Gabapentinoids and opioids combo increases opioid overdose risk postoperatively

Gabapentinoids (gabapentin and pregabalin) are anticonvulsant medications, commonly used for the treatment of chronic neuropathic pain. Their off-label use as adjuvant analgesics following surgery has been found to decrease postoperative pain and opioid consumption and is increasing. However, In December 2019, the US Food and Drug Administration issued a warning on serious breathing difficulties associated with gabapentin and pregabalin in patients with other respiratory risk factors, including the use of opioids. As the use of gabapentinoids perioperatively is increasing and the clinical data on their safety, when coadministered with opioids for postoperative analgesia, is lacking researchers conducted a population-based cohort study in a large, nationwide database of US hospital admissions to assess whether coadministration of gabapentinoids with opioids is associated with increased risk of opioid-related adverse outcomes, including opioid overdose, in surgical patients.

In this cohort study, researchers used propensity score trimming, stratification, and weighting of adults admitted for a major surgery between October 2007 and December 2017 who were treated with opioids on the day of surgery. They also analyzed the Premier Research database conducted from February to April 2020 and identified a total of 5,547,667 patients among which 892 484 were administered with Gabapentinoids and 4 655 183 patients received only opioids. Patients were followed up for as long as 30 days from the day of surgery until deviation from the initial treatment regimen or discharge. The major outcome assessed was an opioid overdose. They also evaluated respiratory complications, unspecified adverse effects of opioid use, and a composite of these 3 outcomes.

Key findings of the study were:

♦ Upon analysis, researchers identified 441 overdose events with absolute risks of 1.4 per 10 000 patients with gabapentinoid exposure and 0.7 per 10 000 patients receiving opioids only.

♦ After propensity score trimming, they included 737 383 patients exposed to gabapentinoids and 3 002 480 patients receiving opioids only.

♦They found that concomitant exposure to gabapentinoids and opioids was associated with increased risk of opioid-related adverse events during the postoperative period, the absolute risk of these events was extremely low.

♦ They reported respiratory complications in 15,177 patients (0.3%) and unspecified adverse effects of opioids in 4,107 patients (less than 0.1%).

♦ They also reported that 17,974 people (0.3%) had a composite outcome of opioid overdose, respiratory complications, and unspecified adverse opioid effects.

♦ They noted respiratory complications (adjusted HR 1.68), unspecified adverse effects of opioids (aHR 1.77) and composite outcome (aHR 1.70) were greater in the gabapentinoid-exposed group than in an opioid only group. These results were consistent across sensitivity analyses.

The authors concluded, "In this real-world cohort study of patients who underwent major surgery, concomitant use of gabapentinoids with opioids was associated with increased risk of opioid overdose and other opioid-related adverse events; however, the absolute risk of adverse events was low".

For further information:

https://jamanetwork.com/journals/jamanetworkopen/fullarticle/2774489