Impact of Pregabalin on Acute and Persistent Postop Pain
We performed this systematic review to assess the analgesic efficacy of perioperative pregabalin. Subgroup analyses and meta-regression were performed to assess the impact of individual dose and frequency of pregabalin administration on analgesic efficacy. We included 55 studies. When all doses and administration regimens were combined, pregabalin was associated with a significant reduction in pain scores at rest and during movement and opioid consumption at 24 h compared with placebo {mean difference [95% confidence interval (CI)]=−0.38 (−0.57, −0.20), −0.47 (−0.76, −0.18), and −8.27 mg morphine equivalents (−10.08, −6.47), respectively}. Patients receiving pregabalin had less postoperative nausea and vomiting and pruritus compared with placebo [relative risk (RR) (95% CI)=0.62 (0.48, 0.80) and 0.49 (0.34, 0.70), respectively]. Sedation, dizziness, and visual disturbance were more common with pregabalin compared with placebo [RR (95% CI)=1.46 (1.08, 1.98), 1.33 (1.07, 1.64), and 3.52 (2.05, 6.04), respectively]. All doses of pregabalin tested (≤75, 100–150, and 300 mg) resulted in opioid sparing at 24 h after surgery. There were no significant differences in acute pain outcomes with pregabalin 100–300 mg between single preoperative dosing regimens and those including additional doses repeated after surgery. Data were insufficient to reach conclusions regarding persistent pain, but limited data available from two studies suggested that pregabalin might be effective for the reduction of neuropathic pain. In conclusion, this review suggests that pregabalin improves postoperative analgesia compared with placebo at the expense of increased sedation and visual disturbances.
Pregabalin is a γ-aminobutyric acid analogue that binds to α2δ subunits of the voltage-gated calcium channels. It reduces the excitability of the dorsal horn neurones after tissue damage. The use of pregabalin for the management of postoperative pain is off-label, and therefore, there are no dosing guidelines for this indication. For other indications, the recommended starting dose is 150 mg day in two to three divided doses, increased within 1 week to 300 mg day with a maximum recommended dose of 600 mg day. Studies investigating the perioperative use of pregabalin used doses ranging from 50 to 300 mg and daily doses ranging from 50 to 750 mg. The efficacy of perioperative administration of pregabalin was investigated in previous meta-analyses, with all showing better postoperative analgesia with pregabalin. Those meta-analyses grouped studies based on the total daily dose of pregabalin. Zhang and colleagues reported that pregabalin doses of <300 and ≥300 mg day reduced 24 h opioid consumption but not pain scores after surgery. Engelman and Cateloy grouped the analysis over a wide time-frame (6 h–7 days after surgery) according to the daily dose of pregabalin (50–150, 225–300, and 600–750 mg) and reported that the lowest effective dose for reducing postoperative analgesic consumption was 225–300 mg with no reduction in pain scores. Since doses were reported in those meta-analyses as total daily dose, it is not clear if the individual dose or frequency of administration of pregabalin affect outcome. For instance, it is not clear from those reviews if individual single doses lower than 225–300 mg have analgesic efficacy or if twice daily dosing of a particular dose of pregabalin would be more effective than single preoperative administration of the same dose. Some studies have investigated the impact of pregabalin on preoperative anxiety, but this was not addressed in those previous meta-analyses. More than 30 studies investigating perioperative pregabalin administration on acute pain outcomes have been published after the publication of those reviews, which included 11 and 18 studies. In addition, while one previous meta-analysis assessed the impact of the perioperative administration of pregabalin on chronic pain, it included only three studies. Seven other studies addressing persistent pain after pregabalin administration have since been published.
Therefore, we performed this systematic review to provide an updated meta-analysis of the impact of pregabalin administration on postoperative pain scores and opioid consumption and investigate whether those outcomes differ according to individual pregabalin dose, frequency of administration, type of anaesthesia, or type of surgery. Secondary aims were to assess the impact of pregabalin administration on anxiety scores and persistent pain, and provide an updated meta-analysis of the side-effects of pregabalin administration.
Abstract and Introduction
Abstract
We performed this systematic review to assess the analgesic efficacy of perioperative pregabalin. Subgroup analyses and meta-regression were performed to assess the impact of individual dose and frequency of pregabalin administration on analgesic efficacy. We included 55 studies. When all doses and administration regimens were combined, pregabalin was associated with a significant reduction in pain scores at rest and during movement and opioid consumption at 24 h compared with placebo {mean difference [95% confidence interval (CI)]=−0.38 (−0.57, −0.20), −0.47 (−0.76, −0.18), and −8.27 mg morphine equivalents (−10.08, −6.47), respectively}. Patients receiving pregabalin had less postoperative nausea and vomiting and pruritus compared with placebo [relative risk (RR) (95% CI)=0.62 (0.48, 0.80) and 0.49 (0.34, 0.70), respectively]. Sedation, dizziness, and visual disturbance were more common with pregabalin compared with placebo [RR (95% CI)=1.46 (1.08, 1.98), 1.33 (1.07, 1.64), and 3.52 (2.05, 6.04), respectively]. All doses of pregabalin tested (≤75, 100–150, and 300 mg) resulted in opioid sparing at 24 h after surgery. There were no significant differences in acute pain outcomes with pregabalin 100–300 mg between single preoperative dosing regimens and those including additional doses repeated after surgery. Data were insufficient to reach conclusions regarding persistent pain, but limited data available from two studies suggested that pregabalin might be effective for the reduction of neuropathic pain. In conclusion, this review suggests that pregabalin improves postoperative analgesia compared with placebo at the expense of increased sedation and visual disturbances.
Introduction
Pregabalin is a γ-aminobutyric acid analogue that binds to α2δ subunits of the voltage-gated calcium channels. It reduces the excitability of the dorsal horn neurones after tissue damage. The use of pregabalin for the management of postoperative pain is off-label, and therefore, there are no dosing guidelines for this indication. For other indications, the recommended starting dose is 150 mg day in two to three divided doses, increased within 1 week to 300 mg day with a maximum recommended dose of 600 mg day. Studies investigating the perioperative use of pregabalin used doses ranging from 50 to 300 mg and daily doses ranging from 50 to 750 mg. The efficacy of perioperative administration of pregabalin was investigated in previous meta-analyses, with all showing better postoperative analgesia with pregabalin. Those meta-analyses grouped studies based on the total daily dose of pregabalin. Zhang and colleagues reported that pregabalin doses of <300 and ≥300 mg day reduced 24 h opioid consumption but not pain scores after surgery. Engelman and Cateloy grouped the analysis over a wide time-frame (6 h–7 days after surgery) according to the daily dose of pregabalin (50–150, 225–300, and 600–750 mg) and reported that the lowest effective dose for reducing postoperative analgesic consumption was 225–300 mg with no reduction in pain scores. Since doses were reported in those meta-analyses as total daily dose, it is not clear if the individual dose or frequency of administration of pregabalin affect outcome. For instance, it is not clear from those reviews if individual single doses lower than 225–300 mg have analgesic efficacy or if twice daily dosing of a particular dose of pregabalin would be more effective than single preoperative administration of the same dose. Some studies have investigated the impact of pregabalin on preoperative anxiety, but this was not addressed in those previous meta-analyses. More than 30 studies investigating perioperative pregabalin administration on acute pain outcomes have been published after the publication of those reviews, which included 11 and 18 studies. In addition, while one previous meta-analysis assessed the impact of the perioperative administration of pregabalin on chronic pain, it included only three studies. Seven other studies addressing persistent pain after pregabalin administration have since been published.
Therefore, we performed this systematic review to provide an updated meta-analysis of the impact of pregabalin administration on postoperative pain scores and opioid consumption and investigate whether those outcomes differ according to individual pregabalin dose, frequency of administration, type of anaesthesia, or type of surgery. Secondary aims were to assess the impact of pregabalin administration on anxiety scores and persistent pain, and provide an updated meta-analysis of the side-effects of pregabalin administration.
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