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Acute Pain


REMIFENTANIL LINKED TO HIGHER MORPHINE NEED POST-SURGERY

Lisa Kuhns, PhD
|
April 16, 2024
Researchers conducted a systematic review and meta-analysis to explore the
effect of remifentanil on acute and chronic postsurgical pain after cardiac
surgery.

Remifentanil may increase morphine consumption after surgery and increase
complications, although evidence does not support incidence of chronic
postsurgical pain after cardiac surgery. These study findings were reported in
the Journal of Clinical Pain.



Researchers conducted a systematic review and meta-analysis to explore the
effect of remifentanil on acute and chronic postsurgical pain after cardiac
surgery. Randomized controlled trials (RCTs) were collected from 5 databases,
and a random-effect model with the generic Mantel-Haenszel method was preferred
for integrating risk ratios (RRs). The primary outcome of the study was chronic
postsurgical pain. Secondary outcomes were scores of postsurgical pain and
morphine consumption within 24 hours after cardiac surgery.

From a total of 1241 articles, 7 studies with 658 patients aged between 32 and
85 years were included after screening. Regarding anesthesia maintenance, 2
studies used propofol in combination with isoflurane or sevoflurane, 4 studies
opted for target-controlled infusion of propofol alone, and 1 study utilized
isoflurane or sevoflurane. For analgesia, 3 studies administered low-dose
remifentanil, while 4 employed high-dose remifentanil. The studies focused on
chronic pain and had follow-up durations exceeding 3 months, with the longest
being 1 year. Despite all studies evaluating the impact of remifentanil on pain
outcomes, they differed in surgery types, sample sizes, and study designs. Most
RCTs in the review had a low risk of bias, except for 3 studies with concerns
about unclear randomization, intervention deviations, and selection of reported
results. Despite these issues, risks for other biases were low. A publication
bias analysis using a funnel plot indicated a low risk of publication bias, as
the distribution was symmetric.



The incidence of chronic postsurgical pain, reported in 4 studies with 415
participants, showed no significant differences between the 2 groups (relative
risk: 1.02; 95% CI, 0.53-1.95; P =.95; I²=59%). While the cumulative Z curve
crossed the traditional boundary, it didn’t cross the Trial Sequential Analysis
(TSA) boundary for benefit or harm and didn’t meet the required information size
(RIS). This suggests that the traditional meta-analysis might indicate a
positive outcome, but it could be a false positive. Further trials are needed
for conclusive verification.

Postsurgical morphine consumption, assessed in 6 studies with 569 participants
and a follow-up of at least 24 hours after surgery, was significantly higher in
the remifentanil group compared with the control group (mean difference: 6.94;
95% CI, 3.65-10.22; P <.01; I²=0%). Stratified analyses for low and high-dose
remifentanil groups both showed higher morphine consumption compared to controls
(low: P =.0009; high: P =.01). The cumulative Z curve surpassed both the
traditional and TSA boundaries, indicating a positive result despite not
reaching the RIS.

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“
Remifentanil has not been considered currently to increase the incidence of
chronic postoperative pain. However, there was moderate certainty evidence that
the use of remifentanil increases the consumption of morphine for analgesia in
the short term, and more direct comparison trials are needed to inform clinical
decision-making with greater confidence.


Postsurgical pain scores, evaluated in 2 studies with 196 participants, showed
no significant differences between the 2 groups (mean difference: 0.09; 95% CI,
-0.36 to 0.55; P =.69; I²=0%). The cumulative Z curve did not cross the
conventional or the TSA boundaries for benefit or harm and did not meet the RIS,
indicating the conclusion is unreliable. Further studies are necessary for
verification.

The quality of evidence for chronic postsurgical pain was low due to high bias
and moderate heterogeneity (I2=53%). Evidence on morphine consumption was
moderate, downgraded for wide confidence intervals. Evidence for postsurgical
pain scores was low and downgraded due to high bias in one study and imprecise
effect estimates.



Study limitations include that postoperative pain management protocols vary
widely, postsurgical pain levels and/or analgesic consumption was not always the
main end point of the included study, and it was not possible for each study to
adopt double-blinding in the choice of anesthesia strategy, which can affect the
results.

Researchers concluded, “Remifentanil has not been considered currently to
increase the incidence of chronic postoperative pain. However, there was
moderate certainty evidence that the use of remifentanil increases the
consumption of morphine for analgesia in the short term, and more direct
comparison trials are needed to inform clinical decision-making with greater
confidence.”





References:

Zhang B, Cai C, Pan Z, Zhuang L, Qi Y. Effect of remifentanil on acute and
chronic postsurgical pain in patients undergoing cardiac surgery: A systematic
review and meta-analysis. Clin J Pain. 2024;40:187-195.
doi:10.1097/AJP.0000000000001183

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When you visit our website, we store cookies on your browser to collect
information. The information collected might relate to you, your preferences or
your device, and is mostly used to make the site work as you expect it to and to
provide a more personalized web experience. However, you can choose not to allow
certain types of cookies, which may impact your experience of the site and the
services we are able to offer. Click on the different category headings to find
out more and change our default settings according to your preference. You
cannot opt-out of our First Party Strictly Necessary Cookies as they are
deployed in order to ensure the proper functioning of our website (such as
prompting the cookie banner and remembering your settings, to log into your
account, to redirect you when you log out, etc.). For more information about the
First and Third Party Cookies used please follow this link.
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These cookies are necessary for the website to function and cannot be switched
off in our systems. They are usually only set in response to actions made by you
which amount to a request for services, such as setting your privacy
preferences, logging in or filling in forms.    You can set your browser to
block or alert you about these cookies, but some parts of the site will not then
work. These cookies do not store any personally identifiable information.

 * FUNCTIONAL COOKIES
   
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   These cookies enable the website to provide enhanced functionality and
   personalisation. They may be set by us or by third party providers whose
   services we have added to our pages.    If you do not allow these cookies
   then some or all of these services may not function properly.

DO NOT SELL PERSONAL INFORMATION

Do Not Sell Personal Information

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   These cookies are set by a range of social media services that we have added
   to the site to enable you to share our content with your friends and
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   building up a profile of your interests. This may impact the content and
   messages you see on other websites you visit.    If you do not allow these
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 * PERFORMANCE COOKIES
   
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   These cookies allow us to count visits and traffic sources so we can measure
   and improve the performance of our site. They help us to know which pages are
   the most and least popular and see how visitors move around the site.    All
   information these cookies collect is aggregated and therefore anonymous. If
   you do not allow these cookies we will not know when you have visited our
   site, and will not be able to monitor its performance.

 * TARGETING COOKIES
   
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   These cookies may be set through our site by our advertising partners. They
   may be used by those companies to build a profile of your interests and show
   you relevant adverts on other sites.    They do not store directly personal
   information, but are based on uniquely identifying your browser and internet
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