The hypothesis that administration of neostigmine in divided doses might accelerate the antagonism of nuromuscular blockade was investigated. Neostigmine 0.05mg/kg was adminsitered either in a single bolus dose (Group I, n=10) or in an initial dose of 0.01 mg/kg 1 minute later (Group II, n=10), 2 minutes later (Group III, n=10) and 3 minutes later (Group IV, n=10) for antagonism of vecuronium- induced blockade. Reversal was attepted at 10 percent spontaneous recovery of twitch height. The mean time (+/-SE) from the first injection of the drug until the train-of-four(TOF) ratio value had reached 0. 75 was signifincantly longer in Group II and IV (594.8+/-63.9 seconds and 555.6+/-22.2 seconds respectively) than Group I and III (380.6+36.0 seconds and 357.8+/-44.2 seconds respectively). It is concluded that adminstration of neostigmine in divided doses with 0. 01 mg/kg and 0.04 mg/kg did not produce a significantly faster reversal of residual vecuronium-induced neuromuscular blockade as compared to a single bolus administration.
Neostigmine* ; Neuromuscular Blockade ; Vecuronium Bromide*

Glycopyrrolate is frequently administered in combination with neostigmine to reverse a neuromus- cular blockade. The dosage was well established at 1/5 of neostigmine. But the authers have often observed a delayed manifestation of relative bradycardia after such a recommended dosage. This is not mentioned in the literature, but this may be due to an insufficient observation period. The authors monitored the change of pulse rate for 1 hour after the administration of the recom. mended dose. Further, the data wIns compared with that obtained after studies of lower and higher doses. The doses were 0.004, 0.008 and 0.012mg/kg of glycopyrrolate with 0.04mg/kg of neostigmine. 1) At all doses, bradycardia relative to the pre-reversal pulse rate was progressive until 30 minutes after injection. 2) As the glycopyrrate dose was increased the degree of bradycardia decreased (-24.7, -20.5, - 15.0 at 30 min.). 3) There was no difference in the immediate change in the pulse rate between the dcsages of 0.008 and 0.012 mg/kg. Change occured at 9 mins. 4) At dosages of 0.004 and 0.008 mg/kg, the pulse rates at 60 min were comparable to their ward pulses, but at a dosage of 0.012 mg/kg, the pulse rate was 8.5 beats/min higher.
Bradycardia ; Glycopyrrolate* ; Heart Rate* ; Neostigmine*

BACKGROUND: Sugammadex is a novel neuromuscular reversal agent, but its associated hypersensitivity reaction and high cost have been obstacles to its widespread use. In the interest of reducing the necessary dosage of sugammadex, the reversal time of the combined use of sugammadex and neostigmine from moderate neuromuscular blockade were investigated. METHODS: The patients enrolled ranged in age from 18 to 65 years old with American Society of Anesthesiologists class 1 or 2. The subjects were randomly assigned into one of the four groups (Group S2, S1, SN, and N; n = 30 per group). The reversal agents of each groups were as follows: S2 - sugammadex 2 mg/kg, S1 - sugammadex 1 mg/kg, SN - sugammadex 1 mg/kg + neostigmine 50 microg/kg + glycopyrrolate 10 microg/kg, N - neostigmine 50 microg/kg + glycopyrrolate 10 microg/kg. The time to recovery of the train-of-four (TOF) ratio was checked in each group. RESULTS: The time to 90% recovery of TOF ratio was 182.6 +/- 88.9, 371.1 +/- 210.4, 204.3 +/- 103.2, 953.2 +/- 379.7 sec in group S2, S1, SN and N, respectively. Group SN showed a significantly shorter recovery time than did group S1 and N (P < 0.001). However, statistically significant differences between the S2 and SN groups were not be observed (P = 0.291). No hypersensitivity reactions occurred in all groups. CONCLUSIONS: For the reversal from rocuronium-induced moderate neuromuscular blockade, the combined use of sugammadex and neostigmine may be helpful to decrease the recovery time and can also reduce the required dosage of sugammadex. However, the increased incidence of systemic muscarinic side effects must be considered.
Glycopyrrolate ; Humans ; Hypersensitivity ; Incidence ; Neostigmine* ; Neuromuscular Blockade*

BACKGROUND: A question was whether it was preferable to give the reversal agent when profound block was present or wait for some spontaneous recovery before antagonizing the block. This study has been conducted to evaluate the reversal effects of neostigmine with divided doses in the rabbits after pancuronium when profound relaxation(PTC=O) or the first twitch of TOF stimulation was appeared (TOF,T1) was confirmed. METHODS: Rabbits(n=60) were randomly allocated to 5 groups. After pancuronium 0.2 mg/kg intravenously, spontaneous recovery was evaluated in group 1. When the profound relaxation(PTC=O) was confirmed at 5 min. after pancuronium, neostigmine 50 ug/kg with atropine 20 ug/kg were injected in group 2. At that time, neostigmine 10 ug/kg with atropine 4 ug/kg were injected and after 3 min. neostigmine 40 ug/kg with atropine 16 ug/kg were injected in group 3. When TOF, Tl was confirmed, neostigmine 50 ug/kg with atropine 20 ug/kg were injected in group 4. At that time, neostigmine and atropine were injected in group 5 as the same way of group 3. RESULTS: The mean time from injection of pancuronium to 95% recovery was 98.9 min. in group 1, 60.3 min. in group 2, 50.9 min. in group 3, 71.0 min. in group 4 and 67.1 min. in group 5. The recovery index was significantly reduced when neostigmine was injected at TOF,T1(p<0.05). The recovery time after neostigmine with divided doses was reduced, but there was no significant difference. CONCLUSIONS: The results of present study suggested that total recovery time was reduced when neostigmine was injected earlier with divided doses than single dose unrelated to profound relaxation.
Atropine ; Muscle Relaxation* ; Neostigmine* ; Pancuronium ; Rabbits* ; Relaxation

The authors have experience of a case of prolonged paresis following administration of galamine triethiodide to a patient undergoing reoperation. The muscular weakness continued for 20 hours, necessitating artificial ventilation intermittently. It was reversed by neostigmine.
Humans ; Muscle Weakness ; Neostigmine ; Paresis* ; Reoperation* ; Ventilation

BACKGROUND: The train-of-four(TOF) fade known as expression of prejuntional receptor binding was useful for evaluating the residual neuromuscular blockade(NMB). The present study was undertaken to investigate the effect of the neostigmine(Neo) on TOF ratio during the recovery from vecuronium(V) or atracurium(A) induced NMB under the general anesthesia. METHODS: Forty healthy adult patients were randomly divided into 4 groups as follows; spontaneous recovery from V-induced NMB(V-C group) or A-induced NMB(A-C group), reversed recovery with Neo at 20% recovery of control first twitch height(T) from V-induced NMB(V-R group) or A-induced NMB(A-R group). TOF ratio at 25 and 75% recovery of T and recovery index(RI) defined as time from 25 to 75% recovery of T were measured. RESULTS: TOF ratios at 25 and 75% recovery of T were 3.7 & 35.8%(V-C group), 8.4 & 46.9%(A-C group), 3.7 & 48.7%(V-R group) and 15.2 & 55.6%(A-R group) respectively(P>0.05). RI were 19.2 min(V-C group), 19.5 min(A-C group), 3.5 min(V-R group), and 5.6 min(A-R group) respectively (P<0.05). CONCLUSIONS: RI were significantly shortened in reversed recovery groups with Neo than spontaneous recovery groups (P<0.05). However TOF ratio at 75% recovery of T1 were not significantly different between spontaneous recovery and reversed recovery groups.
Adult ; Anesthesia, General ; Atracurium ; Humans ; Neostigmine* ; Neuromuscular Blockade* ; Vecuronium Bromide

Fourty pediatric patients anesthetized with halothane-nitrous oxide-oxygen, who received pancronium for the maintenance of muscular relaxation, were divided into two groups. On anesthesia, in group l, atropine(20ug/kg) and neostigmin(40ug/kg), and in group ll, glycopyrrolate(10ug/kg) and neostigmine(40ug/kg) were injected transvenously. The changes in heart rate and arrythmis were then observed. The results were as follows: 1) The safety and effectiveness of both groups in antagonizing the muscarinic actions of neostigmine were demonstrated. 2) Glycopyrrolate produced a significantly smaller change in heart rate than atropine. 3) In both groups, arrhythmis could not be observed.
Anesthesia ; Atropine* ; Glycopyrrolate* ; Heart Rate* ; Heart* ; Humans ; Neostigmine* ; Relaxation

The success of accelerating the onset of neuromvacular blocking drugs by giving them in divided doses encouraged others to attempt the same "priming principle" using reversal agents. Naguib et al and Abdulatif et al demonstrated that the reversal time(time to reach a TOF of 0.75) was reduced when the reversal agent was administered in divided doses at T, 10% of control. But Donati et al and Szalados et al either could not detect any differences in the rate of reversal when anticholinestereses were administered in divided doses. This study hes been conducted to evaluate the reversal effects of neostigmine or pyridostigmine with priming principle in the rabbit after pancuronium injection when pro- found relaxation(PTC=0) was confirmed. Rabbits(n=60) were randomly allocated to 4 groups. After pancuranium 0.2mg/kg IV, the onset and recovery times were evalusted. When the profound relaxation(PTC=0) was confirmed at Smin. after pancuronium injection, neostigmine 50 ug/kg and atropine sulfate (atropine) 20 ug/kg were injected in group 1. At thst time, neostigmine 10/kg and atropine 4 ug/kg were injected and after 3min. neostigmine 40/kg and atropine 16 ug/kg were injected in group 2. At that time, pyridostigmine 250 ug/kg and atropine 20 ug/kg were injected in group 3. At that time, pyridostigmine 50 ug/kg and atropine 4 ug/kg were injected and after 3min. pyridostigmine 200 ug/kg and atropine 16 ug/kg were injected in group 4. The results were as follows :. 1) The time until 75% recovery of twitch amplitude was 53.1+/-12.4min. in group 1, 44.9+/-212.1min. in group 2, 54.9+/-9.7min. in group 3 and 48.2+/-7.1min. in group 4. The reversal times were tended to reduce when the reversal agents were administered with "priming principle" at the profound relaxation. 2) At the profound relaxation the reversal effects of neostigmine were greater than that of pyridostigmine.
Atropine ; Cholinesterase Inhibitors* ; Muscle Relaxation* ; Neostigmine ; Pancuronium ; Pyridostigmine Bromide ; Relaxation

BACKGROUND: Previous studies examining the pharmacodynamic effects of succinylcholine(SCC) on subsequent doses of nondepolarizing muscle relaxants showed potentiation with resultant prolonged respiratory depression or no interaction at all. The interaction between SCC and mivacurium especially has not been investigated in animal and other clinical studies. METHODS: The pharmacodynamic effects of SCC on mivacurium-induced neuromuscular blockade and its reversal were investigated in 10 cats of either sex using the anterior tibialis muscle-sciatic nerve preparation. RESULTS: There was no significant difference at the onset of mivacurium neummuscular blockade between the control group(1.81+/-0.48 min) and SCC-pretreated group(1.86+/-1.04 min). However the duration of action of mivacurium neuromuscular blockade was significantly longer in the SCC-pretreated group(33.08+/-19.13 min) than that of the control group(10.65+/-2.45 min). In the control group recovery indices(RI) were 2.35+/-1.01 min and 0.68+/-0.30 min at spontaneous recovery and antagonism with neostigmine, respectively and in the SCC-pretreated group they were 6.88+/-2.42 min and 1.90+/-0.64 min. RI were significantly shortened by antagonism with neostigmine whether or not SCC was pretreated. In the SCC-pretreated group, RI were significantly longer than in the control group at spontaneous recovery and antagonism with neostigmine. But the maximal recovery and antagonism effect were 100% in all cases. There was no sigriificant difference in the train-of-four ratios measured after antagonism with neostigmine between the control group(0.91+/-0.01) and the SCC-pretreated group(0.93+/-0.06). CONCLUSIONS: The prior administration of SCC prolonged the duration of mivacurium-induced neuromuscular blockade and delayed recovery but had no influence in antagonism with neostigmine in cats.
Animals ; Cats* ; Drug Interactions ; Neostigmine ; Neuromuscular Blockade* ; Respiratory Insufficiency ; Succinylcholine*

BACKGROUND: The reversal of neuromuscular blocker might be accelerated if the anticholinesterase was administered in divided doses. This study has been conducted to evaluate the correct ratio of divided doses of neostigmine for the rapid recovery in the rabbits after pancuronium when the profound relaxation(PTC=0) was confirmed. METHODS: Rabbits(n=60) were randomly allocated to 6 groups. After pancuronium 0.2 mg/kg intravenously, spontaneous recovery was evaluated in group 1. When the profound relaxation(PTC=O) was confirmed at 5 min. after pancuronium, neostigmine 50 ug/kg was injected as a bolus in group 2. At that time, neostigmine was given at 10 ug/kg followed by 40 ug/kg 3 min. later in group 3. At that time, neostigmine was given at 20 ug/kg followed by 30 ug/kg 3 min. later in group 4. At that time, neostigmine was given at 30 ug/kg followed by 20 ug/kg 3 min. later in group 5. At that time, neostigmine was given at 40 ug/kg followed by 10 ug/kg 3 min. later in group 6. RESULTS: The mean time from injection of pancuronium to 95% recovery was 99.3 min. in group 1, 59.8 min. in group 2, 53.2 min. in group 3, 51.5 min. in group 4, 50.8 min. in group 5 and 41.1 min. in group 6. The recovery index was significantly reduced in group 6(p<0.05). CONCLUSIONS: We conclude that the recovery time is reduced when neostigmine is administered in divided doses: a larger priming dose followed by a smaller bolus at profound relaxation.
Muscle Relaxation* ; Neostigmine* ; Neuromuscular Blockade ; Pancuronium* ; Pharmacokinetics ; Rabbits* ; Relaxation