[Update on muscle relaxation : What comes after succinylcholine, rocuronium and sugammadex?] / Update Muskelrelaxation : Was kommt nach Succinylcholin, Rocuronium und Sugammadex?

Due to the great advantages, it is not possible to imagine current practice in anesthesia without the adminstration of muscle relaxants. For a long time the administration of succinylcholine for rapid sequence induction (RSI) was considered to be the state of the art for patients at risk for aspiration. The favorable characteristics are, however, accompanied by many, sometimes severe side effects. Due to the development of non-depolarizing muscle relaxants, in particular rocuronium in combination with sugammadex, there is the possibility to achieve a profile of action similar to succinylcholine with low side effects. After the introduction of sugammadex onto the market, further substances were conceived, which enable a complete encapsulation of muscle relaxants. Calabadion is a very promising new substance for the antagonization of muscle relaxants, which can antagonize the action of steroid as well as benzylisoquinoline types. In the USA new muscle relaxants are currently being tested, which have a rapid onset and the effect can be reversed by L­cysteine. One of the most promising substances is gantacurium, which is currently being tested in the USA in phase III trials. It remains to be seen whether these muscle relaxants, which are not yet on the market and drugs for reversal of neuromuscular blockade have the potential to become a real alternative to the combination of rocuronium and sugammadex.

Electroconvulsive Therapy Considerations for Transgendered Patients.

As the transgender patient population continues to grow, health care providers will need to become aware of elements unique to the transgender community in order to provide the highest quality of care. Neuromuscular blockade with succinylcholine is routinely administered to patients undergoing electroconvulsive therapy (ECT). Decreased amounts or activity of pseudocholinesterase in serum can lead to prolonged duration of muscle paralysis. Causes of reduced action by pseudocholinesterase include genetically abnormal enzymes, reduced hepatic production, pregnancy, and various drug interactions. Estrogen supplementation taken by transitioning patients may affect the duration of neuromuscular blockade.This is a case of a 32-year-old male-to-female transgender patient with prolonged apnea following ECT treatment for severe, refractory depression. Further investigation revealed the patient was on estrogen therapy as a part of her transition and laboratory testing demonstrated reduced serum pseudocholinesterase activity. Further laboratory testing demonstrated reduced serum pseudocholinesterase activity. Succinylcholine dosing was titrated to an appropriate level to avoid prolonged apnea in subsequent ECT treatments. Physicians and other health care providers are faced with a unique population in the transgender community and must be aware of distinctive circumstances when providing care to this group. Of specific interest, many transitioning and transitioned patients can be on chronic estrogen supplementation. Neuromuscular blockade in those patients require attention from the anesthesiology care team as estrogen compounds may decrease pseudocholinesterase levels and lead to prolonged muscle paralysis from succinylcholine.

[Impact of sugammadex on neuromuscular blocking agents use: a multicentric, pharmaco-epidemiologic study in French university hospitals and military hospitals]. / Impact du sugammadex sur les consommations de curares : étude pharmaco-épidémiologique multicentrique dans les centres hospitalo-universitaires et hôpitaux d'instructions des armées français.

INTRODUCTION: Seven Neuromuscular Blocking Agents (NMBA) are commercialized in France. Four of them have an intermediate duration of action. Sugammadex required the use of NMBA slightly employed in clinical practice in France. Its introduction in routine practice could have an impact on NMBA use in clinical practice. This study was then conducted to assess and compare NMBA use before and after the commercialization of sugammadex. MATERIALS AND METHODS: A longitudinal, retrospective, observational study was conducted between 2008 and 2011 in French university hospitals and military hospitals. The consumption data for sugammadex and NMBA were collected using a collection grid which was filled by pharmacists or anesthesiologists. Drug use was measured by the number of vials used divided by the annual number of hospitalizations in surgery and obstetrics (HSO). An overall analysis of the annual frequency of NMBA use was firstly performed, then individual data of each hospital were analyzed. Descriptive statistical analysis including mean, standard deviation, median, minimum and maximum was achieved. RESULTS: Thirty-four out of 39 hospitals participated in the study (87%) and analysis was performed on 26 of them (7%). The data of eight institutions were excluded due to missing values or because of the non-admission of sugammadex in their formulary. The NMBA mostly used were non-steroidal NMBA (75% of market share) with an increased use between 2008 and 2011 concerning atracurium (from 41 to 51 vials of 50mg atracurium used per 100 HSO). The overall analysis revealed an increase of the occurrence of rocuronium (between 2008 and 2011: from 1 to 4.8 vials of 50mg rocuronium used per 100 HSO). Individual analyses on each hospital showed a possible effect of sugammadex introduction on NMBA use in nine hospitals. DISCUSSION AND CONCLUSIONS: The commercialization of sugammadex seems to have induced a discrete increase of steroidal NMBA but non-steroidal NMBA remain the leading agent in France. A long-term follow-up is deserved.

Do we need to use sugammadex at the end of a general anesthesia to reverse the action of neuromuscular bloking agents? Position Paper on Sugammadex use.

Sugammadex, the first selective relaxant-binding agent indicated to reverse the neuromuscular blockade induced during general anesthesia, was recently introduced into clinical practice. In the present report, the following issues pertinent to the use of sugammadex in anesthesia practice are discussed: the intraoperative use of NMBAs and the incidence of postoperative residual curarization (PORC); the efficacy and safety of rocuronium plus sugammadex compared to succinylcholine for rapid sequence induction; the availability of sugammadex in hospitals; and, finally, some relevant legal medical aspects. Sugammadex is considerably more expensive than neostigmine, but its use can be advocated based on its safety and efficacy profile as a reversal agent of steroidal neuro muscular blocking agents (NMBAs), and as a mean to prevent PORC. The availability of sugammadex in Italian hospitals may have a beneficial impact on patient safety. This is due to the fact that PORC is a common and dangerous condition that may lead to postoperative inhalational events, hypoxemia, and pneumonia; and at the moment, it is not completely preventable even when advanced neuro-muscolar monitoring techniques are applied". In the case of rapid sequence intubation (RSI), rocuronium (1.2 mg/kg) administration followed by sugammadex represents a better choice in terms of efficacy and safety than succinylcholine. If a new drug is proven to be safer and more efficient than the one it is replacing, hospitals should consider the new drug and make it available, at least for selected patients or in situations at risk of severe complications. It is reasonable to hypothesize that, when discussing informed consent for elective procedures, patients and families may want to know if the admitting facilities have the superior agent available, and that the absence of such agent could create concerns and complains.

[Muscle relaxants and neuromuscular monitoring - Introduction for a safe clinical application]. / Muskelrelaxanzien und neuromuskuläres Monitoring - Einführung für eine sichere klinische Anwendung.

The use of muscle relaxants facilitates endotracheal intubation and ameliorates the conditions of surgery. But, their use should be controlled - otherwise there will be postoperative residual curarisation which can lead to patient discomfort up to severe medical complications. Therefore, an appropriate surveillance via objective neuromuscular monitoring is essential. This article gives a review of the basic principles of muscle relaxants, their clinical application and the surveillance of their effects and degradation.

Residual neuromuscular block: lessons unlearned. Part II: methods to reduce the risk of residual weakness.

The aim of the second part of this review is to examine optimal neuromuscular management strategies that can be used by clinicians to reduce the risk of residual paralysis in the early postoperative period. Current evidence has demonstrated that frequently used clinical tests of neuromuscular function (such as head lift or hand grip) cannot reliably exclude the presence of residual paralysis. When qualitative (visual or tactile) neuromuscular monitoring is used (train-of-four [TOF], double-burst, or tetanic stimulation patterns), clinicians often are unable to detect fade when TOF ratios are between 0.6 and 1.0. Furthermore, the effect of qualitative monitoring on postoperative residual paralysis remains controversial. In contrast, there is strong evidence that acceleromyography (quantitative) monitoring improves detection of small degrees (TOF ratios >0.6) of residual blockade. The use of intermediate-acting neuromuscular blocking drugs (NMBDs) can reduce, but do not eliminate, the risk of residual paralysis when compared with long-acting NMBDs. In addition, complete recovery of neuromuscular function is more likely when anticholinesterases are administered early (>15-20 minutes before tracheal extubation) and at a shallower depth of block (TOF count of 4). Finally, the recent development of rapid-onset, short-acting NMBDs and selective neuromuscular reversal drugs that can effectively antagonize deep levels of blockade may provide clinicians with novel pharmacologic approaches for the prevention of postoperative residual weakness and its associated complications.

[Short acting muscle relaxants: is neuromuscular monitoring still necessary?]. / Ist neuromuskuläre Uberwachung bei kurzwirkenden Muskelrelaxanzien noch erforderlich?

Neuromuscular blocking agents are used to facilitate intubation and to establish muscle paralysis during surgery. However, postoperative residual blocks are a significant complication following the use of neuromuscular blocking agents with an incidence of approximately 30 % at arrival in the post operative care unit. If they are not identified and adequately treated, residual neuromuscular blocks would increase the risk for muscle fatigue, hypoventilation, swallowing disorders, and aspiration. These complications may result in postoperative pulmonary disease. Therefore, monitoring of neuromuscular block is essential not only to detect residual paralysis postoperatively but also to maintain adequate muscle paralysis for surgery. Moreover, the response of individual patients to a particular drug can be variable and needs to be determined for the individual patient in a clinical situation. Sugammadex, the newly developed steroidal muscle relaxant encapsulator, is another important step to optimize treatment with neuromuscular blocking agents but will not replace neuromuscular monitoring. Since qualitative assessment has been shown to be insufficient to validly measure neuromuscular block in the anesthetized patient, it should be monitored quantitatively. Only using this technique and treating residual blocks where required, life threatening complications can certainly be avoided.

Physiology and biology of neuromuscular transmission in health and disease.

The introduction of powerful and contemporary research techniques has allowed for an increasingly detailed understanding of neuromuscular transmission. The classic model of nerve signaling to muscle using acetylcholine has been well described. Newer discovery points toward a more complex signaling system with adaptive receptor physiology and a multifaceted action response scheme for muscle relaxants. Although adding complexity, these newer discoveries help align experimentally derived knowledge with clinical observations. In this review, new concepts relative to neuromuscular transmission in health and disease are discussed, including a detailed discussion of acetylcholine and acetylcholine receptor physiology. Recent elucidations of the pathophysiologic responses to neuromuscular injury and its clinical implications are also detailed.

Reversal of profound, high-dose rocuronium-induced neuromuscular blockade by sugammadex at two different time points: an international, multicenter, randomized, dose-finding, safety assessor-blinded, phase II trial.

BACKGROUND: Sugammadex (Org 25969), a novel, selective relaxant binding agent, was specifically designed to rapidly reverse rocuronium-induced neuromuscular blockade. The efficacy and safety of sugammadex for the reversal of profound, high-dose rocuronium-induced neuromuscular blockade was evaluated. METHODS: A total of 176 adult patients were randomly assigned to receive sugammadex (2, 4, 8, 12, or 16 mg/kg) or placebo at 3 or 15 min after high-dose rocuronium (1.0 or 1.2 mg/kg) during propofol anesthesia. The primary endpoint was time to recovery of the train-of-four ratio to 0.9. Neuromuscular monitoring was performed using acceleromyography. RESULTS: Sugammadex administered 3 or 15 min after injection of 1 mg/kg rocuronium decreased the median recovery time of the train-of-four ratio to 0.9 in a dose-dependent manner from 111.1 min and 91.0 min (placebo) to 1.6 min and 0.9 min (16 mg/kg sugammadex), respectively. After 1.2 mg/kg rocuronium, sugammadex decreased time to recovery of train-of-four from 124.3 min (3-min group) and 94.2 min (15-min group) to 1.3 min and 1.9 min with 16 mg/kg sugammadex, respectively. There was no clinical evidence of reoccurrence of neuromuscular blockade or residual neuromuscular blockade. Exploratory analysis revealed that prolongation of the corrected QT interval considered as possibly related to sugammadex occurred in one patient. Another two patients developed markedly abnormal arterial blood pressure after sugammadex that lasted approximately 15 min. CONCLUSION: Sugammadex provides a rapid and dose-dependent reversal of profound neuromuscular blockade induced by high-dose rocuronium (1.0 or 1.2 mg/kg) in adult surgical patients.

Effect of dexmedetomidine premedication on the intraocular pressure changes after succinylcholine and intubation.

BACKGROUND: Succinylcholine is still recommended for some situations in open globe injuries. However, the use of succinylcholine is associated with an increase in intraocular pressure (IOP). This may be deleterious in open globe injuries. No method has previously been shown to abolish completely this rise in the IOP. We investigated whether dexmedetomidine, an alpha-2 agonist, could attenuate this increase in the IOP after succinylcholine and intubation. METHODS: Forty patients with no pre-existing eye disease undergoing general anaesthesia were randomly premedicated by i.v. dexmedetomidine 0.6 microg kg(-1), or saline. Heart rate (HR), mean arterial pressure (MAP), and IOP (using Schioetz tonometer) were measured before, after the premedication, after thiopental, after succinylcholine, immediately after intubation, and then every 2 min for 6 min. RESULTS: Succinylcholine and intubation increased IOP in both groups. However, in the dexmedetomidine group, the IOP rise was not different from the baseline value (P=0.65) and was significantly lower than in the saline group (P=0.003). After intubation, the MAP in the control group was higher than that in the dexmedetomidine group (P=0.041) and exceeded the baseline value (P<0.001). The HR also showed less fluctuation in the dexmedetomidine group than in the saline group. CONCLUSIONS: We conclude that dexmedetomidine could be a beneficial premedication in open globe injuries.

[Neuromuscular blockades. Agents, monitoring and antagonism]. / Neuromuskuläre Blockade. Substanzen, Uberwachung, Antagonisierung.

Currently, the main aims of using neuromuscular blocking agents during general anaesthesia are the improvement of surgical and intubation conditions. Neuromuscular blocking agents themselves are neither analgesic nor anaesthetic. All agents interact with the acetylcholinergic receptor at the neuromuscular junction and induce a blockade either through a continuous activation imitating the effect of acetylcholine or through a competitive antagonism against acetylcholine. Succinylcholine is the only depolarizing muscle relaxant that is in clinical use. Non-depolarizing neuromuscular blockers may be grouped by their chemical structure into benzylisoquinolines or aminosteroids, and cover the complete range from short and intermediate, to long acting agents. Possible adverse drug reactions to the single agents are also related to their mechanism of action. Moreover, pharmacokinetic properties and effects such as histamine liberation could play an important role when choosing a myorelaxant. The depth of a neuromuscular block and recovery from paralysis can be monitored using qualitative and quantitative techniques. Therefore, the monitoring of neuromuscular recovery plays an important role in the prevention of postoperative complications due to residual paralysis. In case of residual paralysis, cholinesterase inhibitors are suitable for reversal.

Age-related changes in tolerance to the marine algal excitotoxin domoic acid.

During an incident of toxic mussel poisoning, the epileptogenic excitotoxin domoic acid (DOM) was associated with lasting neurological deficits mainly in older patients (), suggesting supersensitivity to excitotoxins is a feature of brain aging. Here, hippocampal slices from young (3 months) and aged (26-29 months) Sprague Dawley rats were assessed by CA1 field potential analysis before and after preconditioning with DOM. In naïve slices from young animals, DOM produced initial hyperexcitability followed by significant dose-dependent reductions in population spike amplitude during prolonged application. Following toxin washout, only small changes in neuronal activity were evident during a second application of DOM, suggesting that a resistance to the effects of DOM occurs in hippocampal slices which have undergone prior exposure to DOM. This inducible tolerance was not antagonized by the NMDA receptor blockers APV or MK-801, nor was it diminished by the group I, II or III mGluR blockers AIDA, CPPG and EGLU. Likewise, neither the AMPA/KA blocker CNQX nor the VSCC blocker nifedipine were effective in blocking tolerance induction in young slices. Field potential analysis revealed significant age-related reductions in CA1 EPSP strength, population spike amplitude and paired-pulse inhibition, but aged slices did not differ in sensitivity to DOM relative to young. However, aged CA1 failed to exhibit any tolerance to DOM following preconditioning, suggesting that a loss of inducible neuroprotective mechanisms may account for increased sensitivity to excitotoxins during aging.

Skeletal muscle relaxants: pharmacodynamics and pharmacokinetics in different patient groups.

Muscle relaxants can be safely administered during anaesthesia, providing the basic pharmacodynamic and pharmacokinetic characteristics of the compounds together with the physiological status of the patient are known. In this review the pharmacodynamics and pharmacokinetics of the neuromuscular blocking agents are discussed and related to the physical health or disease state of groups of patients.