Arm-to-arm variation when evaluating neuromuscular block: an analysis of the precision and the bias and agreement between arms when using mechanomyography or acceleromyography.

BACKGROUND: Studies comparing acceleromyography and mechanomyography indicate that the two methods cannot be used interchangeably. However, it is uncertain to what extent differences in precision between the methods and the naturally occurring arm-to-arm variation have influenced the results of these studies. Accordingly, the purpose of this study was to examine the precision and the arm-to-arm variation, when the same method is used on both of the arms. METHODS: In the first part (n=20), mechanomyography was applied bilaterally and in the second part acceleromyography (n=20). Anaesthesia was induced with propofol and opioid, and neuromuscular block with rocuronium 0.6 mg kg(-1). The precision of the two methods and the bias and limits of agreement between the arms were evaluated using train-of-four (TOF) stimulation, without and with referral to the initial baseline value, that is, normalization. RESULTS: Both methods were found to be precise (<5% variation) without any difference between the dominant and non-dominant arms. There were no significant biases between the arms, except for the onset time obtained with acceleromyography, which was 10% longer for the dominant arm. However, the individual differences (limits of agreement) were wide (0.20-0.25 at TOF 0.90). Normalization during recovery did not change bias or limits of agreement between the arms. CONCLUSIONS: In the research setting, acceleromyography and mechanomyography are both precise methods without difference between the arms. Although there is no mean bias between the arms, both methods show wide individual differences (limits of agreement), which might to a large extend explain the differences often found when two different methods are compared on the contralateral arms. ClinicalTrial.gov identifier: NCT00472121; URL: http://clinicaltrials.gov/ct2/show/study/NCT00472121.

Acceleromyography and mechanomyography for establishing potency of neuromuscular blocking agents: a randomized-controlled trial.

BACKGROUND: Acceleromyography (AMG) is increasingly being used in neuromuscular research, including in studies establishing the potency of neuromuscular blocking and reversal agents. However, AMG is insufficiently validated for use interchangeably with the gold standard, mechanomyography (MMG) for this purpose. The aim of this study was to compare AMG and MMG for establishing dose-response relationship and potency, using rocuronium as an example. METHODS: We included 40 adult patients in this randomized-controlled single-dose response study. Anaesthesia was induced and maintained with propofol and opioid. Neuromuscular blockade was induced with rocuronium 100, 150, 200 or 250 microg/kg. Neuromuscular monitoring was performed with AMG (TOF-Watch SX) with pre-load (Hand Adapter) at one arm and MMG (modified TOF-Watch SX) on the other, using 0.1 Hz single twitch stimulation. Dose-response relationships were determined for both recording methods using log (dose) against probit (maximum block). The obtained slopes of the regression lines, ED(50), ED(95) and the maximum block were compared. RESULTS: The ED(50) and ED(95) [95% confidence interval (CI)] for AMG were 185 microg/kg(167-205 microg/kg) and 368 microg/kg(288-470 microg/kg), compared with 174 microg/kg(159-191 microg/kg) and 338 microg/kg(273-418 microg/kg) for MMG. There were no statistically significant biases in maximum block, ED(50), ED(95) or slopes obtained with the two methods. CONCLUSION: Our results indicate that any possible difference between AMG and MMG is so small that it justifies AMG to be used for establishing the potency of neuromuscular blocking agents. However, the wide CIs show that we cannot rule out a 13% higher ED(50) and a 26% higher ED(95) for AMG.

The undesirable effects of neuromuscular blocking drugs.

Neuromuscular blocking drugs are designed to bind to the nicotinic receptor at the neuromuscular junction. However, they also interact with other acetylcholine receptors in the body. Binding to these receptors causes adverse effects that vary with the specificity for the cholinergic receptor in question. Moreover, all neuromuscular blocking drugs may cause hypersensitivity reactions. Often the symptoms are mild and self-limiting but massive histamine release can cause systematic reactions with circulatory and respiratory symptoms and signs. At the end of anaesthesia, no residual effect of a neuromuscular blocking drug should be present. However, the huge variability in response to neuromuscular blocking drugs makes it impossible to predict which patient will suffer postoperative residual curarization. This article discusses the undesirable effects of the currently available neuromuscular blocking drugs including the definitions, diagnosis and causes of hypersensitivity reactions and postoperative residual curarisation.

Remifentanil vs. alfentanil for direct laryngoscopy: a randomized study comparing two total intravenous anaesthesia techniques. TIVA for direct laryngoscopy.

The ideal anaesthesia for direct laryngoscopy is profound and yet brief. The present study sought to determine whether a new anaesthetic technique based on infusion of the ultra short-acting opioid remifentanil was superior to our routine alfentanil multiple-dose technique in terms of haemodynamic stability, stress responses and recovery. A total of 58 patients were randomized to receive propofol and either remifentanil or alfentanil as part of a total intravenous anaesthesia. In the remifentanil group, systolic blood pressure during anaesthesia remained significantly lower than baseline values, while it increased significantly in the alfentanil group. None of the patients receiving remifentanil showed stress responses (hypertension, tachycardia, somatic or autonomic responses), compared to 22 patients (79%) in the alfentanil group (P < 0.0001). In the remifentanil group, hypotension or bradycardia requiring intervention arose in 5 (18%) and 3 patients (11%); neither response was seen in the alfentanil group. The period from the end of propofol infusion until extubation was 5 min longer in the remifentanil group (P < 0.0001), whereas the time from extubation until discharge was similar in the two groups. Thus, neither technique showed sufficient haemodynamic stability, and further studies are needed to determine optimal dosages of propofol and opioid.

[Research in Danish departments of anesthesiology at the turn of the century. A bibliometric analysis]. / Forskning ved danske anaestesiologiske afdelinger ved årtusindeskiftet. En bibliometrisk analyse.

INTRODUCTION: This investigation was based on the surmise that the scientific activity in the specialty of anaesthesiology and intensive care medicine in Denmark is declining. MATERIAL AND METHODS: A quantitative and qualitative analysis of the development in Danish anaesthesiological research during the seven-year period of 1992-1998 was performed with bibliometrical methods and a count of the PhD and doctoral theses produced by Danish anaesthesiologists during that period. RESULTS: In the period investigated, a total of 906 scientific articles were published, of which 749 (83%) originated from university hospitals. Total production decreased by 15% between the two-year periods of 1992-1993 and 1997-1998, whereas the output from university hospitals alone decreased by 10%. The number of scientific publications per anaesthesiologist decreased by 34%, corresponding to 6.7% per year. The quality of the research published, as examined by the cumulative and average impact, showed a slight increase. The number of PhD and doctoral theses per year showed no change. DISCUSSION: Research activity in Danish anaesthesiology is declining, and the specialty seems to be losing scientific ground, both nationally and internationally.

Prolonged residual paralysis after a single intubating dose of rocuronium.

It is often argued that neuromuscular monitoring is unnecessary when only one dose of an intermediate-acting neuromuscular blocking agent is given. This case report documents that it may take more than 3.5 h before it is possible to antagonize a block caused by a normal dose of rocuronium (0.6 mg kg(-1)). Possible causes of the extremely prolonged duration of action are discussed, as is the importance of quantitative neuromuscular monitoring.

Good clinical research practice in pharmacodynamic studies of neuromuscular blocking agents II: the Stockholm revision.

The set of guidelines for good clinical research practice (GCRP) in pharmacodynamic studies of neuromuscular blocking agents, which was developed following an international consensus conference in Copenhagen, has been revised and updated following the second consensus conference in Stockholm in 2005. It is hoped that these guidelines will continue to help researchers in the field and assist the pharmaceutical industry and equipment manufacturers in enhancing the standards of the studies they sponsor.

Succinylcholine neuromuscular blockade in subjects heterozygous for abnormal plasma cholinesterase.

The relationship between plasma cholinesterase genotype and duration and type of succinylcholine neuromuscular blockade was studied in 43 anesthetized patients heterozygous for abnormal plasma cholinesterase using train-of-four nerve stimulation. Twenty-eight patients were heterozygous for the usual and the atypical gene (E1uE1a), eight were heterozygous for the usual and the silent gene (E1uE1s), three were heterozygous for the usual and the fluoride-resistant gene (E1uE1f), three were heterozygous for the fluoride-resistant and the atypical gene (E1fE1a), and one was heterozygous for the fluoride-resistant and the silent gene (E1fE1s). Mean time to 90 per cent recovery of twitch height in patients with genotypes E1uE1a, E1uE1s, and E1uE1f (14.6, 12.4, and 12.0 min, respectively) was significantly prolonged compared to patients with normal cholinesterase genotype (9.3 min). No significant difference was found between the three groups of patients with one abnormal gene (E1uE1a, E1uE1s, and E1uE1f). In 13 (46 per cent) of the 28 patients with genotype E1uE1a the twitch height did not return to control for more than 15 min after the administration of succinylcholine and in three patients (10.7 per cent) for more than 20 min after succinylcholine. The four patients with abnormal genes on both chromosomes (E1fE1a and E1fE1s) all showed significantly prolonged paralysis following the administration of succinylcholine (mean time to 90 per cent twitch recovery was 30 min). Patients heterozygous for the usual and one of the abnormal genes (E1uE1a, E1uE1s, and E1uE1f) had typically depolarizing blocks following the administration of succinylcholine, 1 mg/kg. Patients with abnormal genes on both chromosomes (E1fE1a and E1fE1s), however, all showed desensitization type of neuromuscular blockade (phase II block).

Why, how and when to monitor neuromuscular function.

BACKGROUND: Traditionally, anaesthetists evaluate the effect of neuromuscular blocking agents clinically. We observe the fasciculations following injection of succinylcholine, the movements of the reservoir bag, the spontaneous movements of the patient, headlift etc. However, with the advent of new fast acting neuromuscular blocking agents and the increasing awareness of the problems of postoperative residual neuromuscular block there is an mounting understanding of the importance of a more objective assessment of the neuromuscular function during anaesthesia. PURPOSE OF LECTURE: In this lecture I shall give my personal bias on whether or not routine monitoring of neuromuscular function during anaesthesia is essential. Also, I shall try to answer the question "why, how and when should we monitor neuromuscular function during clinical anaesthesia?"

Why should I change my practice of anaesthesia: neuromuscular blocking agents.

BACKGROUND: Recently, four neuromuscular blocking agents have been introduced into clinical practice. The drug companies claim that these new drugs offer several important advantages. But is this true? Do the new neuromuscular blocking agents add anything to our clinical practice, and will their introduction really benefit our patients? Or will it only benefit the economy of the companies? PURPOSE OF THE LECTURE: In this lecture I shall try to update you on these new drugs and give you my personal bias on when to use the different (new and old) neuromuscular blocking agents.

Dose-response relationship and time course of action of rocuronium bromide in perspective.

The available evidence indicates that rocuronium is one of the least potent non-depolarizing muscle relaxants, having a clinical duration, recovery index and reversal time similar to those of atracurium and vecuronium. The onset time, however, is significantly shorter than that of currently used non-depolarizing muscle relaxants. Rocuronium seems to be potentiated by the inhalational anaesthetics to the same degree as vecuronium. This effect is clinically most significant when using a continuous infusion of rocuronium. There is no difference in potency of rocuronium between adult and elderly patients, but it is not clear yet whether the potency differs between adults and neonates, infants or children. The onset time, duration of action, and recovery index are prolonged in elderly patients and the onset time, duration of action, and recovery index are longer in infants than in children.

Neuromuscular monitoring.

This review summarizes recent reports on the techniques and the use of methods for monitoring neuromuscular function during anaesthesia. The latest news on the use of acceleromyography in the face and hand, on laryngeal and diaphragmal surface electromyography, on acoustic myography, on evaluation of intense neuromuscular block, and on postoperative residual curarization is presented and discussed. It is concluded that available evidence suggests that more attention should be paid by the anaesthetist to the problems of residual curarization and hence to proper monitoring of neuromuscular function using objective methods.

Increased sensitivity to succinylcholine in a patient heterozygous for the silent and the fluoride-resistant gene.

Increased sensitivity to succylcholine may be due to inherited variants of serum cholinesterase (acylcholine-acylhydrolase, E.C.3.1.1.8). Four different allelic genes at locus E1 controlling human serum cholinesterase have been identified: the normal gene Eu1, the atypical gene Ea1, the fluoride-resistant gene Ef1, and the silent gene Es1. These 4 genes give rise to 10 possible genotype combinations. The sensitivity of some of these genotypes to succinylcholine, as, for instance, homozygotes for the atypical enzyme Ea1 Ea1, is well documented. However, the relation between some of the rarer genotypes and the sensitivity to succinylcholine is less well clarified. The present report represents the 1st case in which a peripheral nerve stimulator has been used to substantiate the increased succinylcholine sensitivity of a patient heterozygous for the silent and the fluoride-resistant gene, and the 2nd published case of prolonged apnea following succinylcholine in a patient carrying the Ef1 Es1 genotype for abnormal serum cholinesterase.