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Gabapentinoids -- gabapentin (Neurontin) or pregabalin (Lyrica) -- added to opioids the day of surgery increased the risk of opioid overdose and other adverse events, though absolute risks were low.

In an observational study of about 5.5 million surgical admissions -- including nearly 900,000 patients who received gabapentinoids with opioids, the rest who received opioids only -- 441 overdose events occurred. Absolute risk of overdose was 1.4 per 10,000 patients with gabapentinoid exposure and 0.7 per 10,000 patients with opioids only, reported Katsiaryna Bykov, PharmD, ScD, of Brigham and Women's Hospital and Harvard Medical School, and colleagues in .

After propensity score trimming, adjusted HR for opioid overdose was 1.95 (95% CI 1.49-2.55) and the number needed to treat for an additional overdose to occur was 16,914 patients (95% CI 11,556-31,537).

Perioperative use of gabapentinoids is increasing in the U.S., Bykov said. "These drugs are not approved for postoperative pain and their risk-benefit profile in this setting, particularly when co-administered with opioids, is not completely understood," she noted.

"For a particular patient, the benefits of multimodal postoperative analgesia that includes gabapentinoids may outweigh the risks, but physicians need to keep in mind that these drugs have side effects and may behave in an additive way when co-administered with opioids," Bykov told 乌鸦传媒.

Since the CDC issued its about opioid prescribing, physicians have been looking for ways to limit opioid prescribing without compromising patient safety or pain relief, observed Joseph Pergolizzi Jr., MD, of Naples Anesthesia and Physician Associates in Florida, in an .

Gabapentinoids are anticonvulsants often used to treat neuropathic pain syndromes. "Of concern is the fact that gabapentinoids are associated with sedation and, when combined with opioids, can potentiate central nervous system depression," Pergolizzi noted. Interest in adjunctive gabapentinoids for postsurgical patients "likely arises more from a desire to minimize opioid consumption than from the benefits specific to these anticonvulsants themselves," he added.

But reducing overall opioid consumption does not necessarily translate to reducing opioid-associated adverse events, Pergolizzi pointed out. "As combination analgesia gains traction for in-hospital acute painful conditions such as postsurgical pain, it is important to be guided by evidence rather than intuition," he wrote.

"The evidence in support of the analgesic benefit of gabapentinoids combined with opioids for postoperative analgesia is equivocal; there is no real support that adding gabapentinoids to opioid pain relievers offers additive, much less synergistic, enhancements to pain control," he said.

The study looked at 5,547,667 adults in the database who were admitted for major surgery to a U.S. hospital between October 2007 and December 2017. All were treated with opioids the day of surgery. Patients had a mean age of about 64 and approximately 60% were women.

About 16% (892,484 patients) received gabapentinoids with opioids. Gabapentinoid use rose substantially during the study period: 29.8% who had surgery in 2017 received gabapentinoids, compared with 6.2% during the first year of the study period.

Mean opioid dose on the day of surgery was 277.1 morphine milligram equivalents (MMEs) in the gabapentinoid-exposed group and 307.3 MMEs in the opioids-only group. Postoperative stay was about 4 days in each group.

Of the group who received gabapentinoids with opioids, 61.2% used gabapentin, 35.1% used pregabalin, and 3.7% used both. Gabapentinoids were more likely to be used after knee or hip arthroplasty and less likely used for pain management of coronary artery bypass grafting (CABG), hysterectomy, or hip fracture procedures.

Respiratory complications occurred in 15,177 patients (0.3%) and 4,107 patients (less than 0.1%) had unspecified adverse effects of opioids. A total of 17,974 people (0.3%) had a composite outcome of opioid overdose, respiratory complications, and unspecified adverse opioid effects.

Respiratory complications were greater in the gabapentinoid-exposed group (adjusted HR 1.68, 95% CI 1.59-1.78). Unspecified adverse effects of opioids also were higher (adjusted HR 1.77, 95% CI 1.61-1.93), as was the composite outcome (adjusted HR 1.70, 95% CI 1.62-1.79). Results were consistent across sensitivity analyses.

The study had several limitations, Bykov and colleagues noted. It relied on coding data from discharge abstracts; some opioid-related adverse events may not have been coded as overdoses. Exposure assessment was based on medication charge codes, and it's possible some MME amounts were not precise for intravenous opioids or if not all the charged amount was used. Unmeasured confounders also may have influenced results.

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