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Diana Faulds - One of the best experts on this subject based on the ideXlab platform.
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CisAtracurium Besilate. A review of its pharmacology and clinical potential in anaesthetic practice.
Drugs, 1997Co-Authors: Harriet M. Bryson, Diana FauldsAbstract:: CisAtracurium Besilate (besylate) is a nondepolarising neuromuscular blocking agent with an intermediate duration of action. It is the R-cis, R'-cis isomer of Atracurium Besilate and is approximately 3-fold more potent than the mixture of isomers that constitute the parent drug. The ED95 for cisAtracurium Besilate (dose required to produce 95% suppression of twitch response to nerve stimulation) in adults is 0.05 mg/kg during N2O/O2 opioid anaesthesia. As for Atracurium Besilate, the primary route of elimination of cisAtracurium Besilate is by spontaneous degradation. CisAtracurium Besilate is not associated with dose-related histamine release (at bolus doses of < or = 8 x ED95) and, consistent with this, has demonstrated cardiovascular stability in both healthy patients (< or = 8 x ED95) and those with coronary artery disease (< or = 6 x ED95). In clinical trials, cisAtracurium Besilate has been used successfully to facilitate intubation (at 2 to 4 x ED95) and as a muscle relaxant during surgery and in intensive care. Compared with vecuronium, cisAtracurium Besilate was associated with a significantly faster recovery after continuous infusion in patients in intensive care. Relative to Atracurium Besilate, cisAtracurium Besilate has a lower propensity to cause histamine release is more potent but has a slightly longer onset time at equipotent doses. It also offers a more predictable recovery profile than vecuronium after prolonged use in patients in intensive care. Thus, comparative data provide some indication of the potential of cisAtracurium Besilate as an intermediate-duration neuromuscular blocking agent but further comparisons with other like agents are required to define precisely its relative merits.
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CisAtracurium Besilate
Drugs, 1997Co-Authors: Harriet M. Bryson, Diana FauldsAbstract:Synopsis CisAtracurium Besilate (besylate) is a nondepolarising neuromuscular blocking agent with an intermediate duration of action. It is the R-cis,R′-cis isomer of Atracurium Besilate and is approximately 3-fold more potent than the mixture of isomers that constitute the parent drug. The ED_95for cisAtracurium Besilate (dose required to produce 95% suppression of twitch response to nerve stimulation) in adults is 0.05 mg/kg during N_2O/O_2 opioid anaesthesia. As for Atracurium Besilate, the primary route of elimination of cisAtracurium Besilate is by spontaneous degradation. CisAtracurium Besilate is not associated with dose-related histamine release (at bolus doses of≤8 × ED95) and, consistent with this, has demonstrated cardiovascular stability in both healthy patients (≤8 × ED95) and those with coronary artery disease (≤6 × ED95). In clinical trials, cisAtracurium Besilate has been used successfully to facilitate intubation (at 2 to 4× ED95) and as a muscle relaxant during surgery and in intensive care. Compared with vecuronium, cisAtracurium Besilate was associated with a significantly faster recovery after continuous infusion in patients in intensive care. Relative to Atracurium Besilate, cisAtracurium Besilate has a lower propensity to cause histamine release, is more potent but has a slightly longer onset time at equipotent doses. It also offers a more predictable recovery profile than vecuronium after prolonged use in patients in intensive care. Thus, comparative data provide some indication of the potential of cisAtracurium Besilate as an intermediate-duration neuromuscular blocking agent but further comparisons with other like agents are required to define precisely its relative merits. Pharmacodynamic Properties The ED95 of cisAtracurium Besilate (dose required to produce 95% suppression of twitch response to nerve stimulation) is approximately 0.05 mg/kg in adults and children during N_2O/O_2/opioid anaesthesia and 0.04 mg/kg during halothane/N_2O/O_2 anaesthesia in children. The degree and duration of neuromuscular block produced by cisAtracurium Besilate increases and time to maximum neuromuscular block decreases in a dose-dependent manner. CisAtracurium Besilate 0.1 mg/kg (2 × ED95) produces 99 to 100% twitch suppression within 4.6 to 5.8 minutes compared with 2.4 to 3.7 minutes after a 0.15 mg/kg dose (3 × ED95) and 2.7 to 3.8 minutes after 0.2 mg/kg (4 × ED95). The time to maximum effect was delayed by approximately 1 minute in the elderly and in patients with renal failure and shortened by almost 1 minute in patients with end-stage liver disease. Clinical duration of neuromuscular block (i.e. time from injection to 25% twitch recovery) ranges from 33 to 45 minutes after cisAtracurium Besilate 0.1 mg/kg (2 × ED95) and is approximately 55 minutes after cisAtracurium Besilate 0.15 mg/kg (3 × ED95) during either barbiturate/N_2O/O_2 or propofol/N_2O/O_2 anaesthesia. Doubling the dose of cisAtracurium Besilate from 0.1 to 0.2 mg/kg increased the clinical duration of effect by 16 to 23 minutes. Once started, recovery (i.e. 5 to 95% or 25 to 75% recovery indices) was independent of dose over the range 0.1 to 0.4 mg/kg. Recovery rate was unaffected by age, renal failure or end-stage liver disease, but appeared to be slower following the use of sevoflurane in children. As for other nondepolarising agents, recovery from neuromuscular block with cisAtracurium Besilate can be effectively accelerated by administration of an anticholinesterase agent once recovery has started. CisAtracurium Besilate, at doses of ≤8 × ED95 in adult patients, was not associated with any significant changes in mean blood pressure or heart rate. In patients with coronary artery disease, doses of-≤6 × ED95 were not associated with a ≥20% decrease in mean arterial pressure in any patient; the incidence of other haemodynamic changes did not differ between cisAtracurium Besilate (0.1 or 0.3 mg/kg) or vecuronium (0.1 or 0.3 mg/kg) recipients. CisAtracurium Besilate at doses of ≤8 × ED95 is not associated with dose-related changes in median plasma histamine levels. Pharmacokinetic Properties CisAtracurium Besilate undergoes temperature and pH-dependent chemical (Hofmann) degradation. This is the main route by which the drug is broken down and accounts for 77% of its total clearance. CisAtracurium Besilate degrades to form laudanosine and the corresponding monoquaternary acrylate (which in turn is broken down to a monoquaternary alcohol and then laudanosine). Although the liver and kidneys play only a small role in the excretion of cisAtracurium Besilate, urinary and hepatic elimination pathways are important for the metabolites of laudanosine. The apparent volume of distribution of cisAtracurium Besilate at steady-state ranges from 0.11 to 0.16 L/kg in healthy adults. However, because these values do not allow for peripheral elimination of the drug, it is likely that they are underestimates. CisAtracurium Besilate is cleared from the body at a rate of 0.27 to 0.34 L/h/kg, with an elimination half-life of 22 to 35 minutes. Clinical Potential Good or excellent intubating conditions were achieved after 120 seconds in 89 to 100% of patients receiving cisAtracurium Besilate 0.15 mg/kg (3 × ED95). This was a similar result to that achieved with Atracurium Besilate 0.5 mg/kg (2 × ED95) after 120 seconds. At 4 × ED95 of cisAtracurium Besilate (0.2 mg/kg), good or excellent intubating conditions were generally achieved after 90 seconds in 95 to 100% of patients; poorer results attained with this dose in 2 European studies may have been attributable to the fact that midazolam was not administered as part of the induction regimen. In adult patients undergoing elective surgery, the mean infusion rate of cisAtracurium Besilate required to maintain approximately 95% block ranged from 1.2 to 1.5 µg/kg/min during N_2O/O_2/opioid or propofol anaesthesia. Mean infusion requirements for children (aged 2 to 12 years) were 1.6 and 1.8 µg/kg/ min in 2 studies. The 25 to 75% recovery index ranged from 15 to 18 minutes in adults and 11 or 14 minutes in children after a continuous infusion of cisAtracurium Besilate. Limited data indicate that recovery is independent of duration of infusion or the number of maintenance doses administered, but this requires confirmation. For adult patients in intensive care, the mean infusion rate of cisAtracurium Besilate required to maintain adequate neuromuscular block ranged between 2.6 and 3.2 µg/kg/min. The mean time to 70% recovery of the ratio of the fourth to the first train-of-four response after an infusion duration of at least 12 hours was significantly faster in cisAtracurium Besilate than vecuronium recipients (68 vs 387 minutes). Tolerability According to an overview of all clinical data (n=946), events possibly related to cisAtracurium Besilate were bradycardia (0.4%), hypotension (0.2%), flushing (0.2%), bronchospasm (0.2%) and rash (0.1%). No event was reported at a frequency of >1%. In comparative clinical studies, flushing was reported in 0% of patients receiving cisAtracurium Besilate (2 to 4 × ED95) versus 0 to 11% of patients receiving Atracurium Besilate (2 × ED95). Dosage and Administration In adult patients, cisAtracurium Besilate 0.15 or 0.2 mg/kg following induction with propofol/N_2O/O_2 generally produces good or excellent intubating conditions at 2 and 1.5 minutes, respectively. A longer time to intubation may be required in the elderly, in patients with renal failure or with lower doses of cisAtracurium Besilate. In children (aged 2 to 12 years), the recommended initial dose is 0.1 mg/kg administered during halothane or opioid anaesthesia. Doses should be individualised and neuromuscular function should be monitored during drug administration, as for any muscle relaxant. For prolonged surgery, maintenance doses of cisAtracurium Besilate 0.03 mg/kg should be used. Each additional maintenance dose maintains neuromuscular block for approximately 20 minutes. For continuous infusion of cisAtracurium Besilate, an initial infusion rate of 3 µg/kg/min is suggested, followed by a rate of 1 to 2 µg/kg/min to maintain 89 to 99% block during opioid/N_2O/O_2 anaesthesia. A 30 to 40% reduction in infusion rate should be considered during isoflurane or enflurane anaesthesia; greater reductions may be necessary if anaesthesia is prolonged. In adult patients in intensive care, an infusion rate of approximately 3 (range 0.5 to 10.2) µg/kg/min should provide adequate neuromuscular block, although requirements may vary with time.
Yp Wang - One of the best experts on this subject based on the ideXlab platform.
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HICH-PERFORMANCE LIQUID CHROMATOGRAPHY OF Atracurium Besilate
Acta pharmaceutica Sinica, 1994Co-Authors: Yp WangAbstract:The separation and determination of Atracurium Besilate and its three stereoisomerswere studied, Atracurium Besilate and its related compounds ,and the three stereoisomers of.(±)Atracurium Besilate were fairly well separated with a nitrile- bonded phase column By acetonitrile-water-phosphoric acid-sulphuric acid(92 :8:0.4:0.03)mobile phase and methanol-sulphuric acid(1000 :1)mobile phase , respectively. The influence of the component concentrations of the mobilephase system on the retention and resolution was investigated. The results indicate that the methodgives good reproducibility and wide response linearity. The detection limit of Atracurium Besilate was10 ng.This method can be applied to the routine analysis and clinical determination of AtracuriumBesilate。
Harriet M. Bryson - One of the best experts on this subject based on the ideXlab platform.
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CisAtracurium Besilate. A review of its pharmacology and clinical potential in anaesthetic practice.
Drugs, 1997Co-Authors: Harriet M. Bryson, Diana FauldsAbstract:: CisAtracurium Besilate (besylate) is a nondepolarising neuromuscular blocking agent with an intermediate duration of action. It is the R-cis, R'-cis isomer of Atracurium Besilate and is approximately 3-fold more potent than the mixture of isomers that constitute the parent drug. The ED95 for cisAtracurium Besilate (dose required to produce 95% suppression of twitch response to nerve stimulation) in adults is 0.05 mg/kg during N2O/O2 opioid anaesthesia. As for Atracurium Besilate, the primary route of elimination of cisAtracurium Besilate is by spontaneous degradation. CisAtracurium Besilate is not associated with dose-related histamine release (at bolus doses of < or = 8 x ED95) and, consistent with this, has demonstrated cardiovascular stability in both healthy patients (< or = 8 x ED95) and those with coronary artery disease (< or = 6 x ED95). In clinical trials, cisAtracurium Besilate has been used successfully to facilitate intubation (at 2 to 4 x ED95) and as a muscle relaxant during surgery and in intensive care. Compared with vecuronium, cisAtracurium Besilate was associated with a significantly faster recovery after continuous infusion in patients in intensive care. Relative to Atracurium Besilate, cisAtracurium Besilate has a lower propensity to cause histamine release is more potent but has a slightly longer onset time at equipotent doses. It also offers a more predictable recovery profile than vecuronium after prolonged use in patients in intensive care. Thus, comparative data provide some indication of the potential of cisAtracurium Besilate as an intermediate-duration neuromuscular blocking agent but further comparisons with other like agents are required to define precisely its relative merits.
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CisAtracurium Besilate
Drugs, 1997Co-Authors: Harriet M. Bryson, Diana FauldsAbstract:Synopsis CisAtracurium Besilate (besylate) is a nondepolarising neuromuscular blocking agent with an intermediate duration of action. It is the R-cis,R′-cis isomer of Atracurium Besilate and is approximately 3-fold more potent than the mixture of isomers that constitute the parent drug. The ED_95for cisAtracurium Besilate (dose required to produce 95% suppression of twitch response to nerve stimulation) in adults is 0.05 mg/kg during N_2O/O_2 opioid anaesthesia. As for Atracurium Besilate, the primary route of elimination of cisAtracurium Besilate is by spontaneous degradation. CisAtracurium Besilate is not associated with dose-related histamine release (at bolus doses of≤8 × ED95) and, consistent with this, has demonstrated cardiovascular stability in both healthy patients (≤8 × ED95) and those with coronary artery disease (≤6 × ED95). In clinical trials, cisAtracurium Besilate has been used successfully to facilitate intubation (at 2 to 4× ED95) and as a muscle relaxant during surgery and in intensive care. Compared with vecuronium, cisAtracurium Besilate was associated with a significantly faster recovery after continuous infusion in patients in intensive care. Relative to Atracurium Besilate, cisAtracurium Besilate has a lower propensity to cause histamine release, is more potent but has a slightly longer onset time at equipotent doses. It also offers a more predictable recovery profile than vecuronium after prolonged use in patients in intensive care. Thus, comparative data provide some indication of the potential of cisAtracurium Besilate as an intermediate-duration neuromuscular blocking agent but further comparisons with other like agents are required to define precisely its relative merits. Pharmacodynamic Properties The ED95 of cisAtracurium Besilate (dose required to produce 95% suppression of twitch response to nerve stimulation) is approximately 0.05 mg/kg in adults and children during N_2O/O_2/opioid anaesthesia and 0.04 mg/kg during halothane/N_2O/O_2 anaesthesia in children. The degree and duration of neuromuscular block produced by cisAtracurium Besilate increases and time to maximum neuromuscular block decreases in a dose-dependent manner. CisAtracurium Besilate 0.1 mg/kg (2 × ED95) produces 99 to 100% twitch suppression within 4.6 to 5.8 minutes compared with 2.4 to 3.7 minutes after a 0.15 mg/kg dose (3 × ED95) and 2.7 to 3.8 minutes after 0.2 mg/kg (4 × ED95). The time to maximum effect was delayed by approximately 1 minute in the elderly and in patients with renal failure and shortened by almost 1 minute in patients with end-stage liver disease. Clinical duration of neuromuscular block (i.e. time from injection to 25% twitch recovery) ranges from 33 to 45 minutes after cisAtracurium Besilate 0.1 mg/kg (2 × ED95) and is approximately 55 minutes after cisAtracurium Besilate 0.15 mg/kg (3 × ED95) during either barbiturate/N_2O/O_2 or propofol/N_2O/O_2 anaesthesia. Doubling the dose of cisAtracurium Besilate from 0.1 to 0.2 mg/kg increased the clinical duration of effect by 16 to 23 minutes. Once started, recovery (i.e. 5 to 95% or 25 to 75% recovery indices) was independent of dose over the range 0.1 to 0.4 mg/kg. Recovery rate was unaffected by age, renal failure or end-stage liver disease, but appeared to be slower following the use of sevoflurane in children. As for other nondepolarising agents, recovery from neuromuscular block with cisAtracurium Besilate can be effectively accelerated by administration of an anticholinesterase agent once recovery has started. CisAtracurium Besilate, at doses of ≤8 × ED95 in adult patients, was not associated with any significant changes in mean blood pressure or heart rate. In patients with coronary artery disease, doses of-≤6 × ED95 were not associated with a ≥20% decrease in mean arterial pressure in any patient; the incidence of other haemodynamic changes did not differ between cisAtracurium Besilate (0.1 or 0.3 mg/kg) or vecuronium (0.1 or 0.3 mg/kg) recipients. CisAtracurium Besilate at doses of ≤8 × ED95 is not associated with dose-related changes in median plasma histamine levels. Pharmacokinetic Properties CisAtracurium Besilate undergoes temperature and pH-dependent chemical (Hofmann) degradation. This is the main route by which the drug is broken down and accounts for 77% of its total clearance. CisAtracurium Besilate degrades to form laudanosine and the corresponding monoquaternary acrylate (which in turn is broken down to a monoquaternary alcohol and then laudanosine). Although the liver and kidneys play only a small role in the excretion of cisAtracurium Besilate, urinary and hepatic elimination pathways are important for the metabolites of laudanosine. The apparent volume of distribution of cisAtracurium Besilate at steady-state ranges from 0.11 to 0.16 L/kg in healthy adults. However, because these values do not allow for peripheral elimination of the drug, it is likely that they are underestimates. CisAtracurium Besilate is cleared from the body at a rate of 0.27 to 0.34 L/h/kg, with an elimination half-life of 22 to 35 minutes. Clinical Potential Good or excellent intubating conditions were achieved after 120 seconds in 89 to 100% of patients receiving cisAtracurium Besilate 0.15 mg/kg (3 × ED95). This was a similar result to that achieved with Atracurium Besilate 0.5 mg/kg (2 × ED95) after 120 seconds. At 4 × ED95 of cisAtracurium Besilate (0.2 mg/kg), good or excellent intubating conditions were generally achieved after 90 seconds in 95 to 100% of patients; poorer results attained with this dose in 2 European studies may have been attributable to the fact that midazolam was not administered as part of the induction regimen. In adult patients undergoing elective surgery, the mean infusion rate of cisAtracurium Besilate required to maintain approximately 95% block ranged from 1.2 to 1.5 µg/kg/min during N_2O/O_2/opioid or propofol anaesthesia. Mean infusion requirements for children (aged 2 to 12 years) were 1.6 and 1.8 µg/kg/ min in 2 studies. The 25 to 75% recovery index ranged from 15 to 18 minutes in adults and 11 or 14 minutes in children after a continuous infusion of cisAtracurium Besilate. Limited data indicate that recovery is independent of duration of infusion or the number of maintenance doses administered, but this requires confirmation. For adult patients in intensive care, the mean infusion rate of cisAtracurium Besilate required to maintain adequate neuromuscular block ranged between 2.6 and 3.2 µg/kg/min. The mean time to 70% recovery of the ratio of the fourth to the first train-of-four response after an infusion duration of at least 12 hours was significantly faster in cisAtracurium Besilate than vecuronium recipients (68 vs 387 minutes). Tolerability According to an overview of all clinical data (n=946), events possibly related to cisAtracurium Besilate were bradycardia (0.4%), hypotension (0.2%), flushing (0.2%), bronchospasm (0.2%) and rash (0.1%). No event was reported at a frequency of >1%. In comparative clinical studies, flushing was reported in 0% of patients receiving cisAtracurium Besilate (2 to 4 × ED95) versus 0 to 11% of patients receiving Atracurium Besilate (2 × ED95). Dosage and Administration In adult patients, cisAtracurium Besilate 0.15 or 0.2 mg/kg following induction with propofol/N_2O/O_2 generally produces good or excellent intubating conditions at 2 and 1.5 minutes, respectively. A longer time to intubation may be required in the elderly, in patients with renal failure or with lower doses of cisAtracurium Besilate. In children (aged 2 to 12 years), the recommended initial dose is 0.1 mg/kg administered during halothane or opioid anaesthesia. Doses should be individualised and neuromuscular function should be monitored during drug administration, as for any muscle relaxant. For prolonged surgery, maintenance doses of cisAtracurium Besilate 0.03 mg/kg should be used. Each additional maintenance dose maintains neuromuscular block for approximately 20 minutes. For continuous infusion of cisAtracurium Besilate, an initial infusion rate of 3 µg/kg/min is suggested, followed by a rate of 1 to 2 µg/kg/min to maintain 89 to 99% block during opioid/N_2O/O_2 anaesthesia. A 30 to 40% reduction in infusion rate should be considered during isoflurane or enflurane anaesthesia; greater reductions may be necessary if anaesthesia is prolonged. In adult patients in intensive care, an infusion rate of approximately 3 (range 0.5 to 10.2) µg/kg/min should provide adequate neuromuscular block, although requirements may vary with time.
Jennifer M. Hunter - One of the best experts on this subject based on the ideXlab platform.
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Selecting Neuromuscular-Blocking Drugs for Elderly Patients
Drugs & Aging, 2003Co-Authors: Tristan M. Cope, Jennifer M. HunterAbstract: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 (succinylchol-ine 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.
Tristan M. Cope - One of the best experts on this subject based on the ideXlab platform.
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Selecting Neuromuscular-Blocking Drugs for Elderly Patients
Drugs & Aging, 2003Co-Authors: Tristan M. Cope, Jennifer M. HunterAbstract: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 (succinylchol-ine 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.