Early Reversal of Rapacuronium with Neostigmine 

1999 ◽  
Vol 91 (1) ◽  
pp. 51-57 ◽  
Author(s):  
Robert Purdy ◽  
David R. Bevan ◽  
Francois Donati ◽  
Lance J. Lichtor

Background Rapacuronium is a rapid-onset, short-acting neuromuscular relaxant. This multiple-center study determined neuromuscular recovery when neostigmine was given 2 or 5 min after rapacuronium. Methods One hundred seventeen patients were randomized to receive two different doses of rapacuronium and to receive neostigmine in two different doses and at two different times. During propofol anesthesia with nitrous oxide, oxygen, and fentanyl, 1.5 or 2.5 mg/kg rapacuronium was given 1 min before tracheal intubation. Neuromuscular block was measured by train-of-four ulnar nerve stimulation every 12 s: The adductor pollicis force of contraction was recorded mechanomyographically. Two or five minutes after rapacuronium was administered, 0.05 or 0.07 mg/kg neostigmine was administered and recovery was compared with that of control patients who received no neostigmine. Results Both doses of rapacuronium produced 100% block in all but one patient, who exhibited 97% block. Neostigmine accelerated recovery in all groups. After 1.5 mg/kg rapacuronium, the time to 25% T1 twitch recovery decreased from a mean of 16 min in control patients to mean values of 8-10 min in the treatment groups: The time to train-of-four ratio of 0.7 decreased from 38 min to 17-19 min. After 2.5 mg/kg rapacuronium, the time to 25% T1 was reduced from 23 min to 11-12 min, and the time to train-of-four ratio of 0.7 decreased from 54 min to 26-32 min. Recovery was not different among the the groups that received different doses and timing of neostigmine. Conclusions Recovery of intense rapacuronium block was accelerated by early neostigmine administration. When given 2 min after rapacuronium, neostigmine was as effective as after 5 min, and 0.05 mg/kg neostigmine was comparable to 0.07 mg/kg neostigmine.

1999 ◽  
Vol 91 (6) ◽  
pp. 1648-1648 ◽  
Author(s):  
Rafael Miguel ◽  
Thomas Witkowski ◽  
Hideo Nagashima ◽  
Robert Fragen ◽  
Richard Bartkowski ◽  
...  

Background This study compares the neuromuscular blocking and cardiovascular effects of rapacuronium (ORG 9487), a new aminosteroid nondepolarizing muscle relaxant, to recommended intubating doses of succinylcholine and mivacurium. Methods Adult patients were randomized in an open-label fashion to receive 1-5 microg/kg fentanyl before 1.5 mg/kg propofol induction followed by 1.5 or 2.5 mg/kg rapacuronium, 1.0 mg/kg succinylcholine, or 0.25 mg/kg mivacurium (i.e., 0.15 mg/kg followed by 0.1 mg/kg 30 s later). Results Patient neuromuscular blockade status was monitored by measuring the train-of-four response to a supramaximal stimulus at the ulnar nerve every 12 s. Percentage of the first twitch of the train-of-four (T1) at 60 s was similar in patients receiving 1.5 mg/kg rapacuronium, 2.5 mg/kg rapacuronium, and succinylcholine and was significantly less than in patients in the mivacurium group (26, 16, and 18%, respectively, vs. 48%; P < 0.01). Times to 80% T1 depression were also similar among patients in the 1.5 mg/kg rapacuronium, 2.5 mg/kg rapacuronium, and succinylcholine groups and significantly longer in the mivacurium group (62, 54, and 54 s, respectively, vs. 112 s; P < 0.01). Clinical duration was longer in all groups compared with the succinylcholine group; however, clinical duration in the 1.5 mg/kg rapacuronium group was shorter compared with the mivacurium group (15 vs. 21 min, respectively; P < 0.01). Heart rate changes were mild in the 1.5 mg/kg rapacuronium, succinylcholine, and mivacurium groups. The patients in the 2.5 mg/kg rapacuronium group had significantly higher heart rates compared with patients in the mivacurium group. No differences were found in blood pressure changes among patients in the four groups. Conclusions Rapacuronium, 1.5 and 2.5 mg/kg, produced neuromuscular blockade as rapidly as succinylcholine and significantly faster than mivacurium. Although succinylcholine continued to show the shortest duration, 1.5 mg/kg rapacuronium used a rapid onset and a relatively short duration and may be considered an alternative to succinylcholine.


Author(s):  
Fabián Murillo Gómez ◽  
Mário Fernando De Góes

<p><span>The aim of this study is to determine the effect of different silane-containing solutions on ceramic-cement bonding and their interaction with different dual-cure resin cements. Forty five glass- ceramic plaques (IPS e.max CAD®) were sandblasted with aluminum oxide for 5s, etched with 10% hydrofluoric acid gel (HF) for 20s and then divided in three groups of 15 each to be treated with different silane-containing solutions: RelyX Ceramic Primer® (AS), Scotchbond Universal® (SU), Clearfil Ceramic Primer® (CP). Then each group was divided in five groups of three plaques to receive the following dual-cure resin cements: Conventional: RelyX Ultimate (RU), RelyX ARC (AR), VarioLink II (VL); and two self-adhesive: RelyX UNICEM 2 (U2), and BiFix (BF). Eight cement cylinders of each cement were distributed on each plaque and polymerized, summarizing 24 cylinders per group. After 24 h storage in relative humidity at 37°C, each cylinder was subjected to a microshear testing. Failure mode was analyzed using scanning electron microscopy (SEM). Data were statistically analyzed with two-way ANOVA (resin cement and silane ) and Tukey test (p≤0.05). Both factors significantly influenced the results and also interaction between them was detected (p=0.0001). μSBS was significantly higher when ceramic was treated with AS for all cements. Most of cements showed no statistically different means when treated with SU and CP, except BF-SU and AR-CP that showed significantly lower means within their treatment groups. Some incomplete polymerization areas were observed in SEM images for those cases. Cohesive failure in resin cement type was predominant with higher results while adhesive with lower results. The sole silane solution improved better bonding than the universal adhesive and the ceramic primer. In general, universal adhesive and ceramic primer produced acceptable mean values and they were statistically comparable. Compatibility between silane solutions and dual-cure resin cements may be material dependent. </span></p>


1996 ◽  
Vol 84 (3) ◽  
pp. 562-565 ◽  
Author(s):  
Olli Erkola ◽  
Pekka Rautoma ◽  
Olli A. Meretoja

Background To ensure rapid recovery of neuromuscular block, it might be useful to administer a short-acting relaxant after a long-acting one. Therefore, the interaction between pancuronium and mivacurium was investigated when mivacurium was administered during the recovery from pancuronium block. Methods After written informed consent, 41 adult patients were studied during propofol/alfentanil/nitrous oxide/oxygen anesthesia. Neuromuscular function was monitored using an electromyographic (EMG) method. AFter a stable EMG calibration response, cumulative doses of pancuronium were given to establish a 95% neuromuscular block. In the control group, and ED95 dose of 100 microg/kg mivacurium was administered instead of pancuronium. When the EMG response after pancuronium or mivacurium had recovered to 25% of the baseline, a single randomized intravenous bolus dose of 10 or 70 microg/kg mivacurium was given. Thereafter, spontaneous recovery of the neuromuscular function was recorded. Results The time from pancuronium until T1 25% EMG recovery was 38 +/- 12 min (mean +/- SD). The respective times after 10 or 70 microg/kg mivacurium were 28 +/- 8 and 54 +/- 7 min in the pancuronium group or 3 +/- 1 (n=3) and 10 +/- 4 min in the mivacurium group (P=0.0001). Times to 95% EMG recovery after 10 or 70 microgm/kg mivacurium were 77 +/- 14 and 97 +/- 16 min in the pancuronium group and 11 +/- 3 and 20 +/- 7 min in the mivacurium group, respectively (P&lt;0.0001). Recovery indexes after 10 or 70 microg/kg mivacurium group, respectively (P&lt;0.0001). Recovery indexes after 10 or 70 microg/kg mivacurium wre 26 +/- 4 and 22 +/- 6 min in the pancuronium group or 7 +/- 3 (n=3) and 5+/- 2 min in the mivacurium group, respectively (P&lt;0.0001). Times from the administration of 10 or 70 microg/kg mivacurium until train-of-four ration 0.7 were 94 +/- 16 and 111 +/- 14 min in the pancuronium group and 12 +/- 4 and 22 +/- 8 min in the mivacurium group, respectively (P&lt;0.0001). Conclusions After pancuronium, mivacurium is not a short acting neuromusclar blocking agent.


2017 ◽  
Vol 127 (3) ◽  
pp. 441-449 ◽  
Author(s):  
László Asztalos ◽  
Zoltán Szabó-Maák ◽  
András Gajdos ◽  
Réka Nemes ◽  
Adrienn Pongrácz ◽  
...  

Abstract Background Rocuronium-induced neuromuscular block that spontaneously recovered to a train-of-four count of four can be reversed with sugammadex 0.5 or 1.0 mg/kg. We investigated whether these doses of sugammadex can also reverse vecuronium at a similar level of block. Methods Sixty-five patients were randomly assigned, and 64 were analyzed in this controlled, superiority study. Participants received general anesthesia with propofol, sevoflurane, fentanyl, and vecuronium. Measurement of neuromuscular function was performed with acceleromyography (TOF-Watch-SX, Organon Teknika B.V., The Netherlands ). Once the block recovered spontaneously to four twitches in response to train-of-four stimulation, patients were randomly assigned to receive sugammadex 0.5, 1.0, or 2.0 mg/kg; neostigmine 0.05 mg/kg; or placebo. Time from study drug injection to normalized train-of-four ratio 0.9 and the incidence of incomplete reversal within 30 min were the primary outcome variables. Secondary outcome was the incidence of reparalysis (normalized train-of-four ratio less than 0.9). Results Sugammadex, in doses of 1.0 and 2.0 mg/kg, reversed a threshold train-of-four count of four to normalized train-of-four ratio of 0.9 or higher in all patients in 4.4 ± 2.3 min (mean ± SD) and 2.6 ± 1.6 min, respectively. Sugammadex 0.5 mg/kg reversed the block in 6.8 ± 4.1 min in 70% of patients (P &lt; 0.0001 vs. 1.0 and 2.0 mg/kg), whereas neostigmine produced reversal in 11.3 ± 9.7 min in 77% of patients (P &gt; 0.05 vs. sugammadex 0.5 mg/kg). The overall frequency of reparalysis was 18.7%, but this incidence varied from group to group. Conclusions Sugammadex 1.0 mg/kg, unlike 0.5 mg/kg, properly reversed a threshold train-of-four count of four vecuronium-induced block but did not prevent reparalysis.


2014 ◽  
Vol 121 (1) ◽  
pp. 59-67 ◽  
Author(s):  
Christoph Czarnetzki ◽  
Edömér Tassonyi ◽  
Christopher Lysakowski ◽  
Nadia Elia ◽  
Martin R. Tramèr

Abstract Background: Magnesium enhances the effect of rocuronium. Sugammadex reverses rocuronium-induced neuromuscular block. The authors investigated whether magnesium decreased the efficacy of sugammadex for the reversal of rocuronium-induced neuromuscular block. Methods: Thirty-two male patients were randomized in a double-blinded manner to receive magnesium sulfate (MgSO4) 60 mg/kg or placebo intravenously before induction of anesthesia with propofol, sufentanil, and rocuronium 0.6 mg/kg. Neuromuscular transmission was monitored using TOF-Watch SX® acceleromyography (Organon Ltd., Dublin, Ireland). In 16 patients, sugammadex 2 mg/kg was administered intravenously at reappearance of the second twitch of the train-of-four (moderate block). In 16 further patients, sugammadex 4 mg/kg was administered intravenously at posttetanic count 1 to 2 (deep block). Primary endpoint was recovery time from injection of sugammadex to normalized train-of-four ratio 0.9. Secondary endpoint was recovery time to final T1. Results: Average time for reversal of moderate block was 1.69 min (SD, 0.81) in patients pretreated with MgSO4 and 1.76 min (1.13) in those pretreated with placebo (P = 0.897). Average time for reversal of deep block was 1.77 min (0.83) in patients pretreated with MgSO4 and 1.98 min (0.58) in those pretreated with placebo (P = 0.572). Times to final T1 were longer compared with times to normalized train-of-four ratio 0.9, without any difference between patients pretreated with MgSO4 or placebo. Conclusion: Pretreatment with a single intravenous dose of MgSO4 60 mg/kg does not decrease the efficacy of recommended doses of sugammadex for the reversal of a moderate and deep neuromuscular block induced by an intubation dose of rocuronium.


Author(s):  
Jennifer M. Hunter ◽  
Thomas Fuchs-Buder

Over the past 70 years since the introduction of d-tubocurarine, the search for an ideal neuromuscular blocking agent has led to the development of the depolarizing drug, succinylcholine (suxamethonium), with its rapid onset of action and plasma metabolism, and a series of non-depolarizing agents of which there are two groups: benzylisoquinoliniums (e.g. atracurium, cisatracurium and mivacurium) and aminosteroidal agents (e.g. pancuronium, vecuronium and rocuronium). The need to monitor neuromuscular block perioperatively to ensure the appropriate dose of any neuromuscular blocking drug is given has led to the development of several nerve stimulation techniques. Particularly useful clinically are the train-of-four twitch response, double-burst stimulation, and the post-tetanic count. Their benefits and limitations are considered in this chapter. The most suitable equipment to monitor neuromuscular block and the appropriate anatomical sites for stimulation are discussed. To prevent residual block with its pathophysiological consequences such as upper airway and pharyngeal dysfunction and potential respiratory failure at the end of surgery, antagonizing agents are used. These are of two types: anticholinesterases such as neostigmine and edrophonium, and the γ‎-cyclodextrin, sugammadex. The pharmacodynamics and pharmacokinetics of neuromuscular blocking drugs and their antagonists are altered by the extremes of age, obesity, and several disease states including renal and hepatic failure, neuromuscular disorders, and critical illness. The altered response to all these drugs in these pathologies, which is related to their metabolism and excretion, is considered in detail, together with their other side-effects including the particular disadvantages to the use of succinylcholine.


2006 ◽  
Vol 104 (4) ◽  
pp. 667-674 ◽  
Author(s):  
Iben F. Sorgenfrei ◽  
Kathrine Norrild ◽  
Per Bo Larsen ◽  
Jakob Stensballe ◽  
Doris Østergaard ◽  
...  

Background Sugammadex (Org 25969) forms a complex with steroidal neuromuscular blocking agents, thereby reversing neuromuscular block. This study investigated the dose-response relation, safety, and pharmacokinetics of sugammadex to reverse rocuronium-induced block. Methods Twenty-seven male surgical patients aged 18-64 yr were randomly assigned to receive placebo or sugammadex (0.5, 1.0, 2.0, 3.0, or 4.0 mg/kg) for reversal of 0.6 mg/kg rocuronium-induced neuromuscular block. Anesthesia was induced and maintained using intravenous fentanyl and propofol. Neuromuscular function was assessed using acceleromyography. Sugammadex or placebo was administered at reappearance of T2 of the train-of-four. The primary efficacy variable was the time required for recovery to a train-of-four ratio of 0.9. Results Sugammadex decreased median recovery time in a dose-dependent manner from 21.0 min in the placebo group to 1.1 min in the group receiving 4.0 mg/kg sugammadex. Doses of sugammadex of 2.0 mg/kg or greater reversed rocuronium-induced neuromuscular block within 3 min. A median of 59-77% of sugammadex was excreted unchanged in the urine within 16 h, mostly in the first 8 h. Sugammadex increased the proportion of the rocuronium dose excreted unchanged in the urine (from a median of 19% in the placebo group to 53% in the 4.0-mg/kg group within 16 h). Sugammadex was safe and well tolerated. No evidence of recurarization was observed in any patient. Conclusion At doses of 2.0 mg/kg or greater, sugammadex safely reversed 0.6 mg/kg rocuronium-induced neuromuscular block in a dose-dependent manner. Sugammadex enhanced renal excretion of rocuronium and was excreted unchanged by the kidneys.


2011 ◽  
Vol 51 (2) ◽  
pp. 115 ◽  
Author(s):  
C. A. Rosales-Nieto ◽  
H. G. Gamez-Vazquez ◽  
J. Gudino-Reyes ◽  
E. A. Reyes-Ramirez ◽  
M. Eaton ◽  
...  

The present study evaluated possible modulation of the buck effect by nutritional and metabolic cues during the transition to the breeding season in adult goats with divergent bodyweight (BW) and body condition (BCS) at 27°N. In mid-February, goats (Boer × Spanish, n = 32) were assigned to receive one of the following two experimental diets to fulfill different allowances of nutritional requirements: (1) 100% (n = 16; BW = 52.3 ± 1.5 kg, BCS = 1.6 ± 0.1 units; T-100) or (2) 150% (n = 16; BW = 60.9 ± 2.4 kg, BCS = 1.6 ± 0.1 units; T-150) from February to August. Blood samples were collected to analyse thyroxine (T4), triiodothyronine (T3), non-esterified fatty acids (NEFA), triglycerides (Tg) and progesterone (P4). Final BW and BCS favoured (P < 0.001) the T-150 group (74.9 ± 2.8 v. 56.3 ± 1.4 kg, and 4.4 ± 0.2 v. 1.9 ± 0.1 units, respectively). However, mean values for NEFA, Tg, T3 and T4 did not differ (P > 0.05) between the experimental groups. Thereafter, in early August, half of the does in each diet treatment were randomly selected for determining the response to the ‘male effect’ (WM), forming the following two treatment groups: (1) T-100-WM (n = 8), or (2) T-150-WM (n = 8); the remaining does formed two groups without male exposure (WOM), as follows: (3) T-100-WOM (n = 8) and (4) T-150-WOM (n = 8). To evaluate ovarian activity, blood samples were collected from all does on Days 2–4 during the 14-day period after the male exposure. On Day 12, all does exposed to males (16/16), irrespective of the nutritional treatment, depicted ovulatory activity, whereas only 3/16 (18.75%) T-WOM does did, indicating a significant (P < 0.001) difference between these treatment groups. The increased nutritional level of the T-150 group during the anoestrous season did not result in an early onset of ovulatory activity. Does demonstrated similar metabolic hormones and concentrations of blood metabolites between the two nutritional treatments (100 v. 150% of the nutritional requirements), suggesting a high physiological plasticity between the groups, stabilising their metabolism according to the nutritional history female goats faced, and generating similar reproductive outcomes. The male effect seems to be enough to induce oestrus during the late anoestrous season, irrespective of BCS and BW.


2000 ◽  
Vol 92 (4) ◽  
pp. 1002-1009 ◽  
Author(s):  
George H. Meakin ◽  
Olli A. Meretoja ◽  
Johann Motsch ◽  
Tomi Taivainen ◽  
Kari Wirtavuori ◽  
...  

Background The aim of this study was to determine the dose or doses of the new rapid-onset, short-acting, neuromuscular blocking drug rapacuronium that would provide satisfactory conditions for tracheal intubation at 60 s in infants and children. Methods Sixty-five infants (&lt; 1 yr), 51 younger children (1-6 yr), and 49 older children (7-12 yr) were studied. Anesthesia was induced with thiopental-nitrous oxide-oxygen. Tracheal intubation was attempted 60 s after administration of one of five doses of rapacuronium (0.5, 1.0, 1.5, 2.0, or 2.5 mg/kg) and intubating conditions were assessed using a four-point scale. Following tracheal intubation, anesthesia was maintained with nitrous oxide-oxygen and alfentanil (12.5-50 microg/kg) as necessary. Neuromuscular transmission was monitored in an uncalibrated fashion using an acceleromyograph. Results Intubating conditions were good or excellent at 60 s in all infants after doses of 1.5 mg/kg or more and in all younger and older children after doses of 2.0 mg/kg or more. The duration of action of rapacuronium was dose- and age-dependent. Mean times to reappearance of the third twitch of the train-of-four (TOF; T3) were less than 10 min in infants at doses of 1.5 mg/kg or less and in younger and older children at doses of 2.0 mg/kg or less. Recovery of T3 after 1.0-2.0 mg/kg rapacuronium was significantly slower in infants compared with younger (P = 0.001) and older (P = 0.02) children. Five adverse experiences were related to rapacuronium administration: Bronchospasm (two instances), tachycardia (one instance), and increased salivation (two instances). None were serious. Conclusions Doses of 1.5 and 2.0 mg/kg rapacuronium can produce satisfactory intubating conditions at 60 s in anesthetized infants and children, respectively, and are associated with a short duration of action.


2002 ◽  
Vol 96 (1) ◽  
pp. 45-50 ◽  
Author(s):  
Hans Kirkegaard ◽  
Tom Heier ◽  
James E. Caldwell

Background Because tactile evaluation is the most common form of clinical neuromuscular monitoring, this study examines the relative efficacy of antagonizing residual block at different levels of recovery of the tactile train-of-four (TOF) response. Methods Anesthesia was induced in 64 adults with 2-5 microg/kg fentanyl and 1-3 mg/kg propofol and maintained with fentanyl, propofol, and nitrous oxide. The tactile response of the adductor pollicis to TOF stimulation was evaluated at one arm, and the mechanomyographic response was recorded at the other. Patients received 0.15 mg/kg cisatracurium and were randomized to receive 0.07 mg/kg neostigmine on reappearance of the first (group I), second (group II), third (group III), or fourth (group IV) tactile TOF response (16 patients per group). Times from administration of neostigmine until the TOF ratio recovered to 0.7 (R0.7), 0.8 (R0.8), and 0.9 (R0.9) were measured. Results Data are presented as median with range in parentheses. R0.7 was 10.3 (5.9-23.4), 7.6 (3.2-14.1), 5.0 (2.0-18.4), and 4.1 (2.4-11.0) min in groups I, II, III, and IV, respectively (P &lt; 0.05, group I &gt; II, III, and IV, group II &gt; IV). R0.8 was 16.6 (8.9-30.7), 9.8 (5.3-25.0), 8.3 (3.8-27.1), and 7.5 (3.0-74.5) min in groups I, II, III, and IV, respectively (P &lt; 0.05, group I &gt; II, III, and IV, group II &gt; IV). R0.9 was 22.2 (13.9-44.0), 20.2 (6.5-70.5), 17.1 (8.3-46.2), and 16.5 (6.5-143.3) min in groups I, II, III, and IV, respectively (no intergroup differences). Ten minutes after neostigmine, a TOF ratio of 0.7 or greater was achieved in 50, 75, 88, and 93% of patients in groups I, II, III, and IV, respectively (P &lt; 0.05 group I &gt; II, III, and IV). At 30 min, a TOF ratio of 0.9 or less was observed in 21, 13, 13, and 7% of patients in groups I, II, III, and IV respectively (no intergroup differences). Conclusions To achieve rapid (within 10 min) reversal to a TOF ratio of 0.7 in more than 87% of patients, three or four tactile responses should be present at the time of neostigmine administration. It was not possible within 30 min to achieve a TOF ratio of 0.9 in all patients, regardless of the number of tactile responses present at neostigmine administration.


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