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Rocuronium bromide: time-course of action in underweight, normal weight, overweight and obese patients.

The duration of action and recovery of 0.6 mg kg-1 rocuronium in underweight, normal weight, overweight and obese patients were investigated. Forty-eight patients were divided into four groups, according to their body mass index, and were given 0.6 mg kg-1 rocuronium. The onset time, the duration 25% and either the spontaneous or induced recovery were measured according to the random assignment. The onset time in the obese group was shorter 60 (50-90) s compared to the other groups (underweight: 95 (40-320) s, normal: 95 (50-200) s, overweight: 90 (50-260) s, but the difference did not reach the level of statistical significance. The duration 25% was slightly prolonged in the obese patients (31.5 (21.0-61.0) min) when compared to the underweight (25.0 (15.0-37.0) min), normal weight (26.0 (20.0-36.0) min) and overweight (27.0 (19.0-35.0) min) patients. No differences were observed in spontaneous (9.5-12.5 min) and induced (2.5-3.5 min) recovery.

Androstanols↗

Dose-response and time-course of effect of rocuronium bromide in paediatric patients.

We determined dose-response curves and spontaneous recovery of neuromuscular function following a single ED95 dose of rocuronium in 10 infants (1-11 months old), 20 children (2-12 years old) and 20 adults (20-40 years old) during nitrous oxide-oxygen-thiopentone-alfentanil anaesthesia. Neuromuscular block was recorded as adductor pollicis EMG following a supramaximal train-of-four ulnar nerve stimuli at 10 s intervals. ED95 values were significantly less for infants than for children or adults (255 +/- 62, 402 +/- 68 and 350 +/- 78 micrograms kg-1, respectively, P = 0.0001). Time-course of recovery from an average 94% neuromuscular block was similar in all age groups with a 25-75% recovery time of 6.5 +/- 1.8, 5.7 +/- 1.8 and 6.7 +/- 1.6 min in infants, children and adults, respectively. Thus, rocuronium is an intermediate-acting muscle relaxant in all age groups.

Adult↗

Dose-response and time-course of action of rocuronium bromide.

Rocuronium is a new aminosteroidal muscle relaxant, the main feature of which is a low potency compared to other aminosteroidal muscle relaxants. The ED95 is approximately 0.3 mg kg-1, although the estimated potency may vary slightly with different modes of stimulation and under different anaesthetic techniques. The low potency is associated with a rapid onset of effect, a 2-3 x ED95 dose producing the maximum effect in 1-2 min. The duration of action is, however, comparable to other intermediate drugs such as atracurium and vecuronium. The estimated potency is similar in adults and the elderly, although the ED95 may be slightly higher in children. Rocuronium is affected in the same way as vecuronium by the use of volatile anaesthetic agents.

Adolescent↗

The pharmacokinetics of rocuronium bromide in hepatic cirrhosis.

The pharmacokinetics of aminosteroid neuromuscular blocking drugs have been shown to be altered in patients with hepatic cirrhosis. A reduced clearance and prolonged elimination half-life of pancuronium and vecuronium have been demonstrated. Pharmacokinetic studies of the newest aminosteroid neuromuscular blocking agent, rocuronium, performed in a small number of cirrhotic patients, have proved inconclusive, apart from noting a higher central volume of distribution than in healthy patients. This difference may result in a slightly delayed onset of neuromuscular block. Nevertheless, rocuronium, even in cirrhotic patients, has the fastest onset of action of any non-depolarizing neuromuscular blocking agent. Further pharmacokinetic studies are necessary of this drug in hepatic cirrhosis.

Androstanols↗

Evaluation of neuromuscular effects and antagonism of rocuronium bromide: a preliminary report.

Twenty ASA I-II patients received either 2 or 3 x ED95 doses of rocuronium bromide during nitrous oxide, oxygen, propofol, fentanyl-based anaesthesia. The mean times to maximum block were 98 s and 74 s and the mean duration of clinical relaxation (recovery to 25% T1) was 35 min and 46 min following 620 micrograms kg-1 and 930 micrograms kg-1, respectively. Neuromuscular blockade was antagonized with either neostigmine or edrophonium from a twitch height of 25%. Although there was no significant difference between the recovery times neostigmine appeared to give more consistent antagonism of rocuronium-induced blockade.

Adolescent↗

Time-course of action and intubating conditions with rocuronium bromide under propofol-alfentanil anaesthesia.

Thirty ASA I and II patients received either an intubating dose of 0.6 mg kg-1 rocuronium (2 x ED95, group 1) or 0.06 mg kg-1 as a priming dose followed by an intubating dose of 0.24 mg kg-1 rocuronium (group 2) 4 min later. Anaesthesia was induced with propofol (2.0 mg kg-1) and alfentanil (0.02 mg kg-1) and maintained with nitrous oxide/oxygen and propofol (6.0 mg kg-1 h-1). Neuromuscular function was monitored mechanomyographically and electromyographically with train-of-four (TOF) stimulation at the wrist every 10 s. The following parameters were measured and compared between the two groups: time to 90% block (intubation time), time to maximum block (onset time), and the times for T1 (25%, 75% and 90%) and TOF > 70%. In group 1 the intubation time was significantly shorter (40 +/- 10 s) than in group 2 (51 +/- 11 s). Intubating conditions were good or excellent in both groups. The clinical duration of action was 28 +/- 8 min in group 1 and 15 +/- 3 min in group 2, respectively. Mechanomyography showed a significantly faster development of neuromuscular block than electromyography. The comparison of mechanomyographically and electromyographically measured recovery times did not show any differences. In 60% of the patients a priming dose of 0.06 mg kg-1 was followed by a considerable decrease in neuromuscular function.

Adult↗

Rocuronium bromide in the ICU: dose finding and pharmacokinetics.

Thirty patients requiring elective ventilation in the ICU received either intermittent boluses (25 patients) or a continuous infusion (five patients) of rocuronium. Degree of block was monitored by train-of-four stimuli and maintained at one twitch either observed or palpated. All patients were sedated with intermittent doses or an infusion of 0.14-0.4 microgram kg-1 h-1 of midazolam and received a continuous infusion of either sufentanil or fentanyl (0.25-2.0 micrograms kg-1 h-1). Control of ventilation was better with the continuous infusion of rocuronium, but these patients also had a more intense block receiving 9.9 +/- 1.3 micrograms kg-1 min-1 as compared to 6.4 +/- 2.3 micrograms kg-1 min-1 in the bolus group. Elimination half-time, volume of distribution at steady-state, and mean residence time were significantly greater than in surgical patients receiving comparable infusions, but plasma clearance was similar.

Adolescent↗

Intubation conditions and time-course of action of low-dose rocuronium bromide in day-case dental surgery.

A relatively small dose of rocuronium (0.45 mg kg-1) was compared with equipotent doses of atracurium (0.35 mg kg-1) and vecuronium (0.075 mg kg-1) for ease of intubation at 60 s. All patients could be intubated but the proportion with excellent or good conditions was much greater with rocuronium. Mean clinical duration of effect of this dose was 22.2 min. There was no correlation between intubating conditions and the degree of block of the adductor policis.

Adult↗

The influence of hypothermia (surface cooling) on the time-course of action and on the pharmacokinetics of rocuronium in humans.

Hypothermia prolongs the time-course of action of non-depolarizing neuromuscular blocking agents. The mechanism, however, is unknown. We studied the influence of hypothermia (by surface cooling, nasopharyngeal temperature < or = 31 degrees C) on the time-course of action and on the pharmacokinetics of rocuronium in humans. Nineteen neurosurgical patients were divided into hypothermic and normothermic groups. Hypothermia (30.4 +/- 0.8 degrees C (mean +/- SD)) increased the duration of action, temperature dependently, and delayed the recovery. Hypothermia reduced the plasma clearance significantly (2.17 +/- 0.62 vs. 4.26 +/- 0.50 mL kg-1 min-1, P = 0.004), did not change the volume of distribution (224 +/- 64 vs. 232 +/- 60 mL kg-1 min-1, P = 1.0), and prolonged the mean residence time (108 +/- 39 vs. 56 +/- 19 mL kg-1 min-1, P = 0.01). We conclude that hypothermia prolongs the duration of action of rocuronium and delays spontaneous recovery and that altered pharmacokinetics, such as a decreased clearance, play an important role in this.

Androstanols↗

Cost analysis of neuromuscular blocking agents in the operating room: cisatracurium, atracurium, vecuronium and rocuronium.

Cisatracurium (C), Atracurium (A), Rocuronium (R) and Vecuronium (V) are four neuromuscular blockers (NMB) used in the operating room with similar efficacy, defined as adequate muscle relaxation, but different pharmacokinetics. C and A have organ-independent elimination, A is associated with histamine release and R has a shorter onset time. The objective of this study was to economically compare these four NMB from the hospital point of view in order to facilitate drug selection. A cost analysis was performed. Only direct costs were considered and data were collected through a retrospective chart review. A total of 151 patient charts were randomly selected. Differences between patients receiving one of the four NMB were evaluated by ANOVA or Kruskal-Wallis tests. Then a multiple linear regression analysis was conducted. In the chart review, no significant difference was observed between the four groups of patients in age, weight or surgery duration (p > 0.05). Multiple regression analysis revealed that atracurium was on average PTA 237 (1 Euro = PTA 166) cheaper per surgery than any other NMB after adjusting for other factors (p < 0.01) and there is no significant difference in cost between the other three NMBs (p > 0.1). We recommend the use of rocuronium when a quick onset is needed and the patient does not have hepatic failure, cisatracurium when a haemodynamic instability is possible and atracurium in the remaining cases. If just one NMB can be included in the drug formulary we would select cisatracurium due to its pharmacological advantages over atracurium with a small increment in cost.

Adult↗

Dosage of neostigmine for reversal of rocuronium block from two levels of spontaneous recovery.

Spontaneous recovery, and recovery following neostigmine 20, 35 or 50 microgram.kg-1 administered at 10 or 25% of recovery of the first twitch of the train-of-four, was assessed in 80 patients after rocuronium administration under continued isoflurane anaesthesia. In an additional 40 patients, isoflurane administration was discontinued and neostigmine 35 or 50 microgram.kg-1 was given at 10 or 25% recovery. The administration of neostigmine reduced the recovery times significantly. A neostigmine dose of 20 microgram.kg-1 resulted in slower recovery compared with the higher doses, particularly when reversal was attempted at a first twitch height of 10%. Higher doses of neostigmine given at a first twitch height of 25% resulted in rapid reversal of block [mean (SD) times of 7.0 (4.8) and 6.4 (1.9) min with the 35 and 50 microgram.kg-1 doses, respectively, for attaining a train-of-four ratio of 0.8]. Discontinuing isoflurane did not alter recovery times. The incidence of emetic symptoms did not differ between groups, including one group that received atropine instead of glycopyrronium in combination with neostigmine. We conclude that rocuronium block can be antagonised safely using a neostigmine dose of 35 microgram.kg-1, although recovery may be slightly slower if administered at a first twitch of 10% of control.

Adjuvants, Anesthesia↗

Anaesthesia with remifentanil and rocuronium for caesarean section in a patient with long-QT syndrome and an automatic implantable cardioverter-defibrillator.

A 24-year-old woman with congenital long-QT syndrome (LQTS) required caesarean section at 32 weeks' gestation. Her risk of premature death from malignant ventricular tachyarrhythmias had necessitated implantation of an automatic cardioverter-defibrillator (AICD) with pacemaker capability. The patient expressed a preference for general anaesthesia. To minimise the risk of increased serum catecholamine concentrations and consequent ventricular arrhythmias, an analgesia-based regimen was chosen. With cardioversion, defibrillation, and antitachycardia pacing functions of the AICD selectively deactivated, anaesthesia was induced with bolus doses of thiopentone and remifentanil. Rocuronium was used for neuromuscular block. Anaesthesia was maintained with nitrous oxide and isoflurane, supplemented by a remifentanil infusion. We outline the pathophysiology and treatment of LQTS, and discuss the anaesthetic management of an obstetric patient with the congenital syndrome. This is the first reported case of caesarean section in a patient with an AICD, and the first description of the use of either remifentanil or rocuronium in LQTS.

Journal Article↗

[Assessment of intubation time and conditions under the influence of rocuronium].

PURPOSE: To evaluate the tracheal intubating conditions when intubation time is determined by the onset time of the neuromuscular block either of the adductor pollicis (AP) or of the orbicularis oculi muscle (OO). METHODS: In this prospective, double blind, randomised study, 40 adults ASA I-II undergoing general anaesthesia with tracheal intubation were allocated to two groups (n = 20) according to the reference muscle (AP or OO) used to determine the appropriate intubation time. Induction of anaesthesia was achieved with 5-7 mg.kg-1 thiopentone, 1.5-2.5 micrograms.kg-1 fentanyl and 0.9 mg.kg-1 rocuronium (3 x ED95) for muscular relaxation. Supramaximal train of four stimulation of the ulnar and facial nerve every 10 sec was used to monitor the neuromuscular block. After visual loss of AP or OO contraction, tracheal intubation and quality of intubation assessment were performed by two independent anaesthetists. Data are expressed as mean and standard error of the mean (X +/- SEM). RESULTS: Curarisation time of the OO was shorter (110 +/- 4.9 sec) than that of the AP (144 +/- 5.5 sec; P < 0.0001). Intubation conditions were excellent in 95% and good in 5% of the patients in the AP group whereas in the OO group only 65% of the patients had excellent and 20% good intubation conditions (P < 0.05). Coughing was observed in 15% of patients in the OO group during tracheal intubation. CONCLUSION: Monitoring neuro-muscular activity of the AP using TOF to determine the appropriate tracheal intubation time and conditions in patients paralysed with rocurorium is more clinically relevant than monitoring the OO muscle.

Adult↗

Cumulation characteristics of cisatracurium and rocuronium during continuous infusion.

PURPOSE: The dissimilar pharmacokinetic properties of cisatracurium (CIS) and rocuronium (ROC) predict different potential for drug cumulation when these drugs are administered by continuous infusion. A study was therefore undertaken to compare cumulation potential of CIS and ROC during surgical procedures of relatively long duration (2-4 hr). METHODS: Sufentanil/propofol-N2O anesthesia was administered to 40 ASA I and II adults. In a double-blind protocol, patients were randomly allocated to receive a continuous i.v. infusion of either CIS or ROC, titrated in progressive increments or decrements as required to achieve and maintain 95 +/- 5% depression of the T1 response of the adductor pollicis muscle, using a Datex NMT-100 Relaxograph EMG monitor applied at the wrist. At the end of surgery, 60 microg x kg(-1) neostigmine plus 15 microg x kg(-1) atropine were administered for reversal. RESULTS: The duration of infusion was 104 +/- 33 min in group CIS and 110 +/- 23 min in group ROC (P=NS). In both groups, a progressive decrease in potency-adjusted infusion rates was observed after 30 min, then stabilized beyond 60 min. When allowing for an initial period of stabilization, mean potency-adjusted infusion requirements were: CIS 0.81 +/- 0.02 microg x kg(-1) x min(-1) and ROC 5.58 +/- 1.94 microg x kg(-1) x min(-1). There were no differences between groups at any time with regard to potency-adjusted infusion requirements necessary to maintain 90-99% block (P=NS). However, drug costs/hr for maintenance of neuromuscular block were less with CIS ($3.57 +/- 0.09) than with ROC ($6.03 +/- 0.27), P < 0.001. CONCLUSION: When adjusted to equipotency, infusion requirements of CIS and ROC vary at similar rates during general anesthesia. Despite pharmacokinetic differences, neither drug demonstrates cumulation for infusion lasting up to 3.5 hr.

Adult↗

[Influence of gender on the intubation conditions with rocuronium].

PURPOSE: There is increasing evidence for gender differences in the pharmacokinetics and pharmacodynamics of anaesthetic drugs and neuromuscular blocking agents, e.g. rocuronium (Roc). Females require 30% less Roc than males to achieve the same degree of neuromuscular block and onset times are shorter. However, whether this leads to an improvement of the intubation conditions in females is unclear. METHODS: After approval of the ethics committee 60 female and 60 male patients were each randomised into 2 groups to receive 0.6 mg/kg body weight Roc or 1.0 mg/kg succinylcholine (Sux; control group). Induction: thiopentone (5 mg/kg), fentanyl (3 microg/kg) then Roc (Roc groups) or Sux (Sux groups) and tracheal intubation after 60 s. Time to intubation, glottic exposure and intubating conditions were assessed. RESULTS: Men were significantly larger and heavier (p<0.001) than women, but the body mass index was comparable (ns). Number of attempts, time to intubation, and Cormack grades were comparable (ns). However, the rate of clinically acceptable intubation conditions was significantly higher in the female compared to the male Roc group: 80% vs 47%, p<0.05. The incidence of clinically acceptable intubation conditions in the female Roc and Sux groups were similar (80%). CONCLUSION: The intubation conditions after Roc were significantly better in women than in men. The differences were Roc-related and did not occur in the control groups.

Adult↗

[Severe anaphylaxis from rocuronium].

Muscle relaxant drugs are the most frequent cause of anaphylactic and anaphylactoid reactions during anaesthesia. We report a case of a life-threatening anaphylactic reaction during induction of anaesthesia with severe bronchospasm as the first clinical symptom. Mechanical ventilation was nearly impossible. The patient required a multimodal antiallergic therapy and a high-dose catecholamine therapy for stabilization. Rocuronium was identified as the allergic agent using intradermal testing.

Anaphylaxis↗

Pharmacodynamics of rocuronium with and without prior administration of succinylcholine.

STUDY OBJECTIVES: To compare succinylcholine (S) and rocuronium (R) used for endotracheal intubation, and to assess the possible action of S on subsequently administered R. DESIGN: Double-blind, randomized, phase III study. SETTING: University Medical Center. PATIENTS: 24 ASA physical status I and II patients, ages 28 to 65, undergoing general anesthesia for abdominal procedures. INTERVENTION: Double-blind administration of R 600 mcg/kg (Group A) or S 1 mg/kg was achieved with open label R 150 mcg/kg. Standardized general anesthetic technique with sodium thiopental, fentanyl, and nitrous oxide in oxygen was administered. MEASUREMENTS AND MAIN RESULTS: Neuromuscular junction was tested by ulnar nerve stimulation and mechanomyograph. Intubation was attempted at 80% first twitch depression of train-of-four. Heart rate and blood pressure were recorded throughout. Onset times were 74 +/- 37 seconds for S and 130 +/- 46 seconds for R. Intubation times were 76 +/- 29 seconds for S and 85 +/- 23 seconds for R (no significant difference). Good to excellent intubation conditions were achieved in both groups. S given prior to R decreased onset time and increased duration of R, when compared with R given alone. No drug related cardiovascular events were noted. CONCLUSION: Rapid intubation conditions can be obtained after both S and R. Given its overall safety profile, R can be used when S is contraindicated, or in healthy patients with no apparent difficult airway, when procedures are expected to last more than 25 minutes.

Adult↗

Antagonism of profound cisatracurium and rocuronium block: the role of objective assessment of neuromuscular function.

STUDY OBJECTIVE: The purpose of this study is to determine the incidence of significant (train-of-four [TOF] ratio <0.70), but clinically undetectable (TOF ratio >0.40), residual neuromuscular block after neostigmine antagonism of profound cisatracurium (CIS) or rocuronium (ROC) block. DESIGN: Prospective, randomized, open-label study. SETTING: University hospital. PATIENTS: Forty ASA physical status I and II undergoing elective surgical procedures. INTERVENTIONS: Anesthesia was induced with propofol 1.5 to 2.5 mg/kg IV plus fentanyl 2 to 4 mug/kg and maintained with N(2)O/desflurane plus narcotic supplementation. The electromyographic response of the adductor pollicis was recorded. Train-of-four stimulation was given every 20 seconds. Twitch height (T1) and TOF fade ratio were continuously recorded. In group 1 (n = 20), neuromuscular block was induced with CIS 0.10 mg/kg, and T1 was maintained at 5% of control by a constant infusion of CIS until the end of surgery. One minute after the termination of the infusion, neostigmine 0.05 mg/kg was administered. T1 and TOF values were monitored continuously for the next 20 minutes. Group 2 (n = 20) is identical to group 1 except that the initial drug was ROC 0.60 mg/kg, and paralysis was maintained with an infusion of ROC. MEASUREMENTS AND MAIN RESULTS: There were no significant differences in the recovery patterns of CIS vs ROC. The duration (bolus to end of infusion) in both groups averaged 2.7 hours, and the mean cumulative dose of relaxant approximated 4 x the ED(95). T1 at the time of reversal was 6% (4%-10%) of control. Mean TOF ratios at 10, 15, and 20 minutes were 0.55, 0.71, and 0.0.81, respectively. Return to a TOF ratio >0.40 was always achieved in 15 minutes or less. However, at 20 minutes postreversal, 5 of 40 subjects had TOF ratios <0.70 and only 11 individuals had recovered to a TOF ratio of 0.90 or greater. CONCLUSIONS: Most clinicians cannot detect tactile fade once the TOF ratio exceeds 0.40. When reversing profound block, an objective monitor of neuromuscular function is required if the extent of residual block is to be assessed with any confidence.

Adult↗