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PubMedDate not supplied

Postoperative analgesia and antiemetic efficacy after subarachnoid neostigmine in orthopedic surgery.

BACKGROUND AND OBJECTIVES: The efficacy of operatively administered spinal neostigmine to provide analgesia and that of different antiemetics to prevent neostigmine-related nausea and vomiting were evaluated in patients undergoing tibial or ankle reconstruction. METHODS: One hundred patients were randomized to five groups (n = 20). The intravenous antiemetic test drug (except propofol) was given as premedication in the holding room, after intravenous midazolam, 0.05 mg/kg. The subarachnoid drugs administered were 20 mg bupivacaine (0.5%) in conjunction with 100 micrograms neostigmine, except for the saline group (S group), which received bupivacaine and saline. The S group, the neostigmine group (N group), and the propofol group (P group) received saline as the intravenous test drug. The droperidol group (D group) received intravenous droperidol 0.5 mg, and the metoclopramide group (M group) received intravenous metoclopramide 10 mg. The P group had a continuous intravenous propofol infusion (2-4 mg/kg/hr), started 10 minutes after the spinal injection. Nausea, emetic episodes, and the need for analgesic (disclofenac) or antiemetic medication were recorded for the first 24 hours following surgery and scored by a 10-cm visual analog scale (VAS). RESULTS: Subarachnoid neostigmine 100 micrograms did not affect subarachnoid bupivacaine analgesia as measured by time to first rescue analgesic in most patients, but it decreased the overall 24-hour visual analog scale (VAS) scores and the need for postoperative analgesics in 24 hours (P < .001). The incidence of intraoperative nausea and vomiting was higher in the N, D, and M groups than in the S group (P < .001). Following surgery, the 3-hour VAS assessment for emesis was higher for the N, P, and M groups than for the S group (P < .05). The overall 24-hour assessment was similar among groups. CONCLUSIONS: Subarachnoid neostigmine reduced postoperative pain scores and analgesic requirements. Whether it prolonged the duration of action of diclofenac or enhanced the mechanisms involved in spinal analgesia cannot be determined from these data. Although propofol and droperidol appeared to be more effective during and after surgery, respectively, all neostigmine groups were associated with a high consumption of antiemetics.

Adult↗

PubMed1999

Dosage of neostigmine for reversal of rocuronium block from two levels of spontaneous recovery.

Spontaneous recovery, and recovery following neostigmine 20, 35 or 50 microgram.kg-1 administered at 10 or 25% of recovery of the first twitch of the train-of-four, was assessed in 80 patients after rocuronium administration under continued isoflurane anaesthesia. In an additional 40 patients, isoflurane administration was discontinued and neostigmine 35 or 50 microgram.kg-1 was given at 10 or 25% recovery. The administration of neostigmine reduced the recovery times significantly. A neostigmine dose of 20 microgram.kg-1 resulted in slower recovery compared with the higher doses, particularly when reversal was attempted at a first twitch height of 10%. Higher doses of neostigmine given at a first twitch height of 25% resulted in rapid reversal of block [mean (SD) times of 7.0 (4.8) and 6.4 (1.9) min with the 35 and 50 microgram.kg-1 doses, respectively, for attaining a train-of-four ratio of 0.8]. Discontinuing isoflurane did not alter recovery times. The incidence of emetic symptoms did not differ between groups, including one group that received atropine instead of glycopyrronium in combination with neostigmine. We conclude that rocuronium block can be antagonised safely using a neostigmine dose of 35 microgram.kg-1, although recovery may be slightly slower if administered at a first twitch of 10% of control.

Adjuvants, Anesthesia↗

PubMed1980

Neuromuscular blockade by neostigmine in anaesthetized man.

The tetanic and single twitch responses of the adductor pollicis muscle were used to study the neuromuscular effects of neostigmine in 26 patients anaesthetized with thiopentone and nitrous oxide. Neostigmine 2.5 mg i.v. given 5 min after exposure to halothane antagonized non-depolarizing neuromuscular block, whereas a second dose give 2-5 min later depressed the peak tetanic contraction and re-established tetanic fade. In the absence of halothane the second dose of neostigmine had less effect. Recovery of the single twitch was not impaired by the second dose. A single dose of neostigmine 5 mg rapidly antagonized the competitive block of the tetanic response but the subsequent slight depression of the peak contraction and the brief reappearance of fade were less than after 5 mg given in two doses of 2.5 mg. In patients who were not given neuromuscular blocking drugs, one or two injections of neostigmine 2.5 mg caused a substantial reduction in the peak tetanic contraction and severe tetanic fade which persisted for about 20 min; the single twitch was slightly potentiated. The neostigmine block of the tetanic response could be antagonized by gallamine and potentiated by suxamethonium. These findings indicate that neostigmine in clinical doses can produce an acetylcholine-induced block which be a potential hazard in anaesthetic practice.

Anesthesia, General↗

PubMed1986

Antagonism of profound neuromuscular blockade induced by vecuronium or atracurium. Comparison of neostigmine with edrophonium.

The effectiveness of neostigmine 0.07 mg kg-1 and edrophonium 0.8 mg kg-1 as antagonists of profound neuromuscular blockade induced by vecuronium 0.1 mg kg-1 or atracurium 0.5 mg kg-1 was studied in 59 healthy patients. The antagonists were administered 5 min after total ablation of the twitch response and the end-point of recovery was a train-of-four ratio of 70%. In 30 patients given vecuronium the mean time to reach this point (duration TOF70) was 66.7 min in the control group (no antagonist), 43.5 min in the group given neostigmine and 59.8 min in the group given edrophonium. The duration TOF70 was shorter in the neostigmine group than in the control (P less than 0.01) and edrophonium (P less than 0.01) groups. The duration TOF70 did not differ from control in the edrophonium group. In 29 patients given atracurium, the durations TOF70 were 66.4, 44.1 and 54.9 min in the control, neostigmine and edrophonium groups, respectively. The durations TOF70 in the neostigmine (P less than 0.01) and edrophonium (P less than 0.01), groups were shorter than control. The duration TOF70 of the neostigmine group was shorter than in the edrophonium group (P less than 0.01). These results show that profound neuromuscular blockade cannot be rapidly antagonized by either of these two agents, but if reversal is required under these circumstances, neostigmine would be the more effective drug.

Adult↗

PubMed1987

Use of neostigmine in the antagonism of residual neuromuscular blockade produced by vecuronium.

Recovery from neuromuscular block produced by vecuronium was studied in 50 patients using electromyography and the train-of-four technique. Twenty patients received neostigmine 2.5 mg, 10 when the initial response of the train-of-four was 50% of control and 10 when it was 10%. Neostigmine 5 mg was investigated in a similar manner and in 10 patients spontaneous recovery was studied. In all patients the time to 70% recovery of the initial response and of the train-of-four ratio was followed. Neostigmine significantly reduced the time to 70% recovery of both ratios with both degrees of block, but neostigmine 5.0 mg did not give a substantially more rapid recovery than 2.5 mg. No evidence of a neostigmine-induced block was encountered. neostigmine 2.5 mg was rapidly effective in antagonizing vecuronium-induced block, even when initial recovery was only slight: there was no advantage in using neostigmine 5.0 mg.

Adult↗

PubMed1994

Optimum dose of neostigmine at two levels of atracurium-induced neuromuscular block.

There is controversy about the optimum dose of neostigmine for antagonizing neuromuscular block. We have studied 57 patients undergoing gynaecological surgery to establish a dose-response relationship when neostigmine was given to antagonize atracurium-induced block. Anaesthesia was induced with thiopentone and fentanyl and maintained with nitrous oxide and enflurane in oxygen and neuromuscular block was produced with a bolus of atracurium 0.5 mg kg-1. At the time of antagonism of block, three groups received neostigmine 20, 40 or 80 micrograms kg-1 at 5-10% recovery of the compound muscle action potential of the adductor pollicis (profound block) and three groups received one of these doses at 40-50% neuromuscular recovery (light block). At profound block, antagonism was prolonged by reducing the dose of neostigmine from 40 micrograms kg-1 to 20 micrograms kg-1, but not shortened by increasing the dose from 40 micrograms kg-1 to 80 micrograms kg-1. At light block, there was no significant difference between the three groups in the time taken to reach a train-of-four ratio of 0.7. There was little benefit in increasing the dose of neostigmine from 40 micrograms kg-1 to 80 micrograms kg-1 when antagonizing profound neuromuscular block. When light block was antagonized, neostigmine 20 micrograms kg-1 was the optimum dose. We suggest that smaller doses of neostigmine than are given commonly produce adequate antagonism of atracurium-induced neuromuscular block.

Adult↗

PubMed2002

Microinjection of neostigmine into the pontine reticular formation of C57BL/6J mouse enhances rapid eye movement sleep and depresses breathing.

STUDY OBJECTIVES: The cholinergic model of rapid eye movement (REM) sleep has contributed significantly to understanding sleep neurobiology and sleep-dependent respiratory depression. The model has been used extensively in cat and rat, but no previous studies have demonstrated cholinergic REM sleep enhancement in mouse. The present study used microinjection of neostigmine into pontine reticular formation of mouse to test the hypothesis that enhancing pontine cholinergic neurotransmission would cause increased REM sleep and sleep disordered breathing. DESIGN: Mice (n=8) were anesthetized and implanted with electrodes for measuring cortical electroencephalogram (EEG). Stainless steel cannulae were stereotaxically implanted to permit subsequent microinjections of 50 nl neostigmine (0.133 microg; 8.8 mM) or saline into the pontine reticular formation. Following recovery, an intensive within-subjects design was used to obtain measures of sleep/wake states, breathing, and locomotor activity. Inferential statistics were provided by t-tests. A probability value of < 0.05 indicated statistical significance. SETTING: NA. PATIENTS OR PARTICIPANTS: NA. INTERVENTIONS: NA. MEASUREMENTS AND RESULTS: Behavioral observations and manual scoring of polygraphic recordings showed that neostigmine produced a REM sleep-like state. EEG power analysis using Fast Fourier Transformation confirmed that pontine neostigmine caused EEG activation. Plethysmography demonstrated significantly disordered breathing. Compared to waking, pontine microinjection of neostigmine decreased respiratory rate (-64%) and minute ventilation (-75%). Pontine neostigmine significantly increased duration of inspiration (138%) and expiration (140%) above waking levels and decreased inspiratory flow (-69%). Additional studies showed that pontine neostigmine significantly depressed locomotor activity. CONCLUSIONS: This study is the first to demonstrate cholinergic REM sleep enhancement in unanesthetized, intact mouse. The results encourage future studies to characterize similarities and differences in cholinergic REM sleep enhancement in additional inbred strains and in transgenic mice. Such comparisons will help characterize sleep and breathing as intermediate phenotypes that are determined, in part, by the lower level phenotype of pontine cholinergic neurotransmission.

Animals↗

PubMed1997

Studies on the safety of glucose and paraben-containing neostigmine for intrathecal administration.

Initial toxicity testing of neostigmine for intrathecal (IT) injection was performed with preservative-free isobaric solution, yet currently available formulations contain the preservatives methyl- and propylparaben and are usually mixed with glucose to yield hyperbaric solutions. Since it has been proposed that preservatives and hyperbaricity increase the risk of neurotoxicity after IT injection, we examined the safety of chronically administered IT neostigmine containing these additives in sheep and rats. Rats receiving daily IT injections of glucose alone or of glucose with preservative-containing neostigmine, 5 and 10 microg, exhibited dose-related antinociception, tremor, and rigidity. In comparison to our previously published study of neostigmine injection in solution without glucose, rats receiving IT neostigmine with glucose displayed less rigidity, tremor, and salivation. Sheep receiving daily injection of glucose alone or with preservative-containing neostigmine, 1 mg, for 14 days exhibited no histologic evidence of neurotoxicity, nor did they exhibit abnormalities in cerebrospinal fluid chemistry aside from those caused by inflammation. Spinal cord histologic examination in both species revealed fibrosis and inflammation secondary to the catheter without evidence of neuronal damage. These studies support the safety of paraben- and glucose-containing IT neostigmine.

Analgesia, Epidural↗

PubMed1999

Early and late reversal of rocuronium and vecuronium with neostigmine in adults and children.

UNLABELLED: We investigated the influence of the timing of neostigmine administration on recovery from rocuronium or vecuronium neuromuscular blockade. Eighty adults and 80 children were randomized to receive 0.45 mg/kg rocuronium or 0.075 mg/kg vecuronium during propofol/fentanyl/N2O anesthesia. Neuromuscular blockade was monitored by train-of-four (TOF) stimulation and adductor pollicis electromyography. Further randomization was made to control (no neostigmine) or reversal with 0.07 mg/kg neostigmine/0.01 mg/kg glycopyrrolate given 5 min after relaxant, or first twitch (T1) recovery of 1%, 10%, or 25%. Another eight adults and eight children received 1.5 mg/kg succinylcholine. At each age, spontaneous recovery of T1 and TOF was similar after rocuronium and vecuronium administration but was more rapid in children (P < 0.05). Spontaneous recovery to TOF0.7 after rocuronium and vecuronium administration in adults was 45.7 +/- 11.5 min and 52.5 +/- 15.6 min; in children, it was 28.8 +/- 7.8 min and 34.6 +/- 9.0 min. Neostigmine accelerated recovery in all reversal groups (P < 0.05) by approximately 40%, but the times from relaxant administration to TOF0.7 were similar and independent of the timing of neostigmine administration. Recovery to T1 90% after succinylcholine was similar in adults (9.4 +/- 5.0 min) and children (8.4 +/- 1.1 min) and was shorter than recovery to TOF0.7 in any reversal group after rocuronium or vecuronium administration. Recovery from rocuronium and vecuronium blockade after neostigmine administration was more rapid in children than in adults. Return of neuromuscular function after reversal was not influenced by the timing of neostigmine administration. These results suggest that reversal of intense rocuronium or vecuronium neuromuscular blockade need not be delayed until return of appreciable neuromuscular function has been demonstrated. IMPLICATIONS: These results suggest that reversal of intense rocuronium or vecuronium neuromuscular blockade need not be delayed until return of appreciable neuromuscular function has been demonstrated. Although spontaneous and neostigmine-assisted recovery is more rapid in children than in adults, in neither is return of function as rapid as after succinylcholine administration.

Adult↗

PubMed1999

The effects of antagonizing residual neuromuscular blockade by neostigmine and glycopyrrolate on nausea and vomiting after ambulatory surgery.

UNLABELLED: The effects of neostigmine on the incidence of postoperative nausea and vomiting (PONV) are controversial. In this study, we evaluated the effects of neostigmine and glycopyrrolate on the incidence of PONV and the need for antiemetics in patients undergoing ambulatory surgery. One hundred healthy patients undergoing outpatient surgical procedures were included in the study. A standardized anesthetic technique was used for all patients. Patients were randomized to receive either mivacurium (n = 50) or rocuronium (n = 50) to achieve muscle paralysis. Bolus doses of mivacurium 2-4 mg or rocuronium 5-10 mg were administered to maintain one or two twitches of the train-of-four stimulation of the ulnar nerve at the wrist. After surgery, residual neuromuscular blockade was reversed with neostigmine 2.5 mg i.v. and glycopyrrolate 0.5 mg i.v. only if clinically deemed necessary (i.e., fade on train-of-four stimulation, inadequate tidal volume, reduced hand grip, or inability to maintain head lift). The incidence of PONV and the need for antiemetics were recorded in the post-anesthesia care unit (PACU), in the phase II unit, and 24 h after surgery. We compared patients who received neostigmine (n = 40) for reversal of residual neuromuscular blockade with those who did not (n = 60). More patients receiving rocuronium required reversal drugs than those receiving mivacurium (68% vs 10%). There were no differences in the incidence of nausea (18% vs 15%), vomiting (8% vs 12%), and the need for antiemetics (13% in both the groups) in the PACU between patients who received neostigmine and those who did not. In addition, the duration of PACU stay and the time to home-readiness were also similar between the groups. We conclude that, compared with rocuronium, the use of mivacurium decreases the need for reversal drugs. In addition, reversal of residual neuromuscular blockade with neostigmine does not increase the incidence of PONV or the need for antiemetic medications in patients undergoing ambulatory surgery. IMPLICATIONS: In this study, we showed that the incidence of postoperative nausea and vomiting and the need for antiemetics do not increase with the use of neostigmine and glycopyrrolate for reversal of residual muscle paralysis.

Adult↗

PubMed2000

An analysis of drug interaction between morphine and neostigmine in rats with nerve-ligation injury.

UNLABELLED: Intrathecal neostigmine reverses mechanical allodynia in humans and animals. The efficacy of morphine in a neuropathic pain state is still controversial. This study examines the antiallodynic interaction between morphine and neostigmine in a rat model of neuropathic pain. Rats were prepared with tight ligation of left L5-6 (fifth and sixth lumbar) spinal nerves and chronic intrathecal catheter implantation. Mechanical allodynia was measured by using application of von Frey hairs to the left hindpaw. Morphine (1, 3, 10, and 30 microg) and neostigmine (0.3, 1, 3, and 10 microg) were administered intrathecally to obtain the dose-response curves and the 50% effective dose (ED(50)) for each drug. ED(50) values and fractions of the ED(50) values (1/2, 1/4, and 1/8) were administered intrathecally in an equal dose ratio to establish the ED(50). Isobolographic and fractional analyses for the drug interaction were performed. Intrathecal morphine produced a moderate antagonism of the tactile allodynia. A morphine-neostigmine combination produced a dose-dependent increase in withdrawal threshold of the lesioned hind paw with reduced side effects. Both analyses revealed a synergistic interaction after the coadministration of morphine and neostigmine. These experiments suggest that the antiallodynic action of a morphine-neostigmine combination is synergistic at the spinal level. IMPLICATIONS: This study indicates that, by using both isobolographic and fractional analyses, the antiallodynic effect of intrathecal morphine and neostigmine is synergistic when coadministered intrathecally. In a rat model of neuropathic pain, the intrathecal morphine produced a moderate antagonism on touch-evoked allodynia at the spinal level.

Analgesics, Opioid↗

PubMed1979

4-Aminopyridine potentiates neostigmine and pyridostigmine in man.

To elucidate the interaction of 4-aminopyridine with neostigmine and pyridostigmine, the authors studied 57 anesthetized surgical patients using a technique of constant infusion of pancuronium to quantitate antagonist activity. 4-Aminopyridine, 0.15 or 0.35 mg/kg, produced no antagonism, while 0.5 mg/kg produced a mean 24 +/- 6 per cent (peak) antagonism. The dose that produced 50 per cent antagonism (ED50) of neostigmine alone was 22 micrograms/kg; with 0.35 mg/kg 4-aminopyridine, it was 7 micrograms/kg. The ED50 of pyridostigmine alone was 110 micrograms/kg; with 0.35 mg/kg 4-aminopyridine, it was 27 micrograms/kg. 4-Aminopyridine prolonged the onset times of both neostigmine and pyridostigmine, but prolonged the duration of action of neostigmine only. At a given level of antagonism of pancuronium, adding 4-aminopyridine 0.35 mg/kg, to neostigmine and to pyridostigmine decreased the amounts of atropine needed to prevent a change in heart rate by 68 and 70 per cent, respectively. The authors conclude that 4-aminopyridine potentiates antagonism of a pancuronium-induced neuromuscular blockade by neostigmine or pyridostigmine. Also, less atropine is needed to prevent cardiac muscarinic stimulation when 4-aminopyridine is used with either neostigmine or pyridostigmine.

Adult↗

PubMed1989

Recovery from vecuronium neuromuscular blockade following neostigmine administration in infants, children, and adults during halothane anesthesia.

To determine whether neostigmine had different effects in pediatric patients during vecuronium neuromuscular blockade, the rate of recovery following neostigmine administration was compared in infants (n = 8), children (n = 10), and adults (n = 10) during nitrous oxide-halothane anesthesia. After induction of anesthesia, patients received 100 micrograms/kg of vecuronium. The EMG response of the adductor pollicis was monitored after train-of-four (TOF) stimulation of the ulnar nerve every 20 s. When the first twitch of TOF spontaneously recovered to 10% of control value, neostigmine was injected (40 micrograms/kg in adults, 30 micrograms/kg in infants and children). During the first few minutes following neostigmine administration, no differences were observed between the three groups. After the 8 min, recovery was more rapid in children than in infants and adults up to and including the 15th min. Ten minutes after neostigmine administration, the first twitch (mean +/- SD) reached 97 +/- 3%, 99 +/- 2%, and 97 +/- 5% of control value in infants, children, and adults, respectively; TOF ratio was greater in children (0.96 +/- 0.03) than in either adults (0.82 +/- 0.17) or in infants (0.83 +/- 0.14) (P less than 0.05). During the first minutes after neostigmine administration, the lack of difference in TOF recovery in the three groups suggests that neostigmine is the main factor of recovery. In contrast, the more complete recovery after the eighth minute in children could be due to the faster rate of spontaneous recovery from vecuronium induced neuromuscular blockade in children.

Adult↗

PubMed1990

Can early administration of neostigmine, in single or repeated doses, alter the course of neuromuscular recovery from a vecuronium-induced neuromuscular blockade?

The authors sought to determine whether neostigmine, given at a time when no response to peripheral nerve stimulation could be elicited, hastened recovery from a vecuronium-induced neuromuscular blockade (NMB). The effect of neostigmine (70 micrograms/kg) in antagonizing a profound (no-twitch) vecuronium-induced (0.1 mg/kg) NMB in 40 healthy patients was studied. Patients were randomly assigned to one of four groups specifying the sequence of neostigmine administration. Fifteen minutes after the administration of vecuronium, when there was no detectable twitch response, each patient received either neostigmine (70 micrograms/kg) with glycopyrrolate (15 micrograms/kg) or an equivalent volume of normal saline (placebo). When T1 (the first response in the train-of-four [TOF] sequence) recovered to 10% of control, patients again received either neostigmine with glycopyrrolate in the same doses as before or the placebo. The following variables were measured: times from vecuronium injection until T1 recovered to 10% (t [10]) and 90% (t [90]) of control, and time until the TOF ratio was equal to 75% (t [TOF75]). Mean values of t (90) and t (TOF75) were shorter (54.7-75.2 min and 60.4-79.5 min, respectively) for the three groups who received neostigmine as compared with patients who received two doses of placebo (104.3 and 122.6 min, respectively). There were no differences in the t (90) and t (TOF75) values among the three groups who received neostigmine.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

PubMed1996

Dose responses for neostigmine and edrophonium as antagonists of mivacurium in adults and children.

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.

Adult↗

PubMed1999

Study of three different doses of epidural neostigmine coadministered with lidocaine for postoperative analgesia.

BACKGROUND: Intrathecal neostigmine produces analgesia in volunteers and patients. However, the use of epidural neostigmine has not been investigated. The purpose of the current study was to define the analgesic effectiveness of epidural neostigmine coadministered with lidocaine and side effects in patients after minor orthopedic procedures. METHODS: After Institutional Review Board approval and informed consent, 48 patients (n = 12) undergoing knee surgery were randomly allocated to one of four groups and studied in a prospective way. After 0.05-0.1 mg/kg intravenous midazolam premedication, patients were randomized to receive 20 mg intrathecal bupivacaine plus epidural lidocaine (85 mg) with saline (control group); 1 microg/kg epidural neostigmine (1 microg group); 2 microg/kg epidural neostigmine (2 microg group); or 4 microg/kg epidural neostigmine (4 microg group). The concept of the visual analog scale, which consisted of a 10-cm line with 0 equaling "no pain at all" and 10 equaling "the worst possible pain" was introduced. Postoperatively, pain was assessed using the visual analog scale, and intramuscular 75 mg diclofenac was available at patient request. RESULTS: Groups were demographically the same and did not differ in intraoperative characteristics (blood pressure, heart rate, ephedrine consumption, oxyhemoglobin saturation, sensory loss before start of surgery, or duration of sensory motor block). The visual analog scale score at first rescue analgesic and the incidence of adverse effects were similar among groups (P > 0.05). The time (min +/- SD) to first rescue analgesic was as follows: control group: 205+/-48; 1-microg group: 529+/-314; 2-microg group: 504+/-284; 4-microg group: 547+/-263 (P < 0.05). The analgesic consumption (number of intramuscular diclofenac injections [mean, 25th-75th percentile]) in 24 h was as follows: control group: 3 [3 or 4]; 1-microg group: 1 [1 or 2]; 2-microg group: 2 [1 or 2]; 4-microg group: 2 [1-3] (P < 0.05). The 24-h-pain visual analog scale score (cm +/- SD) that represents the overall impression for the last 24 h was as follows: control group: 5+/-1.6; 1-microg group: 1.6+/-1.8; 2-microg group: 1.4+/-1.6; 4-microg group: 2.2+/-1.9 (P < 0.005). The incidence of adverse effects was similar among groups (P > 0.05). CONCLUSION: Epidural neostigmine (1, 2, or 4 microg/kg) in lidocaine produced a dose-independent analgesic effect (approximately 8 h) compared to the control group (approximately 3.5 h), and a reduction in postoperative rescue analgesic consumption without increasing the incidence of adverse effects.

Adult↗

PubMed2002

The influence of mild hypothermia on the pharmacokinetics and time course of action of neostigmine in anesthetized volunteers.

BACKGROUND: The pharmacokinetics, maximum effect, and time course of action of neostigmine were studied in seven human volunteers. METHODS: Each volunteer was studied twice, during both normothermia and hypothermia. Anesthesia was induced with 30 microg/kg alfentanil and 3 mg/kg propofol, and was maintained with 60-70% nitrous oxide and 0.7-0.9% isoflurane. The mechanical response of the adductor pollicis to train-of-four stimulation of the ulnar nerve was recorded, and central body temperature maintained stable at either less than 34.5 degrees C or greater than 36.5 degrees C by surface cooling or warming. Before neostigmine administration, a stable 5% twitch height was obtained by an infusion of vecuronium, and the infusion rate remained unchanged thereafter. Neostigmine, 70 microg/kg, was then infused over 2 min, and blood samples for estimation of neostigmine concentrations were collected at intervals for 240 min. RESULTS: With hypothermia, the central volume of distribution of neostigmine decreased by 38%, and onset time of maximum effect increased (4.6 vs. 5.6 min). Hypothermia did not change the clearance (696 ml/min), maximum effect, or duration of action of neostigmine. CONCLUSIONS: The efficacy of neostigmine as an antagonist of vecuronium-induced neuromuscular block is not altered by mild hypothermia.

Adult↗

PubMed1993

Intranasal versus intravenous neostigmine in myasthenia gravis: assessment by computer analysis of saccadic eye movements.

Intranasal (i.n.) neostigmine has been developed to obtain a quicker onset of action and a more adaptable dosage regimen than oral neostigmine. The effect of this neostigmine formulation in myasthenia gravis (MG) was studied by means of computer analysis of saccadic eye movements (SEMs). Six MG patients were selected on the basis of a positive effect of Tensilon on hypometria of the first saccade. The effect of the i.v. formulation (0.5 mg) was compared to 1, 2, 3, and 4 puffs of i.n. neostigmine (one puff = 4.6 mg). The drug effect on SEMs was monitored at intervals up to 2 h. Administration of i.v. neostigmine produced a marked effect immediately after the injection and the benefit lasted over 1 h. Following administration of i.n. neostigmine a marked effect was found for two, three, and four puffs. The drug effect was evident within 3 min, peaked at 18-33 min, and lasted over 2 h. Our data indicate the efficacy of the new formulation of neostigmine in MG as measured by means of quantitative analysis of SEMs.

Administration, Intranasal↗