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Premedication for intubation in newborn infants; pain assessment, pharmacokinetics and pharmacodynamics

Norman, Elisabeth LU (2011) In Lund University, Faculty of Medicine Doctorial dissertation Series 2011:61.
Abstract (Swedish)
Popular Abstract in Swedish

För tidigt födda barn genomgår intensivvård under en period när de är väldigt sårbara pga instabil cirkulation och ett omoget centralt nervsystem under snabb utveckling. Tillräcklig behandling av smärta är av största betydelse eftersom stark smärtupplevelse kan medföra skadliga omedelbara kroppsreaktioner, men också neurologiska och neuropsykologiska seneffekter. Det finns ingen “gyllene standard” för objektiv smärtskattning, och inte heller några “evidens-grundade” rekommendationer för nedsövning och smärtstillning vid införande av luftvägstub (intubation) hos nyfödda barn i behov av respiratorbehandling.

Syftet med detta forskningsprojekt var att undersöka förutsättningarna för... (More)
Popular Abstract in Swedish

För tidigt födda barn genomgår intensivvård under en period när de är väldigt sårbara pga instabil cirkulation och ett omoget centralt nervsystem under snabb utveckling. Tillräcklig behandling av smärta är av största betydelse eftersom stark smärtupplevelse kan medföra skadliga omedelbara kroppsreaktioner, men också neurologiska och neuropsykologiska seneffekter. Det finns ingen “gyllene standard” för objektiv smärtskattning, och inte heller några “evidens-grundade” rekommendationer för nedsövning och smärtstillning vid införande av luftvägstub (intubation) hos nyfödda barn i behov av respiratorbehandling.

Syftet med detta forskningsprojekt var att undersöka förutsättningarna för objektiv smärtskattning med amplitud-integrerat EEG (aEEG), att utveckla en säker och effektiv förbehandling inför intubation och att studera farmakokinetik och farmakodynamik, läkemedels omsättning i och effekter på kroppen, hos de använda läkemedlen.

Vi undersökte svaret av tre olika sorters smärtstimulus hos nyfödda friska fullgångna barn med hjälp av aEEG/EEG och smärtskalor. Tiopental farmakokinetik studerades i moderns blod och navelsträngsblod efter förlossning med kejsarsnitt i tiopentalnarkos, och hos nyfödda barn som erhållit detta läkemedel inför kirurgiskt ingrepp. För tidigt födda nyfödda barn i behov av snar intubation inkluderades till att få antingen “Rapid Sequence Induction”, RSI, med glykopyrron, tiopental, succinylkolin och remifentanil eller atropin och morfin i en randomiserad kontrollerad studie, RCT. Lättheten att utföra åtgärden var den primära utfallsparametern. Tidsåtgången och villkoren för ingreppet skattades, fysiologiska och biokemiska parametrar, aEEG och smärtskalor registrerades under och efter intubationen.

Ingen typ av smärtsam stimuli gav förändringar i EEG-relaterad frontal asymmetri. Överföring av tiopental via moderkakan skapade ett koncentrationsförhållande mor: barn 0.7, och halveringstiden hos barnen var 8 timmar, beroende av vikt och ålder efter födelsen. I RCT noterades bättre förhållande och kortare tid för intubationen med RSI, och för morfingruppen uppmättes sänkning av hjärtfrekvens och ökning av blodtryck under intubationen och en gradvis tilltagande blodtryckssänkning med samtidig sänkning av hjärnaktiviteten under sex timmar efter intubationen. EEG parametrar kvarstod signifikant sänkta under 24 timmar.

Resultaten av detta doktorsarbete visar att kortikalt EEG-svar, mätt som förändring i frontal asymmetri, inte är användbart för att skatta smärta hos nyfödda barn. Vidare, att tiopental kan administreras inför intubation hos för tidigt födda och fullgångna nyfödda barn, dock med dosjustering utefter vikt och eventuell förlossningsanestesi hos modern, om givet första fyra timmarna efter födelsen. RSI medger optimala förutsättningar och kortare tidsåtgång för intubation än morfin, som bör undvikas pga cirkulatorisk och neurofysiologisk depression under och efter intubationen. (Less)
Abstract
Preterm infants undergo intensive care during a vulnerable period with hemodynamic instability and a rapidly developing and immature CNS. Adequate pain management is essential, since pain experience might lead to acute physiological reactions as well as neurological and neuropsychological sequels. There is no “golden standard” for objective pain assessment, and no evidence-based recommendations for premedication before endotracheal intubation in newborn infants.

The aims of the research project were to investigate the possibilities to objectively assess pain with amplitude-integrated EEG (aEEG), to develop a safe and effective strategy for premedication before tracheal intubation, and to study pharmacokinetics and pharmacodynamics... (More)
Preterm infants undergo intensive care during a vulnerable period with hemodynamic instability and a rapidly developing and immature CNS. Adequate pain management is essential, since pain experience might lead to acute physiological reactions as well as neurological and neuropsychological sequels. There is no “golden standard” for objective pain assessment, and no evidence-based recommendations for premedication before endotracheal intubation in newborn infants.

The aims of the research project were to investigate the possibilities to objectively assess pain with amplitude-integrated EEG (aEEG), to develop a safe and effective strategy for premedication before tracheal intubation, and to study pharmacokinetics and pharmacodynamics of the chosen drugs in the preterm infant population.

The responses to three different types of noxious stimuli in healthy term infants were measured with aEEG/EEG and pain scales. Thiopental pharmacokinetics was assessed in maternal and cord blood after caesarean section in thiopental anesthesia, and in newborn infants receiving thiopental before neonatal surgery. Preterm infants needing semi-urgent intubation were enrolled to receive either Rapid Sequence Induction (RSI) with glycopyrrolate, thiopental, suxamethonium and remifentanil or atropine and morphine in a blinded randomized controlled trial (RCT). The main outcome measure was good intubation conditions, secondary were procedural duration, as well as changes in physiological and biochemical parameters, aEEG and pain scales that were monitored during and after the intubation.

There were no changes in frontal EEG asymmetry to the different noxious stimuli. Thiopental placental transfer ratio was 0.7, and the median terminal half-life of thiopental in the infants was 8 hours depending on weight and postnatal age. The RCT demonstrated superior intubation conditions and shorter duration in the RSI group. Compared to RSI, the morphine group had prolonged heart rate decrease and mean arterial blood pressure (MABP) increase during intubation, and a progressive MABP decrease concomitant with neurophysiologic depression for 6 h afterwards. Neurophysiologic parameters were significantly depressed for 24 h.

The results of these studies indicate that responses in cortical activity, registered as EEG frontal asymmetry, are not useful for clinical assessment of pain responses in newborn infants. Further, thiopental can be used as premedication for intubation in preterm and term infants, with dose adjustments for maternal dosage and infant weight when administered during the first four hours after birth. The RSI used in the trial can be implemented in clinical practice. Morphine should be avoided because of circulatory and neurophysiologic depression during and after the intubation. (Less)
Please use this url to cite or link to this publication:
author
supervisor
opponent
  • Professor Tibboel, Dick, Department of Paediatric Surgery, Erasmus University, Medical center, Spophia Childrens´Hospital, rotterdam, The Netherlands
organization
publishing date
type
Thesis
publication status
published
subject
keywords
Premedication, pain, premature, newborn, aEEG, randomized controlled trial, thiopental, morphine, remifentanil, rapid sequence induction, ibntubation, pharmacokinetics, pharmacodynamics
in
Lund University, Faculty of Medicine Doctorial dissertation Series
volume
2011:61
pages
155 pages
publisher
Division of Paediatrics, Department of clinical Sciences, Lund University, Sweden
defense location
Belfrage-salen, D15, BMC, Lund
defense date
2011-05-21 09:00
ISSN
1652-8220
ISBN
978-91-86871-10-9
language
English
LU publication?
yes
id
ed4a432a-199e-462c-bdd7-9753190f7c20 (old id 1917442)
date added to LUP
2011-05-04 08:44:19
date last changed
2016-09-19 08:44:48
@phdthesis{ed4a432a-199e-462c-bdd7-9753190f7c20,
  abstract     = {Preterm infants undergo intensive care during a vulnerable period with hemodynamic instability and a rapidly developing and immature CNS. Adequate pain management is essential, since pain experience might lead to acute physiological reactions as well as neurological and neuropsychological sequels. There is no “golden standard” for objective pain assessment, and no evidence-based recommendations for premedication before endotracheal intubation in newborn infants.<br/><br>
The aims of the research project were to investigate the possibilities to objectively assess pain with amplitude-integrated EEG (aEEG), to develop a safe and effective strategy for premedication before tracheal intubation, and to study pharmacokinetics and pharmacodynamics of the chosen drugs in the preterm infant population.<br/><br>
The responses to three different types of noxious stimuli in healthy term infants were measured with aEEG/EEG and pain scales. Thiopental pharmacokinetics was assessed in maternal and cord blood after caesarean section in thiopental anesthesia, and in newborn infants receiving thiopental before neonatal surgery. Preterm infants needing semi-urgent intubation were enrolled to receive either Rapid Sequence Induction (RSI) with glycopyrrolate, thiopental, suxamethonium and remifentanil or atropine and morphine in a blinded randomized controlled trial (RCT). The main outcome measure was good intubation conditions, secondary were procedural duration, as well as changes in physiological and biochemical parameters, aEEG and pain scales that were monitored during and after the intubation.<br/><br>
There were no changes in frontal EEG asymmetry to the different noxious stimuli. Thiopental placental transfer ratio was 0.7, and the median terminal half-life of thiopental in the infants was 8 hours depending on weight and postnatal age. The RCT demonstrated superior intubation conditions and shorter duration in the RSI group. Compared to RSI, the morphine group had prolonged heart rate decrease and mean arterial blood pressure (MABP) increase during intubation, and a progressive MABP decrease concomitant with neurophysiologic depression for 6 h afterwards. Neurophysiologic parameters were significantly depressed for 24 h.<br/><br>
The results of these studies indicate that responses in cortical activity, registered as EEG frontal asymmetry, are not useful for clinical assessment of pain responses in newborn infants. Further, thiopental can be used as premedication for intubation in preterm and term infants, with dose adjustments for maternal dosage and infant weight when administered during the first four hours after birth. The RSI used in the trial can be implemented in clinical practice. Morphine should be avoided because of circulatory and neurophysiologic depression during and after the intubation.},
  author       = {Norman, Elisabeth},
  isbn         = {978-91-86871-10-9},
  issn         = {1652-8220},
  keyword      = {Premedication,pain,premature,newborn,aEEG,randomized controlled trial,thiopental,morphine,remifentanil,rapid sequence induction,ibntubation,pharmacokinetics,pharmacodynamics},
  language     = {eng},
  pages        = {155},
  publisher    = {Division of Paediatrics, Department of clinical Sciences, Lund University, Sweden},
  school       = {Lund University},
  series       = {Lund University, Faculty of Medicine Doctorial dissertation Series},
  title        = {Premedication for intubation in newborn infants; pain assessment, pharmacokinetics and pharmacodynamics},
  volume       = {2011:61},
  year         = {2011},
}