Efficacy Between Low- and High-Dose Gabapentinoids
There is no difference in postoperative pain, opioid consumption, or complications between low-dose and high-dose gabapentinoids. However, the use of gabapentinoids may lead to increased risk of confusion among elderly patients and respiratory depression with concurrent use of opioids.
Anesthesia and Analgesia in Total Joint Arthroplasty (2020)
Developed by: American Association of Hip and Knee Surgeons, American Society of Regional Anesthesia and Pain Medicine, American Academy of Orthopaedic Surgeons, The Hip Society, and The Knee Society

Rationale

Three high quality studies evaluated the difference in dosing of gabapentinoids and their effects on postoperative pain, opioid consumption, and complications after primary TJA.[7,9,13] Two studies evaluated high- and low-doses of gabapentin while one study evaluated high- and low-doses of pregabalin. Both studies that evaluated gabapentin found that there was no difference in pain scores between high- and low-dose gabapentin.[7,9] One of these studies also evaluated opioid consumption and found there was no difference in opioid consumption between high- and low-dose gabapentin groups.[9]

One study directly compared 75 mg of pregabalin twice a day for 6 weeks compared to 150 mg of pregabalin twice a day for 6 weeks postoperatively.[13] The study found no difference in opioid consumption or complications between the two doses except for constipation which was more frequent in the low-dose group.

The strength of recommendation is moderate given there is only one high quality study comparing high- and low-dose pregabalin, and studies comparing gabapentin to placebo found no difference in postoperative pain and opioid consumption with a lack of consistency in measures/scales for these high priority outcomes. It is the opinion of the workgroup that gabapentinoids be used cautiously especially when given concurrently with opioids or used in the elderly given pregabalin is associated with increased risk of postoperative sedation. Recent publications by the Food and Drug Administration (FDA) and other surgical subspecialties have highlighted these concerns regarding respiratory depression with concurrent use of opioids and gabapentinoids.[15–18] A recent database study by Ohnuma et al. also found a dose-dependent association with gabapentinoids and postoperative pulmonary complications after total hip and knee arthroplasty.[19] It is the opinion of the workgroup that pregabalin may cause increased sedative effects in the elderly and should be used with caution in this population. Given the limited high quality evidence evaluating safety and dosage, it is the consensus of this group that when gabapentinoids are utilized after primary TJA, the lowest clinically efficacious dose should be used to minimize the risk of complications.