Effects of concurrent intravenous morphine sulfate and naltrexone hydrochloride on end-tidal carbon dioxide.docVIP

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Effects of concurrent intravenous morphine sulfate and naltrexone hydrochloride on end-tidal carbon dioxide.doc

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Effects of concurrent intravenous morphine sulfate and naltrexone hydrochloride on end-tidal carbon dioxide

Golietal.HarmReductionJournal2012,9:13 /content/9/1/13 RESEARCH OpenAccess Effectsofconcurrentintravenousmorphine sulfateandnaltrexonehydrochlorideonend-tidal carbondioxide VeeraindarGoli1,2,5*,LynnRWebster3,MichaelJLamson1,JodyMCleveland1,KennethWSommerville1,2 and EricCarter4 Abstract Background:Respiratorydepression,apotentiallyfatalside-effectofopioid-overdose,maybereversedbytimely administrationofanopioidantagonist,suchasnaloxoneornaltrexone.Tamperingwithaformulationofmorphine sulfateandsequesterednaltrexonehydrochlorideextendedreleasecapsules(MS-sNT)releasesboththeopioid morphineandtheantagonistnaltrexone.Astudyinrecreationalopioid-usersindicatedthatmorphineand naltrexoneinjectedinthe25:1ratio(duplicatingtheratiooftheformulation)foundMS-sNTreducedmorphine- inducedeuphoriceffectsvsintravenous(IV)morphinealone.Inthesamestudy,theeffectsofmorphine+ naltrexoneonend-tidalcarbondioxide(EtCO2),ameasureofrespiratory-depression,wereevaluatedandthese dataarereportedhere. Methods:Single-center,placebo-controlled,double-blindcrossoverstudy.Non-dependentmaleopioiduserswere randomizedtoreceivesingleIVdosesofplacebo,30mgmorphinealone,and30mgmorphine+1.2mg naltrexone.EtCO2wasmeasuredbynoninvasivecapnography. Results:SignificantdifferencesinEtCO2least-squaresmeansacrossalltreatmentsformaximaleffect(Emax )and areaundertheeffectcurve(AUE0-2,AUE0-8,AUE0-24)weredetected(allp≤0.0011).EtCO2Emax valuesformorphine +naltrexoneweresignificantlyreducedvsmorphinealone(42.9mmHgvs47.1mmHg,p0.0001)andwere notsignificantlydifferentvsplacebo(41.9mmHg).Mediantimetoreachmaximaleffect(TEmax)wasdelayedfor morphine+naltrexonevsmorphinealone(5.0hvs1.0h). Conclusions:Resultsprovidepreliminaryevidencethatthenaltrexone:morphineratiowithinMS-sNTissufficientto significantlyreduceEtCO2whenadministeredintravenouslytonon-dependentmalerecreationalopioid-users. Furtherstudieswithmultiplemeasuresofrespiratory-functionarewarrantedtodetermineifriskofrespiratory depressionisalsoreducedbynaltrexone