Comparison of Clinical Outcomes in Nonintubated Patients with Severe Alcohol Withdrawal Syndrome Treated with Continuous-Infusion Sedatives: Dexmedetomidine versus Benzodiazepines

Study Objective To compare efficacy and safety outcomes in nonintubated patients with severe alcohol withdrawal syndrome (AWS) who required a continuous infusion of a benzodiazepine or dexmedetomidine in addition to standard medical therapy for AWS. Design Retrospective cohort study. Setting Two hos...

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Veröffentlicht in:Pharmacotherapy 2014-09, Vol.34 (9), p.910-917
Hauptverfasser: Crispo, Angela L., Daley, Mitchell J., Pepin, Jodie L., Harford, Paul H., Brown, Carlos V.R.
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container_end_page 917
container_issue 9
container_start_page 910
container_title Pharmacotherapy
container_volume 34
creator Crispo, Angela L.
Daley, Mitchell J.
Pepin, Jodie L.
Harford, Paul H.
Brown, Carlos V.R.
description Study Objective To compare efficacy and safety outcomes in nonintubated patients with severe alcohol withdrawal syndrome (AWS) who required a continuous infusion of a benzodiazepine or dexmedetomidine in addition to standard medical therapy for AWS. Design Retrospective cohort study. Setting Two hospitals within the same network that used different treatment strategies for AWS. Patients A total of 61 nonintubated adults who received a continuous infusion of either a benzodiazepine (BZD) (lorazepam or midazolam; 33 patients) or dexmedetomidine (DEX) (28 patients) for severe AWS between April 1, 2011, and October 31, 2012, as well as standard medical therapy for AWS. Measurements and Main Results The primary outcome was a composite end point including rates of respiratory distress requiring endotracheal intubation or occurrence of alcohol withdrawal seizures. No significant differences in the composite end point were noted between the BZD and DEX groups (9.1% and 7.1%, respectively, p>0.99) or its individual components of respiratory distress (9.1% and 7.1%, respectively, p>0.99) or alcohol withdrawal seizures (0% and 3.6%, respectively, p=0.46). The DEX group received a lower median total dose of lorazepam equivalents after initiation of the study drug (median [interquartile range] 105 [60–199.5] mg in the BZD group vs 3.5 [0–12] mg in the DEX group), but this did not translate into a reduced requirement for endotracheal intubation or decreased length of stay. DEX was associated with more adverse drug events including hypotension and bradycardia. Of concern, DEX may impair the ability to assess symptoms appropriately and administer BZDs in a symptom‐triggered fashion. Although the total cost of hospitalization was similar between groups, DEX was associated with a higher study drug cost per patient. Conclusion DEX demonstrated a BZD‐sparing effect in the treatment of AWS; however, this surrogate end point should be interpreted with caution. Although this study cannot disprove the possibility of a protective effect of DEX in preventing the requirement for endotracheal intubation in patients with AWS, an increased rate of adverse drug events and increased study drug costs were observed. If DEX is used in clinical practice, it should only be used as adjunctive therapy with BZDs that have a proven benefit in AWS.
doi_str_mv 10.1002/phar.1448
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Design Retrospective cohort study. Setting Two hospitals within the same network that used different treatment strategies for AWS. Patients A total of 61 nonintubated adults who received a continuous infusion of either a benzodiazepine (BZD) (lorazepam or midazolam; 33 patients) or dexmedetomidine (DEX) (28 patients) for severe AWS between April 1, 2011, and October 31, 2012, as well as standard medical therapy for AWS. Measurements and Main Results The primary outcome was a composite end point including rates of respiratory distress requiring endotracheal intubation or occurrence of alcohol withdrawal seizures. No significant differences in the composite end point were noted between the BZD and DEX groups (9.1% and 7.1%, respectively, p&gt;0.99) or its individual components of respiratory distress (9.1% and 7.1%, respectively, p&gt;0.99) or alcohol withdrawal seizures (0% and 3.6%, respectively, p=0.46). The DEX group received a lower median total dose of lorazepam equivalents after initiation of the study drug (median [interquartile range] 105 [60–199.5] mg in the BZD group vs 3.5 [0–12] mg in the DEX group), but this did not translate into a reduced requirement for endotracheal intubation or decreased length of stay. DEX was associated with more adverse drug events including hypotension and bradycardia. Of concern, DEX may impair the ability to assess symptoms appropriately and administer BZDs in a symptom‐triggered fashion. Although the total cost of hospitalization was similar between groups, DEX was associated with a higher study drug cost per patient. Conclusion DEX demonstrated a BZD‐sparing effect in the treatment of AWS; however, this surrogate end point should be interpreted with caution. Although this study cannot disprove the possibility of a protective effect of DEX in preventing the requirement for endotracheal intubation in patients with AWS, an increased rate of adverse drug events and increased study drug costs were observed. If DEX is used in clinical practice, it should only be used as adjunctive therapy with BZDs that have a proven benefit in AWS.</description><identifier>ISSN: 0277-0008</identifier><identifier>EISSN: 1875-9114</identifier><identifier>DOI: 10.1002/phar.1448</identifier><identifier>PMID: 24898418</identifier><language>eng</language><publisher>United States: Blackwell Publishing Ltd</publisher><subject>Adult ; Aged ; Alcohol ; alcohol withdrawal syndrome ; benzodiazepines ; Benzodiazepines - adverse effects ; Benzodiazepines - therapeutic use ; Cohort Studies ; critical care ; dexmedetomidine ; Dexmedetomidine - adverse effects ; Dexmedetomidine - therapeutic use ; Ethanol - adverse effects ; Female ; Humans ; Hypnotics and Sedatives - adverse effects ; Hypnotics and Sedatives - therapeutic use ; Infusions, Intravenous ; Intubation ; lorazepam ; Lorazepam - adverse effects ; Lorazepam - therapeutic use ; Male ; Medical treatment ; midazolam ; Midazolam - adverse effects ; Midazolam - therapeutic use ; Middle Aged ; Retrospective Studies ; Severity of Illness Index ; Substance Withdrawal Syndrome - drug therapy ; Treatment Outcome</subject><ispartof>Pharmacotherapy, 2014-09, Vol.34 (9), p.910-917</ispartof><rights>2014 Pharmacotherapy Publications, Inc.</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c4618-3f40ed6fb945f265d25b0db904fe632a79473284c06c73f1fc0e3769c48a9e1b3</citedby><cites>FETCH-LOGICAL-c4618-3f40ed6fb945f265d25b0db904fe632a79473284c06c73f1fc0e3769c48a9e1b3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://onlinelibrary.wiley.com/doi/pdf/10.1002%2Fphar.1448$$EPDF$$P50$$Gwiley$$H</linktopdf><linktohtml>$$Uhttps://onlinelibrary.wiley.com/doi/full/10.1002%2Fphar.1448$$EHTML$$P50$$Gwiley$$H</linktohtml><link.rule.ids>314,776,780,1411,27901,27902,45550,45551</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/24898418$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Crispo, Angela L.</creatorcontrib><creatorcontrib>Daley, Mitchell J.</creatorcontrib><creatorcontrib>Pepin, Jodie L.</creatorcontrib><creatorcontrib>Harford, Paul H.</creatorcontrib><creatorcontrib>Brown, Carlos V.R.</creatorcontrib><title>Comparison of Clinical Outcomes in Nonintubated Patients with Severe Alcohol Withdrawal Syndrome Treated with Continuous-Infusion Sedatives: Dexmedetomidine versus Benzodiazepines</title><title>Pharmacotherapy</title><addtitle>Pharmacotherapy</addtitle><description>Study Objective To compare efficacy and safety outcomes in nonintubated patients with severe alcohol withdrawal syndrome (AWS) who required a continuous infusion of a benzodiazepine or dexmedetomidine in addition to standard medical therapy for AWS. Design Retrospective cohort study. Setting Two hospitals within the same network that used different treatment strategies for AWS. Patients A total of 61 nonintubated adults who received a continuous infusion of either a benzodiazepine (BZD) (lorazepam or midazolam; 33 patients) or dexmedetomidine (DEX) (28 patients) for severe AWS between April 1, 2011, and October 31, 2012, as well as standard medical therapy for AWS. Measurements and Main Results The primary outcome was a composite end point including rates of respiratory distress requiring endotracheal intubation or occurrence of alcohol withdrawal seizures. No significant differences in the composite end point were noted between the BZD and DEX groups (9.1% and 7.1%, respectively, p&gt;0.99) or its individual components of respiratory distress (9.1% and 7.1%, respectively, p&gt;0.99) or alcohol withdrawal seizures (0% and 3.6%, respectively, p=0.46). The DEX group received a lower median total dose of lorazepam equivalents after initiation of the study drug (median [interquartile range] 105 [60–199.5] mg in the BZD group vs 3.5 [0–12] mg in the DEX group), but this did not translate into a reduced requirement for endotracheal intubation or decreased length of stay. DEX was associated with more adverse drug events including hypotension and bradycardia. Of concern, DEX may impair the ability to assess symptoms appropriately and administer BZDs in a symptom‐triggered fashion. Although the total cost of hospitalization was similar between groups, DEX was associated with a higher study drug cost per patient. Conclusion DEX demonstrated a BZD‐sparing effect in the treatment of AWS; however, this surrogate end point should be interpreted with caution. Although this study cannot disprove the possibility of a protective effect of DEX in preventing the requirement for endotracheal intubation in patients with AWS, an increased rate of adverse drug events and increased study drug costs were observed. If DEX is used in clinical practice, it should only be used as adjunctive therapy with BZDs that have a proven benefit in AWS.</description><subject>Adult</subject><subject>Aged</subject><subject>Alcohol</subject><subject>alcohol withdrawal syndrome</subject><subject>benzodiazepines</subject><subject>Benzodiazepines - adverse effects</subject><subject>Benzodiazepines - therapeutic use</subject><subject>Cohort Studies</subject><subject>critical care</subject><subject>dexmedetomidine</subject><subject>Dexmedetomidine - adverse effects</subject><subject>Dexmedetomidine - therapeutic use</subject><subject>Ethanol - adverse effects</subject><subject>Female</subject><subject>Humans</subject><subject>Hypnotics and Sedatives - adverse effects</subject><subject>Hypnotics and Sedatives - therapeutic use</subject><subject>Infusions, Intravenous</subject><subject>Intubation</subject><subject>lorazepam</subject><subject>Lorazepam - adverse effects</subject><subject>Lorazepam - therapeutic use</subject><subject>Male</subject><subject>Medical treatment</subject><subject>midazolam</subject><subject>Midazolam - adverse effects</subject><subject>Midazolam - therapeutic use</subject><subject>Middle Aged</subject><subject>Retrospective Studies</subject><subject>Severity of Illness Index</subject><subject>Substance Withdrawal Syndrome - drug therapy</subject><subject>Treatment Outcome</subject><issn>0277-0008</issn><issn>1875-9114</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2014</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp1kcFu1DAQhiMEotvCgRdAlrjAIa2dOHbCbRtKt6jatuyiHi0nmWhdEjvYTrfb1-IF8XaXHpA4WRp9882M_yh6R_AxwTg5GVbSHhNK8xfRhOQ8iwtC6MtoghPOY4xxfhAdOncXUMJo8jo6SGhe5JTkk-h3afpBWuWMRqZFZae0qmWHrkZfmx4cUhrNjVbaj5X00KBr6RVo79Ba-RVawD1YQNOuNivTodtQa6xcB8FioxsbDGhp4anxiS-N9kqPZnTxhW5Hp8LYBTTBeQ_uM_oCDz004E2vGqUBBbkbHToF_WgaJR9hCFX3JnrVys7B2_17FP34erYsZ_Hl1flFOb2Ma8pIHqctxdCwtipo1iYsa5Kswk1VYNoCSxPJC8rTJKc1ZjVPW9LWGFLOiprmsgBSpUfRx513sObXCM6LXrkauk5qCBcIkjGMC445D-iHf9A7M1odtttSjIVBOAvUpx1VW-OchVYMVvXSbgTBYpuk2CYptkkG9v3eOFbhT57Jv9EF4GQHrFUHm_-bxPVs-n2vjHcdynl4eO6Q9qcIC_JM3M7PBZ5lN8vk242Yp38Ajr67rQ</recordid><startdate>201409</startdate><enddate>201409</enddate><creator>Crispo, Angela L.</creator><creator>Daley, Mitchell J.</creator><creator>Pepin, Jodie L.</creator><creator>Harford, Paul H.</creator><creator>Brown, Carlos V.R.</creator><general>Blackwell Publishing Ltd</general><general>Wiley Subscription Services, Inc</general><scope>BSCLL</scope><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>7QP</scope><scope>7TK</scope><scope>K9.</scope><scope>7X8</scope></search><sort><creationdate>201409</creationdate><title>Comparison of Clinical Outcomes in Nonintubated Patients with Severe Alcohol Withdrawal Syndrome Treated with Continuous-Infusion Sedatives: Dexmedetomidine versus Benzodiazepines</title><author>Crispo, Angela L. ; 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Calcified Tissue Abstracts</collection><collection>Neurosciences Abstracts</collection><collection>ProQuest Health &amp; Medical Complete (Alumni)</collection><collection>MEDLINE - Academic</collection><jtitle>Pharmacotherapy</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Crispo, Angela L.</au><au>Daley, Mitchell J.</au><au>Pepin, Jodie L.</au><au>Harford, Paul H.</au><au>Brown, Carlos V.R.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Comparison of Clinical Outcomes in Nonintubated Patients with Severe Alcohol Withdrawal Syndrome Treated with Continuous-Infusion Sedatives: Dexmedetomidine versus Benzodiazepines</atitle><jtitle>Pharmacotherapy</jtitle><addtitle>Pharmacotherapy</addtitle><date>2014-09</date><risdate>2014</risdate><volume>34</volume><issue>9</issue><spage>910</spage><epage>917</epage><pages>910-917</pages><issn>0277-0008</issn><eissn>1875-9114</eissn><abstract>Study Objective To compare efficacy and safety outcomes in nonintubated patients with severe alcohol withdrawal syndrome (AWS) who required a continuous infusion of a benzodiazepine or dexmedetomidine in addition to standard medical therapy for AWS. Design Retrospective cohort study. Setting Two hospitals within the same network that used different treatment strategies for AWS. Patients A total of 61 nonintubated adults who received a continuous infusion of either a benzodiazepine (BZD) (lorazepam or midazolam; 33 patients) or dexmedetomidine (DEX) (28 patients) for severe AWS between April 1, 2011, and October 31, 2012, as well as standard medical therapy for AWS. Measurements and Main Results The primary outcome was a composite end point including rates of respiratory distress requiring endotracheal intubation or occurrence of alcohol withdrawal seizures. No significant differences in the composite end point were noted between the BZD and DEX groups (9.1% and 7.1%, respectively, p&gt;0.99) or its individual components of respiratory distress (9.1% and 7.1%, respectively, p&gt;0.99) or alcohol withdrawal seizures (0% and 3.6%, respectively, p=0.46). The DEX group received a lower median total dose of lorazepam equivalents after initiation of the study drug (median [interquartile range] 105 [60–199.5] mg in the BZD group vs 3.5 [0–12] mg in the DEX group), but this did not translate into a reduced requirement for endotracheal intubation or decreased length of stay. DEX was associated with more adverse drug events including hypotension and bradycardia. Of concern, DEX may impair the ability to assess symptoms appropriately and administer BZDs in a symptom‐triggered fashion. Although the total cost of hospitalization was similar between groups, DEX was associated with a higher study drug cost per patient. Conclusion DEX demonstrated a BZD‐sparing effect in the treatment of AWS; however, this surrogate end point should be interpreted with caution. Although this study cannot disprove the possibility of a protective effect of DEX in preventing the requirement for endotracheal intubation in patients with AWS, an increased rate of adverse drug events and increased study drug costs were observed. If DEX is used in clinical practice, it should only be used as adjunctive therapy with BZDs that have a proven benefit in AWS.</abstract><cop>United States</cop><pub>Blackwell Publishing Ltd</pub><pmid>24898418</pmid><doi>10.1002/phar.1448</doi><tpages>8</tpages></addata></record>
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subjects Adult
Aged
Alcohol
alcohol withdrawal syndrome
benzodiazepines
Benzodiazepines - adverse effects
Benzodiazepines - therapeutic use
Cohort Studies
critical care
dexmedetomidine
Dexmedetomidine - adverse effects
Dexmedetomidine - therapeutic use
Ethanol - adverse effects
Female
Humans
Hypnotics and Sedatives - adverse effects
Hypnotics and Sedatives - therapeutic use
Infusions, Intravenous
Intubation
lorazepam
Lorazepam - adverse effects
Lorazepam - therapeutic use
Male
Medical treatment
midazolam
Midazolam - adverse effects
Midazolam - therapeutic use
Middle Aged
Retrospective Studies
Severity of Illness Index
Substance Withdrawal Syndrome - drug therapy
Treatment Outcome
title Comparison of Clinical Outcomes in Nonintubated Patients with Severe Alcohol Withdrawal Syndrome Treated with Continuous-Infusion Sedatives: Dexmedetomidine versus Benzodiazepines
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