. The gastroscopy results were "gastric polyps," and gastroscopic "polypectomy" was performed. The patient was advised to avoid succinylcholine use. The patient's serum cholinesterase level was reviewed 3 months later, and the result was 215 U/L. Double heterozygous mutations are the cause of BChE deficiency of this woman in this study, including a novel mutation NM_000055.4: c.666_669del (p.Phe223Glufs*38). A review of the literature reveals considerable variation in the hotspot variants of the BCHE gene across different populations. The Chinese population displays a higher prevalence of the silent type, which is more sensitive to anesthetics such as succinylcholine. Clinical manifestations of congenital BCHED were not significant. This study avoided a potential anesthetic accident, and the novel variant enriched the BCHE gene mutation spectrum.

Clinical Study of Flumazenil Antagonizing Remimazolam on Nausea and Vomiting After Gynecologic Day Surgery.

To evaluate the effect of flumazenil antagonizing remimazolam on postoperative nausea and vomiting (PONV) after gynecologic day surgery. 141 cases of gynaecological daycase surgery patients in Weifang People's Hospital were selected, randomized into group F (flumazenil group, 71 cases) and group C (control group, 70 cases). Dexamethasone 5 mg, flurbiprofen axetil 50 mg, and droperidol 1 mg were given intravenously before induction of anesthesia in both groups. Anesthesia induction: Remimazolam 0.25mg / kg was injected within 1 minute. After the patient fell asleep, mivacurium chloride 0.2mg / kg was injected for 30 seconds and alfentanil 20ug / kg was injected for 30 seconds. Anesthesia maintenance: Remimazolam 1mg/kg/h and alfentanil 40ug/kg/h were continuously pumped by micro pump. Stopping the injection of remimazolam and alfentanil at the end of the operation. Flumazenil 0.2 mg was given to antagonize remimazolam in group F after 1 minute. Group C was given an equal volume of saline. The incidence of PONV in the postoperative PACU and over a 24-hour period, patient awakening time, and general patient information were recorded. The incidence of PONV in both groups within 24 hours was 50.70% in group F was significantly higher than 32.86% in group C. The difference was statistically significant (P < 0.05). The incidence of PONV in the PACU was 5.6% in group F and 8.6% in group C. The difference was not statistically significant (p > 0.05). Flumazenil antagonism of remimazolam increases the incidence of PONV within 24 hours in gynecologic day surgery patients and has no significant effect on the incidence of PONV in the PACU.

Effect of low-dose propofol combined with dexamethasone on the prevention of postoperative nausea and vomiting in gynaecological day surgery under remimazolam-based general anesthesia.

To observe the effect of low-dose propofol combined with dexamethasone on the prevention of postoperative nausea and vomiting (PONV) in gynaecological day surgery under remimazolam-based general anesthesia. A total of 120 patients, aged from 18 to 65 years old, American Society of Anesthesiologists grade I or II, were scheduled to undergo hysteroscopy under total intravenous anesthesia. The patients were divided into 3 groups (n = 40 each): dexamethasone plus saline group (DC group), dexamethasone plus droperidol group (DD group) and dexamethasone plus propofol group (DP group). Dexamethasone 5 mg and flurbiprofen axetil 50 mg were given intravenously before induction of general anesthesia. Anesthesia induction: remimazolam 6 mg/kg/hours was continuously pumped until sleep and slow intravenous injection of alfentanil 20 ug/kg and mivacurium chloride 0.2 mg/kg was given. Anesthesia maintenance: remimazolam 1 mg/kg/hour and alfentanil 40 ug/kg/hours were continuously pumped. After the start of surgery, DC group was given 2 mL saline, DD group was given droperidol 1 mg, and DP group was given propofol 20 mg. Primary outcome: incidence of PONV in the postanesthesia care unit (PACU). Secondary outcome: incidence of PONV in patients within 24 hours after surgery, as well as general patient data, duration of anesthesia, the recovery time of patients, dose of remimazolam and alfentanil, etc. In PACU, patients of group DD and DP showed less PONV than those in group DC (P < .05). Within 24 hours after operation, there was no significant difference in the incidence of PONV among the 3 groups (P > .05), but the incidence of vomiting in DD group and DP group was significantly lower than that in DC group (P < .05). There was no significant difference in general data, anesthesia time, the recovery time of patients and dosage of remimazolam and alfentanil among the 3 groups (P > .05). The effect of low-dose propofol combined with dexamethasone to prevent PONV under remimazolam-based general anesthesia was similar to that of droperidol combined with dexamethasone, both of which significantly reduced the incidence of PONV in the PACU compared to dexamethasone alone. However, low-dose propofol combined with dexamethasone had little effect on the incidence of PONV within 24 hours compared to dexamethasone alone and only reduced the incidence of postoperative vomiting in patients.

Retracted: Comparative Analysis of the Anesthesia Effect of Cisatracurium Besylate and Mivacurium Chloride Otolaryngology Surgery

Retracted: Comparative Analysis of the Anesthesia Effect of Cisatracurium Besylate and Mivacurium Chloride Otolaryngology Surgery

Comparative Analysis of the Anesthesia Effect of Cisatracurium Besylate and Mivacurium Chloride Otolaryngology Surgery.

Objective The aim is to investigate and compare the anesthesia effect of cisatracurium besylate and mivacurium chloride otolaryngology surgery. Materials and Methods 108 patients who underwent ENT surgery under general anesthesia in our hospital from November 2021 to March 2022 were recruited for retrospective analysis, in which patients in the experimental group A were anesthetized with cisatracurium besylate and patients in the experimental group B were anesthetized with mivacurium, and the anesthetic effects and recovery of the two groups were compared and analyzed. Results There was no significant difference in mean arterial pressure, heart rate, and pulse oximetry levels between the two groups at the six time points of admission, anesthesia induction, intubation, end of operation, recovery of consciousness, and extubation (all P > 0.05). The train of four stimulation values at end of operation, recovery of consciousness, and extubation were significantly higher than those of the experimental group A (all P > 0.05). The recovery time of self-consciousness, extubation time, and eye-opening time of the experimental group B were significantly shorter than those of the experimental group A, and the occurrence of agitation was significantly less than that of the experimental group A (all P > 0.05). The total incidence of adverse conditions in the experimental group B was significantly lower than that in the experimental group A (P > 0.05). Conclusion Compared with cisatracurium besylate in otolaryngology surgery, mivacurium chloride anesthesia offers a promising route with respect to less impact on hemodynamics, faster postoperative recovery, absence of the accumulation of neuromuscular blockade, less adverse reactions, and higher safety.

A Companion Diagnostic for Personalizing Mivacurium at the Point-of-Care

Mivacurium chloride is envisioned as the “gold-adjunct” in anesthesia and emergency medicine. People across the world are administered mivacurium in emergency situations as clinicians prefer it among the frequently used neuromuscular blockers thanks to its rapid action and short duration. Mivacurium is promptly degraded and deactivated by plasma cholinesterase enzyme (PChE), however during emergency situations, some individuals were found to be unable to metabolize mivacurium shortly after its injection, resulting in prolonged paralysis and potentially lethal respiratory apnea. The most clinically significant cause of this residual paralysis and apnea is the reduced cholinesterase ability to effectively hydrolyze mivacurium. Hitherto, monitoring of mivacurium enzymatic degradation has been remaining a long-standing challenge for analytical chemists as well as anesthesiologists. Firstly, it undergoes rapid hydrolysis by the PChE-enzyme 8 min post-injection, therefore, frequent sampling all through the first minutes after mivacurium administration is mandatory. Secondly, its isolation from biological specimens is extremely difficult due to its chemical properties which involves both hydrophilic and lipophilic characteristics. These challenges impede the development of a universal protocol to be established for screening of PChE-activity towards mivacurium and which clearly identifies patients susceptible to prolonged paralysis. In this study, we designed a point-of-care (PoC) potentiometric sensor that can perform tracking of mivacurium enzymatic degradation kinetics with high accuracy and rapidly. Real serum samples were utilized for in vitro estimation of the rate of mivacurium metabolism, where values of 227 μmol l−1 and 62 μM min−1 were obtained for the characteristic parameters of the enzymatic reaction, Km and Vmax, respectively. Correlation of the results obtained using the proposed approach and earlier LC-MS/MS study is shown.

Effect of mivacurium on bispectral index value during general anesthesia induction in pediatric patients

Effect of mivacurium on bispectral index value during general anesthesia induction in pediatric patients

Muscle relaxation effect and safety of mivacurium in patients with early hepatocirrhosis

Objective To observe muscle relaxation effect and safety of mivacurium in hepatocirrhosis patients, and provide a guidance in its clinical application. Methods Candidates for elective laparoscopic surgery were divided into a hepatocirrhosis group(group C, n=32) and a non hepatocirrhosis group (group N, n=25). Muscular relaxation monitor was applied with a train of four stimulation(TOF). The intubation dosage was 0.2 mg/kg. Tracheal intubation was performed when train of four stimulation ratio(TOFr, T4∶T1) was 0, and pump infusion of mivacurium was started when muscle relaxation began to recover (TOFr>0) with a velocity of 0.6 mg·kg-1·h-1, which was switched to 0.3 mg·kg-1·h-1 and then stopped in 30 min and 20 min prior to end of suturing in group C and group N respectively. The key parameter included plasma cholinesterase(PchE) activity, histamine concentration, variation of MAP, HR, onset time of mivacurium, acting duration of the first dose, time of TOFr recovery, time from drug withdrawal to extubation, and recovery index. Results The PchE activity were(4 304±901) U/L and (6 227±1 289) U/L in two groups (P 0.05). The mean histamine concentrations of all patients were (0.196±0.020), (0.238±0.021), (0.278±0.024) μg/L prior to intravenous injection of mivacurium and in 5 min and 10 min post to injection, there were significant differences between the three times points(P 0.05). The duration of the first dose were(20±4) min and (16±3) min respectively, the recovery of TOFr to 75% were (35±10) min and (24±5) min, time from drug withdrawal to extubation were (35±9) min and (24±7) min, and there were significant differences between the two groups (P<0.05). Conclusions The plasma histamine concentration increase slightly without significant influence on MAP and HR, with satisfactory intubation conditions, good muscle relaxation and fast recovery from muscle relaxation when mivacurium was applied in patients with early hepatic cirrhosis. Compared with non hepatic cirrhosis patients, the time of muscle relaxation recovery induced by mivacurium was longer in hepatic cirrhosis patients, but compared with other muscle relaxant, it still had obvious advantages. Because mivacurium didn't directly depend on the liver to metabolize, so it could reduce the burden of liver on drug metabolism. It is recommended to be applied in patients with early hepatic cirrhosis. Key words: Cirrhosis of liver; Mivacurium chloride; Histamine; Cholinesterase; Monitoring of muscle relaxation

Optimal degree of neuromuscular blockade for inhibiting obturator nerve-muscle responses induced by transurethral resection of bladder tumor with general anesthesia

Objective To evaluate the optimal degree of neuromuscular blockade for inhibiting obturator nerve-muscle responses induced by transurethral resection of bladder tumor (TURBT) with general anesthesia. Methods Ninety American Society of Anesthesiologists physical status Ⅰ-Ⅲ patients of both sexes, aged 26-64 yr, weighing 50-80 kg, scheduled for elective TURBT for lateral bladder wall tumors with general anesthesia, were divided into 3 groups (n=30 each) using a random number table: low-dose mivacurium group (group L), medium-dose mivacurium group(group M)and high-dose mivacurium group (group H). After mivacurium 0.15 mg/kg was injected intravenously during anesthesia induction, mivacurium was continuously infused at a rate of 0.2, 0.3 and 0.4 mg·kg-1·h-1 in L, M and H groups, respectively, until the end of operation.Neuromuscular blockade was continuously monitored during operation.When T1% and TOF count(TOFC)disappeared, post tetanic count(PTC)was used.ROC curve was applied to analyze the relationship between the occurrence of obturator nerve-muscle responses and degree of neuromuscular blockade. Results T1% and TOFC were recorded in 16 patients (15 cases in group L, 1 case in group M) during the resection of tumor, and the obturator nerve-muscle response was observed in all of these patients.In the other 74 patients, T1% and TOFC disappeared, and PTC recorded was 10.0±3.1 (group L, n= 15), 6.0 ± 3.5 (group M, n=29) and 4.0±2.2 (group H, n=30). Among the 74 patients, the obturator nerve-muscle response was found in 18 patients (8 cases in group L, 10 cases in group M). The area under the ROC curve of PTC value in predicting the occurrence of obturator nerve-muscle responses was 0.882 with a PTC cut-off of 9(P<0.05). The sensitivity and specificity were 87.3% and 72.2%, respectively. Conclusion In order to inhibit the obturator nerve-muscle response during TURBT with general anesthesia, the optimal degree of neuromuscular blockade should be kept not more than 9 for PTC. Key words: Anesthesia, general; Obturator nerve; Urologic surgical procedures; Neuromuscular blockade

Evaluation of mivacurium-induced release of histamine in patients undergoing general anesthesia

Objective To evaluate mivacurium-induced release of histamine in the patients undergoing general anesthesia.Methods Eighty patients of both sexes,aged 19-58 yr,weighing 42-75 kg,of ASA physical status Ⅰ or Ⅱ,undergoing ureteroscopy under general anesthesia,were randomly divided into 2 groups (n =40 each) using a random number table:rocuronium group (group R) and mivacurium group (group M).Anesthesia was induced with iv midazolam 0.04 mg/kg,fentanyl 3 μg/kg,etomidate 0.3 mg/kg,and mivacurium 0.20 mg/kg (group M) or rocuronium 0.75 mg/kg (group R).Streamlined liner of the pharynx airway (SLIPA) was inserted for mechanical ventilation.PET CO2 was maintained at 35-40 mmHg.Anesthesia was maintained with fentanyl and propofol.Before muscle relaxant administration,at 3 min after muscle relaxant administration and at 5 min after insertion of SLIPA,venous blood samples were collected for determination of plasma histamine concentrations (by HPLC) and the histamine release was classified.Results Compared with group R,the plasma histamine concentration and histamine release were increased at 3 min after muscle relaxant administration in group M.No fatal responses caused by histamine release were found in the two groups.Conclusion Although mivacurium induces release of histamine,it can still be safely used for the patients undergoing ureteroscopy under general anesthesia. Key words: Androstanols ; Histamine ; Anesthesia, general

Effects of pri ming different low-dose rocurium on pharmacodynamics of mivacurium

To explore the effects of pri ming rocuronium on neuromuscular blockade produced by mivacurium. Ethical approval was granted by the medical ethics committee of our hospital with a reference number of C-2013-018-01. A total of 120 ASA physical status I and II patients undergoing selective otorhinolaryngologic surgery under general anesthesia signed the form of informed consent. And they were randomly divided by a random number table into 4 groups. After a standardized imidazole-propofol-fentanyl induction, they received a saline placebo injection (GroupI) and a pri ming dose of rocuronium 0.06 mg/kg (GroupII) , rocuronium 0.075 mg/kg (Group III) and rocuronium 0.1 mg/kg (Group IV). An intubating dose of mivacurium 0.15 mg/kg was offered 3 minutes later. Anesthesia was maintained with propofol and remifentanyl continuous infusion. Neuromuscular block was monitored with train of four (TOF) stimulation. The onset time, reappearance of T1 (DUR TOFc 1), times of T1 25% and 75% recovery, recovery index and times of TOF25%, 75% and 90% recovery were recorded. The onset time of mivacurium was significantly shorter and the times of T1 25% and 75% recovery were significantly longer in groups of II, III and IV than those in groupI. No significant difference existed in recovery index among 4 groups. The onset time of mivacurium became progressively shorter with the growing pri ming dose of rocurium among three experiment groups. And it was not statistically significant. Pri ming rocuronium decreases the onset and intubating times of mivacurium without effect on recovery index. No significant difference exists in drug effect among 3 experiment groups.

Effects of promethazine or dexamethasone pretreatment on histamine release induced by mivacurium in pediatric patients

Objective To evaluate the effects of promethazine or dexamethasone pretreatment on histamine release induced by mivacurium in pediatric patients.Methods Eighty pediatric patients,of ASA physical status Ⅰ or Ⅱ,aged 4-10 yr,weighing 14-30 kg,scheduled for elective tonsillectomy and adenoidectomy,were randomized into 4 groups (n =20 each) using a random number table:rocuronium group (group R),mivacurium group (group M),dexamethasone + mivacurium group (group DM) and promethazine + mivacurium group (group PM).Dexamethasone 0.2 mg/kg and promethazine 0.5 mg/kg were injected intramuscularly at 60 min before anesthesia in DM and PM groups,respectively.Anesthesia was induced with midazolam,propofol,fentanyl and rocuronium 600 μg/kg (in group R) or mivacurium 200 μg/kg (in M,MD and MP groups).At 1 min before administration of muscle relaxants and 1,3 and 5 min after administration of muscle relaxants,MAP and HR were recorded,blood samples were taken from the radial artery for determination of plasma histamine concentrations,and the cutaneous adverse reactions were observed.Results Compared with group R,MAP was significantly decreased at T1-3,HR and plasma histamine concentrations were increased at Ti,2,and the grade of cutaneous adverse reactions was increased in group M,MAP was decreased at T1,2,HR was increased at T1-3,plasma histamine concentrations were increased at T1 in group DM,and plasma histamine concentrations were increased at T1 in group PM.Compared with group M,MAP was significantly increased at T2 in group DM,MAP was increased and HR was decreased at T1-3,plasma histamine concentrations were decreased at T1,2 in group PM,and the grade of cutaneous adverse reactions was decreased in DM and PM groups.Conclusion Promethazine pretreatment can decrease the mivacurium-caused release of histamine in pediatric patients,while dexamethasone pretreatment has no such effects. Key words: Dexamethasone ; Promethazine ; Ischemic preconditioning; Androstanols ; Histamine ; Child

English

BACKGROUND: Suxamethonium, a depolarizing muscle relaxant has remained the undisputed drug for aiding intubation and an ideal drug for securing the airway because of its capabilities to produce excellent intubating conditions within 60 seconds & short duration of action but is contraindicated in certain clinical conditions because of its side effects.AIM: The present study was undertaken to compare the intubating conditions as well as duration of actions of Suxamethonium 1 mg kg-1 and mivacurium chloride, a new benzylisoquinolium non-depolarizing muscle relaxant with relatively rapid onset and short duration of action, 0.25mg kg-1 at 60 seconds. METHODS: After institutional approval and informed consent, 60 ASA I and II pediatric patients posted for elective tonsillectomies were grouped into 30 patients each. We compared the intubating conditions and duration of action of Suxamethonium 1 mg kg -1 and mivacurium chloride0.25mg kg -1 at 60 seconds. Cardiovascular responses and any side effects related to histamine release were also studied. Statistical analysis: Statistical tools used in present study are student't' test and 'chi squared' test. RESULTS: In group I, the intubating conditions in all the 30 patients were excellent except in 1 patient.In group II, 18 out of 30 patients had excellent intubating conditions, 7 patients had good, 3 patients fair and 2 patients had poor intubating conditions. CONCLUSIONS: The present study concluded that Suxamethonium produces excellent intubating conditions in 100% and mivacurium produces good to excellent intubating conditions in 83% at 60 seconds. Mivacurium chloride can be employed when Suxamethonium is contraindicated but Suxamethonium remains

Two optimized synthetic pathways toward a chiral precursor of Mivacurium chloride and other skeletal muscle relaxants

A chiral precursor of Mivacurium chloride, (R)-5′-methoxylaudanosine, was prepared using two different methods. The chiral resolution of racemic 5′-methoxylaudanosine, typically used in industry, was carried out in parallel with a procedure consisting of asymmetric transfer hydrogenation (ATH) and reductive methylation. A novel one-pot synthetic step was developed for the synthesis of racemic 5′-methoxylaudanosine. In both routes, the enantioselectivity was high but further purification was necessary to reach the level of a pharmaceutical standard. The individual synthetic steps reported herein can also be used for the synthesis of analogous bistetrahydroisoquinoline-based skeletal muscle relaxants.

Mivacurium in the past, present and future

Mivacurium chloride is the member of benzylisoquinolinium nondepolarizing neuromuscular blocking agents currently available for use in the operating room or intensive care unit. Its advantages include the shortest-acting, nondepolarizing muscle relaxant and rapid metabolism by plasma cholinesterase. Because mivacurium has noncumulative pharmacodynamic properties, it is very well suited for administration by infusion. It should be found its place among the other available nondepolarizing relaxants that are widely used in anesthesia for day surgery. Because the drug has no potentially neurotoxic effects, it can be safely used in neurosurgery. This article reviews its physicochemical properties and pharmacokinetics and pharmacodynamics. Key words: Nondepolarizing; Neuromuscular relaxants; Mivacurium chloride

Mivacurium chloride, as an adjunct to fentanyl and atropine, is beneficial for nonemergent endotracheal intubation of neonates,

Mivacurium chloride, as an adjunct to fentanyl and atropine, is beneficial for nonemergent endotracheal intubation of neonates,

Detection of Quaternary Ammonium Drugs in Equine Urine by Liquid Chromatography-Mass Spectrometry

Quaternary ammonium drugs are anticholinergic agents and some of which have been known to be abused in equine sports. A general screening method for this class of drugs in equine urine by liquid chromatography-mass spectrometry (LC-MS) has not been reported. The paper describes an efficient LC-MS-MS method for the simultaneous detection and confirmation of twenty quaternary ammonium drugs at low ng mL−1 in equine urine after solid-phase extraction. Quaternary ammonium drugs were extracted from equine urine by solid-phase extraction using ISOLUTE® CBA SPE Columns and analysed by LC-MS-MS in the positive electrospray ionisation mode. Separation of twenty quaternary ammonium drugs (the quaternary ammonium ions of edrophonium chloride, pyridostigmine bromide, neostigmine bromide, bretylium tosylate, ipratropium bromide, tubocurarine chloride, N-butylscopolammonium bromide, mepenzolate bromide, rocuronium bromide, clidinium bromide, pipenzolate bromide, isopropamide iodide, glycopyrronium bromide, alcuronium chloride, oxyphenonium bromide, propantheline bromide, tridihexethyl chloride, vecuronium bromide, mivacurium chloride and pancuronium bromide) was achieved in a reversed phase column with a mixture of aqueous ammonium formate (pH 3.0, 10 mM) and acetonitrile as the mobile phase. Detection and confirmation of the twenty quaternary ammonium drugs at about 5 ng mL−1 in equine urine could be achieved within 22 min using product-ion scan MS-MS. The target analytes were detected by examination of extracted-ion chromatograms of their product ions. Drugs spiked in different equine urine (n = 15) were consistently detected. Negative samples (n = 30) of normal post-race equine urine have also been analysed, no matrix interference at the targeted masses and retention times was observed. The method was successfully applied to the analyses of drug-administration samples. Other method validation data including reproducibility and recovery will also be presented. An LC-MS-MS method for the simultaneous detection and confirmation of twenty quaternary ammonium drugs in equine urine was developed. The methodology should be applicable to other biological matrices such as human urine.

Selecting Neuromuscular-Blocking Drugs for Elderly Patients

The physiological changes that occur with increasing age can have significant effects on the pharmacokinetics of neuromuscular-blocking drugs. Changes in cardiac output can affect drug distribution and therefore the speed of onset of neuromuscular block. A decrease in muscle mass and increase in body fat with age can also affect their distribution. The deterioration in renal and hepatic function associated with aging affects the clearance and elimination of many neuromuscular-blocking drugs. The effects of these physiological changes on the pharmacokinetics of neuromuscular-blocking agents may not become apparent clinically in healthy individuals until the age of at least 75 years. There is very little evidence to suggest any alteration in the sensitivity of the neuromuscular junction to neuromuscular-blocking drugs with increasing age. Neuromuscular-blocking drugs that undergo a significant degree of organ-dependent elimination, such as pancuronium bromide, vecuronium bromide, rocuronium bromide and doxacurium chloride, may have a significantly prolonged duration of action in elderly patients. These drugs can be used safely in elderly patients if the anaesthetist is aware of their altered pharmacokinetics in this patient group. Appropriate changes must be made to drug dosage and dose intervals. As the pharmacokinetic changes can be unpredictable, monitoring of neuromuscular block is strongly advised when using these drugs in such patients. The risk of residual block occurring postoperatively after the use of pancuronium bromide increases with age. The duration of action of mivacurium chloride may also be prolonged in the elderly; this change has not been demonstrated to be a result of an alteration in plasma cholinesterase activity. In contrast, there is no evidence of an alteration in the action of suxamethonium chloride (succinylcholine chloride) with increasing age. Atracurium besilate and cisatracurium besilate undergo predominantly organ-independent elimination. Onset of block with these two drugs may be prolonged in the elderly, but their clinical duration of action does not alter significantly with age, making them particularly suitable for use in this patient group. Although atracurium besilate may cause histamine release, there is little evidence of it producing haemodynamic changes in the elderly. Its (1R,1R')-isomer, cisatracurium besilate, has very little direct or indirect cardiovascular effect and is, therefore, the most suitable nondepolarising agent to use in elderly patients.

Pharmacodynamics of mivacurium chloride in 13- to 18-yr-old adolescents with thermal injury

Burned patients demonstrate resistance to the effects of non-depolarizing blocking drugs as a result of acetylcholine receptor changes. They also have decreased activity of plasma cholinesterase (PCHE), which metabolizes mivacurium. We hypothesized that decreased PCHE activity would decrease metabolism of mivacurium, and counteract the receptor-related resistance following burns. Thirteen burned patients and six controls, aged 13-18 yr were followed in 27 studies. The burned patients were sub-classified as having 10-30% or >30% body surface area burn and were studied whenever possible at < or =6 days, and at 1-12 weeks after the burn. Mivacurium pharmacodynamics were examined following a bolus (0.15 mg kg(-1)) dose, and during and after a continuous infusion. Following a bolus, the onset time and the maximal effect were similar to controls. Recovery was prolonged in the 10-30% burn group at 1-12 weeks (P<0.008), with a similar trend in the >30% burn group at < or =6 days (P<0.082) compared with controls. The infusion requirements for mivacurium were not increased in the burned groups. The PCHE activity was decreased in all burn groups and was inversely related to recovery following the bolus (r=0.73, P<0.001) and the infusion (r=0.69, P<0.001). In contrast to previous studies with non-depolarizers in burned patients, normal mivacurium doses can produce paralysis, at least as rapidly as in controls, but with a possibility of a prolonged recovery from block. The standard dose of mivacurium in the presence of decreased PCHE activity is in effect, a relative overdose that explains the above findings. Mivacurium is an effective drug for use in burns, irrespective of time after, or magnitude of burn injury.

Succinylcholine pretreatment using gallamine or mivacurium during rapid sequence induction in children: a randomized, controlled study

Study Objective: To determine if pretreatment with either gallamine or mivacurium before succinylcholine in children is associated with reduction in fasciculations; postoperative myalgias; or serum levels of potassium, creatinine phosphokinase (CPK), and myoglobin. Design: Prospective, randomized, double-blinded study. Setting: Operating room at a children’s hospital. Patients: 45 ASA physical status IE children, aged 3 to 15 years, scheduled for emergency surgery. Interventions: The children received either normal saline 0.5 mL, mivacurium chloride 0.03 mg · kg -1 , or gallamine triethiodide 0.04 mg · kg -12 minutes prior to rapid sequence induction (RSI) using thiopental sodium 5 mg · kg -1, fentanyl 2 μg · kg -1 , and succinylcholine 2 mg · kg -1. Measurements: Serum potassium concentration (0, 3, 5, 7.5, and 15 min), myoglobin concentration (5 and 15 min), and CPK concentration (0 min and 24 hr). Fasciculation and myalgia were rated on a 0 to 3 score. Main Results: There was no difference between groups for fasciculation (p = 0.87) or myalgia score (p = 0.52). The mivacurium group had significantly less increase in potassium at 5 minutes (0.45 vs. 0.0, p = 0.01), myoglobin at 5 minutes (56 vs . 2, p < 0.001), myoglobin at 15 minutes (128 vs . 2.5, p < 0.001), and CPK at 24 hours (399 vs . 138, p < 0.001) following succinylcholine when compared with normal saline. Additionally, we found a significant level of association (p < 0.001) between fasciculation and myoglobin levels and fasciculation and CPK levels (p < 0.001). Gallamine was not effective in reducing the increase of potassium, myoglobin, or CPK. However, the dose of gallamine used for pretreatment was 13 times less than the dose of mivacurium. Conclusions: Administration of mivacurium 0.03 mg · kg -1 intravenously 2 minutes before administration of succinylcholine 2 mg · kg -1 in children is effective in reducing the increase in serum potassium at 5 minutes, the increase in myoglobin at 5 minutes and 15 minutes, and the increase in CPK at 24 hours.