Use Of Neuromuscular Blocking Drugs Research Articles

Drug related critical incidents

Drug related incidents are a common form of reported medical errors. This paper reviews the critical incidents related to drug errors reported from the main operating theatre suite in a teaching hospital in a developing country from January 1997 to December 2002. Each report was evaluated individually by two reviewers using a structured process. During this period, 44 874 anaesthetics were administered; 768 critical incidents were reported, 165 (21%) of which were related to drug errors. Underdosage, side-effect/drug reaction and syringe swap were the most common. A total of 76% were classified as preventable; 56% due to human error and 19% due to system error. High risk incidents accounted for 10% of all drug errors and most of these were related to the use of neuromuscular blocking drugs. This analysis has been found useful in addressing some issues about priorities.

The use of neuromuscular blocking drugs in adult cardiac surgery: results of a national postal survey.

Available data suggest that the choice of neuromuscular blocking drugs (NMBDs) can influence early clinical recovery of the fast-track cardiac surgical patient. The aim of this study was to use a survey tool to determine practice patterns of anesthesiologists for the use of NMBDs in the cardiac surgical setting. We mailed a survey to one third of the 3295 active members of the Society of Cardiovascular Anesthesiologists. A follow-up letter and survey were sent to each individual who did not respond to the initial mailing. After the second mailing, 459 surveys were returned, yielding a response rate of 43%. Pancuronium was listed as the primary NMBD used in the majority of patients undergoing cardiopulmonary bypass (69%) and off-pump (41%) procedures. Only 28% of respondents routinely used a peripheral nerve stimulator to monitor neuromuscular blockade in the operating room. Residual neuromuscular blockade was routinely reversed before tracheal extubation by only 9% of cardiac anesthesiologists. This survey demonstrates that long-acting NMBDs are often administered to fast-track cardiac patients. Peripheral nerve stimulator monitoring is rarely used in the operating room or intensive care unit, and reversal drugs (anticholinesterases) are infrequently administered in the postoperative period. This postal survey of cardiac anesthesiologists demonstrates that long-acting muscle relaxants are frequently administered to fast-track cardiac surgical patients. Neuromuscular blockade is rarely monitored or reversed in this patient population.

Tracheal intubating conditions using propofol and remifentanil target‐controlled infusions

Using target-controlled infusions (TCI) we aimed to determine the most appropriate dose of remifentanil required for intubation, using a steady effect-site concentration of propofol and without the use of neuromuscular blocking drugs. Sixty ASA III patients presenting for elective surgery were randomly allocated to one of three groups. Anaesthesia was induced in all patients using a target-controlled infusion of propofol 6.5 microg x ml(-1). This was reduced to 3 microg x ml(-1) after 1 min. Each group received a different TCI of remifentanil, 19, 15 or 11 ng x ml(-1), which was reduced to 10, 8 or 6 ng x ml(-1), respectively, after 1 min. Laryngoscopy and intubation were attempted at 4 min. Laryngoscopy and ease of intubation were assessed using a standard scoring system. Intubation was considered satisfactory in 75% of patients in groups 1 and 2 and 35% of patients in group 3. Intubation was successful in 20/20, 19/20 and 15/20 patients in groups 1, 2 and 3, respectively. Pulse oximetry, heart rate and noninvasive arterial pressure were measured pre-induction, and at intervals until after laryngoscopy and intubation. Mean arterial pressure (MAP) and heart rate decreased following induction of anaesthesia in all groups, which was statistically significant. Following laryngoscopy, MAP and heart rate increased, but were significantly less than the corresponding baseline values.

Atracurium is associated with postoperative residual curarization

Residual paralysis following the use of neuromuscular blocking drugs remains a clinical problem. As part of departmental quality assurance, we examined the degree of postoperative residual curarization (PORC) following atracurium. Forty patients undergoing general anaesthesia involving atracurium were studied. Quantitative neuromuscular monitoring (mechanomyography, Myograph 2000, Biometer, Denmark) was performed by assessing the response to supramaximal train-of-four (TOF) stimulation of the ulnar nerve. Anaesthesia was provided by non-participating clinicians who were blinded to the study data. A TOF ratio </=0.7 at extubation was classified as PORC. At antagonism of neuromuscular block, 70% (28/40) of patients had a TOF ratio </=0.7, and 65% (26/40) of patients had a TOF ratio </=0.7 at extubation. Peripheral nerve stimulator use was associated with a longer interval from antagonism of block to extubation (P=0.01), but was not associated with differences in atracurium dosage or a reduction in PORC at extubation. Patients with TOF ratio </=0.7 at extubation had surgery of shorter duration [59 (SEM 6) vs 103 (9) min, P<0.001], greater doses of atracurium relative to the duration of surgery [6 (1) vs 11 (1) micro g kg(-1) min(-1), P<0.005], and shorter intervals from administration of last dose of atracurium to antagonism of neuromuscular block [29 (2) vs 53 (9) min, P<0.005] and from antagonism to extubation [6 (1) vs 15 (4) min, P<0.01]. Duration of surgical procedure was the sole multivariate predictor of PORC [odds ratio 0.94 (95% confidence intervals 0.91-0.98), P<0.01]. PORC remains a clinical problem despite use of intermediate-duration neuromuscular blocking drugs and peripheral nerve stimulators. Patients undergoing procedures of short duration may be at risk of inappropriately early tracheal extubation, possibly due to work pressures. The association between suboptimal antagonism of neuromuscular blockade and short procedures needs reinforcement during postgraduate training and departmental quality assurance.

Atracurium is associated with postoperative residual curarization

Background. Residual paralysis following the use of neuromuscular blocking drugs remains a clinical problem. As part of departmental quality assurance, we examined the degree of postoperative residual curarization (PORC) following atracurium. Methods. Forty patients undergoing general anaesthesia involving atracurium were studied. Quantitative neuromuscular monitoring (mechanomyography, Myograph 2000, Biometer, Denmark) was performed by assessing the response to supramaximal train‐of‐four (TOF) stimulation of the ulnar nerve. Anaesthesia was provided by non‐participating clinicians who were blinded to the study data. A TOF ratio ≤0.7 at extubation was classified as PORC. Results. At antagonism of neuromuscular block, 70% (28/40) of patients had a TOF ratio ≤0.7, and 65% (26/40) of patients had a TOF ratio ≤0.7 at extubation. Peripheral nerve stimulator use was associated with a longer interval from antagonism of block to extubation (P=0.01), but was not associated with differences in atracurium dosage or a reduction in PORC at extubation. Patients with TOF ratio ≤0.7 at extubation had surgery of shorter duration [59 (sem 6) vs 103 (9) min, P<0.001], greater doses of atracurium relative to the duration of surgery [6 (1) vs 11 (1) µg kg–1 min–1, P<0.005], and shorter intervals from administration of last dose of atracurium to antagonism of neuromuscular block [29 (2) vs 53 (9) min, P<0.005] and from antagonism to extubation [6 (1) vs 15 (4) min, P<0.01]. Duration of surgical procedure was the sole multivariate predictor of PORC [odds ratio 0.94 (95% confidence intervals 0.91–0.98), P<0.01]. Conclusions. PORC remains a clinical problem despite use of intermediate‐duration neuromuscular blocking drugs and peripheral nerve stimulators. Patients undergoing procedures of short duration may be at risk of inappropriately early tracheal extubation, possibly due to work pressures. The association between suboptimal antagonism of neuromuscular blockade and short procedures needs reinforcement during postgraduate training and departmental quality assurance. Br J Anaesth 2002; 89: 766–9

Neuromuscular blockade: Inadvertent extubation of the partially paralyzed patient

Residual neuromuscular block is common after the use of neuromuscular blocking drugs during anesthesia. Although careful reversal [table: see text] techniques usually result in adequate return of neuromuscular recovery, sometimes it is not possible to achieve full recovery of neuromuscular block. Ventilatory support and maintenance of a patent airway are required until recovery can be demonstrated. In those situations, in which some TOF fade is still obvious, the anesthesiologist should consider retaining the endotracheal tube in position; it is not a sign of failure to return a patient whose trachea is still intubated to the postanesthesia care unit. The inadvertent extubation of patients who are partially paralyzed results in increased postoperative morbidity.

Intensive care sedation: a review of current British practice.

Sedation is central to the management of intensive care patients. Many different techniques have been tried, all have potential side effects, and some have been associated with serious adverse effects. The aim of this work is to establish current sedation practice in British ICUs; the use of neuromuscular blocking drugs and the indications for their use, the use of sedation policies and scoring systems, the influence of cost on drug choice, and the use of propofol for sedation in paediatric patients. A postal survey sent to all units identified in the Directory of Emergency Services. Two hundred and fifty-five replies were received from 323 questionnaires (79% response rate). The replies show that alfentanil, morphine, midazolam, and propofol are the most widely used drugs for sedation, and that changes occur in sedation policy with the time a patient spends in intensive care. Atracurium is the most widely used neuromuscular blocking drug, but the number of patients who receive therapeutic paralysis is relatively small and the indications for its use in different units is consistent. Propofol is used by many ICUs for the sedation of children despite reports linking its use to mortality in children and the advice of the regulatory authorities. Drugs used for the sedation of patients in intensive care have changed since previous surveys. The sedation policy of most units relies on the combination of small numbers of drugs. Sedation policies now seem to concentrate on achieving a lightly sedated co-operative patient.

Clinical uses and controversies of neuromuscular blocking agents in infants and children.

To review the pharmacology of neuromuscular blocking drugs (NMBDs), their use in critically ill or injured infants and children, and the relevance of developmental changes in neuromuscular transmission. Computerized search of the medical literature. Studies specifically examining the following were reviewed: a) the developmental changes in neuromuscular transmission; b) the pharmacokinetics and pharmacodynamics of all clinically available NMBDs in neonates, infants, children, and adults; and c) clinical experience with NMBDs in the critical care setting. Particular attention was directed toward studies in the pediatric population. Neuromuscular transmission undergoes maturational changes during the first 2 months of life. Alterations in body composition and organ function affect the pharmacokinetics and pharmacodynamics of the NMBDs throughout active growth and development. Numerous NMBDs have been developed during the last two decades with unique pharmacologic profiles and potential clinical advantages. The NMBDs are routinely used in critically ill or injured patients of all ages. This widespread use is associated with rare but significant clinical complications, such as prolonged weakness. Significant gaps in our knowledge of the pharmacokinetics and pharmacodynamics of NMBDs in infants and children continue to exist. Alterations in electrolyte balance and organ-specific drug metabolism may contribute to complications with the use of NMBDs in the critical care arena.

BISPECTRAL INDEX

S58 INTRODUCTION: Awareness during general anesthesia, particularly with use of neuromuscular blocking drugs, is a potential risk. Bispectral index (BIS), a processed EEG, has been shown to be useful in monitoring the level of consciousness [1]. This study measured arousal and level of consciousness reflected by BIS during endotracheal intubation, a noxious stimulus, during general anesthesia (GA) at our institution. METHODS: With IRB approved consent, 100 patients aged 18 to 70 yrs of either sex, ASA class I or II, were studied. Following placement of intravenous canula in the non-dominant arm and routine monitors and BIS (Model A 1000 EEG, Aspect Medical Systems, Inc.), a tourniquet (pressure > 150 above SBP) was applied on the dominant arm. Patients practiced squeezing the investigator's hand on command, first once and then following a positive response, twice. Anesthesia was then induced by the method of choice of the anesthesia team. Patients were commanded to squeeze the hand every 30 seconds from the time of induction until 5 min. following endotracheal intubation. BIS, heart rate and blood pressure were continuously recorded. The isolation of the forearm was assured with a peripheral nerve stimulator. Throughout the study, the anesthesia team was unaware of the patients' responses to command or the BIS. All patients were interviewed twenty four hours later about awareness and recall. Data were analyzed using Student's t-test and linear regression. P< 0.05 was considered significant. RESULTS: Sixteen patients responded by squeezing the hand twice on command (arousal group). Two patients responded by squeezing the hand once and were included in the non-arousal group. (Table 1)Table 1The increase in BIS from the start of laryngoscopy to the end of endotracheal intubation in the arousal group was approximately 10 units vs. 3.5 in the non-arousal group (P<0.001). There was no difference in heart rate or mean arterial pressure. None of the patients reported any awareness or recall. DISCUSSION: The study demonstrates that 16% of the patients were aroused by noxious stimulus during routine induction of anesthesia. Patients with higher BIS values (higher levels of consciousness) had an increased incidence of arousal and their BIS response to noxious stimulus was significantly greater than patients with lower initial BIS values. BIS may be valuable in determining the level of consciousness (depth of hypnosis) prior to noxious stimuli encountered during GA.

Awareness with Recall During General Anesthesia

In Response: Dr. Metz addresses the important issue of muscular relaxation and awareness during general anesthesia. Indeed, the use of neuromuscular blocking drugs seems to be a prerequisite for awareness and recall [1,2]. Only very few case reports of awareness without paralysis have been published [3,4]. In our recent study, there were three patients with possible awareness in whom muscle relaxants were not used [5]. However, these were all patients with very unspecific memories, and their recollections may have originated in the recovery room or may even have been illusions or hallucinations. The data regarding the use of muscle relaxants in the study material [5] are shown in Table 1. Several relaxants were used during the study. In the database of 554 anesthetic records that we used for the analysis, atracurium was used for 63.2% of cases, succinylcholine for 10.8%, vecuronium for 3.4%, pancuronium for 1.4%, and rocuronium for 0.2%. We created a Table in which we summed all relaxants as either used or not used. The Table wasanalyzed with Yates corrected chi squared statistics, as the expected frequencies in the group of patients with awareness were low.Table 1: The Use of Muscle Relaxants Versus Awareness with RecallThere was no statistically significant difference in the frequency of use of muscle relaxants. However, when only patients with objective intraoperative memories are considered (Groups 2 and 3 in the original study), all the patients with awareness received muscle relaxants, and there seems to be a trend toward the use of relaxant drugs among patients with awareness. In the original study, we used a regression model to measure the statistical significance of the various anesthetics used. We believe that one must interpret the data of a frequency Table very cautiously because the dosing of the drugs does not play any role in such a table. However, we strongly agree with Dr. Metz that muscle relaxants should be used as sparingly as possibly so as to give the anesthetized patient an opportunity to signal awareness by movement. Seppo O-V Ranta, MD Department of Anaesthesia; Children's Hospital; Helsinki University; FIN-00290 Helsinki, Finland Markku Hynynen, MD Department of Anaesthesia and Intensive Care; Jorvi Hospital; FIN-02740 Espoo, Finland

TWITCHER: a device to stimulate thumb twitch response to ulnar nerve stimulation.

To design and fabricate a device to simulate evoked thumb adduction in response to ulnar nerve stimulation. We implemented a computer-controlled, motorized thumb (TWITCHER) that responds to ulnar nerve stimulation by an unmodified peripheral nerve stimulator. Clinically realistic response patterns are generated for both depolarizing and non-depolarizing muscle relaxants and three modes of stimulation (single twitch, train-of-four, tetanus). The device has been used in a full-scale patient simulator for the last six years. TWITCHER has been well received by participants in simulation exercises including the use of neuromuscular blocking drugs.

A Multicenter Study of Bispectral Electroencephalogram Analysis for Monitoring Anesthetic Effect

Bispectral analysis (BIS) of the electroencephalogram (EEG) has been shown in retrospective studies to predict whether patients will move in response to skin incision. This prospective multicenter study was designed to evaluate the real-time utility of BIS in predicting movement response to skin incision using a variety of general anesthetic techniques. Three hundred patients from seven study sites received an anesthetic regimen expected to give an approximately 50% movement response at skin incision. EEG was continuously recorded via an Aspect B-500 monitor and BIS was calculated in real time from bilateral frontocentral channels displayed on the monitor. Half of the patients were randomized to a treatment group in which anesthetic drug doses were increased to produce a lower BIS. In the control group, BIS was recorded, but no action taken on the data displayed. A determination of movement in response to skin incision was made in the 2 min succeeding incision. Retrospective pharmacodynamic modeling was performed using STANPUMP to estimate effect-site concentrations of intravenously administered anesthetics. BIS values were significantly higher in the control group (66 +/- 19) versus the BIS-guided group, in which additional anesthesia was administered to produce a lower BIS (51 +/- 19). The movement response rate was significantly higher in the control group at 43% compared with 13% in the BIS-guided group, but response rates were low at sites which used larger doses of opioids. Logistic regression analysis showed that BIS, estimated opioid effect-site concentrations, and heart rate (in that order) were the best predictors of movement at skin incision. This study demonstrates that dosing anesthetic drugs to lower BIS values achieves a lower probability of movement in response to surgical stimulation. BIS is a significant predictor of patient response to incision, but the utility of the BIS depends on the anesthetic technique being used. When drugs such as propofol or isoflurane are used as the primary anesthetic, changes in BIS correlate with the probability of response to skin incision. When opioid analgesics are used, the correlation to patient movement becomes much less significant, so that patients with apparently "light" EEG profiles may not move or otherwise respond to incision. Therefore, the adjunctive use of opioid analgesics confounds the use of BIS as a measure of anesthetic adequacy when movement response to skin incision is used as the primary end point.

筋弛緩薬の理に叶った使用法の臨床的考察（原標題は英語）

筋弛緩薬の理に叶った使用法の臨床的考察（原標題は英語）

Postal survey on the long-term use of neuromuscular block in the intensive care.

To assess the long-term use of neuromuscular blocking (NMB) agents in intensive care, especially with reference to the potential problems of the long-term use of NMB drugs in the intensive care unit (ICU). A postal survey questionnaire was sent to 409 ICUs in Great Britain. Two hundred thirty-eight completed questionnaires were returned and analysed. Most ICUs were anaesthetist-led (85.8%) with only five ICUs being staffed by full-time intensivists. Facilitation of mechanical ventilation and increased intracranial pressure were the main indications for the prolonged use of neuromuscular blockade. Atracurium and vecuronium (83%) were administered most commonly by bolus alone (13.8%), bolus followed by continuous infusion (23.9%) or continuous infusion only (60.9%). The most frequently cited criteria for the use of either vecuronium or stracurium were their pharmacokinetics and haemodynamic stability. Neuromuscular block was most commonly monitored clinically (91.7%), with only 8.3% of the responders using a peripheral nerve stimulator. All responders indicated the concomitant use of sedatives (propofol/midazolam alone or in combination in 89.4% of responders) and/or opioids (morphine, fentanyl or alfentanil in 74.8% of respondents) with muscle relaxants. Most responders agreed that while neuromuscular block in the ICU population may provide advantages, it cannot be considered benign. Indeed, a great majority consider that NMB agents should be used only as a last option and -for as short a period as possible.

Intensive Care Unit Neuromuscular Syndrome?

Intensive Care Unit Neuromuscular Syndrome?

Neuromuscular Blocking Drugs and the Critical Care Patient

SummaryAs the management of critically ill and emergency patients intensifies and veterinary surgical procedures become more complex, more sophisticated methods of support are becoming necessary. Emergency and critical care patients are excellent candidates for the use of neuromuscular blocking drugs. The main advantage of the current generation of neuromuscular blocking drugs compared to earlier agents is that they provide muscle relaxation with little or no cardiovascular effects. The pharmacology and physiology of neuromuscular blocking drugs are discussed, and their use is described with specific references to critical care patients. Monitoring techniques are described and reversal of neuromuscular blockade as well as potential side effects and adverse reactions arediscussed.

Economic Considerations in the Use of Neuromuscular Blocking Drugs

Economic Considerations in the Use of Neuromuscular Blocking Drugs

Allergische und pseudoallergische Reaktionen in der Anästhesie - Teil I: Pathogenese, Risikofaktoren, Substanzen

In this article we present a survey on the pathogenesis of allergic or pseudoallergic reactions in anaesthesia, the risk factors and the responsible substances. The incidence of anaphylactoid reactions is between 1:3500 and 1:20,000 anaesthetic cases. The estimated mortality rate amounts to 3-6%. Neuromuscular blocking drugs account for most of the cases of significant anaphylactoid reactions (59-70%). However, the incidence of latex-related reactions in increasing. Risk factors for anaphylaxis are a history of IgE-mediated drug allergy, repeated anaesthesias, atopy, hyperventilation tetany, and the use of neuromuscular blocking drugs in females. Risk factors for pseudoallergic reactions are emotional stress, atopic predisposition, increased sensitivity for histamin, hyperventilation tetany and female gender.

Muscle relaxants in renal disease.

The use of neuromuscular blocking drugs during anaesthesia for patients with chronic renal failure is discussed. The disadvantages of the older non-depolarizing agents, such as tubocurarine, alcuronium, and pancuronium are outlined, as are the significant benefits of the use of atracurium or vecuronium in these patients. Preliminary reports on the new non-depolarizing drugs, pipecuronium, mivacurium, doxacurium, and rocuronium are also noted.

Economic considerations in the use of neuromuscular blocking drugs

The acceptance of new and increasingly expensive technologies is a major component of the rising costs of health care. While the practice of anesthesia has been relatively immune from the effects of cost containment, it is inevitable that practitioners will have to justify costly practices. Available pharmacoeconomic methods can be applied to the use of all anesthetic drugs, particularly neuromuscular blocking drugs. Cost-effectiveness analysis allows the practicing anesthesiologist to prioritize the use of neuromuscular blocking drugs to maximize their benefit while reducing unnecessary costs.