Suxamethonium Vecuronium

Rocuronium is a desacetoxy analogue of vecuronium which is stable in solution and formulated as an aqueous ready-to-use solution. It was deliberately designed as a low-potency relaxant in an attempt to develop a non-depolarising agent which would have a fast onset of action, closer to that of suxamethonium. The basis for this development was the observation that potency and the speed of onset... 

Nevertheless, some interactions of benzodiazepines with muscle relaxants used in anesthesia have been described. Diazepam has been reported to potentiate the effects of tubocurare (163) and gallamine (164) and to reduce the effects of suxamethonium (164). However, in 113 patients undergoing general anesthesia, intravenous diazepam 20 mg, lorazepam 5 mg, and lormetaze-pam 2 mg did not potentiate the neuromuscular blocking effects of vecuronium or atracurium (162). 

In 113 patients undergoing general anesthesia, intravenous midazolam 15 mg slowed recovery of the twitch height after vecuronium and atracurium compared with diazepam. The recovery index was not altered (162). However, in another study in 20 patients, midazolam 0.3 mg/kg did not affect the duration of blockade, recovery time, intensity of fasciculations, or adequacy of relaxation for tracheal intubation produced by suxamethonium 1 mg/kg, nor the duration of blockade and adequacy of relaxation for tracheal intubation produced by pancuronium 0.025 mg/kg in incremental doses until 99% depression of muscle-twitch tension was obtained (161). Furthermore, in 60 patients undergoing maintenance anesthesia randomly assigned to one of six regimens (etomidate, fentanyl, midazolam, propofol, thiopental plus nitrous oxide, or isoflurane plus nitrous oxide), midazolam did not alter rocuronium dosage requirements (165). 

A 65-year-old man undergoing elective sternal debridement and rewiring was given a prophylactic infusion of vancomycin 1 g preoperatively. Anesthesia was induced with thiopental, suxamethonium, and fentanyl, and maintained with fentanyl, vecuronium, and isoflurane. A few minutes after wound irrigation with bacitracin (about 25U/ml), his blood pressure fell precipitously, necessitating intravenous fluids and adrenaline. His face and arms were flushed. Afterwards, he reported having had a rash several years before after the use of an over-the-counter ointment composed of polymyxin B, bacitracin, and neomycin. 

Hemodilution (for example the replacement of 1 liter of blood by dextran-40) increased the potencies and prolonged the actions of suxamethonium, pancuronium, D-tubocurarine, and vecuronium (SEDA-17, 151) (105). To avoid this, blood collection should be carried out before the administration of anesthetic drugs. 

For tracheal intubation the usual dose is 0.1 mg/kg. When given after suxamethonium, 0.05 mg/kg is sufficient for good abdominal relaxation. Further doses of about one-quarter to one-third of the initial dose are given at intervals of 30-40 minutes to maintain relaxation. Reversal is easily achieved with neostigmine, provided there is some spontaneous return of neuromuscular transmission beforehand. If the evoked twitch height is less than 10% of the control value, there can be difficulty in reversing the blockade this apphes to aU non-depolarizing relaxants, except perhaps vecuronium and atracurium. 

The matemofetal transfer or rocuronium, as indicated by a fetaFmatemal plasma concentration ratio of 0.16, is between that of vecuronium and pancuronium (32). When rocuronium was used for cesarean section, no adverse effects on the fetus were observed (32). With regard to the duration of rocuronium-induced paralysis and the relatively high incidence of failed intubations in obstetric patients, however, it was agreed that rocuronium should be considered for rapid-sequence intubation for cesarean section only if suxamethonium is contraindicated (33-35). 

Findlay GP, Spittal MJ. Rocuronium pretreatment reduces suxamethonium-induced myalgia comparison with vecuronium. Br J Anaesth 1996 76(4) 526-9. 

Pancuronium and vecuronium (Fig. 11.39) were designed to act like tubocurarine, but with a steroid nucleus acting as the spacer . The distance between the quaternary nitrogens is 1.1 nm as compared to 1.4 nm in tubocurarine. Acyl groups were also added to introduce two acetylcholine skeletons into the molecule in order to improve affinity for the receptor sites. These compounds have a rapid onset of action and do not affect blood pressure. However, they are not as rapid in onset as suxamethonium and also last too long (45 minutes). 

The inhalational anaesthetics increase the effects of the neuromuscular blockers to differing extents, but nitrous oxide appears not to interact significantly. Ketamine has been reported to potentiate the effects of atracurium. Propofol does not appear to interact with mivacurium or vecuronium. Xenon is reported not to interact with mivacurium or rocuronium, and has less effect than sevoflurane on vecuronium neuromuscular blockade. Bradycardia has been seen in patients given vecuronium with eto-midate or thiopental. Propofol can cause serious bradycardia if it is given with suxamethonium (succinylcholine) without adequate antimuscarinic premedication, and asystole has been seen when fentanyl, propofol and suxamethonium were given sequentially. 

The duration of paralysis due to suxamethonium was reduced in one study by 20% when diazepam (150 micrograms/kg) was also given and the recovery time was shortened. Diazepam also slightly reduced the time to 25% and 75% recovery of twitch height in patients given vecuronium by about 15% (not statistically significant). In animals, diazepam increased the mean dose of rocuronium required by 13%, but this was not statistically significant. ... 

In other studies diazepam was found to have no significant effect on the neuromuscular blockade due to alcuronium, atracurium, gaiiamine, pancuronium, suxamethonium " or tubocurarine. " " Lo-razepam and lormetazepam have been reported to have little or no effects on atracurium or vecuronium, and midazolam has been reported to have no eftect on suxamethonium or pancuronium. ... 

Bambuterol can prolong the recovery time from neuromuscular blockade with suxamethonium (succinylcholine) or mivacuiium. A case report describes modestly enhanced neuromuscular blockade when pancuronium or vecuronium were given after intravenous salbutamoL... 

An isoiated case report describes potentiation of tubocurarine and pancuronium by orai verapamii. However, long-term oral nifedipine did not aiter vecuronium or atracurium effects, and iong-term therapy with various caicium-channel blockers did not interact with rocuronium. Caicium-channei blockers do not increase the piasma potassium rise due to suxamethonium (succi-nyichoiine). 

One report suggests that recovery from the neuromuscular blocking effects of suxamethonium (succinyichoiine) is prolonged by ci-metidine, but this may possibiy have been due to the presence of metociopramide. Four other reports say that no interaction occurs between suxamethonium and either cimetidine, famotidine or ranitidine. Cimetidine, but not ranitidine, has been reported to increase the effects of vecuronium. Cimetidine does not aiter the effects of atracurium or rocuronium and ranitidine does not aiter the effects of atracurium. 

Not understood. Studies with human plasma failed to find any evidence that cimetidine in therapeutic concentrations inhibits the metabolism of suxamethonium. However, metoclopramide may do and therefore is possibly the drug responsible for any interaction seen. In vitro studies with very high cimetidine concentrations found inhibition of plasma cholinesterase (pseudocholinesterase) activity. The cimetidine/vecuro-nium interaction is not understood, but it has been suggested that cimetidine may reduce the hepatic metabolism of vecuronium. ... 

Information seems to be limited to the reports cited. The most likely explanation for the discord between the cimetidine/suxamethonium results is that in the one study reporting increased suxamethonium effects some of the patients were also given metoclopramide, which can inhibit plasma cholinesterase and prolong the effects of suxamethonium (see also Neuromuscular blockers + Metoclopramide , p.l27). In four other studies, cimetidine and other H2-receptor antagonists did not alter suxamethonium effects. Therefore, it seems unlikely that an interaction exists. There is some evidence that cimetidine may slightly prolong the effects of vecuronium, but ranitidine appears not to interact. Atracurium and rocuro-nium appear not to be affected. Overall these possible interactions seem to be of little clinical significance. 

The effects of cisatracurium, mivacurium, pancuronium, rocuro-nium, tubocurarine, vecuronium, and probably other competitive neuromuscular blockers can be increased and prolonged by magnesium sulfate given parenterally. There is some evidence that magnesium may interact similarly with suxamethonium (succinylcholine), but also evidence from well-controlled trials that it does not. 

A man recovering from neuromuseular bloekade with suxamethonium (with some evidence of residual Phase II bloek) developed almost total muscle paralysis and apnoea when given an intravenous infusion of vancomycin. He recovered spontaneously when the vancomycin was stopped, but it took several hours. The neuromuseular blockade due to vecuronium was increased in a patient when given an infusion of vancomycin (I g in 250 mL of saline over 35 minutes). Transient apnoea and apparent cardiac arrest have also been described in a patient following a I-g intravenous injection of vancomycin given over 2 minutes. However, in both of these cases the vancomycin was given more rapidly than the current recommendations. It is now known that rapid infusion of vancomycin can provoke histamine release, which can result in apnoea, hypotension, anaphylaxis and muscular spasm, effects similar to those seen in these two patients. 

Ono K, Manabe N, Ohta Y, Mmta K, Kosaka F. Influence of suxamethonium c the actic of subsequently administered vecuronium or pancuronium. BrJAnaeslh( 9Z9)62, 324-6. 

An isolated report describes marked resistance to the effects of suxamethonium (succinylcholine) and vecuronium, apparently due to the long-term use of testosterone. Another case reports resistance to vecuronium in a patient with elevated plasma testosterone levels. 

Two new nondepolarizing bis-benzyl tetrahydro isoquinoline muscle relaxants with negligible cardiovascular effects are now undergoing clinical trials. Mivacurium (BW B1090U) (65a) has a short-lasting action, with an ED95 of 0.1 mg/kg. The substance is rapidly hydrolysed by plasma cholinesterase—at nearly 90% of the rate of suxamethonium—and some hydrolysis by liver esterases may also take place as well. The recovery time is about half that of vecuronium and atracurium. Minor cutaneous side effects occur sometimes (551-553). Mivacurium has been approved for general use (1992). 

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