Formulation and Evaluation of Lidocaine Base Ethosomes for Transdermal Delivery
BACKGROUND:Although transdermal preparations of local anesthetics have been used to reduce pain caused by skin surgery, these preparations cannot effectively penetrate through the epidermis because of the barrier formed by the stratum corneum and the thick epidermis. Ethosomes can effectively transp...
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| Veröffentlicht in: | Anesthesia and analgesia 2013-08, Vol.117 (2), p.352-357 |
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| creator | Zhu, Xiaoliang Li, Fuli Peng, Xuebiao Zeng, Kang |
| description | BACKGROUND:Although transdermal preparations of local anesthetics have been used to reduce pain caused by skin surgery, these preparations cannot effectively penetrate through the epidermis because of the barrier formed by the stratum corneum and the thick epidermis. Ethosomes can effectively transport drugs across the skin because of their thermodynamic stability, small size, high encapsulation efficiency, and percutaneous penetration. We evaluated lidocaine base ethosomes by measuring their loading efficiency, encapsulation efficiency, thermodynamic stability, and percutaneous penetration capability in vitro, and their effectiveness and cutaneous irritation in vivo.
METHODS:Lidocaine base ethosomes were prepared using the injection-sonication-filter method. Size, loading efficiency, encapsulation efficiency, and stability were evaluated using a Zetasizer and high performance liquid chromatography. Formulation was determined by measuring the maximum encapsulation efficiency in the orthogonal test. Percutaneous penetration efficiency in vitro was analyzed using a Franz-type diffusion cell experiment. In vivo effectiveness was analyzed using the pinprick test. Cutaneous irritancy tests were performed on white guinea pigs, followed by histopathologic analysis. The results were compared with lidocaine liposomes as well as lidocaine delivered in a hydroethanolic solution.
RESULTS:Lidocaine base ethosomes composed of 5% (w/w) egg phosphatidyl choline, 35% (w/w) ethanol, 0.2% (w/w) cholesterol, 5% (w/w) lidocaine base, and ultrapure water had a mean maximum encapsulation of 51% ± 4%, a mean particle size of 31 ± 3 nm, and a mean loading efficiency of 95.0% ± 0.1%. The encapsulation efficiency of lidocaine base ethosomes remained stable for 60 days at 25°C ± 1°C (95% confidence interval [CI], −1.12% to 1.34%; P = 0.833). The transdermal flux of lidocaine base differed significantly for the 3 preparations (F = 120, P < 0.001), being significantly greater from ethosomes than from liposomes (95% corrected CI, 1129–1818 µg/(cm·h); P < 0.001), and from hydroethanolic solution (95% corrected CI, 1468–2157 µg/(cm·h); P < 0.001). Lidocaine base ethosomes had a shorter onset time and longer duration in vivo than did lidocaine base liposomes or lidocaine delivered in a hydroethanolic solution. Lidocaine base ethosomes showed no evidence of dermal irritation in guinea pigs.
CONCLUSIONS:Ethosomes are potential carriers of local anesthetics across the skin and may have applic |
| doi_str_mv | 10.1213/ANE.0b013e3182937b74 |
| format | Article |
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METHODS:Lidocaine base ethosomes were prepared using the injection-sonication-filter method. Size, loading efficiency, encapsulation efficiency, and stability were evaluated using a Zetasizer and high performance liquid chromatography. Formulation was determined by measuring the maximum encapsulation efficiency in the orthogonal test. Percutaneous penetration efficiency in vitro was analyzed using a Franz-type diffusion cell experiment. In vivo effectiveness was analyzed using the pinprick test. Cutaneous irritancy tests were performed on white guinea pigs, followed by histopathologic analysis. The results were compared with lidocaine liposomes as well as lidocaine delivered in a hydroethanolic solution.
RESULTS:Lidocaine base ethosomes composed of 5% (w/w) egg phosphatidyl choline, 35% (w/w) ethanol, 0.2% (w/w) cholesterol, 5% (w/w) lidocaine base, and ultrapure water had a mean maximum encapsulation of 51% ± 4%, a mean particle size of 31 ± 3 nm, and a mean loading efficiency of 95.0% ± 0.1%. The encapsulation efficiency of lidocaine base ethosomes remained stable for 60 days at 25°C ± 1°C (95% confidence interval [CI], −1.12% to 1.34%; P = 0.833). The transdermal flux of lidocaine base differed significantly for the 3 preparations (F = 120, P < 0.001), being significantly greater from ethosomes than from liposomes (95% corrected CI, 1129–1818 µg/(cm·h); P < 0.001), and from hydroethanolic solution (95% corrected CI, 1468–2157 µg/(cm·h); P < 0.001). Lidocaine base ethosomes had a shorter onset time and longer duration in vivo than did lidocaine base liposomes or lidocaine delivered in a hydroethanolic solution. Lidocaine base ethosomes showed no evidence of dermal irritation in guinea pigs.
CONCLUSIONS:Ethosomes are potential carriers of local anesthetics across the skin and may have applicability for other percutaneous drugs that require rapid onset.</description><identifier>ISSN: 0003-2999</identifier><identifier>EISSN: 1526-7598</identifier><identifier>DOI: 10.1213/ANE.0b013e3182937b74</identifier><identifier>PMID: 23744957</identifier><language>eng</language><publisher>United States: International Anesthesia Research Society</publisher><subject>Administration, Cutaneous ; Anesthetics, Local - administration & dosage ; Anesthetics, Local - chemistry ; Anesthetics, Local - metabolism ; Anesthetics, Local - toxicity ; Animals ; Chemistry, Pharmaceutical ; Cholesterol - chemistry ; Chromatography, High Pressure Liquid ; Drug Carriers ; Drug Stability ; Edema - chemically induced ; Edema - pathology ; Erythema - chemically induced ; Erythema - pathology ; Ethanol - chemistry ; Guinea Pigs ; Lidocaine - administration & dosage ; Lidocaine - chemistry ; Lidocaine - metabolism ; Lidocaine - toxicity ; Liposomes ; Pain Threshold - drug effects ; Particle Size ; Permeability ; Phosphatidylcholines - chemistry ; Rats ; Rats, Sprague-Dawley ; Skin - drug effects ; Skin - metabolism ; Skin - pathology ; Skin Absorption ; Skin Irritancy Tests</subject><ispartof>Anesthesia and analgesia, 2013-08, Vol.117 (2), p.352-357</ispartof><rights>International Anesthesia Research Society</rights><rights>2013 International Anethesia Research Society</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c4734-bb5d42cca90b305fd6d244f7f20e7ce985fd0669fbd3c6e90a50bd2bb688a0043</citedby><cites>FETCH-LOGICAL-c4734-bb5d42cca90b305fd6d244f7f20e7ce985fd0669fbd3c6e90a50bd2bb688a0043</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttp://ovidsp.ovid.com/ovidweb.cgi?T=JS&NEWS=n&CSC=Y&PAGE=fulltext&D=ovft&AN=00000539-201308000-00011$$EHTML$$P50$$Gwolterskluwer$$H</linktohtml><link.rule.ids>314,776,780,4595,27901,27902,65206</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/23744957$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Zhu, Xiaoliang</creatorcontrib><creatorcontrib>Li, Fuli</creatorcontrib><creatorcontrib>Peng, Xuebiao</creatorcontrib><creatorcontrib>Zeng, Kang</creatorcontrib><title>Formulation and Evaluation of Lidocaine Base Ethosomes for Transdermal Delivery</title><title>Anesthesia and analgesia</title><addtitle>Anesth Analg</addtitle><description>BACKGROUND:Although transdermal preparations of local anesthetics have been used to reduce pain caused by skin surgery, these preparations cannot effectively penetrate through the epidermis because of the barrier formed by the stratum corneum and the thick epidermis. Ethosomes can effectively transport drugs across the skin because of their thermodynamic stability, small size, high encapsulation efficiency, and percutaneous penetration. We evaluated lidocaine base ethosomes by measuring their loading efficiency, encapsulation efficiency, thermodynamic stability, and percutaneous penetration capability in vitro, and their effectiveness and cutaneous irritation in vivo.
METHODS:Lidocaine base ethosomes were prepared using the injection-sonication-filter method. Size, loading efficiency, encapsulation efficiency, and stability were evaluated using a Zetasizer and high performance liquid chromatography. Formulation was determined by measuring the maximum encapsulation efficiency in the orthogonal test. Percutaneous penetration efficiency in vitro was analyzed using a Franz-type diffusion cell experiment. In vivo effectiveness was analyzed using the pinprick test. Cutaneous irritancy tests were performed on white guinea pigs, followed by histopathologic analysis. The results were compared with lidocaine liposomes as well as lidocaine delivered in a hydroethanolic solution.
RESULTS:Lidocaine base ethosomes composed of 5% (w/w) egg phosphatidyl choline, 35% (w/w) ethanol, 0.2% (w/w) cholesterol, 5% (w/w) lidocaine base, and ultrapure water had a mean maximum encapsulation of 51% ± 4%, a mean particle size of 31 ± 3 nm, and a mean loading efficiency of 95.0% ± 0.1%. The encapsulation efficiency of lidocaine base ethosomes remained stable for 60 days at 25°C ± 1°C (95% confidence interval [CI], −1.12% to 1.34%; P = 0.833). The transdermal flux of lidocaine base differed significantly for the 3 preparations (F = 120, P < 0.001), being significantly greater from ethosomes than from liposomes (95% corrected CI, 1129–1818 µg/(cm·h); P < 0.001), and from hydroethanolic solution (95% corrected CI, 1468–2157 µg/(cm·h); P < 0.001). Lidocaine base ethosomes had a shorter onset time and longer duration in vivo than did lidocaine base liposomes or lidocaine delivered in a hydroethanolic solution. Lidocaine base ethosomes showed no evidence of dermal irritation in guinea pigs.
CONCLUSIONS:Ethosomes are potential carriers of local anesthetics across the skin and may have applicability for other percutaneous drugs that require rapid onset.</description><subject>Administration, Cutaneous</subject><subject>Anesthetics, Local - administration & dosage</subject><subject>Anesthetics, Local - chemistry</subject><subject>Anesthetics, Local - metabolism</subject><subject>Anesthetics, Local - toxicity</subject><subject>Animals</subject><subject>Chemistry, Pharmaceutical</subject><subject>Cholesterol - chemistry</subject><subject>Chromatography, High Pressure Liquid</subject><subject>Drug Carriers</subject><subject>Drug Stability</subject><subject>Edema - chemically induced</subject><subject>Edema - pathology</subject><subject>Erythema - chemically induced</subject><subject>Erythema - pathology</subject><subject>Ethanol - chemistry</subject><subject>Guinea Pigs</subject><subject>Lidocaine - administration & dosage</subject><subject>Lidocaine - chemistry</subject><subject>Lidocaine - metabolism</subject><subject>Lidocaine - toxicity</subject><subject>Liposomes</subject><subject>Pain Threshold - drug effects</subject><subject>Particle Size</subject><subject>Permeability</subject><subject>Phosphatidylcholines - chemistry</subject><subject>Rats</subject><subject>Rats, Sprague-Dawley</subject><subject>Skin - drug effects</subject><subject>Skin - metabolism</subject><subject>Skin - pathology</subject><subject>Skin Absorption</subject><subject>Skin Irritancy Tests</subject><issn>0003-2999</issn><issn>1526-7598</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2013</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqFkUlPxDAMhSMEgmH5Bwj1yKXgbG1yZBkWaQQXOFdJ42oKaQNJC-Lf09EABw7gi_Ws92zpMyGHFE4oo_z07G5-AhYoR04V07y0pdggMypZkZdSq00yAwCeM631DtlN6WmSFFSxTXYYL4XQspyR-6sQu9GboQ19ZnqXzd-MH9cyNNmidaE2bY_ZuUmYzYdlSKHDlDUhZg_R9Mlh7IzPLtG3bxg_9slWY3zCg6--Rx6v5g8XN_ni_vr24myR16LkIrdWOsHq2miwHGTjCseEaMqGAZY1ajWNoCh0Yx2vC9RgJFjHrC2UMgCC75Hj9d6XGF5HTEPVtalG702PYUwVFZRJqUCvrGJtrWNIKWJTvcS2M_GjolCtUFYTyuo3yil29HVhtB26n9A3u8mg1ob34AeM6dmP7xirJRo_LP_bLf6Iwqok1zmbYqAmka9eR_knE42RrQ</recordid><startdate>201308</startdate><enddate>201308</enddate><creator>Zhu, Xiaoliang</creator><creator>Li, Fuli</creator><creator>Peng, Xuebiao</creator><creator>Zeng, Kang</creator><general>International Anesthesia Research Society</general><general>International Anethesia Research Society</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7X8</scope></search><sort><creationdate>201308</creationdate><title>Formulation and Evaluation of Lidocaine Base Ethosomes for Transdermal Delivery</title><author>Zhu, Xiaoliang ; Li, Fuli ; Peng, Xuebiao ; Zeng, Kang</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c4734-bb5d42cca90b305fd6d244f7f20e7ce985fd0669fbd3c6e90a50bd2bb688a0043</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2013</creationdate><topic>Administration, Cutaneous</topic><topic>Anesthetics, Local - administration & dosage</topic><topic>Anesthetics, Local - chemistry</topic><topic>Anesthetics, Local - metabolism</topic><topic>Anesthetics, Local - toxicity</topic><topic>Animals</topic><topic>Chemistry, Pharmaceutical</topic><topic>Cholesterol - chemistry</topic><topic>Chromatography, High Pressure Liquid</topic><topic>Drug Carriers</topic><topic>Drug Stability</topic><topic>Edema - chemically induced</topic><topic>Edema - pathology</topic><topic>Erythema - chemically induced</topic><topic>Erythema - pathology</topic><topic>Ethanol - chemistry</topic><topic>Guinea Pigs</topic><topic>Lidocaine - administration & dosage</topic><topic>Lidocaine - chemistry</topic><topic>Lidocaine - metabolism</topic><topic>Lidocaine - toxicity</topic><topic>Liposomes</topic><topic>Pain Threshold - drug effects</topic><topic>Particle Size</topic><topic>Permeability</topic><topic>Phosphatidylcholines - chemistry</topic><topic>Rats</topic><topic>Rats, Sprague-Dawley</topic><topic>Skin - drug effects</topic><topic>Skin - metabolism</topic><topic>Skin - pathology</topic><topic>Skin Absorption</topic><topic>Skin Irritancy Tests</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Zhu, Xiaoliang</creatorcontrib><creatorcontrib>Li, Fuli</creatorcontrib><creatorcontrib>Peng, Xuebiao</creatorcontrib><creatorcontrib>Zeng, Kang</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>Anesthesia and analgesia</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Zhu, Xiaoliang</au><au>Li, Fuli</au><au>Peng, Xuebiao</au><au>Zeng, Kang</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Formulation and Evaluation of Lidocaine Base Ethosomes for Transdermal Delivery</atitle><jtitle>Anesthesia and analgesia</jtitle><addtitle>Anesth Analg</addtitle><date>2013-08</date><risdate>2013</risdate><volume>117</volume><issue>2</issue><spage>352</spage><epage>357</epage><pages>352-357</pages><issn>0003-2999</issn><eissn>1526-7598</eissn><abstract>BACKGROUND:Although transdermal preparations of local anesthetics have been used to reduce pain caused by skin surgery, these preparations cannot effectively penetrate through the epidermis because of the barrier formed by the stratum corneum and the thick epidermis. Ethosomes can effectively transport drugs across the skin because of their thermodynamic stability, small size, high encapsulation efficiency, and percutaneous penetration. We evaluated lidocaine base ethosomes by measuring their loading efficiency, encapsulation efficiency, thermodynamic stability, and percutaneous penetration capability in vitro, and their effectiveness and cutaneous irritation in vivo.
METHODS:Lidocaine base ethosomes were prepared using the injection-sonication-filter method. Size, loading efficiency, encapsulation efficiency, and stability were evaluated using a Zetasizer and high performance liquid chromatography. Formulation was determined by measuring the maximum encapsulation efficiency in the orthogonal test. Percutaneous penetration efficiency in vitro was analyzed using a Franz-type diffusion cell experiment. In vivo effectiveness was analyzed using the pinprick test. Cutaneous irritancy tests were performed on white guinea pigs, followed by histopathologic analysis. The results were compared with lidocaine liposomes as well as lidocaine delivered in a hydroethanolic solution.
RESULTS:Lidocaine base ethosomes composed of 5% (w/w) egg phosphatidyl choline, 35% (w/w) ethanol, 0.2% (w/w) cholesterol, 5% (w/w) lidocaine base, and ultrapure water had a mean maximum encapsulation of 51% ± 4%, a mean particle size of 31 ± 3 nm, and a mean loading efficiency of 95.0% ± 0.1%. The encapsulation efficiency of lidocaine base ethosomes remained stable for 60 days at 25°C ± 1°C (95% confidence interval [CI], −1.12% to 1.34%; P = 0.833). The transdermal flux of lidocaine base differed significantly for the 3 preparations (F = 120, P < 0.001), being significantly greater from ethosomes than from liposomes (95% corrected CI, 1129–1818 µg/(cm·h); P < 0.001), and from hydroethanolic solution (95% corrected CI, 1468–2157 µg/(cm·h); P < 0.001). Lidocaine base ethosomes had a shorter onset time and longer duration in vivo than did lidocaine base liposomes or lidocaine delivered in a hydroethanolic solution. Lidocaine base ethosomes showed no evidence of dermal irritation in guinea pigs.
CONCLUSIONS:Ethosomes are potential carriers of local anesthetics across the skin and may have applicability for other percutaneous drugs that require rapid onset.</abstract><cop>United States</cop><pub>International Anesthesia Research Society</pub><pmid>23744957</pmid><doi>10.1213/ANE.0b013e3182937b74</doi><tpages>6</tpages><oa>free_for_read</oa></addata></record> |
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| subjects | Administration, Cutaneous Anesthetics, Local - administration & dosage Anesthetics, Local - chemistry Anesthetics, Local - metabolism Anesthetics, Local - toxicity Animals Chemistry, Pharmaceutical Cholesterol - chemistry Chromatography, High Pressure Liquid Drug Carriers Drug Stability Edema - chemically induced Edema - pathology Erythema - chemically induced Erythema - pathology Ethanol - chemistry Guinea Pigs Lidocaine - administration & dosage Lidocaine - chemistry Lidocaine - metabolism Lidocaine - toxicity Liposomes Pain Threshold - drug effects Particle Size Permeability Phosphatidylcholines - chemistry Rats Rats, Sprague-Dawley Skin - drug effects Skin - metabolism Skin - pathology Skin Absorption Skin Irritancy Tests |
| title | Formulation and Evaluation of Lidocaine Base Ethosomes for Transdermal Delivery |
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