The Use of Intrathecal Midazolam in Humans: A Case Study of Process

Yaksh, Tony L.; Allen, Jeffrey W.

doi:10.1213/01.ane.0000122638.41130.bf

Cited by 84 publications

(69 citation statements)

References 76 publications

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“…22 Sympathetic nervous system function remains intact after intrathecal midazolam. [23][24][25] This sparing effect on sympathetic nervous system may explain lesser degree of hypotension and bradycardia in midazolam group in our study.…”

Section: Discussionsupporting

confidence: 48%

A comparative study of intrathecal nonopioid adjuvants to hyperbaric bupivacaine for spinal anaesthesia

Joshi¹,

Khadke²

2017

Int J Basic Clin Pharmacol

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Background: Intrathecal drugs when used as adjuvant to spinal anaesthesia produce substantial anti-nociception and potentiate analgesia of bupivacaine. This study was planned to evaluate the effects of intrathecal non opioid drugs-clonidine, midazolam, neostigmine and magnesium sulphate on duration of analgesia, characteristics of SA and hemodynamic stability when added to 0.5% hyperbaric bupivacaine for spinal anaesthesia.Methods: In this randomized, prospective, double blind study, 100 ASA physical status I and II adults patients posted for elective lower abdominal surgery were divided into 4 groups (n=25). Group BN received preservative free neostigmine 25µg, group BMG received Mgso4 50mg, group BC received clonidine 30µg and BM received midazolam 2mg with 15mg hyperbaric bupivacaine. Duration of postoperative analgesia, effect on onset and duration of sensory and motor block, incidence of side effects was noted. Continuous variables were compared using one way Analysis of Variance (ANOVA).Results: The duration of postoperative analgesia was significantly prolonged in BM group 391.64 (132.98) minutes, followed by BN group 308.76 (127.40), BC group 296.60 (52.77) and BMG group 252.2 (86.76). The numbers of analgesic doses in 24 hours were significantly less in BM group. One patient required additional analgesia in BM group as against 40%, 36% and 64% in BN, BC, BMG group respectively. The duration of sensory block was significantly prolonged in group BM followed by group BC and BN.Conclusions: Intrathecal midazolam provides superior analgesia without clinically relevant side effects. The onset of analgesia was rapid and duration prolonged with intrathecal midazolam followed by neostigmine and clonidine.

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Section: Discussionsupporting

confidence: 48%

A comparative study of intrathecal nonopioid adjuvants to hyperbaric bupivacaine for spinal anaesthesia

Joshi¹,

Khadke²

2017

Int J Basic Clin Pharmacol

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“…At the spinal level enhanced GABA-Aactivity has been shown to have effects upon motor function [243]. The use of intrathecal midazolam in man has been reported as noted above.…”

Section: Adverse Eventsmentioning

confidence: 87%

“…The use of intrathecal midazolam in man has been reported as noted above. However, there has been concern about the potential for spinal toxicity [243,244]. While several systematic assessments of toxicity have shown distinct deleterious reactions [245,246], others have failed to observed toxicity [56].…”

Section: Adverse Eventsmentioning

confidence: 99%

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Current and Future Issues in the development of spinal agents for the management of pain

Yaksh¹,

Fisher²,

Hockman³

et al. 2016

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Targeting analgesic drugs for spinal delivery reflects the fact that while the conscious experience of pain is mediated supraspinally, input initiated by high intensity stimuli, tissue injury and/or nerve injury is encoded at the level of the spinal dorsal horn and this output informs the brain as to the peripheral environment. This encoding process is subject to strong upregulation resulting in hyperesthetic states and downregulation reducing the ongoing processing of nociceptive stimuli reversing the hyperesthesia and pain processing. The present review addresses the biology of spinal nociceptive processing as relevant to the effects of intrathecally-delivered drugs in altering pain processing following acute stimulation, tissue inflammation/injury and nerve injury. The review covers i) the major classes of spinal agents currently employed as intrathecal analgesics (opioid agonists, alpha 2 agonists; sodium channel blockers; calcium channel blockers; NMDA blockers; GABA A/B agonists; COX inhibitors; ii) ongoing developments in the pharmacology of spinal therapeutics focusing on less studied agents/targets (cholinesterase inhibition; Adenosine agonists; iii) novel intrathecal targeting methodologies including gene-based approaches (viral vectors, plasmids, interfering RNAs); antisense, and toxins (botulinum toxins; resniferatoxin, substance P Saporin); and iv) issues relevant to intrathecal drug delivery (neuraxial drug distribution), infusate delivery profile, drug dosing, formulation and principals involved in the preclinical evaluation of intrathecal drug safety.Keywords: Adenovirus transfection, dorsal horn, neurotoxins, pain pathways, spinal drug delivery, spinal analgesics, toxicity. RATIONALETargeting analgesic drugs for direct spinal delivery reflects the fact that while the conscious experience of pain is mediated supraspinally, input initiated by high intensity stimuli, tissue injury and/or nerve injury is encoded at the level of the spinal dorsal horn. Thus, high intensity (e.g., nociceptive) stimulation activates populations of small primary afferents, generating an intensity-dependent increase in activity of second order dorsal horn projection neurons. This excitation is transmitted through spinofugal projection pathways to higher centers, such as the somatosensory thalamus -somatosensory cortex, and to the medial thalamus -limbic cortices that are respectively believed to underlie the sensory-discriminative and affectivemotivational components of the pain experience [1-3]. The dorsal horn encoding process reflects a remarkable plasticity wherein the input-output function of the spinal dorsal horn is subject to pronounced regulation by local neuronal and nonneuronal circuits as well as supraspinal (bulbospinal) input. Thus, following tissue or nerve injury there is an enhanced neuronal response to moderate or low intensity stimuli, e.g., *Address correspondence to this author at the University of California, San Diego, Anesthesia Research Lab 0818, 9500 Gilman Dr. LaJolla, CA 92093, USA; ...

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“…Some clinical studies have discussed the efficacy of midazolam in producing analgesia, when administered intrathecally and epidurally for labor and postoperative pain (24,25). In the present study, we evaluated the effect of midazolam in combination with lidocaine.…”

Section: Discussionmentioning

confidence: 99%

The Effect of Intravenous Midazolam on Duration of Spinal Anesthesia

et al. 2015

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Background: A variety of systemic and intrathecal adjuvants to local anesthetics have been found to expand the duration and improve the quality of spinal block and decrease pain after surgeries. Objectives: The aim of this study was to evaluate the effect of the addition of midazolam to lidocaine for spinal anesthesia in lower abdomen and lower limb surgeries. Patients and Methods: In a prospective, randomized, double blind study, 36 patients aged 20 to 60 years, and American Society of Anesthesiologists (ASA) I or II, were randomly allocated to receive either intravenous midazolam (30 μg/kg) or placebo in spinal anesthesia. Level of sensory block, time to achieve maximum motor and sensory block, duration of sensory and motor block, recovery time, side effects, heart rate, blood pressure, arterial oxygen saturation and sedation score were measured and analyzed using the SPSS software version 15 by t-test and ANOVA. Data were considered significant at 0.05. Results:The motor block duration in midazolam and control group was 82.9 ± 27.3 and 59.1 ± 26.5, respectively (P = 0.01). However the duration of sensory block was not different between the two groups (P = 0.07). The median of sensory block level was at T8 and T10 in midazolam and control group (P = 0.02). Recovery time was more prolonged in the midazolam group (P = 0.002). Hemodynamic indices did not show any significant differences between the two groups. Conclusions: Addition of 30 μg/kg midazolam to lidocaine for spinal anesthesia improved duration of motor block and increased intraoperative sedation score without causing side effects in patients' requiring lower abdomen and lower limb surgery.

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The Use of Intrathecal Midazolam in Humans: A Case Study of Process

Cited by 84 publications

References 76 publications

A comparative study of intrathecal nonopioid adjuvants to hyperbaric bupivacaine for spinal anaesthesia

A comparative study of intrathecal nonopioid adjuvants to hyperbaric bupivacaine for spinal anaesthesia

Current and Future Issues in the development of spinal agents for the management of pain

The Effect of Intravenous Midazolam on Duration of Spinal Anesthesia

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