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Biomedical subjects

T Fuchs-Buder

Publications and source records attributed to T Fuchs-Buder.

At least 37 records · Page 2Linked to original sources

Cerebrospinal fluid concentrations of atracurium, laudanosine and vecuronium following clinical subarachnoid hemorrhage.

BACKGROUND: Neuromuscular blocking agents may exert central nervous system effects when they reach the brain. This study assessed the concentrations and the time course of passage of vecuronium, atracurium, and its metabolite laudanosine in the cerebrospinal fluid (CSF) of patients undergoing intracranial aneurysm clipping. METHODS: Twenty-five patients with subarachnoid hemorrhage were randomly allocated to receive an intravenous infusion of vecuronium (n=13) or atracurium (n=12). Arterial blood and lumbar CSF were sampled before and 1, 2, 3, 4 and 8 h after the start of the relaxant infusion. The samples were analyzed by liquid chromatography-electrospray ionization mass spectrometry (vecuronium) and high-pressure liquid chromatography (atracurium and laudanosine). RESULTS: The data of 20 patients (10 in both groups) were analyzed. In 11 CSF samples from five patients atracurium was detected in concentrations from 10 to 50 ng/ml. Laudanosine was retrieved in all CSF samples at 1, 2, 3, 4 and 8 h; the highest CSF concentration of laudanosine occurred at 3 h [38 (18-63) ng/ml: median (range)]. Vecuronium was not found in any CSF sample. CONCLUSION: Significant concentrations of atracurium and laudanosine but not of vecuronium were detected in the CSF of patients during and immediately after intracranial aneurysm surgery.

Adolescent↗

Spontaneous movements, local reactions and pain on injection of rocuronium. A comparison between female and male patients.

BACKGROUND: We investigated the incidence of withdrawal, local reactions and pain on injection of rocuronium in 120 adult ASA I-II patients undergoing general anaesthesia (group A: 60 male patients, group B: 60 female patients). METHODS: After induction of anaesthesia with propofol and remifentanil, rocuronium 0.6 mg kg(-1) was injected in a separate intravenous cannula on the opposite arm. The patient's response to the injection of rocuronium was graded using a four-point scale. The appearance of local signs (i.e. erythema, venous sequelae) on the arm where rocuronium had been injected was recorded at the end of the injection as well as 1 h and 24 h after recovery from anaesthesia. Moreover, patients were asked 24 h after recovery from anaesthesia whether they had recall of pain or movements in this arm during induction of anaesthesia. RESULTS: In 26 of the 120 patients (22%) included, withdrawal reactions after injection of rocuronium were observed. Of these 26 patients, 16 (13%) had severe movements. The overall incidence of withdrawal reactions after rocuronium as well as the incidence of severe reactions was significantly higher in female patients compared to male patients (overall incidence: 18 females (30%) vs. 8 males (13%), P<0.05; severe reaction: 13 females (22%) vs. 3 males (5%), P<0.05). No local reactions were observed and no patient remembered any pain or movements during induction of anaesthesia. CONCLUSION: The incidence and the degree of withdrawal reactions in response to the injection of rocuronium were significantly higher in women than in men. This was not associated with adverse clinical consequences for the patient's outcome.

Adult↗

Blockade and activation of the human neuronal nicotinic acetylcholine receptors by atracurium and laudanosine.

BACKGROUND: Curaremimetic nondepolarizing muscle relaxants are widely used in clinical practice to prevent muscle contraction either during surgery or during intensive care. Although primarily acting at the neuromuscular junction, these compounds can cause adverse effects, including modification of cardiac rhythm, arterial blood pressure, and in the worst cases, triggering of seizures. In this study, we assessed the interaction of atracurium and its metabolite, laudanosine, with neuronal nicotinic receptors. METHODS: The human neuronal nicotinic receptors alpha4beta2, alpha3beta4, alpha3alpha5beta4, and alpha7 are heterologously expressed in Xenopus laevis oocytes, and the effect of atracurium and its degradation product, laudanosine, were studied on these receptors. RESULTS: Atracurium and laudanosine inhibited in the micromolar range the major brain alpha4beta2 receptor and the ganglionic alpha3beta4 or alpha3beta4alpha5 and the homomeric alpha7 receptors. For all four receptors, inhibition was rapid and readily reversible within less than 1 min. Atracurium blockade was competitive at alpha4beta2 and alpha7 receptors but displayed a noncompetitive blockade at the alpha3beta4 receptors. Inhibition at this receptor subtype was not modified by alpha5. Laudanosine was found to have a dual mode of action; first, it competes with acetylcholine and, second, it blocks the ionic pore by steric hindrance. At low concentrations, these two drugs are able to activate both the alpha4beta2 and the alpha3beta4 receptors. CONCLUSION: Adverse effects observed during atracurium administration may be attributed, at least partly, to an interaction with neuronal nicotinic receptors.

Animals↗

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.

Adult↗

Use of reversal agents in day care procedures (with special reference to postoperative nausea and vomiting).

There is some confusion about the contribution of reversal of residual paralysis to the occurrence of postoperative nausea and vomiting. The aim of this review is to discuss whether antagonism of residual paralysis is a cause of postoperative nausea and vomiting, and to assess the risk of residual paralysis if the reversal is omitted. Data from a meta-analysis published before 1998 were considered, along with trials published after that date to assess the influence of reversal of residual paralysis on postoperative nausea and vomiting, and the likelihood of harm when antagonism was omitted. Moreover, an overview of pathophysiological consequences, incidence and clinical consequences of residual paralysis is given and the actual criteria of the adequacy of neuromuscular recovery presented. When emetic outcomes are combined across all trials and all different neostigmine doses, there is no beneficial effect from omitting neostigmine on postoperative nausea and vomiting, but there is some evidence of a dose-responsiveness with neostigmine; higher doses may have emetic properties. However, omitting reversal introduces a non-negligent risk of residual paralysis. An improved understanding of the pathological consequences of residual paralysis (i.e. impaired laryngeal and pharyngeal muscle function, alterations in hypoxic ventilatory control, reduced margin of safety) led to establishment of more rigorous criteria for defining adequacy of neuromuscular recovery. A train-of-four ratio of > or = 0.9 is now accepted as the index of adequate recovery of neuromuscular function. Applying this new definition, residual paralysis becomes a frequent adverse side-effect. Neuromuscular recovery should therefore be routinely monitored in ambulatory patients and residual paralysis prevented by reversing neuromuscular block.

Ambulatory Surgical Procedures↗

[Time course of neuromuscular blockade after rocuronium. A comparison between women and men].

BACKGROUND: We studied 40 patients (20 female and 20 male) undergoing elective surgery under general anaesthesia to evaluate the effect of gender on the pharmacodynamics of rocuronium. METHODS: Using electromyography (EMG) we determined the maximal neuromuscular block and time course of action of 0.45 mg/kg rocuronium (1.5 x ED95). RESULTS: Age and body mass index were comparable between females and males (38 (+/- 8) vs. 37 (+/- 10) years and 24.2 (+/- 2.9) vs. 25.2 (+/- 1.7) kg/m2. However, significant differences in weight and height were found between females and males (65.7 +/- 9.3 kg vs. 77.5 +/- 5.5 kg; p < 0.01 and 178 +/- 6.8 cm vs. 164 +/- 6.7 cm; p < 0.01). Onset time was shorter in females (168 +/- 65 s vs. 211 +/- 56 s; p < 0.05). Maximal neuromuscular blockade after 0.45 mg/kg rocuronium was 94 (+/- 3) % in females and 89 (+/- 6) % in males; p < 0.01. Clinical duration was increased in females (23 +/- 5 min vs. 17 +/- 5 min; p < 0.05), while the recovery index was comparable between both groups (9 +/- 4 min in females and 9 +/- 3 min in males; n.s.). CONCLUSION: Compared to men neuromuscular blockade after 0.45 mg/kg rocuronium was more pronounced in women. The onset time was shortened and the clinical duration increased in female patients.

Adult↗

Mivacurium or vecuronium for paediatric ENT surgery. Clinical experience and cost analysis.

BACKGROUND: The present study compared the quality of neuromuscular block and costs after equipotent doses of mivacurium and vecuronium in the context of paediatric ENT surgery. METHODS: A total of 30 children undergoing elective tonsillectomy were included and randomised in two groups (n = 15 for each) according to the neuromuscular blocking agent (NMBA) used. Anaesthesia was induced with alfentanil (15 micrograms/kg), propofol (3 mg/kg) and either 0.2 mg/kg mivacurium or 0.14 mg/kg vecuronium. For maintenance of anaesthesia propofol (8-12 mg/kg/h) was given. Neuromuscular block was assessed by electromyography using train-of four stimulation and the following parameters were quantified: Twitch height (T1) 2 min after the initial bolus of the myorelaxant; duration until recovery to 10% T1, number and duration of bolus injections of the myorelaxant needed to maintain neuromuscular block to a T1 < 10%. In addition, the intubating conditions, number of patients needing pharmacological reversal at the end of surgery, adverse reactions and the costs for neuromuscular block and pharmacological antagonization were assessed. RESULTS: Intubation conditions were comparable between both study groups: mivacurium--excellent: 7, good: 5, not acceptable: 1; vecuronium--excellent: 11, good: 4 (n.s.). T1 at 2 min was 16 (15)% for mivacurium and 6 (9)% for vecuronium (P < 0.05). Time to 10% T1 recovery was 6.1 (1.7) min for mivacurium and 21.8 (3.7) min for vecuronium (P < 0.01). In the mivacurium group 7 repetitive doses (range: 4-18) were needed to maintain T1 < 10% during surgery, whereas children treated with vecuronium needed only 1 maintenance dose (range: 0-2) (P < 0.01). Two children in the mivacurium group and 11 in the vecuronium group required pharmacological reversal of the NMB at the end of surgery (P < 0.01). The overall costs of NMB were significantly higher in the mivacurium group as compared to vecuronium 12.88 (4.5) Euro vs 9.96 (2.4) Euro; P < 0.05. CONCLUSIONS: In conclusion, mivacurium-induced NMB is of very short duration in paediatric patients, and therefore repetitive doses are required to maintain a deep neuromuscular block. Nevertheless, residual paralysis is less frequent after mivacurium. The neuromuscular block after mivacurium was more expensive and residual paralysis less frequent compared to vecuronium.

Child↗

Remifentanil and propofol without muscle relaxants or with different doses of rocuronium for tracheal intubation in outpatient anaesthesia.

BACKGROUND: The use of muscle relaxants in outpatient anaesthesia is controversial; some authors recommend an induction regimen including propofol and opioids without muscle relaxants. This study evaluated the requirements for rocuronium after remifentanil/propofol. METHODS: We examined in four groups of ASA I-II patients (n= 30 for each) the intubating conditions three minutes after induction of anaesthesia with remifentanil 0.5 microg kg(-1) min(-1), propofol 2 mg kg(-1) without muscle relaxants or with different doses of rocuronium (0.6 mg kg(-1), 0.45 mg kg(-1), 0.3 mg kg(-1)) applying the criteria proposed by the Copenhagen Consensus Conference. In the second part of the study the time course of neuromuscular block was determined by electromyography using train-of-four (TOF) stimulation. To this end, another 60 ASA I-II patients were randomly assigned to receive remifentanil 0.5 microg kg(-1) min(-1), propofol 2 mg kg(-1) and either rocuronium 0.6 mg kg(-1), 0.45 mg kg(-1), 0.3 mg kg(-1), or 0.3 mg kg(-1) followed by neostigmine 40 microg kg(-1) and atropine 20 microg kg(-1) at a T1 recovery of 10% (n=15 for each). RESULTS: Intubating conditions were good or excellent in 30 patients after rocuronium 0.6 mg kg(-1) and in 18 patients when rocuronium was omitted (P<0.01). After 0.45 mg kg(-1) and 0.3 mg kg(-1) rocuronium the numbers were 29 and 30 patients, respectively. Reducing rocuronium from 0.6 mg kg(-1) to 0.45 mg kg(-1) or 0.3 mg kg(-1) increased the onset time from 136 (35) s to 199 (34) s and 249 (52) s (mean (SD)), (P<0.01); the clinical duration decreased from 38 (10) min to 24 (8) min and 16 (5) min, respectively (P<0.01); and the duration to a TOF-ratio of 0.8 decreased from 60 (11) min to 45 (9) min and 34 (7) min (P<0.01). After rocuronium 0.3 mg kg(-1) this time interval further decreased to 22 (3) min when neostigmine was given at a T1 of 10% (P<0.01 compared with spontaneous recovery after rocuronium 0.3 mg kg(-1)). CONCLUSION: After remifentanil/propofol intubation conditions were poor in 40% of patients without muscle relaxants; adding reduced doses of rocuronium to this regimen improved the intubation conditions significantly. In addition, reducing the initial dose of rocuronium markedly shortened its time course of action.

Adult↗

[Rocuronium for anesthesia induction in elective procedures. Time course of muscular blockade and intubation after administration of 2-compartment ED95 (0.6 mg/kg) and dose reduction (0.4 mg/kg)].

BACKGROUND: Rocuronium is a non-depolarising neuromuscular blocking agent structurally related to vecuronium. The compound has a rapid onset and an intermediate duration of action. The rapid onset is of importance in patients at risk for pulmonary aspiration, for elective induction of anaesthesia slower onset properties generally are accepted. In this context, we asked whether the induction dose of rocuronium may be reduced to doses smaller than 2 x ED95 in situations in which slower onset properties may be acceptable. METHODS: The time course of neuromuscular block and intubating conditions of two different doses rocuronium, 2 x ED95 (0.6 mg/kg) and 1.3 x ED95 (0.4 mg/kg), were investigated in 90 patients. We first determined the time course of neuromuscular block using electromyography (EMG), n = 15 for each group. In the second part the intubating conditions 3 min after injection of either rocuronium 0.6 mg/kg or rocuronium 0.4 mg/kg were evaluated, n = 30 for each group. RESULTS: In the present study reduction of the dose of rocuronium led to a slower onset (148 +/- 32 s vs. 220 +/- 30 s; P < 0.05) and a shorter clinical duration (21 min +/- 4 vs. 36 +/- 7 min; P < 0.05). The recovery index was modified by the dose reduction: 11 +/- 3 min after 0.6 mg/kg rocuronium and 9 +/- 2 min after 0.4 mg/kg. After both doses of rocuronium the intubating conditions were good to excellent, no difference between both rocuronium groups were found. CONCLUSION: In the present study dose reduction from 0.6 mg/kg rocuronium to 0.4 mg/kg rocuronium led to a slower onset and reduced clinical duration. However, the intubating conditions, evaluated 3 min after injection of the muscle relaxant were comparable. This offers new possibilities for muscle relaxation for surgical or diagnostic procedures of short duration and may reduce costs.

Adult↗

Antagonism of vecuronium-induced neuromuscular block in patients pretreated with magnesium sulphate: dose-effect relationship of neostigmine.

We have investigated the dose-effect relationship of neostigmine in antagonizing vecuronium-induced neuromuscular block with and without magnesium sulphate (MgSO4) pretreatment. Neuromuscular block was assessed by electromyography with train-of-four (TOF) stimulation. First, we determined neostigmine-induced recovery in patients pretreated with MgSO4 (group A) or saline (group B) (n = 12 each). The height of T1, 5 min after neostigmine, was 43 (7)% in group A and 65 (6)% in group B (P < 0.01). Respective values after 10 min were 59 (7)% and 83 (5)% (P < 0.01). TOF ratio, 5 min after neostigmine, was 29 (6)% in group A and 29 (5)% in group B. Respective values after 10 min were 38 (11)% and 51 (7)% (P < 0.01). To gain insight into the mechanisms leading to delayed recovery after MgSO4, we calculated assisted recovery, defined as neostigmine-induced recovery minus mean spontaneous recovery. Spontaneous recovery was assessed in another 24 patients. Patients in group C received MgSO4/vecuronium and patients in group D vecuronium only (n = 12 each). Five minutes after neostigmine, assisted recovery was 22 (7)% in the MgSO4 pretreated patients and 28 (6)% in controls (P < 0.05). Ten minutes after neostigmine, values were 24 (7)% and 22 (6)%. Maximum assisted recovery was not influenced by MgSO4 pretreatment (27 (6)% in group A and 32 (6)% in group B) and time to maximum effect was comparable between groups: 6 (4-10) min and 7 (5-8) min, respectively. We conclude that neostigmine-induced recovery was attenuated in patients treated with MgSO4. This was mainly a result of slower spontaneous recovery and not decreased response to neostigmine.

Adult↗