Dose Responses for Neostigmine and Edrophonium as Antagonists of Mivacurium in Adults and Children

1996 ◽  
Vol 84 (2) ◽  
pp. 354-361. ◽  
Author(s):  
Joan C. Bevan ◽  
Claude Tousignant ◽  
Catherine Stephenson ◽  
Lee Blackman ◽  
Eleanor Reimer ◽  
...  
Keyword(s):  
Nitrous Oxide ◽  
Spontaneous Recovery ◽  
Neuromuscular Block ◽  
Random Allocation ◽  
Physical Status ◽  
Train Of Four ◽  
Adults And Children ◽  
Dose Responses ◽  
Oxide Anesthesia ◽  
Stimulation Of

Background Reversal of neuromuscular blockade induced with pancuronium, d-tubocurarine, or doxacurium is achieved using smaller doses of neostigmine in adults than in children. Also, pancuronium- and doxacurium-induced blockade is reversed with smaller doses of edrophonium in children than in adults. The purpose of this study was to compare the spontaneous and neostigmine- and edrophonium-assisted recovery of mivacurium-induced neuromuscular block in adults and children. Methods Fifty-four adults, aged 40.1 +/- 10.9 yr, and 54 children, aged 4.9 +/- 0.7 yr, physical status ASA 1-2, were studied during propofol/fentanyl/nitrous oxide anesthesia. A Datex relaxograph was used to monitor the electromyographic response of the adductor pollicis to train-of-four stimulation of the ulnar nerve every 10 s. After induction of anesthesia, 0.2 mg x kg(-1) intravenous mivacurium was administered followed by an infusion to maintain 90-95% T1 block. At the end of surgery, one of four doses of neostigmine (5, 10, 20, and 50 micrograms x kg(-1)) or edrophonium (100, 200, 400, and 1,000 micrograms x kg(-1)) or placebo was given, by random allocation, when T1 had recovered to 10%. Values of T1 and train-of-four were measured for 10 min. Results Spontaneous recovery proceeded more rapidly in children than in adults. At 10 min, T1 had recovered to 97 +/- 2% (SD) in children compared with 69 +/- 11% in adults and train-of-four to 84 +/- 5% versus 30 +/- 13% (P<0.0001). In children, 10 min after reversal, recovery of T1 and train-of-four was not different from control after edrophonium and was enhanced only by the larger doses of neostigmine. In adults, recovery was accelerated by both edrophonium and neostigmine. Five minutes after reversal, recovery was improved by either drug in adults and in children. Conclusions Spontaneous recovery from mivacurium- induced neuromuscular block is more rapid in children than in adults. Ten minutes after attempted reversal, recovery is accelerated by edrophonium and usually by neostigmine in adults but not in children. Thus, when reversal is required, edrophonium may be preferred to neostigmine.

Residual Block after Mivacurium with or without Edrophonium Reversal in Adults and Children

1996 ◽  
Vol 84 (2) ◽  
pp. 362-367. ◽  
Author(s):  
David R. Bevan ◽  
Raymond Kahwaji ◽  
John M. Ansermino ◽  
Eleanor Reimer ◽  
Michael F. Smith ◽  
...  
Keyword(s):  
Ulnar Nerve ◽  
Neuromuscular Block ◽  
Saline Group ◽  
Neuromuscular Blocking ◽  
Postanesthesia Care Unit ◽  
Random Allocation ◽  
Train Of Four ◽  
Residual Neuromuscular Block ◽  
Residual Block ◽  
Stimulation Of

Background The rapid recovery from mivacurium- induced neuromuscular block has encouraged omission of its reversal. The purpose of this study was to determine, in children and in adults, whether failure to reverse mivacurium neuromuscular block was associated with residual neuromuscular block on arrival in the postanesthesia care unit. Methods In 50 children, aged 2-12 yr, and 50 adults, aged 20-60 yr, anesthesia was induced and maintained with propofol and fentanyl, and neuromuscular block was achieved by an infusion of mivacurium, to maintain one or two visible responses to train-of-four (TOF) stimulation of the ulnar nerve. At the end of surgery, mivacurium infusion was stopped, and 10 min later, reversal was attempted with saline or 0.5 mg x kg(-1) edrophonium by random allocation. On arrival in the postanesthesia care unit, a blinded observer assessed patients clinically and by stimulation of the ulnar nerve with a Datex electromyogram in the uncalibrated TOF mode. Results Children arrived in the postanesthesia care unit 8.2 +/- 3-4 min after reversal of neuromuscular block and showed no sign of weakness, either clinically or by TOF stimulation. Although TOF ratio was greater in children who had received edrophonium (1.00 +/- 0.05 vs. 0.93 +/- 0.01, P<0.01), TOF was >0.7 in all children. Adults arrived in the postanesthesia care unit 12.9 +/- 5.3 min after reversal of neuromuscular block(P<0.01 vs. children). Six in the saline group demonstrated weakness (two required immediate reversal of neuromuscular block, and TOF was <0.7 in four others), compared with TOF <0.7 in only one of the edrophonium group (P<0.05). Conclusions This study demonstrated that, in adults, failure to reverse mivacurium neuromuscular block was associated with an increased incidence of residual block. Such weakness was not observed in children receiving similar anesthetic and neuromuscular blocking regimens.

scholarly journals Recovery from Mivacurium Block with or without Anticholinesterase following Continuous Infusion in Obstetric Patients

1996 ◽  
Vol 24 (5) ◽  
pp. 585-589 ◽  
Author(s):  
G. S. K. Jan ◽  
W. N. Tong ◽  
A. M. H. Chan ◽  
T. W. C. Hui ◽  
J. W. R. Lo
Keyword(s):  
Nitrous Oxide ◽  
Cholinesterase Activity ◽  
Spontaneous Recovery ◽  
Neuromuscular Block ◽  
Plasma Cholinesterase ◽  
Nerve Stimulator ◽  
Group I ◽  
Group Time ◽  
Train Of Four ◽  
Recovery Group

Neostigmine antagonism after suxamethonium followed by mivacurium chloride bolus and infusion was studied. Thirty ASA group I or II patients were given mivacurium 0.15 mg/kg followed by infusion during nitrous oxide-enflurane-pethidine anaesthesia. Train of four (TOF) stimuli were applied to the ulnar nerve at the wrist and TOF twitch height and ratio measured by TOF-GUARD nerve stimulator. Mivacurium infusion was titrated to give a 90% block of first twitch height. Patients were randomized into two groups. Group I patients recovered from the mivacurium block spontaneously while Group II patients were given neostigmine 0.05 mg/kg and atropine 0.02 mg/kg. Time to reach train of four ratio (TOFR) of 25%, 50% and 70% were measured. This study demonstrated a mean infusion rate of 5.1±1.8 μg/kg/min to maintain a 90% neuromuscular block. In the spontaneous recovery group, time to reach TOFR of 25%, 50% and 70% were 9.3±2.7 min, 13.5±3.0 min and 16.7±3.0 min respectively while the corresponding times in the neostigmine group were 5.2±1.7 min, 10.9±2.2 min and 16.1±7.4 min respectively. There were significant differences in the time taken to TOFR of 25% (P<0.0001) and 50% (P<0.05) but no difference in the time taken for TOFR to return to 70%. We concluded that mivacurium is suitable for use in caesarean section despite a decrease in plasma cholinesterase activity. Neostigmine antagonism is not required as a routine.

The Relationship between Acceleromyographic Train-of-four Fade and Single Twitch Depression

2002 ◽  
Vol 96 (3) ◽  
pp. 583-587 ◽  
Author(s):  
Aaron F. Kopman ◽  
Monika M. Klewicka ◽  
George G. Neuman
Keyword(s):  
Nitrous Oxide ◽  
Neuromuscular Block ◽  
Neuromuscular Function ◽  
Muscle Relaxants ◽  
Initial Value ◽  
Control Value ◽  
Single Twitch ◽  
Train Of Four ◽  
End Tidal ◽  
The Relationship

Background During offset of nondepolarizing neuromuscular block, a train-of-four (TOF) fade ratio of 0.70 or greater is considered to reliably indicate the return of single twitch height (T1) to its control value. Studies using mechanomyography or electromyography confirm this observation. The authors' impressions when using the acceleromyograph as a neuromuscular monitor did not support these results. Therefore, the authors studied the relation between T1 and the TOF ratio (when measured by acceleromyography) during recovery from neuromuscular block. Methods Sixteen adult patients were studied. Anesthesia was induced with intravenous opioid plus 2.0-2.5 mg/kg propofol. Laryngeal mask placement or tracheal intubation was accomplished without the use of muscle relaxants. Anesthesia was maintained with nitrous oxide, desflurane (2.0-3.0%, end-tidal), and fentanyl. The response of the thumb to ulnar nerve stimulation was recorded with the TOF-Guard acceleromyograph (Organon Teknika BV, Boxtel, The Netherlands). TOFs were administered every 15 s. After final calibration, 0.15 mg/kg mivacurium was administered. No further relaxants were administered. T1 and the TOF ratio were then recorded until the TOF ratio had returned to its initial value (+/- 5%). Results At a TOF ratio of 0.70 (during recovery of neuromuscular function), T1 averaged only 69 +/- 8% of control. At a TOF ratio of 0.90, T1 averaged 86 +/- 5% of control. To achieve 90% recovery of T1, a TOF ratio of 0.93 +/- 0.08 was required. Conclusion Assumptions regarding the relation between T1 and the TOF ratio derived from studies using mechanomyography and electromyography do not necessarily apply to observations obtained using acceleromyography.

scholarly journals Sensitivity to Rocuronium-Induced Neuromuscular Block and Reversibility with Sugammadex in a Patient with Myotonic Dystrophy

2012 ◽  
Vol 2012 ◽  
pp. 1-4 ◽  
Author(s):  
Akihiro Kashiwai ◽  
Takahiro Suzuki ◽  
Setsuro Ogawa
Keyword(s):  
General Anesthesia ◽  
Myotonic Dystrophy ◽  
Neuromuscular Blockade ◽  
Spontaneous Recovery ◽  
Neuromuscular Block ◽  
High Sensitivity ◽  
Additional Dose ◽  
Fast Recovery ◽  
Train Of Four ◽  
The Times

We report a patient with myotonic dystrophy who showed prolonged rocuronium-induced neuromuscular blockade, although with a fast recovery with sugammadex. During general anesthesia with propofol and remifentanil, the times to spontaneous recovery of the first twitch (T1) of train of four to 10% of control values after an intubating dose of rocuronium 1 mg/kg and an additional dose of 0.2 mg/kg were 112 min and 62 min, respectively. Despite the high sensitivity to rocuronium, sugammadex 2 mg/kg administered at a T1 of 10% safely and effectively antagonized rocuronium-induced neuromuscular block in 90 s.

scholarly journals Reversal of Profound Neuromuscular Block by Sugammadex Administered Three Minutes after Rocuronium

2009 ◽  
Vol 110 (5) ◽  
pp. 1020-1025 ◽  
Author(s):  
Chingmuh Lee ◽  
Jonathan S. Jahr ◽  
Keith A. Candiotti ◽  
Brian Warriner ◽  
Mark H. Zornow ◽  
...  
Keyword(s):  
Spontaneous Recovery ◽  
Neuromuscular Block ◽  
High Dose ◽  
Serious Adverse Events ◽  
Duration Of Action ◽  
Parallel Group ◽  
Train Of Four ◽  
American Society ◽  
American Society Of Anesthesiologists ◽  
Mean Time

Background Rocuronium in intubation doses provides similar intubation conditions as succinylcholine, but has a longer duration of action. This study compared time to sugammadex reversal of profound rocuronium-induced neuromuscular block with time to spontaneous recovery from succinylcholine. Methods One hundred and fifteen adult American Society of Anesthesiologists Class I-II surgical patients were randomized to this multicenter, safety-assessor-blinded, parallel group, active-controlled, Phase IIIa trial. Anesthesia was induced and maintained with propofol and an opioid. Neuromuscular transmission was blocked and tracheal intubation facilitated with 1.2 mg/kg rocuronium or 1 mg/kg succinylcholine. Sugammadex (16 mg/kg) was administered 3 min after rocuronium administration. Neuromuscular function was monitored by acceleromyography. The primary efficacy endpoint was the time from the start of relaxant administration to recovery of the first train-of-four twitch (T(1)) to 10%. Results One hundred and ten patients received study treatment. Mean times to recovery of (T(1)) to 10% and (T(1)) to 90% were significantly faster in the rocuronium-sugammadex group (4.4 and 6.2 min, respectively), as compared with the succinylcholine group (7.1 and 10.9 min, respectively; all P &lt; 0.001). Timed from sugammadex administration, the mean time to recovery of (T(1)) to 10%, (T(1)) to 90%, and the train-of-four (T(4)/T(1)) ratio to 0.9 was 1.2, 2.9, and 2.2 min, respectively. Reoccurrence of the block was not observed. There were no serious adverse events related to study treatments. Conclusion Reversal of profound high-dose rocuronium-induced neuromuscular block (1.2 mg/kg) with 16 mg/kg sugammadex was significantly faster than spontaneous recovery from 1 mg/kg succinylcholine.

Criteria of Adequate Clinical Recovery from Neuromuscular Block

2003 ◽  
Vol 98 (5) ◽  
pp. 1278-1280 ◽  
Author(s):  
Srinivasa N. Raja ◽  
Hassan H. Ali
Keyword(s):  
Nerve Stimulation ◽  
Spontaneous Recovery ◽  
Neuromuscular Block ◽  
Complete Recovery ◽  
Neuromuscular Function ◽  
Surgical Patients ◽  
Tetanic Stimulation ◽  
Clinical Recovery ◽  
Single Twitch ◽  
Train Of Four

This study was undertaken to compare the sensitivities of the train-of-four response (2 Hz for 2 s), the single twitch (0.15 Hz), and the tetanic response (50 Hz for 5 s) as indices of residual nondepolarizing block. Spontaneous or induced recovery of evoked thumb adduction in response to ulnar nerve stimulation was studied. One hundred and seven adult surgical patients were divided according to the relaxant used, into six groups. We found that when the single twitch recovered to control height, the train-of-four ratio was well below 1.0. This ratio was significantly lower during spontaneous recovery than following neostigmine antagonism of the block (P &lt; 0.01). The tetanic response was fully sustained when the train-of-four ratio was above 0.7. When the ratio was less than 0.7, variable degrees of fade of tetanus were evident. Analysis of variance indicated similar train-of-four ratios among the six groups at complete recovery of the single twitch irrespective of the relaxant technique used (P &lt; 0.1). It is concluded that a train-of-four ratio of 0.7 or higher reliably indicates the recovery of the single twitch to control height and a sustained response to tetanic stimulation at 50 Hz for 5 s. The clinical significance of this study is as follows: the train-of-four response provides the same indication of clinical recovery from nondepolarizing block as obtained from tetanic stimulation at a physiological frequency; and reliance on the recovery of the single twitch to control height as a criterion of spontaneous return to normal clinical neuromuscular function may be misleading.

scholarly journals Reversal of Rocuronium-induced (1.2 mg/kg) Profound Neuromuscular Block by Sugammadex

2007 ◽  
Vol 107 (2) ◽  
pp. 239-244 ◽  
Author(s):  
Hans D. de Boer ◽  
Jacques J. Driessen ◽  
Marco A. E. Marcus ◽  
Hans Kerkkamp ◽  
Marten Heeringa ◽  
...  
Keyword(s):  
Adverse Events ◽  
Neuromuscular Blockade ◽  
Recovery Time ◽  
Neuromuscular Block ◽  
Dependent Manner ◽  
Physical Status ◽  
Serious Adverse Events ◽  
Train Of Four ◽  
American Society ◽  
American Society Of Anesthesiologists

Background Reversal of rocuronium-induced neuromuscular blockade can be accomplished by chemical encapsulation of rocuronium by sugammadex, a modified gamma-cyclodextrin derivative. This study investigated the efficacy and safety of sugammadex in reversing rocuronium-induced profound neuromuscular blockade at 5 min in American Society of Anesthesiologists physical status I and II patients. Methods Forty-five American Society of Anesthesiologists physical status I and II patients (aged 18-64 yr) scheduled to undergo surgical procedures (anticipated anesthesia duration &gt;/= 90 min) were randomly assigned to a phase II, multicenter, assessor-blinded, placebo-controlled, parallel, dose-finding study. Anesthesia was induced and maintained with propofol and an opioid. Profound neuromuscular blockade was induced with 1.2 mg/kg rocuronium bromide. Sugammadex (2.0, 4.0, 8.0, 12.0, or 16.0 mg/kg) or placebo (0.9% saline) was then administered 5 min after the administration of rocuronium. Neuromuscular function was monitored by acceleromyography, using train-of-four nerve stimulation. Recovery time was the time from the start of administration of sugammadex or placebo, to recovery of the train-of-four ratio to 0.9. Safety assessments were performed on the day of the operation and during the postoperative and follow-up period. Results A total of 43 patients received either sugammadex or placebo. Increasing doses of sugammadex reduced the mean recovery time from 122 min (spontaneous recovery) to less than 2 min in a dose-dependent manner. Signs of recurrence of blockade were not observed. No serious adverse events related to sugammadex were reported. Two adverse events possibly related to sugammadex were reported in two patients (diarrhea and light anesthesia); however, both patients recovered without sequelae. Conclusions Sugammadex rapidly and effectively reversed profound rocuronium-induced neuromuscular blockade in humans and was well tolerated.

Pharmacokinetics of Cisatracurium in Patients Receiving Nitrous Oxide/Opioid/Barbiturate Anesthesia

1996 ◽  
Vol 84 (2) ◽  
pp. 300-308. ◽  
Author(s):  
Cynthia A. Lien ◽  
Virginia D. Schmith ◽  
Matthew R. Belmont ◽  
Amy Abalos ◽  
David F. Kisor ◽  
...  
Keyword(s):  
Nitrous Oxide ◽  
Maximum Concentration ◽  
Elective Surgery ◽  
Neuromuscular Block ◽  
Duration Of Action ◽  
Elimination Half ◽  
Train Of Four ◽  
Release Histamine ◽  
Nondepolarizing Muscle Relaxant ◽  
Hofmann Elimination

Background Cisatracurium, one of the ten isomers in atracurium, is a nondepolarizing muscle relaxant with an intermediate duration of action. It is more potent and less likely to release histamine than atracurium. As one of the isomers composing atracurium, it presumably undergoes Hofmann elimination. This study was conducted to describe the pharmacokinetics of cisatracurium and its metabolites and to determine the dose proportionality of cisatracurium after administration of 2 or 4 times the ED(95). Methods Twenty ASA physical status 1 or 2 patients undergoing elective surgery under nitrous oxide/opioid/barbiturate anesthesia were studied. Patients received a single rapid intravenous bolus does of 0.1 or 0.2 mg x kg-1 (2 or 4 times the ED(95), respectively) cisatracurium. All patients were allowed to recover spontaneously to a train-of-four ratio &gt; or = 0.70 after cisatracurium-induced neuromuscular block. Plasma was extracted, acidified, and stored frozen before analysis for cisatracurium, laudanosine, the monoquaternary acid, and the monoquaternary alcohol metabolite. Results The clearances (5.28 +/- 1.23 vs. 4.66 +/- 0.67 ml x min(-1) x kg(-1) and terminal elimination half-lives (22.4 +/- 2.7 vs. 25.5 +/- 4.1 min) were not statistically different between patients receiving 0.1 mg x kg(-1) and 0.2 mg x kg(-1), respectively. Maximum concentration values for laudanosine averaged 38 +/- 21 and 103 +/- 34 ng x ml(-1) for patients receiving the 0.1 and 0.2 mg x kg(-1) doses, respectively. Maximum concentration values for monoquaternary alcohol averaged 101 +/- 27 and 253 +/- 51 ng x ml(-1), respectively. Monoquaternary acid was not quantified in any plasma sample. Conclusions Cisatracurium undergoes Hofmann elimination to form laudanosine. The pharmacokinetics of cisatracurium are independent of dose after single intravenous doses of 0.1 and 0.2 mg x kg(-1).

scholarly journals Effects of nitrogen and phosphorus additions on nitrous oxide emission in a nitrogen-rich and two nitrogen-limited tropical forests

2016 ◽  
Vol 13 (11) ◽  
pp. 3503-3517 ◽  
Author(s):  
Mianhai Zheng ◽  
Tao Zhang ◽  
Lei Liu ◽  
Weixing Zhu ◽  
Wei Zhang ◽  
...  
Keyword(s):  
Nitrous Oxide ◽  
Tropical Forests ◽  
N2o Emission ◽  
N Deposition ◽  
Soil N ◽  
N Addition ◽  
Old Growth ◽  
Old Growth Forest ◽  
P Addition ◽  
Stimulation Of

Abstract. Nitrogen (N) deposition is generally considered to increase soil nitrous oxide (N2O) emission in N-rich forests. In many tropical forests, however, elevated N deposition has caused soil N enrichment and further phosphorus (P) deficiency, and the interaction of N and P to control soil N2O emission remains poorly understood, particularly in forests with different soil N status. In this study, we examined the effects of N and P additions on soil N2O emission in an N-rich old-growth forest and two N-limited younger forests (a mixed and a pine forest) in southern China to test the following hypotheses: (1) soil N2O emission is the highest in old-growth forest due to the N-rich soil; (2) N addition increases N2O emission more in the old-growth forest than in the two younger forests; (3) P addition decreases N2O emission more in the old-growth forest than in the two younger forests; and (4) P addition alleviates the stimulation of N2O emission by N addition. The following four treatments were established in each forest: Control, N addition (150 kg N ha−1 yr−1), P addition (150 kg P ha−1 yr−1), and NP addition (150 kg N ha−1 yr−1 plus 150 kg P ha−1 yr−1). From February 2007 to October 2009, monthly quantification of soil N2O emission was performed using static chamber and gas chromatography techniques. Mean N2O emission was shown to be significantly higher in the old-growth forest (13.9 ± 0.7 µg N2O-N m−2 h−1) than in the mixed (9.9 ± 0.4 µg N2O-N m−2 h−1) or pine (10.8 ± 0.5 µg N2O-N m−2 h−1) forests, with no significant difference between the latter two. N addition significantly increased N2O emission in the old-growth forest but not in the two younger forests. However, both P and NP addition had no significant effect on N2O emission in all three forests, suggesting that P addition alleviated the stimulation of N2O emission by N addition in the old-growth forest. Although P fertilization may alleviate the stimulated effects of atmospheric N deposition on N2O emission in N-rich forests, this effect may only occur under high N deposition and/or long-term P addition, and we suggest future investigations to definitively assess this management strategy and the importance of P in regulating N cycles from regional to global scales.

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