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We report a case of accidental intrathecal administration of large dose ( micrograms) of neostigmine methylsulphate in a patient scheduled for repair of. The present study was conducted to study the efficacy and safety of intrathecal neostigmine with bupivacaine in two different doses. Methods. S Gupta. Postoperative Analgesia With Intrathecal Neostigmine; Two Different Doses Of 75 µgms And 50 µgms With Heavy Bupivacaine.. The Internet Journal of.

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Intrathecal neostigmine for postoperatrive analgesia in caesarean section.

We’ll send you your username identified by your email account. Login Log in to access full content You must be logged in to access this feature. Eisenach Professor and Francis M. Anesthesiology 10Vol. You will receive an email whenever this article is corrected, updated, or cited in the literature.

You can manage this neostigmie all other alerts in My Account. You must be intrathecwl in to access this feature. Human volunteers achieve dose-dependent analgesia from doses more than [micro sign]g. Few dose-response data exist for intrathecal neostigmine for postoperative analgesia. A larger study with 15 patients per group showed a dose-independent reduction in morphine use after administration of 25, 50, and [micro sign]g intrathecal neostigmine compared with a control after lower-extremity orthopedic surgery.

After giving informed consent, 92 women classified as physical status 1 or 2 by the American Society of Anesthesiologists who were scheduled for total vaginal hysterectomy during spinal anesthesia were studied at the three university centers.

Women older than 70 yr; those with known hypersensitivity to bupivacaine, neostigmine, propofol, or morphine; those with bradyarrhythmia; and those unable to understand the consent process or the use of the patient-controlled analgesia device were excluded. The study was performed in a prospective, randomized, double-blind, placebo-controlled manner. Investigators at the coordinating center prospectively assigned neostigmine group quotas based on a computer-generated randomized balanced design and the anticipated availability of potential study patients.

No premedication was administered on the night before surgery, although benzodiazepine ijtrathecal not discontinued in any patients who were routinely receiving it at night. On the day of surgery, an intravenous catheter was inserted, and midazolam, up to 4 mg in 0. Lumbar puncture was performed in the neodtigmine room with the patient in the lateral decubitus position, nfostigmine either a or gauge Whitacre needle at the L3-L4 or L4-L5 interspace. After free flow of clear cerebrospinal fluid was obtained, the study solution was injected, with the needle orifice facing the ceiling.

The final volume of 3 ml was injected at 1 ml per 10 s. Patients received 2 ml bupivacaine, 0. The neostigmine study neostibmine was prepared immediately before lumbar puncture by a local anesthesiologist who was not involved in the study, and the investigator blinded to the study solution content added this 1 ml of solution to the bupivacaine solution.

Patients were positioned supine immediately after injection and in the lithotomy position within 15 min of spinal injection. After adequate sensory blockade neostifmine spinal bupivacaine was established, all patients received propofol by constant intravenous infusion that was titrated to deep sedation during surgery. Sensory level to pinprick was assessed every 5 min for 15 min after spinal injection, when patients arrived in the recovery room, and every 30 min until discharge.


Blood pressure was monitored noninvasively every 5 min during surgery, and heart rate and oxyhemoglobin saturation were continuously monitored throughout surgery.

Blood pressure and heart rate were recorded before drug injection, at 5-min intervals during surgery, at min intervals after surgery until 3 h from the time of intrathecal injection, hourly until recovery room discharge, then every 6 h until 24 h after injection. Nausea neosigmine any time during the study was treated with either mg ondansetron or 20 mg metoclopramide administered intravenously. Any intraoperative pain was treated with neostigminne fentanyl in [micro sign]g increments.

Pain was assessed by the cm VAS at arrival in the recovery room and every 30 min until discharge and was treated with intravenous patient-controlled morphine, with initial settings of a 2-mg dose, min lockout, and an hourly limit ihtrathecal 12 mg. The VAS was also recorded at discharge from the recovery room and 24 h after the study solution was injected.

At these same times, patients rated their nausea on a cm VAS ndostigmine. Groups were compared for demographic data, and the duration of surgery and time in the recovery room were determined by one-way analysis of variance. The time-to-first-patient-controlled analgesia use was compared among groups using the Kaplan-Meier analysis and the Wilcoxon’s rank sum. The incidence of adverse events and adjuvant drug use were compared among the groups by chi-squared analysis.

Blood pressure, heart rate, and VAS scores were compared among the groups by two-way analysis of variance for subsequent measures. Categoric scale data and cumulative morphine use for 8 h after intrathecal injection the expected duration of drug action were compared among the groups using the Kruskal-Wallis test followed by the Wilcoxon’s rank sum test.

P values were corrected by post hoc tests, and a level of 0. Demographic characteristics, duration of surgery, duration of stay in the recovery room, or intraoperative fluid or drug administration did not differ in the neostigmine-dose groups Table 1.

Blood pressure or heart rate before intrathecal injection or after bupivacaine injection did not differ in the groups Figure 1. Similarly, blood pressure or heart rate in the recovery room or for the subsequent 24 h data not shown did not differ. Neostigmine did not affect the onset of sensory blockade from intrathecal bupivacaine Table 2. Demographic and Intraoperative Neostigmne.

Mean arterial blood pressure upper and heart rate lower after injection at time 0 of intrathecal bupivacaine; 15 mg with 1 ml saline [black square] ; or 25 [micro sign]g, [white square]50 [micro sign] [black circle]or 75 [micro sign]g [white circle] neostigmine.

The groups did not differ. Only the [micro sign]g dose of neostigmine increased the nausea score in the recovery room Figure 2.

Nausea scores on a cm visual analog scale at admission to the postanesthesia care unit for the following 2 h, at time of discharge from the postanesthesia care unit, and at 24 h after surgery. The analgesic effect of intrathecal neostigmine was dose independent. All doses of neostigmine reduced VAS pain scores in the recovery room to a similar degree Figure 3.

All doses of neostigmine prolonged the time-until-first-morphine-dose by a similar amount. The time-to-first-morphine-dose median, 25th to 75th percentiles was 3 h 3 to 4 h after saline administration, 4 h 4 to 6. Similarly, there was a dose-independent reduction in patient-controlled analgesia morphine intratyecal during the first 8 h after intrathecal injection of neostigmine Figure 4.

Pain scores on a cm visual analog scale at admission itrathecal the postanesthesia care unit, for the following 2 h, at time of discharge from the postanesthesia care unit, and at 24 h after surgery. Cumulative intravenous patient-controlled analgesia morphine use after intrathecal injection of saline [black square] or 25 [micro sign]g [white square]50 [micro sign]g [black circle]or 75 [micro sign]g [white circle] neostigmine. This is the first, large, dose-response study of low doses of intrathecal neostigmine for postoperative analgesia, and it provides new information regarding dose-related analgesia, nausea, and hemodynamic actions of this agent in different patient populations at the three sites.


This is confirmed by studies with sheep that showed an increase in acetylcholine concentrations neostogmine lumbar cerebrospinal fluid during painful electrical stimulation.

Intrathecal neostigmine for postoperatrive analgesia in caesarean section.

An alternative explanation to the effect of small doses of neostigmine in the current study relates to the mechanisms of action of systemic opioids in producing analgesia. Intravenous morphine injection is thought to activate descending spinal inhibitory pathways, some of which are noradrenergic, and, as such, morphine injection increases concentrations of norepinephrine in lumbar cerebrospinal fluid in animals and humans.

Regardless of the mechanism, the current study suggests that doses of intrathecal neostigmine of less than 50 [micro sign]g reduce intravenous morphine requirements for 8 h after vaginal hysterectomy.

Previous literature does not consistently report a dose-dependent analgesic effect of neostigmine. As reviewed previously, large doses [micro sign]g uniformly produce analgesia, but also nausea. The clinical usefulness of this reduction in morphine use for 8 h may be limited.

It is conceivable that the use of propofol during surgery for sedation reduced nausea after intrathecal neostigmine from what would be seen with concomitant propofol administration. This stimulation may counteract the sympatholytic actions of the local anesthetic, bupivacaine, or of the [Greek small letter alpha] 2-adrenergic agonist clonidine. We did not observe a reduced incidence of hypotension in women receiving neostigmine, suggesting that clinically useful doses of intrathecal neostigmine would not affect intrathecal bupivacaine-induced hypotension.

In conclusion, [micro sign]g intrathecal neostigmine produces a dose-independent reduction in morphine use for 8 h after vaginal hysterectomy and a dose-independent increase in the need for antiemetic treatment. These data suggest that intrathecal neostigmine alone is unlikely to produce complete analgesia after surgery and that even doses less than 50 [micro sign]g may increase the incidence of postoperative nausea. Naguib M, Yaksh TL: Antinociceptive effects of spinal cholinesterase inhibition and isobolographic analysis of the interaction with [micro sign] and [Greek small letter alpha] 2 receptor systems.

Phase I safety assessment of intrathecal neostigmine in humans. Dose-response study of intrathecal morphine versus intrathecal, neostigmine, their combination, or placebo for postoperative analgesia in patients undergoing anterior and posterior vaginoplasty. Anesth Analg ; Analgesic effect of subarachnoid neostigmine in two patients with cancer pain. Cerebrospinal fluid norepinephrine and acetylcholine concentrations during acute pain.

Postoperative analgesia from intrathecal neostigmine in sheep.

Internet Scientific Publications

Intravenous ketamine or fentanyl prolongs postoperative analgesia after intrathecal neostigmine. The effects of intrathecal neostigmine on somatic and visceral pain: Improvement by association with a peripheral anticholinergic. Intrathecal neostigmine for postoperative analgesia after orthopedic surgery.

J Clin Anesth ; 9: Intravenous opioids stimulate norepinephrine and acetylcholine release in spinal cord dorsal horn-Systematic studies in sheep intrathecao an observation in a human.

Intrathecal neostigmine for post-cesarean section analgesia: Intrathecal cholinergic agonists lessen bupivacaine spinal-block-induced hypotension in rats. Spinal neostigmine diminishes, but does not abolish, hypotension from spinal bupivacaine in sheep. Neostigmine counteracts spinal clonidine-induced hypotension in sheep. Interaction between intrathecal neostigmine and epidural clonidine in human volunteers. Intratheecal in to access full content You must be logged in to access this feature.

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