Atracurium Research Articles

Measurement of Hemodynamic Changes Caused by Administration of Atracurium Besylate after Pretreatment with Anti-histamine Agent

Background: Hemodynamic changes through the histamine-induced release of atracurium are relatively common, but can be particularly dangerous in hemodynamically unstable patients. This study evaluated the effectiveness of a pretreatment with an anti-histamine agent before the administration of atracurium in the prevention of histamine-induced hemodynamic changes. Methods: Forty-eight ASA class I and II patients were assigned to four groups. Groups 1 and 2 were assigned to receive atracurium through a bolus 0.5 mg/kg. Groups 3 and 4 were assigned to receive atracurium through a bolus 1.0 mg/kg. Group 1 and 3 were pretreated with pheniramine (H1-blocker) and ranitidine (H2-blocker) intravenously before the induction of general anesthesia. After induction, Hemosonic TM 100 was installed and the following hemodynamic parameters were measured: systemic vascular resistance (SVR), cardiac index (CI), heart rate (HR) and blood pressure (BP) immediately before, 1, 2, 3, 5 and 10 min after the rapid administration of the atracurium bolus befo re the skin incision. Results: Groups 1 and 3 showed more stable hemodynamics than groups 2 and 4. Group 2 showed more significant changes in the SVR, CI, BP, HR than group 1 (P ＜ 0.05). Group 4 showed more significant changes in the SVR, CI, BP, HR than group 3, and some cases were significant hemodynamically (P ＜ 0.05). Group 4 showed more significant changes in the SVR, CI, BP, HR than group 2 (P ＜ 0.05). Conclusions: Pretreatment with an anti-histamine drug prior to the administration of atracurium can be effective in attenuating

The effect of neostigmine and atropine combination on postoperative nausea and vomiting after arthroscopic surgery

Postoperative nausea and vomiting prolong the time spent in postanesthesia recovery units. In this study, we investigated the effect of neostigmine and atropine combination, used to avoid residual curarization, on nausea and vomiting. The study included 40 ASA I-II patients who were planned to have a short-term arthroscopic operation. The patients were administered a single dose of 0.4 mg/kg atracurium besylate for muscle relaxation, and then, were randomly divided into two groups. In group I, neuromuscular blockade was eliminated with 1.5 mg neostigmine and 0.5 mg atropine, whereas group II patients underwent spontaneous resolution. The patients were evaluated for nausea and vomiting and the need for antiemetic drugs in the recovery unit, patient room, and on the postoperative second day. There were no significant differences between the two groups with respect to hemodynamic parameters and peripheral oxygen saturation. The mean operation time did not differ significantly (p>0.05), but the mean extubation time was significantly shorter in group I (p<0.05). No significant differences were observed for the occurrence of nausea and vomiting and the need for antiemetic drugs in the recovery unit, patient room, and on the postoperative second day (p>0.05). In patients undergoing arthroscopic surgery, it is safe to use neostigmine and atropine combination before extubation to avoid residual neuromuscular blockade associated with the use of non-depolarizing myorelaxants.

The Danger With Neuromuscular Blocking Agents

It is not uncommon to find a variety of neuromuscular blocking agents (NMBs) (eg, succinylcholine chloride, atracurium besylate [Tracium], vecuronium bromide, and pancuronium bromide) in the emergency department because of the urgent need for these medications during unplanned endotracheal intubations. Used primarily to support skeletal muscle relaxation prior to intubation procedures,1 these medications are commonly found in trauma/resuscitation rooms, medication stock cabinets and refrigerators, rapid sequence intubation boxes, and even in the pockets of responding anesthesia personnel. Although these medications frequently are used for intubation, they must be used with extreme caution. Although no more errors occur with NMBs than with other medications, these “high-alert” drugs have the propensity to cause serious harm when an error occurs.2 Unfortunately, a variety of reports of serious errors have been associated with these medications, commonly related to look-alike packaging and storage issues. Consider the following scenarios below and whether they could actually happen in your emergency department.

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.

The effect of intratracheal and intravenous lidocaine in hydrochloric acid-induced acute lung injury in rabbits

The aim of this study was to show the effect of intratracheal (IT) and intravenous (IV) lidocaine on haemodynamic and arterial blood gas values in hydrochloric acid (HCl) induced-acute lung injury (ALI) in rabbits. Twenty New Zealand rabbits were randomly divided into for groups of five. An endotracheal tube was placed through a tracheostomy in all animals following ketamine hydrochloride (50 mg/kg, intramuscularly) induced anaesthesia. Maintenance of anaesthesia was achieved by the use of ketamine hydrochloride 10 mg/kg/h and atracurium besylate 1 mg/kg/h. The animals were ventilated with Pressure Control mod for 3 hours and the parameters of ventilation were FiO2: 1.0, RR: 80/min, Vt: 8 ml/kg, I/E: 1/2, PEEP: 5 cmH2O. Intratracheal HCl (2 ml/kg), was given following tracheostomy in all animals. Five minutes after the application of HCl the group 1 received IV lidocaine (2 mg/kg), group 2 received IT lidocaine (2 mg/kg), group 3 received IV lidocaine (4 mg/kg) and group 4 received IT lido-caine (4 mg/kg). We recorded mean arterial blood pressures (MAP), heart rate (HR) every 60 min. We measured arterial blood gas values (PaO2, PaCO2, pH) at beginning of the study, at 90th and 180th minutes. Data were compared by Mann–Whitney U-test. A P value of less than 0.05 was considered to indicate statistical significance. MAP levels of group 2 and group 4 were higher than group 1 and group 3 at 120th and 180th minutes (P < 0.05). HR levels of group 2 were lower than the other groups at 120th and 180th minutes (P < 0.05). PaO2 levels of group 1 were higher than the other groups at 180th minute (P < 0.001). There was no significant difference between four groups regarding PaCO2, pH. In conclusion, IT and IV lidocaine (2 mg/kg) given after 5 min of HCl application had a beneficial effect on the haemodynamic and arterial blood gas values in acute lung injury in rabbits model.

Newer neuromuscular blocking agents: how do they compare with established agents?

Rapacuronium bromide (rapacuronium; ORG-9487) is a nondepolarising muscle relaxant (NMBA) with a low potency [90% effective dose (ED90) 1 mg/kg], which to some extent is responsible for its rapid onset of action. Because of the high plasma clearance (5.3 to 11.1 mg/kg/min) of rapacuronium, its clinical duration of action following single bolus doses up to 2 mg/kg in adults is short (i.e. <20 minutes). Rapacuronium forms a pharmacologically active 3-desacetyl metabolite, ORG-9488, which may contribute to a delay in spontaneous recovery after repeat bolus doses or infusions. After rapacuronium 1.5 mg/kg clinically acceptable intubating conditions are achieved within 60 to 90 seconds in the majority of adult and elderly patients undergoing elective anaesthesia. However, in a rapid-sequence setting. intubating conditions are less favourable after rapacuronium 1.5 to 2.5 mg/kg than after succinylcholine. The most prominent adverse effects of rapacuronium (tachycardia, hypotension and bronchospasm) are dose-related, and in particular pulmonary adverse effects are observed more frequently under conditions of a rapid-sequence induction in adults. Therefore, it seems worthwhile to consider only doses of rapacuronium < or = 1.5 mg/kg to facilitate rapid tracheal intubation, and to use succinylcholine or rocuronium rather than rapacuronium in a rapid-sequence setting. Rapacuronium, however, is a suitable alternative to mivacurium chloride (mivacurium) and succinylcholine for short procedures (e.g. ambulatory anaesthesia). Rocuronium bromide (rocuronium) is a relatively low-potent, intermediateacting NMBA. Its main advantage is the rapid onset of neuromuscular block whereby good or excellent intubating conditions are achieved within 60 to 90 seconds after rocuronium 0.6 mg/kg (2 x ED95), and within 60 to 180 seconds after smaller doses (1 to 1.5 x ED95). Larger doses of rocuronium (> or = 1 mg/kg) seem to be suitable for rapid-sequence induction under relatively light anaesthesia. However, it is still a matter of controversy whether, in the case of an unanticipated difficult intubation, the long duration of rocuronium administered in such large doses outweighs the many adverse effects of succinylcholine. Rocuronium has mild vagolytic effects and does not release histamine, even when administered in large doses. Rocuronium is primarily eliminated via the liver and its pharmacokinetic profile is similar to that of vecuronium bromide (vecuronium). Unlike vecuronium, rocuronium has no metabolite. Cisatracurium besilate (cisatracurium), the IR-cis, 1'R-cis isomer of atracurium besilate (atracurium) is approximately 4 times more potent than atracurium. The onset time of cisatracurium is significantly slower than after equipotent doses of atracurium. The recommended intubating dose is 0.15 to 0.2 mg/kg (3 to 4 times ED95). Over a wide range of clinically relevant doses the recovery properties of cisatracurium are affected by neither the size of the bolus dose nor by the duration of infusion. Unlike atracurium, cisatracurium does not trigger histamine release. Like atracurium, cisatracurium undergoes Hofmann elimination. In contrast to atracurium, cisatracurium does not undergo hydrolysis by nonspecific plasma esterases. Moreover, about 77% of the drug is cleared by organ-dependent mechanisms.

Pharmacokinetics and dynamics of atracurium infusions after paediatric orthotopic liver transplantation

We examined the pharmacokinetics and pharmacodynamics of atracurium besylate and its metabolites in children after orthotopic liver transplantation (OLT), as a suitable model for critically ill children. Ten children were studied after OLT on return to the intensive care unit (ICU). The mean (range) age was 36 (7-78) months, and weight 6-24.2 kg. Atracurium was started at induction of anaesthesia and adjusted in the ICU according to clinical need. Neuromuscular block was measured using accelerometry (TOFguard) and the train-of-four (TOF) ratio or count. Arterial plasma samples for atracurium and metabolites taken before, 12-hourly during, and at frequent intervals after the infusion were analysed by HPLC. The mean (range) maximum infusion rate during steady-state conditions was 1.44 (0.48-3.13) mg kg(-1) h(-1) and the duration of infusion 36.9 (22.5-98.4) h. Tachyphylaxis was not observed. The mean terminal half-life (t1/2) for atracurium was 18.8 (12-32.3) min. The steady-state plasma clearance (CLss) was 13.9 (7.9-20.3) ml min(-1) kg(-1) and the terminal volume of distribution (Vz) 390 (124-551) ml kg(-1); both were higher than in adults after successful OLT. The maximum concentration (Cmax) of laudanosine was 1190 (400-1890) ng ml(-1) and t1/2 was 3.9 (1.1-6.7) h. The renal clearance of laudanosine was 0.9 (0.1-2.5) ml min(-1) kg(-1) and increased with urine flow, but there was no significant relationship with serum creatinine. EEG spikes were confirmed in one child only; the corresponding laudanosine Cmax was 720 ng ml(-1). Monoquaternary alcohol Cmax was 986 (330-1770) ng ml(-1) and t1/2 42.9 (30-57.7) min. Mean recovery time on stopping the atracurium infusion to a TOF ratio >0.75 was 23.6 (12-27) min. Atracurium is an effective and safe neuromuscular blocking agent in this population. Laudanosine concentrations are not excessive if graft function is satisfactory.

Directly Coupled Chiral HPLC−NMR and HPLC−CD Spectroscopy as Complementary Methods for Structural and Enantiomeric Isomer Identification: Application to Atracurium Besylate

Directly coupled HPLC−NMR spectroscopy has now become a standard, commercially available technique for mixture characterization. Here the extension of the technique to chiral HPLC separation is reported and it is shown that HPLC−NMR together with HPLC−CD provide complementary approaches for the identification of structural isomers and enantiomers. The general approach has been exemplified using the neuromuscular blocking agent atracurium besylate, which comprises a mixture of 10 isomers in various proportions as four racemic pairs and two meso compounds. Diagnostic reporter resonances in the 1H NMR spectrum of atracurium besylate were assigned using a combination of one-dimensional and two-dimensional NMR experiments at 750 MHz. Stop-flow 750-MHz 1H NMR spectroscopy was used on-line after chiral column HPLC separation to identify the enantiomeric pairs, to distinguish the meso compounds, and to identify key configurational features of the isomers. The parallel HPLC−CD experiments served to assign the enan...

PRIMING WITH CISATRACURIUM A DOSE RANGING STUDY

S322 INTRODUCTION: Cisatracurium besylate (CAB) is a potent non-depolarizing muscle relaxant with an ED95 of 0.05 mg/kg in adults. Compared with its stereoisomer atracurium besylate (AB), CAB lacks histamine release and consequently offers a more stable hemodynamic profile. However, the time to maximal block for equipotent doses with CAB is up to 2 min longer than with AB [1]; therefore in order to shorten CAB onset time, 4XED95 dose has been recommended for tracheal intubation in adults. This study assesses the pharmacodynamic effects of the priming technique on different intubating doses of CAB. MATERIALS AND METHODS: This is an open label randomized study. After obtaining IRB approval and written informed consent, 40 adult female patients, ASA I-III, undergoing elective surgery under general anesthesia, were enrolled into one of 4 groups (Table 1). All patients were premedicated with midazolam 2-4 mg iv and induced with thiopental 3-5 mg/kg and sufentanil up to 0.5 mcg/kg. An inhalational mixture of N2 O/O2 (60/40%) was delivered after 3 min of pre-oxygenation. Mechanomyography assessed the neuromuscular function of the adductor pollicis by stimulating the ulnar nerve with TOF every 12 sec. After obtaining a stable baseline, a priming dose (CAB or placebo) was administered, followed 4 min later by the intubating dose. All patients were intubated at T1 <or=to20% and the degree of vocal cords relaxation was evaluated according to the criteria of Lund and Stovner [2]. Anesthesia was maintained with isoflurane up to 0.7% ET in a mixture of N2 O/O2 (60/40%) and sufentanil used as clinically indicated. Ventilation was adapted to produce 30-37 mmHg ETCO2 and local temperature was maintained >33.5[degree sign]C. If deemed necessary, reversal with neostigmine or edrophonium was allowed only after T1 spontaneous recovery >25%.Table 1: Priming and intubating doses of CAB in each group. Number of patients in parenthesis.RESULTS: Table 2 and Table 3 show the intubating conditions and the pharmacodynamic data in all groups. As this is an interim report, statistical analysis has been withheld until an additional 20 patients are enrolled.Table 2: Intubating conditions in different groups.Table 3: Pharmacodynamic data represented as mean +/- standard deviation.DISCUSSION: Group 2 seems to benefit the most from the priming technique of CAB when compared to the other groups. In this group, 3XED95 offered an onset time comparable with that of Groups 3 and 4 and allowed an earlier spontaneous recovery. Neither Single Twitch nor TOF ratio have shown any significant depression or fade respectively after the priming dose, which may preclude a possible muscle weakness in an awake patient. Even though the priming technique did not accelerate the onset in Group 3 in comparison with Group 4, it is evident that overall intubation conditions at T1 <or=to20% were better in Group 3. ACKNOWLEDGMENT: This project is supported by GlaxoWellcome.

Clinical pharmacokinetics of cisatracurium besilate.

Cisatracurium besilate, one of the 10 stereoisomers that comprise atracurium besilate, is a nondepolarising neuromuscular blocking agent with an intermediate duration of action. Following a 5- to 10-sec intravenous bolus dose of cisatracurium besilate to healthy young adult surgical patients, elderly patients and patients with renal or hepatic failure, the concentration versus time profile of cisatracurium besilate is best characterised by a 2-compartment model. The volume of distribution (Vd) of cisatracurium besilate is small because of its relatively large molecular weight and high polarity. Cisatracurium besilate undergoes Hofmann elimination, a process dependent on pH and temperature. Unlike atracurium besilate, cisatracurium besilate does not appear to be degraded directly by ester hydrolysis. Hofmann elimination, an organ independent elimination pathway, occurs in plasma and tissue, and is responsible for approximately 77% of the overall elimination of cisatracurium besilate. The total body clearance (CL), steady-state Vd and elimination half-life of cisatracurium besilate in patients with normal organ function are approximately 0.28 L/h/kg (4.7 ml/min/kg), 0.145 L/kg and 25 minutes, respectively. The magnitude of interpatient variability in the CL of cisatracurium besilate is low (16%), a finding consistent with the strict physiological control of the factors that effect the Hofmann elimination of cisatracurium besilate (i.e. temperature and pH). There is a unique relationship between plasma clearance and Vd because the primary elimination pathway for cisatracurium besilate is not dependent on organ function. There are minor differences in the pharmacokinetics of cisatracurium besilate in various patient populations. These differences are not associated with clinically significant differences in the recovery profile of cisatracurium besilate, but may be associated with differences in the time to onset of neuromuscular block.

Modulation of rat brain synaptosomal plasma membrane achieved by atracurium and its metabolite laudanosine.

Atracurium besylate and laudanosine cause excitement and seizures when introduced into the central nervous system of laboratory animals. We examined the modulation of lipid-protein interaction in the lipid environment of rat brain synaptosomal plasma membrane (SPM)-bound enzymes as a possible mechanism leading to these effects. The effect of various concentrations of atracurium besylate and laudanosine, or of varying duration of SPM, on the activity of Na+/K+-stimulated ATPase, Mg2+-stimulated ATPase and 5'-nucleotidase were assessed. The modulation of lipid protein interaction by laudanosine was estimated on the basis of the temperature dependence and cooperative behaviour of Na+/K+-stimulated ATPase. The effect of atracurium besylate or laudanosine on Na+/K+-stimulated ATPase activity was biphasic. Maximal enzyme stimulation appeared at 10(-4) M atracurium besylate or 10(-8) M laudanosine, and at 30 min of pre-incubation with both drugs. Arrhenius plots of Na+/K+-stimulated ATPase showed a transition temperature of 23.0 +/- 1.2 degrees C in control SPM and shifted to 16.5 +/- 0.9 degrees C (p < 0.01) in SPM treated with 10(-8) M laudanosine. The Hill coefficients for the allosteric inhibition of Na+/K+-stimulated ATPase by fluoride decreased from 1.99 +/- 0.22 in controls to 1.06 +/- 0.11 (p < 0.001) in the presence of 10(-8) M laudanosine. Our results suggest that laudanosine, one of the principal metabolites of atracurium besylate, affects nerve cell function in rats through the perturbation of the membrane lipid structure accompanied by SPM-bound enzyme dysfunction.

Hypotension After Pancreatic Reperfusion During Combined Kidney–Pancreas Transplantation

OMBINED kidney‐pancreas transplantation (KPTx) is an accepted and ever-increasing therapeutic option for patients suffering for diabetes mellitus (DM) type I who had developed end-stage renal failure (ESRF). Two of the main goals of this surgical procedure are capable of improving significantly the quality of life of these subjects: (1) recovery of renal function; (2) euglicemic state without insulin supplementation. 1 Correction of the metabolic abnormalities could prevent (or delay) the onset of severe secondary complications. Patients considered for combined KPTx manifest most of the multisystem dysfunctions associated with both diseases; generally, they are in poor medical condition and more prone to develop perioperative complications. Arterial hypertension and preoperative cardiac dysfunction secondary to autonomic neuropathy and microvascular changes are frequent findings in these patients and could be responsible for the cardiovascular complications occurring during surgery or in the immediate postoperative period: silent coronary artery disease has been reported in 20% to 40% of the candidates and hypertensive cardiomyopathy is a frequent echocardiographic finding in individuals affected by ESRF. 2 Because preoperative cardiovascular impairment has been associated with high morbidity and mortality and decreased graft survival, perioperative hemodynamic stability has been considered essential for the early functional recovery of the grafts and for the containment of postoperative complications. 3 Recent advances in invasive hemodynamic monitoring and anesthetic techniques made it possible to preserve or improve cardiovascular homeostasis. However, studies dealing with the hemodynamic profile during KPTx are scarce. In this paper we will describe the cardiovascular changes occurring during the various phases of surgery, specifically addressing the problem of hypotension following pancreatic reperfusion. 3 PATIENTS AND METHODS Our series includes 17 patients (mean age, 32 6 17 years) admitted to combined KPTx for ESRF and severe DM type 1. Eighty percent of the patients were affected by severe hypertension; one had ejection fraction lower than 40%. Heart rate and rhythm, pulse oxymetry, right atrial (RAP), and radial artery pressures were continuously monitored in all the cases. Right heart catheterization with a modified Swan‐Ganz catheter (SG cath Intellicath, Baxter) for complete invasive hemodynamic monitoring (pulmonary capillary wedge pressure [PWP] and cardiac output [CO] for continuous monitoring) was used in eight patients. Systemic vascular resistance (SVR, dynes sec 21 /cm 25 ) was calculated according to standard formulae. Hemodynamic data reported in this paper were recorded after the induction of the anesthesia (baseline, A), 5 minutes before (pre-pancreas reperfusion, B) and 2 minutes after pancreas reperfusion (post-pancreas reperfusion, C), 2 minutes after renal reperfusion (post-kidney reperfusion, D), and at the end of surgery (end of surgery, E). Severe arterial hypotension following pancreas reperfusion was considered mean arterial pressure (MAP) less than 70 mm Hg or less than 70% of the baseline values. General anesthesia and mechanical ventilation were used in all the patients: anesthesia was induced with thiopental and maintained with fentanyl and isoflurane (0.8 to 1.2% in air/O2 mixture 50%); atracurium besylate was used for muscle relaxation. Data are presented as mean 6 SD. Statistical analysis was performed using ANOVA. A P value # .05 was considered statistically significant.

Do intensive care drug infusions support microbial growth?

The potential for commonly infused drug solutions to support or inhibit microbial growth was explored in this study. Drugs examined were midazolam HCl, morphine sulphate, fentanyl citrate, pethidine HCl, bupivacaine HCl, atracurium besylate, vecuronium bromide, adrenaline, dopamine, dobutamine, noradrenaline, isoprenaline, glyceryl trinitrate, sodium nitroprusside and propofol. All drugs were studied in both diluted and undiluted forms. Of the 15 medications investigated, all except propofol were found to be bactericidal and to reduce fungal growth.

The clinical pharmacology of cisatracurium

Cisatracurium (51W89) is one of the ten stereoisomers of atracurium, accounting for about 15% of the racemate. The ED95 of cisatracurium was determined to be about 50 micrograms/kg (cation, molecular weight 929), while the ED95 of atracurium (besylate salt, molecular weight 1245) was 250 micrograms/kg. Thus, on a molar basis in adult patients, cisatracurium is about 3.5 times as potent as the racemic atracurium mixture. We compared atracurium with cisatracurium in healthy adult patients and found an almost identical pharmacodynamic profile. In children, an ED95 of about 40 micrograms/kg was determined, while a 1-min-longer onset of cisatracurium was found in geriatric than in young adult patients. The presence of chronic renal failure did not prolong the duration of action of cisatracurium. The recovery of neuromuscular transmission from a cisatracurium infusion of up to 145 h was investigated in intensive care unit patients. Their time from the end of infusion to a train-of-four ratio > 0.7 (68 +/- 18 min) was on average only some 70% longer than after an infusion of cisatracurium for 2 h in normal surgical patients. In another study, no signs of histamine release nor any clinically relevant cardiovascular effects of cisatracurium were found in doses up to eight times ED95.

Upper oesophageal sphincter function during general anaesthesia.

The effect of anaesthesia on the upper oesophageal sphincter response to acid in the distal oesophagus and hypopharynx, and the effect of atracurium besylate on acid migration into the hypopharynx, was studied in 102 patients undergoing elective varicose vein surgery. Group 1 (n = 48) received a general anaesthetic and the muscle relaxant atracurium besylate whereas group 2 (n = 54) received a general anaesthetic without relaxation. Upper oesophageal sphincter tone was significantly lower in patients receiving muscle relaxants ('sphinctometer output', eight versus 14, P < 0.05). Sixteen patients (16 per cent) had reflux into the distal oesophagus during anaesthesia (nine in group 1 and seven in group 2, P not significant), of whom seven had reflux to the hypopharynx. There was no difference in incidence of hypopharyngeal acid exposure between groups. Upper oesophageal sphincter tone did not alter in response to reflux into the distal oesophagus or hypopharynx in either group. The upper oesophageal sphincter fails to protect the hypopharynx under general anaesthesia even if patients do not receive a muscle relaxant.

Avaliação comparativa entre o besilato de atracúrio e o cloreto de alcurônio sobre a frequência cardíaca e a ventilometria de cães anestesiados com halotano

Vinte cães provenientes da rotina anestésico-cirúrgica do Hospital de Clínicas Veterinárias da Universidade Federal de Santa Maria (UFSM), foram divididos em 2 grupos, I e II. e submetidos ao bloqueio neuromuscular com besilato de atracúrio 0,5mg/kg IV ou cloreto de alcurônio 0,1mg/kg IV consecutivamente. Foram monitorados a ventilometria, a freqüência cardíaca e o tempo de bloqueio neuromuscular dos animais que receberam besilato de atracúrio, submetidos à reversão espontânea, enquanto que a reversão do bloqueio produzido com cloreto de alcurônio foi realizada aos 60 minutos após instalação deste pela administração de neostigmina precedida de sulfato de atropina. Os resultados obtidos demonstraram diminuição do volume corrente pulmonar para ambos os grupos à partir da reversão do bloqueio, com diminuição significativa para o grupo que recebeu cloreto de alcurônio até vinte minutos após reversão e diferença estatisticamente significativa entre os grupos aos 20 minutos após reversão. Houve diminuição nos valores de frequência cardíaca à partir dos 10 minutos após indução anestésica até 30 minutos decorridos do bloqueio para ambos os grupos, com significando estatística no grupo que recebeu besilato de atracúrio. O tempo médio de bloqueio com besilato de atracúrio foi de 49,07 ± 12,67 minutos.

Chemical stability and adsorption of atracurium besylate injections in disposable plastic syringes.

Atracurium besylate (AB) is supplied as a sterile, non-pyrogenic aqueous solution for intravenous use. Hospitals pre-fill disposable plastic syringes with these solutions so that they are ready for immediate use when required. Drug loss due to potential adsorption on to the plastic material of the syringes has not been studied. Atracurium is also administered by intravenous infusion using a diluted solution in either 5% dextrose injection (USP) or 0.9% sodium chloride injection USP. Drug solutions not used within 24 h are usually discarded, resulting in tremendous waste. The purpose of these investigations was to determine the adsorption behaviour of atracurium when stored in plastic syringes, and to study the degradation of atracurium in i.v. fluids. For the adsorption study, 10 mg/ml solutions were used, whereas the diluted infusion solutions were prepared to contain 0.5 mg/ml of atracurium. Drug degradation was monitored using a stability-indicating high-performance liquid chromatography method. Degradation studies were conducted at 5 degrees C, 25 degrees C and 40 degrees C. Refrigeration was observed to improve drug stability. The manufacturer's recommended expiry period was too conservative. Storage at room temperature for up to 6 weeks can be safely recommended, without significant loss of chemical stability.

Stability and compatibility of admixtures of intravenous ciprofloxacin and selected drugs

The stability and compatibility of ciprofloxacin with selected drugs in intravenous admixtures were studied. Ciprofloxacin 2 mg/mL in 5% dextrose was combined with each of 22 other drugs at concentrations commonly used in clinical practice. Each combination was maintained at room temperature (approximately 22 °C) in constant fluorescent light. Immediately after preparation and at 6 and 24 hours, each admixture was examined visually in normal fluorescent room light and the pH value was determined. For samples lacking visible precipitates or having pH changes of not more than 1 unit, ciprofloxacin concentration was assayed by using high-performance liquid chromatography. When combined with ciprofloxacin, 14 of the study drugs did not alter the concentration of ciprofloxacin, including amikacin sulfate, atracurium besylate, aztreonam, cimetidine hydrochloride, dobutamine hydrochloride, fluconazole, gentamicin sulfate, metronidazole (intravenous, ready to use), midazolam hydrochloride, norepinephrine bitartrate, pancuronium bromide, potassium chloride, tobramycin sulfate, and vecuronium bromide. There were five drugs that were determined to be incompatible with ciprofloxacin because of precipitate formation (amphotericin B, ampicillin sodium/sulbactam sodium, cefuroxime sodium, piperacillin sodium, and sodium bicarbonate). Incompatibility with ciprofloxacin based on pH changes of more than 1 unit was found with four drugs: ampicillin sodium/sulbactam sodium, ceftazidime, metronidazole hydrochloride (powder only), and ticarcillin disodium/clavulanate potassium. Intravenous ciprofloxacin 2 mg/mL admixed in 5% dextrose was stable and compatible with 14 of the 22 test drugs for up to 24 hours at room temperature. The other eight drugs should not be combined with ciprofloxacin.

Pharmacokinetics of 1R-cis 1'R-cis atracurium besylate (51W89) and plasma laudanosine concentrations in health and chronic renal failure

To ascertain the effects of chronic renal failure on the pharmacokinetics of 1R-cis 1'R-cis atracurium besylate (a stereoisomer, designated 51W89), we gave a bolus dose of 0.1 mg kg-1 (2 x ED95) to 17 patients with end-stage renal failure and to 15 patients with normal renal function undergoing elective surgery. All patients received thiopentone, fentanyl and midazolam i.v. and 70% nitrous oxide in oxygen. Blood samples were obtained over 8 h and plasma analysed for 51W89 and laudanosine concentration, using high pressure liquid chromatography. A two-compartment model was fitted to the 51W89 plasma concentration data using the NONMEM program, to estimate pharmacokinetic variables and to determine the influence of renal failure, age, weight and sex. Clearance of 51W89 was found to be reduced by 13% in renal failure. The typical value of T1/2 beta was 4.2 min longer in renal failure than in the healthy patients (34.2 vs 30.0 min, P < 0.005). In the healthy patients, clearance of 51W89 was greater in males, but it decreased with increasing age by approximately 1.5 ml min-1 yr-1. Mean plasma laudanosine concentrations were significantly higher in the renal failure group; nevertheless, they were approximately one-tenth of those reported after atracurium.

Synergism Between Atracurium and Mivacurium Compared with That Between Vecuronium and Mivacurium

Synergism Between Atracurium and Mivacurium Compared with That Between Vecuronium and Mivacurium