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 IT neostigmine has been used as an adjunct to spinal anesthesia.

The purpose of this study was to determine whether a combination of low-dose neostigmine IT would enhance analgesia of a fixed dose of fentanyl IT, in patients undergoing unilateral total knee replacement TKR surgery with spinal intrwthecal. A G epidural catheter was introduced through the L3—L4 interspace with patient in the sitting position, followed by spinal anesthesia administration through the L3—L4 interspace.

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Fifteen milligrams of hyperbaric bupivacaine 3 ml plus the test drug 0. The test drug was normal saline 0. Characteristics of sensory and motor block, heart rate, and blood pressure were recorded intraoperatively.

Postoperatively, pain scores, postoperative nausea and vomiting PONV scores, and sedation scores, and postoperative analgesic dose were recorded. Forty-five patients were enrolled in this study and 43 patients were subjected to statistical intratheca. The incidence of nausea and vomiting was not increased in group III patients. The addition of 1 mcg neostigmine IT increased the duration of analgesia and decreased the neostigmune consumption in 24 h in TKR. There was no increase in the incidence of adverse effects.

Intrathecal IT neostigmine has been used as an adjunct to spinal anesthesia SA for the prevention neostihmine acute perioperative pain. It has been shown to potentiate opioid analgesia[ 1 — 4 ] while reducing undesirable side effects such as somnolence and respiratory depression.

The benefits of adding lower neostigmine intratecal to potentiate fentanyl analgesia, however, have not been evaluated to date. We planned to determine whether combination of low-dose 1 mcg neostigmine IT would enhance analgesia from a fixed IT dose of fentanyl, in patients undergoing unilateral total knee replacement TKR surgery with SA. After obtaining the institutional ethics intrthecal clearance and written informed consent, 45 adult patients of American Society of Anaesthesiologists ASA 1 or 2, undergoing unilateral TKR surgery under regional anesthesia, were included in the study.

Patients were randomly allocated into three groups of 15 patients each. Patients were premedicated with 0. A G epidural catheter was introduced through the L3—L4 interspace with patient in the sitting intrathdcal, followed by SA through the L3—L4 interspace. A total volume of 3.

The IT drug injected was 15 mg hyperbaric bupivacaine 3 ml plus the test drug 0. Patients were placed in the supine position immediately after spinal injection.

One anesthesiologist prepared the drug and administered the IT drug, while another anesthesiologist, who was blinded to the drug randomization, monitored the intraoperative and postoperative period. Intraoperative sensory loss assessment was done using pin-prick test at 5, 10, 15, 20 min after IT injection of the study drug and every 30 min thereafter, until the end of surgery.

Motor blockade of lower extremities was measured using 4-point modified Bromage scale at 5 min intervals for the first 20 min after injection of the IT drug. Blood pressure was monitored noninvasively every 5 min throughout the surgery, and heart rate and oxyhemoglobin saturation were monitored continuously throughout the surgery.

Postoperative assessment included pain scores, postoperative nausea and vomiting PONV scores 5-point scaleand sedation scores 4-point scalerecorded at min interval for first 4 h and then 4 hourly thereafter, for 24 h postoperatively. Subsequently, an epidural top up of 8 ml of 0. The total number of rescue analgesics administered in 24 h was noted.

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Nausea was scored by the patient using a 5-point scale. One or more emetic episodes were treated using ondansetron 4 mg IV. For patients experiencing more than one episode of nausea, the scores were averaged. However, to compensate for possible dropouts, we included 15 patients in each group. The data were analyzed statistically. Demographic data age, weight, height, gender and duration of surgery were compared among the groups by one-way analysis of variance.

Blood pressure, heart rate, maximum level and time to attain peak level of sensory block, time to complete motor blockade, and VAS scores were compared among the groups by two-way analysis of variance followed by Mann—Whitney test.

The duration of complete analgesia, duration of effective analgesia, and the number of rescue analgesics in 24 h was compared using Kruskal—Wallis test, applied along with Mann—Whitney test.

A total of 45 patients were recruited for the study. Two patients, one each from groups I and II, were excluded from the study as general anesthesia had to be administered due to the failure of SA and accidental dislodgement of epidural catheter, respectively. The maximum level of sensory block, time to peak sensory block, and time to complete motor block were comparable among the groups [ Table 3 ].

The intraoperative hemodynamic characteristics were also comparable and intraoperative mephenteramine consumption was similar among the groups. Analgesia characteristics are shown in Table 4. The baseline postoperative VAS scores were comparable in the three groups. Six patients in the control group required antiemetic once and only two patients twice. However, six patients in the fentanyl group and two patients in the fentanyl—neostigmine group received ondansetron once and no patient in either group needed antiemetic twice or more.

A dose-independent reduction of postoperative analgesia requirement and dose-dependent increase in the incidence of PONV has been demonstrated using various doses of IT neostigmine with bupivacaine.

However, the study was underpowered. Moreover, the risk of delayed respiratory depression with the use of neuraxial morphine is a great concern. We therefore hypothesized that 1 mcg IT neostigmine would augment the analgesic efficacy of IT fentanyl and bupivacaine, without increasing the incidence of untoward side effects.

As TKR surgery involves severe pain in the postoperative period, we performed our study in this subset of patients. All patients who received IT neostigmine in combination with IT bupivacaine and fentanyl required less epidural top ups in 24 h. However, no increase in the incidence of nausea and vomiting was noted with addition of 1 mcg neostigmine IT to fentanyl—bupivacaine IT combination. IT injection of neostigmine produces analgesic effects.

The inhibition of spinal cholinesterase by neostigmine results in an increase of endogenous acetylcholine, which is most likely released from intrinsic cholinergic neurons within the dorsal horn of the spinal cord. A possible explanation for the effect of small doses of IT neostigmine in enhancing the duration of analgesia produced by opioid relates to the mechanism of action of opioids in producing analgesia. Opioid increases the concentration of norepinephrine in lumbar cerebrospinal fluid which in turn produces analgesia in part by activating spinal cholinergic neurons to release acetylcholine.

In our study, the time to reach maximum level of sensory block and the peak level attained was not influenced by the inntrathecal of IT neostigmine.

Similar effect was demonstrated by Lauretti et al ,[ 25 ] in patients undergoing vaginal hysterectomy. This is possibly due to a difference in the onset of action of IT neostigmine[ 26 ] and IT bupivacaine. No patient in the IT neostigmine—fentanyl—bupivacaine group developed intraoperative intrrathecal or bradycardia requiring treatment. Although similar effects on hemodynamics during SA using low-dose IT neostigmine were observed by few researchers,[ 7neoatigmine ] this could not be explained on the basis of cardiostimulatory effect of spinal neostigmine as this requires large doses in humans.

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Use of low-dose IT neostigmine in an attempt to reduce the incidence of untoward side effects, particularly PONV, while retaining its analgesic efficacy has been tried by many investigators. In patients undergoing below knee surgery, Lauretti et al [ 8 ] showed a dose-independent reduction of postoperative analgesia intratheccal, but a dose-dependent increase in the incidence of PONV following addition of various doses of IT neostigmine ranging from 25 to mcg neosigmine 15 mg of hyperbaric bupivacaine 0.

Even the dose as low as 6. We observed a lower incidence of emesis and lesser need for antiemetic though not significant in patients receiving 1 mcg IT neostigmine as an adjunct to IT bupivacaine and IT fentanyl. This could be due to lower VAS scores in this group. All patients were either awake or arousable to command in the postoperative period. The commercially available preparation of neostigmine containing methylparaben as an antioxidant was used in the present study.

Although solutions containing preservatives should not be injected IT, methyl- and propyl-paraben have not been demonstrated to be toxic. Phase I tolerability and safety study of the commercially available neostigmine formulations in human volunteers found no evidence of toxicity. In conclusion, the addition of 1 mcg neostigmine IT increased the duration of postoperative analgesia and decreased the analgesic consumption in TKR surgery.

National Center for Biotechnology InformationU. J Anaesthesiol Clin Pharmacol. Author information Copyright and License information Disclaimer. This is an open-access article distributed under the terms of the Creative Commons Attribution-Noncommercial-Share Alike 3.

This article has been cited by other articles in PMC. Abstract Background and Aim: Intrathecal fentanyl, intrathecal neostigmine, spinal neostigmine, total knee neostigmlne surgery.

Introduction Intrathecal IT neostigmine has been used as an adjunct to spinal anesthesia SA for the prevention of acute perioperative pain. Materials and Methods After obtaining the institutional ethics committee clearance and written informed consent, 45 adult patients of American Society of Anaesthesiologists ASA 1 or 2, undergoing unilateral TKR surgery under regional anesthesia, were included in the study. Table 1 Study groups. Open in a separate neoxtigmine.

Results A total of 45 patients were recruited for the study. Table 2 Demographic characteristics and surgical duration. Table 3 Characteristics of subarachnoid block. Table 4 Analgesia characteristics.

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Discussion A dose-independent reduction of postoperative analgesia requirement and dose-dependent increase in the incidence of PONV has been demonstrated using various doses of IT neostigmine with bupivacaine. Footnotes Source of Support: Nil Conflict of Interest: Flodmark S, Wrammer T. The analgesia action of morphine, serine, and prostigmine studied by a modified Handy-Wolff-Goodel method. Comparison of the antinociceptive activity of physostigmine, oxotremorine and morphine in the mouse.

Combined intrathecal fentanyl and neostigmine: Dose response study of intrathecal morphine versus intrathecal neostigmine, their combination, or placebo for postoperative analgesia in patients undergoing anterior and posterior vaginoplasty. Effect of physostigmine on morphine-induced postoperative pain and somnolence. Activation of cholinergic mechanisms in the medulla oblongata reverse intravenous opioid-induced respiratory depression. J Pharmacol Exp Ther. Dose-response intrahhecal of spinal neostigmine added to bupivacaine spinal anesthesia in volunteers.

Intrathecal neostigmine for post operative analgesia after orthopaedic surgery.