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Pain induced by propofol - clinical studies on drug composition and adminstration

Liljeroth, Elisabeth LU (2007)
Abstract (Swedish)
Popular Abstract in Swedish

De senaste 25 åren har flera nya narkosläkemedel registrerats och fått stort genomslag i vårt land. Den främsta orsaken är att dessa läkemedel medger ett snabbare uppvaknande och bättre postoperativt välbefinnande, vilket gör att många patienter snabbare kan återvända hem efter sina operationer. Propofol (2,6-di-isopropylfenol) som är ett av våra mest använda intra-venösa narkosläkemedel, ger behaglig sömn, snabbt uppvaknande och obetydligt postoperativt illamående.



I samband med nedsövningen kan dock propofol orsaka smärta vid injektionsstället hos upp till 90 % av patienterna. Eftersom problemet är så vanligt, har smärta vid injektion av propofol av narkosläkare bedömts vara... (More)
Popular Abstract in Swedish

De senaste 25 åren har flera nya narkosläkemedel registrerats och fått stort genomslag i vårt land. Den främsta orsaken är att dessa läkemedel medger ett snabbare uppvaknande och bättre postoperativt välbefinnande, vilket gör att många patienter snabbare kan återvända hem efter sina operationer. Propofol (2,6-di-isopropylfenol) som är ett av våra mest använda intra-venösa narkosläkemedel, ger behaglig sömn, snabbt uppvaknande och obetydligt postoperativt illamående.



I samband med nedsövningen kan dock propofol orsaka smärta vid injektionsstället hos upp till 90 % av patienterna. Eftersom problemet är så vanligt, har smärta vid injektion av propofol av narkosläkare bedömts vara det idag sjunde viktigaste kliniska problemet inom modern anestesi. Koncentrationen av fritt propofol i den vattenlösliga fasen av injektions-lösningen har betydelse för uppkomsten av denna smärta.



Det allmänna syftet med de fem undersökningarna som ligger till grund för denna avhandling var att på patienter som ska sövas inför kirurgiska ingrepp utvärdera och jämföra olika sätt att minska den smärta som kan uppkomma när man sprutar in propofol i ett ytligt blodkärl för att söva patienten. I de första tre undersökningarna [I-III] använde vi en äldre beredning av propofol löst i en blandning av vatten och fett innehållande enbart långa fettkedjor (LCT), medan vi i de tre avslutande undersök-ningarna [III-V] använde en nyare propofolberedning med både medel-långa (MCT) och långa fettkedjor.



I den första undersökningen [I] studerade vi vad som händer om man samtidigt ger dropp till patienterna. Vi upptäckte att smärtan inte påverkas av om man samtidigt ger ett dropp via samma plastnål i kärlet, men att smärtan försvinner något snabbare.



I den andra undersökningen [II] utvärderade vi effekten av två olika injektionshastigheter av propofol. Vi upptäckte inget samband mellan hur snabbt man sprutar in propofolet i blodkärlet och hur ofta smärta upp-kommer eller hur länge den varar.



I den tredje undersökningen [III] jämfördes smärtan av MCT/LCT-propofol med smärtan av LCT propofol. Vi upptäckte att MCT/LCT-propofol gav upphov till mindre smärta än LCT-propofol.



Den fjärde undersökningen [IV] gjordes för att utvärdera effekten av avstängt blodflöde från det kärl där propofolet sprutas in. Vi upptäckte att avstängning av kärlet ökar smärtan vid injektionsstället men inte påverkar hur länge den varar. Detta talar för att den lokala smärtan som framkallas av propofol försvinner medan läkemedlet fortfarande finns kvar i blodkärlet, vilket gav oss idén till den avslutande undersökningen.



I den femte undersökningen [V] utvärderade vi om man kan påverka injektionssmärtan genom att först ge en liten dos propofol. Vi fann att måttlig till svår injektionssmärta kan minskas genom att på detta sätt dela upp propofoldosen.



Våra studier visar att MCT/LCT-propofol ger mindre smärta vid injektionsstället än LCT-propofol, och att måttlig och svår smärta minskar om huvuddosen föregås av en liten dos propofol via samma plastnål i blodkärlet. Båda dessa tekniker kan till vardags användas i samband med praktiskt taget alla nedsövningar. Är det bråttom att söva ned patienten bör man dock undvika att dela upp doserna och istället injicera propofolet vid ett och samma tillfälle. (Less)
Abstract
Over the last 25 years a number of new anaesthetic drugs have been introduced on the market to allow for better patient satisfaction and faster recovery after anaesthesia and sedation. Propofol (2,6-di-isopropylphenol), one of our most common iv anaesthetics, is associated with pleasant sleep and rapid recovery with little postoperative nausea. When used for anaesthetic induction propofol causes severe or even intolerable pain or discomfort on injection in up to 90 % of patients. Pain on injection of propofol is even ranked by anaesthesiologists as the seventh most important clinical problem in modern anaesthesia.



The concentration of free propofol within the aqueous phase of the drug formula is believed to be... (More)
Over the last 25 years a number of new anaesthetic drugs have been introduced on the market to allow for better patient satisfaction and faster recovery after anaesthesia and sedation. Propofol (2,6-di-isopropylphenol), one of our most common iv anaesthetics, is associated with pleasant sleep and rapid recovery with little postoperative nausea. When used for anaesthetic induction propofol causes severe or even intolerable pain or discomfort on injection in up to 90 % of patients. Pain on injection of propofol is even ranked by anaesthesiologists as the seventh most important clinical problem in modern anaesthesia.



The concentration of free propofol within the aqueous phase of the drug formula is believed to be particularly associated with injection pain. The general aim of these studies was to investigate if we could reduce the local pain induced by iv propofol by various clinical measures. Traditional long-chain triglyceride (LCT) emulsions of propofol were used in studies I-III, while a new medium- and long-chain triglyceride (MCT/LCT) formula was used in studies III-V. Both formulas were used and compared in study III.



In study I the influence of a carrier fluid was evaluated. Simultaneous iv infusion of carrier fluid was found not to influence pain intensity but to decrease the duration of pain at the site of propofol injection.



In study II we investigated the effect of various bolus rates of propofol on pain at site of injection. There were no differences in the incidence, intensity or duration of pain between the faster and slower rates compared.



In study III we compared the influence of two different formulas of propofol on local pain at the site of administration. Propofol emulsions based on MCT/LCT were associated with lower pain intensity than those based on LCT only.



Study IV was designed to examine if local venous occlusion applied during and immediately after injection of propofol reduces the intensity of pain at the site of injection. Venous occlusion was found to increase the intensity but not the duration of pain at the site of propofol injection, indicating that the pain response to propofol fades during prolonged intravascular exposure.



Study V was carried out to examine if pain on injection of propofol can be reduced by previous low-dose administration of propofol by the same iv route. A lower incidence of moderate or severe local pain was induced by propofol after the low dose of propofol had been administered.



Our most important results show that formulas of propofol based on MCT/LCT are associated with less pain at the site of iv injection than are traditional LCT formulas. Furthermore the incidence of moderate to severe propofol-induced pain can be reduced by previous injection of a low dose of propofol by the same iv route.



These measures can easily be taken by any anaesthetist in virtually any clinical situation not calling for rapid induction of anaesthesia. (Less)
Please use this url to cite or link to this publication:
author
supervisor
opponent
  • professor Raeder, Johan, Oslo
organization
publishing date
type
Thesis
publication status
published
subject
keywords
intravenous, Medicin (människa och djur), Medicine (human and vertebrates), pain, propofol, injection
publisher
Department of Anaesthesiology and Intensive Care, Lund
defense location
Jubileumsaulan, Medicinskt Forskningscentrum, ingång 59, Universitetssjukhuset MAS, Malmö
defense date
2007-02-02 09:15
ISSN
1652-8220
ISBN
91-85559-4
language
English
LU publication?
yes
id
c63177da-0377-49f3-9b24-5c9d28a135bb (old id 547920)
date added to LUP
2007-09-12 08:28:35
date last changed
2016-09-19 08:44:56
@phdthesis{c63177da-0377-49f3-9b24-5c9d28a135bb,
  abstract     = {Over the last 25 years a number of new anaesthetic drugs have been introduced on the market to allow for better patient satisfaction and faster recovery after anaesthesia and sedation. Propofol (2,6-di-isopropylphenol), one of our most common iv anaesthetics, is associated with pleasant sleep and rapid recovery with little postoperative nausea. When used for anaesthetic induction propofol causes severe or even intolerable pain or discomfort on injection in up to 90 % of patients. Pain on injection of propofol is even ranked by anaesthesiologists as the seventh most important clinical problem in modern anaesthesia.<br/><br>
<br/><br>
The concentration of free propofol within the aqueous phase of the drug formula is believed to be particularly associated with injection pain. The general aim of these studies was to investigate if we could reduce the local pain induced by iv propofol by various clinical measures. Traditional long-chain triglyceride (LCT) emulsions of propofol were used in studies I-III, while a new medium- and long-chain triglyceride (MCT/LCT) formula was used in studies III-V. Both formulas were used and compared in study III.<br/><br>
<br/><br>
In study I the influence of a carrier fluid was evaluated. Simultaneous iv infusion of carrier fluid was found not to influence pain intensity but to decrease the duration of pain at the site of propofol injection.<br/><br>
<br/><br>
In study II we investigated the effect of various bolus rates of propofol on pain at site of injection. There were no differences in the incidence, intensity or duration of pain between the faster and slower rates compared.<br/><br>
<br/><br>
In study III we compared the influence of two different formulas of propofol on local pain at the site of administration. Propofol emulsions based on MCT/LCT were associated with lower pain intensity than those based on LCT only.<br/><br>
<br/><br>
Study IV was designed to examine if local venous occlusion applied during and immediately after injection of propofol reduces the intensity of pain at the site of injection. Venous occlusion was found to increase the intensity but not the duration of pain at the site of propofol injection, indicating that the pain response to propofol fades during prolonged intravascular exposure.<br/><br>
<br/><br>
Study V was carried out to examine if pain on injection of propofol can be reduced by previous low-dose administration of propofol by the same iv route. A lower incidence of moderate or severe local pain was induced by propofol after the low dose of propofol had been administered.<br/><br>
<br/><br>
Our most important results show that formulas of propofol based on MCT/LCT are associated with less pain at the site of iv injection than are traditional LCT formulas. Furthermore the incidence of moderate to severe propofol-induced pain can be reduced by previous injection of a low dose of propofol by the same iv route.<br/><br>
<br/><br>
These measures can easily be taken by any anaesthetist in virtually any clinical situation not calling for rapid induction of anaesthesia.},
  author       = {Liljeroth, Elisabeth},
  isbn         = {91-85559-4},
  issn         = {1652-8220},
  keyword      = {intravenous,Medicin (människa och djur),Medicine (human and vertebrates),pain,propofol,injection},
  language     = {eng},
  publisher    = {Department of Anaesthesiology and Intensive Care, Lund},
  school       = {Lund University},
  title        = {Pain induced by propofol - clinical studies on drug composition and adminstration},
  year         = {2007},
}