The Effect of Adding Subarachnoid Epinephrine to Hyperbaric Bupivacaine and Morphine for Repeat Cesarean Delivery: A Double-Blind Prospective Randomized Control Trial

Katz, Daniel; Hamburger, Joshua; Gutman, D.; Wang, R.; Lin, Hung‐Mo; Marotta, M; Zahn, Jeffrey; Beilin, Yaakov

doi:10.1213/ane.0000000000002542

Cited by 18 publications

(11 citation statements)

References 25 publications

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“…“Opioid and α2-adrenoceptor (AR) agonists are analgesic when administered in the spinal cord and show a clinically beneficial synergistic interaction when co-administered”, according to Chabot-Doré et al [ 20 ]. Many other studies have confirmed such an effect for mu and delta OPR as well as for a wide range of adrenergic agonists ranging from amphetamines to clonidine (e.g., [ 45 , 46 , 47 , 48 , 49 , 50 , 51 , 52 , 53 , 54 , 55 , 56 , 57 , 58 ]). The enhancement of opioid function by adrenergic agonists, particularly amphetamines, has been observed in other systems as well, such as opioid-mediated reward and related behaviors [ 59 , 60 , 61 , 62 , 63 , 64 , 65 ]; glucose uptake in the brain [ 66 ]; and on guinea pig ileum contractions induced by morphine, which are also enhanced by serotonin [ 67 , 68 , 69 ].…”

Section: Introductionmentioning

confidence: 83%

Adrenergic Agonists Bind to Adrenergic-Receptor-Like Regions of the Mu Opioid Receptor, Enhancing Morphine and Methionine-Enkephalin Binding: A New Approach to “Biased Opioids”?

Root‐Bernstein

Turke

Subhramanyam

et al. 2018

IJMS

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Extensive evidence demonstrates functional interactions between the adrenergic and opioid systems in a diversity of tissues and organs. While some effects are due to receptor and second messenger cross-talk, recent research has revealed an extracellular, allosteric opioid binding site on adrenergic receptors that enhances adrenergic activity and its duration. The present research addresses whether opioid receptors may have an equivalent extracellular, allosteric adrenergic binding site that has similar enhancing effects on opioid binding. Comparison of adrenergic and opioid receptor sequences revealed that these receptors share very significant regions of similarity, particularly in some of the extracellular and transmembrane regions associated with adrenergic binding in the adrenergic receptors. Five of these shared regions from the mu opioid receptor (muOPR) were synthesized as peptides and tested for binding to adrenergic, opioid and control compounds using ultraviolet spectroscopy. Adrenergic compounds bound to several of these muOPR peptides with low micromolar affinity while acetylcholine, histamine and various adrenergic antagonists did not. Similar studies were then conducted with purified, intact muOPR with similar results. Combinations of epinephrine with methionine enkephalin or morphine increased the binding of both by about half a log unit. These results suggest that muOPR may be allosterically enhanced by adrenergic agonists.

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Section: Introductionmentioning

confidence: 83%

Adrenergic Agonists Bind to Adrenergic-Receptor-Like Regions of the Mu Opioid Receptor, Enhancing Morphine and Methionine-Enkephalin Binding: A New Approach to “Biased Opioids”?

Root‐Bernstein

Turke

Subhramanyam

et al. 2018

IJMS

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“…The most commonly used technique in leg fracture surgery is epidural anesthesia, which provides both perioperative surgical anesthesia and postoperative analgesia. Early postoperative mobilization and rehabilitation along with minimal pain and discomfort are the main objectives of the modern orthopedic surgery (14, 25-27).…”

Section: Discussionmentioning

confidence: 99%

“…Dexmedetomidine as an adjunct directly increases the block time through the direct modulating of receptors on motor neurons and posterior horn sensory neurons of the spinal cord or their synapses (12, 13). The analgesic effects of epidural bupivacaine when administered alone last almost 4 - 6 h, but epidural morphine is effective for 12 - 24 h (14). The comparison of dexmedetomidine and fentanyl as intrathecal adjuvant drugs to bupivacaine showed that dexmedetomidine could prolong motor and sensory blockade and reduce the anesthetics consumption during the initial 24 h post-surgery (15).…”

Section: Introductionmentioning

confidence: 99%

Comparison of Dexmedetomidine and Morphine as Adjuvants to Bupivacaine for Epidural Anesthesia in Leg Fracture Surgery: A Randomized Clinical Trial

et al. 2019

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BackgroundEpidural block approach and drugs are common options for improving the sensory and motor block duration and postoperative pain management.ObjectivesThe study aimed to compare the analgesic effects of dexmedetomidine and morphine as adjuvants to bupivacaine for epidural anesthesia in leg fracture surgery.MethodsThis prospective clinical trial was conducted on patients (n = 80, age range: 18 - 60 years) categorized as ASA class I or II. After a clinical examination, the patients were allocated to receive either lumbar epidural bupivacaine + morphine (BM) (12 mL bupivacaine 0.5% + morphine 2 mg) or bupivacaine + dexmedetomidine (BD) (12 mL bupivacaine 0.5% + dexmedetomidine 1 µg/kg). After drug administration, the sensory block level was assessed at 2-min intervals using the Cold Swab method until it reached the T12 level. At the T12 level of sensory block, the surgery began when motor block reached grade 3 of the modified Bromage scale.ResultsThe BD group had a significantly shorter time to reach the sensory and motor block than the BM group (P < 0.001). The duration of sensory and motor block was significantly longer in the group BD than in the BM group (P < 0.001). Moreover, the BD group showed lower VAS scores (P < 0.0001) and longer time to first analgesia demand than the BM group.ConclusionsCombined bupivacaine + dexmedetomidine prolongs the sensory and motor block duration and controls postoperative pain more effectively, indicating that it is an appropriate combination for epidural anesthesia.

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“…Cross-talk between opioid receptors and adrenergic receptors has been well-characterized both in laboratory and clinical studies. Opioid compounds such as morphine and the enkephalins enhance adrenergic receptor activity [1][2][3][4][5][6][7][8][9][10][11][12][13][14][15], while adrenergic compounds such as epinephrine, norepinephrine, and propranolol enhance opioid receptor activity [16][17][18][19][20][21][22][23][24][25][26][27][28][29][30][31]. This enhancement is characterized by several unusual characteristics.…”

Section: Introductionmentioning

confidence: 99%

Co-Evolution of Opioid and Adrenergic Ligands and Receptors: Shared, Complementary Modules Explain Evolution of Functional Interactions and Suggest Novel Engineering Possibilities

Root‐Bernstein¹,

Churchill²

2021

Life

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Cross-talk between opioid and adrenergic receptors is well-characterized and involves second messenger systems, the formation of receptor heterodimers, and the presence of extracellular allosteric binding regions for the complementary ligand; however, the evolutionary origins of these interactions have not been investigated. We propose that opioid and adrenergic ligands and receptors co-evolved from a common set of modular precursors so that they share binding functions. We demonstrate the plausibility of this hypothesis through a review of experimental evidence for molecularly complementary modules and report unexpected homologies between the two receptor types. Briefly, opioids form homodimers also bind adrenergic compounds; opioids bind to conserved extracellular regions of adrenergic receptors while adrenergic compounds bind to conserved extracellular regions of opioid receptors; opioid-like modules appear in both sets of receptors within key ligand-binding regions. Transmembrane regions associated with homodimerization of each class of receptors are also highly conserved across receptor types and implicated in heterodimerization. This conservation of multiple functional modules suggests opioid–adrenergic ligand and receptor co-evolution and provides mechanisms for explaining the evolution of their crosstalk. These modules also suggest the structure of a primordial receptor, providing clues for engineering receptor functions.

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The Effect of Adding Subarachnoid Epinephrine to Hyperbaric Bupivacaine and Morphine for Repeat Cesarean Delivery: A Double-Blind Prospective Randomized Control Trial

Cited by 18 publications

References 25 publications

Adrenergic Agonists Bind to Adrenergic-Receptor-Like Regions of the Mu Opioid Receptor, Enhancing Morphine and Methionine-Enkephalin Binding: A New Approach to “Biased Opioids”?

Adrenergic Agonists Bind to Adrenergic-Receptor-Like Regions of the Mu Opioid Receptor, Enhancing Morphine and Methionine-Enkephalin Binding: A New Approach to “Biased Opioids”?

Comparison of Dexmedetomidine and Morphine as Adjuvants to Bupivacaine for Epidural Anesthesia in Leg Fracture Surgery: A Randomized Clinical Trial

Co-Evolution of Opioid and Adrenergic Ligands and Receptors: Shared, Complementary Modules Explain Evolution of Functional Interactions and Suggest Novel Engineering Possibilities

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