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Saturday, March 22, 2014
Gabapentin and Pregabalin: The Latest Ingredients in Multimodal Analgesia

Post-operative analgesia is extremely important after spine surgery, especially as patients expect shorter hospital stays and more procedures are done on an outpatient basis. Opioids and NSAIDs have been the mainstays of treatment, though both have serious side effects and many surgeons feel NSAIDs are contra-indicated after fusion. As such, efforts have been made to develop multimodal analgesia regimens, and neuromodulating medicines such as gabapentin and pregabalin have been shown to be effective adjuncts to opioids and NSAIDs. Additionally, spine surgery can be associated with longer-term neuropathic pain, and it is possible that early use of neuromodulating medications can reduce the risk of this. It is on this background that Dr. Khurana and colleagues from India peformed a double-blind RCT comparing the use of gabapentin, pregabalin, and placebo as part of a multimodal analgesia protocol following lumbar discectomy. They randomized 30 patients to each group, with each patient receiving the allocated treatment pre-operatively and then every eight hours post-operatively for 7 days. In addition, each patient received an IV dose of diclofenac and also received IV tramadol as a rescue medication while hospitalized. Outcome measures included a Visual Analog Scale (VAS) for pain at rest and with motion, the Oswestry Disability Index (ODI), and the Prolo economic and functional score. These were evaluated frequently over the first 72 hours and then followed out to 3 months. In the acute post-operative period, gabapentin and pregabalin were associated with significantly lower VAS scores and less tramadol use compared to placebo. At 3 months, the gabapentin and pregabalin groups had significantly better VAS, ODI, and Prolo scores compared to the placebo group as well. Additionally, the pregabalin group had a moderate but significant advantage over gabapentin on the VAS, ODI, and Prolo scores at 3 months. Side effects and complications related to the medications were mild and included primarily sedation and nausea.

 

This study represents a high quality study that clearly demonstrates an advantage to gabapentin and pregabalin compared to placebo, albeit a relatively modest one. Given that the side effect profiles of the medications at the dosage used in the study was acceptable—about 10% of patients reported sedation—these medications should be considered as part of a multimodal analgesic protocol as they improved patient pain and function and reduced the need for opioids. Additionally, the longer-term benefit at 3 months is interesting and may represent how early modulation of certain pain pathways can prevent the development of chronic pain in some patients. This study has some limitations, namely that the duration of hospitalization and post-hospitalization use of analgesics was not recorded or reported. In the United States, most lumbar diskectomies are performed on an outpatient basis, so the use of IV narcotics is very limited. It seems as though the patients in this study were admitted for a period of time, and it is unclear if they were prescribed oral opioids or NSAIDs upon discharge. Most multimodal analgesic protocols would include oral NSAIDs and opioids, and it is unclear to what degree these were used in this study. Another limitation is the authors’ decision to convert the ODI to a categorical outcome, which obscures the magnitude of differences between the groups. While the pregabalin group had a greater proportion of patients with an ODI score of less than 20% at 3 months compared to the gabapentin and placebo groups, the actual mean scores were not reported and the differences may have been small. Despite these limitations, this high quality RCT provides relatively strong evidence that gabapentin and pregabalin modestly decrease pain and improve function following lumbar discectomy, even out to 3 months. Hopefully a similar but larger study with a better defined post-discharge protocol will be performed in the future to confirm these results.


Please read Dr. Khurana’s paper on this article in the March 15 issue. Does this change how you view the perioperative use of gabapentinoids in lumbar discectomy? Let us know by leaving a comment on The Spine Blog.

Adam Pearson, MD, MS
Associate Web Editor

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Spine Journal
This Blog provides a forum for discussion about high impact articles published in Spine, including the bi-annual publication of "Evidenced-Based Recommendations for Spine Surgery." Website users can use this forum to discuss how the articles have affected their practice and query the authors about their findings and recommendations.

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