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PubMed1999

Intrathecal neostigmine and sufentanil for early labor analgesia.

BACKGROUND: Recent efforts to improve the combined spinal epidural (CSE) technique have focused on adding opioids to other classes of analgesics. In this study, the authors used intrathecal neostigmine in combination with intrathecal sufentanil to investigate the usefulness of neostigmine for reducing side effects and prolonging the duration of sufentanil. METHODS: One hundred six healthy pregnant women in labor were enrolled in this study, which was divided into four phases. In all phases, patients received a CSE anesthetic while in the lateral position. In phase I, three groups of six women each received intrathecal neostigmine, 5, 10, or 20 microg, in an open-label, dose-escalating safety assessment. In phase II, 24 women received intrathecal sufentanil alone to establish an ED50 (dose that produces > 60 min of labor analgesia in 50% of patients). In phase III, an ED50 was established for sufentanil combined with a fixed dose of neostigmine (10 microg). In phase IV, 40 women received either twice the ED50 of sufentanil alone or twice the ED50 of sufentanil plus neostigmine, 10 microg. RESULTS: Neostigmine alone had no adverse effects on maternal vital signs, fetal heart rate, or Apgar scores. Neostigmine, 20 microg, produced analgesia in one patient and severe nausea and vomiting in another. The ED50 for intrathecal sufentanil alone was 4.1 +/- 0.31 microg, and the ED50 for intrathecal sufentanil combined with neostigmine, 10 microg, was 3.0 +/- 0.28 microg. The duration of analgesia and side effects from double these ED50s (sufentanil, 9 microg, or sufentanil, 6 microg, plus neostigmine, 10 microg) were similar between groups. CONCLUSIONS: The 10-microg intrathecal neostigmine dose alone produced no analgesia or side effects, but reduced the ED50 of intrathecal sufentanil by approximately 25%. Additionally, doses approximately double these ED50s each produced a similar duration of analgesia and side effects, indicating intrathecal neostigmine shifts the dose-response curve for intrathecal sufentanil to the left.

Adult↗
PubMedDate not supplied

Effects of neostigmine and glycopyrrolate on pulmonary resistance in spinal cord injury.

Preliminary findings in subjects with spinal cord injury (SCI) suggest that neostigmine administered intravenously increases colonic tone, increases colonic contractions, and facilitates bowel evacuation. Of concern are potential pulmonary side effects, including an increase in airway secretions and bronchospasm. The objectives of the study were to determine the effects of intravenously administered neostigmine or neostigmine combined with glycopyrrolate on forced oscillation indices in persons with SCI. Pulmonary resistances at 5 Hz (R5) and 20 Hz (R20) were measured with the use of an impulse oscillation system (IOS) in 11 subjects with SCI. Values were obtained before and after the intravenous administration of 2 mg of neostigmine alone and, on a separate day, before and after the administration of 2 mg of neostigmine combined with 0.4 mg of glycopyrrolate. Baseline R5 and R20 values before neostigmine correlated significantly with baseline values before neostigmine combined with glycopyrrolate. Following neostigmine, mean R5 values increased 25% and mean R20 values increased 18%. Following neostigmine combined with glycopyrrolate, mean R5 values fell 9% and mean R20 values fell 7%. In summary, baseline IOS values obtained on 2 different days were highly reproducible in this population. Neostigmine alone induced significant bronchoconstriction, whereas neostigmine combined with glycopyrrolate caused bronchodilation.

Adult↗
PubMed1995

Time to peak effect of neostigmine at antagonism of atracurium- or vecuronium-induced neuromuscular block.

STUDY OBJECTIVE: (1) To determine the time to peak effect of neostigmine (time to peak antagonism) during atracurium- or vecuronium-induced neuromuscular block; and (2) to determine the effect on time to peak effect of neostigmine during atracurium-induced neuromuscular block, when the dose of neostigmine is increased from 35 micrograms/kg to 70 micrograms/kg. DESIGN: Prospective, randomized clinical study. SETTING: Gynecologic operating room suite at a university hospital. PATIENTS: 45 ASA I and II women admitted for gynecologic laparotomy. INTERVENTIONS: Anesthesia was performed with thiopental sodium, fentanyl, halothane, nitrous oxide, and atracurium or vecuronium. Train-of-four (TOF) stimulation and mechanomyography were used to monitor neuromuscular transmission. Neostigmine was administered while a constant degree of neuromuscular block was maintained at a twitch height at a point between 4% and 11% of the control twitch height, using a continuous infusion of atracurium or vecuronium. The patients were randomized to three groups, with 15 patients in each group. Group 1 received atracurium block antagonized with neostigmine 35 micrograms/kg; group 2 received vecuronium block antagonized with neostigmine 35 micrograms/kg; and group 3 received atracurium block antagonized with neostigmine 70 micrograms/kg. MEASUREMENTS AND MAIN RESULTS: The degree of neuromuscular block at antagonism was similar in the three groups. Time to peak effect (mean +/- SD) on TOF ratio was significantly longer in Group 1 (9.7 +/- 3.0 minutes) versus Group 2 (6.6 +/- 1.4 minutes; (p < 0.05). The time to peak effect on TOF ratio during atracurium-induced block was reduced from 9.7 +/- 3.0 minutes to 6.3 +/- 2.0 minutes when the dose of neostigmine was increased from 35 micrograms/kg to 70 micrograms/kg (p < 0.05). The peak effect on TOF ratio was significantly greater in Group 3 compared with Group 1 (p < 0.05), while it was similar in groups 1 and 2. CONCLUSION: The time to peak effect of neostigmine 35 micrograms/kg is about 6 to 10 minutes when antagonizing a constant degree of atracurium- or vecuronium-induced neuromuscular block at a twitch height at a point between 4% and 11%. Even though the time to peak effect was longer with atracurium than with vecuronium, clinically significant differences between the antagonizing effect of atracurium versus vecuronium block were not demonstrated. The time to peak effect during atracurium-induced block decreased when the dose of neostigmine was increased from 35 micrograms/kg to 70 micrograms/kg.

Adult↗
PubMed1997

Intrathecal neostigmine for postoperative analgesia after orthopedic surgery.

STUDY OBJECTIVE: To establish a dose-response curve for the analgesic effect of intrathecal neostigmine in patients undergoing below knee surgery with spinal anesthesia. To assess adverse effects, principally nausea and vomiting. DESIGN: Randomized, double-blind, prospective study. SETTING: Teaching hospital. PATIENTS: 60 ASA physical status I and II premedicated patients undergoing orthopedic surgery (tibial or ankle reconstruction). INTERVENTION: Spinal anesthesia was performed at the sitting position, L3-L4 interspace, 4 ml final volume, injected at a rate of 1 ml/10 sec. The control group (CG) received 15 mg hyperbaric bupivacaine 0.5% plus saline. The 25 micrograms neostigmine group (25NG) received 15 mg hyperbaric bupivacaine plus 25 micrograms neostigmine; the 50 micrograms neostigmine group (50NG) received 15 mg hyperbaric bupivacaine plus 50 micrograms neostigmine; and the 100 micrograms neostigmine group (100NG) received 15 mg hyperbaric bupivacaine plus 100 micrograms neostigmine. Patients were placed supine after the spinal punction. MEASUREMENTS AND MAIN RESULTS: Time to first rescue analgesics, analgesia, and adverse effects at constant intervals were assessed using the 10 cm visual analog scale (VAS). Intrathecal neostigmine produced a dose-independent reduction in the postoperative rescue analgesic consumption (p < 0.0001). The time to first rescue analgesics was similar among groups (p > 0.05), and the overall 24-hour VAS pain scores were lowest for patients who had spinal neostigmine (p < 0.02). The 100NG group had the highest incidence of postoperative nausea and vomiting of all the groups (p < 0.05). CONCLUSION: Intrathecal neostigmine produced a dose-independent analgesia and a dose-dependent incidence of adverse effects with the doses studied.

Adult↗
PubMed1998

The efficacy of intrathecal neostigmine, intrathecal morphine, and their combination for post-cesarean section analgesia.

UNLABELLED: We designed this study to evaluate the postoperative analgesic efficacy and safety of intrathecal (i.t.) neostigmine, i.t. morphine, and their combination in patients undergoing cesarean section under spinal anesthesia. Seventy-nine term parturients were randomly divided into four groups to receive isotonic sodium chloride solution 0.2 mL, neostigmine 25 microg, morphine 100 microg, or the combination of i.t. neostigmine 12.5 microg and morphine 50 microg with i.t. 0.5% hyperbaric bupivacaine 12 mg. There were no significant differences among the four groups with regard to spinal anesthesia, maternal blood pressure and heart rate, or fetal status. Postoperative analgesia was provided by i.v. patient-controlled analgesia (PCA) using fentanyl and ketorolac. Compared with the saline group, the time to first PCA use was significantly longer in the neostigmine group (P < 0.001), with lower 24-h analgesic consumption (P < 0.001). Nausea and vomiting were the most common side effects of i.t. neostigmine (73.7%). Analgesic effectiveness was similar between the neostigmine and morphine groups. Compared with the neostigmine group, the combination group had significantly prolonged analgesic effect and reduced 24-h PCA consumption (P < 0.05) with less severity of nausea and vomiting (P = 0.058). Compared with the morphine group, the combination group tended to have prolonged times to first PCA use (P = 0.054) with a lower incidence of pruritus (P < 0.03). IMPLICATIONS: Intrathecal (i.t.) neostigmine 25 microg produced postoperative analgesia for cesarean section similar to that of i.t. morphine 100 microg, but with a high incidence of nausea and vomiting. The combination of i.t. neostigmine 12.5 microg and i.t. morphine 50 microg may produce better postoperative analgesia with fewer side effects than i.t. neostigmine 25 microg or i.t. morphine 100 microg alone.

Adult↗
PubMed2001

The interaction between intrathecal neostigmine and GABA receptor agonists in rats with nerve ligation Injury.

UNLABELLED: Nerve ligation injury may produce a pain syndrome that includes tactile allodynia. Reversal effects on tactile allodynia have been demonstrated after the intrathecal administration of gamma-aminobutyric acid (GABA) receptor agonists or cholinesterase inhibitors in rats. We examined the drug interactions between neostigmine and muscimol or baclofen in a rat model of nerve ligation injury. Rats were prepared with tight ligation of the left L5-6 spinal nerves and chronic intrathecal catheter implantation. Tactile allodynia was measured by applying von Frey filaments ipsilateral to the lesioned hindpaw. Thresholds for paw withdrawal were assessed. Neostigmine (0.3-10 microg), muscimol (0.1-10 microg), and baclofen (0.1-3.0 microg) were administered to obtain the dose-response curve and the 50% effective dose (ED(50)). Fractions of ED(50) values were administered intrathecally to establish the ED(50)s of drug combinations (neostigmine-muscimol and neostigmine-baclofen). The drug interactions were performed. Intrathecal neostigmine, muscimol, baclofen, and their combinations produced a dose-dependent increase in withdrawal threshold of the lesioned hindpaw. Both analyses revealed a synergistic interaction for the neostigmine-muscimol combination, whereas the effect of the neostigmine-baclofen combination was additive. These results suggest that the activation of both muscarinic and GABA(A) receptors is required for synergistic interaction. IMPLICATIONS: This study indicates that drug interaction is synergistic for the neostigmine-muscimol combination, whereas the effect of the neostigmine-baclofen combination is additive. In a rat model of nerve ligation injury, neostigmine, muscimol, baclofen, and their combinations provide an antagonism on touch-evoked allodynia at the spinal level.

Animals↗
PubMed1998

Postoperative analgesia by intra-articular neostigmine in patients undergoing knee arthroscopy.

BACKGROUND: Recently, the spinal administration of neostigmine was shown to produce a dose-dependent analgesia. However, this analgesia is limited by adverse effects. The purpose of this study was to examine the analgesic action of peripheral muscarinic receptors by administering intra-articular neostigmine after operation in patients undergoing knee arthroscopy. METHODS: Sixty patients (classified as American Society of Anesthesiologists status I or II) having arthroscopic meniscus repair during general anesthesia were randomized to receive, in a double-blind manner, after operation 125, 250, or 500 microg intra-articular neostigmine; 2 mg intra-articular morphine; or as control groups intra-articular saline or 500 microg neostigmine given subcutaneously (s.c.). Visual analog pain scores (VAS), duration of analgesia as defined by first demand for patient-controlled analgesia by morphine, and subsequent 48-h consumption of morphine were evaluated. RESULTS: Intra-articular (500 microg) neostigmine resulted in significant VAS reduction 1 h after injection compared with patients given intra-articular saline and with those given intra-articular morphine. Analgesia lasted longer after 500 microg intra-articular neostigmine (350 +/- 126 min) compared with intra-articular morphine (196 +/- 138 min; P < 0.05) or with the control groups (intra-articular saline, 51 +/- 11 min; s.c. neostigmine, 46 +/- 8 min; P < 0.05). The need for supplementary analgesia was significantly higher in control groups than for patients given intra-articular morphine or 500 microg intra-articular neostigmine. No significant analgesic effects were observed for the two lower doses of intra-articular neostigmine. Among all study groups, no adverse effects were observed. CONCLUSIONS: Intra-articular injection of the acetylcholinesterase inhibitor neostigmine produced a moderate but significant analgesic effect. Several mechanisms such as the hyperpolarization of neurons, reduction in the release of pronociceptive neurotransmitters, or activation of the nitric oxide-cyclic guanosine monophosphate pathway might mediate this peripheral cholinergic antinociception by elevating endogenous acetylcholine.

Adult↗
PubMed1998

Cerebrospinal fluid pharmacokinetics and pharmacodynamics of intrathecal neostigmine methylsulfate in humans.

BACKGROUND: This study defines the cerebrospinal fluid (CSF) pharmacokinetics of neostigmine after intrathecal injection in humans and its effect on CSF acetylcholine, and it correlates physiologic effects with neostigmine dose and CSF acetylcholine concentrations. METHODS: The CSF was sampled via an indwelling spinal catheter in 12 volunteers receiving intrathecal neostigmine (50-750 microg) and analyzed for neostigmine and acetylcholine. Pharmacokinetic and pharmacodynamic analyses were performed with NONMEM. Effect-site models linked the time course of the neostigmine concentration with the time course of analgesia. RESULTS: Acetylcholine concentrations increased from <20 pmol/ml at baseline to >100 pmol/ml within 15 min of neostigmine injection. The pharmacokinetics of intrathecal neostigmine were best described by a triexponential function with an absorption phase. Individual predicted concentrations varied 100-fold. Post hoc Bayesian estimates described the observed neostigmine concentrations with a median error of 22% and did not show systematic model misspecification. Individual estimates of effect site concentration producing a 50% maximal effect for foot visual analog scale analgesia correlated with the magnitude of individual CSF neostigmine concentrations. CONCLUSIONS: Intrathecal neostigmine concentrations can be well described by a triexponential disposition function, but the intersubject variability is large. The correlation between intersubject variability in concentration and intersubject variability in 50% maximal effect for foot analgesia suggests that both are offset by a common scalar, possibly the distance from the site of injection to the sampling and effect sites. These data provide the basis for the hypothesis of "observation at a distance" to describe the pharmacodynamics of intrathecally administered drugs.

Acetylcholine↗
PubMed1999

Early reversal of rapacuronium with neostigmine.

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.

Adult↗
PubMed2005

Epidural administration of neostigmine and clonidine to induce labor analgesia: evaluation of efficacy and local anesthetic-sparing effect.

BACKGROUND: Epidural clonidine produces analgesia without motor impairment, and is associated with a local anesthetic-sparing effect during labor. The authors have recently demonstrated that epidural neostigmine initiates selective labor analgesia devoid of adverse effects. Both drugs possess common analgesic mechanisms mediated through spinal acetylcholine release. This study evaluates their epidural combination in parturients. METHODS: At the beginning of labor, parturients were randomly allocated to one of five groups to receive one of the following after a test dose: 150 microg epidural clonidine, 750 microg neostigmine, or 75 microg clonidine combined with 250, 500, or 750 microg neostigmine. A pain score (visual analog scale, 0-100) was recorded before administration and at regular intervals until request for a supplemental injection. Subsequent analgesia was provided by continuous epidural infusion of ropivacaine. RESULTS: Parturients did not differ regarding demographic data and initial pain score. Clonidine 150 microg , neostigmine 750 microg , and 75 microg clonidine plus 250 microg neostigmine produced ineffective and short-lasting effects. Clonidine 75 microg plus 500 microg neostigmine and 75 microg clonidine plus 750 microg neostigmine presented comparable durations of 90 +/- 32 and 108 +/- 38 min (mean +/- SD), respectively, and final analgesic efficacies, with 72.2% and 84%, respectively, of the parturients reporting a visual analog scale score of less than 30 out of 100 after 30 min. Ropivacaine use was significantly reduced in all clonidine groups (average, 9.5 mg/h) in comparison with neostigmine alone (17 +/- 3 mg/h). No adverse effects were observed for 75 mug clonidine combined with any dose of neostigmine while maternal sedation (20%) and hypotension (33%) occurred with 150 microg clonidine alone. CONCLUSIONS: Epidural clonidine, 75 microg , with 750 microg neostigmine is an effective combination to initiate selective labor analgesia without adverse effects. Clonidine use further reduces local anesthetic consumption throughout the course of labor.

Anesthesia, Epidural↗
PubMed2006

Factors predicting successful outcome following neostigmine therapy in acute colonic pseudo-obstruction: a prospective study.

AIM: To evaluate predictors of neostigmine response in patients with acute colonic pseudo-obstruction. METHODS: Twenty-seven patients with acute colonic pseudo-obstruction were enrolled in the study. All patients had received initial conservative management such as nil orally, nasogastric suction, rectal tube placement and correction of electrolyte imbalance for the first 24 h. Those who did not resolve with conservative management received 2 mg neostigmine intravenously. The same dose was repeated after 24 h in patients who did not response to the first dose (initial non-responders), or in those patients who relapsed after an initial response (initial responders). All non-responders to neostigmine underwent colonoscopic decompression followed by 2 mg neostigmine infusion for 30 min. A sustained response was defined as the resolution of symptoms and colonic dilatation on a plain radiograph. RESULTS: The study enrolled 27 patients; 18 were male (67%), and the median age was 60 years (range 18-78 years). Eight (30%) patients had spontaneous resolution. Initial response with neostigmine was observed in 16 (84%) patients, of which 10 (63%) had a sustained response. Nine patients (three initial non-responders and six initial responders) had received a second dose of neostigmine. A sustained response was seen only in five initial responders. Four patients who did not respond to neostigmine underwent colonoscopic decompression followed by neostigmine infusion and had a sustained response. Neostigmine responders were more likely to be postoperative patients (11 of 15 (73%) vs one of four (25%), P = 0.07), less likely to have electrolyte imbalance and to be on antimotility agents (three of 15 (20%) vs four of four (100%), P = 0.009 and two of 15 (13%) vs four of four (100%), P = 0.003). CONCLUSIONS: Electrolyte imbalance and usage of anti-motility agents are factors associated with a poor response, while postoperative patients showing good response to neostigmine therapy.

Acute Disease↗
PubMed2005

Infusion of neostigmine-glycopyrrolate for bowel evacuation in persons with spinal cord injury.

Defecatory complications are common after spinal cord injury (SCI) and have been attributed, in part, to an imbalance of the autonomic nervous system between parasympathetic and sympathetic effects on the colon. Because parasympathetic (i.e., cholinergic) input to the bowel may be downregulated after SCI, it was hypothesized that neostigmine, a medication that increases cholinergic tone by blocking the metabolism of acetylcholine, might promote bowel evacuation in these persons. Since neostigmine is known to cause bradycardia and bronchoconstriction, we also assessed whether these side-effects could be prevented by coadministration of neostigmine with glycopyrrolate, an anticholinergic agent that has limited activity on the muscarinic receptors of the colon. The hypothesis was tested in 13 persons with SCI in whom videofluoroscopy was carried out after instillation of a barium oatmeal paste into the rectum and descending colon. On separate days, subjects received, in a randomized, blinded design, one of three intravenous infusates (normal saline, 2 mg neostigmine, or 2 mg neostigmine + 0.4 mg glycopyrrolate). The effect of these infusates on bowel evacuation of the barium paste, heart rate, and airway resistance was determined. Both neostigmine and neostigmine + glycopyrrolate resulted in prompt bowel evacuation. The nadir heart rate was lower after neostigmine alone than with the combination. Neostigmine administration increased both total and central airway resistance, an effect that was not observed with the coadministration of glycopyrrolate. Other side-effects of neostigmine and the combination of drugs included muscle fasciculations and dry mouth, both of which were mild and short-lived. Abdominal cramping was noted in subjects with spinal cord lesions below thoracic level 10. These results indicated that neostigmine/glycopyrrolate administration is safe and well tolerated in persons with chronic SCI.

Adult↗
PubMed1996

Optimum time for neostigmine reversal of atracurium-induced neuromuscular blockade.

PURPOSE: The aim of the study was to determine the optimum time for administration of neostigmine during recovery from atracurium-induced neuromuscular blockade. METHODS: The study comprised 103 patients anaesthetised with midazolam, fentanyl, thiopentone, halothane, and nitrous oxide. Relaxation was induced with atracurium 0.5 mg. kg-1 and maintained with supplements of 0.15 mg. kg-1. The ulnar nerve was stimulated with train-of-four (TOF) and double burst stimulation (DBS). Evoked MMG responses were recorded. Patients were randomized to spontaneous recovery (n = 20) or to assisted recovery by neostigmine (0.07 mg.kg-1) at varying intervals (6-50 min) from the last atracurium dose (n = 83). RESULTS: The reversal time (time from administration of neostigmine to TOF ratio 0.7) was always < 13 min, when T1 (first twitch in TOF) was detectable or when D1 (first twitch in DBS) was > 5%. Total assisted recovery time (time from last supplemental atracurium dose to TOF ratio 0.7) increased with increasing T1 and D1 twitch heights (P < 0.05). The curve fitted to the scattergram with total assisted recovery time vs time from last atracurium supplement to neostigmine administration decreased to reach a minimum after which it increased to approach the line of identity. The minimum of the curve (total assisted recovery time 30.7 min) was reached when neostigmine was given 18.6 min after last atracurium supplement. At this time the T1 and D1 twitch height averaged 4 and 8% respectively. If prolongation of the minimum total recovery time of 2.5% is accepted, neostigmine can be given at T1 and D1 twitch height values of 0 to 8% and 4 to 15%, respectively. CONCLUSION: The optimum time for neostigmine administration, taking both the reversal time and total recovery time into consideration, is when 0 < T1 < 8% or when 5 < D1 < 15%. Giving neostigmine at more profound degrees of blockade prolongs reversal time, while giving neostigmine later in the recovery phase prolongs total recovery time.

Adolescent↗
PubMed2001

Intrathecal bupivacaine with morphine or neostigmine for postoperative analgesia after total knee replacement surgery.

PURPOSE: To compare the postoperative analgesic efficacy and safety of intrathecal (IT) neostigmine and IT morphine in patients undergoing total knee replacement under spinal anesthesia. METHODS: Sixty patients scheduled for elective total knee replacement under spinal anesthesia were randomly divided into three equal groups which received IT 0.5% hyperbaric bupivacaine 15 mg with either normal saline 0.5 mL, neostigmine 50 microg, or morphine 300 microg. The maximal level of sensory block, duration of analgesia, time to use of rescue analgesics, the overall 24-hr and four-hour interval visual analogue scale (VAS) pain score, and the incidence of adverse effects were recorded for 24 hr after administration. RESULTS: There was no significant difference in maximal level of sensory block among the three groups. The morphine group had a later onset of postsurgical pain and longer time to first rescue analgesics than the neostigmine group (P <0.05). Overall 24-hr VAS pain scores were significantly higher in the saline group vs the morphine and neostigmine groups (P <0.05). Motor block lasted significantly longer in the neostigmine group than in the morphine and saline groups (P <0.05). The incidence of adverse effects was similar in the neostigmine and morphine groups except for pruritus (70%) occurring more frequently in the morphine group than in the neostigmine and saline groups (0%; P <0.05). Overall satisfaction rates were better in the neostigmine group than in the morphine and saline groups (P <0.05). CONCLUSIONS: IT neostigmine 50 microg produced postoperative analgesia lasting about seven hours with fewer side effects and better satisfaction ratings than IT morphine 300 microg.

Aged↗
PubMed1998

Effects of neostigmine and atropine on basal and handling-induced acetylcholine output from ventral hippocampus.

The involvement of muscarinic autoreceptors in the regulation of hippocampal acetylcholine levels during acetylcholinesterase inhibition was examined by perfusing the acetylcholinesterase inhibitor neostigmine bromide (10, 100 or 1000 nM) alone and in the presence of the muscarinic receptor antagonist atropine methylnitrate (10 microM), in resting and behaviourally-activated animals. In resting animals, local perfusion of neostigmine caused a dose-dependent increase in acetylcholine levels. Coadministration of atropine did not affect basal levels in the presence of 10 nM neostigmine, but increased acetylcholine levels approximately four and 11-fold in the presence of 100 nM and 1000 nM neostigmine, respectively. In animals which were behaviourally activated by handling, acetylcholine levels increased two- to three-fold in the presence of all neostigmine concentrations. However, the handling-induced increase in acetylcholine levels was somewhat smaller with 1000 nM neostigmine as compared to 10 nM neostigmine. Atropine had no effect on handling-induced acetylcholine output in the presence of 10 nM neostigmine, but caused greater and longer increases in the presence of 100 nM and 1000 nM neostigmine. These data indicate that acetylcholine levels are greatly reduced by autoinhibition at higher levels of acetylcholine esterase inhibition. The handling-evoked increase in acetylcholine levels is only moderately affected by the level of acetylcholinesterase inhibition, despite the participation of autoreceptors in the handling effect at higher levels of acetylcholinesterase inhibition.

Acetylcholine↗
PubMed1998

Combined intrathecal fentanyl and neostigmine: therapy for postoperative abdominal hysterectomy pain relief.

STUDY OBJECTIVE: To evaluate the analgesic action of spinal neostigmine as part of a multimodal analgesic therapy approach including spinal neostigmine and spinal fentanyl for postoperative pain relief DESIGN: Randomized, prospective study. SETTING: Teaching hospital. PATIENTS: 50 ASA physical status I and II patients undergoing abdominal hysterectomy. INTERVENTIONS: Patients were assigned to one of five groups (n = 10) to receive 15 mg bupivacaine plus 1 ml of the test drug intrathecally. The control group (CG) received saline as the test drug, the fentanyl group (FG) received 25 microg fentanyl; the neostigmine group (NG) received 25 microg neostigmine; the fentanyl-neostigmine 10 microg group (FNG10) was given 10 microg fentanyl plus 10 microg neostigmine; and the fentanyl-neostigmine 25 microg group (FNG25) received 25 microg fentanyl plus 25 microg neostigmine. Pain and nausea were evaluated using a 10-cm visual analog scale (VAS). MAIN RESULTS: The analgesic consumption, in 24 hours was greatest in CG, next highest in NG, FG, and FNG10 where consumption was the same in the three groups; and least in FNG25 (p < 0.05). The time to first rescue analgesic medication was greatest for FNG25 compared with the other groups (>5 hours compared with 2 to 3 hours; p < 0.05). VAS showed no statistically significant differences for pain impression, intraoperative and postoperative nausea, or occurrence of vomiting (p > 0.05). CONCLUSION: The combination of 25 microg neostigmine with 25 microg fentanyl given intrathecally with 15 mg of hyperbaric bupivacaine delayed postoperative pain and lowered the number of rescue analgesics. Because the better quality of analgesia was obtained with an increased (although not statistically significant difference) incidence of untoward side effects, larger samples should be studied before its routine use is recommended.

Adult↗
PubMed1999

Neostigmine for the treatment of acute colonic pseudo-obstruction.

BACKGROUND: Acute colonic pseudo-obstruction -- that is, massive dilation of the colon without mechanical obstruction -- may develop after surgery or severe illness. Although it may resolve with conservative therapy, colonoscopic decompression is sometimes needed to prevent ischemia and perforation of the bowel. Uncontrolled studies have suggested that neostigmine, may be an effective treatment. METHODS: We studied 21 patients with acute colonic pseudo-obstruction. All had abdominal distention and radiographic evidence of colonic dilation, with a cecal diameter of at least 10 cm, and had had no response to at least 24 hours of conservative treatment. We randomly assigned 11 to receive 2.0 mg of neostigmine intravenously and 10 to receive intravenous saline. A physician who was unaware of the patients' treatment assignments recorded clinical response (defined as prompt evacuation of flatus or stool and a reduction in abdominal distention), abdominal circumference, and measurements of the colon on radiographs. Patients who had no response to the initial injection were eligible to receive open-label neostigmine three hours later. RESULTS: Ten of the 11 patients who received neostigmine had prompt colonic decompression, as compared with none of the 10 patients who received placebo (P<0.001). The median time to response was 4 minutes (range, 3 to 30). Seven patients in the placebo group and the one patient in the neostigmine group without an initial response received open-label neostigmine; all had colonic decompression. Two patients who had an initial response to neostigmine required colonoscopic decompression for recurrence of colonic distention; one eventually underwent subtotal colectomy. Side effects of neostigmine included abdominal pain, excess salivation, and vomiting. Symptomatic bradycardia developed in two patients and was treated with atropine. CONCLUSIONS: In patients with acute colonic pseudo-obstruction who have not had a response to conservative therapy, treatment with neostigmine rapidly decompresses the colon.

Abdominal Pain↗
PubMed1987

Interaction of adrenaline with neostigmine and tubocurarine at the skeletal neuromuscular junction.

The effects of neostigmine, and of neostigmine with adrenaline, on the response of the rat isolated hemidiaphragm to stimulation of the phrenic nerve are reported. Neostigmine augmented the response: a maximum augmentation occurred at a concentration of 6.4 X 10(-7) mol litre-1. At greater concentrations of neostigmine the response was reduced. Adrenaline in the absence of neostigmine produced no significant change in the contraction response. However, in the presence of neostigmine further augmentation occurred and achieved a maximum in the presence of adrenaline 3.2 X 10(-7)-1.3 X 10(-6) mol litre-1. Adrenaline 4.0 X 10(-8)-1.3 X 10(-6) mol litre-1 combined with neostigmine 4.0 X 10(-8)-6.4 X 10(-7) mol litre-1 reversed tubocurarine-induced neuromuscular blockade more effectively than neostigmine alone (P less than 0.001). Adrenaline appeared to enhance the antagonistic effect of neostigmine by increasing acetylcholine release and by enhancing the response at the post-junctional acetylcholine receptor.

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