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Add another downside to the use of gabapentinoids.
Rahman et al. (Rahman
2024) looked at patients with COPD in Quebec who were begun on gabapentinoids for indications of epilepsy, neuropathic
pain, or other chronic pain. Compared to matched COPD patients not taking gabapentinoids, there was an increased risk for severe COPD
exacerbation across the indications of epilepsy (HR 1.58), neuropathic pain (HR
1.35), and other chronic pain (HR 1.49) and overall (HR 1.39). The authors
conclude that their results support recent warnings from Health Canada and the
US FDA about breathing difficulties associated with gabapentinoids.
However, there has also been an interesting positive study
regarding gabapentin. In general, gabapentinoids have
not been very successful in reducing the need for opioids in patients
undergoing surgery and have possibly increased the risk of postoperative
respiratory depression in patients also receiving opioids (see, for example,
our December 2023 What's New in the Patient Safety World column Postop
Gabapentin No Better Than Placebo). But the new study from Sweden found
that using gabapentin as part of a multimodal analgesia bundle did reduce the
need for opioids in patients undergoing colorectal surgery (Gedda
2023).
A care bundle consisting of an individualized opioid
regimen, regular gabapentinoids, and clonidine as a
rescue analgesic was introduced gradually in 842 patients who underwent major
colorectal surgery. Over the study period, median opioid usage decreased from
75 MME (morphine milligram equivalents) in 2016 to 22 MME in 2019 (P < .001),
and the proportion of patients receiving 45 MME or less increased from 35% to
66% (P < .001). An individualized opioid strategy, the use of
gabapentin, and increasing age were factors associated with less opioid
consumption, while the use of clonidine was associated with more opioid intake.
The authors concluded that regular gabapentin and an individualized opioid
regimen were particularly strongly associated with this decrease and should be
further evaluated as components of multimodal, opioid-free postoperative
analgesia.
In the Gedda study, regular gabapentinoids
were implemented as a standard order set of oral gabapentin 300 mg twice on the
day of surgery followed by 300 mg 3 times daily from day 1 until 7 to 10 days
after surgery. A lower dose was used in patients aged 80 years or older and in
patients with a reduced renal clearance (eGFR of less than 50). Those doses
were chosen to minimize the risk of adverse events. Only 2% of study
participants discontinued gabapentin due to a suspected adverse reaction. The
adverse reactions were all mild and fully reversible.
The authors note that their results contradict findings in a
meta-analysis on gabapentinoids in postoperative
analgesia (Verret
2020), which concluded that gabapentinoids
provide clinically irrelevant analgesia and are associated with too many
serious adverse effects to be considered effective. Gedda et al. believe that
dosing and the timing of the doses can be a part of an explanation, since the
dose of gabapentin used was in the low dosage range. In addition, most
participants in their study consumed no or small amounts of opioids, which may
explain the absence of respiratory depression. Also, many previous studies
began gabapentinoids pre-operatively, whereas in the
Gedda study they were only used post-operatively. Note also that, in our December
2023 What's New in the Patient Safety World column Postop
Gabapentin No Better Than Placebo), we noted that in the GAP trial opioid
use did favor gabapentin for non-cardiac thoracic and abdominal procedures over
the first few post-operative days, being roughly 30% lower at several time
points. But it was felt that this was statistically significant but not
clinically significant. Maybe not so insignificant, in view of the Gedda study!
Particularly in view of the negative effect of opioids on
bowel function, it is desirable to find regimens that reduce the need for
opioids in major colorectal surgery. Maybe its too early to give up on gabapentinoids to reduce the need for post-op opioids, but
we still need to keep in mind the many potential downsides they may have.
Some of our prior columns on safety issues with gabapentinoids:
·
December 2023 Postop
Gabapentin No Better Than Placebo
References:
Rahman AA, DellAniello S, Moodie
EEM, et al. Gabapentinoids and Risk for Severe
Exacerbation in Chronic Obstructive Pulmonary Disease: A Population-Based
Cohort Study. Ann Intern Med 2024; Epublished 16
January 2024
https://www.acpjournals.org/doi/10.7326/M23-0849
Gedda C, Nygren J, Garpenbeck A, et
al. Multimodal Analgesia Bundle and Postoperative Opioid Use Among Patients
Undergoing Colorectal Surgery. JAMA Netw Open 2023; 6(9):
e2332408
https://jamanetwork.com/journals/jamanetworkopen/fullarticle/2808960
Verret M,
Lauzier F, Zarychanski R, et
al. Canadian Perioperative Anesthesia Clinical Trials (PACT) Group.
Perioperative use of gabapentinoids for the
management of postoperative acute pain: a systematic review and
meta-analysis. Anesthesiology
2020; 133(2): 265-279
Gabapentin in post-surgery pain (GAP trial)
https://www.isrctn.com/ISRCTN63614165
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