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AbdelRady MM, Abdelrahman KA, Ali WN, Ali AM, AboElfadl GM. Fentanyl versus midazolam added to bupivacaine for spinal analgesia in children undergoing infraumbilical abdominal surgery: A randomized clinical trial. EGYPTIAN JOURNAL OF ANAESTHESIA 2022. [DOI: 10.1080/11101849.2022.2031810] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/19/2022] Open
Affiliation(s)
- Marwa Mahmoud AbdelRady
- Lecturer in Anesthesia and Intensive Care Department, Faculty of Medicine, Assiut University, Assiut, Egypt
| | | | - Wesam Nashat Ali
- Lecturer in Anesthesia and Intensive Care Department, Faculty of Medicine, Assiut University, Assiut, Egypt
| | - Ahmed Mohammed Ali
- Lecturer in General Surgery Department, Faculty of Medicine, Assiut University, Assiut, Egypt
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Amin OAI, Ibrahem MAM, Salem DAE. Nalbuphine versus Midazolam as an Adjuvant to Intrathecal Bupivacaine for Postoperative Analgesia in Patients Undergoing Cesarean Section. J Pain Res 2020; 13:1369-1376. [PMID: 32606903 PMCID: PMC7295533 DOI: 10.2147/jpr.s242545] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/17/2019] [Accepted: 04/25/2020] [Indexed: 11/23/2022] Open
Abstract
Background and Purpose Adding adjuvants to intrathecal hyperbaric bupivacaine provides long analgesic duration with less adverse effects. The aim of this study was to compare intrathecal nalbuphine versus midazolam in patients undergoing cesarean section. Clinical Trial ID NCT03918187. Patients and Methods This was a prospective randomized controlled study conducted on 90 females undergoing cesarean section under spinal anesthesia who were randomly allocated to three equal groups of 30 patients each: group C received hyperbaric bupivacaine 12.5 mg plus 0.5 mL saline, group N received hyperbaric bupivacaine 12.5 mg plus 1 mg nalbuphine, group M received hyperbaric bupivacaine 12.5 mg plus 2.5 mg midazolam. The onset and duration of sensory and motor block, effective analgesic time, analgesic requirements, adverse effects, sedation, and Apgar scores were recorded. Results There was significant rapid onset of sensory and motor block (1.95±.44 and 3.50±0.43 min) with slower regression of sensory block and time to bromage I (211.6±13.2 and 219.8±20.2 min) in group N compared to groups M, C (p < 0.001), with statistically significant rapid onset and long duration of both blocks in group M compared to C (p<0.001). The effective analgesic time was significantly prolonged in group N (263.7±16.3) compared to groups M and C (224.2 ± 18.6, 185.5±17.45), respectively, (p<0.001) and prolonged in group M compared to C (p<0.001), with increase in analgesic requirement in group C compared to groups N and M (p<0.001) and no significant difference between groups N and M. There was higher sedation score in groups N, M (1.78±0.63, 2.75±0.54), respectively, compared to group C (0.61±0.12) (p<0.001) with lower Apgar score in group M (6.9±0.73) at one minute than in groups N, C (7.1±0.91, 7.7±0.84) (p<0.001). There was no significant difference between groups regarding the adverse effects. Conclusion Adding 1 mg nalbuphine to 12.5 mg hyperbaric bupivacaine provided more effective postoperative analgesia than adding 2.5 mg midazolam, with less non-significant adverse effects in midazolam group in patients undergoing elective cesarean section.
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Ibrahim M, Gomaa E. Efficacy of midazolam addition to local anesthetic in peribulbar block : Randomized controlled trial. Anaesthesist 2019; 68:143-151. [PMID: 30627737 DOI: 10.1007/s00101-018-0525-3] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/01/2018] [Revised: 11/21/2018] [Accepted: 11/24/2018] [Indexed: 10/27/2022]
Abstract
BACKGROUND Peribulbar block is considered a safe option for patients undergoing cataract surgery. The limited duration of regional eye blocks was shown to be the main problem. The objective of this study was to evaluate the effects of adjuvant midazolam (in two concentrations) to lidocaine in the peribulbar block. MATERIAL AND METHODS This study included 90 adult patients aged 40-70 years undergoing cataract surgery. Each patient was appointed to one of three groups. Group C received a single injection of a peribulbar block using a combination of lidocaine 2% and hyaluronidase 15 IU/ml, group M1 received a combination of lidocaine 2%, hyaluronidase 15 IU/ml plus midazolam 50 µg/ml and group M2 received lidocaine 2%, hyaluronidase 15 IU/ml plus midazolam 100 µg/ml. RESULTS The quality of the peribulbar block showed significant improvement among groups by one-way ANOVA (p = 0.002). The mean onset time of the sensory block was significantly shorter in the M2 and M1 groups (1.66 min and 2.17 min, respectively) compared to the control group C (2.52 min), while the onset of lid and globe akinesia lacked significance between the three groups (p = 0.23 and 0.06, respectively). Significance in mean values was found between the control (C) and M2 groups regarding orbicularis oculi function, digital spear pressure, topical anesthetic sting and the total score (P-values = 0.004, 0.016, 0.033 and 0.001, respectively). The duration of lid akinesia and sensory anesthesia were significantly different between the three groups (P = 0.048 and P<0.001, respectively) whereas the duration of globe akinesia was insignificant (P = 0.432). CONCLUSION Addition of midazolam to local anesthetic significantly improved the quality of peribulbar block, hastened the onset of sensory anesthesia, lid and globe akinesia and increased the duration of analgesia without notable side effects.
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Affiliation(s)
- M Ibrahim
- Department of Anesthesiology, Faculty of Medicine, Zagazig University, Zagazig, Egypt.
- Al Jedaani Hospital - AL Safa Dist., Prince Moteb Street, P.O.Box 7500, 21462, Jeddah, Saudi Arabia.
| | - E Gomaa
- Department of Anesthesiology, Faculty of Medicine, Zagazig University, Zagazig, Egypt
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Exploring Nonopioid Analgesic Agents for Intrathecal Use. Neuromodulation 2018. [DOI: 10.1016/b978-0-12-805353-9.00068-1] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/18/2022]
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Swain A, Nag DS, Sahu S, Samaddar DP. Adjuvants to local anesthetics: Current understanding and future trends. World J Clin Cases 2017; 5:307-323. [PMID: 28868303 PMCID: PMC5561500 DOI: 10.12998/wjcc.v5.i8.307] [Citation(s) in RCA: 120] [Impact Index Per Article: 15.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/05/2017] [Revised: 05/03/2017] [Accepted: 05/19/2017] [Indexed: 02/05/2023] Open
Abstract
Although beneficial in acute and chronic pain management, the use of local anaesthetics is limited by its duration of action and the dose dependent adverse effects on the cardiac and central nervous system. Adjuvants or additives are often used with local anaesthetics for its synergistic effect by prolonging the duration of sensory-motor block and limiting the cumulative dose requirement of local anaesthetics. The armamentarium of local anesthetic adjuvants have evolved over time from classical opioids to a wide array of drugs spanning several groups and varying mechanisms of action. A large array of opioids ranging from morphine, fentanyl and sufentanyl to hydromorphone, buprenorphine and tramadol has been used with varying success. However, their use has been limited by their adverse effect like respiratory depression, nausea, vomiting and pruritus, especially with its neuraxial use. Epinephrine potentiates the local anesthetics by its antinociceptive properties mediated by alpha-2 adrenoreceptor activation along with its vasoconstrictive properties limiting the systemic absorption of local anesthetics. Alpha 2 adrenoreceptor antagonists like clonidine and dexmedetomidine are one of the most widely used class of local anesthetic adjuvants. Other drugs like steroids (dexamethasone), anti-inflammatory agents (parecoxib and lornoxicam), midazolam, ketamine, magnesium sulfate and neostigmine have also been used with mixed success. The concern regarding the safety profile of these adjuvants is due to its potential neurotoxicity and neurological complications which necessitate further research in this direction. Current research is directed towards a search for agents and techniques which would prolong local anaesthetic action without its deleterious effects. This includes novel approaches like use of charged molecules to produce local anaesthetic action (tonicaine and n butyl tetracaine), new age delivery mechanisms for prolonged bioavailability (liposomal, microspheres and cyclodextrin systems) and further studies with other drugs (adenosine, neuromuscular blockers, dextrans).
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Shukla U, Prabhakar T, Malhotra K, Srivastava D. Dexmedetomidine versus midazolam as adjuvants to intrathecal bupivacaine: A clinical comparison. J Anaesthesiol Clin Pharmacol 2016; 32:214-9. [PMID: 27275052 PMCID: PMC4874077 DOI: 10.4103/0970-9185.182105] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/18/2023] Open
Abstract
BACKGROUND AND AIMS Trials are being carried out to identify an adjuvant to intrathecal bupivacaine that preferably potentiates postoperative analgesia. This prospective, randomized, double-blind study was aimed to compare the onset and duration of sensory and motor block, postoperative analgesia and adverse effects of dexmedetomidine or midazolam given with 0.5% hyperbaric bupivacaine for spinal anesthesia. MATERIAL AND METHODS A total of 80 patients, scheduled for vaginal hysterectomies, were randomly allocated to Group D (n = 40) to receive intrathecally 3.0 mL 0.5% hyperbaric bupivacaine +5 ug dexmedetomidine in 0.5 mL of normal saline; and Group M (n = 40) to receive 3 mL of 0.5% hyperbaric bupivacaine +2 mg midazolam in 0.4 mL (5 mg/mL) +0.1 mL normal saline. The onset, duration of sensory and motor block, time to first postoperative analgesia and side effects were noted. Power and Sample size (PS) version 3.0.0.34 was used for power and sample size calculation. Statistical analysis was performed using Microsoft (MS) Office Excel software with the Student's t-test and Chi-square test (level of significance P = 0.05). RESULTS Duration of sensory, motor blockade and time to the first requirement of analgesia were significantly higher in Group D. Postoperative visual analog scale was significantly less in Group D than Group M. Both groups were similar with respect to sedation, hemodynamic variables and side-effects. CONCLUSION Intrathecal dexmedetomidine was better adjuvant than midazolam as it produces significantly longer duration of sensory block, reduced doses of postoperative analgesic agents with comparable side-effects.
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Affiliation(s)
- Usha Shukla
- , Department of Anaesthesiology and Critical Care, U. P. Rural Institute of Medical Sciences and Research, Saifai, Etawah, Uttar Pradesh, India
| | - Tallamraju Prabhakar
- Department of Anaesthesiology and Critical Care, Era Medical College, Lucknow, Uttar Pradesh, India
| | - Kiran Malhotra
- , Department of Anaesthesiology and Critical Care, U. P. Rural Institute of Medical Sciences and Research, Saifai, Etawah, Uttar Pradesh, India
| | - Dheeraj Srivastava
- Department of Community Medicine, U. P. Rural Institute of Medical Sciences and Research, Saifai, Etawah, Uttar Pradesh, India
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Gupta A, Kamat H, Kharod U. Efficacy of intrathecal midazolam in potentiating the analgesic effect of intrathecal fentanyl in patients undergoing lower limb surgery. Anesth Essays Res 2015; 9:379-83. [PMID: 26712978 PMCID: PMC4683495 DOI: 10.4103/0259-1162.164650] [Citation(s) in RCA: 9] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/02/2022] Open
Abstract
Introduction: The intrathecal administration of combination of drugs has a synergistic effect on the subarachnoid block characteristics. This study was designed to study the efficacy of intrathecal midazolam in potentiating the analgesic duration of fentanyl along with prolonged sensorimotor blockade. Materials and Methods: In a double-blind study design, 75 adult patients were randomly divided into three groups: Group B, 3 ml of 0.5% hyperbaric bupivacaine; Group BF, 3 ml of 0.5% hyperbaric bupivacaine + 25 mcg of fentanyl; and Group BFM, 3 ml of 0.5% hyperbaric bupivacaine + 25 mcg of fentanyl + 1 mg of midazolam. Postoperative analgesia was assessed using visual analog scale scores and onset and duration of sensory and the motor blockade was recorded. Results: Mean duration of analgesia in Group B was 211.60 ± 16.12 min, in Group BF 420.80 ± 32.39 min and in Group BFM, it was 470.68 ± 37.51 min. There was statistically significant difference in duration of analgesia between Group B and BF (P = 0.000), between Group B and BFM (P = 0.000), and between Group BF and BFM (P = 0.000). Both the onset and duration of sensory and motor blockade was significantly prolonged in BFM group. Conclusion: Intrathecal midazolam potentiates the effect of intrathecal fentanyl in terms of prolonged duration of analgesia and prolonged motor and sensory block without any significant hemodynamic compromise.
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Affiliation(s)
- Anshu Gupta
- Department of Anaesthesia, Lady Hardinge Medical College, New Delhi, India
| | - Hemlata Kamat
- Department of Anaesthesia, Pramukhswami Medical College, Anand, Gujarat, India
| | - Utpala Kharod
- Department of Anaesthesia, Pramukhswami Medical College, Anand, Gujarat, India
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Selvaraj V, Ray T. Midazolam as an adjuvant to intrathecal lignocaine: A prospective randomized control study. Saudi J Anaesth 2015; 9:393-6. [PMID: 26543455 PMCID: PMC4610082 DOI: 10.4103/1658-354x.159462] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/04/2022] Open
Abstract
CONTEXT Unfortunately in the past decade, phenomenon of transient neurologic symptoms (TNS) cast doubts on the use of lignocaine for spinal anesthesia. Intrathecal midazolam has been proved to have its role in relieving neuropathic pain. We attempted to study the role of midazolam as an adjuvant to intrathecal lignocaine. AIMS The primary objective of the study was to evaluate the effect of intrathecal midazolam as an adjuvant to spinal lignocaine in terms of quality and duration of spinal sensory blockade. The secondary objectives are to study the effect on hemodynamics and the incidence of TNS. SETTINGS AND DESIGN A prospective randomized control double-blinded study in American Society of Anesthesiology I and II surgical population. MATERIALS AND METHODS Hundred healthy adult patients scheduled for elective infraumbilical surgery were randomly assigned to group A patients received spinal anesthesia with 1.5 ml of 5% lignocaine heavy with 0.4 ml of 0.9% saline and group B (control group) received spinal anesthesia with 1.5 ml of 5% heavy lignocaine with 0.4 ml of preservative-free 0.5% midazolam. STATISTICAL ANALYSIS USED Z test for study parameters and analysis of variance was used for hemodynamic parameters in the same group. P < 0.05 was considered statistically significant. RESULTS Midazolam resulted in improved quality of sensory blockade in terms of early onset, increased duration of effective analgesia, and delayed two segment regression time and also decreases the incidence of TNS with intrathecal lignocaine. CONCLUSIONS Midazolam is an effective adjuvant to intrathecal lignocaine.
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Affiliation(s)
- Venkatesh Selvaraj
- Department of Anesthesiology, MKCG Medical College, Berhampur University, Brahmapur, Odisha, India
| | - Tapan Ray
- Department of Anesthesiology, MKCG Medical College, Berhampur University, Brahmapur, Odisha, India
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Abdollahpour A, Azadi R, Bandari R, Mirmohammadkhani M. Effects of Adding Midazolam and Sufentanil to Intrathecal Bupivacaine on Analgesia Quality and Postoperative Complications in Elective Cesarean Section. Anesth Pain Med 2015; 5:e23565. [PMID: 26473100 PMCID: PMC4602227 DOI: 10.5812/aapm.23565] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/12/2014] [Revised: 11/24/2014] [Accepted: 01/31/2015] [Indexed: 12/20/2022] Open
Abstract
BACKGROUND Intrathecal adjutants can be used for regional anesthesia (RA) in cesarean section to improve its quality in terms of time and complications. Some previous studies focused on the effects of adding sufentanil and/or midazolam to bupivacaine and compared each with using bupivacaine alone. However, there has been no study to assess the effects of using sufentanil and midazolam in combination with bupivacaine. OBJECTIVES The aim of this study was to evaluate and compare properties (time of achievement/recovery of sensory/motor blocks; and time to request opium), complications (nausea, vomiting, shivering and hypotension), and neonatal first minute Apgar score with and without the addition of midazolam (M) or sufentanil (S) to bupivacaine (B) through intrathecal injection for spinal anesthesia, after the cesarean section. PATIENTS AND METHODS In this double blind randomized clinical trial participants were randomly allocated to three equal groups: Group B (2.5 cc of bupivacaine 0.5% + 1 cc normal saline 0.9%), Group BM (2.5 cc of bupivacaine + 0.02 mg/kg midazolam) and Group BS (2.5 cc of bupivacaine 0.5% + 0.7 cc normal saline 0.9% + 1.5 µg of sufentanil, 0.3 cc). We used analysis of variance (ANOVA), post hoc test with Bonferroni adjustment, and chi-square test for statistical analysis; the analyses were performed using the SPSS-16 software. Given a significant level of 0.05, overall and pair-wise comparisons were made. RESULTS Seventy-five females participated in the study with no significant age difference (mean ± standard deviation (SD): 28.60 ± 6.06, 28.12 ± 5.29 and 28.76 ± 3.97 year; P = 0.9). Except for "time to motor block recovery" (P = 0.057), the overall differences among the three groups was significant in terms of "time to sensory/motor block" (P < 0.001), "time to sensory block recovery" (P < 0.001), and "time to request opium" (P < 0.001). In all pair-wise comparisons there was no significant difference between the BM and BS group, except for "time to request opium", which was longer in the BS group (P < 0.001). The occurrence of nausea (P = 0.02), postoperative shivering (P = 0.01) and hypotension (P < 0.001) were significantly different between the groups, unlike vomiting, where the difference was not significant (P = 0.2). All neonates had an Apgar score of nine. CONCLUSIONS The findings showed that adding sufentanil or midazolam to bupivacaine shortens the onset of spinal anesthesia and increases the time duration of anesthesia; however it does not change the motor block recovery time. Adding sufentanil delays the first request for narcotic analgesics while adding midazolam leads to a decrease in nausea and hypotension. Adding sufentanil or midazolam does not have any deleterious effect on infants' Apgar scores. However, increases shivering in patients.
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Affiliation(s)
- Abolfazl Abdollahpour
- Department of Anesthesiology, Kowsar Hospital, Semnan University of Medical Sciences, Semnan, Iran
| | - Raheleh Azadi
- Department of Anesthesiology, Kowsar Hospital, Semnan University of Medical Sciences, Semnan, Iran
| | - Razieh Bandari
- Department of Nursing,School of Rehabilitation, University of Social Welfare and Rehabilitation Sciences, Tehran, Iran
| | - Majid Mirmohammadkhani
- Research Center for Social Determinants of Health, Department of Commiunity Medicine, School of Medicine, Semnan University of Medical Sciences, Semnan, Iran
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Honarmand A, Safavi M, Nemati K, Oghab P. The efficacy of different doses of Midazolam added to Lidocaine for upper extremity Bier block on the sensory and motor block characteristics and postoperative pain. J Res Pharm Pract 2015; 4:160-166. [PMID: 26312256 PMCID: PMC4548436 DOI: 10.4103/2279-042x.162359] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/27/2022] Open
Abstract
OBJECTIVE This study was designed to evaluate the effect of different doses of midazolam on anesthesia and analgesia quality when added to lidocaine during the intravenous regional anesthesia (IVRA). METHODS One hundred and forty patients underwent hand surgery were randomly allocated into four groups to receive 3 mg/kg lidocaine 2% diluted with saline to a total volume of 40 mL in the control Group L-C (n = 35), 30 μg/kg midazolam plus 3 mg/kg lidocaine 2% diluted with saline to a total volume of 40 mL in the midazolam Group L-M1 (n = 35), 40 μg/kg midazolam plus 3 mg/kg 2% lidocaine diluted with saline to a total volume of 40 mL in the midazolam Group L-M2 (n = 35), and 50 μg/kg midazolam plus 3 mg/kg lidocaine 2% diluted with saline to a total volume of 40 mL in the midazolam Group L-M3 (n = 35). Sensory and motor block and recovery times, tourniquet pain, intra-operative analgesic requirement, and visual analog scale (VAS) scores were recorded. FINDINGS Onset time of sensory and motor block in L-M3 Group was shorter than the L-M2 and L-M1 and L-C Groups (P < 0.001). Furthermore, prolonged sensory (P = 0.005) and motor recovery time (P = 0.001) in L-M3 were longer than the other groups. Intra-operative VAS score and intra-operative fentanyl consumption in L-M3 were lower than the other groups (P < 0.001). The numbers of patients needed to pethidine in Group L-M3 were significantly less compared with the other groups (P = 0.035). VAS scores were significantly lower in Group L-M3 in different time intervals in the postoperative period compared with the other groups (P < 0.001). CONCLUSION Addition of 50 μg/kg midazolam for IVRA (Group L-M3) enhanced intra-operative analgesia and improved anesthesia quality better than other groups receiving lower midazolam doses as well as a control group.
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Affiliation(s)
- Azim Honarmand
- Department of Anesthesia, Anesthesiology and Critical Care Research Center, Isfahan University of Medical Sciences, Isfahan, Iran
| | - Mohammadreza Safavi
- Department of Anesthesia, Anesthesiology and Critical Care Research Center, Isfahan University of Medical Sciences, Isfahan, Iran
| | - Koorosh Nemati
- Department of Anesthesia, Anesthesiology and Critical Care Research Center, Isfahan University of Medical Sciences, Isfahan, Iran
| | - Padideh Oghab
- Department of Anesthesia, Anesthesiology and Critical Care Research Center, Isfahan University of Medical Sciences, Isfahan, Iran
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Bharti N, Batra YK, Negi SL. Efficacy of intrathecal midazolam versus fentanyl for endoscopic urology surgery. SOUTHERN AFRICAN JOURNAL OF ANAESTHESIA AND ANALGESIA 2015. [DOI: 10.1080/22201181.2015.1028216] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/05/2023]
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El-Baradey GF, Elshmaa NS. The efficacy of adding dexamethasone, midazolam, or epinephrine to 0.5% bupivacaine in supraclavicular brachial plexus block. Saudi J Anaesth 2014; 8:S78-83. [PMID: 25538528 PMCID: PMC4268535 DOI: 10.4103/1658-354x.144083] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/08/2022] Open
Abstract
Aims: The aim was to assess the effectiveness of adding either dexamethasone or midazolam in comparison with epinephrine addition to 0.5% bupivacaine in supraclavicular brachial plexus block. Settings and Design: This is a prospective randomized controlled observer-blinded study. Subjects and Methods: This study was carried out in Tanta University Hospital on 60 patients of both sexes; American Society of Anesthesiologists physical Status I and II, age range from 18 to 45 years undergo elective surgery to upper limb. All patients were anesthetized with ultrasound guided supraclavicular brachial plexus block and randomly divided into three groups (each group 20 patients) Group E (epinephrine): 30 mL bupivacaine 0.5%with 1:200,000 epinephrine (5 μg/mL). Group D (dexamethasone): 30 mL bupivacaine 0.5% and dexamethasone 8 mg. Group M (midazolam): 30 ml bupivacaine 0.5% and midazolam 50 μg/kg. The primary outcome measures were onset and duration of sensory and motor block and time to first analgesic request. Statistical Analysis Used: The windows version of SPSS 11.0.1 (SPSS Inc., Chicago, IL, USA) was used for statistical analysis. Data were presented in form of mean ± standard deviation multiple analysis of variance (ANOVA) was used to compare the three groups and Scheffe test was used after ANOVA. Power of significance P < 0.05 was considered to be statistically significant. Results: Onset of sensory and motor block was significantly rapid (P < 0.05) in Groups D and M in comparison with Group E. Time of administration of rescue analgesic, duration of sensory and motor block showed significant increase (P < 0.05) in Group D in comparison with Group M which showed significant increase (P < 0.05) in comparison with Group E. Conclusions: In comparison with epinephrine and midazolam addition of dexamethasone to bupivacaine had rapid onset of block and longer time to first analgesic request with fewer side-effects.
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Affiliation(s)
- Ghada F El-Baradey
- Department of Anesthesia and ICU, Faculty of Medicine, Tanta University, Tanta, Egypt
| | - Nagat S Elshmaa
- Department of Anesthesia and ICU, Faculty of Medicine, Tanta University, Tanta, Egypt
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Stuart P. Novel additives to neuraxial blockade. SOUTHERN AFRICAN JOURNAL OF ANAESTHESIA AND ANALGESIA 2014. [DOI: 10.1080/22201173.2011.10872740] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/24/2022]
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Salimi A, Nejad RA, Safari F, Mohajaerani SA, Naghade RJ, Mottaghi K. Reduction in labor pain by intrathecal midazolam as an adjunct to sufentanil. Korean J Anesthesiol 2014; 66:204-9. [PMID: 24729842 PMCID: PMC3983416 DOI: 10.4097/kjae.2014.66.3.204] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/21/2013] [Revised: 07/12/2013] [Accepted: 08/29/2013] [Indexed: 11/10/2022] Open
Abstract
BACKGROUND Anesthesia today has strived to decrease labor pain in a tolerable and controllable fashion. Intrathecal midazolam has been introduced as an adjunct to analgesics. The study was planned to assess the efficacy, safety and duration of analgesia produced by intrathecal midazolam adjunct to sufentanil in decreasing labor pain. METHODS In a randomized clinical trial 80 parturient included in the study. The two groups were matched for age, cervical dilation, gravid, gestational age, and other demographic characteristics. Combination of sufentanil and midazolam administered intrathecally to experimental group and compared to sufentanil group. Time to reach maximum block, and pain score was measured and recorded. RESULTS Groups were matched for age and weight and other demographic characteristic. No significant adverse effect was seen in both groups including decrease in Apgar score. Duration of analgesia was 92.0 ± 12.7 in sufentanil group and 185.2 ± 15.2 minutes in midazolam and sufentanil group which was significantly different (P = 0.002). Numeric rating scale score was significantly lower in midazolam group compare to sufentanil group at 120 min (P = 0.01), 150 min (P = 0.0014), and 180 min (P = 0.001). CONCLUSIONS Intrathecal midazolam as an adjunct to opioid could significantly enhance analgesia in labor pain with no significant adverse effect. Intrathecal injection of midazolam is an appropriate alternative to parenteral or epidural analgesia in small hospital settings.
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Affiliation(s)
- Alireza Salimi
- Department of Anesthesiology, Loghman Hospital, Tehran, Iran
| | - Reza Amin Nejad
- Department of Anesthesiology, Loghman Hospital, Tehran, Iran
| | - Farhad Safari
- Department of Anesthesiology, Loghman Hospital, Tehran, Iran
| | | | | | - Kamran Mottaghi
- Department of Anesthesiology, Loghman Hospital, Tehran, Iran
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Abstract
Midazolam, despite of being the commonest benzodiazepine used in anaesthesia and perioperative care, is a relatively newer addition to the list of adjuvant used in subarachnoid block. Midazolam causes spinally mediated analgesia and the segmental analgesia produced by intrathecal midazolam is mediated by the benzodiazepine-GABA receptor complex. Initial animal studies questioned the safety of intrathecal midazolam in terms of possible neurotoxicity. However subsequent clinical studies also failed to show any neurotoxicity of high dose midazolam even on long-term use. Addition of intrathecal midazolam to bupivacaine significantly improves the duration and quality of spinal anaesthesia and provides prolonged perioperative analgesia without any significant side effects. Clinical studies also reported its safety and efficacy in pregnant women, but some studies also reported mild sedation with intrathecal midazolam. It is also reported to decrease the incidence of PONV. Intrathecal midazolam does not have any clinically significant effect on perioperative hemodynamics.
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Midazolam activates the intrinsic pathway of apoptosis independent of benzodiazepine and death receptor signaling. Reg Anesth Pain Med 2012; 36:343-9. [PMID: 21701267 DOI: 10.1097/aap.0b013e318217a6c7] [Citation(s) in RCA: 40] [Impact Index Per Article: 3.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/29/2023]
Abstract
BACKGROUND AND OBJECTIVES Midazolam has neurotoxic properties when administered neuraxially in vivo. Furthermore, midazolam induces neurodegeneration in neonatal animal models in combination with other general anesthetics. Therefore, this study focuses on the mechanism of neurotoxicity by midazolam in neuronal and nonneuronal cells. The study aims to evaluate the apoptotic pathway and to investigate the protective effects of the benzodiazepine antagonist flumazenil and the caspase inhibitor N-(2-quinolyl)valyl-aspartyl-(2,6-difluorophenoxy)-methylketone. METHODS The apoptosis-inducing effect of preservative-free midazolam on human lymphoma and neuroblastoma cell lines was evaluated using flow cytometric analysis of early apoptotic stages (annexin V/7AAD) and caspase 3 activation. B-cell lymphoma (Bcl2) protein overexpressing and caspase 9-deficient lymphoma cells were used to determine the role of the mitochondrial (intrinsic) pathway. Caspase 8-deficient and Fas-associated protein with death domain (FADD)-deficient cells were used to evaluate the death receptor (extrinsic) pathway. The protective effects of flumazenil and the caspase inhibitor N-(2-quinolyl)valyl-aspartyl-(2,6-difluorophenoxy)-methylketone were investigated in neuroblastoma cells and primary rat neurons using metabolic activity assays (2,3-bis(2-methoxy-4-nitro-5-sulfophenyl)-2H-tetrazolium-5-carboxanilide) and immunofluorescence microscopy. RESULTS Midazolam induced apoptosis in all investigated cell types in a concentration-dependent manner, indicated by flow cytometry. Bcl2-overexpression and caspase 9 deficiency protected against toxicity, whereas caspase 8 or FADD deficiency had no effect. Pancaspase inhibition had a strong protective effect, whereas flumazenil did not inhibit midazolam-induced apoptosis. CONCLUSIONS Midazolam induces apoptosis via activation of the mitochondrial pathway in a concentration-dependent manner. The mechanism of midazolam toxicity switches from caspase-dependent apoptosis to necrosis with increasing concentrations. The induction of apoptosis and necrosis by midazolam is presumably unrelated to GABAA receptor pathway signaling.
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Joshi SA, Khadke VV, Subhedar RD, Patil AW, Motghare VM. Comparative evaluation of intrathecal midazolam and low dose clonidine: efficacy, safety and duration of analgesia. A randomized, double blind, prospective clinical trial. Indian J Pharmacol 2012; 44:357-61. [PMID: 22701246 PMCID: PMC3371459 DOI: 10.4103/0253-7613.96321] [Citation(s) in RCA: 9] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/23/2011] [Revised: 11/12/2011] [Accepted: 02/28/2012] [Indexed: 11/06/2022] Open
Abstract
Background: The study was planned to assess the comparative efficacy, safety and duration of analgesia produced by low-dose clonidine and midazolam when used as adjuvant for spinal anesthesia. Materials and Methods: This is a randomized, participant and observer blind, prospective, parallel group clinical trial. Fifty ASA grade I and II patients posted for lower abdominal surgery were randomly allocated into two groups. BC group received spinal clonidine 30 μg and BM group received preservative-free midazolam 2 mg with 15 mg hyperbaric bupivacaine. Postoperative analgesia, analgesic requirement in 24 hours, onset and duration of block, hemodynamic stability and adverse effects were observed (P<0.05 – considered significant, P<0.01 considered highly significant). Results: The duration of postoperative analgesia was prolonged in BM group (391.64 ± 132.98 min) than BC group (296.60 ± 52.77 min) (P<0.01). The mean verbal rating pain score was significantly less in BM group than BC group (P<0.01). The number of analgesic doses in 24 hours were significantly less in BM group (P<0.05). Nine patients (36%) in BC group required additional analgesia as against none in BM group (P<0.01). The onset of sensory block and peak sensory level was significantly earlier in BM group as compared to BC group. Duration of sensory block was longer in BM group (P<0.05). Subjects in BC group(36%) had bradycardia as compared to none in BM group (P<0.01). Hypotension was observed in 44% patients in BC group as against 16% in BM group (P<0.05). Conclusion: Postoperative analgesia with clonidine is short lived with some bradycardia. Intrathecal midazolam provides superior analgesia without clinically relevant adverse effects.
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Affiliation(s)
- Suchita A Joshi
- Department of Anaesthesiology and Pharmacology, Shri Bhausaheb Hire Govt. Medical College, Dhule, Maharashtra, India.
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Effect of intra-articular injection of midazolam and/or bupivacaine on postoperative analgesia after arthroscopic knee surgery. EGYPTIAN JOURNAL OF ANAESTHESIA 2012. [DOI: 10.1016/j.egja.2011.11.004] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/21/2022] Open
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Kim S, Seo J, Jeon Y. Antiemetic effects of midazolam added to fentanyl-ropivacaine patient-controlled epidural analgesia after subtotal gastrectomy: A prospective, randomized, double-blind, controlled trial. Curr Ther Res Clin Exp 2010; 71:298-308. [PMID: 24688151 DOI: 10.1016/j.curtheres.2010.10.005] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 08/30/2010] [Indexed: 10/18/2022] Open
Abstract
BACKGROUND Nausea and vomiting are frequent adverse effects of patient-controlled epidural analgesia (PCEA) with opioids. OBJECTIVE This study was designed to assess the antiemetic effect of midazolam added to fentanyl-ropivacaine PCEA. METHODS In a prospective, randomized, double-blind, controlled trial, smoking patients with gastric cancer undergoing elective subtotal gastrectomy were evenly allocated to 1 of 2 treatment groups to manage postoperative pain: 0.2% ropivacaine mixed with fentanyl 4 μg/mL and midazolam 0.2 mg/mL (test group) or 0.2% ropivacaine mixed with fentanyl 4 μg/mL (control group). The PCEA infusion was set to deliver 4 μL/h of the study solution, with a bolus of 2 mL per demand and a 15-minute lockout time. The incidence of postoperative nausea and vomiting (PONV), pain intensity, sedation score, usage of rescue analgesia and rescue antiemetic, respiratory depression, urinary retention, and pruritus were recorded at 2, 6, 12, 24, 48, and 72 hours after surgery. Total infused volume of PCEA at 72 hours after surgery was measured. RESULTS A total of 60 patients were approached and randomized to treatment. No patients were excluded by exclusion criteria and all enrolled patients completed this study. Incidence of nausea (7% vs 33%; P = 0.02) in the test group was significantly lower than in the control group. The overall frequency of PONV in the test group was significantly less than that of the control group (7% vs 40%; P = 0.006). In addition, the mean (SD) infused volume of PCEA in the test group was significantly lower than that in the control group (392.3 [68.9] vs 351.2 [49.8] mL; P = 0.01). However, there were no significant differences in pain intensity, usage of rescue antiemetics and rescue analgesics, and mild pruritus between groups. No patient reported moderate or severe sedation, respiratory depression, or hypoxemia. In addition, there were no severe adverse events. CONCLUSIONS Midazolam added to fentanyl-ropivacaine PCEA was associated with a significant reduction in the incidence of PONV compared with fentanyl-ropivacaine alone, and a significant decrease in the amount of PCEA administered without a significant increase in adverse events in these patients who underwent subtotal gastrectomy.
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Affiliation(s)
- Sioh Kim
- Department of Anesthesiology and Pain Medicine, Kyungpook National University Hospital, Daegu, Republic of Korea
| | - Jeongwon Seo
- Department of Anesthesiology and Pain Medicine, Kyungpook National University Hospital, Daegu, Republic of Korea
| | - Younghoon Jeon
- Department of Anesthesiology and Pain Medicine, School of Dentistry, Kyungpook National University, Daegu, Republic of Korea
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Chiba S, Nishiyama T, Yoshikawa M, Yamada Y. The antinociceptive effects of midazolam on three different types of nociception in mice. J Pharmacol Sci 2009; 109:71-7. [PMID: 19122369 DOI: 10.1254/jphs.08094fp] [Citation(s) in RCA: 14] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/21/2022] Open
Abstract
Antinociceptive effects of systemically administered midazolam remain controversial. The present study was performed to investigate its antinociceptive effects on different types of nociception in mice. Four different doses of midazolam (1, 3, 10, and 30 mg/kg) were administered intraperitoneally (i.p.). Saline was used as a control. The hot plate test, tail pressure test, acetic acid writhing test, the running wheel test, and the balance beam test were performed following the drug administration. In the hot plate test and tail pressure test, i.p. midazolam produced significant antinociceptive effects with the 50% effective dose (ED(50)) of 3.46 mg/kg [confidence interval (CI), 1.99 - 6.01 mg/kg] and 3.52 mg/kg (CI, 2.77 - 4.47 mg/kg), respectively. In the acetic acid writhing test, i.p. midazolam also produced significant antinociceptive effects. In the running wheel test, no mice stopped running after saline or midazolam at 1, 3, or 10 mg/kg, but all mice stopped running 30 and 45 min after i.p. administration of midazolam at 30 mg/kg. In the balance beam test, 30 min after i.p. administration of saline or midazolam at 1, 3, and 10 mg/kg, all mice were able to stay on the beam for 90 s, none of them could with midazolam at 30 mg/kg. In conclusion, systemically administered midazolam had antinociceptive effects on acute thermal, acute mechanical, and acute inflammatory-induced nociception in mice. The antinociceptive potency of midazolam was the same for both acute thermal-induced nociception and mechanical-induced nociception.
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Affiliation(s)
- Shunsuke Chiba
- Department of Anesthesiology, The University of Tokyo, Faculty of Medicine, Tokyo, Japan.
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A Dose-Ranging Study of Intraarticular Midazolam for Pain Relief After Knee Arthroscopy. Anesth Analg 2008; 107:669-72. [DOI: 10.1213/ane.0b013e3181770f95] [Citation(s) in RCA: 13] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/05/2022]
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Midazolam inhibits cardiac nociception evoked by coronary artery occlusion in rats. Eur J Anaesthesiol 2008; 25:479-84. [PMID: 18289449 DOI: 10.1017/s0265021508003815] [Citation(s) in RCA: 10] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/07/2022]
Abstract
BACKGROUND AND OBJECTIVES This study was designed to investigate the potential existence of the response of neurons in the parafascicular nucleus of the thalamus to acute myocardial ischaemia induced by selective coronary artery occlusion and the effects of midazolam on the response in rats. METHODS The left anterior descending branch of the coronary artery was instrumented with a snare occluder in anaesthetized Sprague-Dawley rats. A single-barrel glass microelectrode was used for recording the unit discharges of the neuron in the parafascicular nucleus. The neuron responding only to noxious somatic stimulation was further examined for the response to coronary artery occlusion. Once the effect of coronary artery occlusion on the discharges was detected, the pharmacological effects of midazolam and flumazenil were examined. RESULTS It was observed that the discharge rate of the neuron was markedly increased following coronary artery occlusion. Midazolam attenuated the increase in the discharges of the neuron induced by coronary artery occlusion (P < 0.05). The effect of midazolam was reversed by flumazenil. CONCLUSIONS The parafascicular nucleus is involved in the modulation of cardiac nociception and midazolam possesses antinociceptive property in modulating cardiac pain.
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Effects of Intrathecal Midazolam on Postoperative Analgesia When Added to a Bupivacaine-Clonidine Mixture. Reg Anesth Pain Med 2006. [DOI: 10.1097/00115550-200611000-00005] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/27/2022]
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Kunz M, Scholl KE, Schu U, Lautenbacher S. GABAergic modulation of diffuse noxious inhibitory controls (DNIC): a test by use of lorazepam. Exp Brain Res 2006; 175:363-71. [PMID: 16816943 DOI: 10.1007/s00221-006-0558-8] [Citation(s) in RCA: 14] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/25/2005] [Accepted: 05/11/2006] [Indexed: 11/25/2022]
Abstract
Diffuse noxious inhibitory controls (DNIC) are an important supra-spinal mechanism of pain inhibition. Neurotransmitters and modulators involved in DNIC are serotonin and endogenous opioids. The influence of substances binding to the GABA(A) receptor complex, which has been suggested to play an important role in descending pain inhibition on DNIC has not yet been investigated. The aim of the present study was to find out whether the inhibitory action of DNIC might also be mediated by GABAergic mechanisms. Therefore, DNIC modulation via GABAergic mechanisms was studied in a double blind, placebo-controlled crossover design by oral application of 0.02 mg/kg(body weight )lorazepam in 20 healthy subjects. DNIC inhibition was induced by heterotopically administered tonic heat. The inhibitory effect was assessed by use of a multiple staircase method, measuring electrocutaneous detection, and pain thresholds in parallel. Concurrent tonic heat stimuli, at both painful and non-painful levels, significantly increased the electrical pain threshold whereas the electrical detection threshold was not affected. This pain-specific inhibitory effect did not differ significantly between sessions with lorazepam and placebo. Accordingly, lorazepam did not modify the inhibitory action of DNIC although lorazepam generally increased heat pain threshold. The results of the present study provided no evidence for DNIC being mediated by activation of the GABA(A) receptor complex.
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Affiliation(s)
- Miriam Kunz
- Physiological Psychology, Otto-Friedrich University Bamberg, Markusplatz 3, Bamberg 96045, Germany.
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Abstract
UNLABELLED Early preclinical work demonstrated the potential role of spinal benzodiazepine pharmacology in regulating spinal nociceptive transmission. We review this preclinical activity and the evolving implementation of intrathecal midazolam in humans for pain management. Important elements in this development for use in humans are issues pertinent to safety and the preclinical reports that have increased our understanding of intrathecal midazolam toxicity. We seek to emphasize the time course of these studies and how they merged to provide enabling data that drove the clinical implementation. In the case of midazolam, we point to the potential issues that arose when preclinical safety data were unreasonably ignored and how consideration of preclinical safety data can serve to facilitate drug development by demonstrating reasonable safety profiles that document the minimal degree of potential risk to the patient. Issues that are of continuing relevance to the use of intrathecal midazolam, including issues of formulation and kinetics, are considered. IMPLICATIONS The intrathecal use of midazolam has evolved over 20 years though a combination of preclinical and clinical investigations. We review the time course of this development to define critical elements that should be pursued in reducing the risk associated with the clinical use of a novel spinal drug.
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Affiliation(s)
- Tony L Yaksh
- Department of Anesthesiology, University of California, San Diego, La Jolla, California
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Shah FR, Halbe AR, Panchal ID, Goodchild CS. Improvement in postoperative pain relief by the addition of midazolam to an intrathecal injection of buprenorphine and bupivacaine. Eur J Anaesthesiol 2004; 20:904-10. [PMID: 14649343 DOI: 10.1017/s0265021503001455] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/07/2022]
Abstract
BACKGROUND AND OBJECTIVE Intrathecal injections of the benzodiazepine midazolam have been reported to cause antinociception in animals and pain relief in human beings, including the potentiation of opioid analgesia. This study compared the efficacy of the addition of midazolam to a mixture of buprenorphine and bupivacaine used for spinal anaesthesia. METHODS The study was prospective, randomized, and observer blinded. It involved 60 patients (30 per group), ASA I and II, age 20-40 yr, undergoing minor and intermediate lower abdominal surgery under spinal anaesthesia. Patients were randomized into two groups: the control group received a spinal injection of hyperbaric bupivacaine (15 mg) plus buprenorphine (0.15 mg) and the experimental group received a spinal injection of the same two drugs and doses but supplemented with intrathecal midazolam (2 mg). RESULTS The duration of postoperative analgesia in the control group was 9.24 +/- 2.57 h (mean +/- SEM), and 21.33 +/- 12.69 h in the midazolam treated group (P < 0.001). Patients treated with intrathecal midazolam had better pain relief judged by visual analogue score on coughing (P = 0.0013) and a nursing mobility score (P < 0.0001). Adverse effects were minor and their incidence was similar in both groups. CONCLUSIONS We conclude that intrathecal midazolam 2 mg improves the quality and duration of postoperative pain relief afforded by intrathecal buprenorphine and bupivacaine.
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MESH Headings
- Abdomen/surgery
- Adult
- Analgesics, Opioid/adverse effects
- Analgesics, Opioid/therapeutic use
- Anesthesia, Spinal
- Anesthetics, Combined/adverse effects
- Anesthetics, Combined/therapeutic use
- Anesthetics, Intravenous/adverse effects
- Anesthetics, Intravenous/therapeutic use
- Anesthetics, Local/adverse effects
- Anesthetics, Local/therapeutic use
- Bupivacaine/adverse effects
- Bupivacaine/therapeutic use
- Buprenorphine/adverse effects
- Buprenorphine/therapeutic use
- Chi-Square Distribution
- Drug Synergism
- Humans
- Injections, Spinal
- Midazolam/adverse effects
- Midazolam/therapeutic use
- Pain Measurement
- Pain, Postoperative/drug therapy
- Pain, Postoperative/prevention & control
- Prospective Studies
- Time Factors
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Affiliation(s)
- F R Shah
- Department of Anaesthesiology, B.Y.L. Nair Ch. Hospital and TN. Medical College, Mumbai, India
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Supraspinal and spinal cord opioid receptors are responsible for antinociception following intrathecal morphine injections. Eur J Anaesthesiol 2004. [DOI: 10.1097/00003643-200403000-00003] [Citation(s) in RCA: 15] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/26/2022]
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Improvement in postoperative pain relief by the addition of midazolam to an intrathecal injection of buprenorphine and bupivacaine. Eur J Anaesthesiol 2003. [DOI: 10.1097/00003643-200311000-00008] [Citation(s) in RCA: 22] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/25/2022]
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Bharti N, Madan R, Mohanty PR, Kaul HL. Intrathecal midazolam added to bupivacaine improves the duration and quality of spinal anaesthesia. Acta Anaesthesiol Scand 2003; 47:1101-5. [PMID: 12969103 DOI: 10.1034/j.1399-6576.2003.00186.x] [Citation(s) in RCA: 33] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/23/2022]
Abstract
BACKGROUND The antinociceptive action of intrathecal midazolam is well documented. In this prospective study, we investigated the addition of midazolam to intrathecal bupivacaine on the duration and quality of spinal blockade. METHODS Forty ASA I or II adult patients undergoing lower abdominal surgery were selected for the study. The patients were randomly allocated to receive 3 ml of 0.5% hyperbaric bupivacaine intrathecally either alone or with 1 mg of midazolam using a combined spinal epidural technique. The duration and quality of sensory and motor block, perioperative analgesia, haemodynamic changes, and sedation levels were assessed. RESULTS The duration of sensory block (i.e. time to regression to the S2 segment) was significantly longer in the midazolam group than the control group (218 min vs. 165 min; P < 0.001). The duration of motor block was also prolonged in the midazolam group as compared with the control group (P < 0.01). In 90% of the patients in the midazolam group, the quality of block was adequate during the intra-operative period as compared with only 65% of the patients in the control group (P < 0.05). The duration of effective analgesia was longer in the midazolam group than in the control group (199 vs. 103 min; P < 0.001). Blood pressure, heart rate, oxygen saturation and sedation scores were comparable in both groups. No neurological deficit or other significant adverse effects were recorded. CONCLUSION The addition of intrathecal midazolam to bupivacaine significantly improves the duration and quality of spinal anaesthesia and provides prolonged perioperative analgesia without significant side-effects.
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Affiliation(s)
- N Bharti
- Department of Anaesthesiology and Intensive Care, All India Institute of Medical Sciences, New Delhi, India.
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Nishiyama T, Hanaoka K. The synergistic interaction between midazolam and clonidine in spinally-mediated analgesia in two different pain models of rats. Anesth Analg 2001; 93:1025-31. [PMID: 11574377 DOI: 10.1097/00000539-200110000-00045] [Citation(s) in RCA: 26] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/26/2022]
Abstract
UNLABELLED Both midazolam, a benzodiazepine gamma-aminobutyric acid type A receptor agonist, and clonidine, an alpha2-adrenergic receptor agonist, induce spinally-mediated analgesia. We investigated the analgesic interaction of spinally-administered midazolam and clonidine in their effects on acute and inflammatory nociception. Rats implanted with lumbar intrathecal catheters were injected intrathecally with saline (control), midazolam (1 to 100 microg), or clonidine (0.1 to 3 microg) to test for their responses to thermal stimulation to the tail (tail-flick test) and subcutaneous formalin injection into the hind paw (formalin test). The effects of the combination of midazolam and clonidine on both stimuli were tested by isobolographic analysis by using the 50% effective doses. The general behavior and motor function were examined as side effects. When combined, the 50% effective doses of midazolam (clonidine) decreased from 1.57 microg (0.26 microg) to 0.29 g (0.05 microg) in the tail-flick test and from 1.34 microg (0.12 microg) and 1.21 microg (0.13 microg) to 0.05 microg (0.005 microg) and 0.13 microg (0.015 microg) in Phase 1 and 2 of the formalin test, respectively. Side effects did not increase by using the combination. These results suggest a favorable combination of intrathecal midazolam and clonidine in the management of acute and inflammatory pain after proper neurotoxicologic studies. IMPLICATIONS Spinally-administered midazolam, a benzodiazepine, and clonidine, an alpha2-adrenergic receptor agonist, have significant synergistic effects on thermally-induced acute and formalin-induced inflammatory pain.
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Affiliation(s)
- T Nishiyama
- Department of Surgical Center, The Institute of Medical Science, The University of Tokyo, Tokyo, Japan.
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Cox RF, Collins MA. The effects of benzodiazepines on human opioid receptor binding and function. Anesth Analg 2001; 93:354-8 , 3rd contents page. [PMID: 11473860 DOI: 10.1097/00000539-200108000-00024] [Citation(s) in RCA: 9] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/26/2022]
Abstract
UNLABELLED We performed in vitro studies to investigate the potential interaction of benzodiazepines with cloned human opioid receptor subtypes. Midazolam, chlordiazepoxide, and diazepam directly displaced [(3)H]-diprenorphine binding from kappa and delta receptors, but not mu receptors, whereas flumazenil was inactive. These benzodiazepines also stimulated (35)S-GTPgammaS binding in membranes containing human kappa receptors, and the effect of midazolam was prevented by a selective kappa antagonist. Midazolam was also weakly active at delta-receptor activation, whereas all three were inactive at mu receptors. The results suggest that the analgesic efficacy reported for intrathecal benzodiazepines may be attributed, in part, to direct interaction with kappa-opioid receptors. IMPLICATIONS Several human and animal studies have shown analgesic effects of benzodiazepines after spinal injection. Our results show that large concentrations of midazolam, chlordiazepoxide, and diazepam displace the binding of [(3)H]-diprenorphine-an opiate radioligand from kappa receptors. In an in vitro functional assay, midazolam is a weak agonist at the delta-opioid receptor, whereas all three benzodiazepines are kappa-opioid agonists. These findings may partially explain the mechanism of benzodiazepine-induced spinal analgesia.
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Affiliation(s)
- R F Cox
- Department of Receptor Biochemistry, GlaxoSmithKline, Research Triangle Park, North Carolina 17709, USA.
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Nishiyama T, Gyermek L, Lee C, Kawasaki-Yatsugi S, Yamaguchi T. Synergistic analgesic effects of intrathecal midazolam and NMDA or AMPA receptor antagonists in rats. Can J Anaesth 2001; 48:288-94. [PMID: 11305832 DOI: 10.1007/bf03019761] [Citation(s) in RCA: 13] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/28/2022] Open
Abstract
PURPOSE To investigate the interaction of midazolam and N-methyl-D-aspartate (NMDA) receptor or -amino-3-hydroxy-5-methyl isoxazole-4-propionic acid (AMPA) receptor antagonist on the effects of persistent inflammatory nociceptive activation. METHODS Male Sprague-Dawley rats were implanted with lumbar intrathecal catheters and were tested for their responses to subcutaneous formalin injection into the hindpaw. Saline, midazolam (1 to 100 microg), AP-5 (I to 30 microg), a NMDA receptor antagonist, or YM872 (0.3 to 30 microg), an AMPA receptor antagonist was injected intrathecally 10 min before formalin injection. The combinations of midazolam and AP-5 or YM872 in a constant dose ratio based on the 50% effective dose (ED50) were also tested and were analysed with an isobologram. RESULTS Dose-dependent effects were observed with midazolam (ED50 was 1.34 microg and 1.21 microg in phase 1 and 2 of the formalin test, respectively), AP-5 (7.64 microg and 1.4 microg) and YM872 (0.24 microg and 0.21 microg). Synergistic effects in both phases were obtained when combining midazolam with AP-5 or YM872. The ED50 of midazolam decreased to 0.012 microg (phase 1) and 0.27 microg (phase 2) with AP-5 and to 0.09 microg (phase 1) and 0.35 microg (phase 2) with YM872 (P < 0.01). CONCLUSIONS These results suggest a functional coupling of benzodiazepine-aminobutyric acid (GABA)A receptor with NMDA and AMPA receptors in acute and persistent inflammatory nociceptive mechanisms in the spinal cord.
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Affiliation(s)
- T Nishiyama
- Department of Surgical Center, Institute of Medical Science, University of Tokyo, Japan.
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Kim MH, Lee YM. Intrathecal midazolam increases the analgesic effects of spinal blockade with bupivacaine in patients undergoing haemorrhoidectomy. Br J Anaesth 2001; 86:77-9. [PMID: 11575414 DOI: 10.1093/bja/86.1.77] [Citation(s) in RCA: 60] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/31/2022] Open
Abstract
In the present double-blind study we aimed to evaluate the postoperative analgesic effects of intrathecal midazolam with bupivacaine following haemorrhoidectomy. Forty-five patients were randomly allocated to one of three groups: the control group received 1 ml of 0.5% heavy bupivacaine plus 0.2 ml of 0.9% saline intrathecally, group BM1 received 1 ml of 0.5% bupivacaine plus 0.2 ml of 0.5% preservative-free midazolam and group BM2 received 1 ml of 0.5% bupivacaine plus 0.4 ml of 0.5% midazolam. Time to first analgesia was significantly greater in the midazolam groups than in the placebo and significantly less in the BM1 group than in the BM2 group.
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Affiliation(s)
- M H Kim
- Department of Anaesthesiology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea
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Taira Y, Nakakimura K, Matsumoto M, Sakabe T. Spinal and supraspinal midazolam potentiates antinociceptive effects of isoflurane. Br J Anaesth 2000; 85:881-6. [PMID: 11732524 DOI: 10.1093/bja/85.6.881] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/12/2022] Open
Abstract
The effects of lumbar intrathecal (i.t.) and intracerebroventricular (i.c.v.) midazolam on nociception during isoflurane anaesthesia were studied in rats using the tail-flick test. Rats received i.t. midazolam 2 and 4 microg or i.c.v. midazolam 4 and 8 microg during 1.1, 1.2 and 1.3% isoflurane or without isoflurane. Neither i.t. nor i.c.v. midazolam alone at doses studied influenced nociceptive responses. 1.1% isoflurane showed a minimum antinociceptive effect which was not influenced by i.t. or i.c.v. midazolam. 1.2 and 1.3% isoflurane produced moderate antinociception which was markedly potentiated by both i.t. and i.c.v. midazolam. The effects of midazolam shown in the present study are different from the reported effects of midazolam on opioid-induced antinociception; where spinally administered midazolam potentiates and supraspinal midazolam inhibits the antinociceptive effects of morphine. The present results suggest that midazolam potentiates isoflurane-induced antinociception at doses where no effect is seen alone.
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Affiliation(s)
- Y Taira
- Department of Anesthesiology-Resuscitology, Yamaguchi University School of Medicine, Ube, Japan
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Mercier FJ, Benhamou D. Promising non-narcotic analgesic techniques for labour. BAILLIERE'S CLINICAL OBSTETRICS AND GYNAECOLOGY 1998; 12:397-407. [PMID: 10023428 DOI: 10.1016/s0950-3552(98)80074-6] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 11/22/2022]
Abstract
Epidural analgesia and spinal analgesia are the most effective techniques for relieving labour pain. Basically, local anaesthetics (i.e. bupivacaine) and opioids (i.e. fentanyl or sufentanil), especially when combined, produce excellent analgesia with minimal motor blockade. However, none of these agents is devoid of side-effects and analgesia remains sometimes imperfect, suggesting that new drugs would be welcome. Adrenalin and clonidine act on a2-adrenoceptors in the spinal cord and both have been found to improve analgesia. These two drugs have already been used in many patients and studies because the absence of neurotoxicity has been well documented. Clonidine looks more attractive, although sedation and hypotension limit its use. Other analgesic drugs are promising alternatives but are still at an experimental or very early clinical stage. Neostigmine and ketamine (without preservative) are not neurotoxic while midazolam neurotoxicity is still controversial. Intravenous remifentanil might prove useful when neuraxial analgesia is contraindicated.
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Affiliation(s)
- F J Mercier
- Département d'Anesthésie-Réanimation, Hôpital Antoine Béclère, Clamart, France
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Güleç S, Büyükkidan B, Oral N, Özcan N, Tanriverdi B. Comparison of caudal bupivacaine, bupivacaine-morphine and bupivacaine-midazolam mixtures for post-operative analgesia in children. Eur J Anaesthesiol 1998. [DOI: 10.1097/00003643-199803000-00007] [Citation(s) in RCA: 16] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/25/2022]
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Gulec S, Buyukkidan B, Oral N, Ozcan N, Tanriverdi B. Comparison of caudal bupivacaine, bupivacaine-morphine and bupivacaine-midazolam mixtures for post-operative analgesia in children. Eur J Anaesthesiol 1998. [DOI: 10.1111/j.0265-0215.1998.00262.x] [Citation(s) in RCA: 10] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/28/2022]
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