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      Effect of Intrathecal Midazolam in the Severity of Pain in Cesarean Section: A Randomized Controlled Trail

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          Abstract

          Background

          The benzodiazepines are used primarily for anxiolysis, amnesia and sedation. However, recent investigations have shown that some forms of this group of drugs have also direct effect on pain. This study aims to determine the effect of midazolam in reducing the severity of pain in women scheduled for elective cesarean section.

          Methods

          In a prospective, double blind randomized controlled trial, two groups parallel study, was conducted in Imam Reza/Moatazedi Hospital, an affiliate of Kermanshah University of Medical Sciences. Parturient women who met study inclusion criteria were consecutively assigned into either experimental (n=62) or control groups (n=62). Women in the experimental group received bupivacaine (10 mg) plus intrathecal midazolam (2 mg/ml) (BM) and those in the control group received bupivacaine plus normal saline (BNS). The outcome pain severity was measured by Verbal Numerical Rating Scale.

          Results

          In comparison with the BNS group, mothers in the BM group reported a significant relief in pain (15 min and 120 min) after the surgery. There were no significant differences between the groups regarding the intensity of pain 5, 30, 60 and 240 min after the surgery. The average time until the first dose of additional analgesic, per mother’s request was 142.18±55.19 min in the BNS vs 178.06±77.33 min in the BM group.

          Conclusion

          Combination of bupivacaine plus intrathecal midazolam was an effective anesthetic technique to provide improvement in pain. The onset of sedation was faster in the BM group compared with the BNS group. The duration of effective analgesia, and the time for regression of sensory analgesia was the same in both groups in our study. However, incidence of nausea and vomiting was higher in the experimental group.

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          Most cited references44

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          Midazolam: pharmacology and uses.

          Midazolam is an imidazobenzodiazepine with unique properties when compared with other benzodiazepines. It is water soluble in its acid formulation but is highly lipid soluble in vivo. Midazolam also has a relatively rapid onset of action and high metabolic clearance when compared with other benzodiazepines. The drug produces reliable hypnosis, amnesia, and antianxiety effects when administered orally, intramuscularly, or intravenously. There are many uses for midazolam in the perioperative period including premedication, anesthesia induction and maintenance, and sedation for diagnostic and therapeutic procedures. Midazolam is preferable to diazepam in many clinical situations because of its rapid, nonpainful induction and lack of venous irritation. Compared with thiopental, midazolam is not as rapid acting nor predictable in hypnotic effect. It will not replace thiopental as an induction agent. Advantages of midazolam over thiopental are those of the more versatile pharmacologic properties of a benzodiazepine compared with a barbiturate such as amnestic and anxiolytic properties. Midazolam should be a useful addition to the formulary.
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            Cauda equina syndrome after continuous spinal anesthesia.

            Four cases of cauda equina syndrome occurring after continuous spinal anesthesia are reported. In all four cases, there was evidence of a focal sensory block and, to achieve adequate analgesia, a dose of local anesthetic was given that was greater than that usually administered with a single-injection technique. We postulate that the combination of maldistribution and a relatively high dose of local anesthetic resulted in neurotoxic injury. Suggestions that may reduce the potential for neurotoxicity are discussed. Use of a lower concentration and a "ceiling" or maximum dose of local anesthetic to establish the block should be considered. If maldistribution of local anesthetic is suspected (as indicated by a focal sensory block), the use of maneuvers to increase the spread of local anesthetic is recommended. If such maneuvers prove unsuccessful, the technique should be abandoned.
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              Ketamine and midazolam neurotoxicity in the rabbit.

              Ketamine and midazolam can produce analgesia following intrathecal administration in rabbits. However, neurotoxicity studies are required before these agents can be considered safe for clinical use. The aim of this study was to evaluate by histologic and blood-brain barrier (BBB) studies whether ketamine or midazolam could be used as an alternative to local anesthetics or opioids to produce spinal analgesia. Forty white New Zealand rabbits were randomly assigned to four groups of 10. In the conscious animal, 0.3 ml 0.9% saline solution, 1% lidocaine, 1% ketamine, or 0.1% midazolam was intrathecally injected intracisternally using a modification of the technique of Yaksh et al. Light and fluorescence microscopy were performed on transverse spinal cord sections by a neuropathologist unaware of the administered agents. All spinal cord section slides were scored within four zones: upper cervical, lower cervical, median thoracic, and lumbar segments. Spinal cord homogeneous lesions with higher scores than those of lidocaine-treated animals were considered abnormal. The BBB study showed evidence of neurotoxicity for ketamine, whereas light microscopy indicated no significant differences in comparison with saline and lidocaine. Midazolam-treated rabbits showed significant changes in both BBB and light microscopy studies. In view of these results, the intrathecal use of midazolam should be avoided in humans. Lesions observed following ketamine suggest the need for further experimental studies of the solvent and different ketamine enantiomers to establish definitively the safety of intrathecal free ketamine in humans.
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                Author and article information

                Journal
                Iran Red Crescent Med J
                Iran Red Crescent Med J
                Kowsar
                Iranian Red Crescent Medical Journal
                Kowsar
                2074-1804
                2074-1812
                May 2012
                30 May 2012
                : 14
                : 5
                : 276-282
                Affiliations
                [1 ]Department of Anesthesiology, Critical Care and Pain Management, Imam Reza Hospital, Kermanshah University of Medical Sciences, Kermanshah, Iran
                [2 ]College of Medicine, Charls Drew University of Medicine and Sciences, Los Angeles, CA, USA
                [3 ]Semel Institute for Neuroscience and Human Behavior, David Geffen School of Medicine, University of California, CA, USA
                [4 ]Karolinska Institute, Stockholm, Sweden
                Author notes
                [* ]Correspondence: Alireza Ahmadi, MD, Department of Anesthesiology, Critical Care and Pain Management, Imam Reza Hospital, Kermanshah University of Medical Sciences, Bolvar Shahid Beheshti, Kermanshah 6718818838, Iran. Tel.: +98-918-8581019, Fax: +98-831-4282670, E-mail: ahmadiar1012@ 123456yahoo.com
                Article
                3398634
                22829986
                d697f339-1dea-461d-a8e0-fc98c48f8b80
                Copyright © 2012, Kowsar Corp.

                This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

                History
                : 12 November 2011
                : 10 January 2012
                Categories
                Original Article

                Medicine
                cesarean section,intrathecal,midazolam,bupivacaine,pain
                Medicine
                cesarean section, intrathecal, midazolam, bupivacaine, pain

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