[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.

[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.

[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.

The effects of antagonizing residual neuromuscular blockade by neostigmine and glycopyrrolate on nausea and vomiting after ambulatory surgery.

UNLABELLED: The effects of neostigmine on the incidence of postoperative nausea and vomiting (PONV) are controversial. In this study, we evaluated the effects of neostigmine and glycopyrrolate on the incidence of PONV and the need for antiemetics in patients undergoing ambulatory surgery. One hundred healthy patients undergoing outpatient surgical procedures were included in the study. A standardized anesthetic technique was used for all patients. Patients were randomized to receive either mivacurium (n = 50) or rocuronium (n = 50) to achieve muscle paralysis. Bolus doses of mivacurium 2-4 mg or rocuronium 5-10 mg were administered to maintain one or two twitches of the train-of-four stimulation of the ulnar nerve at the wrist. After surgery, residual neuromuscular blockade was reversed with neostigmine 2.5 mg i.v. and glycopyrrolate 0.5 mg i.v. only if clinically deemed necessary (i.e., fade on train-of-four stimulation, inadequate tidal volume, reduced hand grip, or inability to maintain head lift). The incidence of PONV and the need for antiemetics were recorded in the post-anesthesia care unit (PACU), in the phase II unit, and 24 h after surgery. We compared patients who received neostigmine (n = 40) for reversal of residual neuromuscular blockade with those who did not (n = 60). More patients receiving rocuronium required reversal drugs than those receiving mivacurium (68% vs 10%). There were no differences in the incidence of nausea (18% vs 15%), vomiting (8% vs 12%), and the need for antiemetics (13% in both the groups) in the PACU between patients who received neostigmine and those who did not. In addition, the duration of PACU stay and the time to home-readiness were also similar between the groups. We conclude that, compared with rocuronium, the use of mivacurium decreases the need for reversal drugs. In addition, reversal of residual neuromuscular blockade with neostigmine does not increase the incidence of PONV or the need for antiemetic medications in patients undergoing ambulatory surgery. IMPLICATIONS: In this study, we showed that the incidence of postoperative nausea and vomiting and the need for antiemetics do not increase with the use of neostigmine and glycopyrrolate for reversal of residual muscle paralysis.

The effect of mivacurium pretreatment on intra-ocular pressure changes induced by suxamethonium.

Forty patients without eye disease, undergoing elective nonophthalmic surgery, were studied in a double-blind, randomised, placebo-controlled study evaluating the efficacy of mivacurium pretreatment in attenuating the rise in intra-ocular pressure in response to suxamethonium administration, laryngoscopy and intubation. The patients were randomly allocated to receive either mivacurium 0.02 mg.kg-1 or normal saline as pretreatment 3 min before a rapid sequence induction technique using alfentanil, propofol and suxamethonium. Suxamethonium induced a significant increase in intra-ocular pressure in the control group but not in the mivacurium pretreatment group (mean (SEM) increase = 3.5 (1.2) mmHg vs. 0.4 (0.8) mmHg, p < 0.05). There was a decrease in intra-ocular pressure in both groups after laryngoscopy and intubation with no significant difference between the two groups. These results show that mivacurium pretreatment is effective in preventing the increase in intra-ocular pressure after suxamethonium administration.

Antagonism of suxamethonium-induced jaw muscle contracture in rats.

Masseter muscle rigidity (MMR) induced during general anaesthesia by suxamethonium is a clinical problem that may interfere with tracheal intubation. We have investigated the relation between twitch tension and contracture response to suxamethonium in rats. Rats were anaesthetized with 1% halothane (1.35 MAC). Jaw muscle temperature was maintained at either 37 or 41 degrees C while rectal temperature was kept at 37 degrees C by radiant heat. Twitch tension was produced by nerve stimulation at 0.2 Hz. Rats were pretreated with either a low dose of vecuronium (0.03 mg kg-1) or dantrolene (0.8 mg kg-1). Thereafter suxamethonium 750 micrograms kg-1 was administrated i.v. Low-dose vecuronium pretreatment significantly (90%) decreased suxamethonium-induced jaw muscle contracture (JMC) with minimal (3%) twitch block during local hyperthermia. Low-dose dantrolene pretreatment also reduced JMC (81% at 37 degrees C and 82% at 41 degrees C) while decreasing twitch by 30% at 37 degrees C and 31% at 41 degrees C. Both vecuronium and dantrolene at doses that minimally depressed the twitch response antagonized suxamethonium-induced JMC. We speculate that pretreatment with low-dose vecuronium decreases suxamethonium-induced MMR clinically.

Comparison of rocuronium and mivacurium to succinylcholine during outpatient laparoscopic surgery.

Tracheal intubating conditions and neuromuscular effects of succinylcholine, rocuronium, and mivacurium were studied in 100 healthy women undergoing outpatient laparoscopic surgery. After a standardized fentanyl-thiopental induction, tracheal intubation was facilitated with succinylcholine 1 mg/kg in Groups I (n = 23) and II (n = 25), rocuronium 0.6 mg/kg in Group III (n = 27), or mivacurium 0.2 mg/kg in Group IV (n = 25). If clinically indicated, bolus doses of rocuronium 5-10 mg (Groups I and III) or mivacurium 2-4 mg (Groups II and IV) were administered during the maintenance period. Anesthesia was maintained with desflurane and nitrous oxide 60% in oxygen. At the end of the surgery, residual neuromuscular block was reversed with edrophonium 0.5 mg/kg and atropine 10 micrograms/kg, if needed. The neuromuscular function was assessed using electromyography with a train-of-four mode of stimulation every 10 s at the wrist. Intubating conditions 90 s after succinylcholine and rocuronium were significantly better than after mivacurium. The onset time (from the end of injection until 95% suppression of the first twitch [T1]) for succinylcholine (63 +/- 21 s and 62 +/- 17 s in Groups I and II, respectively) were significantly shorter than for rocuronium (158 +/- 76 s) or mivacurium (210 +/- 93 s). Moreover, the onset times for rocuronium were significantly shorter than mivacurium. The recovery times (of T1 to 25% of the control value) were significantly shorter with succinylcholine and mivacurium than rocuronium. Significantly fewer patients needed reversal of residual neuromuscular blockade after mivacurium compared to rocuronium. One patient in Group I and six patients in Group IV displayed erythema on the upper body. Postoperative myalgia were experienced by 16% of the patients in Groups I and II compared to none in Groups III and IV. There was on difference in the incidence of postoperative nausea and vomiting among the four groups. In conclusion, rocuronium appears to be an acceptable alternative to succinylcholine for tracheal intubation. However, rocuronium's longer duration of action increases the need for reversal drugs. When rapid tracheal intubation is unnecessary, mivacurium is also an acceptable alternative to succinylcholine and is associated with a more rapid spontaneous recovery than rocuronium.

Effects of magnesium sulphate on suxamethonium-induced complications during rapid-sequence induction of anaesthesia.

Twenty patients were studied in a double-blind manner to investigate whether magnesium sulphate, when given during a rapid-sequence induction of anaesthesia, lessens the side effects caused by suxamethonium. Patients were randomly allocated to two groups; equal volumes of either magnesium sulphate (40 mg.kg-1) or saline were given during rapid-sequence induction of anaesthesia, after thiopentone but before the administration of suxamethonium (1.5 mg.kg-1). The changes in the serum potassium concentration, the degree of muscle fasciculations and the presence of postoperative myalgia were recorded. The mean serum potassium concentration increased by 0.08 mmol.l-1 in the magnesium group and by 0.1 mmol.l-1 in the control group at 2 min after injection of suxamethonium; in neither group was there a significant increase from baseline values. The systolic blood pressure and heart rate increased in both groups after tracheal intubation. The incidence of fasciculations was significantly lower in the magnesium group. Magnesium did not clinically prolong muscle relaxation. There was no difference between the groups in the incidence of myalgia after surgery (one patient in each group). Since no significant increase in the serum potassium concentration was demonstrated, no assessment could be made of the effect of magnesium sulphate on the serum potassium concentration after administration of suxamethonium.

Effects of different antagonists on depolarization of cultured chick myotubes by cobra venom cardiotoxins and Pyrularia thionin from the plant Pyrularia pubera.

Cardiotoxins (3.12 and 3.12.1) purified from cobra venom (Naja naja siamensis) are basic single-chain polypeptides of about 60 residues. Although they depolarize nerve and muscle cells and have cytolytic effects, their mechanism of action is still unknown. Pyrularia thionin (P-thionin) isolated from nuts of the parasitic plant Pyrularia pubera is a strongly basic, single-chain polypeptide containing 47 residues. It is known to be haemolytic and cytotoxic, and to depolarize muscle cells, but its mechanism of action is unclear. The present studies explored the possible similarities between P-thionin and cobra venom cardiotoxins by comparing their effects on depolarization of cultured chick skeletal muscle cells in the presence and absence of possible antagonists. Cardiotoxins and P-thionin depolarized cultured chick skeletal muscle cells, but with P-thionin showing a steeper concentration-dependence. Ca2+ was more effective at reducing cardiotoxin action than P-thionin, while the Ca(2+)-channel blockers Ni2+ (100 microM) and verapamil (100 microM) had no blocking effects on the toxins. Ca2+ may block the binding of both toxins. Indomethacin (100 microM, an inhibitor of cyclooxygenase), quinacrine and dexamethasone (100 microM, inhibitors of phospholipase A2) did not block the effects of the toxins, implying that the actions on cultured chick skeletal muscle cells are not due to activation of endogenous phospholipase A2.