Sugammadex reverses neuromuscular block induced by 3-desacetyl-vecuronium, an active metabolite of vecuronium, in the anaesthetised rhesus monkey

BACKGROUND AND OBJECTIVE3-Desacetyl-vecuronium is an active metabolite of the neuromuscular blocking agent (NMBA) vecuronium, which might lead to residual paralysis after prolonged administration of vecuronium in critically ill patients with renal failure. This study investigated the ability of suga...

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Veröffentlicht in:European journal of anaesthesiology 2011-04, Vol.28 (4), p.265-272
Hauptverfasser: Staals, Lonneke M, van Egmond, Jan, Driessen, Jacques J, de Boer, Hans D, van de Pol, Francien, Bom, Anton H, Booij, Leo HDJ
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container_end_page 272
container_issue 4
container_start_page 265
container_title European journal of anaesthesiology
container_volume 28
creator Staals, Lonneke M
van Egmond, Jan
Driessen, Jacques J
de Boer, Hans D
van de Pol, Francien
Bom, Anton H
Booij, Leo HDJ
description BACKGROUND AND OBJECTIVE3-Desacetyl-vecuronium is an active metabolite of the neuromuscular blocking agent (NMBA) vecuronium, which might lead to residual paralysis after prolonged administration of vecuronium in critically ill patients with renal failure. This study investigated the ability of sugammadex to reverse 3-desacetyl-vecuronium-induced neuromuscular block (NMB) in the anaesthetised rhesus monkey. METHODSExperiments were performed in anaesthetised female rhesus monkeys. After bolus intravenous injection of vecuronium (n = 8) or 3-desacetyl-vecuronium (n = 8) 10 μg kg (ED90), a continuous infusion of the same NMBA was started to maintain the first twitch of the train-of-four (TOF) at 10% of baseline value. The infusion was stopped and NMB recovered spontaneously. The procedure was repeated, but immediately after stopping the infusion, an intravenous bolus dose of sugammadex 0.5 or 1.0 mg kg was given. For each NMBA, four placebo experiments were performed, in which the second recovery from NMB was also spontaneous. For all experiments, time to recovery of the TOF ratio to 90% was retrieved. RESULTSAfter administration of sugammadex for reversal of 3-desacetyl-vecuronium-induced NMB, recovery was significantly faster than spontaneous recovery. Mean time to recovery of TOF to 90% was 3.2 min (sugammadex 0.5 mg kg) and 2.6 min (1.0 mg kg), compared to spontaneous recovery (17.6 min). For vecuronium-induced NMB, mean time to recovery of TOF to 90% was 17.1 min (0.5 mg kg) and 4.6 min (1.0 mg kg), compared to spontaneous recovery (23.4 min). CONCLUSIONSugammadex rapidly and effectively reversed 3-desacetyl-vecuronium-induced NMB in the rhesus monkey, at a lower dose than that needed to reverse vecuronium-induced NMB.
doi_str_mv 10.1097/EJA.0b013e328340894f
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This study investigated the ability of sugammadex to reverse 3-desacetyl-vecuronium-induced neuromuscular block (NMB) in the anaesthetised rhesus monkey. METHODSExperiments were performed in anaesthetised female rhesus monkeys. After bolus intravenous injection of vecuronium (n = 8) or 3-desacetyl-vecuronium (n = 8) 10 μg kg (ED90), a continuous infusion of the same NMBA was started to maintain the first twitch of the train-of-four (TOF) at 10% of baseline value. The infusion was stopped and NMB recovered spontaneously. The procedure was repeated, but immediately after stopping the infusion, an intravenous bolus dose of sugammadex 0.5 or 1.0 mg kg was given. For each NMBA, four placebo experiments were performed, in which the second recovery from NMB was also spontaneous. For all experiments, time to recovery of the TOF ratio to 90% was retrieved. RESULTSAfter administration of sugammadex for reversal of 3-desacetyl-vecuronium-induced NMB, recovery was significantly faster than spontaneous recovery. Mean time to recovery of TOF to 90% was 3.2 min (sugammadex 0.5 mg kg) and 2.6 min (1.0 mg kg), compared to spontaneous recovery (17.6 min). For vecuronium-induced NMB, mean time to recovery of TOF to 90% was 17.1 min (0.5 mg kg) and 4.6 min (1.0 mg kg), compared to spontaneous recovery (23.4 min). CONCLUSIONSugammadex rapidly and effectively reversed 3-desacetyl-vecuronium-induced NMB in the rhesus monkey, at a lower dose than that needed to reverse vecuronium-induced NMB.</description><identifier>ISSN: 0265-0215</identifier><identifier>EISSN: 1365-2346</identifier><identifier>DOI: 10.1097/EJA.0b013e328340894f</identifier><identifier>PMID: 21157358</identifier><language>eng</language><publisher>England: European Society of Anaesthesiology</publisher><subject>Action Potentials ; Animals ; Electric Stimulation ; Female ; gamma-Cyclodextrins - administration &amp; dosage ; gamma-Cyclodextrins - pharmacology ; Infusions, Intravenous ; Injections, Intravenous ; Macaca mulatta ; Neuromuscular Junction - drug effects ; Neuromuscular Nondepolarizing Agents - administration &amp; dosage ; Neuromuscular Nondepolarizing Agents - pharmacology ; Recovery of Function ; Time Factors ; Vecuronium Bromide - administration &amp; dosage ; Vecuronium Bromide - analogs &amp; derivatives ; Vecuronium Bromide - pharmacology</subject><ispartof>European journal of anaesthesiology, 2011-04, Vol.28 (4), p.265-272</ispartof><rights>2011 European Society of Anaesthesiology</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c3978-5c6cf27fd6fe21bc80b26dbd8eeefc109021400f71091619e5e8bfd97416ae0c3</citedby><cites>FETCH-LOGICAL-c3978-5c6cf27fd6fe21bc80b26dbd8eeefc109021400f71091619e5e8bfd97416ae0c3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>315,781,785,27928,27929</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/21157358$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Staals, Lonneke M</creatorcontrib><creatorcontrib>van Egmond, Jan</creatorcontrib><creatorcontrib>Driessen, Jacques J</creatorcontrib><creatorcontrib>de Boer, Hans D</creatorcontrib><creatorcontrib>van de Pol, Francien</creatorcontrib><creatorcontrib>Bom, Anton H</creatorcontrib><creatorcontrib>Booij, Leo HDJ</creatorcontrib><title>Sugammadex reverses neuromuscular block induced by 3-desacetyl-vecuronium, an active metabolite of vecuronium, in the anaesthetised rhesus monkey</title><title>European journal of anaesthesiology</title><addtitle>Eur J Anaesthesiol</addtitle><description>BACKGROUND AND OBJECTIVE3-Desacetyl-vecuronium is an active metabolite of the neuromuscular blocking agent (NMBA) vecuronium, which might lead to residual paralysis after prolonged administration of vecuronium in critically ill patients with renal failure. This study investigated the ability of sugammadex to reverse 3-desacetyl-vecuronium-induced neuromuscular block (NMB) in the anaesthetised rhesus monkey. METHODSExperiments were performed in anaesthetised female rhesus monkeys. After bolus intravenous injection of vecuronium (n = 8) or 3-desacetyl-vecuronium (n = 8) 10 μg kg (ED90), a continuous infusion of the same NMBA was started to maintain the first twitch of the train-of-four (TOF) at 10% of baseline value. The infusion was stopped and NMB recovered spontaneously. The procedure was repeated, but immediately after stopping the infusion, an intravenous bolus dose of sugammadex 0.5 or 1.0 mg kg was given. For each NMBA, four placebo experiments were performed, in which the second recovery from NMB was also spontaneous. For all experiments, time to recovery of the TOF ratio to 90% was retrieved. RESULTSAfter administration of sugammadex for reversal of 3-desacetyl-vecuronium-induced NMB, recovery was significantly faster than spontaneous recovery. Mean time to recovery of TOF to 90% was 3.2 min (sugammadex 0.5 mg kg) and 2.6 min (1.0 mg kg), compared to spontaneous recovery (17.6 min). For vecuronium-induced NMB, mean time to recovery of TOF to 90% was 17.1 min (0.5 mg kg) and 4.6 min (1.0 mg kg), compared to spontaneous recovery (23.4 min). 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van Egmond, Jan ; Driessen, Jacques J ; de Boer, Hans D ; van de Pol, Francien ; Bom, Anton H ; Booij, Leo HDJ</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c3978-5c6cf27fd6fe21bc80b26dbd8eeefc109021400f71091619e5e8bfd97416ae0c3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2011</creationdate><topic>Action Potentials</topic><topic>Animals</topic><topic>Electric Stimulation</topic><topic>Female</topic><topic>gamma-Cyclodextrins - administration &amp; dosage</topic><topic>gamma-Cyclodextrins - pharmacology</topic><topic>Infusions, Intravenous</topic><topic>Injections, Intravenous</topic><topic>Macaca mulatta</topic><topic>Neuromuscular Junction - drug effects</topic><topic>Neuromuscular Nondepolarizing Agents - administration &amp; dosage</topic><topic>Neuromuscular Nondepolarizing Agents - pharmacology</topic><topic>Recovery of Function</topic><topic>Time Factors</topic><topic>Vecuronium Bromide - administration &amp; dosage</topic><topic>Vecuronium Bromide - analogs &amp; derivatives</topic><topic>Vecuronium Bromide - pharmacology</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Staals, Lonneke M</creatorcontrib><creatorcontrib>van Egmond, Jan</creatorcontrib><creatorcontrib>Driessen, Jacques J</creatorcontrib><creatorcontrib>de Boer, Hans D</creatorcontrib><creatorcontrib>van de Pol, Francien</creatorcontrib><creatorcontrib>Bom, Anton H</creatorcontrib><creatorcontrib>Booij, Leo HDJ</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><jtitle>European journal of anaesthesiology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Staals, Lonneke M</au><au>van Egmond, Jan</au><au>Driessen, Jacques J</au><au>de Boer, Hans D</au><au>van de Pol, Francien</au><au>Bom, Anton H</au><au>Booij, Leo HDJ</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Sugammadex reverses neuromuscular block induced by 3-desacetyl-vecuronium, an active metabolite of vecuronium, in the anaesthetised rhesus monkey</atitle><jtitle>European journal of anaesthesiology</jtitle><addtitle>Eur J Anaesthesiol</addtitle><date>2011-04</date><risdate>2011</risdate><volume>28</volume><issue>4</issue><spage>265</spage><epage>272</epage><pages>265-272</pages><issn>0265-0215</issn><eissn>1365-2346</eissn><abstract>BACKGROUND AND OBJECTIVE3-Desacetyl-vecuronium is an active metabolite of the neuromuscular blocking agent (NMBA) vecuronium, which might lead to residual paralysis after prolonged administration of vecuronium in critically ill patients with renal failure. This study investigated the ability of sugammadex to reverse 3-desacetyl-vecuronium-induced neuromuscular block (NMB) in the anaesthetised rhesus monkey. METHODSExperiments were performed in anaesthetised female rhesus monkeys. After bolus intravenous injection of vecuronium (n = 8) or 3-desacetyl-vecuronium (n = 8) 10 μg kg (ED90), a continuous infusion of the same NMBA was started to maintain the first twitch of the train-of-four (TOF) at 10% of baseline value. The infusion was stopped and NMB recovered spontaneously. The procedure was repeated, but immediately after stopping the infusion, an intravenous bolus dose of sugammadex 0.5 or 1.0 mg kg was given. For each NMBA, four placebo experiments were performed, in which the second recovery from NMB was also spontaneous. For all experiments, time to recovery of the TOF ratio to 90% was retrieved. RESULTSAfter administration of sugammadex for reversal of 3-desacetyl-vecuronium-induced NMB, recovery was significantly faster than spontaneous recovery. Mean time to recovery of TOF to 90% was 3.2 min (sugammadex 0.5 mg kg) and 2.6 min (1.0 mg kg), compared to spontaneous recovery (17.6 min). For vecuronium-induced NMB, mean time to recovery of TOF to 90% was 17.1 min (0.5 mg kg) and 4.6 min (1.0 mg kg), compared to spontaneous recovery (23.4 min). CONCLUSIONSugammadex rapidly and effectively reversed 3-desacetyl-vecuronium-induced NMB in the rhesus monkey, at a lower dose than that needed to reverse vecuronium-induced NMB.</abstract><cop>England</cop><pub>European Society of Anaesthesiology</pub><pmid>21157358</pmid><doi>10.1097/EJA.0b013e328340894f</doi><tpages>8</tpages><oa>free_for_read</oa></addata></record>
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subjects Action Potentials
Animals
Electric Stimulation
Female
gamma-Cyclodextrins - administration & dosage
gamma-Cyclodextrins - pharmacology
Infusions, Intravenous
Injections, Intravenous
Macaca mulatta
Neuromuscular Junction - drug effects
Neuromuscular Nondepolarizing Agents - administration & dosage
Neuromuscular Nondepolarizing Agents - pharmacology
Recovery of Function
Time Factors
Vecuronium Bromide - administration & dosage
Vecuronium Bromide - analogs & derivatives
Vecuronium Bromide - pharmacology
title Sugammadex reverses neuromuscular block induced by 3-desacetyl-vecuronium, an active metabolite of vecuronium, in the anaesthetised rhesus monkey
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