Single dose epidural hydromorphone in labour pain: maternal pharmacokinetics and neonatal exposure
Introduction Epidural hydromorphone could be useful in obstetric analgesia as there is a need for a more water-soluble opioid than sufentanil or fentanyl with prolonged analgesic effect. To our knowledge, the pharmacokinetics of epidural hydromorphone has not been evaluated in parturients. Materials...
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creator | Puhto, Terhi Kokki, Merja Hakomäki, Henriikka Spalding, Michael Gunnar, Teemu Alahuhta, Seppo Vakkala, Merja |
description | Introduction
Epidural hydromorphone could be useful in obstetric analgesia as there is a need for a more water-soluble opioid than sufentanil or fentanyl with prolonged analgesic effect. To our knowledge, the pharmacokinetics of epidural hydromorphone has not been evaluated in parturients.
Materials and methods
In this pilot study, seven healthy parturients were given a single epidural dose of hydromorphone for labour pain. One parturient received 1.5 mg, two 0.75 mg and four 0.5 mg of hydromorphone hydrochloride. Dose was decreased due to nausea and pruritus. Hydromorphone’s effect, adverse effects and plasma concentrations were evaluated. Neonatal drug exposure was evaluated by umbilical vein and artery opioid concentration at birth. Neonatal outcomes were assessed using Apgar and the Neurologic Adaptive Capacity Score (NACS).
Results
All patients received additional levobupivacaine doses on parturients’ requests. The first dose was requested at a median of 163 min (range 19–303 min) after hydromorphone administration. A total of 12 opioid related expected adverse events were reported by seven parturients. All newborn outcomes were uneventful. Hydromorphone’s distribution and elimination after single epidural dose seem similar to that reported for non-pregnant subjects after intravenous hydromorphone administration, but further research is required to confirm this observation.
Conclusions
The optimal dose of hydromorphone in labour pain warrants further evaluation. |
doi_str_mv | 10.1007/s00228-020-02880-6 |
format | Article |
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Epidural hydromorphone could be useful in obstetric analgesia as there is a need for a more water-soluble opioid than sufentanil or fentanyl with prolonged analgesic effect. To our knowledge, the pharmacokinetics of epidural hydromorphone has not been evaluated in parturients.
Materials and methods
In this pilot study, seven healthy parturients were given a single epidural dose of hydromorphone for labour pain. One parturient received 1.5 mg, two 0.75 mg and four 0.5 mg of hydromorphone hydrochloride. Dose was decreased due to nausea and pruritus. Hydromorphone’s effect, adverse effects and plasma concentrations were evaluated. Neonatal drug exposure was evaluated by umbilical vein and artery opioid concentration at birth. Neonatal outcomes were assessed using Apgar and the Neurologic Adaptive Capacity Score (NACS).
Results
All patients received additional levobupivacaine doses on parturients’ requests. The first dose was requested at a median of 163 min (range 19–303 min) after hydromorphone administration. A total of 12 opioid related expected adverse events were reported by seven parturients. All newborn outcomes were uneventful. Hydromorphone’s distribution and elimination after single epidural dose seem similar to that reported for non-pregnant subjects after intravenous hydromorphone administration, but further research is required to confirm this observation.
Conclusions
The optimal dose of hydromorphone in labour pain warrants further evaluation.</description><identifier>ISSN: 0031-6970</identifier><identifier>EISSN: 1432-1041</identifier><identifier>DOI: 10.1007/s00228-020-02880-6</identifier><identifier>PMID: 32363420</identifier><language>eng</language><publisher>Berlin/Heidelberg: Springer Berlin Heidelberg</publisher><subject>Adult ; Analgesia ; Analgesia, Epidural - adverse effects ; Analgesia, Obstetrical - adverse effects ; Analgesics ; Analgesics, Opioid - administration & dosage ; Analgesics, Opioid - adverse effects ; Analgesics, Opioid - pharmacokinetics ; Apgar Score ; Biomedical and Life Sciences ; Biomedicine ; Childbirth & labor ; Epidural ; Female ; Fentanyl ; Humans ; Hydromorphone - administration & dosage ; Hydromorphone - adverse effects ; Hydromorphone - pharmacokinetics ; Infant, Newborn ; Intravenous administration ; Labor Pain - drug therapy ; Male ; Maternal-Fetal Exchange ; Narcotics ; Nausea ; Neonates ; Newborn babies ; Opioids ; Pain ; Pain perception ; Pharmacokinetics ; Pharmacokinetics and Disposition ; Pharmacology/Toxicology ; Pilot Projects ; Pregnancy ; Pruritus ; Sufentanil ; Umbilical vein ; Young Adult</subject><ispartof>European journal of clinical pharmacology, 2020-07, Vol.76 (7), p.969-977</ispartof><rights>The Author(s) 2020</rights><rights>The Author(s) 2020. This work is published under http://creativecommons.org/licenses/by/4.0/ (the “License”). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c474t-d1835ed903865e8600a71ec1d2b5cd6fd5f81c30ca87b3fe561368bdbf3820543</citedby><cites>FETCH-LOGICAL-c474t-d1835ed903865e8600a71ec1d2b5cd6fd5f81c30ca87b3fe561368bdbf3820543</cites><orcidid>0000-0002-8277-5429</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://link.springer.com/content/pdf/10.1007/s00228-020-02880-6$$EPDF$$P50$$Gspringer$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://link.springer.com/10.1007/s00228-020-02880-6$$EHTML$$P50$$Gspringer$$Hfree_for_read</linktohtml><link.rule.ids>230,314,776,780,881,27901,27902,41464,42533,51294</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/32363420$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Puhto, Terhi</creatorcontrib><creatorcontrib>Kokki, Merja</creatorcontrib><creatorcontrib>Hakomäki, Henriikka</creatorcontrib><creatorcontrib>Spalding, Michael</creatorcontrib><creatorcontrib>Gunnar, Teemu</creatorcontrib><creatorcontrib>Alahuhta, Seppo</creatorcontrib><creatorcontrib>Vakkala, Merja</creatorcontrib><title>Single dose epidural hydromorphone in labour pain: maternal pharmacokinetics and neonatal exposure</title><title>European journal of clinical pharmacology</title><addtitle>Eur J Clin Pharmacol</addtitle><addtitle>Eur J Clin Pharmacol</addtitle><description>Introduction
Epidural hydromorphone could be useful in obstetric analgesia as there is a need for a more water-soluble opioid than sufentanil or fentanyl with prolonged analgesic effect. To our knowledge, the pharmacokinetics of epidural hydromorphone has not been evaluated in parturients.
Materials and methods
In this pilot study, seven healthy parturients were given a single epidural dose of hydromorphone for labour pain. One parturient received 1.5 mg, two 0.75 mg and four 0.5 mg of hydromorphone hydrochloride. Dose was decreased due to nausea and pruritus. Hydromorphone’s effect, adverse effects and plasma concentrations were evaluated. Neonatal drug exposure was evaluated by umbilical vein and artery opioid concentration at birth. Neonatal outcomes were assessed using Apgar and the Neurologic Adaptive Capacity Score (NACS).
Results
All patients received additional levobupivacaine doses on parturients’ requests. The first dose was requested at a median of 163 min (range 19–303 min) after hydromorphone administration. A total of 12 opioid related expected adverse events were reported by seven parturients. All newborn outcomes were uneventful. Hydromorphone’s distribution and elimination after single epidural dose seem similar to that reported for non-pregnant subjects after intravenous hydromorphone administration, but further research is required to confirm this observation.
Conclusions
The optimal dose of hydromorphone in labour pain warrants further evaluation.</description><subject>Adult</subject><subject>Analgesia</subject><subject>Analgesia, Epidural - adverse effects</subject><subject>Analgesia, Obstetrical - adverse effects</subject><subject>Analgesics</subject><subject>Analgesics, Opioid - administration & dosage</subject><subject>Analgesics, Opioid - adverse effects</subject><subject>Analgesics, Opioid - pharmacokinetics</subject><subject>Apgar Score</subject><subject>Biomedical and Life Sciences</subject><subject>Biomedicine</subject><subject>Childbirth & labor</subject><subject>Epidural</subject><subject>Female</subject><subject>Fentanyl</subject><subject>Humans</subject><subject>Hydromorphone - administration & dosage</subject><subject>Hydromorphone - adverse effects</subject><subject>Hydromorphone - pharmacokinetics</subject><subject>Infant, Newborn</subject><subject>Intravenous administration</subject><subject>Labor Pain - drug therapy</subject><subject>Male</subject><subject>Maternal-Fetal Exchange</subject><subject>Narcotics</subject><subject>Nausea</subject><subject>Neonates</subject><subject>Newborn babies</subject><subject>Opioids</subject><subject>Pain</subject><subject>Pain perception</subject><subject>Pharmacokinetics</subject><subject>Pharmacokinetics and Disposition</subject><subject>Pharmacology/Toxicology</subject><subject>Pilot Projects</subject><subject>Pregnancy</subject><subject>Pruritus</subject><subject>Sufentanil</subject><subject>Umbilical vein</subject><subject>Young Adult</subject><issn>0031-6970</issn><issn>1432-1041</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2020</creationdate><recordtype>article</recordtype><sourceid>C6C</sourceid><sourceid>EIF</sourceid><sourceid>BENPR</sourceid><recordid>eNp9UU1P3DAUtFAr2FL-QA-VpZ7TPtuxYzhUqhD9kJA4tD1bjv2ya7qxg50g-PeYLtBy4WD5MPNm3rwh5B2Djwyg-1QAONcNcKhPa2jUHlmxVvCGQctekRWAYI067uCAvCnlEoDJYxD75EBwoUTLYUX6nyGut0h9KkhxCn7Jdks3tz6nMeVpkyLSEOnW9mnJdLIhntDRzphjpU0bm0fr0p8QcQ6uUBs9jZiinSuKN1MqS8a35PVgtwWPHv5D8vvr2a_T7835xbcfp1_OG9d27dx4poVEXxfUSqJWALZj6JjnvXReDV4OmjkBzuquFwNKxYTSve8HoTnIVhySzzvdaelH9A7jXLOYKYfR5luTbDDPkRg2Zp2uTSdAAe-qwIcHgZyuFiyzuayha9BieMtkvakU9zZ8x3I5lZJxeHJgYO57MbteTO3F_O3FqDr0_v_dnkYei6gEsSOUCsU15n_eL8jeAQ6_mws</recordid><startdate>20200701</startdate><enddate>20200701</enddate><creator>Puhto, Terhi</creator><creator>Kokki, Merja</creator><creator>Hakomäki, Henriikka</creator><creator>Spalding, Michael</creator><creator>Gunnar, Teemu</creator><creator>Alahuhta, Seppo</creator><creator>Vakkala, Merja</creator><general>Springer Berlin Heidelberg</general><general>Springer Nature B.V</general><scope>C6C</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>3V.</scope><scope>7RV</scope><scope>7TK</scope><scope>7U9</scope><scope>7X7</scope><scope>7XB</scope><scope>88E</scope><scope>8AO</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABUWG</scope><scope>AFKRA</scope><scope>BENPR</scope><scope>CCPQU</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>H94</scope><scope>K9.</scope><scope>KB0</scope><scope>M0S</scope><scope>M1P</scope><scope>NAPCQ</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope><scope>5PM</scope><orcidid>https://orcid.org/0000-0002-8277-5429</orcidid></search><sort><creationdate>20200701</creationdate><title>Single dose epidural hydromorphone in labour pain: maternal pharmacokinetics and neonatal exposure</title><author>Puhto, Terhi ; Kokki, Merja ; Hakomäki, Henriikka ; Spalding, Michael ; Gunnar, Teemu ; Alahuhta, Seppo ; Vakkala, Merja</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c474t-d1835ed903865e8600a71ec1d2b5cd6fd5f81c30ca87b3fe561368bdbf3820543</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2020</creationdate><topic>Adult</topic><topic>Analgesia</topic><topic>Analgesia, Epidural - adverse effects</topic><topic>Analgesia, Obstetrical - adverse effects</topic><topic>Analgesics</topic><topic>Analgesics, Opioid - administration & dosage</topic><topic>Analgesics, Opioid - adverse effects</topic><topic>Analgesics, Opioid - pharmacokinetics</topic><topic>Apgar Score</topic><topic>Biomedical and Life Sciences</topic><topic>Biomedicine</topic><topic>Childbirth & labor</topic><topic>Epidural</topic><topic>Female</topic><topic>Fentanyl</topic><topic>Humans</topic><topic>Hydromorphone - administration & dosage</topic><topic>Hydromorphone - adverse effects</topic><topic>Hydromorphone - pharmacokinetics</topic><topic>Infant, Newborn</topic><topic>Intravenous administration</topic><topic>Labor Pain - drug therapy</topic><topic>Male</topic><topic>Maternal-Fetal Exchange</topic><topic>Narcotics</topic><topic>Nausea</topic><topic>Neonates</topic><topic>Newborn babies</topic><topic>Opioids</topic><topic>Pain</topic><topic>Pain perception</topic><topic>Pharmacokinetics</topic><topic>Pharmacokinetics and Disposition</topic><topic>Pharmacology/Toxicology</topic><topic>Pilot Projects</topic><topic>Pregnancy</topic><topic>Pruritus</topic><topic>Sufentanil</topic><topic>Umbilical vein</topic><topic>Young Adult</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Puhto, Terhi</creatorcontrib><creatorcontrib>Kokki, Merja</creatorcontrib><creatorcontrib>Hakomäki, Henriikka</creatorcontrib><creatorcontrib>Spalding, Michael</creatorcontrib><creatorcontrib>Gunnar, Teemu</creatorcontrib><creatorcontrib>Alahuhta, Seppo</creatorcontrib><creatorcontrib>Vakkala, Merja</creatorcontrib><collection>Springer Nature OA Free Journals</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>ProQuest Central (Corporate)</collection><collection>Nursing & Allied Health Database</collection><collection>Neurosciences Abstracts</collection><collection>Virology and AIDS Abstracts</collection><collection>Health & Medical Collection</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>Medical Database (Alumni Edition)</collection><collection>ProQuest Pharma Collection</collection><collection>Hospital Premium Collection</collection><collection>Hospital Premium Collection (Alumni Edition)</collection><collection>ProQuest Central (Alumni) (purchase pre-March 2016)</collection><collection>ProQuest Central (Alumni Edition)</collection><collection>ProQuest Central UK/Ireland</collection><collection>ProQuest Central</collection><collection>ProQuest One Community College</collection><collection>Health Research Premium Collection</collection><collection>Health Research Premium Collection (Alumni)</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>Nursing & Allied Health Database (Alumni Edition)</collection><collection>Health & Medical Collection (Alumni Edition)</collection><collection>Medical Database</collection><collection>Nursing & Allied Health Premium</collection><collection>ProQuest One Academic Eastern Edition (DO NOT USE)</collection><collection>ProQuest One Academic</collection><collection>ProQuest One Academic UKI Edition</collection><collection>ProQuest Central China</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>European journal of clinical pharmacology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Puhto, Terhi</au><au>Kokki, Merja</au><au>Hakomäki, Henriikka</au><au>Spalding, Michael</au><au>Gunnar, Teemu</au><au>Alahuhta, Seppo</au><au>Vakkala, Merja</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Single dose epidural hydromorphone in labour pain: maternal pharmacokinetics and neonatal exposure</atitle><jtitle>European journal of clinical pharmacology</jtitle><stitle>Eur J Clin Pharmacol</stitle><addtitle>Eur J Clin Pharmacol</addtitle><date>2020-07-01</date><risdate>2020</risdate><volume>76</volume><issue>7</issue><spage>969</spage><epage>977</epage><pages>969-977</pages><issn>0031-6970</issn><eissn>1432-1041</eissn><abstract>Introduction
Epidural hydromorphone could be useful in obstetric analgesia as there is a need for a more water-soluble opioid than sufentanil or fentanyl with prolonged analgesic effect. To our knowledge, the pharmacokinetics of epidural hydromorphone has not been evaluated in parturients.
Materials and methods
In this pilot study, seven healthy parturients were given a single epidural dose of hydromorphone for labour pain. One parturient received 1.5 mg, two 0.75 mg and four 0.5 mg of hydromorphone hydrochloride. Dose was decreased due to nausea and pruritus. Hydromorphone’s effect, adverse effects and plasma concentrations were evaluated. Neonatal drug exposure was evaluated by umbilical vein and artery opioid concentration at birth. Neonatal outcomes were assessed using Apgar and the Neurologic Adaptive Capacity Score (NACS).
Results
All patients received additional levobupivacaine doses on parturients’ requests. The first dose was requested at a median of 163 min (range 19–303 min) after hydromorphone administration. A total of 12 opioid related expected adverse events were reported by seven parturients. All newborn outcomes were uneventful. Hydromorphone’s distribution and elimination after single epidural dose seem similar to that reported for non-pregnant subjects after intravenous hydromorphone administration, but further research is required to confirm this observation.
Conclusions
The optimal dose of hydromorphone in labour pain warrants further evaluation.</abstract><cop>Berlin/Heidelberg</cop><pub>Springer Berlin Heidelberg</pub><pmid>32363420</pmid><doi>10.1007/s00228-020-02880-6</doi><tpages>9</tpages><orcidid>https://orcid.org/0000-0002-8277-5429</orcidid><oa>free_for_read</oa></addata></record> |
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subjects | Adult Analgesia Analgesia, Epidural - adverse effects Analgesia, Obstetrical - adverse effects Analgesics Analgesics, Opioid - administration & dosage Analgesics, Opioid - adverse effects Analgesics, Opioid - pharmacokinetics Apgar Score Biomedical and Life Sciences Biomedicine Childbirth & labor Epidural Female Fentanyl Humans Hydromorphone - administration & dosage Hydromorphone - adverse effects Hydromorphone - pharmacokinetics Infant, Newborn Intravenous administration Labor Pain - drug therapy Male Maternal-Fetal Exchange Narcotics Nausea Neonates Newborn babies Opioids Pain Pain perception Pharmacokinetics Pharmacokinetics and Disposition Pharmacology/Toxicology Pilot Projects Pregnancy Pruritus Sufentanil Umbilical vein Young Adult |
title | Single dose epidural hydromorphone in labour pain: maternal pharmacokinetics and neonatal exposure |
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