The Effect of Lipid Emulsion Infusion on Postmortem Ropivacaine Concentrations in Swine: Endeavoring to Comprehend a Soldier's Death

Lipid emulsion (20%) is advocated as a rescue drug for local anesthetic toxicity. No study has measured the impact of lipid emulsion therapy on postmortem local anesthetic serum levels. We anesthetized Yorkshire swine (n = 11) and standard monitors were placed. The swine received 1.5 mg/kg/min IV ro...

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Veröffentlicht in:Anesthesia and analgesia 2012-04, Vol.114 (4), p.894-900
Hauptverfasser: Buckenmaier, Chester C., Capacchione, John, Mielke, Arthur R., Bina, Saiid, Shields, Cynthia, Kwon, Kyung H., McKnight, Geselle, Fish, David A., Bedocs, Peter
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container_end_page 900
container_issue 4
container_start_page 894
container_title Anesthesia and analgesia
container_volume 114
creator Buckenmaier, Chester C.
Capacchione, John
Mielke, Arthur R.
Bina, Saiid
Shields, Cynthia
Kwon, Kyung H.
McKnight, Geselle
Fish, David A.
Bedocs, Peter
description Lipid emulsion (20%) is advocated as a rescue drug for local anesthetic toxicity. No study has measured the impact of lipid emulsion therapy on postmortem local anesthetic serum levels. We anesthetized Yorkshire swine (n = 11) and standard monitors were placed. The swine received 1.5 mg/kg/min IV ropivacaine until death (asystole). Blood samples were drawn before infusion (baseline) and at 5-minute intervals during the infusion for measurement of blood gases and free, bound, and total serum ropivacaine concentrations via high-performance liquid chromatography. Five swine received ropivacaine only, and 6 swine received ropivacaine plus a single bolus dose of 20% lipid emulsion (1 mg/kg) when the mean arterial blood pressure reached 50 mm Hg. Ropivacaine infusions were terminated at asystole and no resuscitation was initiated. Total ropivacaine dose and time to death were recorded. The swine were cooled (mean temperature, 25.5°C ± 0.8°C at 6 hours postmortem) to reflect morgue conditions. Serum samples were drawn at asystole, 1, 3, and 6 hours postmortem for analysis. Additionally, a craniotomy and laparotomy were performed at those times to remove 1.5 to 3 g each of brain, lung, liver, kidney, and muscle for analysis. Analysis of the postmortem serum ropivacaine concentrations in the control and the lipid-treated animals indicated that both the total (bound and not bound to proteins) and free (not bound to proteins) ropivacaine concentrations were significantly higher in the lipid-treated animals (P = 0.0094 and P = 0.0063, respectively). Furthermore, time had a significant effect on increasing the postmortem free ropivacaine concentrations (P = 0.0095). The lipid group had a statistically significant earlier onset of death (asystole) compared with the control group (P = 0.0274). Tissue analysis indicated that the ropivacaine concentration significantly decreased postmortem in the lung, kidney, and brain tissues of the lipid-treated animals (P = 0.0168, P = 0.0073, and P = 0.0018, respectively). Tissue drug concentrations in the control animals remained unchanged after death. Our data show that postmortem blood samples in swine that experience local anesthetic cardiovascular collapse and are treated with lipid emulsions will result in measurements that cannot be directly extrapolated to premortem drug concentrations.
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No study has measured the impact of lipid emulsion therapy on postmortem local anesthetic serum levels. We anesthetized Yorkshire swine (n = 11) and standard monitors were placed. The swine received 1.5 mg/kg/min IV ropivacaine until death (asystole). Blood samples were drawn before infusion (baseline) and at 5-minute intervals during the infusion for measurement of blood gases and free, bound, and total serum ropivacaine concentrations via high-performance liquid chromatography. Five swine received ropivacaine only, and 6 swine received ropivacaine plus a single bolus dose of 20% lipid emulsion (1 mg/kg) when the mean arterial blood pressure reached 50 mm Hg. Ropivacaine infusions were terminated at asystole and no resuscitation was initiated. Total ropivacaine dose and time to death were recorded. The swine were cooled (mean temperature, 25.5°C ± 0.8°C at 6 hours postmortem) to reflect morgue conditions. Serum samples were drawn at asystole, 1, 3, and 6 hours postmortem for analysis. Additionally, a craniotomy and laparotomy were performed at those times to remove 1.5 to 3 g each of brain, lung, liver, kidney, and muscle for analysis. Analysis of the postmortem serum ropivacaine concentrations in the control and the lipid-treated animals indicated that both the total (bound and not bound to proteins) and free (not bound to proteins) ropivacaine concentrations were significantly higher in the lipid-treated animals (P = 0.0094 and P = 0.0063, respectively). Furthermore, time had a significant effect on increasing the postmortem free ropivacaine concentrations (P = 0.0095). The lipid group had a statistically significant earlier onset of death (asystole) compared with the control group (P = 0.0274). 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No study has measured the impact of lipid emulsion therapy on postmortem local anesthetic serum levels. We anesthetized Yorkshire swine (n = 11) and standard monitors were placed. The swine received 1.5 mg/kg/min IV ropivacaine until death (asystole). Blood samples were drawn before infusion (baseline) and at 5-minute intervals during the infusion for measurement of blood gases and free, bound, and total serum ropivacaine concentrations via high-performance liquid chromatography. Five swine received ropivacaine only, and 6 swine received ropivacaine plus a single bolus dose of 20% lipid emulsion (1 mg/kg) when the mean arterial blood pressure reached 50 mm Hg. Ropivacaine infusions were terminated at asystole and no resuscitation was initiated. Total ropivacaine dose and time to death were recorded. The swine were cooled (mean temperature, 25.5°C ± 0.8°C at 6 hours postmortem) to reflect morgue conditions. Serum samples were drawn at asystole, 1, 3, and 6 hours postmortem for analysis. Additionally, a craniotomy and laparotomy were performed at those times to remove 1.5 to 3 g each of brain, lung, liver, kidney, and muscle for analysis. Analysis of the postmortem serum ropivacaine concentrations in the control and the lipid-treated animals indicated that both the total (bound and not bound to proteins) and free (not bound to proteins) ropivacaine concentrations were significantly higher in the lipid-treated animals (P = 0.0094 and P = 0.0063, respectively). Furthermore, time had a significant effect on increasing the postmortem free ropivacaine concentrations (P = 0.0095). The lipid group had a statistically significant earlier onset of death (asystole) compared with the control group (P = 0.0274). Tissue analysis indicated that the ropivacaine concentration significantly decreased postmortem in the lung, kidney, and brain tissues of the lipid-treated animals (P = 0.0168, P = 0.0073, and P = 0.0018, respectively). Tissue drug concentrations in the control animals remained unchanged after death. Our data show that postmortem blood samples in swine that experience local anesthetic cardiovascular collapse and are treated with lipid emulsions will result in measurements that cannot be directly extrapolated to premortem drug concentrations.</description><subject>Adult</subject><subject>Amides - pharmacokinetics</subject><subject>Amides - toxicity</subject><subject>Anesthesia</subject><subject>Anesthesia. Intensive care medicine. Transfusions. Cell therapy and gene therapy</subject><subject>Anesthetics, Local - pharmacokinetics</subject><subject>Animals</subject><subject>Autopsy</subject><subject>Biological and medical sciences</subject><subject>Fat Emulsions, Intravenous - pharmacology</subject><subject>Humans</subject><subject>Male</subject><subject>Medical sciences</subject><subject>Military Personnel</subject><subject>Swine</subject><issn>0003-2999</issn><issn>1526-7598</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2012</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNpdkd9rFDEQx4Mo9lr9D0TyIj5tze_b-FbOtRYOFVufl1x24kZ3kyXJ9fDdP9ycrRYcBpIJn--E-Q5CLyg5p4zyNxcfu3OyI5QDpy1jlpJd-witqGSqWUvdPkYrQghvmNb6BJ3m_L2WlLTqKTphtFVS6HaFft2MgDvnwBYcHd76xQ-4m_dT9jHgq-D2fy41P8dc5pgKzPhLXPytscYHwJsYLISSTKlcxj7g60N9f4u7MIC5jcmHb7jEys1LghHCgA2-jtPgIb3O-B2YMj5DT5yZMjy_P8_Q1_fdzeZDs_10ebW52DaW8zqJkNYwx410SuzWwlBQdFhrZzRIrdjaSG6JJcwQoS1VgwbStuC4VaCt4I6fIXHX16aYcwLXL8nPJv3sKemPpvbV1P5_U6vs5Z1s2e9mGP6J_rpYgVf3gMnWTC6ZYH1-4KTSLRXy4f9DnAqk_GPaHyD1I5ipjD05huS6YYQyImrRHBfI-W-K1pGn</recordid><startdate>20120401</startdate><enddate>20120401</enddate><creator>Buckenmaier, Chester C.</creator><creator>Capacchione, John</creator><creator>Mielke, Arthur R.</creator><creator>Bina, Saiid</creator><creator>Shields, Cynthia</creator><creator>Kwon, Kyung H.</creator><creator>McKnight, Geselle</creator><creator>Fish, David A.</creator><creator>Bedocs, Peter</creator><general>International Anesthesia Research Society</general><general>Lippincott Williams &amp; Wilkins</general><scope>IQODW</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></search><sort><creationdate>20120401</creationdate><title>The Effect of Lipid Emulsion Infusion on Postmortem Ropivacaine Concentrations in Swine: Endeavoring to Comprehend a Soldier's Death</title><author>Buckenmaier, Chester C. ; Capacchione, John ; Mielke, Arthur R. ; Bina, Saiid ; Shields, Cynthia ; Kwon, Kyung H. ; McKnight, Geselle ; Fish, David A. ; Bedocs, Peter</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c3303-45ca2f3a5f64b74a1e61d79fa9e59627a53c0c02a049c16d9e088ef3c6e9c43f3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2012</creationdate><topic>Adult</topic><topic>Amides - pharmacokinetics</topic><topic>Amides - toxicity</topic><topic>Anesthesia</topic><topic>Anesthesia. 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Cell therapy and gene therapy</topic><topic>Anesthetics, Local - pharmacokinetics</topic><topic>Animals</topic><topic>Autopsy</topic><topic>Biological and medical sciences</topic><topic>Fat Emulsions, Intravenous - pharmacology</topic><topic>Humans</topic><topic>Male</topic><topic>Medical sciences</topic><topic>Military Personnel</topic><topic>Swine</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Buckenmaier, Chester C.</creatorcontrib><creatorcontrib>Capacchione, John</creatorcontrib><creatorcontrib>Mielke, Arthur R.</creatorcontrib><creatorcontrib>Bina, Saiid</creatorcontrib><creatorcontrib>Shields, Cynthia</creatorcontrib><creatorcontrib>Kwon, Kyung H.</creatorcontrib><creatorcontrib>McKnight, Geselle</creatorcontrib><creatorcontrib>Fish, David A.</creatorcontrib><creatorcontrib>Bedocs, Peter</creatorcontrib><collection>Pascal-Francis</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><jtitle>Anesthesia and analgesia</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Buckenmaier, Chester C.</au><au>Capacchione, John</au><au>Mielke, Arthur R.</au><au>Bina, Saiid</au><au>Shields, Cynthia</au><au>Kwon, Kyung H.</au><au>McKnight, Geselle</au><au>Fish, David A.</au><au>Bedocs, Peter</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>The Effect of Lipid Emulsion Infusion on Postmortem Ropivacaine Concentrations in Swine: Endeavoring to Comprehend a Soldier's Death</atitle><jtitle>Anesthesia and analgesia</jtitle><addtitle>Anesth Analg</addtitle><date>2012-04-01</date><risdate>2012</risdate><volume>114</volume><issue>4</issue><spage>894</spage><epage>900</epage><pages>894-900</pages><issn>0003-2999</issn><eissn>1526-7598</eissn><coden>AACRAT</coden><abstract>Lipid emulsion (20%) is advocated as a rescue drug for local anesthetic toxicity. No study has measured the impact of lipid emulsion therapy on postmortem local anesthetic serum levels. We anesthetized Yorkshire swine (n = 11) and standard monitors were placed. The swine received 1.5 mg/kg/min IV ropivacaine until death (asystole). Blood samples were drawn before infusion (baseline) and at 5-minute intervals during the infusion for measurement of blood gases and free, bound, and total serum ropivacaine concentrations via high-performance liquid chromatography. Five swine received ropivacaine only, and 6 swine received ropivacaine plus a single bolus dose of 20% lipid emulsion (1 mg/kg) when the mean arterial blood pressure reached 50 mm Hg. Ropivacaine infusions were terminated at asystole and no resuscitation was initiated. Total ropivacaine dose and time to death were recorded. The swine were cooled (mean temperature, 25.5°C ± 0.8°C at 6 hours postmortem) to reflect morgue conditions. Serum samples were drawn at asystole, 1, 3, and 6 hours postmortem for analysis. Additionally, a craniotomy and laparotomy were performed at those times to remove 1.5 to 3 g each of brain, lung, liver, kidney, and muscle for analysis. Analysis of the postmortem serum ropivacaine concentrations in the control and the lipid-treated animals indicated that both the total (bound and not bound to proteins) and free (not bound to proteins) ropivacaine concentrations were significantly higher in the lipid-treated animals (P = 0.0094 and P = 0.0063, respectively). Furthermore, time had a significant effect on increasing the postmortem free ropivacaine concentrations (P = 0.0095). The lipid group had a statistically significant earlier onset of death (asystole) compared with the control group (P = 0.0274). Tissue analysis indicated that the ropivacaine concentration significantly decreased postmortem in the lung, kidney, and brain tissues of the lipid-treated animals (P = 0.0168, P = 0.0073, and P = 0.0018, respectively). Tissue drug concentrations in the control animals remained unchanged after death. Our data show that postmortem blood samples in swine that experience local anesthetic cardiovascular collapse and are treated with lipid emulsions will result in measurements that cannot be directly extrapolated to premortem drug concentrations.</abstract><cop>Hagerstown, MD</cop><pub>International Anesthesia Research Society</pub><pmid>21865498</pmid><doi>10.1213/ANE.0b013e31822c10b8</doi><tpages>7</tpages></addata></record>
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source MEDLINE; Journals@Ovid LWW Legacy Archive; EZB-FREE-00999 freely available EZB journals
subjects Adult
Amides - pharmacokinetics
Amides - toxicity
Anesthesia
Anesthesia. Intensive care medicine. Transfusions. Cell therapy and gene therapy
Anesthetics, Local - pharmacokinetics
Animals
Autopsy
Biological and medical sciences
Fat Emulsions, Intravenous - pharmacology
Humans
Male
Medical sciences
Military Personnel
Swine
title The Effect of Lipid Emulsion Infusion on Postmortem Ropivacaine Concentrations in Swine: Endeavoring to Comprehend a Soldier's Death
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