[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.

BPC 157: The counteraction of succinylcholine, hyperkalemia, and arrhythmias.

After the demonstration of its life-saving effect in severe hyperkalemia and the recovery of skeletal muscle after injury, pentadecapeptide BPC 157 has been shown to attenuate the local paralytic effect induced by succinylcholine, in addition to systemic muscle disability (and consequent muscle damage). Hyperkalemia, arrhythmias and a rise in serum enzyme values, were counteracted in rats. Assessments were made at 3 and 30min and 1, 3, 5, and 7 days after succinylcholine administration (1.0mg/kg into the right anterior tibial muscle). BPC 157 (10µg/kg, 10ng/kg) (given intraperitoneally 30min before or immediately after succinylcholine or per-orally in drinking water through 24h until succinylcholine administration) mitigated both local and systemic disturbances. BPC 157 completely eliminated hyperkalemia and arrhythmias, markedly attenuated or erradicated behavioral agitation, muscle twitches, motionless resting and completely eliminated post-succinylcholine hyperalgesia. BPC 157 immediately eliminated leg contractures and counteracted both edema and the decrease in muscle fibers in the diaphragm and injected/non-injected anterior tibial muscles. Therefore, the depolarizing neuromuscular blocker effects of succinylcholine were successfully antagonized.

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.

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.

[Interaction between mivacurium and succinylcholine from a different point of view]. / Interacción entre mivacurio y succinilcolina: vista desde otra perspectiva.

OBJECTIVES: Succinylcholine (SCH) may first be used and continue with mivacurium (MIV). MIV has been suggested as a pretreatment. Conflicting results arises from studies on SCH-MIV interaction. The following trial revisits this interaction. PATIENTS AND METHODS: The patients were intubated after randomized administration of 100 microg x Kg(-1) of mivacurium (group 1) or 1 mg x Kg(-1) of succinylcholine and, after 50% recovery, 100 microg x Kg(-1) of mivacurium (group 2). A third group received the same regimen as group 2, preceded by pretreatment with 10 microg x Kg(-1) of mivacurium. Maximum effect (MAX), onset time, the 10%-25% recovery index, and duration of effect of mivacurium were determined by electromyography. In groups 2 and 3, the corrected MAX was defined as the difference between the actual MAX effect and the residual block after administration of succinylcholine, and speed of action was defined as the ratio between MAX or corrected MAX and onset time. Data were subjected to analysis of variance and Student-Newman-Keuls and t tests for bivariate comparisons. A value of P less than 0.05 was considered significant. RESULTS: Groups 2 and 3 had significantly greater MAX effects (97% and 98%, respectively) in comparison with group 1 (93%), shorter onset times (135 and 158 seconds in groups 2 and 3 vs 279 seconds in group 1), and greater speed of action without changes in duration of effect. MAX was halved when corrected (to 47% and 49% in groups 2 and 3, respectively), and speed of action was significantly reduced (from 1.34 and 1.62 seconds/% in groups 2 and 3 respectively, to 2.69 and 3.36 seconds/%). Mivacurium pretreatment did not produce relevant clinical changes. CONCLUSIONS: When mivacurium is used before the effects of succinylcholine disappear, a residual effect is not usually taken into consideration. This study corrected MAX and calculated speed of action, demonstrating a reduction in net block and speed of action, consistent with an antagonistic action when the 2 blockers are administered sequentially.

Interacción entre mivacurio y succinilcolina: vista desde otra perspectiva / Interaction between mivacurium and succinylcholine from a different point of view

OBJETIVOS: La succinilcolina (SC) puede utilizarseinicialmente para continuar con mivacurio (MIV), y estea su vez como precurarizante. Esta interacción da lugara contradicciones y revisarlas es nuestro propósito.PACIENTES Y MÉTODOS: Los pacientes fueron intubadostras utilizar aleatoriamente: MIV 100 µg Kg-1 (grupo 1),SC 1 mg.Kg-1 y al cabo de una recuperación del 50%,MIV 100 µg Kg-1 (grupo 2). En el grupo 3 el mismo régimenprecedido por una precurarización con MIV 10 µgKg-1. Electromiográficamente se determinaron: máximoefecto (MAX), tiempo de comienzo (TC), índice de recuperaciónentre 10-25% y duración clínica (DUR) delMIV. Como MAX corregido (©MAX) consideramos lasustracción del bloqueo remanente al valor actual en losgrupos 2 y 3 y como velocidad de acción (VA) la relaciónentre MAX o ©MAX y TC. Se utilizaron: análisis devarianza, pruebas de Student-Newman-Keuls y T paracomparaciones y p>0,05 como significancia.RESULTADOS: En los grupos 2 y 3 el MIV mostró unsignificativo incremento de MAX (97-98% vs 93), reducciónde TC (135-158 vs 279 segundos) y aumento de laVA, sin modificaciones en la DUR. Usando ©MAX seredujo a la mitad MAX (47-49%) y disminuyó VA (1,34-1,62 segundos/% vs 2,69-3,36). La precurarización noañadió cambios relevantes.CONCLUSIONES: Cuando se utiliza MIV antes de desaparecerlos efectos de la SC, habitualmente no se cuenta conel efecto remanente. Este ensayo corrigió el MAX y calculóla VA, reduciendo el bloqueo neto y la VA, representandoun antagonismo para la secuencia de ambos bloqueantes

OBJECTIVES: Succinylcholine (SCH) may first be usedand continue with mivacurium (MIV). MIV has beensuggested as a pretreatment. Conflicting results arisesfrom studies on SCH-MIV interaction. The followingtrial revisits this interaction.PATIENTS AND METHODS: The patients were intubatedafter randomized administration of 100 µg·Kg-1 of mivacurium(group 1) or 1 mg·Kg-1 of succinylcholine and,after 50% recovery, 100 µg·Kg-1 of mivacurium (group 2).A third group received the same regimen as group 2, precededby pretreatment with 10 µg·Kg-1 of mivacurium.Maximum effect (MAX), onset time, the 10%-25% recoveryindex, and duration of effect of mivacurium weredetermined by electromyography. In groups 2 and 3, thecorrected MAX was defined as the difference between theactual MAX effect and the residual block after administrationof succinylcholine, and speed of action was definedas the ratio between MAX or corrected MAX and onsettime. Data were subjected to analysis of variance and Student-Newman-Keuls and t tests for bivariate comparisons.A value of P less than 0.05 was considered significant.RESULTS: Groups 2 and 3 had significantly greaterMAX effects (97% and 98%, respectively) in comparisonwith group 1 (93%), shorter onset times (135 and 158seconds in groups 2 and 3 vs 279 seconds in group 1),and greater speed of action without changes in durationof effect. MAX was halved when corrected (to 47% and49% in groups 2 and 3, respectively), and speed of actionwas significantly reduced (from 1.34 and 1.62 seconds/%in groups 2 and 3 respectively, to 2.69 and 3.36seconds/%). Mivacurium pretreatment did not producerelevant clinical changes.CONCLUSIONS: When mivacurium is used before theeffects of succinylcholine disappear, a residual effect isnot usually taken into consideration. This study correctedMAX and calculated speed of action, demonstrating areduction in net block and speed of action, consistentwith an antagonistic action when the 2 blockers areadministered sequentially

[Interaction of donepezil and muscular blockers in Alzheimer's disease]. / Interacción entre donepezilo y bloqueantes musculares en la enfermedad de Alzheimer.

A 75-years-old man with Alzheimer's disease, treated with the cholinesterase inhibitor donepezil for 14 months, was scheduled for left colectomy under general anesthesia. During the procedure, succinylcholine-induced relaxation was prolonged and the effect of atracurium besylate was inadequate even at higher doses than those indicated for the patient's weight. Cholinesterase blood tests performed 10 months, 1 month and 10 days before surgery had demonstrated a gradual decrease in the duration of activity of the enzyme. Such an effect, which has been described for cholinesterase inhibitors like neostigmine and donepezil, would explain the prolonged effect of succinylcholine. After ruling out other causes for resistance to atracurium, we conclude that donepezil or its metabolites acted on muscle plaque, blocking acetylcholine hydrolysis and antagonizing atracurium.

Acquired pseudocholinesterase deficiency after high-dose cyclophosphamide.

Succinylcholine, a depolarizing neuromuscular blocking agent used in anesthesia is hydrolyzed in the plasma by the enzyme pseudocholinesterase (PSC). Conditions associated with reduced PSC activity lead to sustained action of succinylcholine and result in prolonged apnea. Cyclophosphamide is an inhibitor of PSC and its suppressive effect may be dose-dependent. We report a case of severe PSC deficiency after high-dose cyclophosphamide at 7 g/m2. The patient received succinylcholine during anesthesia 9 h after chemotherapy and developed prolonged apnea. This case highlights the potential risk of drug-induced PSC deficiency and cautions the use of depolarizing muscular relaxants soon after high-dose cyclophosphamide.

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 diltiazem on calcium ion translocation: a study on isolated frog rectus abdominis muscle.

Diltiazem, a calcium channel blocker was studied to observe its effects on the acetylcholine contractile responses of isolated frog rectus abdominis muscle. This response was modified in a dual manner i.e., initial potentiation, followed by inhibition. Diltiazem may not have anticholinesterase like mechanism, as it potentiated the responses to both acetylcholine and succinylcholine. Rectus muscle preparation, incubated in calcium free frog Ringer, showed dose dependent inhibition of acetylcholine contractile responses by diltiazem. The study suggests that diltiazem inhibits calcium ion influx across receptor operated calcium channels and may also inhibit calcium ion release from intracellular structures.

Neuromuscular interactions between succinylcholine and esmolol in the rat.

To study the neuromuscular interactions between succinylcholine (Sch) and esmolol, we determined the dose-response relationship of Sch and the neuromuscular actions of the 3xED90 dose of Sch, both prior to and following esmolol pretreatment. Twenty rats were anaesthetized with urethane. Train-of-four stimulation was applied every 12 s to the sciatic nerve, and the electromyogram (EMG) of the tibialis anterior muscle was measured. The results showed that the potency of Sch decreased with esmolol pretreatment. The ED50 of Sch increased significantly, from 191 ug/kg to 227 ug/kg after esmolol infusion, p < 0.05. The duration of EMG depression achieved by the 3xED90 dose of Sch decreased significantly with esmolol pretreatment (12 min vs 14 min p < 0.05), and also the onset time was significantly longer (43 sec vs 28 sec, p < 0.05). There were no significant difference between groups with regard to the maximal block or recovery index. The results of two methods of study demonstrated that the pharmacological interaction between Sch and esmolol is antagonistic instead of potentiating.